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Josh Nicholson

and 1 more

Hello, and welcome to Authorea!👋  We're happy to have you join us on this journey towards making writing and publishing smoother, data-driven, interactive, open, and simply awesome. This document is a short guide on how to get started with Authorea, specifically how to take advantage of some of our powerful tools. Of course, feedback and questions are not only welcome, but encouraged--just hit the comment icon at the top of the document 💬and join the conversation.The BasicsAuthorea is a document editing and publishing system built primarily for researchers. It allows you to collaborate on documents and publish them easily. Each Authorea document can include data, interactive figures, and code. But first, let's get started! 1. Sign up.If you're not already signed up, do so at authorea.com/signup.  Tip: if you are part of an organization, sign up with your organizational email.  2. First stepsDuring the signup process you will be asked a few questions: your location, your title, etc. You will be also prompted to join a group. Groups are awesome! They allow you to become part of a shared document workspace. Tip: during signup, join a group or create a new one for your team. Overall, we suggest you fill out your profile information to get the best possible Authorea experience and to see if any of your friends are already on the platform. If you don't do it initially during sign up, don't worry; you can always edit your user information in your settings later on.Once you've landed on your profile page (see below). There are a few things you should immediately do:Add a profile picture. You've got a great face, show it to the world :) For reference, please see Pete, our chief dog officer (CDO), below. Add personal and group information. If you haven't added any personal information, like a bio, a group affiliation, your ORCID, or your location, do it! You might find some people at your organization already part of Authorea, plus it is a great way to build your online footprint, which is always good for getting jobs.
Statistics (1)

Josh Nicholson

and 1 more

At Authorea we're constantly thinking about how to make research writing easier, faster, and more robust from initial idea all the way through publication. Beyond stressing over making Authorea an impeccable experience and tool for researchers, we also like to think outside of the box for new innovative features that may not be on our immediate radar but are things we'd like to focus on at some point in the near future. Authorea X, if you like.Today, we'd like to ask for your feedback on one of the new ideas we're working on. We actively sought your feedback when we redesigned our new editor and would like to continue to involve researchers in the development of Authorea as much as possible. After all, we're building a great experience for you!In our latest brainstorming session, we discussed how we could help researchers improve their writing beyond what we're currently doing.  Specifically, how could we make the writing process one informed by data?  We identified a few key things we thought were important to the researcher based on requests as well as on our own observations and came up with what we're tentatively calling: "the Authorea Fitbit of research writing."  The Authorea Fitbit of researchWhile there are numerous metrics aimed at measuring the output of a researcher and the impact of their work \cite{Abbott_2010}, there is no easy way to track how a researcher is writing.  Some researchers have started manually keeping track of their writing progress on Twitter like the online #acwrimo community or the "thesis-writing tracker" by Achintya Rao of CERN but this is somewhat laborious and really just added work.  We think we can do better than a daily tally.  We can automatically track your writing patterns and share with you in a useful dashboard your typical behavior as well as your progress over a certain period of time. With such a system we would hope to be able to provide answers to the following:What time do I write most frequently at?  What are the most common words that I use?  How frequently do I write?How many words am I writing per day, per week, and per year?These are the things that we think researchers may like to know and thus we started quickly mocking up what this could look like on Authorea.  Our mocks are just initial sketches, heavily inspired by Github, and we hope, with your feedback, that they could become something very useful to researchers.  What would you track about your writing if you could? Tweet at us @authorea or leave a comment on Facebook or this article! 
Prereview main logo

PREreview Team

and 3 more

"If you want to be one year behind, don’t read bioRxiv” – Jeff LeekWelcome to PREreview! On PREreview you can collaboratively write reviews of preprints. This project was born in April 2017 as a collaboration eetween Samantha Hindle and Daniela Saderi, scientists and ASAPbio Ambassadors, with help from Josh Nicholson, at the time working for Authorea. ASAPbio (Accelerating Science And Publication in biology) is a non-profit organization dedicated to spreading the word about preprints to accelerate scientific discovery.As of October 2018, we are proud to have become an official project fiscally sponsored by Code for Science and Society. Learn more in this blog post.We are also proud to announce that we have received funding from the Sloan Foundation and the Wellcome Trust to continue to grow our community. Reed more here and stay tuned for some exciting updates! Our Mission PREreview seeks to diversify peer review in the academic community by crowdsourcing pre-publication feedback to improve the quality of published scientific output, and to train early-career researchers (ECRs) in how to  collaboratively review others' scientific work. We want to facilitate a cultural shift in which every scientist posts, reads, and engages with preprints as standard practice in scholarly publishing. We see PREreview as a hub to support and nurture the growth of a community that openly exchanges timely, constructive feedback on emerging scientific outputs. We believe that by empowering ECRs through peer review training programs, thereby increasing the diversity of researchers involved in the peer review process, PREreview will help establish a healthier and more sustainable culture around research dissemination and evaluation.  
Preprints

Josh Nicholson

and 2 more

Authorea was founded with the mission of improving how researchers write and publish their findings. We created a platform that allows researchers to write across formats, to automatically add and format citations from over 86,594,377 scholarly documents, to directly submit to a growing list of leading journals, and to collaborate easily across continents and disciplines with superior version control.  We built Authorea to be the most powerful editor for researchers because we believe that research is fundamentally important in all aspects of life.  Today, we're happy to announce our latest addition to the Authorea toolset: the ability for researchers assign a digital object identifier (DOI) to their Authorea documents.  With this release, you can now write, cite, host data, and preprint on Authorea.What is a preprint?Preprints are publication-ready research papers that are made public before peer review and formal publication. Preprints are designed to address the speed of scientific communication, the accessibility of knowledge and the existing tendency to report mostly positive results.  Preprints have a long history in research dissemination and are part of the story about how the web was created. They have long been used in physics and math with nearly 10,000 preprints posted per month at ar\(\chi\)iv and are starting to gain rapid adoption in other disciplines like the life sciences.  In fact, the growth of preprints in other disciplines was named one of Science's events that shaped 2016.
Blog image

Josh Nicholson

and 3 more

When you think of blogging you might think of a blog for cuddly cats, party parrots, the '90s, or celebrity gossip (we will not link to any of those, except cuddly cats). You probably do not think of ground breaking research, original ideas, and a powerful mechanism for research communication. And while you may be largely right, there is a world of blogging that is extremely important, a community that we wish to empower and serve with our latest feature release at Authorea, scientific blogging. In this post we wish to highlight how blogging can improve research, improve researchers career prospects, and why researchers should use a system designed for research blogging, like Authorea.Blogging as a place for correcting the scientific recordBlogging has proven to be integral towards maintaining and correcting the scientific literature. In fact, in many cases it is blogs and other forums where scientific fraud as well as common errors are first highlighted and ultimately corrected \cite{Yeo_2016}.  Blogging as a place for publishing "grey literature"Blogging allows researchers to post different types of content, ranging from journal clubs, peer reviews, single-figure observations, class essays, opinions, etc. There is a huge value to the research community to share "different" types of content, blogging allows researchers to easily do that. Blogging as a place of public outreachNearly all original peer-review publications are paywalled. Meaning it is difficult, if not impossible, for the majority of the world to legally access scientific research. Blogs, however, are nearly all completely open and accessible. More than that, they are also often times accessible in language. The discoveries and recommendations for which society invests substantial economic and human capital, should be directly disseminated by the people who really understand them, and not by the media and the political class, who often over-hype and in some case even distort the results. Blogging can be the long sought bridge between academia and the general public, something increasingly becoming required by grant agencies.Blogging as a way to advance your careerBlogs are by and large thought of as a distraction from communicating scientific ideas in a way that "counts." However, blogs can in many cases have a much larger impact on your career by providing you a forum to communicate with the world. Not all careers and hirers have such a limited way of thinking as tenure committees. Want to start blogging today? Create a group with us for free here. Want a custom design? Email us at hi@authorea.com 
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Josh Nicholson

and 4 more

BROOKLYN, NY, July 18, 2017 -- Authorea, the collaborative document editor for researchers, today announced a partnership and direct submission agreement with bioRxiv, the leading preprint server for biological research. The agreement enables researchers writing documents on Authorea to submit preprints directly to bioRxiv with one-click.Josh Nicholson, Chief Research Officer at Authorea says: "bioRxiv is having a tremendous impact in the life sciences. We're excited to work with bioRxiv and their highly engaged community to offer more powerful preprinting capabilities for authors. Authorea's mission is to accelerate scientific discovery by making tools that help researchers write and disseminate their work. bioRxiv is an important partner in this pursuit. "bioRxiv, a non-profit service of Cold Spring Harbor Laboratory funded in part by the Chan Zuckerberg Initiative,  has emerged as the go-to place for life scientists to preprint scholarly research. Today, hundreds of preprints a month are posted, the rate of submission is rising rapidly, and the service now contains more than 11,000 preprints. As life-scientist support swells dramatically, bioRxiv will demonstrate that preprinting in the life sciences is critical to advance the body of research faster than could otherwise be done.Richard Sever, co-founder of bioRxiv, says: "bioRxiv's goal is to speed up research by allowing authors to share work as quickly and easily as possible. Authorea has created a great, next-generation authoring tool for scientists, and we're delighted to integrate with them to allow direct submission. Hopefully this is just the first step in a partnership that will make writing, sharing and discovering papers easier."You can learn more about directly submitting to bioRxiv here.
Einstein ligo2
Research writing and publishing is broken. Hyperbole you say? Perhaps, but I am not sure how else to describe a system where I could have a child faster than I could formally publish a research paper \cite{Björk2013}. A system where I can no longer access some of my own work now that I have left academia or even worse a system where the public could never really access my work despite funding it through Federal grants \cite{Bj_rk_2017}. Sure, there are some cases where these statements are not true but for the most part they are and that is troubling. The list of problems goes on: papers have become harder to read over time and increasingly full of hype or spin \cite{Plav_n_Sigray_2017,Vinkers_2015}, the literature becomes more biased everyday--devoid of "negative results," and most work is largely irreproducible \cite{Collaboration2015,Begley2012} or at the very least never independently verified. So, yes, research publishing is broken and research is being hurt by how it is communicated.  How did it get this way and how can we improve it?Historically, researchers primarily communicated amongst each other by giving talks, publishing books, and writing letters. In 1655 research publishing was formalized with the launch of the first journal, Philosophical Transactions \cite{Oldenburg_1665}. The process remained largely unchanged until the 1960's and 70's, when peer review was introduced (this was facilitated by new technologies like photocopying). And that's mostly it–nothing else has changed despite even the introduction of the industry-changing world wide web. Compare Einstein's 1916 publication \cite{1915SPAW.......844E} on the prediction of gravitational waves to the publication detecting gravitational waves \cite{Abbott_2016}–100 years difference, massive changes in research technologies, identical format and largely the same publication process.
Export 613

Josh Nicholson

and 1 more

Publishing needs to keep up with research writingModern research is written collaboratively, online, and with more accompanying data and media than ever before. The number of collaborators is going up \cite{Adams_2012} and in many cases the time to publish is going up as well \cite{Powell_2016} -- it's truly a time of great change in the research world. At the same time, researchers have more publication options than ever before \cite{Larsen_2010}. The proliferation of publication options means that researchers have endless options for their work. How do researchers choose the best venue for their work? What happens when the first venue declines to publish a piece -- how do the authors find an alternative? How can publishers evolve to these changing demands? Most of the time submission is grueling for authorsAs most seasoned authors know, the submission process is neither easy nor enjoyable. Often there is a long road ahead of submit-reject-reformat-submit-revise-resubmit-proof. It's not fun. One of the most vexing issue for authors is the intense amount of formatting that goes into conforming to a particular journal style. Submission requirements are vastly different from publication to publication and the result is that authors must spend enormous amounts of time preparing manuscripts.Enter AuthoreaAuthorea is an online document editor that is collaborative and format-neutral. Authorea helps researchers write a manuscript in a vanilla style and then output to thousands of styles (see fig \ref{391184}). Authorea users, which number close to 100,000 and are growing daily, may also submit directly to hundreds of journals. 
Ssrn

Josh Nicholson

and 4 more

BROOKLYN, NY, September 12, 2017 -- Authorea, the online document editor for researchers, has partnered with the SSRN, one of the world's leading preprint repositories with recent expansion in the life and physical sciences. The partnership allows researchers to write and edit their documents on Authorea and directly publish their work at SSRN with a few simple clicks.Authorea, launched in 2014, has developed a new way for researchers to write, edit, and collaborate on research documents and today serves over 100,000 researchers from all disciplines.SSRN, launched in 1994, allows researchers to freely share working papers, conference papers, and preprints across 30 disciplines, including Economics, Law, Philosophy, Biology, Chemistry, and others. With over 700,000 research papers, it is the second largest preprint server in the world.Gregg Gordon, CEO of SSRN, says, "Authorea has developed a powerful editor for researchers that makes document editing and collaboration easy. We're excited to be working with Authorea to bring a new way of writing and submission to our community of researchers and are keen on advancing this partnership further over time. Authorea is a dynamic tool enabling scholars to easily write mathematical and scientific formulas all in one document without cumbersome formatting often associated with complicated computations."Josh Nicholson, Chief Research Officer at Authorea, says: “We're excited to partner with SSRN to offer a better way for researchers to write, edit, and publish their documents. Authorea was founded to bring document editing into the 21st century and we're happy to partner with SSRN towards this goal."Step-by-step instructions: How to submit to SSRNSSRN Template: https://www.authorea.com/templates/ssrnPress ContactAdyam Ghebre,Outreach, Authorea+1 (646) 598-9285About AuthoreaAuthorea is an online document editor for research and the place where scientific collaboration happens. Authorea is trusted worldwide by leading researchers writing and publishing content in every discipline, from astrophysics to zoology. The online document editor supports a wide range of markup languages and scientific integrations, including the most popular citation management, graphing, and visualization plugins. Authorea is on a mission to accelerate science through a superior web-based research-writing platform that delivers powerful tools and capabilities to researchers.
Rockerfelleruniv2010

Josh Nicholson

and 2 more

BROOKLYN, NY, March 20, 2017 – Authorea, the online collaborative document editor for researchers, has partnered with Rockefeller University Press (RUP), a leading publisher in the life sciences, to offer better collaboration and submission options for scientists. With this partnership, researchers writing on Authorea can submit directly to The Journal of Cell Biology, The Journal of Experimental Medicine, or The Journal of General Physiology with one-click submission.Authorea has integrated with a growing list of journals in the past year as it pushes to become the one-stop shop for researchers to write collaborative work and disseminate it widely. Researchers writing on Authorea can write in multiple markup languages (including rich text, Markdown, and LaTeX), can easily search, insert, and format citations, as well as automatically format their manuscripts for submission to leading publishers like RUP.The Rockefeller University Press provides scientists and the public with peer-reviewed results of groundbreaking research and vital news and information they can trust. With a strong commitment to quality and integrity, RUP strives to publish excellent science using the latest technologies. It carries out rigorous and fair peer-review, applying the highest standards of novelty, mechanistic insight, data integrity, and general interest. All three journals are led by active scientists in partnership with professional editors, ensuring that RUP represents the communities it serves.Rob O’Donnell, Director of Publishing Technologies at RUP, says: “RUP journals have allowed format-neutral submission for years, making the process fast and efficient for authors. We are happy to integrate with Authorea, who take that efficiency one step further by allowing authors to submit to JCB, JEM, or JGP directly from the authoring tool.”Josh Nicholson, Chief Research Officer at Authorea, says: “We want to make research more robust, open, and impactful. Rockefeller University Press publishes some of the most important journals and research in the world and we’re happy to partner with them to make the writing, submission, and ultimately publication process easier for researchers.”The partnership makes formatting and submitting extremely simple for researchers so that they spend less time formatting and more time on their essential work. With this integration,Press ContactAdyam Ghebre, Outreach, Authorea+1 (646) 598-9285About AuthoreaAuthorea is the online document editor for research and the place where scientific collaboration happens. Authorea is trusted worldwide by leading researchers writing and publishing content in every discipline, from astrophysics to zoology. The online document editor supports a wide range of markup languages and scientific integrations, including the most popular citation management, graphing, and visualization plugins. Authorea is on a mission to accelerate science through a superior web-based research-writing platform that delivers powerful tools and capabilities to researchers.
Aacr

Josh Nicholson

and 2 more

BROOKLYN, NY, August 28 2017 – Authorea, the online document editor for researchers, has partnered with the American Association for Cancer Research (AACR), the world’s first and largest cancer research organization.  By working with the AACR, Authorea aims to help researchers more easily format and submit their papers by offering one-click submission to journals published by the AACR.The AACR, founded in 1907, publishes some of the world’s most important discoveries in cancer research and is comprised of over 37,000 members in 108 countries. Christine Rullo, Publisher and Vice President, Scientific Publications at the AACR, says, “We’re excited to partner with Authorea for a more seamless submission option for researchers writing on Authorea.”Josh Nicholson, Chief Research Officer at Authorea, adds: “Our association with the AACR will help to advance research writing and editing for clinicians and scientists who work in all aspects of cancer research.  Authorea aims to bring document editing into the 21st century while supporting authors in meeting their professional goals.”Launched in 2014 and used by over 100,000 researchers from all disciplines in academia as well as leading private research companies, Authorea allows researchers to collaborate in real-time for an easier and more seamless writing and publishing experience. The journal templates below assist authors in structuring their manuscript as appropriate for each of the AACR journals. Templates• Cancer Research: https://www.authorea.com/templates/cancer_research • Cancer Immunology Research: https://www.authorea.com/templates/cancer_immunology_research• Cancer Prevention Research: https://www.authorea.com/templates/cancer_prevention_research• Molecular Cancer Research: https://www.authorea.com/templates/molecular_cancer_research• Molecular Cancer Therapeutics: https://www.authorea.com/templates/molecular_cancer_therapeutics• Cancer Discovery: https://www.authorea.com/templates/cancer_discovery_research_article • Clinical Cancer Research: https://www.authorea.com/templates/clinical_cancer_research• Cancer Epidemiology, Biomarkers and Prevention: https://www.authorea.com/templates/cancer_epidemiology_biomarkers_and_preventionPress ContactAdyam Ghebre, Outreach, Authorea+1 (646) 598-9285About AuthoreaAuthorea is an online document editor for research and the place where scientific collaboration happens. Authorea is trusted worldwide by leading researchers writing and publishing content in every discipline, from astrophysics to zoology. The online document editor supports a wide range of markup languages and scientific integrations, including the most popular citation management, graphing, and visualization plugins. Authorea is on a mission to accelerate science through a superior web-based research-writing platform that delivers powerful tools and capabilities to researchers.About the American Association for Cancer ResearchFounded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 37,000 laboratory, translational, and clinical researchers; population scientists; other health care professionals; and patient advocates residing in 108 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis, and treatment of cancer by annually convening more than 30 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 21,900 attendees. In addition, the AACR publishes eight prestigious, peer-reviewed scientific journals and a magazine for cancer survivors, patients, and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration, and scientific oversight of team science and individual investigator grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and other policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.
Elife full color horizontal

Josh Nicholson

and 1 more

CAMBRIDGE, UK, Friday, January 13, 2017 -- Authorea, the leading online editor for writing and publishing research documents, is integrating eLife into its submission system to give authors more options for direct submission to journals.eLife, the non-profit initiative backed by leading research funding organizations and led by scientists, operates a platform for research communication that recognizes and encourages responsible practices in science. eLife is now working with Authorea to allow authors to write and submit research directly to the journal as quickly and easily as possible.eLife’s partnership with Authorea aims to reduce the burden of submission on authors. A new document editor for researchers, Authorea makes it easy to write research documents and to host these online or submit them to journals for publication.Authorea gives authors the ability to write in multiple markup languages and host documents directly as standalone preprints. There are also hundreds of export styles for these documents, and Authorea’s recent integration with EJournalPress (EJPress) provides a direct link to eLife, simplifying the journal submission process.Josh Nicholson, Chief Research Officer at Authorea, says: "We're excited to partner with eLife, a major innovator in research publishing. eLife is an ideal submission destination for the tens of thousands of researchers who use Authorea to write groundbreaking research, and we look forward to partnering with eLife to help scientists gain great exposure for their discoveries."Melissa Harrison, Head of Production Operations at eLife, adds: “We’re delighted to be working with Authorea to make the submission process easier for authors. We hope to see this and other partnerships continue over the coming months, so that we can provide our authors with the best possible writing and publishing tools available to them.”For more information, please contact:Emily Packer, Press Officer, eLifee.packer@elifesciences.org01223 855373Adyam Ghebre, Outreach, Authoreaadyam@authorea.com+1 (646) 598-9285About eLifeeLife is a unique collaboration between the funders and practitioners of research to improve the way important research is selected, presented, and shared. eLife publishes outstanding works across the life sciences and biomedicine -- from basic biological research to applied, translational, and clinical studies. All papers are selected by active scientists in the research community. Responses are consolidated by the Reviewing Editor into a single, clear set of instructions for authors, removing the need for laborious cycles of revision and allowing authors to publish their findings quickly. eLife is supported by the Howard Hughes Medical Institute, the Max Planck Society, and the Wellcome Trust. Learn more at elifesciences.org.About AuthoreaAuthorea is the online document editor for research and the place where scientific collaboration happens. Authorea is trusted worldwide by leading researchers writing and publishing content in every discipline, from astrophysics to zoology. The online document editor supports a wide range of markup languages and scientific integrations, including the most popular citation management, graphing, and visualization plugins. Authorea is on a mission to accelerate science through a superior web-based research-writing platform that delivers powerful tools and capabilities to researchers.
Open access

Josh Nicholson

and 5 more

8249

Josh Nicholson

and 3 more

Write, edit, submit, revise, resubmit, resubmit, resubmit, resubmit.... Okay, you get the point: we send our manuscripts to lots of journals. The time formatting and reformatting manuscripts is a pain and it is one we are working to ease.  Your valuable time should be spent on your research, not tiresome formatting.  Today, we've added 8,249 article templates to Authorea! With the addition of these templates we now make it easy for you to write your article for just about any journal out there. We hope you won't submit to all 8,000+ different journals but at least you now have the power to do so!  We've also made it easy for users to create their own templates, so if you see a template missing, please feel free to create one.So...How does it work? It couldn't be any simpler. Just browse our template section for inspiration. Don't start from scratch. Our templates give you a mold that you can shape to your liking. Working feverishly on a research paper, grant proposal, university thesis or a class project? We do them all. Focus on your writing on the web, and enjoy Authorea's single streamlined web view of scholarly text. Once finished, you're truly finished - forget about formatting issues. With just a couple of clicks through our Export flow, you're ready to send in that submission!  Authorea's journal templates follow correct citations guidelines outlined by the journals, at no extra effort for our authors.We're really just getting started. If you need to send a printout to a colleague in draft shape, line-numbered and double-spaced, it's a selection away. Different journal? Same breeze. Your text, data, visuals, and citations will be updated automatically behind the scenes. In the unlikely event you hit a hurdle, our 24/7 support team will be happy to quality control your article and quickly get it back on the fast track to getting published.This is the first step towards making the writing and publication process as seamless as possible but we've got lot's more coming. We hope you'll join us so that we can make scholarly writing and publishing more effective and more enjoyable. Happy writing!
Preprints (1)

Josh Nicholson

and 2 more

The vast majority of academic researchers write their research in Microsoft Word \cite{Pepe_2016}. Word is easy to use due to its what-you-see-is-what-you-get (WYSIWYG) interface, however it is limited in many ways that are necessary for effectively communicating research. It necessitates the use of publishers (some of which have very antiquated models) and it limits the capability to collaborate and share data. Furthermore, it means that proper research publishing and indexing will always be costly as the conversion from Word to HTML and JATS XML (the gold standard of research articles) is an onerous process, often times manually performed "offshore". On Authorea we seek to marry the ease of writing on Word or Google Docs with the power of LaTeX, HTML, and Git.  By doing that we seek to combine the writing and publishing process so that writing is publishing. We believe that this paradigm can not only make communicating research quicker but can also make it drastically cheaper for authors and publishers.The power of LaTeX 💪LaTeX is a powerful markup language used primarily by those in the hard sciences--physicists, computer scientists, mathematicians etc. It is immensely powerful for controlling the presentation of documents, however it comes with a steep learning curve. Want to bold text? In LaTeX you need to write \textbf{bold}. Want to italicize text? Write \textit{italicize}.  In the eyes of some researchers that extra control and access to the underlying layer of markup is a benefit allowing the precise control of typesetting at a professional level.  On the converse, many, if not most, might see this as as being too cumbersome for editing and thus will never use it. At Authorea, we believe that there are strengths and weaknesses of LaTeX. We seek to provide a broad spectrum of LaTeX support so that whether you are Donald Knuth himself or someone who thinks LaTeX is a rubber, you can take advantage of Authorea and the power of LaTeX.  Below, we highlight how we are re-positioning and repurposing LaTeX in a way that is accessible to \textit{all researchers}. 🙃 Labeling and referencing figures and headingsLabeling figures and tables is something that is commonly done when writing a research article but how you do this depends upon how you write research articles. If you're writing in Word or Google Docs, you may refer to a figure or table like this:As seen in Figure 1.If you're writing in LaTeX, you will likely refer to a figure in a different way, like this:As seen in Figure \ref{527885}.While this is not a revolutionary change, it makes editing easier if you're working with multiple figures and you need to change the organization of the document around.  On Authorea, labeling and numbering is updated automatically whenever you add, remove, or move a figure or heading. Insert a new figure or move a figure around and they are automatically re-labelled.  This feature is expected in LaTeX (and commonly used) but is difficult to achieve and consequently use in Word.  We've made it easy for researchers that typically write in Word, as well as LaTeX writers, to label and reference any part of a document.More on labels and references here 👈Powerful document exportingResearchers who write in LaTeX not only write differently than most researchers, they also tend to publish and share their work differently.  Indeed, Figure \ref{527885} highlights the differences in pre-printing (self-publishing) between fields where LaTeX is the norm (arXiv) and where LaTeX is largely unheard of (Life sciences). Although there are many issues and reasons for the differences in preprint growth between disciplines, it can't be ignored that LaTeX helps facilitate preprints by allowing researchers to produce professionally typeset documents on their own.
Goal: To create a set of open source tools that can be easily used by individual researchers, publishers, and scholarly institutions to create web-native, data-rich, JATS-compliant research documents.Authorea, an organization focused specifically on research document creation and conversion, has experience in every mainstream format for academic writing (LaTeX, Word, MarkDown, and RichText) and has built a system supporting many combinations of import-to-export conversion flows. The core conversion tasks of Authorea happen at automatic import or submission of a document. At the same time, the document remains accessible to editors, typesetters, and most importantly, authors, during the main writing flow. Edits, comments and suggestions can be made easily without any knowledge of XML or the underlying document conversion process.  We seek to develop and maintain the following open source components which would allow individuals, publishers, and scholarly organizations to take advantage of and build upon the in-house technology of Authorea -- writing scholarly research documents that are web-native, machine readable, discoverable, and data-rich.An Open APIAuthorea seeks funding to develop a RESTful API with OAuth 2 authentication, which will allow any organization or individual to extract content from, and deposit into, Authorea in a variety of formats. Development of the API will allow individual academics and organizations to use Authorea as a method to convert documents in a many-to-many array of formats, optionally styled to thousands of vendor styles or custom form factors. For example, bioRxiv would be able to utilize an open-source API to completely run their submission and publication process via Authorea, in a manner indistinguishable from that of a leading academic publisher. While the API would be the engine of conversion and publication, bioRxiv could build atop any peer review, and metrics they wish.A toolkit for converting Authorea documents into JATS-compliant XMLAuthorea seeks funding to develop and refine the conversion process of its documents into publisher-grade JATS XML. In combination with opening our ingestion system API and offering an open specification of our internal formats, the implied boost will benefit the entire ecosystem of academic representations. We offer to effectively enable reliable and exhaustive conversion from any of LaTeX/Markdown/Word into JATS XML, and additionally offer automated pipelines for interacting with web vendors that interoperate via these languages.Authorea is currently focused on making it easier for researchers to write and collaborate on documents online within the current publishing paradigm. As such, our end users have no direct need for JATS-XML and we have not devoted resources towards enabling this capacity. That said, JATS-XML conversion is readily achievable by Authorea, and opening up that capacity will have significant payoff for preprint servers, publishers, and institutional repositories. Funding will be used to develop this process for near-exhaustive format coverage, provide a stress test suite for quality assurance, and bootstrap an API endpoint for the JATS output target.An open specification for data-driven scholarly writingThe fundamental enabling technology of Authorea comprises a set of guidelines and conventions for organizing, managing and representing scholarly works and their editing lifecycle. We seek funding to formalize and open these best practices as a cohesive specification for scholarly writing, enabling all of: collaborative writing; powerful version control and history management; academic import/export capabilities; and continuous integration and synchronization with third-party services. As Authorea already aggregates many best-in-class techniques from the state of art, such as the git model of version control, and uses exclusively open formats for its internal representations, we will specify scholarly writing as a logical building block of the open scholarly stack. The specification will cover file system organization, document and auxiliary representations, common workflows and best practices.  
Dear Editor,Herein is my response to manuscript ID 032723590238, entitled [“Why Hermione was better than Harry in almost every respect”] [by Ronald Frump and colleagues] to the [Journal of Squirrel-Puppy Relationships].The authors present [insert general overview of research and key findings]. This research is [well-suited/not-suitable] for the remit of the journal.[Insert any comments regarding potential conflicts of interest, or about areas of relevant expertise that you feel you are lacking].I recommend [accept/minor revisions/major revisions/oblivion], pending x, y, and z.Basic reportingFiguresAre the figures legible, relevant, and integrated into the textDataAre the supporting data included in the manuscript or in a relevant repositoryAre the data presented in a way that is consistent with the FAIR principles (https://www.force11.org/group/fairgroup/fairprinciples)Experimental designWas the way in which the research was conducted the best way to answer the relevant questionsValidity of the findingsAre the conclusions supported by the resultsDo the results contribute to the research field, irrespective of whether they are ‘negative’ or a replication studyGeneral commentsIs the language used appropriate for a scientific publicationIs the structure appropriateAbstractIs the abstract concise, and does it convey the main research findingsAre any key points of context or conclusions missingIntroductionDoes this cover the published literature sufficientlyDoes it provide enough context in which to place the current researchAre any key citations missingIs the history of the research conveyed at all for historical significanceDoes it finish with a paragraph summarising the relevance of the current researchMaterials and methodsAre the methods clear and easy to followCan the methods be replicated if neededAre the source materials/data openly available, and is appropriate justification provided if notWere any statistical analyses applied performed appropriatelyResultsAre the results presented in a coherent fashionAre the results reported in a way that is supported by the dataDiscussionAre the new results placed into context of the relevant literatureIs a balanced argument providedAre the full implications of the new results discussed in sufficient detailConclusionsAre the conclusions supported by the resultsAre they concise and written in an impactful way (not over-embellished)Additional commentsAnything else you want to add that doesn’t fit aboveCongratulations to the authors on a great piece of work, and I look forward to seeing their research [published/rejected/re-written with all of the references to my own tangentially-relevant work included.]Sincerely,[Ralph Lauren]ReferencesAny additional papers you have cited within your report
8t1oarcr
BROOKLYN, NY, May 22, 2017 -- Authorea, the online home for researchers to write and disseminate documents, has partnered with Society for Neuroscience (SfN), the world's leading neuroscience organization. With the partnership researchers interested in submitting to SfN may use Authorea to submit manuscripts directly to eNeuro and The Journal of Neuroscience with one click. The integration greatly reduces formatting and data entry overhead for Authorea users by ensuring documents conform to SfN submission requirements automatically.With the recent launch of its flagship document editor, Authorea has become the go-to place for researchers to write scholarly articles. Researchers have the freedom to write in multiple markup languages, store data alongside in-progress documents, establish collaborative workflows, insert and format citations, and much more. Submitting directly to the world's leading publishers allows any researcher writing on Authorea to have many options for publication.Josh Nicholson, Chief Research Officer at Authorea, says: “We're happy to be working with Society for Neuroscience to make collaboration and publication easier for neuroscientists. We're excited to work with such an important and engaged community.”Society for Neuroscience is the world's largest and most prestigious neuroscience organization with over 40,000 international physicians and scientists. Founded in 1969 it publishes some of the world's leading research in the field of neuroscience.Templates for submission to SfN can be found beloweNeuroeNeuro title pageThe Journal of NeurosciencePress ContactAdyam Ghebre, Outreach, Authorea+1 (646) 598-9285About AuthoreaAuthorea is an online document editor for research and the place where scientific collaboration happens. Authorea is trusted worldwide by leading researchers writing and publishing content in every discipline, from astrophysics to zoology. The online document editor supports a wide range of markup languages and scientific integrations, including the most popular citation management, graphing, and visualization plugins. Authorea is on a mission to accelerate science through a superior web-based research-writing platform that delivers powerful tools and capabilities to researchers.
Upgoer
“If you can't explain it to a six year old, you don't understand it yourself.”Writing is hard. Writing about complex concepts is even harder. Writing about complex concepts with little writing training, that's research communication. And while research writing is difficult and often under-taught, it is critical to the success of a researcher and research. Implicit in the dictum publish or perish, is that you must write. Researchers write papers, syllabi, grants, progress reports and a variety of different documents on a daily basis. Yet researchers don't typically write for the public...or for fun. Today, we'd like to change that, with the Up Goer Five Challenge! A contest that challenges researchers to use only the ten hundred most common words to explain their research. We're offering everyone that participates in the Upgoer five challenge a free premium membership on Authorea for a year! We think such a challenge is great for PIs, postdocs, students, and anyone doing research and it is great for the community and public. We also think it's quite fun!To enter, follow these steps:Signup at authorea.com/signup to create an account.Upon signup, select the group "Up-Goer Five" to join the challenge.Describe your research using the ten hundred most common words with the Up-Goer five text editor. Copy and paste your entry into a public Authorea document.Hit "Publish" on the toolbar to publish your document to the Up-Goer five group.Assign a digital object identifier (DOI) to make it citable.Share it socially and challenge your friends! (#upgoerfive)

Josh Nicholson

and 1 more

The web was built specifically to share research papers amongst scientists. Despite this being the first goal of the modern web, most research is still published behind a paywall. We have recently highlighted famous math papers that reside behind a paywall as well as ten papers that have achieved a near rockstar status in research and the public. Here we systematically look at the top one hundred cited papers of all time and find that 65% of these papers are not open. Stated another way, THE WORLD’S MOST IMPORTANT RESEARCH IS INACCESSIBLE FROM THE MAJORITY OF THE WORLD. A few facts about the top 100 cited papers: 1. The weighted average of all the paywalls is: $32.33, rounding to the nearest cent. 2. There are 1, 088, 779 citations of the Open Access articles, so, if they cost the same on average as the Paywalled articles and were paid for individually, they would cost a total of: $35, 199, 108.44–that’s 14 Bugatti Veyrons, or enough to buy everyone in New York City a Starbucks Tall coffee and chocolate chip cookie. In comparison, the total amount for the paywalled articles, assuming everyone bought the paywalled articles individually, is $54, 722, 252.80. 3. That’s 23 Bugatti Veyrons, or enough to buy everyone in New York City a footlong from Subway. 4. Although 65% of the most cited papers are paywalled, only 61% of those paper’s citations are from paywalled journals. Thus the open access articles in this list are, on average, cited more than the paywalled ones.
Fundingawardsuccessrate rpg

Matteo Cantiello

and 2 more

AbstractPreprints are widely acknowledged to be beneficial to the research community. However, the career implications of an author preprinting their work are unclear. Here we discuss the implications of researchers preprinting their work in terms of precedence, visibility and citation impact, and manuscript editing. In short, we show that researchers that preprint their work have a citation boost ranging from 83% to 269% and that preprints can in practice improve your manuscript and that can limit "scooping."What are preprints?Preprints are publication-ready research articles that have yet to undergo peer review and be formally published. They are free, openly accessible, and widely reusable under permissive copyright licenses.  They accelerate research communication by putting dissemination under researcher control. While preprints are widely viewed as beneficial for research and are the norm in certain disciplines like physics, math, computer science, and statistics, preprinting is relatively new in other disciplines, like the life sciences, psychology, sociology and others.  In these fields - that are new to preprints - questions and confusion can arise around preprinting, potentially hampering their uptake and utility.The benefits of preprintingBelow we highlight the benefits of preprinting your work at the individual level in an effort to encourage researchers to take control of their research. This article aims to show that preprinting is not just good for the community, but also good for the individual scientist, as outlined in "The selfish scientist’s guide to preprint posting" \cite{Kriegeskorte}.Preprints allow researchers to claim precedence on a discoveryWith funding rates at an all-time historic low (see figure \ref{849950}) researchers are hyper-competitive in many aspects of their careers. This competition, while good to an extent, can severely limit data sharing and open discussion, two practices necessary for the advancement of research.  One particular fear of researchers is that they might be "scooped," (ie their discovery is shared by someone else first).  

michaeljdklein

and 1 more

PYTHAGORAS’ THEOREM a² + b² = c² _Pythagoras, 530 BC_ -------------------------------- -------------------------------------------------------------------------------------------------------------------------------------------- ------------------------------ --------- LOGARITHMS logxy = logx + logy _John Napier, 1610_ CALCULUS $ f}{ t} = {h}$ _Newton, 1668_ LAW OF GRAVITY $F = G {r^2}$ _Newton, 1687_ THE SQUARE ROOT OF MINUS ONE i² = −1 _Euler, 1750_ EULER’S FORMULA FOR POLYHEDRA V − E + F = 2 _Euler, 1751_ NORMAL DISTRIBUTION $\psi(x) = {} e^{2~\rho^2}$ _C. F. Gauss, 1810_ WAVE EQUATION ${\partial t^2} = c^2 {\partial x^2}$ _J. D‘Ambert, 1746_ FOURIER TRANSFORM f(ω)=∫−∞∞f(x)e−2 π i x ωdx _J. Fourier, 1822_ NAVIER-STOKES EQUATION $\rho \left ( }{\partial t} + \cdot \nabla \right ) = - \nabla p + \nabla \cdot T + f$ _C. Navier, G. Stokes, 1845_ MAXWELL’S EQUATIONS ∇ ⋅ E = 0 _J. C. Maxwell, 1865_ $\nabla \times E = - {e} {\partial t}$ ∇ ⋅ H = 0 $\nabla \times H = {e} {\partial t}$ SECOND LAW OF THERMODYNAMICS dS ≥ 0 _L. Boltzmann, 1874_ PAYWALL RELATIVITY E = mc² _Einstein, 1905_ PAYWALL SCHRÖDINGER’S EQUATION $ \hbar {\partial t} \psi = H \psi$ _E. Schrödinger, 1927_ PAYWALL INFORMATION THEORY H = −∑p(x)logp(x) _C. Shannon, 1949_ PAYWALL CHAOS THEORY xt + 1 = k xt(1 − xt) _Robert May, 1975_ PAYWALL BLACK-SCHOLES EQUATION ${2} \sigma^2 S^2 {\partial S^2} + r S {\partial S} + {\partial t} - r V = 0$ _F. Black, M. Scholes, 1990_ PAYWALL EULER’S TRANSFORMATION $^\infty (-1)^n a_n = ^\infty (-1)^n {2^{n+1}}$ _Euler, 1755_ PAYWALL RUSSELL’S PARADOX Let R = {x ∣ x ∉ x}, then R ∈ R ⇔ R ∉ R _Russell, 1902_ GÖDEL’S INCOMPLETENESS THEOREM G(x):=¬Prov(sub(x, x)) ⇒ PA ⊢ G(⌜G⌝) ↔ ¬Prov(⌜G(⌜G⌝)⌝) _Gödel, 1931_

Josh Nicholson

and 1 more

Dear Editor,Herein is my response to manuscript ID XXXXX, entitled [“Why Hermione was better than Harry in almost every respect”] [by Ronald Frump and colleagues] to the [Journal of Squirrel-Puppy Relationships].The authors present [insert general overview of research and key findings]. This research is [well-suited/not-suitable] for the remit of the journal.[Insert any comments regarding potential conflicts of interest, or about areas of relevant expertise that you feel you are lacking].I recommend [accept/minor revisions/major revisions/oblivion], pending x, y, and z.Basic reportingFiguresAre the figures legible, relevant, and integrated into the textDataAre the supporting data included in the manuscript or in a relevant repositoryAre the data presented in a way that is consistent with the FAIR principles (https://www.force11.org/group/fairgroup/fairprinciples)Experimental designWas the way in which the research was conducted the best way to answer the relevant questionsValidity of the findingsAre the conclusions supported by the resultsDo the results contribute to the research field, irrespective of whether they are ‘negative’ or a replication studyGeneral commentsIs the language used appropriate for a scientific publicationIs the structure appropriateAbstractIs the abstract concise, and does it convey the main research findingsAre any key points of context or conclusions missingIntroductionDoes this cover the published literature sufficientlyDoes it provide enough context in which to place the current researchAre any key citations missingIs the history of the research conveyed at all for historical significanceDoes it finish with a paragraph summarising the relevance of the current researchMaterials and methodsAre the methods clear and easy to followCan the methods be replicated if neededAre the source materials/data openly available, and is appropriate justification provided if notWere any statistical analyses applied performed appropriatelyResultsAre the results presented in a coherent fashionAre the results reported in a way that is supported by the dataDiscussionAre the new results placed into context of the relevant literatureIs a balanced argument providedAre the full implications of the new results discussed in sufficient detailConclusionsAre the conclusions supported by the resultsAre they concise and written in an impactful way (not over-embellished)Additional commentsAnything else you want to add that doesn’t fit aboveCongratulations to the authors on a great piece of work, and I look forward to seeing their research [published/rejected/re-written with all of the references to my own tangentially-relevant work included.]Sincerely,[Ralph Lauren]ReferencesAny additional papers you have cited within your report

Sergey Brin

and 2 more

This paper was originally published on January 29, 1998 at http://ilpubs.stanford.edu:8090/422/1/1999-66.pdf. This is the HTMLized version, created because such an important paper about the web deserves more than a PDF.AbstractThe importance of a Web page is an inherently subjective matter, which depends on the readers interests, knowledge and attitudes. But there is still much that can be said objectively about the relative importance of Web pages. This paper describes PageRank, a method for rating Web pages objectively and mechanically, effectively measuring the human interest and attention devoted to them. We compare PageRank to an idealized random Web surfer. We show how to efficiently compute PageRank for large numbers of pages. And, we show how to apply PageRank to search and to user navigation.1. Introduction and MotivationThe World Wide Web creates many new challenges for information retrieval. It is very large and heterogeneous. Current estimates are that there are over 150 million web pages with a doubling life of less than one year. More importantly, the web pages are extremely diverse, ranging from "What is Joe having for lunch today?" to journals about information retrieval. In addition to these major challenges, search engines on the Web must also contend with inexperienced users and pages engineered to manipulate search engine ranking functions. However, unlike "at" document collections, the World Wide Web is hypertext and provides considerable auxiliary information on top of the text of the web pages, such as link structure and link text. In this paper, we take advantage of the link structure of the Web to produce a global "importance" ranking of every web page. This ranking, called PageRank, helps search engines and users quickly make sense of the vast heterogeneity of the World Wide Web.1.1 Diversity of Web PagesAlthough there is already a large literature on academic citation analysis, there are a number of significant differences between web pages and academic publications. Unlike academic papers which are scrupulously reviewed, web pages proliferate free of quality control or publishing costs. With a simple program, huge numbers of pages can be created easily, artificially inflating citation counts. Because the Web environment contains competing profit-seeking ventures, attention-getting strategies evolve in response to search engine algorithms. For this reason, any evaluation strategy which counts replicable features of web pages is prone to manipulation. Further, academic papers are well-defined units of work, roughly similar in quality and number of citations, as well as in their purpose to extend the body of knowledge. Web pages vary on a much wider scale than academic papers in quality, usage, citations, and length. A random archived message posting asking an obscure question about an IBM computer is very different from the IBM home page. A research article about the effects of cellular phone use on driver attention is very different from an advertisement for a particular cellular provider. The average web page quality experienced by a user is higher than the quality of the average web page. This is because the simplicity of creating and publishing web pages results in a large fraction of low-quality web pages that users are unlikely to read. There are many axes along which web pages may be differentiated. In this paper, we deal primarily with one - an approximation of the overall relative importance of web pages.1.2 PageRankIn order to measure the relative importance of web pages, we propose PageRank, a method for computing a ranking for every web page based on the graph of the web. PageRank has applications in search, browsing, and traffic estimation. Section 2 gives a mathematical description of PageRank and provides some intuitive justification. In Section 3, we show how we efficiently compute PageRank for as many as 518 million hyperlinks. To test the utility of PageRank for search, we built a web search engine called Google (Section 5). We also demonstrate how PageRank can be used as a browsing aid in Section 7.3.2 A Ranking for Every Page on the Web2.1 Related WorkThere has been a great deal of work on academic citation analysis \cite{Garfield}. Goffman \cite{Goffman_1971}  has published an interesting theory of how information flow in a scientific community is an epidemic process. There has been a fair amount of recent activity on how to exploit the link structure of large hypertext systems such as the web. Pitkow recently completed his Ph.D. thesis on "Characterizing World Wide Web Ecologies"\cite{Pirolli_1996,Catledge_1995} with a wide variety of link-based analysis. Weiss discuss clustering methods that take the link structure into account \cite{Weiss_1996}. Spertus \cite{Spertus_1997} discusses information that can be obtained from the link structure for a variety of applications. Good visualization demands added structure on the hypertext and is discussed in \cite{Mukherjea_1995,Mukherjea_1995a}. Recently, Kleinberg \cite{Kleinberg_1999} has developed an interesting model of the web as Hubs and Authorities, based on an eigenvector calculation on the co-citation matrix of the web. Finally, there has been some interest in what "quality" means on the net from a library community \cite{Tillman}. It is obvious to try to apply standard citation analysis techniques to the web's hypertextual citation structure. One can simply think of every link as being like an academic citation. So, a major page like http://www.yahoo.com/ will have tens of thousands of backlinks (or citations) pointing to it. This fact that the Yahoo home page has so many backlinks generally imply that it is quite important. Indeed, many of the web search engines have used backlink count as a way to try to bias their databases in favor of higher quality or more important pages. However, simple backlink counts have a number of problems on the web. Some of these problems have to do with characteristics of the web which are not present in normal academic citation databases.2.2 Link Structure of the WebWhile estimates vary, the current graph of the crawlable Web has roughly 150 million nodes (pages) and 1.7 billion edges (links). Every page has some number of forward links (outedges) and backlinks (inedges) (see Figure 1). We can never know whether we have found all the backlinks of a particular page but if we have downloaded it, we know all of its forward links at that time.
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_Research Notes of the American Astronomical Society_ (RNAAS) is a publication in the AAS portfolio (alongside ApJ, AJ, ApJ Supplements, and ApJ Letters) through which authors can promptly and briefly share materials of interest with the astronomical community in a form that will be searchable via ADS and permanently archived. The astronomical community has long faced a challenge in disseminating information that may not meet the criteria for a traditional journal article. There have generally been few options available for sharing works in progress, comments and clarifications, null results, and timely reports of observations (such as the spectrum of a supernova), as well as results that wouldn’t traditionally merit a full paper (such as the discovery of a single exoplanet or contributions to the monitoring of variable sources). Launched in 2017, RNAAS was developed as a supported and long-term communication channel for results such as these that would otherwise be difficult to broadly disseminate to the professional community and persistently archive for future reference. Submissions to RNAAS should be brief communications - 1,000 words or fewer [1], and no more than a single figure (e.g. Figure [fig:1]) or table (but not both) - and should be written in a style similar to that of a traditional journal article, including references, where appropriate, but not including an abstract. Unlike the other journals in the AAS portfolio, RNAAS publications are not peer reviewed; they are, however, reviewed by an editor for appropriateness and format before publication. If accepted, RNAAS submissions are typically published within 72 hours of manuscript receipt. Each RNAAS article is issued a DOI and indexed by ADS to create a long-term, citable record of work. Articles can be submitted in  (preferably with the new rnaastex.cls classfile), MS/Word, or via the direct submission in the Authorea or Overleaf online collaborative editors. Authors are expected to follow the AAS’s ethics , including guidance on plagiarism . [1] An easy way to count the number of words in a Research Note is to use the texcount utility installed with most  installations. The call texcount -incbib -v3 rnaas.tex) gives 57 words in the front matter and 493 words in the text/references/captions of this template. Another option is by copying the words into MS/Word, and using “Word Count” under the Tool tab.
 *Department/College *Course Name *Semester Syllabus Part 1: Course InformationInstructor: *Name Office: *Location  Office Hours: *Times & Days Office Telephone: *Phone Number E-mail: *E-mail address (Note: specify your preferred contact)*Course Description *Enter catalog description.                                                  Prerequisit*Enter prerequisite information.GE Area if Applicable *Enter if applicable or remove this heading. Note: General Education courses must display the area they fulfill.Textbook & Course MaterialsRequired TextList required course textbooks. Include detail such as full name of textbook, author, edition, ISBN, description (if desired), and where it can be purchased. If a required text is available online, indicate where it can be accessed. Recommended Texts & Other ReadingsList other readings available and how/where to access them. *Include a general statement such as Other readings will be made available in the course packet/Web site/CILearn environment Course Requirements Internet connection (DSL, LAN, or cable connection desirable) Access to Web site/Other *List other tools, resources, and materials needed by the student for success in the course. Remove the above bullets if you do not plan to use CILearn or another Web-based resource. Course StructureExplain how the course will be delivered. Is it lecture, discussion, activity, or lab-based. How much time is devoted to each component and are there different meeting places students should be aware of (such as labs or activity rooms)? Online Resources List any online resources such as Authorea, a faculty Web site, textbook Web site, or other Web resources that you expect students to access and use. Part 2: Student Learning Outcomes  List the student learning outcomes for this course.  The student learning outcomes for each course can be found on the Curriculum Committee website under Program Areas and Courses (http://senate.csuci.edu/comm/curriculum/). A bulleted list is a good way to display these objectives as shown below:Objective Objective Objective You will meet the objectives listed above through a combination of the following activities in this course: Provide instructions to students on how they are expected to meet the learning objectives for the course. For example: Will most objectives be met through examination? Or through participation? Or through projects? Attend … Complete … Participate …Part 3: Topic Outline/Schedule Week 01: *Topic Details … Week 02: *Topic Details … Week 03: *Topic Details … Week 04: *Topic Details … Week 05: *Topic Details … Note about calendar/schedule. While it is important to clearly indicate the schedule for your course, there are many places where you may do this. Part 4: Grading PolicyGraded Course ActivitiesLate Work Policy  Example: Be sure to pay close attention to deadlines—there will be no make up assignments or quizzes, or late work accepted without a serious and compelling reason and instructor approval.*Include a statement about the timeframe of when to look for grades. Example: Your instructor will update the online grades each time a grading session has been complete—typically X days following the completion of an activity. You will see a visual indication of new grades posted on your home page under the link to this course.Letter Grade Assignment*Include an explanation between the relationship of points earned and final letter grade. Example: Final grades assigned for this course will be based on the percentage of total points earned and are assigned as follows:Part 5: Course PoliciesAttend Class Students are expected to attend all class sessions as listed on the course calendar.*Enter specific points regarding attendance policy here. Participate*If you monitor, track, and/or score student participation, explain how you will keep track and how often students should be accessing the course. Build RapportIf you find that you have any trouble keeping up with assignments or other aspects of the course, make sure you let your instructor know as early as possible. As you will find, building rapport and effective relationships are key to becoming an effective professional. Make sure that you are proactive in informing your instructor when difficulties arise during the semester so that they can help you find a solution.Complete AssignmentsAll assignments for this course will be submitted electronically through CILearn unless otherwise instructed. Assignments must be submitted by the given deadline or special permission must be requested from instructor before the due date. Extensions will not be given beyond the next assignment except under extreme circumstances. All discussion assignments must be completed by the assignment due date and time. Late or missing discussion assignments will effect the student’s grade.Understand When You May Drop This CourseIt is the student’s responsibility to understand when they need to consider disenrolling from a course. Refer to the Channel Islands Course Schedule for dates and deadlines for registration. After this period, a serious and compelling reason is required to drop from the course. Incomplete PolicyUnder emergency/special circumstances, students may petition for an incomplete grade. An incomplete will only be assigned if [*insert condition here]. All incomplete course assignments must be completed within [*insert timeframe here].Inform Your Instructor of Any Accommodations NeededXXXXX is committed to equal educational opportunities for qualified students with disabilities in compliance with Section 504 of the Federal Rehabilitation Act of 1973 and the Americans with Disabilities Act (ADA) of 1990. The purpose of Disability Resource Program is to assist students with disabilities to realize their academic and personal potential. Students with disabilities needing accommodation are required to contact the Disability Program office at XXXX. All requests for accommodations need appropriate advance notice by the student to avoid a delay in services. Please discuss approved accommodations with faculty. Commit to IntegrityAs a student in this course (and at this university) you are expected to maintain high degrees of professionalism, commitment to active learning and participation in this class and also integrity in your behavior in and out of the classroom.Academic Dishonesty PolicyAcademic dishonesty includes such things as cheating, inventing false information or citations, plagiarism and helping someone else commit an act of academic dishonesty. It usually involves an attempt by a student to show possession of a level of knowledge or skill that he/she does not possess. Course instructors have the initial responsibility for detecting and dealing with academic dishonesty. Instructors who believe that an act of academic dishonesty has occurred are obligated to discuss the matter with the student(s) involved. Instructors should possess reasonable evidence of academic dishonesty. However, if circumstances prevent consultation with student(s), instructors may take whatever action (subject to student appeal) they deem appropriate. Instructors who are convinced by the evidence that a student is guilty of academic dishonesty shall assign an appropriate academic penalty. If the instructors believe that the academic dishonesty reflects on the student's academic performance or the academic integrity in a course, the student's grade should be adversely affected. Suggested guidelines for appropriate actions are: an oral reprimand in cases where there is reasonable doubt that the student knew his/her action constituted academic dishonesty; a failing grade on the particular paper, project or examination where the act of dishonesty was unpremeditated, or where there were significant mitigating circumstances; a failing grade in the course where the dishonesty was premeditated or planned. The instructors will file incident reports with the Vice Presidents for Academic Affairs and for Student Affairs or their designees. These reports shall include a description of the alleged incident of academic dishonesty, any relevant documentation, and any recommendations for action that he/she deems appropriate. The Vice President for Student Affairs shall maintain an Academic Dishonesty File of all cases of academic dishonesty with the appropriate documentation. Student may appeal any actions taken on charges of academic dishonesty to the "Academic Appeals Board." The Academic Appeals Board shall consist of faculty and at least one student. Individuals may not participate as members of the Academic Appeals Board if they are participants in an appeal. The decision of the Academic Appeals Board will be forwarded to the President of CSU Channel Islands, whose decision is final. Important Note: Any form of academic dishonesty, including cheating and plagiarism, may be reported to the office of student affairs. Course policies are subject to change. It is the student’s responsibility to check CILearn for corrections or updates to the syllabus.
The title should ideally be fewer than 120 characters, with a clear indication of the biological system under investigation (if appropriate), and should avoid abbreviations and unfamiliar acronyms if possible. Please note that two-part titles – e.g. “What goes up must come down: Oscillations in transcriptional networks” – are not permitted for research papers.Author names and affiliationsA complete list of authors and affiliations should be provided in the paper itself.AbstractThe abstract should be fewer than 150 words and should not contain subheadings. It should provide a clear, measured, and concise summary of the work. If the biological system (species names or broader taxonomic groups if appropriate) is not mentioned in the title, it must be included in the abstract.IntroductionWe encourage a clear and concise style of writing. Various writing guides are available, including Preparing a Manuscript for Submission to a Biomedical Journal (ICMJE) and The Elements of Style (New York: bartleby.com, 1999).ResultsDiscussionMaterials and MethodsAny "personal communications" relating to unpublished data should be incorporated within the main text, in the following format: (Author Initial(s) and Surname, personal communication, Month and Year). Authors should have permission from anyone named in this way and should be aware that a supporting letter will sometimes be requested.Within the Materials and Methods and/or figure legends, we encourage authors to provide complete information about their experiments, analyses, or data collection to ensure that readers can easily understand what was measured and analysed, and can accurately perform the relevant protocols.In cases where a new method within the submission would benefit from step-by-step protocols in addition to the methods described in the article, we would encourage authors to also consider submitting a detailed protocol to Bio-protocol.On first mention, please provide details of any manufacturers in the following format: company name, city, country (or state, if based in the United States).AcknowledgementsIndividuals who have contributed materially to the work, but do not satisfy the authorship criteria should be listed in the acknowledgements section. Authors should seek permission to include any individuals mentioned in the acknowledgements.Competing interestsAt this stage we request that the corresponding author provides a statement of financial and non-financial competing interests on behalf of all authors. Examples include paid employment or consultancy, stock ownership, patent applications, personal relationships with relevant individuals, and membership of an advisory board.Example reference \cite{Nicholson_2015}.

Josh Nicholson

and 3 more

At Authorea we have big goals, not necessarily for ourselves, but for researchers and the scientific community. We envision a world where researchers write and publish their work openly, they include their data inside of interactive figures and seek collaborators and the community to test their work to ensure it is robust. Communication and publishing is dynamic and modern and research moves more efficiently because researchers move more efficiently. This vision may sound idealistic but it is being realized and we are diligently working to build a platform and community to foster it.  Over the last year we have taken tremendous steps towards creating the place to write and disseminate research. We relaunched our new editor only a few months ago and have redesigned nearly every part of Authorea to make it the best place to write research documents, for all researchers.  We've added direct submission to a growing list of leading journals, have introduced the first and only place to preprint in HTML, and introduced a new version control system for writing research papers.  In short, we've done a lot, really fast.We're going to continue to keep innovating but we're taking a brief pause from introducing new features to focus on reliability, usability, and research support. That means, we want to hear from you. What could we do better? What small or big changes on Authorea would help you be more efficient at research writing and publishing? Below are just some of the major highlights of what we've accomplished in the last few months, which do not include the bugs here and there and tweaks made based on user feedback/testing.  Acquire Research Publisher, The Winnower--LinkNew HomepageLaunch Authorea Beta, our new editor--Linkreal-time collaborationautosaveability to write in Markdown, LaTeX, and rich-text all within one articlenew toolbarPartner with Sample of Science--LinkPartner with eLife for direct submission--LinkImproved UX for LaTeX and Markdown rendering.Improved Author Management controlAdd multi-cite capability/improve design UX of citation tool.New pricing--LinkNew browse page--LinkIntroduce new version control system for research writing--LinkNew features page--LinkIntroduce preprinting capabilities and ability to issue DOI on Authorea--LinkAdd \labels, \refs, New commenting system
Mowat1
EXECUTIVE SUMMARYA fundamental principle of Canada’s national identity is that all Canadians should have access to similar levels of public services, regardless of which province they live in. The federal Equalization program is Canada’s most important tool for ensuring this equity among provinces, given that provinces differ in their ability to generate revenues to pay for the services they are each responsible to provide.Over the past decade, several factors have challenged the program’s ability to achieve this goal. The three most important factors have been federal fiscal restraint, Ontario’s qualification for payments, and the role of natural resources, particularly oil. Successive federal governments have introduced and upheld measures to address these challenges. But these measures have themselves created additional problems, particularly for Equalization-receiving provinces. Furthermore, the data used for calculating entitlements may be mis-measuring the differences between provinces that the program is supposed to equalize.Looking forward, these challenges will persist if unaddressed. Ontario may drop in and out of Equalization-receiving status creating unpredictability for the province and potentially for other provinces and the federal government as well. Natural resources will be a continued source of volatility and unequalized fiscal capacity, contributing to a divergence in levels of service between provinces – precisely the outcome the Equalization program was designed to prevent.Unaddressed, these challenges could further derail one of Canada’s most important programs, undermining an important and fundamental Canadian principle. And trying to address them piece-meal will only continue to muddle the situation, as previous ad-hoc solutions have done.The upcoming five-year legislative renewal of the program is the best time to address these issues in a more systematic manner. A set of interconnected reforms, targeting the three challenges noted above and thinking through the potential side effects of their complex interactions is the order of the day.Such reforms should be designed such that they will increase predictability for provinces and the federal government while enhancing the accuracy of the data upon which equalization decisions are made. These changes would benefit the fiscal planning efforts of provinces and the federal government alike. The problematic issue of resource revenue inclusion should also be addressed by including in Equalization calculations only the proportion of provincial resource revenue that gives rise to differences in spending levels among provinces. Lastly, Canada lacks a program to effectively protect provincial revenues from idiosyncratic economic shocks. Improvements to the federal Fiscal Stabilization program should be undertaken to better share fiscal risks across the federation. We propose a set of simple solutions to achieve these goals.
Jsm

Josh Nicholson

and 1 more

Deciding between Authorea and Issuu? Choosing the right way to publish your content online should be based on what is best for your business. Here are some key comparisons to help you decide:1. Presenting content in HTML or PDFToday, content is primarily read on the web. However, content is still largely created for the printed page. This disconnect has lead to the creation of service like Issu, making it possible to display PDFs online in an embedded container. Authorea, a document editor and publisher was designed to be web-native. Content written and published on Authorea is displayed in HTML as well as PDF. By displaying content in HTML Authorea offers groups the following advantagesAbility to read content easily on mobileAbility to track engagement on contentEnhanced SEO (PDFs are not part of the web, only described on the web)Ability to include interactive figures 2. Creating content automatically or with a design teamMany media companies create content designed for the printer (i.e. they create PDFs). The ability to create beautiful PDFs is possible with the work of designers using Indesign or other tools like Sketch. While a beautiful PDF can be created this way, the design and implementation of custom PDFs is time-consuming with most tools. Authorea, allows groups to set up a variety of custom PDF styles that can be recreated from Word, Google Docs, or and Authorea document with the click of a single button. This is one of the real powers of Authorea, we make it easy to produce content by employing LaTeX "under the hood," the world's most advanced typesetting system. If you want to control every pixel, then you might want to utilize a design team. If you want to produce beautiful reports easily without overhead then Authorea might be your best bet.3. CollaborationAuthorea allows people to collaborate simultaneously on their documents. This means that you don't need to send a variety of different file types back and forth via email. With Authorea you can work on one document to create a beautiful report. In this case, writing is publishing.4. Customizable URL and designCreating a PDF to put online? That necessitates you utilizing an editor (Word or Google Docs), a design application (Sketch or Indesign), and a web host (Issuu, Wordpress, etc.). With Authorea you can write, edit, and publish all from Authorea. We allow groups to fully customize the URL and design of the site to make it easy to incorporate Authorea into the publishing process. In fact, it's so easy that we have effectively made writing the same thing as publishing.
Agu logo

Josh Nicholson

and 1 more

BROOKLYN, NY, March 28, 2017 – Authorea, an online collaborative editor for research documents, has partnered with the American Geophysical Union (AGU) to offer one-click direct submission of articles written on Authorea to a collection of leading earth and space science journals published by AGU.AGU, founded in 1919, is a not-for-profit professional organization representing 60,000 members in 137 countries. AGU publishes over 6,000 articles annually across its catalog of journals. Authorea has now integrated direct submission to the following AGU journals:• Earth and Space Science• Earth’s Future• Geochemistry, Geophysics, Geosystems• GeoHealth• Geophysical Research Letters• Global Biogeochemical Cycles• Journal of Advances in Modeling Earth Systems• Journal of Geophysical Research:        – Atmospheres        – Biogeosciences        – Earth Surface        – Oceans        – Planets        – Space Physics        – Solid Earth• Paleoceanography• Radio Science• Reviews of Geophysics• Space Weather• TectonicsAuthorea provides industry leading writing tools for researchers. Authors may write in multiple markup languages (including richtext, Markdown, and LaTeX), can search and insert citations from the web or from another reference manager, and can insert data sources and rich media into the document itself.The partnership streamlines the formatting and submission process for authors. Whereas before authors could spend hours or days formatting documents to meet submission requirements, Authorea automatically formats, packages, and sends submissions to the journal, greatly reducing the time cost of submission for authors.Josh Nicholson, Chief Research Officer at Authorea, says: “We’re excited to partner and work with AGU to make the editing and submission of research articles easier and more efficient for earth and space science researchers. AGU publishes some of the world’s most important research and we’re excited to integrate to make publishing more streamlined and effective.”Brooks Hanson, Director of Publications at AGU, says: “As a leader in scientific collaboration and innovative publishing, we’re always looking for ways to improve our publications, scientific collaboration, and the experience for our authors. In partnering with Authorea, AGU provides our authors and researchers with another tool to simplify the submission process allowing them to spend more time focused on their research and less on formatting submissions.”Press ContactAdyam Ghebre, Outreach, Authorea+1 (646) 598-9285About AuthoreaAuthorea is the online document editor for research and the place where scientific collaboration happens. Authorea is trusted worldwide by leading researchers writing and publishing content in every discipline, from astrophysics to zoology. The online document editor supports a wide range of markup languages and scientific integrations, including the most popular citation management, graphing, and visualization plugins. Authorea is on a mission to accelerate science through a superior web-based research-writing platform that delivers powerful tools and capabilities to researchers.
Dear Editor,Herein is my response to manuscript ID XXXXX, entitled [“Why Hermione was better than Harry in almost every respect”] [by Ronald Frump and colleagues] to the [Journal of Squirrel-Puppy Relationships].The authors present [insert general overview of research and key findings]. This research is [well-suited/not-suitable] for the remit of the journal.[Insert any comments regarding potential conflicts of interest, or about areas of relevant expertise that you feel you are lacking].I recommend [accept/minor revisions/major revisions/oblivion], pending x, y, and z.Basic reportingFiguresAre the figures legible, relevant, and integrated into the textDataAre the supporting data included in the manuscript or in a relevant repositoryAre the data presented in a way that is consistent with the FAIR principles (https://www.force11.org/group/fairgroup/fairprinciples)Experimental designWas the way in which the research was conducted the best way to answer the relevant questionsValidity of the findingsAre the conclusions supported by the resultsDo the results contribute to the research field, irrespective of whether they are ‘negative’ or a replication studyGeneral commentsIs the language used appropriate for a scientific publicationIs the structure appropriateAbstractIs the abstract concise, and does it convey the main research findingsAre any key points of context or conclusions missingIntroductionDoes this cover the published literature sufficientlyDoes it provide enough context in which to place the current researchAre any key citations missingIs the history of the research conveyed at all for historical significanceDoes it finish with a paragraph summarising the relevance of the current researchMaterials and methodsAre the methods clear and easy to followCan the methods be replicated if neededAre the source materials/data openly available, and is appropriate justification provided if notWere any statistical analyses applied performed appropriatelyResultsAre the results presented in a coherent fashionAre the results reported in a way that is supported by the dataDiscussionAre the new results placed into context of the relevant literatureIs a balanced argument providedAre the full implications of the new results discussed in sufficient detailConclusionsAre the conclusions supported by the resultsAre they concise and written in an impactful way (not over-embellished)Additional commentsAnything else you want to add that doesn’t fit aboveCongratulations to the authors on a great piece of work, and I look forward to seeing their research [published/rejected/re-written with all of the references to my own tangentially-relevant work included.]Sincerely,[Ralph Lauren]ReferencesAny additional papers you have cited within your report
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The  participation of scholars and scientists in government has attracted attention since at least the time of Plato. The ancient Greek philosopher envisioned a philosopher-scientist running the Ideal State. However, his own experience in politics was far from ideal and he ended being sold as a slave by the tyrant he had tried to educate. Recently, there has been a resurgence of interest in the participation of academics in cabinets, largely due to the overtly anti-scientific message of the current US administration.In this short post, we aim to assess empirically how the cabinets of the seven countries recently banned from travel to the US (Iran, Iraq, Sudan, Syria, Somalia, Yemen, Libya) compare in number of advanced degrees (degrees above Masters level: MS, MBA, JD, PhD, MD, DVM) and advanced technical degrees (PhD, MD, DVM) compared to the White House cabinet.We used the Central Intelligence Agency (CIA) listing of world leaders  and information on Wikipedia and the web to identify the cabinet members of Iraq, Syria, Iran, Libya, Somalia, Sudan, Yemen, and the United States as of January 2017. All the data that we collected and used for this post is open and available under the Data git folder of this article.ResultsAmong a total of 245 eligible cabinet positions analyzed (ranging from 13 to 42 per country), 79 (32%) were filled by members that attained a graduate degree of higher education.Advanced Degrees: United States ranks firstThe United States' cabinet has the cabinet with the highest number of advanced degrees (MS, MBA, JD, PhD, MD, DVM), with over 60% of its members holding a Masters degree or above (Figure 1).  Iran is second in the list, with about half of its cabinet members holding advanced degrees. 
Sample article 1000

Alberto Pepe

and 2 more

What is the preprint server ArXiv?The ar\(\chi\)iv (pronounced "archive", since \(\chi\) = "chi") is the most popular preprint repository in the world. (Read: What is a preprint?) It was started in 1991 by physicist Paul Ginsparg to become a way to quickly and freely give the scientific community access to the submission-ready research papers, as e-prints. While the arXiv initially covered only the fields of physics and astronomy, it grew over time to encompass other fields, such as computer science, quantitative biology, statistics, and quantitative finance. The rise of arXiv has been mostly limited to fields that use LaTeX, a typesetting system for math-heavy documents. This is because (1) the most efficient way to submit papers to arXiv is by uploading a LaTeX file which gets compiled to PDF, and (2) pre-printing has historically been a practice popular in the hard sciences --- at CERN, it was performed via inter-library exchange of printed copies before the web even existed \cite{pepe2005cern}. However, in recent years, pre-prints are catching on as a legal and free mechanism to openly and quickly share research also in the life sciences (see ASAPbio, and BiorXiv, for example).How do ArXiv and Authorea compare?At first glance, ArXiv and Authorea may not seem related to one another. ArXiv is a content repository, while Authorea is a content creation system. However, Authorea - with the launch of a number of publishing features - is quickly becoming an open repository, as well. Below, we highlight some points of comparison between Authorea and ArXiv.1. More than just a collection of PDFs: web native papers.There is growing consensus in scholarly communication circles that academic publishing needs to move "beyond the PDF" (see Force 11 conference). The PDF is a great portable format for printing, but it is not the best format to share, discuss, and read on the web. Every article on arXiv, being a PDF, is non-actionable. In this respect, the arXiv is a "PDF dump".2. For LaTeX users. And for everyone else too!The ArXiv relies heavily on LaTeX. For Authorea, LaTeX is one of many  formats you can write in. Others include Markdown, and HTML (rich text, like Word!). Authorea offers a format-neutral, web-native platform. Regardless of the format, you render content on the web - not on a separate pane that compiles a PDF (side note, you can still export a PDF). The advantage: Authorea documents are not constrained to the hard sciences and to the LaTeX community. Authorea is for all scholars: from astrophysics to zoology. Authorea's rich text editor is a true WYSIWYG editor (What you see is what you get). It also has the ability to include as much LaTeX and mathematical notation as you need. Every document written in Authorea becomes a beautiful webpage.
William playfair excel exports
Bernersleeproposal

Josh Nicholson

and 3 more

Today's research is truly awesome. Researchers can now analyze and perform experiments that would have been thought impossible only a few decades ago. From the deep sequencing of nearly any animal genome with ease \cite{DePristo_2011} to the discovery of the Higgs Boson \cite{ATLAS_Collaboration_2012}, we are in a period of great innovation and understanding.  And yet, how we share our ideas (i.e. publishing) has not changed very much in nearly 350 years.  In short, scientists are doing 21st-century research, writing on 20th-century tools, and packaging it in 17th-century formats.The fact that research communication hasn't changed in hundreds of years may signal that it works, right? Well in some regards--yes, the work is persistent and we have copies of some of the world's most important ideas (yay librarians!). Yet, in many other regards research communication is failing us: data sharing is rare \cite{Alsheikh_Ali_2011}, the majority of work is hard to access (it's pay-walled) \cite{Bj_rk_2010}, publishing takes months to years to complete \cite{Himmelstein_2016}, and classical peer review does not detect major errors \cite{Smith_2010}. As a consequence, we're now seeing major problems with the reproducibility of findings in disciplines like cancer research and psychology \cite{Begley_2012,eLife_2017,Open_Science_Collaboration_2015}.To understand how we got to where we are today, it is useful to look at the history of research publishing, how and why it got started, and the changes that occured along the way. Here, we outline an very brief history of research publishing, with particular emphasis on preprints, in hopes of providing a stage to discuss what publishing might look like in the near future.A brief history of the research journalThe first journal article, published in 1655, by Philosophical Transactions marked a step towards the formalization of the communication of research in article format \cite{Oldenburg_1665}. As noted in the introductory editorial, research communication was seen as necessary for the advancement of research: "Whereas there is nothing more necessary for promoting the improvement of Philosophical Matters, than the communication of such" \cite{1665}.
Nicotinamide adenine dinucleotide (NAD+), the central redox coenzyme in cellular metabolism functions as a hydride group acceptor, forming NADH with concomitant oxidation of metabolites derived from carbohydrates, amino acids and fats. The NAD+/NADH ratio controls the degree to which such reactions proceed in oxidative versus reductive directions. Whereas fuel oxidation reactions require NAD+ as a hydride acceptor, gluconeogenesis, oxidative phosphorylation, ketogenesis, detoxification of reactive oxygen species (ROS) and lipogenesis require reduced co-factors, NADH and NADPH, as hydride donors (). In addition to its role as a coenzyme, NAD+ is the consumed substrate of enzymes such as poly-ADPribose polymerases (PARPs), sirtuins and cyclic ADPribose synthetases. In redox reactions, the biosynthetic structures of NAD+, NADH, NADP+ and NADPH are preserved. In contrast, PARP, sirtuin and cyclic ADPribose synthetase activities hydrolyze the linkage between the nicotinamide (Nam) and the ADPribosyl moieties of NAD+ to signal DNA damage, alter gene expression, control post-translational modifications and regulate calcium signalling.In animals, NAD+-consuming activities and cell division necessitate ongoing NAD+ synthesis, either through a de novo pathway that originates with tryptophan or via salvage pathways from three NAD+ precursor vitamins, Nam, nicotinic acid (NA) and nicotinamide riboside (NR). Dietary NAD+ precursors, which include tryptophan and the three vitamins, prevent pellagra. Though NR is present in milk, the cellular concentrations of NAD+, NADH, NADP+ and NADPH are much higher than those of other NAD+ metabolites, such that dietary NAD+ precursor vitamins are largely derived from enzymatic breakdown of NAD+. Thus, although milk is a source of NR, the more abundant sources of NR, Nam and NA are unprocessed foods, in which plant and animal cellular NAD+ metabolites are broken down to these compounds. Human digestion and the microbiome play roles in the provision of these vitamins in ways that are not fully characterized. In addition, the conventional NAD+ precursor vitamins, NA and Nam, have long been supplemented into human and animal diets to prevent pellagra and promote growth. Though NR has been available as a GMP-produced supplement since 2013 and animal safety assessment indicates that it is as nontoxic as Nam, no human testing has been reported.Different tissues maintain NAD+ levels through reliance on different biosynthetic routes and precursors (). Because NAD+-consuming activities frequently occur as a function of cellular stresses and produce Nam, the ability of a cell to salvage Nam into productive NAD+ synthesis through Nam phosphoribosyltransferase (NAMPT) activity versus methylation of Nam to N-methylnicotinamide (MeNam) regulates the efficiency of NAD+-dependent processes. NAD+ biosynthetic genes are also under circadian control. Both NAMPT expression and NAD+ levels decline in a number of tissues as a function of aging and overnutrition.High-dose NA but not high-dose Nam is prescribed to treat and prevent dyslipidemias, although its use is limited by painful flushing. Whereas it takes only ∼15 mg per day of NA or Nam to prevent pellagra, pharmacological doses of NA can be as high as 2-4 g. Despite the >100-fold difference in effective dose between pellagra prevention and dyslipidemia treatment, we proposed that the beneficial effects of NA on plasma lipids might simply depend on function of NA as an NAD+ boosting compound. According to this view, sirtuin activation would likely be part of the mechanism because Nam is an NAD+ precursor in most cells but inhibits sirtuins at high doses.On the basis of the ability of NR to elevate NAD+ synthesis, increase sirtuin activity and extend lifespan in yeast, NR has been employed in mice to elevate NAD+ metabolism and improve health in models of metabolic stress. Notably, NR allows mice to resist weight gain on high-fat diet, prevent noise-induced hearing loss and maintain the regenerative potential of stem cells in aging mice, providing a longevity advantage. In addition, the hepatic NAD+ metabolome has been interrogated as a function of prediabetic and type 2 diabetic mouse models. The data indicate that levels of liver NADP+ and NADPH, which are required for resistance to ROS, are severely challenged by diet-induced obesity, and that diabetes and the NAD+metabolome can be partially controlled while diabetic neuropathy can be blocked by oral NR.Data indicate that NR is a mitochondrially favoured NAD+precursor and in vivo activities of NR have been interpreted as depending on mitochondrial sirtuin activities, though not to the exclusion of nucleocytosolic targets. Similarly, nicotinamide mononucleotide (NMN), the phosphorylated form of NR, has been used to treat declining NAD+ in mouse models of overnutrition and aging. Beneficial effects of NMN have been shown to depend on SIRT1. However, because of the abundance of NAD+-dependent processes, the effects of NR and NMN may depend on multiple targets including sirtuins, PARP family members, cADPribose synthetases, NAD+-dependent oxidoreductases and NADPH-dependent ROS detoxification enzymes.To translate NR technologies to people, it is necessary to determine NR oral availability and utilization in different tissues. Here we began with targeted quantitative NAD+ metabolomics of blood and urine in a pilot experiment in which a healthy 52-year-old man took 1,000 mg of NR daily for 7 days. These data indicate that blood cellular NAD+ rose 2.7-fold after one dose of NR and that NA adenine dinucleotide (NAAD) unexpectedly increased 45-fold. We then performed a detailed analysis of 128 mice comparing oral NR, Nam and NA in a manner that eliminated the possibility of circadian artefacts. These data indicate that NR boosts hepatic NAD+ and NAD+- consuming activities to a greater degree than Nam or NA. Further experiments clarified that NR is a direct precursor of NAAD and that NAAD sensitively reports on increased NAD+ metabolism in mouse liver and heart. Finally, we performed a clinical study with 12 healthy human subjects at three single doses of NR. We demonstrated that NR supplementation safely increases NAD+metabolism at all doses and validated elevated NAAD as an unexpected, sensitive biomarker of boosting NAD+. The unique oral bioavailability of NR in mice and people and methods established herein enable clinical translation of NR to improve wellness and treat human diseases.ResultsOral NR increases human blood NAD+ with elevation of NAADGMP-synthesized NR showed no activity as a mutagen or toxin. Despite use as an over-the-counter supplement, no data addressing human availability were available. A healthy 52-year-old male (65 kg) contributed blood and urine before seven days of orally self-administered NR (1,000 mg per morning). Blood was taken an additional nine times during the first day and at 24 h after the first and last dose. Blood was separated into peripheral blood mononuclear cells (PBMC) and plasma before quantitative NAD+ metabolomics by liquid chromatography (LC)-mass spectrometry (MS), which was expanded to quantify methylated and oxidized metabolites of Nam. As shown in Supplementary Table 1 and , the PBMC NAD+ metabolome was unaffected by NR for the first 2.7 h. In six measurements from time zero through 2.7 h, NAD+ had a mean concentration of 18.5 μM; while Nam had a mean concentration of 4.1 μM and the methylated and oxidized Nam metabolite, N-methyl-2-pyridone-5-carboxamide (Me2PY), had a mean concentration of 2.6 μM. However, at 4.1 h post ingestion, PBMC NAD+ and Me2PY increased by factors of 2.3 and 4.2, respectively.In yeast, deletion of NR kinase 1 (NRK1) does not eliminate utilization of NR. As shown in , NR can be phosphorylyzed to Nam by purine nucleoside phosphorylase and still contribute to NAD+ synthesis through Nam salvage. However, as shown in , Nam concentration in the human subject's PBMCs merely fluctuated in a range of 2.6 to 7.1 μM throughout all 11 observations. The 4.2-fold increase in Me2PY concentration at the 4.1 h time point suggests that increased cellular NAD+accumulation is accompanied by increased NAD+-consuming activities linked to increased methylation and oxidation of the Nam product.In the subject's PBMCs at 7.7 and 8.1 h post ingestion, NAD+ and Me2PY peaked, increasing above baseline concentrations by 2.7-fold and 8.4-fold, respectively. At these times, unexpectedly, NAAD, the substrate of glutamine-dependent NAD+ synthetase, which is only expected to be produced in biosynthesis of NAD+from tryptophan and NA, was elevated from less than 20 nM to as high as 0.91 μM. Whereas NAAD lagged the rise in PBMC NAD+ by one time point, the relative rise in PBMC NAD+ was not as pronounced as the spike in NAAD, which was at least 45-fold above the baseline level. Although contrary to expectations, these data suggested that NR might be incorporated into NAAD after formation of NAD+ and chased back to the NAD+ peak as NAD+ declines.Complete NAD+ metabolomic data from the human subject's PBMCs, plasma and urine are provided in , , and Supplementary Tables 1-3. These data show that all of the phosphorylated compounds-NAMN, NAAD, NAD+, NADP+, NMN and ADPR-are found exclusively in blood cells and are not found in plasma or urine. Notably, the peak of NADP+, which represents cellular NADP+ plus NADPH oxidized in extraction, and the peak of ADPR, which signals an increase in NAD+-consuming activities, co-occur with peak NAD+. Using methods optimized for recovery of nucleotides, NR was not recovered. As shown in and , the major time-dependent waste metabolite in plasma and urine was Me2PY, which rose ∼10-fold from pre-dose to time points after NAD+ peaked in PBMCs.NR is the superior hepatic NAD+ precursor vitaminOn the basis of known NAD+ biosynthetic pathways, it was difficult to understand how levels of NAAD rose in human PBMCs after an oral dose of NR. Though NR did not elevate Nam in blood samples at any time during the n=1 experiment, it remained possible that NR was partially converted to Nam before salvage synthesis to NAD+. Such conversion to Nam might allow bacterial hydrolysis of Nam to NA by pncA gene products-potentially in the gut-and subsequent conversion to NAD+ through an NAAD intermediate. NAAD was reported in mouse liver when 500 mg kg −1 of radioactive Nam was injected intraperitoneally (IP) into the body cavity of mice. However, NAAD was observed in kidneys, ovaries, lung, heart and brain in addition to liver in mice IP-injected with 500 mg kg −1 of NA but not Nam. Moreover, careful analysis of mouse liver perfused with radioactive NA and Nam indicated that NAAD is produced from NA but not Nam at physiological concentrations. To our knowledge, formation of blood or tissue NAAD from oral administration of Nam or NR has never been observed.Although some mouse experiments have been done with IP administered NR at dosages of 1,000 mg kg −1 twice per day, NR is active as an oral agent at a daily dose of 400 mg kg −1 by supplementation into food and demonstrated potent NAD+boosting activity in the n=1 human experiment at 15 mg kg −1 (). On the basis of weight/surface area, the conversion between human adult dose and mouse dose is a factor of 12.3 (ref. ), suggesting that mice should be administered 185 mg kg −1 to achieve comparable levels of supplementation with the human pilot experiment. We therefore designed a reverse translational experiment in which mice were administered 185 mg kg −1 of NR or the mole equivalent doses of Nam and NA by oral gavage. To ascertain the timecourse by which these vitamins boost the hepatic NAD+ metabolome without the complication of circadian oscillation of NAD+ metabolism, we euthanized all mice at ∼2 pm. Thus, gavage was performed at 0.25, 1, 2, 4, 6, 8 and 12 h before tissue harvest. To stop metabolism synchronously, mouse livers were harvested by freeze-clamping. As shown in , we additionally performed saline gavages at all time points and euthanized mice for quantitative NAD+ metabolomic analysis to ensure that animal handling does not alter levels of NAD+ metabolites. The flat timecourses of saline gavages established methodological soundness. Baseline levels of hepatic NAD+ metabolites (pmol mg −1) at 2 pm were 1,000±35 for NAD+, 230±29 for Nam, 210±20 for NADP+, 66±13 for ADPR and <15 for all other NAD+metabolites. Hepatic levels of NA, NAR, NAMN, NAAD have baselines of <4. As a point of orientation to quantitative metabolomics in tissue samples, 1,000 pmol mg −1 is ∼1 mM, 200 is ∼200 μM and 10 is ∼10 μM.Targeted NAD+ metabolomics allows simultaneous assessment of functionally important metabolites such as NAD+ and NADP+along with metabolites that could serve as biomarkers of biosynthetic processes, such as NA, NAR, NAMN, NR, NMN and NAAD. In addition, quantification of increases in ADPR, Nam, MeNam, Me2PY and N-methyl-4-pyridone-5-carboxamide (Me4PY) on a common absolute scale with NAD+ permits assessment of increased NAD+-consuming activities associated with NAD+ precursor vitamin supplementation.Hepatic concentrations of 13 NAD+ metabolites were quantified in three to four mice at seven time points after gavage of saline and each vitamin. In addition, on each experimental day, three mice were gavaged with saline and euthanized to serve as time zero samples. Each vitamin produced a temporally distinct pattern of hepatic NAD+ metabolites. Consistent with rapid phosphorylation of NR and NAR by NR kinases, the only NAD+metabolites that do not produce hepatic peaks as a function of gavage of NAD+ precursor vitamins are NR and NAR ( Supplementary Fig. 1a,b). The accumulation curves of some metabolites as a function of each vitamin are strikingly similar. For example, the accumulation of NMN () is nearly identical to that of NAD+ () and NADP+ (), though at a scale of ∼1:400:40, respectively. In addition, the accumulation of Me4PY () is nearly identical to that of Me2PY ( Supplementary Fig. 1c).As shown in , NA produced the least increase in hepatic NAD+and also was 4-6 h faster than NR and Nam in kinetics of hepatic NAD+ accumulation. When NA was provided by oral gavage, liver NA peaked (340±30 pmol mg −1) in 15 min (). Hepatic NA appearance was followed by an expected peak of 220±29 NAAD at 1 h post gavage () and a rise in hepatic NAD+from 990±25 baseline to 2,200±150 at 2 h (). Hepatic NADP+due to NA () rose in parallel to that of hepatic NAD+. In the hours after gavage of NA, as hepatic NAD+ and NADP+ fell, there was clear evidence of enhanced NAD+-consuming activities with significant rises in ADPR (), Nam (), MeNam (), Me2PY ( Supplementary Fig. 1c) and Me4PY (). Thus, oral administration of NA doubled hepatic NAD+ from ∼1 to ∼2 mM through expected intermediates and produced an increase in NAD+ consumption and methylated products, MeNam, Me2PY and Me4PY. Net conversion by the liver of NA to Nam has been documented for decades. Essentially, the liver transiently elevates NAD+ biosynthetic capacity so long as NA is available while increasing NAD+-consuming activities, thereby making Nam available to other tissues. Expression of hepatic NNMT results in net production of MeNam from NAD+ precursors, which stabilizes SIRT1 protein in liver and is associated with better lipid parameters in mice and some human populations.As shown in and consistent with radioactive experiments, oral Nam was not used by the liver as NA because it did not produce a peak of NA at any time after gavage. Though there was a clear increase in hepatic NAD+ 2 h after Nam gavage, the Nam gavage drove increased hepatic NAD+ accumulation from 2 to 8 h with a peak at 8 h (). Nam gavage produced two peaks of Nam in the liver (), the first at 15 min, consistent with simple transport of Nam to liver. The second broad peak was coincident with elevation of NAD+ and NADP+ () and elevation of the NAD+-consuming metabolomic signature of ADPR (), MeNam, Me4PY and Me2PY ( and Supplementary Fig. 1c).Of the metabolites associated with NAD+-consuming activities, ADPR is the only one that must be formed from NAD+ because Nam, MeNam and the oxidized forms of MeNam could appear in liver from the gavaged Nam without conversion to NAD+. Interestingly, of three NAD+ precursor vitamins provided in bolus at equivalent oral doses, Nam provided the least increase in ADPR (). Whereas the area under the curve (AUC) of the Nam-driven rise in hepatic NAD+ indicated a ∼50% advantage of Nam over NA (), there was a >50% deficit in Nam-driven ADPR accumulation versus NA (). This is consistent with the idea that high-dose NA, though not an ideal hepatic NAD+ precursor, is effective as a cholesterol agent whereas Nam is not because high-dose Nam inhibits sirtuins. Notably, NR is active as a cholesterol-lowering agent in overfed mice.As shown in , Nam is expected to proceed through NMN but not NR, NAR, NaMN or NAAD en route to forming NAD+. Though there was no elevation of hepatic NR or NAR with oral Nam, there was also little elevation of hepatic NMN-this metabolite never reached a mean value of 5 pmol mg −1 at any time after Nam administration (). Surprisingly, as shown in , 2-4 h after oral Nam, NAAD was elevated to nearly 200 from a baseline of <2 pmol mg −1. Elevated NAAD occurred during the broad peak of elevated hepatic NAD+ and NADP+ (). These data suggest that the rise in NAAD is a biomarker of increased NAD+synthesis and does not depend on the conventionally described precursors of NAAD, namely NA and tryptophan.As shown in , NR elevated hepatic NAD+ by more than fourfold with a peak at 6 h post gavage. NR also produced the greatest elevation of NMN (), NADP+ (), Nam (), NAMN (), NAAD () and ADPR () in terms of peak height and AUC. Importantly, although gavage of Nam produces a peak of Nam in the liver at 15 min, the peak of Nam from NR gavage corresponds to the peak of NAD+, NMN, NADP+ and ADPR. These data establish that oral NR has clearly different hepatic pharmacokinetics than oral Nam. More NAD+ and NADP+ were produced from NR than from Nam. In addition, there was three times as much accumulation of ADPR, indicating that NR drives greater NAD+-consuming activities in liver than mole equivalent doses of Nam and NA. Though it has been speculated that NR would be a more potent NAD+ and sirtuin-boosting vitamin than conventional niacins, these are the first in vivo data in support of this hypothesis.As was seen in the n=1 human blood experiment, at time points in which the abundant NAD+ metabolites, NAD+ and NADP+, were elevated by NR by ∼twofold or more, NAAD rose from undetectable levels to ∼10% of the level of NAD+, thereby becoming a highly sensitive biomarker of increased NAD+metabolism. Though compounds such as MeNam, Me2PY and Me4PY are also correlated with increased NAD+ synthesis, they are waste products that can be produced without NAD+synthesis, whereas NAAD is functional NAD+ precursor.To test whether NAAD is also elevated in other tissues and through other routes of administration, we euthanized mice after 6 days of NR or saline by IP administration and analysed hepatic and cardiac NAD+ metabolomes. As shown in , steady-state levels of hepatic NAD+ and NADP+ are much more responsive to NR than are steady state levels of cardiac NAD+and NADP+. However, cardiac NAD+ metabolism was clearly elevated on the basis of statistically significant elevation of NMN, Nam, MeNam and Me4PY. Among these metabolites, only NMN, which was elevated in the heart by approximately twofold, could be considered diagnostic for increased NAD+formation. In addition, NAMN and NAAD were increased by about ∼100-fold in heart and liver with NAAD rising to ∼10% of the concentration of heart and liver NAD+ in supplemented animals. These data validate NAAD as a metabolite that sensitively and reliably marks increased NAD+ metabolism even in tissues in which steady-state levels of NAD+ are little changed.NR is incorporated into NAADAppearance of hepatic NAAD after gavage of Nam or NR, and of hepatic NAMN after gavage of NR suggested that there is an NAD+ and/or NMN deamidating activity when NAD+ and NADP+ levels are high. Alternatively, high levels of NAD+metabolites might inhibit glutamine-dependent NAD+synthetase, thereby resulting in accumulation of NAMN and NAAD derived from tryptophan. To test whether NR is incorporated into the peak of NAAD that appears after NR gavage, we synthesized NR with incorporation of deuterium at the ribosyl C2 and 13C into the carbonyl of the Nam moiety. This double-labelled NR was provided to 15 mice by oral gavage at an effective dose of 185 mg kg −1 with the same experimental design used in pharmacokinetic analysis of the three vitamins. The effect of labelled oral NR on the hepatic NAD+metabolome was first assessed at 2 h after gavage-a time point before the rise in the steady-state level of NAD+ ().As shown in , at 2 h, 54% of the NAD+ and 32% of the NADP+contained at least one heavy atom while 5% of the NAD+ and 6% of the NADP+ incorporated both heavy atoms. Because >50% of hepatic NAD+ incorporates label before a rise in NAD+accumulation, it is clear that the NAD+ pool is dynamic. As shown in , the majority of hepatic Nam and MeNam following gavage of double-labelled NR incorporated a heavy atom, necessarily the 13C in Nam. Because NR drives increased NAD+synthesis and ADPR production (), the liberated singly labelled Nam becomes incorporated into NMN and NAD+ in competition with double labelled NR, thereby limiting subsequent incorporation of both labels into the NAD+ pool.Appearance of a peak of NAAD after NR administration could either be due to inhibition of de novo synthesis of NAD+ or from a deamidating activity that occurs at high NAD+. If NAAD is not derived from ingested NR, then it should not incorporate heavy atoms. However, if NAAD is derived from ingested NR, then it should incorporate heavy atoms that reflect the rate at which the putative deamidating activity occurs with respect to NAD+-consuming activities and the degree of heavy atom incorporation into NAD+. As shown in , at the 2 h time point, NAAD contained roughly the same heavy atom composition as NAD+ (), that is, 45% contained at least one heavy atom and 8% incorporated both heavy atoms. Thus, NR is the biosynthetic precursor of NAD+, NADP+ and NAAD. The data suggest that the activity that converts NAD+ to NAAD occurs at high NAD+concentrations at a rate comparable to the rate of NAD+turnover to Nam. Given the lack of formation of NA from either Nam or NR in the mouse liver (), the only other reasonable possibility is that NMN is deamidated to NAMN when NAD+metabolism increases. Incorporation of the Nam and ribosyl moieties of NR into NAAD establishes this metabolite as both a biomarker of increased NAD+ metabolism and a direct product of NR utilization.NR safely increases PBMC NAD+ metabolism and NAAD in peopleThe n=1 human experiment illustrated the potential of 1,000 mg NR to boost human NAD+ metabolism. We therefore conducted a controlled experiment with 12 consented healthy men and women to determine the effect of three single doses of NR on blood and urine NAD+ metabolites with monitoring of subjects for potential adverse events. Considering that the recommended daily allowance of vitamin B3 as Nam or NA is ∼15 mg per adult, we tested three doses of the higher molecular weight compound NR Cl (100, 300 and 1,000 mg) that correspond to 2.8, 8.4 and 28 times recommended daily allowance. Body weights of the subjects varied. However, we had already observed the timecourse of changes in a human NAD+ metabolome with daily doses of 1,000 mg in a healthy 65 kg male. Participants were randomized to receive doses of NR in different sequences with 7-day washout periods between data collection. Participants and investigators were blinded to doses. Blood and urine collections were performed over 24 h following each dose. Participants were asked to self-report perceived discomforts.At 500 mg of niacin, 33 of 33 participants experienced flushing compared with one out of 35 participants on placebo. In this study, two individuals self-reported flushing at the 300 mg dose but not at the 100 mg or 1,000 mg dose, and two individuals self-reported feeling hot at the 1,000 mg dose but not at lower doses. Over the total of 36 days of observation of study participants, there were no serious adverse events and no events that were dose-dependent. To assess whether NR might be associated with authentic and dose-dependent episodes of flushing, future experiments will incorporate a validated flushing symptom questionnaire.As shown in and Supplementary Data Files 1 and 2, the NAD+metabolome was quantified in the PBMC and plasma fractions at pre-dose and at 1, 2, 4, 8 and 24 h after receiving oral NR. Urinary NAD+ metabolites ( Supplementary Data File 3) were quantified in pre-dose, 0-6 h, 6-12 h and 12-24 h collections.As shown in , inbred, chow-fed male mice supplemented with NAD+ precursor vitamins by gavage and euthanized at ∼2 pm produced hepatic NAD+ metabolomic data with little variation. However, blood samples from people exhibited greater variation, due to differing baseline levels of metabolites and variable pharmacokinetics, both of which are likely due to genetic and nutritional changes between subjects (). In PBMCs, eight key metabolites were quantified in at least 10 subjects at all time points at each dose. For each metabolite, we plotted average concentration as a function of dose and time, calculated whether NR elevated that metabolite, plotted the averaged peak concentration of the metabolite as a function of dose, and calculated the dose-dependent AUC of the metabolite attributable to NR supplementation. Unlike a drug metabolism study in which metabolites appear only after administration, most NAD+ metabolites are present before supplementation, such that the AUC attributable to supplementation is a time-zero baseline-subtracted AUC. Thus, it is possible to calculate not only the AUC rise in metabolites but also the per cent increase in AUC in these metabolites attributable to dose-dependent NR supplementation.Collapsing the data into pre-dose versus 24 h levels of each metabolite at all doses, NR significantly elevated PBMC NAD+ (), MeNam () and Me2PY () and significantly elevated PBMC NAAD () at 8 h. In contrast, NR did not produce a statistically significant all-dose elevation of NMN () or Nam () at any time point.The averaged peak concentration of MeNam (), Me2PY () and NAAD () increased monotonically with increased NR doses. Of these metabolites, only NAAD was below the detection limit in individuals before they took NR, qualifying this metabolite as a biomarker of supplementation. Nam () exhibited no tendency towards higher cellular concentrations with higher doses of NR. NMN tended to rise () and NAD+ rose () to higher concentrations of ∼2 and 20 μM, respectively, in people taking 300 and 1,000 mg doses of NR versus people taking 100 mg doses. Thus, 100 mg supplementation produced an average ∼4±2 μM increase in PBMC NAD+, whereas the higher doses produced average ∼6.5±3.5 μM increases in PBMC NAD+. No sex differences were discovered.As was first seen in the n=1 human experiment and in mouse liver experiments, NAAD is the most sensitive biomarker of effective NAD+ supplementation because it is undetectable in the blood of people before supplementation. At all doses, the peak shape of NAAD indicated that NAD+ metabolism is most greatly boosted at 8 h with significant supplementation at 4 h and significant supplementation remaining at 24 h. At the 8 h peak, the average concentration of NAAD was elevated to 0.56±0.26, 0.74±0.27 and 1.24±0.51 μM in PBMCs from volunteers taking 100, 300 and 1,000 mg single doses of NR, respectively.We plotted pre-dose-subtracted AUCs of each metabolite as a function of dose of NR. With the exception of Nam, the levels of which were unaffected by NR, NR produced or tended to produce dose-dependent elevation of the entire NAD+metabolome (). In plasma, levels of meNam, me2PY and me4PY also rose in a dose-dependent manner and were identified at concentrations similar to those in the PBMC fraction. The methylated and oxidized Nam derivatives were accompanied by low levels of NAR, which increased with higher doses of NR. Urinary metabolites were similar to plasma metabolites.In Supplementary Table 4, the average 24 h baseline-subtracted AUC of each metabolite is expressed as a percentage increase in that metabolite at each dose of NR. Once again, Nam and NMN showed essentially no increase in blood cell concentrations with respect to baseline concentrations: averaged AUCs never rose by 50% above baseline. However, NAD+, meNam, me2PY and NAAD rose or tended to rise in dose-dependent manners. The effect size of the rise in NAAD (∼2,900%) was much greater than the effect sizes of the rise in me2PY (∼600%), meNam (∼200%) or NAD+ (∼90%). AUC increases of NAAD, me2PY and meNam achieved statistical significance with respect to lower doses of NR.DiscussionDespite >75 years of human use of NA and Nam and >10 years of preclinical NR research, there has never been a quantitative metabolomic or pharmacokinetic comparison of the three NAD+ precursor vitamins in any system. In terms of elevation of mouse liver NAD+, we discovered that NR is more orally bioavailable than Nam, which is more orally bioavailable than NA (). The three precursors also differ in the degree to which they promote accumulation of ADPR, a measure of sirtuin and other NAD+-consuming activities. As shown in , the ability of NR to elevate ADPR exceeded that of Nam by ∼3-fold. This validates NR as the favoured NAD+ precursor vitamin for increasing NAD+ and NAD+-consuming activities in liver.NR, Nam and NA each have unique pharmacokinetic profiles in mouse liver, both in terms of kinetics of NAD+ formation and the population of NAD+ metabolites as a function of time. As shown in , Nam is the only vitamin precursor of NAD+ that produces elevated hepatic Nam 15 min after oral administration and, as shown in , NA is the only precursor that produces elevated NA 15 min after oral administration. These data exclude the possibility that all three vitamins are utilized through the Preiss-Handler pathway in liver or that oral NR is used exclusively as Nam. Additionally, we have demonstrated that utilization of both NR and extracellular NMN are limited by activity of the NR kinase pathway.When PBMCs were analysed from the first person to ingest NR, NAAD was observed to increase at least 45-fold from a baseline of less than 20 nM to a peak value of nearly 1 μM. This occurred concomitant with a rise in NAD+ from ∼18.5 to 50 μM. NAAD was also observed to be elevated in liver when mice were orally administered NAD+ precursor vitamins. In addition, NR led to striking elevation of NAAD in the heart, a tissue that increases NAD+ metabolism without increasing steady-state NAD+.Surprisingly, NA, the only precursor expected to proceed to NAD+ through an NAAD intermediate, produced the least NAAD. Indeed, although Nam and NR never produced peaks of hepatic NA or NAR, both produced peaks of hepatic NAAD during the periods in which these compounds elevated hepatic NAD+. The temporal basis of the NAAD excursions suggested that elevating NAD+ () not only stimulates accumulation of NAD+-consumption products ADPR (), Nam (), MeNam () and Me4PY (), but also stimulates retrograde production of NAAD () and NAMN (). According to this view, as the rate of NAD+synthesis increases, a previously unknown activity would deamidate NAD+ to NAAD. Alternatively, similar conditions could result in NMN deamidation, giving rise to NAMN and NAAD.In mouse liver, the apparent flux through this pathway is quite significant: the NR-driven peak of NAAD amounted to 10% of the NR-attributable peak of NAD+. Production of high levels of NAAD from NAD+ could therefore account for the NR-stimulated peak in NAMN because NAMN adenylytransferase is a reversible enzyme. Striking elevation (∼100-fold) of NAAD was also seen in the heart of mice supplemented with NR after 6 days of IP administration ().The hypothesis that NAAD is formed from NR in vivo was tested by administering NR labelled in the Nam and ribosyl moieties. As shown in , NR stimulates appearance of double-labelled NAAD (8% of total) at the same time in which 5% of NAD+ is double-labelled. The biochemical basis for a potential NAD+deamidation reaction is unknown. However, glutamine-dependent NAD+ synthetase is irreversible. One intriguing possibility is that NAAD is formed by the long-sought enzyme that forms intracellular NAADP. According to this view, an NADP deamidase may be responsible for formation of NAADP-this same activity might deamidate NAD+ at high concentrations forming NAAD. Unlike ADPR and methylated Nam waste products, NAAD is not only a biomarker of elevated NAD+metabolism but also a reserve metabolite that contributes to elevated NAD+ over time.Finally, in the first clinical study of NR, we established that blood NAD+ metabolism is increased by single 100, 300 and 1,000 mg doses of NR without dose-dependent increases in PBMC Nam or serious adverse events.In people, as in mice, NAAD is the most sensitive biomarker of boosting NAD+. While 1,000 mg of NR elevated PBMC NAD+from ∼12 to ∼18 μM and generated a ∼90% increase in 24 h AUC, NAAD was elevated from below the limit of quantification to ∼1 μM and generated a 2,900% increase in 24 h AUC. The ability to detect NAAD in human samples is expected to aid conduct of clinical testing of NR. Availability of over-the-counter supplements can complicate clinical trials because patients may enrol to obtain compounds they expect to bring benefits and be inclined to take supplements in case they are assigned to placebo. Detection of NAAD should therefore be incorporated in phase II and III trials to eliminate the confounding effects of off-study NR use.MethodsMaterials and reagentsNR Cl was produced under GMP conditions. Me2PY and Me4PY were purchased from TLC PharmaChem Inc. (Vaughan, Ontario, Canada). All other unlabelled analytes were purchased from Sigma-Aldrich (St Louis, MO) at highest purity. Internal standards [ 18O 1]- Nam and [ 18O 1]-NR were prepared as described. [ 18O 1-D 3]-MeNam was prepared by alkylation of [ 18O 1]-Nam with deuterated iodomethane. 13C-NA and [D 4]-NA were purchased from Toronto Chemical Research (Toronto, Ontario, Canada) and C/D/N Isotopes, Inc. (Pointe-Claire, Quebec, Canada), respectively. To prepare [ 13C, D 1]-NR, we first converted 13C-NA to 13C-Nam (ref. ) and D-[2-D 1]-ribose (Omicron Biochemicals, South Bend, IN) to the labelled D-ribofuranose tetraacetate. The labelled D-ribofuranose-tetraacetate and Nam were then used to synthesize double-labelled NR. [ 13C]-labelled nucleotides standards were prepared by growing yeast in U- 13C-glucose and extracting as described.Pilot human experimentAfter overnight fasting, a healthy 52-year-old male self-administered 1,000 mg of NR Cl orally at 8 am on 7 consecutive days. Blood and urine were collected for quantitative NAD+metabolomic analysis. The participant took 0.25 g of NA to assess sensitivity to flushing and self-reported painful flushing that lasted 1 h. No flushing was experienced on NR. The study was submitted for approval by the University of Iowa institutional review board (IRB), which ruled it not subject to human subjects research on the basis of informed self-administration.MiceFor gavage experiments, 12-week-old male C57Bl/6J mice (Jackson Laboratories, Bar Harbour, ME) were housed 3-5 mice per cage on a chow diet (Teklad 7013) for one week before the experiment. Body weight-matched groups were randomly assigned to be given either 185 mg NR Cl per kg body weight ( n=3) or equimole amounts of NA ( n=4) or Nam ( n=4) by saline gavage. On each experimental day, a saline injection ( n=3) was performed and served as time point zero and an additional saline gavage ( n=3) timecourse was performed. To avoid circadian effects, timecourses were established such that all tissue harvests were performed at ∼2 pm. Double-labelled NR ( n=3) was also administered by gavage against a saline control ( n=3). With protocols approved by the University of Iowa Office of Animal Resources, mice were live-decapitated and the medullary lobe of the liver was freeze-clamped at liquid nitrogen temperature. For IP experiments, 6-8-week-old, male C57Bl/6J mice were injected with either PBS or 500 mg NR Cl per kg body weight for 6 days. With protocols approved by the Institutional Animal Care and Use Committee of University of Utah, mice were anaesthetised by chloral hydrate and livers and hearts were freeze-clamped at liquid nitrogen temperature. Tissues were stored at −80 °C before analysis.Clinical trialA randomized, double-blind, three-arm crossover pharmacokinetic study of oral NR chloride was performed at 100, 300 and 1,000 mg doses (Clinicaltrials.gov Identifier NCT02191462). Twelve healthy, non-pregnant subjects (six male and six female) between the ages of 30 and 55 with body mass indices of 18.5-29.9 kg m −2 were recruited and randomized to one of three treatment sequences after screening, passing eligibility criteria and providing informed consent. Overnight fasted subjects received a single morning dose of either 100 mg, 300 mg, or 1,000 mg of NR on 3 test days separated by 7-day periods in which no supplement was given. To evaluate pharmacokinetics, blood was collected and separated into plasma and PBMC fractions for analysis of the NAD+metabolome at pre-dose and again at 1, 2, 4, 8 and 24 h. Urine was collected pre-dose and in 0-6 h, 6-12 h and 12-24 h fractions. Safety, vitals, biometrics, complete blood counts and a comprehensive metabolic panel were assessed at time zero and 24 h after each dose. The study was reviewed and approved by the Natural Health Products Directorate, Health Canada and IRB Services, Aurora, Ontario. Written informed consent was obtained from each subject at the screening visit before all study-related activities.Exclusion criteria: women who were pregnant, breastfeeding or planning to become pregnant during the course of the trial; use of natural health products/dietary supplements within 7 days before randomization and during the course of the study; use of vitamins or St John's Wort 30 days before study enrolment; use of supplements containing NR within 7 days before randomization and the course of the study; use of nutritional yeast, whey proteins, energy drinks, grapefruit and grapefruit juice, dairy products, alcohol for 7 days before the study; consumption of >2 standard alcoholic drinks per day or drug abuse within the past 6 months; smoking; blood pressure ⩾140/90; use of blood pressure medications; use of cholesterol-lowering medications; metabolic diseases or chronic diseases; use of acute over-the-counter medication within 72 h of test product dosing; unstable medical conditions as determined by the qualified investigator; immune compromised conditions including organ transplantation or human immunodeficiency virus; clinically significant abnormal lab results at screening (for example, aspartate transaminase and/or alanine transaminase >2 × upper limit of normal (ULN), and/or bilirubin >2 × ULN); planned surgery during the course of the trial; history of or current diagnosis of any cancer (except successfully treated basal cell carcinoma or cancer in full remission >5 years after diagnosis); history of blood/bleeding disorders; blood donation in the previous 2 months; participation in a clinical research trial within 30 days before randomization; allergy or sensitivity to study supplement ingredients or to any food or beverage provided during the study; cognitive impairment and/or inability to give informed consent; any other condition which in the qualified investigator's opinion may have adversely affected the subject's ability to complete the study or its measures or which may have posed significant risk to the subject.Sample preparation and targeted quantitative metabolomicsDual extractions were carried out for complete analysis of the NAD+ metabolome. For analysis of NR, Nam, NA, MeNam, Me2PY and Me4PY (group A analytes), samples were spiked with 60 pmol of [ 18O 1]-Nam, [ 18O 1]-NR and [D 3, 18O 1]-MeNam and 240 pmol [D 4]-NA (internal standard (IS) A). For analysis of NAD+, NADP+, NMN, NAR, NAMN, NAAD and ADPR (group B analytes), samples were dosed with 13 C-yeast extract (IS B) as described.Human samples. One hundred microlitre of urine was mixed with 20 μl of IS A in 5% (v/v) formic acid or IS B in water for the analysis of group A and B analytes, respectively. Fifty microlitre of ice-cold methanol was added and the mixture vortexed before centrifugation at 16.1k g at 4 °C for 10 min. Supernatants were injected without further dilution and analysed as described below. Standard curves and quality controls for the complete analysis were prepared in the same manner as described for urine samples but in water.To quantify group A analytes in plasma, 100 μl of plasma was added to 20 μl of IS A prepared in 5% (v/v) formic acid and mixed with 400 μl of ice-cold methanol. The mixture was allowed to sit on ice for 20 min then centrifuged as described for urine. After drying under vacuum overnight at 35 °C, the sample was reconstituted in 100 μl of water. To quantify group B analytes, 100 μl of plasma was added to 10 μl of IS B in water and mixed with 300 μl of acetonitrile with vortexing for 15 s. After briefly resting on ice, the samples were centrifuged as above. Supernatants were applied to Phenomenex Phree SPE cartridges (Torrance, CA) and the flow-through collected. 200 μl of aqueous acetonitrile (four volumes acetonitrile: one volume water) was also applied and the flow-through collected. The flow-through from both steps was combined and dried via speed vacuum. Samples were reconstituted in 60 μl of water. Standard curves and quality controls for both analyses were prepared in donor plasma (University of Iowa DeGowin Blood Center, Iowa City, IA) and extracted using the same method employed for plasma samples.PBMC fractions were thawed on ice and simultaneously extracted for both A and B analyses when possible. 100 μl of sample was added to either 20 μl of IS A in 5% formic acid (v/v) or 10 μl IS B in water for quantification of group A and B analytes, respectively. Samples were then mixed with 300 μl of acetonitrile and vortexed for 15 s. Samples were shaken for 5 min at 40 °C then centrifuged as described above. For group A analytes, supernatants were dried via speed vacuum overnight at 35 °C after this step. For group B analytes, supernatant was applied to Phenomenex Phree SPE cartridges and treated in the same manner as described above for quantification of group B analytes in plasma. Immediately before analysis, samples were reconstituted in either 100 μl of 10 mM ammonium acetate with 0.1% formic acid (for group A analyte quantification) or 100 μl of 5% (v/v) aqueous methanol (for group B analyte quantification). Standard curves were prepared in water and processed in the same manner as samples.Murine samples. For the IP experiment, male C57Bl/6J mice were injected with either saline or NR Cl (500 mg kg −1) for 6 days. On the day of tissue harvests, mice were anaesthetized by chloral hydrate before collection of liver and heart both of which were freeze-clamped in liquid nitrogen. All tissues were stored at −80 °C before extraction.Murine liver and heart obtained by freeze-clamp were pulverized using a Bessman pulverizer (100-1,000 mg size) (Spectrum Laboratories, Rancho Dominguez, CA) cooled to liquid N 2 temperatures. Each pulverized liver and heart sample was aliquoted (5-20 mg) into two liquid N 2 cooled 1.5 ml centrifuge tubes, which were stored at −80 °C until analysis. Before extraction, murine liver sample identities were masked and sample order randomized.Before extraction, IS A and IS B were added to separate aliquots resting on dry ice for quantification of group A and B analytes, respectively. Samples were extracted by addition of 0.1 ml of buffered ethanol (three volumes ethanol: one volume 10 mM HEPES, pH 7.1) at 80 °C. Samples were vortexed vigorously until thawed, sonicated in a bath sonicator (10 s followed by 15 s on ice, repeated twice for liver and thrice for heart), vortexed, then placed into a Thermomixer (Eppendorf, Hamburg, Germany) set to 80 °C and shaken at 1,050 r.p.m. for 5 min. Samples were centrifuged as described above. Clarified supernatants were transferred to fresh 1.5 ml tubes and dried via speed vacuum for two h. Before LC-MS analysis, samples were resuspended in 40 μl of 10 mM ammonium acetate (>99% pure) in LC-MS-grade water. Sample preparation following [ 13C 1, D 1]-NR administration differed only in the following respect. In lieu of IS A, 60 pmol of [D 4]-Nam and [D 3, 18O 1]-MeNam and 240 pmol of [D 4]-NA were added to sample. Standard curves were prepared in water without extraction.LC-MS. Separation and quantitation of analytes were performed with a Waters Acquity LC interfaced with a Waters TQD mass spectrometer operated in positive ion multiple reaction monitoring mode as described. MeNam, Me2PY and Me4PY were added to the analysis and detected using the following transitions: MeNam ( m/ z 137>94, cone voltage=8 V, collision energy=20 V); Me2PY ( m/ z 153>107, cone voltage=44 V, collision energy=22 V); and Me4PY ( m/ z 153>136, cone voltage=24 V, collision energy=14 V). For the analysis of urine, plasma and murine liver, heart and blood cells, group A analytes were separated as described for the acid separation. In blood cells, group A analytes were separated on a 2.1 × 150 mm Synergy Fusion-RP (Phenomenex, Torrance, CA) using the same gradient and mobile phase as described for the acid separation. For human samples, group B analytes were separated using the mobile phase and gradient as previously described for the alkaline separation. Murine liver and heart extracts were analysed using a slightly altered alkaline separation on a 2.1 × 100 mm Thermo Hypercarb column. Specifically, flow rate was increased to 0.55 ml min −1 and run time shortened to 11.6 min. Separation was performed using a modified gradient with initial equilibration at 3% B, a 0.9 min hold, a gradient to 50% B over 6.3 min, followed by a 1 min wash at 90% B and a 3 min re-equilibration at 3% B.Analytes in human plasma were quantified by dividing their peak areas by IS peak areas and comparing the ratio to a background-subtracted standard curve. Analytes in all other matrices were quantified by dividing their peak areas by IS peak areas and comparing the ratio to a standard curve in water. Urinary metabolites were normalized to creatinine concentrations. Hepatic metabolites were normalized to wet liver weights.For both human and mouse samples, samples were transferred to Waters polypropylene plastic total recovery vials (Part # 186002639) after extraction or preparation and stored in a Waters Acquity H class autosampler maintained at 8 °C until injection. In all cases, 10 μl of extract was loaded onto the column.For analysis of enrichment in murine liver, metabolites were separated following the same LC procedure described above and detected using a Waters Premier Q-TOF operated in positive ion, full-scan mode. Leucine enkephalin was infused to ensure high mass accuracy. Enrichment data were corrected for natural isotope abundance based on theoretical isotope distribution, 13-carbon abundance skew and the purity of the labelled standard (3/97% [ 13C 1]-NR/[ 13C 1, D 1]-NR). Quantification was performed on the Waters TQD as described above and used to determine the quantity of non-labelled and labelled metabolites. Separation and quantification of analytes was performed with a Waters Acquity LC interfaced with a Waters TQD mass spectrometer operated in positive ion multiple reaction monitoring mode. Enrichment analysis was performed with a Waters Q-TOF Premier mass spectrometer operated in positive ion, full-scan mode with the same LC conditions as described for non-enrichment experiments.Statistical analysesStatistical analyses were performed in GraphPad Prism version 6.00 for Windows, (La Jolla, CA). Sample sizes were sufficiently powered (1- β=0.8, α=0.05) to detect at least a 2-fold difference in NAD+ concentration. Murine liver data were analysed using two-way analysis of variance, whereas human blood cells were analysed using a repeated measure, two-way analysis of variance. Holm-Sidak and Tukey's multiple comparisons tests were performed when comparing more than two groups. AUCs in blood cells were calculated after subtracting pre-dose metabolite concentrations of each experimental series. For mouse data, AUCs were calculated as described after subtracting the saline group for that day and propagating error. Data are expressed as means±s.e.m. Group variances were similar in all cases. A P value<0.05 was considered significant.
Fig1eric
Here we describe "Innovation and Entrepreneurship in Medicine" (IEMed), a short elective course that exposed medical students to innovation and entrepreneurship in digital health.IntroductionEntrepreneurial and software-driven technology companies, known as "tech", are reinventing established industries, including transportation, national defense, and even healthcare. For the past three years, investment in digital health - a broad category of tech including analytics, biosensing, population health management, medical records, and software-driven devices - has exceeded $4B annually. However, implementation of techology into clinical workflow has been slow.Medical students and young physicians are well positioned to contribute to tech's foray into biomedicine for two reasons. First, they are comfortable with technology, which permeates most aspects of their lives as consumers. Second, they possess insight about unmet clinical needs and care delivery.Unfortunately, medical students are not exposed to opportunities in tech even though industry efforts can represent "translational research in its rawest form".ApproachTo address this problem, we created an elective course for second-year medical students at our institution (a private medical school in a large metropolitan city in the United States) called IEMed, which was held in the fall semester and lasted three months. We developed the following learning objectives:Assess a startup using the business model canvas as a framework.Learn about healthcare economics and reimbursement.Appreciate how behavioral economics assesses decision-making.Review advances in digital health and health information technology.Survey accelerators, incubators, and other startup resources.Learn about patents and the fundamentals of intellectual property.Understand the role of angel, seed, & venture capital investors.Meet like-minded students, clinicians, engineers, and startup founders.See how academic clinicians collaborate with the tech industry.Nine students enrolled in 2014, and ten students enrolled in 2015. Each learning objective was explored through a lecture and Q&A featuring a guest speaker with relevant experience. Sessions were also accompanied by suggested readings. We recorded videos of several sessions to provide educational assets to a broader audience. The full course schedule, reading materials, and videos of select sessions were available through a course website.Students also completed a project in teams of three. Each team selected and evaluated a startup company using the "business model canvas": a visual chart describing market strategy, value proposition, infrastructure, customers, finances, etc. ( Figure 1). Each week, teams focused on one component of the canvas, learned more about their startup by conducting research online, or speaking with founders of the startup and/or potential customers, and shared their findings with the class. We also connected medical students with MBA students at our institution's business school to provide input. At the end of the course, teams presented their canvases and discussed clinical implementation and business development strategies.
Abstract goes here. No heading necessary. The exporter will automatically turn this text before the first heading into an abstract.IntroductionLorem ipsum dolor sit amet, consectetur adipiscing elit. Donec at fringilla lorem. Proin rhoncus scelerisque sem sit amet posuere. Pellentesque blandit aliquet ipsum, eu cursus justo porta a. Fusce ligula tellus, dapibus ut lectus et, euismod elementum nisi. Fusce pulvinar magna non purus feugiat, nec elementum arcu porttitor. Nullam sit amet nulla non leo sagittis varius in tincidunt libero. Duis tristique aliquam commodo. Mauris eget luctus nibh, quis interdum metus. Phasellus rhoncus facilisis neque, quis pellentesque libero consequat non. Pellentesque eu vulputate ante, id lacinia felis. Pellentesque nec imperdiet nulla. Etiam quis justo sollicitudin, faucibus leo sed, dignissim nibh. Praesent ut ornare risus. Duis et fringilla odio. Ut at cursus elit.Nullam nibh nisi, rhoncus a dictum fringilla, egestas a nisi. In a dapibus lacus. Nulla est nulla, cursus vel orci quis, suscipit volutpat sapien. Quisque molestie nunc et nunc consectetur, eget rutrum diam dapibus. Maecenas efficitur dolor ac erat mattis, quis egestas orci tristique. Nullam vel odio at neque gravida consequat sed sed nisl. Suspendisse potenti. Aenean consequat condimentum cursus. Pellentesque habitant morbi tristique senectus et netus et malesuada fames ac turpis egestas. Curabitur pharetra enim et accumsan venenatis.Class aptent taciti sociosqu ad litora torquent per conubia nostra, per inceptos himenaeos. Sed mollis tellus in tellus porttitor, a euismod massa commodo. Nulla vestibulum urna euismod, mollis lacus sed, sollicitudin libero. Sed varius lobortis felis eget pretium. Mauris varius metus augue, at luctus orci pharetra eget. Vivamus ac arcu urna. Cras ut augue ac velit porttitor tristique. Curabitur luctus, mi cursus consequat hendrerit, arcu est blandit urna, et rhoncus tortor sapien quis augue. Mauris mattis ac quam nec egestas. Pellentesque quis ipsum non odio venenatis pharetra. Quisque et hendrerit leo. Vivamus commodo neque nec ligula ornare, quis mattis velit fermentum.Grant informationPlease state who funded the work discussed in this article, whether it is your employer, a grant funder etc. Please do not list funding that you have that is not relevant to this specific piece of research. For each funder, please state the funder’s name, the grant number where applicable, and the individual to whom the grant was assigned. If your work was not funded by any grants, please include the line: ‘The author(s) declared that no grants were involved in supporting this work.’AcknowledgmentsThis section should acknowledge anyone who contributed to the research or the article but who does not qualify as an author based on the criteria provided earlier (e.g. someone or an organization that provided writing assistance). Please state how they contributed; authors should obtain permission to acknowledge from all those mentioned in the Acknowledgments section.Please do not list grant funding in this section.References can be listed in any standard referencing style and should be consistent between references within a given article.Reference management systems such as Zotero provide options for exporting bibliographies as BibTeX files. BibTex is a bibliographic tool that is used with LaTeX to help organize the user’s references and create a bibliography. This template contains an example of such a file, sample.bib, which can be replaced with your own.
Dear Editor,Herein is my response to manuscript ID XXXXX, entitled [“Why Hermione was better than Harry in almost every respect”] [by Ronald Frump and colleagues] to the [Journal of Squirrel-Puppy Relationships].The authors present [insert general overview of research and key findings]. This research is [well-suited/not-suitable] for the remit of the journal.[Insert any comments regarding potential conflicts of interest, or about areas of relevant expertise that you feel you are lacking].I recommend [accept/minor revisions/major revisions/oblivion], pending x, y, and z.Basic reportingFiguresAre the figures legible, relevant, and integrated into the textDataAre the supporting data included in the manuscript or in a relevant repositoryAre the data presented in a way that is consistent with the FAIR principles (https://www.force11.org/group/fairgroup/fairprinciples)Experimental designWas the way in which the research was conducted the best way to answer the relevant questionsValidity of the findingsAre the conclusions supported by the resultsDo the results contribute to the research field, irrespective of whether they are ‘negative’ or a replication studyGeneral commentsIs the language used appropriate for a scientific publicationIs the structure appropriateAbstractIs the abstract concise, and does it convey the main research findingsAre any key points of context or conclusions missingIntroductionDoes this cover the published literature sufficientlyDoes it provide enough context in which to place the current researchAre any key citations missingIs the history of the research conveyed at all for historical significanceDoes it finish with a paragraph summarising the relevance of the current researchMaterials and methodsAre the methods clear and easy to followCan the methods be replicated if neededAre the source materials/data openly available, and is appropriate justification provided if notWere any statistical analyses applied performed appropriatelyResultsAre the results presented in a coherent fashionAre the results reported in a way that is supported by the dataDiscussionAre the new results placed into context of the relevant literatureIs a balanced argument providedAre the full implications of the new results discussed in sufficient detailConclusionsAre the conclusions supported by the resultsAre they concise and written in an impactful way (not over-embellished)Additional commentsAnything else you want to add that doesn’t fit aboveCongratulations to the authors on a great piece of work, and I look forward to seeing their research [published/rejected/re-written with all of the references to my own tangentially-relevant work included.]Sincerely,[Ralph Lauren]ReferencesAny additional papers you have cited within your report
Importting

Josh Nicholson

and 2 more

Software started in university aisles and, as such, a lot of software today is academic software. Software programs make researchers' work more efficient and competitive. Here are the five best software tools that can help academics especially in their data-based and authoring practices. Note that all these tools integrate with Authorea - the collaborative word processor for academics.1. GithubFourteen million software developers use Github to collaborate and maintain code repositories. Although originally designed for professional developers, Github has now expanded to the classroom. Authorea is also based on git, so integration between the two platforms is as easy as clicking a button.  This feature allows researchers to work offline and provides access to version controls via Github. Read more about Authorea Github Integration here: Syncing articles to GitHub2. PlotlyAcademics and researchers use Plotly to analyze and to visualize plots and graphs. Plotly generates graphs in a variety of formats. Many of these also have interactive online capabilities. Authorea integrated with Plotly so researchers can create and access interactive graphs.3. Jupyter Notebooks (IPython notebooks)Jupyter is a virtual lab environment that contains mathematics, plots, rich media, text, and code. Instructors across academia use Jupyter to conduct research and easily inspect rerun analyses. Authorea is integrated with Jupyter notebooks so that collaborators can create data-rich manuscripts. 4. AuthoreaAuthorea itself is one of the best tools to write academic papers in collaboration. You may think of it as a Google Docs for academia. Google Docs is the most widely used collaborative editor in the world. Despite its prevalence, it lacks many features for citation management, math, LaTeX, and version control. Authorea makes it easy to import any Google Doc directly into Authorea by simply copying and pasting the URL of the document you wish to import. 
Jingjing liang

David Banys

and 1 more

BackgroundJingjing Liang is Assistant Professor of Forest Ecology at West Virginia University. He is Coordinator of the Global Forest Biodiversity Initiative (GFBI), an international, multi-stakeholder team of foresters and forest scientists supporting cutting-edge research and policy making in forest sciences and related areas.Jingjing is also the lead author of GFBI's first major scientific paper: Positive biodiversity-productivity relationship predominant in global forests \cite{Liang_2016}. The paper, which was written collaboratively in Authorea by a team of over eighty researchers, was published in the the Oct. 14, 2016 issue of Science.InterviewAuthorea: Congratulations on publishing in Science! How long has this paper been in the works?Jingjing Liang: We started the data compilation and analysis in October 2015, and completed the first draft in May, 2016. That being said, our data collection work started a few years ago.Authorea: Your team analyzed a forest inventory of more than 777,000 sample plots in 44 countries containing more than 30 million trees, making this one of the first attempts to gain a global perspective on the effect of biodiversity on ecosystem productivity. Can you contextualize this accomplishment for us?Jingjing Liang: Sure, forest inventory data are among the most expensive data to collect on this planet, because 1) it takes skilled and experienced foresters to do the work, and 2) the transportation and related logistics to and from the sites make an inventory trip very costly. According to my rough estimate, measuring 100 plots in remote areas cost $50,000 per year, so, the measurement of all the GFBI plots alone would cost US$400,000,000. GFBI plot data consist one of the largest ground-sourced data set in the world, and would be valuable in many applications from policy making to research support.Authorea: You argue that the worldwide productivity of forests decreases at an accelerating rate with the loss of biodiversity -- does this mean essentially that it's less costly to preserve biodiversity than it is not to?Jingjing Liang: Yes, also because we have shown in the article that conserving biodiversity can lead to potential forestry dividends that would far exceed the annual cost of effective biodiversity conservation worldwide.Authorea: What do you see for the future of biodiversity-productivity relationship (BPR) analyses?Jingjing Liang: BPR analyses would thrive in two fronts- big data and controlled experiments. The big data approach addresses the observed patterns in natural ecosystems, whereas the experiments addresses the mechanisms behind the foregoing patterns.Authorea: Your paper contained 84 authors in total. How did you coordinate the writing and work with such a large group? Were there advantages and disadvantages to such a collaboration that you faced?Jingjing Liang: It is very challenging and takes lots of patience and respect to others. It  is difficult to please everyone, or anyone in that matter, but science takes collaboration, and collaboration takes mutual respect, compromise, and even sacrifice.Authorea: Was there a key reason why you decided to write your article on Authorea?  What were some of the features you liked?Jingjing Liang: We needed a platform that facilitates manuscript development by a large group. Authorea proves to be the platform that we need. It is easy to register and easy to use. The only thing I would recommend is to set the default of "email each comment to everyone" option to "email none", for a large-group collaboration.For more information on the Global Forest Biodiversity Initiative, please visit: http://www.gfbinitiative.org/research
(A title should be specific, informative, and brief. Use abbreviations only if they are defined in the abstract. Titles that start with general terms then specific results are optimized in searches—delete these notes when done)Enter authors here: A. B. Author1, B. C. Author2, and D. E. Author3(List authors by first name or initial followed by last name and separated by commas. Use superscript numbers to link affiliations, and symbols *†‡ for author notes. For example, X. Jones1*, P. Smith1,2 Authors are individuals who have significantly contributed to the research and preparation of the article. Group authors are allowed, if each author in the group is separately identified in an appendix.)1Affiliation for author 1.2Affiliation for author 2.3Affiliation for author 3.(Affiliations should be preceded by superscript numbers corresponding to the author list. Each affiliation should be run in so that the full affiliation list is a single paragraph.)Corresponding author: first and last name (email@address.edu)†Additional author notes should be indicated with symbols (for example, for current addresses).(include name and email addresses of the corresponding author. More than one corresponding author is allowed in this Word file and for publication; but only one corresponding author is allowed in our editorial system.)Key Points:List up to three key points (at least one is required)Key Points summarize the main points and conclusions of the articleEach must be 140 characters or less with no special characters or acronyms.(The above elements should be on a title page) AbstractThe abstract should be a single-paragraph of less than 250 words, or for Geophysical Research Letters, less than 150 words. A good abstract sets the general question or topic that you are studying for the general reader, provides background on the specific question or problem, briefly describes key data or analyses, and describes the key results and uncertainties. Please avoid acronyms or if used, define them.1 IntroductionThe main text should start with an introduction. Except for short manuscripts (such as comments and replies), the text should be divided into sections, each with its own heading. Sections are numbered (1, 2, 3, etc.). A maximum of four levels of heads may be used, with subsections numbered 1.1., 1.2.; 1.1.1., 1.2.1; 1.1.1.1., and so on. Headings should be sentence fragments. Examples of headings are:2 Materials and Methods2.1 A descriptive heading about methods3 Data, or a descriptive heading about data4 Results, or a descriptive heading about the results5 Conclusions(All figures and tables should be cited in order. For initial submission, please embed figures, tables, and their captions within the main text near where they are cited. At revision, figures should be uploaded separately, as we need separate files for production. Tables and all captions should be moved to the end of the file.)References should use a name-date format, not numbers. Enclose citations in brackets with authors in italics as in: [Smith et al., 2009] or Smith et al. [2009].Acknowledgments, Samples, and DataThe text ends with an acknowledgment section and statement that includes:Any real or perceived financial conflicts of interests for any authorOther affiliations for any author that may be perceived as having a conflict of interest with respect to the results of this paper.A statement that indicates to the reader where the data supporting the conclusions can be obtained (for example, in the references, tables, supporting information, and other databases).Funding information related to the work for all authors should be entered in the form in GEMS as part of your submission. This form in GEMS uses the official Fundref list, which provides a link after publication that is available to funders. Any other funding information not listed in the GEMS form should be included in the acknowledgments and/or cover letter.It is also the appropriate place to thank colleagues and other contributors. AGU does not normally allow dedications.Large data sets should ideally be deposited in a domain repository specializing in that data type or a general repository if a specific domain repository is not available. A directory of some Earth and space science repositories is here: https://copdessdirectory.osf.io/. Other data should be included as file in supporting information. AGU requires that all data necessary to reproduce the reported finding be available at the time of publication. Further information is available here: http://publications.agu.org/author-resource-center/publication-policies/data-policy/AGU recommends use of IGSN’s (International Geo Sample Numbers) for citing samples reported in research papers. The IGSN provides a unique identifier that allows samples to be linked across publications and searched through a central metadata repository. We strongly encourage authors to register samples with an IGSN Allocating Agent and obtain IGSN’s and use them throughout their manuscript, tables, and archived data sets. We recognize IGSN’s during our production process and will provide links in the manuscript and tables to the registered sample descriptions. IGSN’s can be reserved before field seasons, or assigned afterwards. For more information, see http://www.igsn.org.ReferencesAll sources cited in text, tables, figures, and Supporting Information must appear in the main reference list, and all entries in the reference list must be cited in main text. References that are cited in supporting information should also be included in the reference list of the paper and worked into the text, so that they will be indexed and included in citation records and given credit. References are not included in word counts for excess length fees. 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 OMB No. 0925-0001 and 0925-0002 (Rev. 10/15 Approved Through 10/31/2018)BIOGRAPHICAL SKETCHDO NOT EXCEED FIVE PAGES.NAME: Hunt, Morgan CaseyeRA COMMONS USER NAME (credential, e.g., agency login): huntmcPOSITION TITLE: Associate Professor of PsychologyEDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)INSTITUTION AND LOCATIONDEGREE(if applicable) Completion DateMM/YYYY FIELD OF STUDY University of California, BerkeleyB.S05/1990PsychologyUniversity of VermontPh.D.05/1996Experimental PsychologyUniversity of California, BerkeleyPostdoctoral08/1998Public Health and Epidemiology        A. Personal StatementI have the expertise, leadership, training, expertise and motivation necessary to successfully carry out the proposed research project. I have a broad background in psychology, with specific training and expertise in ethnographic and survey research and secondary data analysis on psychological aspects of drug addiction. My research includes neuropsychological changes associated with addiction. As PI or co-Investigator on several university- and NIH-funded grants, I laid the groundwork for the proposed research by developing effective measures of disability, depression, and other psychosocial factors relevant to the aging substance abuser, and by establishing strong ties with community providers that will make it possible to recruit and track participants over time as documented in the following publications. In addition, I successfully administered the projects (e.g. staffing, research protections, budget), collaborated with other researchers, and produced several peer-reviewed publications from each project. As a result of these previous experiences, I am aware of the importance of frequent communication among project members and of constructing a realistic research plan, timeline, and budget. The current application builds logically on my prior work. During 2005-2006 my career was disrupted due to family obligations. However, upon returning to the field I immediately resumed my research projects and collaborations and successfully competed for NIH support. 1. Merryle, R.J. & Hunt, M.C. (2004). Independent living, physical disability and substance abuse among the elderly. Psychology and Aging, 23(4), 10-22.2. Hunt, M.C., Jensen, J.L. & Crenshaw, W. (2007). Substance abuse and mental health among community-dwelling elderly. International Journal of Geriatric Psychiatry, 24(9), 1124-1135.3. Hunt, M.C., Wiechelt, S.A. & Merryle, R. (2008). Predicting the substance-abuse treatment needs of an aging population. American Journal of Public Health, 45(2), 236-245. PMCID: PMC9162292 Hunt, M.C., Newlin, D.B. & Fishbein, D. (2009). Brain imaging in methamphetamine abusers across the life-span. Gerontology, 46(3), 122-145.B. Positions and HonorsPositions and Employment1998-2000 Fellow, Division of Intramural Research, National Institute of Drug Abuse, Bethesda, MD2000-2002 Lecturer, Department of Psychology, Middlebury College, Middlebury, VT2001- Consultant, Coastal Psychological Services, San Francisco, CA2002-2005 Assistant Professor, Department of Psychology, Washington University, St. Louis, MO2007- Associate Professor, Department of Psychology, Washington University, St. Louis, MOOther Experience and Professional Memberships1995- Member, American Psychological Association1998- Member, Gerontological Society of America1998- Member, American Geriatrics Society2000- Associate Editor, Psychology and Aging2003- Board of Advisors, Senior Services of Eastern Missouri2003-05 NIH Peer Review Committee: Psychobiology of Aging, ad hoc reviewer2007-11 NIH Risk, Adult Addictions Study Section, membersHonors2003 Outstanding Young Faculty Award, Washington University, St. Louis, MO2004 Excellence in Teaching, Washington University, St. Louis, MO2009 Award for Best in Interdisciplinary Ethnography, International Ethnographic SocietyC. Contribution to Science1. My early publications directly addressed the fact that substance abuse is often overlooked in older adults. However, because many older adults were raised during an era of increased drug and alcohol use, there are reasons to believe that this will become an increasing issue as the population ages. These publications found that older adults appear in a variety of primary care settings or seek mental health providers to deal with emerging addiction problems. These publications document this emerging problem but guide primary care providers and geriatric mental health providers to recognize symptoms, assess the nature of the problem and apply the necessary interventions. By providing evidence and simple clinical approaches, this body of work has changed the standards of care for addicted older adults and will continue to provide assistance in relevant medical settings well into the future. I served as the primary investigator or co-investigator in all of these studies.a. Gryczynski, J., Shaft, B.M., Merryle, R., & Hunt, M.C. (2002). Community based participatory research with late-life addicts. American Journal of Alcohol and Drug Abuse, 15(3), 222-238.b. Shaft, B.M., Hunt, M.C., Merryle, R., & Venturi, R. (2003). Policy implications of genetic transmission of alcohol and drug abuse in female nonusers. International Journal of Drug Policy, 30(5), 46-58.c. Hunt, M.C., Marks, A.E., Shaft, B.M., Merryle, R., & Jensen, J.L. (2004). Early-life family and community characteristics and late-life substance abuse. Journal of Applied Gerontology, 28(2),26-37.d. Hunt, M.C., Marks, A.E., Venturi, R., Crenshaw, W. & Ratonian, A. (2007). Community-based intervention strategies for reducing alcohol and drug abuse in the elderly. Addiction, 104(9), 1436-1606. PMCID: PMC9000292 2. In addition to the contributions described above, with a team of collaborators, I directly documented the effectiveness of various intervention models for older substance abusers and demonstrated the importance of social support networks. These studies emphasized contextual factors in the etiology and maintenance of addictive disorders and the disruptive potential of networks in substance abuse treatment. This body of work also discusses the prevalence of alcohol, amphetamine, and opioid abuse in older adults and how networking approaches can be used to mitigate the effects of these disorders.a. Hunt, M.C., Merryle, R. & Jensen, J.L. (2005). The effect of social support networks on morbidity among elderly substance abusers. Journal of the American Geriatrics Society, 57(4), 15-23.b. Hunt, M.C., Pour, B., Marks, A.E., Merryle, R. & Jensen, J.L. (2005). Aging out of methadone treatment. American Journal of Alcohol and Drug Abuse, 15(6), 134-149.c. Merryle, R. & Hunt, M.C. (2007). Randomized clinical trial of cotinine in older nicotine addicts. Age and Ageing, 38(2), 9-23. PMCID: PMC9002364 3. Methadone maintenance has been used to treat narcotics addicts for many years but I led research that has shown that over the long-term, those in methadone treatment view themselves negatively and they gradually begin to view treatment as an intrusion into normal life. Elderly narcotics users were shown in carefully constructed ethnographic studies to be especially responsive to tailored social support networks that allow them to eventually reduce their maintenance doses and move into other forms of therapy. These studies also demonstrate the policy and commercial implications associated with these findings.a. Hunt, M.C. & Jensen, J.L. (2003). Morbidity among elderly substance abusers. Journal of the Geriatrics, 60(4), 45-61.b. Hunt, M.C. & Pour, B. (2004). Methadone treatment and personal assessment. Journal Drug Abuse, 45(5), 15-26.c. Merryle, R. & Hunt, M.C. (2005). The use of various nicotine delivery systems by older nicotine addicts. Journal of Ageing, 54(1), 24-41. PMCID: PMC9112304d. Hunt, M.C., Jensen, J.L. & Merryle, R. (2008). The aging addict: ethnographic profiles of the elderly drug user. NY, NY: W. W. Norton & Company.Complete List of Published Work in MyBibliography: http://www.ncbi.nlm.nih.gov/sites/myncbi/collections/public/1PgT7IEFIAJBtGMRDdWFmjWAO/?sort=date&direction=ascendingD. Additional Information: Research Support and/or Scholastic PerformanceOngoing Research SupportR01 DA942367 Hunt (PI) 09/01/08-08/31/16Health trajectories and behavioral interventions among older substance abusersThe goal of this study is to compare the effects of two substance abuse interventions on health outcomes in an urban population of older opiate addicts.Role: PI R01 MH922731 Merryle (PI) 12/15/07-11/30/15Physical disability, depression and substance abuse in the elderlyThe goal of this study is to identify disability and depression trajectories and demographic factors associated with substance abuse in an independently-living elderly population.Role: Co-Investigator Faculty Resources Grant, Washington University 08/15/09-08/14/15Opiate Addiction DatabaseThe goal of this project is to create an integrated database of demographic, social and biomedical information for homeless opiate abusers in two urban Missouri locations, using a number of state and local data sources.Role: PICompleted Research Support R21 AA998075 Hunt (PI) 01/01/11-12/31/13Community-based intervention for alcohol abuseThe goal of this project was to assess a community-based strategy for reducing alcohol abuse among older individuals.Role: PI

Josh Nicholson

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NEW YORK, NY, January 18, 2016 -- Sample of Science and the collaborative writing platform Authorea have partnered to empower researchers around the world to share materials samples more efficiently. Development of novel materials is a growing area of research and the Sample of Science and the Authorea partnership makes it easier for researchers to write brief descriptions of their materials and share the samples with other scientists."Sample of Science is solving an important problem in the field of chemistry and materials sciences. We are happy that Authorea can serve as the writing platform for submissions to Sample of Science. If samples from experiments are made more openly accessible, it can help make research more efficient -- something we value greatly” said Alberto Pepe, CEO of Authorea. “Authorea and Sample of Science share a passion for giving researchers great tools that help them do better work.”Sharing samples of newly synthesized materials is an important step in the research cycle. For example, a carbon material developed in Berlin can subsequently be validated or utilized by research groups in Boston. Scientists who want to increase the visibility of their research and facilitate new experiments can write brief descriptions of their novel materials samples using the Authorea platform. All materials, together with brief descriptions, will be made available on the Sample of Science portal.Felix Evert, managing director of Sample of Science, is certain that the partnership will improve the research process for scientists who synthesize novel materials. “Better science is all about enabling researchers to disseminate the right information more efficiently. Authorea is an excellent digital writing tool. The lean online template for submission of brief sample descriptions is ideal for chemists and materials scientists who want to communicate their findings quickly," Evert explains. For more information, please visit: Sample of Science was founded in 2015 as a digital platform which connects researchers synthesizing novel materials with researchers who need them. The platform publishes open access description of novel materials and facilitates interdisciplinary collaborations based on materials from experiments. The company is located at the Freie Universität Berlin which is also one of the first cooperation partners of Sample of Science. www.sampleofscience.com    Felix Evert    Phone +49 162 276 2928    felix.evert@sampleofscience.comAuthorea is the online document editor for researchers that is accelerating scientific discover. Authorea is trusted worldwide by leading researchers writing and publishing content in every discipline, from astrophysics to zoology. The online document editor supports a wide range of markup languages and scientific integrations, including the most popular citation management, graphing, and visualization plugins. www.authorea.com    Adyam Ghebre    Phone +1 646 598-9285    adyam@authorea.com
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Josh Nicholson

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BROOKLYN, NY, NOVEMBER 10, 2016 --Authorea (http://www.authorea.com), the online collaborative platform for researchers, today announced it has acquired The Winnower (https://www.thewinnower.com), a pioneering research publisher that offers advanced publishing tools to individual authors.With the acquisition, Authorea enhances the foremost online platform for researchers to write, cite, collaborate, host data, and publish all in one place. The acquisition follows a financing round led by Lux Capital and joined by Bloomberg Beta, the John S. and James L. Knight Foundation, TechHammer, ff Venture Capital, and New York Angels."We are building a powerful toolset for researchers to collaborate," said Authorea CEO Dr. Alberto Pepe. “We're supporting a research model that puts the author first, allowing him or her to write technical research documents online -- with a data layer underneath -- and to control fully the output and dissemination of that effort. We're pleased to welcome aboard the team at The Winnower, which will help provide additional publishing options to our researchers."The Winnower, founded by Dr. Joshua Nicholson in 2014, is a leading publisher of preprints and grey literature -- outputs that are often overlooked by traditional publishers."The Winnower offers traditional research publishing tools, such as a digital object identifier and permanent archival, to non-traditional documents like Reddit r/science Ask-Me-Anything (AMA) transcripts, blog posts, preprints, grant applications, citizen science reports, and more," said Dr. Nicholson. "We're delighted to join the forward-thinking team at Authorea. We share the mission of accelerating scientific discovery through superior research communication tools, and a big part of that is providing authors the tools to control their research from initial spark to output."##
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Alberto Pepe

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IntroAs academics transition to digital journal publishing, the Open Access (OA) movement, which aims to make research freely available at or soon after publication, is picking up record speed. According to a recent Simba report titled Open Access Journal Publishing 2016-2020, “the number of OA research articles published annually is growing at double the rate of the complete spectrum of research articles.” The report also found that about a third of all research articles currently published are OA, when factoring in those with complete embargo periods.The rise in OA publishing comes as a result of scholars banding together to reveal the mounting cost of research access for institutions and individuals, such as those behind the Cost of Knowledge Project who started a boycott of Elsevier, which now has profit margins exceeding 30%. At the same time governments and funding bodies have introduced new OA mandates and calls for early sharing of research. Such as the Wellcome Trust, Bill & Melinda Gates Foundation, and others who this February urged journals and research funding agencies to sign a pledge to make all papers related to the Zika virus OA in the wake of the public health crisis.Yet, despite the scholarly community embracing OA publishing, the Authorea team reveals that 65 of the most cited papers in the world are still behind often hefty paywalls, inaccessible to those who can’t afford article fees or journal subscriptions. Today this pattern continues with more groundbreaking articles being published in journals with prohibitive paywalls. As the drumbeat for OA gets louder, it’s apparent that researchers and journal publishers must come together to find sustainable ways to make such research freely accessible.Among promising OA solutions is preprint servers, or online databases of manuscripts posted by scholars prior to formal publication.In this guide we’ll look at the place of preprints in the digital publishing landscape for journals and scholars, including:How preprints are helping scholars and journals make research more openChallenges to be addressed when publishing via preprintsNew publishing models journals are pioneering using preprint serversLet’s get started!Preprints and the modern publishing landscapeResearchers utilize the most advanced tools in the world to perform their experiments. From massively parallel computing clusters approaching exoscale computation power to high-powered microscopes redefining the limits of resolution, we're in age where the tools we use to perform research are truly awesome. However, such innovations have fallen short when it comes to how researchers write or ultimately publish their work.  In short, scientists are doing 21st century research, writing it on 20th century tools, and packaging it in 17th century formats.The origin of scholarly journals: 300 years with little changeThe first scholarly article, published in 1655 in Philosophical Transactions, was an important step for researchers towards formalizing and preserving the scholarly record.  Recognizing the importance of research communication, the opening editorial stated:"Whereas there is nothing more necessary for promoting the improvement of Philosophical Matters, than the communication of such."Over the ensuing centuries new publications from The Lancet in 1823 to Virchows Archiv in 1847 were launched (fun fact: Thomas Wakely launched The Lancet at age 27 and Rudolf Virchow launched Virchow's Archiv at the age of 26). Considered radical in their time, these journals and others soon grew in prominence becoming the standard method for communicating research. Many of which are now household names and contain some of the world’s most important findings.The increasing volume of academic publications brought about a formalized peer review system in the early 19th century and with it an increase in technological capabilities over time, like structured typesetting, which were largely born out of a desire to share research better. In the 1960’s the way scholars consumed and disseminated their research began to change... at least for some researchers.In the 1960’s, while the majority of researchers communicated via journals exclusively, a subset of researchers began to utilize new forms of communication. Physicists began to share their paper manuscripts directly with each other prior to them being peer reviewed or published in a journal. These shared manuscripts become known as “preprints.” Databases in the US and in Germany housed the bibliographic information of preprints and facilitated their sharing, which eventually became so widespread it became onerous and even unfeasible to manage for those without adequate resources.  Indeed, the library at the Stanford Linear Accelerator Center (SLAC), which housed preprints, was receiving thousands of preprints per year at one point, a large amount of information at the time to be organized and collected.Preprints and the webTo deal with the growing amount of bibliographic information accumulating at SLAC a computer database was developed, termed the Stanford Physics Information Retrieval System (SPIRES).  SPIRES not only organized bibliographic information, creating a standard used across universities, but also allowed for researchers to email the database and request that a list of preprints be sent to them. Since papers could not be emailed at the time, the system relied on snail mail.While SPIRES greatly improved the flow of information, it often still took weeks for preprints to reach their requester’s mailbox.  A typesetting system called .tex introduced in the late 70’s early ‘80s soon changed this by allowing researchers to write their documents in a specified manner that could be emailed and downloaded and compiled without the need for physical mail.Soon researchers, primarily physicists, were emailing and downloading .tex files at great rates hastening the process of research communication, which again created the problem of information overload.  To manage this process, in March 1989 Tim Berners-Lee wrote a paper modestly entitled, "Information Management: A Proposal." Soon after the World Wide Web, Berners-Lee’s own invention, and with it a central preprint repository, later to be named arXiv, were born.What researchers are saying about preprintsThe rise of open research sharing, the web, and a central preprint repository drastically changed how researchers communicate their research. However, these advances did not penetrate all research disciplines and to this day preprints have struggled to gain widespread adoption.  Nevertheless, in recent years preprint usage has been on the rise and there are now preprint repositories for various disciplines including arXiv, for math, physics and other sciences; BioArXiv, for biology; SocArXiv, for social sciences; as well as discipline-agnostic repositories like Authorea."New technology does a better job of finding me stuff to read than the table of contents of any given journal (Pubchase, custom RSS feeds, Twitter recs from respected colleagues).  Especially with the option of versioning articles, I think this system would capture much of the current value of peer review, be faster, and more sustainable."- Angela DePace, Assistant Professor, Department of Systems Biology, Harvard Medical School"Posting preprints offers people the chance to be more thoroughly evaluated, which is especially beneficial for younger scientists."-James Fraser, Assistant Professor, UCSFOne limitation that has held back the widespread adoption of preprints is the confusion over whether you can still publish in a traditional journal after posting a preprint. This fear, despite the fact that most preprints on arXiv are ultimately published in journals, arises from the so-called Ingelfinger rule that limits duplicate publications as well as communication by some publishers that has cast an artificial uncertainty into the decision making process of researchers.Nevertheless, there are clear rules for writing and posting of preprints and journals are quickly embracing preprints in wider disciplines.  In fact, some journals have even instituted "preprint editors" to solicit preprints for journal publication off of repositoriesPreprints reshaping the author experiencePreprint servers arose with the use of new technology, specifically authors writing their documents in .tex files.  Today, much of the world is able to write online and even execute their own programs for data analyses.  Despite this widespread adoption of technology, scientific papers remain primarily static objects (PDFs) and generally require typesetting to be done by journal publishers.New collaborative writing tools, such as Authorea, simplify this process by allowing authors to produce manuscripts that are not limited to just text and image but also allow rich media such as datasets, software, source code, and videos. Tools like Authorea make it easy to write, cite, collaborate, host, and to preprint. By putting the control of typesetting in the hands of authors that write in markdown, latex or rich text control of publishing is shifted towards the research community, not just professional publishers.5 Ways you can start using preprints to publishCheck preprint policies at journals to which you’re considering submittingEmail the editors of the journal you plan to submit to if you’re unsure about their preprint policiesUse collaborative writing tools to write and post preprintsShare your preprints with colleagues via social media and email to solicit feedbackEducate and encourage others to share their work openlyThe role of preprints in academic journal publishingIn the digital scholarly communication landscape the primary value of preprints for researchers is that preprints allow them to disseminate their work faster and to a much wider audience than they could in traditional paywalled journals. A recent Editage Insights article titled, “The role of preprints in research dissemination“ details why many scholars are choosing to submit their work to preprints prior to formal journals. Among primary benefits are that preprints:Give scholars working on time-sensitive projects a way communicate their research while undergoing peer reviewCan serve as a way for scholars to establish priority over a particular research discovery or methodEnsure that an OA version of scholars’ work will be available regardless of where they formally publishThe increase in preprint use, along with scholars publicly coming together to endorse preprints, such as those at the 2016 ASAPbio meeting, is forcing journal publishers to address the place of preprints in the publishing landscape.Preprints and Green OADespite “preprint” sounding like something reserved for pre-publication, “preprint” servers and published journals don’t have to be as separate as their names suggest. Preprints have actually been a driving force behind Green OA, in which scholars deposit their articles into an institutional repository or subject repository in order to make a version of their work OA. Depending on the requirements of the journal, Green OA preprints may be manuscripts or copies of final articles.Among leaders of the Green OA movement is Stevan Harnad, Professor in the Department of Psychology at Université du Québec à Montréal and Affiliate Professor in Electronics and Computer Science at University of Southampton, UK.In 1994 Harnad published the Subversive Proposal stating that researchers should self-archive their research articles to make them free for all online. Self-archiving later went on to become “Green OA” (and OA journals became “Gold OA”). Harnad also commissioned the first OA repository software, EPrints, in 1999. Since then, Green OA via repositories and preprint servers has become increasingly popular.When asked how Green OA should work, Harnad says it’s simple.“All researchers should self-archive their articles immediately upon acceptance for publication by depositing them in their institutional OA repository. And all institutions and funders should mandate this.”How journals can facilitate Green OA via preprintsIn order to use preprint servers to make research Green OA,scholars need journal support. “Open Access compliance: How publishers can reach the recommended standards,” a 2016 report released by Jisc, outlines some key ways publishers and journals can take action to help scholars make their research OA. Among steps Jisc outlines are:Making clear OA policies easily accessible on journal websitesEnsuring embargo periods, if deemed necessary, meet funder requirements and are reasonable to the academic communityApplying Digital Object Identifiers (DOIs) to all articles, so scholars can link the different versions of their workAdopting ORCID IDs, which can be used to populate institutional repositories and track OA complianceProviding journal and article level OA licensing terms to clarify any differences at either levelAs journal publishers continue to work out whether they’re ready to transition to an OA model, supporting Green OA by allowing authors to submit manuscripts they’ve posted to preprints is a great place to start. By considering manuscripts scholars have uploaded to preprint servers publishers can better meet institutional and funder OA mandates as well as scholar expectations. A key aim journal publishers must have to facilitate Green OA is to provide clear policies for preprints, so there is no confusion among scholars as to whether they can upload their manuscript to a preprint server prior to formal publication.Importance of clear preprint policiesA recent article in the Journal of Librarianship and Information Science titled "What does ‘green’ open access mean? Tracking twelve years of changes to journal publisher self-archiving policies," traces the self-archiving policies over the last 12 years of the original 107 publishers listed on the SHERPA/RoMEO Publisher Policy Database. The study found that while the volume of publishers allowing self-archiving has increased by 12%, the volume of restrictions around self-archiving has increased by 119%.Many preprint limitations enacted by publishers are not immediately apparent, making it vital for submitting authors and journal editors to carefully review publishers’ self-archiving policies to ensure they’re comfortable with the stances the journals they’re working with are taking. Confusing preprint policies can slow down Green OA and even deter scholars from submitting to preprint servers, due to unfounded fears of being penalized for publishing their paper in two places.With OA publishing becoming an expectation among the academic community, today some journal editors are speaking out in instances of publishers increasing the cost of research access or enacting policies to limit OA options. In some cases where editors and publishers haven’t been able to work out differences editors have actually left the publisher to start OA friendly counterparts to old journals.An early example is Michael Rosenzweig, Professor of Ecology and Evolutionary Biology at the University of Arizona, who in 1998 became one of the first editors-in-chief to leave his publisher when he led the editorial board of Evolutionary Ecology in declaring independence from the journal’s then publisher, International Thomson. Evolutionary Ecology’s editorial board left in protest of high subscription costs which, despite the editors’ best efforts to combat them, were rising at a rate of 19% a year. The editors started a new Green OA journal titled Evolutionary Ecology Research. Since then more journals have followed suit, including the editorial board of  Elsevier journal Lingua, who also left in protest of prohibitive price hikes and started their own journal Glossa.Peter Suber, director of the Harvard Office for Scholarly Communication, Senior Researcher at the Berkman Center, Senior Researcher at SPARC, and Research Professor of Philosophy at Earlham College, has been following the trajectory of editors leaving their publishers to start more OA friendly journals. Since the late ’80s he’s maintained the “Journal declarations of independence” list that he started on the Open Access Directory (OAD) website with OAD co-founder Robin Peek.Suber believes that if publishers do not address prohibitive paywalls and OA policies it’s only a matter of time before more editors take a stand and launch solo journals on their own.“Every time a journal declaration of independence takes place, frustrated editors at other journals will think about whether they should follow suit, because they will know it can be done,” said Suber.Questions surrounding preprint publicationsPreprints aren’t without questions to be worked out. Some publishers have been wary of fully endorsing preprints due to perceived challenges in the preprint model. Among those who’ve voiced uncertainty about preprints is Emilie Marcus, Editor-in-Chief of Cell and CEO of Cell Press.Questions and uncertainties about preprints raised by Marcus include:Are preprints by themselves valid publications and should preprints be citable?If preprints are citable, do scholars have to read through all preprint literature in addition to published articles to account for preprints in their references?Is there an optimal number of preprints per discipline and what should that be?A concern among some scholars and publishers is that preprints don’t go through peer review, and post-publication vetting of preprints isn’t generally guaranteed or monitored. Though, pre-publication peer review is also an imperfect process with room for error. Uncertain manuscript vetting is a key concern among publishers when it comes to preprints, making some including Marcus, regard preprints as ways of accelerating the sharing of ideas but not a “publishing” solution. However, this isn’t the only way to view preprints. There are editors who are establishing new methods to link preprints and formal journals making research more open as a result.Journals pioneering new preprint publishing modelsA primary contention some publishers and editors have with preprints is that they lack the validation of formal journal articles. But what if preprint manuscripts were actually vetted and peer reviewed? Enter the vision of the overlay journal. Overlay journals are open access journals that perform the peer review function of a traditional journal but, rather than directly accepting manuscript submissions, pull in manuscripts from a preprint server.Overlay journals started appearing in the 1990s beginning with Physical review D, the first partial overlay journal launched by Paul Ginsparg in 1996. From there more overlay journals followed. Generally, in the overlay model journal editors vet submissions, coordinate peer review, and then, rather than publishing accepted articles in an issue, they republish final versions to a preprint server along with a DOI. Overlay journals can be open access or use subscription models for final versions.Some editors have been able to make their journals both free to read and free to publish in via the overlay model. Among examples are Peter Coles, Professor of Theoretical Astrophysics at Cardiff University, who founded the Open Journal of Astrophysics and Royal Society Research Professor and Fields Medalist Timothy Gowers who founded the new math journal Discrete Analysis. Both Coles’ and Gowers’ journals work in tandem with arXiv. The journals are formal publications, which can be abstracted, indexed, and accrue impact.As a new overlay journal Discrete Analysis is taking steps to further develop the publishing model. Discrete Analysis stands out from other overlay journals because it has a formal publication website, which includes article categories visitors can choose from to access complete article listings and designated pages for each of its articles with an image and description. In this way Discrete Analysis offers readers a journal browsing experience on its website while still using arXiv to handle the publishing process.Discrete Analysis manages peer review and publishes its journal via Scholastica. Using Scholastica’s arXiv integration authors are able to submit papers they already posted to the arXiv for consideration by Discrete Analysis editors. The journal’s editorial board then coordinates peer review for all submissions and accepted manuscripts are edited and re-uploaded to arXiv as final versions with DOIs. The journal has already published top research including editor Terence Tao’s article on crowdsourcing the solution to the Erdős discrepancy problem.For Timothy Gowers and other overlay journal founders and supporters, the primary goal of the overlay model is to lower the barrier to publishing OA and speed up research dissemination.“I want to be aggressively modern. I want to use the internet properly – when you’ve got something, you post it,” Gowers explained. “We’re not pretending to be a traditional journal, we’re something else.”The overlay model presents a much leaner publishing approach that eliminates the costs of time and budget journals must usually allocate to “printing services,” such as typesetting, making the publishing process quicker and more affordable. It’s one of many new OA publishing models out there for journals to explore.ClosingResearch dissemination has not dramatically changed since the Royal Society published the first scholarly journal, Philosophical Transactions, in 1665. However, today’s digital publishing age is starting to transform the way scholars and journals approach research publication, spurring important questions about the traditional paywalled publishing model. With the shift towards digital publishing, OA, and new impact indicators, it’s becoming harder for publishers to justify the need for “printing” costs. Additionally, factors like a journal’s Impact Factor and the clout of its publisher are becoming less important to authors, making them more likely to consider alternatives to “band-name” paywalled journals. Rather, scholars, as well as universities, funding bodies, and government organizations, are encouraging researchers and journals to take steps to make content freely accessible. Preprint servers are one tool that is helping to facilitate Green OA via the archiving of preprints and even Gold (free to read) and Diamond (free to read and free to publish) OA via new overlay journal models that virtually eliminate publisher costs. Now's an exciting and significant time for the academic community to address the place of preprints in the publishing landscape.  Tools for researchers and journal editors to do their work in a modern way are now at hand; it’s time to start utilizing them.
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Write, edit, submit, revise, resubmit, resubmit, resubmit, resubmit.... Okay, you get the point: we send our manuscripts to lots of journals. The time formatting and reformatting manuscripts is a pain and it is one we are working to ease.  Your valuable time should be spent on your research, not tiresome formatting.  Today, we've added 8,249 article templates to Authorea! With the addition of these templates we now make it easy for you to write your article for just about any journal out there. We hope you won't submit to all 8,000+ different journals but at least you now have the power to do so!  We've also made it easy for users to create their own templates, so if you see a template missing, please feel free to create one.So...How does it work? It couldn't be any simpler. Just browse our template section for inspiration. Don't start from scratch. Our templates give you a mold that you can shape to your liking. Working feverishly on a research paper, grant proposal, university thesis or a class project? We do them all. Focus on your writing on the web, and enjoy Authorea's single streamlined web view of scholarly text. Once finished, you're truly finished - forget about formatting issues. With just a couple of clicks through our Export flow, you're ready to send in that submission!  Authorea's journal templates follow correct citations guidelines outlined by the journals, at no extra effort for our authors.We're really just getting started. If you need to send a printout to a colleague in draft shape, line-numbered and double-spaced, it's a selection away. Different journal? Same breeze. Your text, data, visuals, and citations will be updated automatically behind the scenes. In the unlikely event you hit a hurdle, our 24/7 support team will be happy to quality control your article and quickly get it back on the fast track to getting published.This is the first step towards making the writing and publication process as seamless as possible but we've got lot's more coming. We hope you'll join us so that we can make scholarly writing and publishing more effective and more enjoyable. Happy writing!