This is a journal club review of Moderate developmental alcohol exposure reduces repetitive alternation in a zebrafish model of fetal alcohol spectrum disorders, posted on bioRxiv (DOI: 10.1101/370072)

Steven Burgess (0000-0003-2353-7794), Samuel Fernandes, Antony Digrado, Charles Pignon, Elsa de Becker, Naomi Housego Day, Lusya Manukyan, Stephanie Cullum, Isla Causon, Iulia Floristeanu, Young Cho, Freya Way, Judy Savitskya, Robert Collison, Aoife Sweeney, Pietro Hughes, Cindy Chan AbstractThis review is compiled from notes taken by the UIUC Plant Physiology preprint journal club during a one hour session on 2018-07-30. The review refers to the preprint "Natural variation in stomata size contributes to the local adaptation of water-use efficiency in Arabidopsis thaliana" by Hannes Dittberner, Arthur Korte, Tabea Mettler-Altmann, Andreas Weber, Grey Monroe, and Juliette de Meaux ( doi: https://doi.org/10.1101/253021) published on BioRxiv.ReviewIn the paper “Natural variation in stomata size contributes to the local adaptation of Water use efficiency in Arabidopsis thaliana” Dittberner et al. (2018) investigated the genetic basis of water use efficiency using genome wide association analysis. Findings included (1) that there is substantial variation in stomatal size and patterning in A. thaliana accessions (2) decreased stomata size correlates with increased water use efficiency (3) two novel QTL affecting WUE independently of stomatal patterning (4) water use efficiency is a polygenic trait and (5) natural selection contributed to the establishment of variation in WUE in accordance with climatic conditions.The findings are in accordance with previous studies looking at genetic variation in stomatal size and patterning in A. thaliana (Delgado et al. 2011; Monda et al. 2016), the role of natural selection in WUE of tomato (Muir et al. 2014), analysis of genomic variation in WUE in A. thaliana (Easlon et al. 2014; Aliniaeifard and van Meeteren 2014) and the extensive literature correlating a decrease in stomatal size with increased water use efficiency in many species.We were impressed by the significant technical advance presented in the form of automated stomatal counting and suggest more could be made of this aspect of the paper. For example the we suggest inclusion of the term ‘high-throughput’ in the title, and think it would be helpful to include a picture of how the screening system works in the introduction.Further, we found the conclusion that water use efficiency is a polygenic trait very interesting. The implications are important for studies aimed at the improvement of photosynthesis/WUE through conventional breeding or genetic manipulation. We wonder if there are other papers which have already discussed the potential polygenic nature of stomatal traits? Yoo et al. (2011) mentions different genes involved in WUE and stomatal patterning. This kind of paper could have been worth-mentioning in the discussion.The identification of two novel QTL, not otherwise known to influence water use efficiency or to be related to stomatal patterning and regulation was particularly intriguing, and these two genes provide a great starting point for further analysis in future publications.Major commentsWe believe the kinship matrix accounts for relatedness, and is usually called the k model. To account for population structure one could use principal components, combining these two approaches is known as the Q+K model. It would be helpful to include a citation for calculating the kinship matrix as there are multiple methods available. It might also be worth providing QQplots to show whether including population structure is necessary or not for this study.We found the use of a Bonferroni correction in the analysis quite conservative, there are other options such as Benjamini-Hochberg adjusted p-values that could lead to declaring other SNPs as significant. Also, from the GWAS results, there seem to be other SNPs popping up - although, not significant. It might be worth using an alternative to p-values when investigating the possible biological significance of outstanding SNPs on a Manhattan plot - such as selecting the top 10 hits for investigation.Minor comments:Keywords: Consider revisiting, as many of the keywords are already on the title. Additionally, it would be helpful to include terms rather than acronyms which are not familiar to non-experts.Introduction: Would be good to include examples of some of the limitations to automated confocal microscopy approaches to orientate readers.Line 143: (Atwell et al., 2010). This citation doesn't seem to be right. If the author is referring to genomic heritability it could cite de los Campos et al. (2015).Methods: Would like to see further information on the methodology used for carbon isotope discrimination in the main textResults: Might consider using the term ‘genetic-heritability’ rather than ‘pseudo-heritability’Results: Direct comparison with previously reported dC13 values for accessions that have been demonstrated to differing WUE would be helpful.Figure 4: the text on the figure is likely to be too small to see properlyLine 505: “soil composition...” This is a really interesting point about the complexity of environmental effects on plant physiology. It might be helpful to provide some explanation for readers less familiar with soil content. (e.g. water holding content and effect on root structure - e.g.https://doi.org/10.1073/pnas.1721749115)Line 499-500. Repetition of text on 498-499Results: It would be helpful to share where the functional annotation for genes come from. This gene appears to be involved in mRNA decapping. There is only one publication, which found it is involved in PAMP triggered immunity, plants were dwarf in stature. TAIR does not annotate a role in cell differentiation (10.15252/embj.201488645)Discussion: It is interesting to see a comparison with a related species and how the observed pattern is consistent between the two.Data accessibility: This is excellent. Great to see that all data and code will be made available and deposited in a permanent repository!ReferencesAliniaeifard and van Meeteren (2014) J Exp Bot. 65(22): 6529–6542.de los Campos et al. (2015) PLoS Genet 11(5): e1005048. doi:10.1371/journal.pgen.1005048Delgado et al. (2011) Ann Bot.; 107(8): 1247–1258Easlon et al. (2014) Photosynth Res 119: 119. https://doi.org/10.1007/s11120-013-9891-5Monda et al. (2016) Plant Physiol, 170: 1435–1444Muir et al. (2016) Genetics. 2014 Dec; 198(4): 1629–1643.

This is a review of Maekawa et al. bioRxiv 293050; doi: https://doi.org/10.1101/352278 posted on June 20, 2018. In this paper, the authors mined the transcriptomes of 50 different accession of wild barley, generating a rich library of natural variants of the MLA immune receptor—a classical nucleotide-binding domain and leucine-rich repeat-containing (NLR) protein. They grouped the MLA variants in two subfamilies with all receptors known to be effective against the powdery mildew fungus grouping in one subfamily.

Title: Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia. Authors: Gerard Minuesa, Steven K Albanese, Arthur Chow, Alexandra Schurer, Sun-Mi Park, Christina Z. Rotsides, James Taggart, Andrea Rizzi, Levi N. Naden, Timothy Chou, Saroj Gourkanti, Daniel Cappel, Maria C Passarelli, Lauren Fairchild, Carolina Adura, Fraser J Glickman, Jessica Schulman, Christopher Famulare, Minal Patel, Joseph K Eibl, Gregory M Ross, Derek S Tan, Christina S Leslie, Thijs Beuming, Yehuda Goldgur, John D Chodera, Michael G Kharas Date of submission to bioRxiv: May 14, 2018 __________________________________________________________________________________ Dear Authors, Thank you for posting your manuscript titled Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia as a preprint on bioRxiv! We reviewed this work at our journal club at the Structural Genomics Consortium, University of Toronto. Compiled comments from the attendants are below. To structure the feedback, we used the quick worksheet guidelines published on PREreview. We hope this feedback will be useful to improve the manuscript. Kind regards, PreReview Journal Club  Members, Structural Genomics Consortium, University of Toronto__________________________________________________________________________________ What is the main question the study attempts to answer?Can chemical inhibition of Musashi2’s RNA-binding function be used to selectively target myeloid leukemia cells?How does Ro 08-2750 inhibit MSI RNA-binding activity? What is (are) the hypothesis?Small molecule antagonism of the RNA binding domain of MSI2 has therapeutic potential in the treatment of acute myeloid leukemia. Ro-08-2750 binds at an RNA-interacting site and competitively inhibits RNA binding of MSI2. What techniques/analyses do the researchers adopt to test their hypothesis(es)? The authors use biophysical assays, computational structural biology, cell biology techniques, and an animal model. These methods are all common to preclinical drug development and are appropriate to address the outlined hypothesis and in most cases adequately address the question being asked. Why is this study relevant? Understanding of RNA biology and its importance in human health has expanded greatly in recent years. While proteins with RNA binding domains have been implicated in disease, they are typically thought of as “undruggable” as they often lack defined pockets. MSI2 overexpression is common in AML patients with poor clinical prognosis. This study highlights that (1) RRM domains can be targeted by a small molecule antagonist and (2) that this approach may have therapeutic value in the treatment of AML. Write here any general comments you might have about the research approach. Structural studiesThe structure-activity-relationship was clearly described considering a lack of a co-crystal structure.Given that residues F66, F97 and R100 of MSI2 are also conserved in MSI1, it would have been interesting to see how Ro 08-2750 compares between both proteins. Biophysical AssaysIt would be interesting to see measurements of compound binding to MSI2, for example ITC or thermal shift assays. Cell BiologyThe assays used appeared to be well thought out and provided good evidence for target engagement and therapeutic potential in cellular models of AML. However, given the genetic diversity of AML, it would be informative to include a sentence to describe why MOLM13 and K562 cells were selected for these studies. Write here any specific comment you might have about experimental approaches and methods used in the study.In the discussion the authors state that Ro 08-2750 is the first “selective MSI inhibitor”. MSI2 was compared to SYNCRIP for selectivity; however, given the extensive repertoire of RNA binding domains found in the human genome, we feel that a more extensive characterization is warranted to make a definitive statement. This could be accomplished by either utilizing a biotinylated compound for pulldowns and MS-id or by measuring binding to a panel of RRMs.It would be interesting to see KD/KO studies alongside compound treatment to evaluate to what degree this compound may phenocopy genetic perturbation of MSI2 in AML. In addition, it would also be cool to see how the mutants deficient in Ro binding are functional in cells, which may hint at potential mechanisms of resistance. For the mouse data presented it would be informative to the reader to include both survival and tumour volume data. Additionally, have the authors done any experiments to test the suitability of this compound for in vivo use (ex. What is the PK of Ro?).Additional biophysical assay to measure direct binding of the compound to MSI2’s RRM domain would be informative, ex. ITC or thermal shift assay.Structural studiesWe found that the molecular dynamics analysis greatly complemented the structural data and enabled a thorough description of the potential binding mechanism for the Ro compounds. It would be useful to note whether co-crystallization of MSI2 and Ro was attempted, though the mutagenesis experiments provided evidence of the importance of interactions with F66, R100, and F97. It is unclear why YANK was selected to perform alchemical analysis given that the program has not yet been extensively validated and carries a “Use at your own risk!” warning. It would have been reassuring to see these calculations carried out with a more validated software.Write here any specific comment/note about figures in the paper (this could be related to the way data are displayed and your ability to understand the results just by looking at the figures).Extended figure 7 appears to be mislabeled in text and extended figure 8 is missing.For figure 3d, we felt it would be easier to interpret if annexin V + cells were normalized to the DMSO control.For the RNA-IP experiments, we would suggest that this data be presented as % input, akin to a ChIP experiment.  This would account for any changes in gene expression that may confound the interpretation of this result as well as allow the authors to probe RNAs that should not change in response to compound (ie. negative control) Write here any additional comment you might have (this includes minor concerns such as typos and structure of the manuscript).On line 216: what does “proximal” mean here?Classically, the term inhibitor would be reserved for a compound disrupting an enzymatic activity. Here, antagonist may be a more appropriate term. Any supplementary tables listed in the text should be included for readers/reviewers.  

Diurnal active photolocation enhances predator detection in a marine fishMatteo Santon, Pierre-Paul Bitton, Jasha Dehm, Roland Fritsch,  Ulrike K. Harant, Nils Anthes,  Nico K. Michielsdoi: https://doi.org/10.1101/324202     Who we are:We are a group of zoologists at different career stages with a diverse background. We have started a preprint review journal club in order to discuss topics across our different areas of concentration to stay up-to-date with the latest research and get practice writing reviews. We selected this preprint, “Diurnal active photolocation enhances predator detection in a marine fish,” by Matteo Santon et al. due to the interesting experimental design and general interest of the topic. This manuscript built upon a body of previous work in a logical, easy-to-read way. The authors demonstrate experimentally that diurnal active photolocation exists in diurnal fish and that it aids in predator detection. We were generally impressed by the experimental design and the thorough treatment of the topic. We do, however, have a few questions that we could not answer by reading the manuscript and also some comments on the presentation of the information. Questions:For the lab experiment: a. What kind of glass was used for the partition between the triplet and the predator? This is explicitly stated for the field experiment (spectrally neutral Evotron Plexiglas), but we were wondering if the same glass was used in the laboratory experiments?b. What is the purpose of the “sub-optimal substrate” strip of gravel along the long side of the tank and why is it not included in the schematic drawing of the setup? c. In lines 200-201, the authors state, “Both stimuli were simultaneously present in the tank, but only one was visible to the triplefins.” Here we would like to know how they prevented visibility of one stimulus and suggest that the spatial relationship be stated or illustrated more clearly.

“In silence and movement you can show the reflection of people.”  Marcel Marceau

I remember the thrill of walking on the theater stage for the first time. At the age of eleven I took a local bus from our village to the closest town, Kranj, to go to a library. Although, I was a very shy boy, I had the strongest desire to be an actor since the age of seven. Before that I was determined to be a catholic priest. That was not the best profession to mention in communistic Yugoslavia, when teacher asked you who you are going to be when you grow up. It was a late fall afternoon, I was on the way to the library passing The Preseren Theater in Kranj. Some unknown force made me turn around and go to the back entry and ring the doorbell. I rang once, twice, I was shaky yet my body stood there like I was glued to the floor. As the doorbell rang, my mind was telling me run, hide, and forget about it. I pressed the doorbell third time, when I heard a voice from the top of the stairs. “Can I help you?” the voice from up above asked; it felt like God’s voice. My mouth acted on its own, “I want to be an actor!” It felt like when God called to Moses. The light on the stairs came up and a middle aged man came down the stairs. The expression on his face was priceless. He didn’t know if it was a prank or if I am serious. He just asked me for my name and phone number and said that they will call me. I was trembling and wanted to disappear from the face of earth on one hand, but being proud of myself to express out loud my inner desire; my inner truth. Looking back now, I know that in order to live your own truth, one must try to open the door to the unknown. You need to enter the darkness, where the smallest light will seem to be the brightest light. It might not be a coincidence after all, that the theatre stage is a dark enclosed space, but when the lights are turned on, the actors’ job is to bring their truth on the stage. The difference between actors and audience is that actors are people who dare to open up their soul and let their truth out. The audience laughs, cries or thinks ‘Oh, my God, that’s me!’, but they would never dare to show that vulnerable part of themselves. At the beginning stages of theater in Ancient Greece, they invented the term catharsis or katharsis, which means "purification" or "cleansing". It’s the purification and purgation of emotions, especially pity and fear; through art or any extreme change in emotion resulting in renewal and restoration. Catharsis in Ancient Greece was associated with God coming down on them. And what is God? He is the Light. He is the Truth. There are movies, I don’t particularly care much about, but I admire the actors who dare to do things I wouldn’t. An example would be Jim Carey. Wow, does he dare! An actress who seems to be nominated for Oscars every year is Meryl Streep. Are there movies with her I couldn’t care less for? Sure there are, but I would still watch them just to see her outstanding performance. She is versatile; she is different in every role that she ever played. Does that mean she is not showing her true self? Does it mean she is a total bitch in her personal life, just the way she is in the movie Devil Wears Prada? I don’t know her personally, but she doesn’t seem a bitch to me. I believe any character she portrays is actually her truth. But how can one person have so many truths? Heraclitus said, “No man ever steps in the same river twice, for it's not the same river and he's not the same man.” We are constantly changing. Being an actor means being your true self in circumstances thescript and director suggest. Stanislavsky called this suggested circumstances. Modern Hollywood calls it choices, which might not be the best term in my opinion. My acting teachers Vladimir Davidovich Tarasenko and Galina Georgievna Yerohina said within the first two weeks of our training, “There are no good actors. There are only strong actors.” What makes an actor strong? Being able and willing to open his or her soul and let the personal truth out. The second thing a strong actor must possess is a strong imagination. In a private setting we can all be strong actors. Just close your eyes and picture yourself going down the bright stairs. Feel the stairs; hear the sound of your steps. When you get to the bottom of these stairs there is a beautiful garden with flowers of any possible color. You can smell them. You see the tree and sit underneath it. Warm sun and fresh spring breeze is caressing your face. Do you feel it? Can you hear the birds in the tree above you? Can you smell the flowers? What’s the taste in your mouth? If you practice meditation, you know how it can change your mood. It might be just for a moment or it might be lasting much longer. Meditations, hypnosis, acting, are all based on the same principles. The only difference is, as an actor you dare to do it with open eyes and in front of the audience. Some actors feel they can express their truth better by being under the influence of alcohol, marijuana or other drugs. I have done experiments myself over the years of my acting career. I came to the conclusion; my truth under an influence was kind of obscured. During my auditions I might have felt that I am doing a brilliant job. But when I got sober and I saw the tape, I saw myself as an imposter who is trying to imitate someone else’s truth. I have also noticed, while being under an influence, I have loved myself in art and not the art in myself. Yes, I agree that it may fly for some roles, but at some point you start imitating and repeating yourself. Being an actor you are always a bit above ground, so using alcohol or drugs will just make you so light that you can be blown far, far away. That said, I believe addicts can find a new path by getting trained to be actor. I believe being true to yourself can cure many things. You don’t need to become an actor, but acting training can help you on your spiritual and personal path. When we lie, we are not doing a favor to another person. But telling the truth might be hurtful, you may say. Not if it is said at the right place, at the right time and with the right intention. In order to do that, you need to evaluate the situation really well. That is exactly what actors do; evaluate the situation and the suggested circumstances. After I moved to Los Angeles, I tried to take acting classes to spruce up my craft. I ran into several acting teachers that were repeatedly saying to all students how great we were. I felt they only wanted the money and they didn’t care about helping actors get to the next level. So, I gave up on taking classes and instead started offering them. I was surprised how my students got offended when I told them theysimply stink in a certain scene they showed me. Very quickly I realized Hollywood actors have much bigger egos than acting students in Russia. In the Academy I learned to take good and bad criticism and apply it to my growth as an actor; that’s the way I see it. That’s the way I believe. After that experience I decided to start taking, under my wing, only students that can handle the truth. Of course I always try to evaluate the situation and I have softened my approach as a critic. Although, I still always tell my students everything I think. For an acting teacher it is important to accept student’s personal truth when criticizing their work. When I taught a master class in Crete (Greece), I had students from various countries, but the majority was from Greece. Since my best friend is Greek, I knew their temperament and their gestures are very different than mine. There I had a student that I just couldn’t believe when she did a short scene. I told her, “I don’t believe you because of the way you move your arms.” Either she doesn’t move them enough or she moves them too much. She admitted, in her real life, she uses hands much more when she acts. I told her to repeat the scene and use her hands as she would in her everyday life. The scene came to life. It is hard to learn living the truth, but we get used to it. When you wash dishes with the water that is very hot, you can decide to add some cold water to it or you quickly wash it under the hot water. If you go with the second choice and repeat it every day, I can guarantee before a month is over, the hot water will feel comfortable. Solid and regular training helps you to become a master of your craft and be comfortable in every situation you find yourself in. Practice, practice, practice! There is no wrong or right. It is just truth or lie. Will the audience believe you or not. And do not forget to love art in you and not you in art.

Well known Dirichlet series include: \zeta(s) = ^\infty {k^s}\\ {\zeta(s)} = ^\infty {k^s}\\ {\zeta(s)} = ^\infty {k^s} If we define the inverse Dirichlet transform to map like \zeta(s) \to 1 \\ {\zeta(s)} \to \mu(k) \\ {\zeta(s)} \to \lambda(k) then we can track less standard variations by creating ratios of zeta functions: {\zeta(s)}\to A210826(k) \\ \zeta(s)^2 \to d(n) = \tau(n) \\ {\zeta(s^2)} \to (k)\\ {\zeta(s^2)} \to {k^q} \\ {2})}{\zeta(s+{2})} \to {k} \\ = ? Consider the duality of ζ(s)→Γ(s) with inverse Mellin transform... DIRICHLET SHIFT OPERATOR We could consider an operator O− (O+) which shifts the argument of a zeta function by −1 (+1). Then use something like the product and quotient rules, to define this on Dirichlet generating functions O^-[\zeta(s)] = \zeta(s-1) \\ O^-[\zeta(s)\zeta(s-1)] = \zeta(s-1)^2 + \zeta(s)\zeta(s-2)\\ O^-[{\zeta(s)}] = {\zeta(s)^2} we can then define the ’number theoretic derivative’ of a function for this latter one we appear to have {\zeta(s)} \to \lambda(n)*A000188(n)\\ {\zeta(s)^2} \to A074722(n) so as ζ(2s)/ζ(s)→λ(n) we could say $$ \delta \lambda(n) = \lambda(n)*A000188(n) - A074722(n) = 0,-1,-2,0,-4,1,-6,-4,-2,1,-10,-4,-12,1,-2,-2,-16,\cdots $$ where clearly, we have every prime, δλ(p)=1 − p, this is nice. We have depending on definition \delta \mu(n) = -A007431(n) \mu(n)-A007431(n) this is $$ \delta \mu(n) = - \phi(d) \mu({d}) $$ and therefore $$ \phi(n) = - \delta \mu(d) $$ then \delta |\mu(n)| = \delta {\zeta(2s)} = {\zeta(2s)^2} = {\zeta(2s)} - {\zeta(2s)^2} \\ \delta |\mu(n)|= A063659(n) - H(n) where H(n)=1 unless n = 9, 16, 18...?, and 2 otherwise. It seems that $$ {\zeta(s)} = ^\infty {(k^2)^s} = ^\infty }(k)\phi()}{k^s} $$ then there is the convolutions $$ {\zeta(2s)^2} = |\mu(n)|*_D }(n)\phi() = |\mu({d})|}(d)\phi() = }(n)\phi() + (1-}(n)) = H(n) $$ we have \delta \tau(n) = 2 \sigma_1(n)\\ \delta \sigma_1(n) = n \tau(n) + \sigma_2(n)\\ \delta \sigma_2(n) = n \sigma_1(n) + \sigma_3(n)\\ \delta \sigma_k(n) = n (n) + (n) noting that σ−1(n)=σ₁(n)/n, also then \delta n\tau(n) = 2 \sigma_1(n) \\ \delta \tau(n) = 2 \sigma_1(n)\\ \delta^2 \tau(n) = 2n \tau(n) + 2 \sigma_2(n) \\ \delta^3 \tau(n) = (4+2n)\sigma_1(n) + 2 \sigma_3(n) By thinking carefully about the linearity of derivatives and implying the δ is a linear operator, then we can easily show that \delta ^k \log(n) = n^k \log(n) for all integer k. In fact in general $$ \delta ^k \log^l(n) = n^k \log^l(n) $$ A stunning result appears to be $$ \delta \Lambda(n) = \log(n^{\phi(n)}) $$ for which the DGF is $$ {\zeta(s)^2} - {\zeta(s)} $$ FURTHER OPERATORS Consider the operator $$ \kappa = [{\zeta(s)} \delta \zeta(s)] $$ such that a factor of ζ(s) is applied, the derivative taken, and then the factor removed. $$ \kappa \zeta(s) = {\zeta(s)} \delta \zeta(s)^2 = {\zeta(s)} 2 \zeta(s)\zeta(s-1) = 2 \zeta(s-1) $$ therefore $$ \kappa 1 = k $$ we also have \kappa \zeta(s-1) \to {\zeta(s)} + \zeta(s-2) \\ \kappa k = P(k) + k^2 where P(k) is A018804(k). We can consider more complicated operators $$ \epsilon = 1 + \delta + \delta^2 + \delta^3 + \cdots $$ then $$ \epsilon \zeta(s) \to \zeta(s) + \zeta(s-1) + \zeta(s-2) + \cdots $$ which implies $$ \epsilon 1 = 1 + k + k^2 + k^3 + \cdots = {1-k} $$ KERNEL GUIDED TRANSFORM For the Lambert transform we have the nicve property that $$ ^\infty a_n {1-x^n} = ^\infty b_n x^n $$ where the relationship is $$ b_n = a_n $$ but we can generalise this by realising that $$ ^\infty a_n f(x^n) = ^\infty b_n x^n $$ where $$ f(x) = ^\infty \kappa(n) x^n $$ generates a new transform, we then know for κ(n)=1, we have the Lambert transform. RATIO OF SIGMA If we let $$ \kappa(n)={\sigma_1(n^2)} $$ then it seems if an bn ζa ζb ------- ------------------ ------------------------------- ------------------------------- μ(n) nϕ(n) 1/ζ(s) ${\zeta(s)}$ ϕ(n) n² ${\zeta(s)}$ ζ(s − 2) μ(n)² A034444(n)=d*(n) ζ(s)/ζ(2s) ζ(s)²/ζ(2s) σ₁(n) ... ζ(s)ζ(s − 1) ζ(s − 2)ζ(s)² n σ₂ ζ(s − 1) ζ(s)ζ(s − 2) If we let $$ \kappa(n)=\phi(n) $$ then it seems if an bn ζa ζb ------ ------------------------- ------------------------------- ----------------------------------- ϕ(n) ∑d|nϕϕ ${\zeta(s)}$ ${\zeta(s)^2}$ μ(n) ∑d|nϕμ ${\zeta(s)}$ ${\zeta(s)^2}$ 1 n ζ(s) ζ(s − 1) n $^n gcd(n,k)$ ζ(s − 1) ζ(s − 1)²/ζ(s) If we let $$ \kappa(n)=\mu(n) $$ then it seems if an bn ζa ζb ------ -------- ------------------------------- --------------------------------- ϕ(n) ∑d|nϕμ ${\zeta(s)}$ ${\zeta(s)^2}$

This is a review of the preprint entitled " On the overlap between scientific and societal taxonomic attention - insights for conservation", by Ivan Jarić, Ricardo A. Correia, David L. Roberts, Jörn Gessner, Yves Meinard, and Franck Courchamp. The preprint was originally posted on bioRxiv on June 3, 2018 (http://dx.doi.org/10.1101/334573). Our journal club reviewed this preprint in the meeting of July 6, 2018.

A document by Benedict Irwin, written on Authorea.

This is a journal club review of Differential encoding of predator fear in the ventromedial hypothalamus and periaqueductal grey, posted on bioRxiv (DOI: 10.1101/283820)

Preface This article provides a discussion about knowledge and how the University practice of and ideology behind knowledge dissemination to the public fits within our current Economy of Knowledge Abundance. Here, I suggest that University methods for knowledge delivery to the public need to be reconsidered and approached in a different way. I begin to discuss how faculty can start to think and address the problem of knowledge dissemination to the public in a knowledge abundance economy. In the last two sections, I also provide a way for how Presidents, Vice Presidents or Chancellors of Research (VPR’s/VCR’s), Provosts, and other Upper Administrative leaders of Universities can support this approach in conjunction with State Regents/Education Boards/Board of Trustees. Introduction Knowledge dissemination is a phrase that is used ubiquitously across the academic landscape. Originally, knowledge dissemination practices were based on the pre-Knowledge Abundance Economy Era or the Era of Knowledge Scarcity. In the Era of Knowledge Scarcity, Universities were considered by many to be a beacon of knowledge and thus it was imperative that Universities and the individuals in them set up mechanisms to provide knowledge to the public. As more knowledge was provided and technological acuity increased it prompted the use and development of technological “Knowledge Systems”, (a.k.a. knowledge-based systems) - especially in the context of knowledge management (KM). In this context, a knowledge-base is defined as a collection of complex structured and unstructured information used by a computer system. This term, knowledge base (KB), was originally employed in connection with expert systems (a.k.a. experts). So, it is not surprising to hear in Academic circles KB being used frequently in this way – “That we, individuals in the University, are contributing to the knowledge base”. Which is an approach that works very well within the context of traditional academic knowledge dissemination practices and ideology.* From an Academic perspective, there is a knowledge base/s and someone in the Academy will add to it. Again, this assumes that knowledge is stable, knowledge is wanted or needed, and that it is valued by the public.  Our Changing World However, we no longer live in the Era of Knowledge Scarcity. Universities and Industries along with their corresponding knowledge management systems have had to wrestle with this scenario for at least the last three decades. “Knowledge Systems”, (a.k.a. knowledge-based systems), now must account for a knowledge base (KB) that approaches infinity. In addition, there are now mechanisms that the public recognizes and uses like a KB. Examples of these would be Facebook, Twitter, LinkedIn, Tumbler, Snap Chat. In many cases, even the Google Search Engine is being used like a KB for the public. There are now more than 200 social media sites and by other estimates there are more than 800 social media sites that are and can be used as a KB. This does not include the numerous websites and webpages that the public is using as KBs. The total global population in January 2018 was estimated to be 7.593 Billion. A summary of the 2018 Global Social Media Research Summary Report shows that the number of people using social media went up by 13% in 2018 to 3.196 Billion since last year. The number of internet users world-wide went up by 7% in 2018 to 4.021 Billion compared to last year. The number of active mobile phone social users went up by 4% to 2.958 Billion since last year. All of this suggests that there has been a change in what and how the public obtains, envisions, prioritizes, and counts as knowledge.   Defining Knowledge in the New Economy Our understanding of what constitutes knowledge has changed in the last 10 to 15 years for the public. Meaning that the ideology and practice of knowledge dissemination to the public is now a little bit of a misnomer. Because knowledge, especially for the public, implies a use function. This must not only be of use to the individual providing it but also to those who receive it. For example, if someone claims that they have knowledge of a subject and cannot demonstrate/show that knowledge to someone else, then the knowledge claimed is put into question. Knowledge must have a multi-user function. Most dictionaries describe knowledge as facts, information, and skills acquired by a person through experience or education; or, as the theoretical or practical understanding of a subject or awareness or familiarity gained by experience of a fact or situation. For western philosophers and scholars of knowledge, defining knowledge appears to have been debated for centuries. Some older known philosophers and scholars known for these debates include but are not limited to Kant, Locke, Plato, Kripke, Gettier, Blackburn, Nozick, Kirkham, Wittgenstein, and Moore. Aspects of this debate over what is knowledge still goes on today.** Currently under a western perspective, there is wide-spread agreement on three conditions, but not consensus, on what constitutes knowledge. They are: if the person believes the statement to be true; the statement is in fact true; and if the person is justified in believing the statement to be true. These three conditions embody Justification, Truth, and Belief or JTB for short. One can find a short synopsis on JTB by clicking here. Both the dictionary and scholarly definitions of knowledge are correct. Showing how both definitions are correct is a topic for another discussion. However, in the context of the public and our current (new) knowledge abundance economy, synthesis of the dictionary and scholarly definition of knowledge can be best understood in general through the following definition. Knowledge can be described as useful, or recognized as being useful, coherent well-organized packets or containers of information that embody at least the three JTB conditions. When this packet or container (of information) is used by the receiving individual, the container is opened, and the organized information inside is interpreted under JTB conditions into some usable form called knowledge. The reason that a particular container would be used can be as simple or basic as an individual wanting to understand a little more about a topic. Note: Above, the phrase, “some usable form called knowledge”, was used because one hundred percent (100%) knowledge transfer is a persistent myth. Corruption, perversion, and misinterpretation of knowledge happens among individuals and groups – regardless of educational attainment. Aspects of these coherent well-organized packets or containers of information can also be just useful enough for someone to reject or modify. This would still constitute knowledge. Rejection or modification of knowledge could be based on a number of things, for example - religion, ignorance, illness, stupidity, and the Dunning-Kruger Effect. Discussion points that would generate much debate between philosophers and other scholars of knowledge. If all these points are considered, this could imply any knowledge disseminated, under academic traditional practices, to the public would be considered disseminated potential-stored knowledge or organized information rather than knowledge itself. This would be somewhat analogous to potential energy and the idea behind a photon (in general, a packet of energy). Disseminated knowledge is similar to potential energy because it has yet to be acquired, used, or put into motion by the public user within the context of a system. The system here includes: individuals mental models; distributors, sharers, and users of the disseminated potential-stored knowledge; a medium; type of delivery; and already existing information external and internal to the distributors, shares, and users.   Disseminated knowledge is also like a photon, because disseminated knowledge acts and behaves as a subatomic “Conceptual” particle. It has a certain frequency, speed, velocity, and transfer potential. Just like there could be wasted packets of energy (photons) there could be wasted packets of organized information (potential knowledge).   University Knowledge Dissemination and the Public in the Era of Knowledge Abundance What has happened and is currently happening, is that many coherent well-organized packets of information, when released (disseminated), don’t get used, and stay in their most basic form (that is, they’re untapped). The basic form of knowledge is useful coherent well-organized packets of information. Traditional academic knowledge dissemination practices become increasingly limited in an abundance environment. This occurs in an abundance paradigm because the knowledge base exponentially approaches infinity. Under these circumstances, formal knowledge representation (formal knowledge bases and their systems) are easily converted into constantly changing semi-formal, formal, and informal ways of knowing by the public to depict the world. These depictions are based on the cultural norms of the individual, group, or subgroup represented in the public. More importantly with the wide use of mediums like Facebook, LinkedIn, Google preferences, and etc., individuals, groups, and subgroups can either create or house their own knowledge base or pseudo-knowledge base systems. Result being, that for better or for worse, individuals or groups in the public are increasingly accessing knowledge from sources other than the University or well-established and tested knowledge systems. This also allows individuals, groups, or subgroups to pick and use the first pieces of coherent well-packaged information (knowledge) available that works for them. Even if it is wrong. Thus, in this abundance economy, knowledge may not be seen by the public as stable (such as coming from a stable fact-checked knowledge base), knowledge may no longer be needed or wanted, and there is enough knowledge that at any point in time that different types of knowledge can be viewed as having little to no value. Reconsidering Our Approach Disseminating knowledge to the public in an abundance of knowledge economy does not guarantee its use. Knowledge disseminated to the public without the public being able to use it, is waste. In fact, it might not be considered knowledge at all, just more information. In a knowledge abundance economy, knowledge must have a receiver/user to be knowledge. This suggests that knowledge is also finite and not indefinite. In other words, for the public, knowledge has an expiration date. In addition, universities and faculty in them are increasingly being forced to reconsider how they interact with the public. This has been due to several changes in the national and international landscape (e.g. state funding, governmental funding, politics, usefulness of the University conversations initiated by the public, declining enrollment, increasing ethnic and gender diversity, proliferation of social media, and national and international wicked societal problems). One critical step that would help universities successfully navigate this new landscape and economy would be to tweak how individuals/faculty in the University approach a community. This would require universities and faculty to change their ideological values about and practice concerning, “disseminating knowledge to the public”. Individuals/faculty would need to highly value and embrace some new perspectives, like “sharing, communicating, mobilizing, translating, managing, and propagating knowledge with and for the public”. Such a suggestion implies a more strategic approach. It implies understanding and working with those whom the information will be most relevant before the sharing, communication, translation, management, propagation, and mobilization process begins. This requires individuals and universities to know and develop relationships with the public outside the context of a recruitment mindset, a project need, or a requirement to get funding. It may also mean that it might be required, in some cases, that knowledge be co-constructed with the relevant individuals or groups in the public. Full or partial infrastructure needed to advance and support these approaches are already in place at many universities nationally and internationally. This infrastructure is typically comprised of Societal Benefit Professionals (SBPs). A few examples of SBPs at universities that could be better utilized for this endeavor are: community engagement and engaged scholarship professionals; broader impacts professionals (for the National Science Foundation, other agencies, and in general); and knowledge mobilizers, brokers, and translators. There are also a number of Societal Benefit Organizations (SBOs) that act as “boundary organizations” that could be used for this purpose to help share, communicate, translate, propagate, and mobilize University knowledge with and for the public. Boundary organizations sit either inside or outside the University and work with individuals in the Academy and in the public. In addition, several different types of University technology transfer centers, marketing offices, and communication departments and colleges could be employed with numerous types of SBPs and SBOs to support this proposed approach. However, for universities to fully embrace these new perspectives there must be high-level administrative support, a change in University culture, and a revaluing of what matters in departments concerning tenure. This starts with Presidents, Vice Presidents and Chancellors for Research (VPR/VCR), Provosts, and other Upper Administrative leaders embracing this change through formal University structures. Approach for Vice Presidents and Vice Chancellors of Research (VPR/VCR) For VPR’s and VCR’s, this means to create Assistant or Associate Vice President or Chancellor for Research, Society, and Impact (VPRSI/VCRSI) positions in their organizations. These VPRSI/VCRSI positions would support, engage, and work with and for “ALL” researchers and society to help an institution, VPR/VCR office, graduate and undergraduate students, and specifically faculty navigate their research with, for, and in the context of the public domain to maximize research impact. In addition, VPRSI’s/VCRSI’s and their offices would help individuals/faculty evaluate the effectiveness of their research impact endeavors and the research impact for an entire University.  This position would also allow University systems and VPR/VCR offices to effectively take advantage of the relationship between increased researcher public positive engagement and increased University funding. This relationship between public engagement and funding is a phenomenon that has not been adequately explored in the United States (US). However, as research funding is challenged, the relationship between public engagement and research expenditures is becoming a greater focus in the US and internationally.  Funding for research is not the only driver for increased institutional, office of VPR/VCR, and faculty/researcher engagement with the public. A culture change is beginning to happen throughout the world in which the society is requiring Universities to provide, work for, and with the public to increase the impact of University research. This impact implies an emphasis on the end user and not solely the researcher and University. There are now several national and international mechanisms bringing together individuals and organizations in the non-profit sector, government, Academy, and Industry to support and better address the public call for a Societal-Centric Research University Impact Culture. A few examples of these national and international mechanisms include the: National Alliance for Broader Impacts Summit in the US; Knowledge Mobilization Forum in Canada; and the International Impact of Science Conference. Note: The Impact of Science Conference is not just focused on the impact of science. It is concerned with the impact of social science, arts, humanities, and all aspects of research impact in the public domain.   Approach for Presidents, Provosts, Other High-Level Administrators, and Governance Boards For Presidents, Provosts, and other Upper Administrators this means to modify the University tenure guidelines and/or mandate an increased departmental and faculty value on being “Public Facing” in tenure considerations. A way that State Regents and other boards that perform similar functions could support this approach is by providing a public proclamation on the value of “Public Facing”. Public facing is when an individual/s, group, organization, entity, company, or University decides through their procedures, actions, professional responsibilities, and policies to have and encourage better: relationships; interactions; sharing; attention; mobilization; and communication (could be with the help of others) so that they can be more reciprocally involved and open to and with the public.*** “Public Facing” is used to accomplish at least three major objectives. These three major goals are to: create large positive public impacts; allow the public access and more equitable and effective use of information; and help individual, groups, and universities emphasize outcomes and outputs rather than only outputs and activities in the public sphere. In the context of knowledge dissemination to the public, most University tenure guidelines are either non-existent or outdated – based on 13th – mid 20th century values on knowledge. Times when knowledge scarcity was considered the norm. These outdated values on knowledge have shaped University departmental and faculty beliefs and values on what matters for tenure. Many departments and the faculty in them still adhere to an “Ivory Tower Approach” on knowledge as the primary indicator of tenure worthiness. This is evident by the low value put on “Public facing” by Committee A’s/tenure committees, already tenured faculty, and departmental/school chairs in departments across the nation.   Summary Times have changed, the world has changed, we have moved past the Era of Knowledge Scarcity, and are not going back. We are now in the Age of Knowledge Abundance. It is time for our University, departmental, and faculty tenure policies and values to reflect the current times, the current age, and how the public currently deals with knowledge. In a public domain, “Knowledge is art, a useful gift, it needs to be shared, and those who successfully share it in a way that it gets used are well-respected and highly esteemed artists”. These well-respected and highly-esteemed individuals embody public facing. After all, knowledge dissemination from the public’s perspective, equates to just providing more information if it has no use or perceived as useful. Simply because anyone can provide information in this age. How useful is that?     Notes* In health fields and medical universities in the US and around the world, there has been increased movement away from traditional University knowledge dissemination practices. Knowledge dissemination is now being shifted and/or equated to knowledge translation practices. Knowledge translation is more in line with knowledge mobilization depending on the field of study, profession, or industry. This is especially salient in Canada. Like knowledge mobilization, knowledge translation also seeks to put knowledge into action with the end user in mind. Many times, with emphasis on impact in terms of the non-academic user. **It is important to recognize that there are other notions and thoughts to what constitutes knowledge. Many of these notions come from civilizations well-established before European Western Civilizations. These civilizations influenced western scholarly thought on knowledge. Examples of these are Asian, Indigenous, and African civilizations. For the purposes of this article, this will be discussed in further detail at another time. *** Public Facing was a phrase used by Dr. Karlos Hill in a conversation he and I had that summarized my advice on how institutions, organizations, individuals, and faculty could be more impactful in today’s knowledge abundance environment.

We can transform functions in the summands of an Engel expansion to sequence terms and or generating functions. A list gives E\left[{G(1+n)G(2+n)(2,2)_n}\right] \to A273935 = n!(n-1)!(2^n-1) \\ E\left[{G(1+n)G(2+n)}\right] \to A010790 = n!(n-1)! \\ E\left[{G(1+n)G(3+n)}\right] \to A129464 = -n(n+1)(n-1)!^2 \\ E\left[ 2^{-n^2-n+{24}} \pi ^{{2}+{4}} G(n+3)}{A^{3/2} G\left(n+{2}\right)}\right] = C(n) = {(n+1)!n!} \\ E\left[{\Gamma(n+1)}\right] \to 1,1,2,3,4,5,6,7,8,9, \cdots \,n \\ E\left[{\Gamma(n+1)^2}\right] \to 1,1,4,9,16,25,36,49,\cdots \,n^2 \\ E\left[{G(1+n)}\right] \to 1,1,1,2,6,24,120,720, \cdots \, n! \\ this is generated by the product of the reciprocals of the sequence terms ^n {a(k)} = E^{-1}(a(n))

Consider a transform that acts on a function to extract the product series coefficient. For example if a function allows a series expansion f(x) = ^\infty (1 + a_k x^k) = ^\infty b_k x^k then we define the transform K of f to be K_x[f](s) = a_s likewise the inverse transform gives K_s^{-1}[a_s](x) = f(x) then by definition of the Pochhammer-q function we have K_x[{2}(-1,x)_{\infty}] = 1 \\ K_x[(q,q)_{\infty}] = -1 then certain functions with number theoretic potential can be defined by the inverse transform K_s^{-1}[\lambda(s)] \\ K_s^{-1}[\mu(s)] \\ K_s^{-1}[\phi(s)] \\ K_s^{-1}[\Omega(s)] \\ for functions λ(s),μ(s),.. the Liouville function, Moebius function, totient function etc. If we attempt to extract the coefficeints of a well known function, for example \exp(x) = (1+1x)(1+{2})(1-{3})(1+{8})(1-{5})(1+{72})\cdots we find that the coefficients of odd prime powers p are −1/p. We find that _x\left[{1-x}\right](s) = (s) which is the characteristic function of non-zero powers of 2, which comes from the interpretation of that number of ways to partition each number into powers of 2 is 1. We have b_7 = (a_1a_2a_4 + a_3a_4 + a_2a_5 + a_1a_6 + a_7) which is clearly a sum over the ways to make 7 from unique choices of k. Whereas terms like a_5 = b_5 - b_2 b_3 + b_1 b_2 b_2 - b_1 b_4 + b_1 b_1 b_3 - b_1 b_1 b_1 b_2 where the signs seem to correspond to the number of terms and repeats are now allowed. This gives b_n = \left(^n [k_1=n]a_{k_1}\right) + \left(^n^n [k_1+k_2=n]a_{k_1}a_{k_2}\right) + \cdots and then a_n = \left(^n [k_1=n]b_{k_1}\right) - \left(^n^n [k_1+k_2=n]g_{k_1 k_2}b_{k_1}b_{k_2}\right) + \cdots where the gkl correct for multiplicities.

The Quantum brain (QB) question.Thanks to the so-called Copenhagen interpretation, quantum mechanics has been connected with consciousness since its early days. The group around Niels Bohr suggested that  an observer is an essential part of quantum mechanics. Schrödinger's cat was an attempt to questioning that idea, not to explain it. Although many alternative interpretation have been proposed since then, the Copenhagen interpretation is still the predominant which will be found in most text books. 

It is a thing of no great difficulty to raise objections against another man's oration,—nay, it is a very easy matter; but to produce a better in its place is a work extremely troublesome.  -PlutarchIntroduction Although many twin studies have been conducted (which is quite an understatement; there are almost 9,000 hits for "twin study" on PubMed!), there have long been critics who argue that they are scientifically worthless. Obviously, the behavior geneticists who conduct these studies with the aim of separating the influences of genes from that of environment are none too happy about people calling one of their favorite research designs fatally flawed. So how do they respond, and are their responses more compelling than the original criticisms? I will dig into these in this article (which will be long, so be warned).First, I should define what a twin study is in this context. When the phrase "twin study" is used, it is almost always used to refer to a study using the so-called "classical twin design" (abbreviated CTD). So for the rest of this paper, I will use the phrase "twin study" to refer only to studies using the CTD. This type of study involves comparing monozygotic (MZ) twins and dizygotic (DZ) twins with the purpose of estimating how much of the variation in a given trait (i.e. %) is due to genes, a.k.a. "heritability". The way this is done in the CTD is by calculating concordance (the degree of similarity between each twin in a pair; referred to as correlation if a disease is being studied rather than a normal trait) on the trait in question for the monozygotic twins and dizygotic twins separately, and comparing the two concordances. (Important note: monozygotic twins-aka "identical twins"-are assumed to share 100% of their genes, while dizygotic twins-aka "fraternal twins"-only share 50% of theirs. More on the first of these assumptions later.) These concordances are then converted into an estimate of heritability (in this case, narrow-sense heritability, h2, which only includes additive genetic effects) using this formula (known as Falconer's formula):h2 = 2(rMZ - rDZ)Where rMZ and rDZ are, respectively, the phenotypic correlation (for traits) or concordance (for diseases) between MZ twins, and that between DZ twins, on the trait/disease of interest.\cite{Mayhew_2017}Thus, when this formula is used (which it typically is in twin studies), if the concordance is higher among monozygotic twins than among dizygotic twins, this is taken to be due to genetic differences between the two sets of twins, and will yield a nonzero heritability estimate. In contrast, if the concordance rates were the same between MZ and DZ twins on the trait, it would indicate an estimated narrow-sense heritability of zero for the trait, under the CTD model\cite{Guo2001}. This is obvious from looking at the formula above, where rMZ and rDZ being equal makes the value of h2 equal to 0. Note that the extent to which h2 > 0 is often conflated with the extent to which a trait is under "genetic influence" in the twin study literature.Final note: there are two other components to this model: shared and nonshared environment. The three components of the model, to recap, are: additive genetic variance (A), shared/common environment (C), and nonshared environment (E). Thus it is often called the "ACE model".\cite{hh2005} The basic idea behind this model is that total phenotypic variance is exactly equal to the sum of each of these three components: A + C + E.But there have long been many criticisms of the specific way that twin studies are conducted, and critics claim that such studies can't really separate genetic and environmental contributions to any trait. But Beatty et al. (2002) inform us that such critics are mistaken: "..., satisfactory responses to critics (see for example, Bouchard, 1993, 1994; Goldsmith, 1983; Lykken, 1995; Martin, Boomsma, & Machin, 1997; Scarr & Carter-Saltzman, 1979; Segal, 1997, 1999) have led contemporary behavior geneticists to describe the twins design as “the perfect natural experiment” (Martin et al., 1997. p. 387)."\cite{Beatty_2002}, (p. 2)Oh, so that's good to know, apparently criticisms of twin studies have already been conclusively refuted. So I'll go back to these sources later in this article to see if they actually conclusively show that critics of the twin method are wrong about its purported uselessness.Criticism 1: The equal environments assumptionFor decades, critics of twin studies have argued that they don't really separate the influence of genes and environment on a specific trait because the validity of their heritability estimates depends on the so-called "equal environments assumption" (abbreviated EEA). This is the assumption that the within-twin similarity of environmental exposures that are relevant for the causation of the trait being studied are equal for MZ and DZ twins. In other words, it assumes that MZ twins experience equally similar environments as do DZ twins, at least with regard to the environmental factors that can cause the trait being studied. If this assumption is wrong, it will lead to heritability estimates that are also wrong: if MZ twins experience more similar environments than DZ twins, this can produce higher concordance rates without any genetic influence on the trait whatsoever.\cite{Guo2001}As you may have guessed, there is a lot of evidence that MZ twins experience more similar environments than do DZ twins (for a summary, see \cite{Simons2012}; see also Joseph 2002, Horwitz et al. 2003, Rende et al. 2005). In fact, even an article by BGists aiming to defend the validity of twin studies acknowledged that "There is overwhelming evidence that MZ twins are treated more similarly than their DZ counterparts" (Evans & Martin 2000). But to be fair, that's not necessarily the same as the kind of fundamental invalidating flaw critics often portray violations of the EEA to be. Typically, behavior geneticists respond to this evidence by making one or more of the following arguments (hereafter referred to as "argument #", where "#" is the number listed corresponding to each argument immediately below):Greater environmental similarity between twins in a pair is not significantly associated with greater phenotypic similarity. This argument is based on the assumption that the EEA does not have to be entirely valid for all environmental factors, but instead just for those that are "trait-relevant", i.e. that have a causal effect on whatever trait is being studied. The practice of defining the EEA as applying only to "trait-relevant" environmental factors is common in behavior genetic research (e.g. \cite{Mitchell2007}, \cite{Bouchard_2002},\cite{Kendler_1993}). This argument further claims that the hypothesis that the EEA is invalid for trait-relevant environmental factors must be tested rather than assumed to always be true, after which studies are cited and/or performed that supposedly test this definition of the EEA. These "EEA-test" studies come in many forms: a) "perceived zygosity" or "misclassified twin" studies, a specific type of twin study designed to test the EEA. Such studies take advantage of the fact that some MZ twins are perceived as being DZ and vice versa. The idea is that if greater genetic similarity between MZ twins is what makes them more similar, then actual zygosity should have a greater impact on twin similarity, i.e. MZ twins should be more phenotypically similar to each other than DZ twins even if the MZ twins are incorrectly perceived as DZ. By contrast, if greater environmental similarity (such as is, presumably, experienced by twins perceived to be MZ, whether they are actually MZ or not) explains the greater phenotypic similarity of MZ twins relative to DZ twins, then MZ twins perceived as DZ should be no more phenotypically similar to each other than are DZ twins correctly perceived as DZ. Indeed, actual zygosity has been found to be more strongly associated with twin concordance in multiple such studies.\cite{Conley_2013} b) studies aimed at correlating physical similarity and phenotypic similarity between twins in a pair, and if no such (statistically significant) correlation is found, then it is concluded that the EEA is "valid" in that it doesn't significantly affect heritability estimates for whatever trait is being studied.\cite{Kendler_1993} c) studies including perceived zygosity as well as other measures of environmental similarity, controlling for such measures, and then comparing the "corrected" MZ and DZ correlations to see if the difference between the two correlations remains significant. Two such studies have found that it does.\cite{LaBuda_1997}\cite{CRONK_2002} Greater environmental similarity between members of an MZ twin pair than a DZ twin pair, rather than causing the greater phenotypic similarity between MZ than DZ twins, is actually due to the MZ twins' greater genetic similarity. This argument posits that because MZ twins are more genetically similar than DZ twins, they are treated more similarly and have more similar behavior, which in turn leads to the environments of MZ twins being more similar than those of DZ twins. Many twin researchers have made this argument since at least the 1950s. It has been widely criticized as circular because it assumes that the greater genetic similarity between MZ than DZ twins causes their greater phenotypic similarity, which is also what it purports to demonstrate.\cite{Joseph_2012} Non-CTD studies that do not rely on the EEA generate similar heritability estimates to CTD studies for the same trait. Ostensibly, the similar results generated by these non-CTD methods "validate" the EEA on which CTD studies depend. The word "validate" or derivatives thereof is often used in this literature (for two recent examples, see \cite{Kendler_2014} and \cite{BARNES_2014}). The methodologies of these studies include twins reared apart, adoption studies, and full- vs. half-sibling studies.\cite{BARNES_2014}Response by critics of behavior geneticsCriticism 1: Response to Argument 1Joseph commonly rebuts this argument by pointing out that it reveals a different standard of logical inference that twin researchers use in assessing twin studies versus family studies. Specifically, according to twin researchers, the greater similarity of environments among MZ compared to DZ twins does not necessarily invalidate the classical twin method as a means of separating genetic and environmental influences, but the greater similarity of environments shared by members of the same family relative to members of the general population does necessarily invalidate the ability of family studies to separate such influences. For this reason, Joseph argues that twin researchers are guilty of special pleading by arguing that standards that apply to family studies should not apply to classical twin studies. As an example, he wrote in 2002 that: "genetic researchers acknowledge that family studies do not prove the existence of genetic factors—since the clustering of a condition among family members could be caused by purely environmental factors. However, no one to my knowledge has argued for a “trait-relevant EEA” for family studies; that is, the claim that family studies prove the existence of genetic influences unless specific environmental factors shared by family members are demonstrated to have a causal relationship to the condition in question. Quite the contrary; family studies are acknowledged to be confounded by the simple fact that family members share a common environment. In the same way, the twin method is confounded by the greater environmental similarity of MZ twins, regardless of whether the specific trait-relevant environmental factors are known."\cite{Joseph_2002}, (p. 76)Joseph also notes that by using this argument and defining the EEA as needing to be "trait-relevant", twin researchers attempt to falsely claim that the burden lies on critics of the classical twin method to prove that MZ environments are more similar than those of DZ twins specifically with regard to those environmental factors that affect a given trait. He also points out some other logical problems with this argument in some of his papers.\cite{jay2013}\cite{Joseph_2002}In addition, Joseph and other researchers have been highly critical of the EEA-test studies cited as part of this argument.\cite{jay2013,Joseph_2012}\cite{Richardson_2005}\cite{Beckwith_2008}Criticism 1: Response to Argument 2Joseph has noted the following about this argument: "...this is a circular argument, because twin researchers' conclusion that MZ-DZ differences are explained by genetics is based on assuming the very same thing."\cite{jay2013}, (p. 5) Furthermore, he points out some other logical issues with it, such as that it portrays "...children (twins) as behaving according to a genetic behavioral blueprint, yet somehow parents and other adults have themselves tossed aside the blueprint and are able to flexibly change their behavior and treatment of others on the basis of the twins' behavior and personalities," which he wittily sums up with the phrase "Genetically-programmed human children, meet your ever-so-flexible human parents." He has also pointed out another problem with this argument, namely that "...even if twins do indeed create more similar environments for themselves because of their greater genetic similarity, MZ pairs could still show much higher concordance for psychiatric disorders than DZ pairs for purely environmental reasons."\cite{Joseph_2012}

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For many years, it has been speculated that consciousness and cognition could be the based on quantum information  (Atmanspacher 2015) which opposes the view  that  quantum coherence, the primary basis of quantum computing (Nielsen 2010), cannot survive in complex biological systems (Koch 2006, Tegmark 2000). However, recent findings in photosynthesis (Engel 2007, Collini 2010)  have challenged this view suggesting that only long-range quantum coherence between molecules can account for its efficiency in light-harvesting. Here, we investigated if long-range quantum coherence may also play a decisive role in brain function. We found  surprisingly that the cardiac pressure pulse  evoked  zero-quantum coherence (iZQC) (Warren 1998) which were by a magnitude higher than theoretically expected.  From this finding, we concluded that underlying physiological process is  - cautiously speaking - of an unknown macroscopic non-classical kind. The process reveals it importance by it temporal appearance; during consciousness it is highly synchronized with the cardiac pulse,  while during sleep,  no or only sporadic  iZQC could be detected. This findings suggest that this non-classical phenomenon is most likely a necessity for consciousness. 

Frequency of disturbance alters diversity, function, and underlying assembly mechanisms of complex bacterial communitiesEzequiel Santillan, Hari Seshan, Florentin Constancias, Daniela I. Drautz-Moses, Stefan Wuertz, May 4th 2018, bioRxiv[doi: https://doi.org/10.1101/313585] Understanding the effects of disturbance on ecosystem function and diversity has many potential applications in microbial ecology and human disease biology. In this paper, the authors tackled the long-standing question of how different disturbance frequencies affect bacterial community diversity and function. To do so, activated-sludge communities within laboratory-scale microcosms were exposed to toxic 3-chloroaniline (3-CA) at varying frequencies. Ecosystem function and community diversity were measured weekly by measuring biomass and organic carbon, ammonia, and toxin removal as proxies for ecosystem function and T-RFLP 16S rRNA gene fingerprinting and shotgun metagenomics were performed to examine variation in bacterial diversity and community composition. This work is an excellent example of integrating genomic and functional analysis, thereby providing a more thorough understanding of the effects of disturbance frequency on microbial community diversity and function. Interestingly, both genetic methods yielded similar results, suggesting that the less expensive gene fingerprinting method could be sufficient when sequencing resources are limited. We particularly commend the use of multiple alpha-diversity measurements and the inclusion of abundance-related indices, which are less method dependent and allow results to be compared between studies. Ultimately, the authors propose the "Intermediate Stochasticity Hypothesis,” which suggests that stochastic processes produce higher diversity assemblages at intermediate disturbance frequencies while deterministic processes produce lower diversity assemblages at low and high disturbance frequencies. Overall, this paper is a fascinating and substantial contribution to microbial ecology. There are, however, a few issues that we feel could be improved in future versions of the manuscript.   Major concerns:This comment is unique to the preprint. The manuscript references multiple figures available in the supplementary materials, but these materials were not made available as part of the preprint. This hindered our ability to understand the fine points of the experiments. We encourage the authors to upload the supplementary materials to bioRxiv. 1. Figure 2 is an integral figure to the manuscript because it showcases the effects of 3-CA disturbance frequencies on community performance, namely organic carbon and toxin removal (plots A, C)  and nitrification products (plots B, D). In the Materials and Methods section (lines 353-356), the authors state that these parameters were measure weekly, which leads to the assumption that data is available for days 7, 15, 21, and 35, even though only the data from days 7 and 35 are included in the figure (is there T0 data?). The results section refers to supplementary figures S2 and S3 in addition to Figure 2, so these supplementals may portray the data of interest. However, since these data are so important to the overall conclusions, we believe it should be available in the main text. One way to accomplish this could be to have one plot per variable with time on the x-axis and different colors for each disturbance frequency. The number of plots could be reduced by not including Volatile Suspended Solids (VSS) results in the main text. In Figure 2A, the COD removal and 3-CA removal is not monotonously decreasing relative to the disturbance frequency (specifically, level 2 and 4). We figured that this was due to the number of days since the disturbance being different for each disturbance frequency at measurement time on day 7. We encourage the authors to mention and explain this in the text, as this was a puzzling feature of the results for us for some time. It also calls into question the appropriateness of the weekly measurements, especially given that some disturbance level will be highly correlated to this rhythm of measurement (level 1 disturbance will always happen on the same day of the measurements, while level 2 and others will drift). 2. Along with disturbance frequency, varied intensity and duration of disturbance and differing sampling frequencies (e.g- data collection every two days or  bi-weekly, larger spread of intermediate disturbance levels) might produce a different pattern of microbial community diversity and function. Questions we can ask are: would the system reach the observed IDH pattern at an early stage? Would the intermediate levels still follow the IDH model? We would be very interested in the authors opinions on these topics, perhaps in the discussion section. 

A review of the Biorxiv preprint entitled: Links between environment, diet, and the hunter-gatherer microbiomeGabriela K Fragiadakis, Samuel A Smits, Erica D Sonnenburg, William Van Treuren, Gregor Reid, Rob Knight, Alphaxard Manjurano, John Changalucha, Maria Gloria Dominguez-Bello, Jeff Leach, Justin L SonnenburgPosted to Bioarxiv on May 15, 2018doi: https://doi.org/10.1101/319673

IPlease summarize what you view as the key point(s) of the manuscript and the importance of the content to the readers of this periodical. The paper presents (and provides a brief tutorial) automan a framework to automate computational simulations. It also demonstrates how the framework has been used for the author publication describing EDAC-SPH. The paper presents a clear guide on how scientist of all discipline can build (or use) tools to help improve their computational pipeline to increase reproducibility. What do you see as this manuscript's contribution to the literature in this field? While, the proposed approach is not ground breaking, it is certainly a very good example of good practice. The author should be commended for the effort in making their work reproducible and sharing the tool they built to make it possible. What do you see as the strongest aspect of this manuscript? The manuscript is well written, clear and give sufficient details so that others can build on the author’s work. The article fit nicely in the category 1) and 3) of the CiSE CFP. I would even encourage the author to include a bit more about the specific use case they describe (EDAC-SPH). What do you see as the weakest aspect of this manuscript? It would have been interesting for the author to explore how their tools could integrate in modern continuous integration tool chains. I personally believe that such software engineering practices should be (strongly) encouraged in the scientific community, and I believe the author framework could easily be adapted to such concern. I would encourage the author to look into this if time/space constraints permit. A simple toy example running a few problem on Travis or CircleCI may be a good start. Comments The paper is good and fit well with the objective of CiSE. I would encourage the author to: Describe in a bit more details how the framework has been used leading to the EDAC-SPH publication (vs how it works). Experiment or at least discuss feasibility of integration in continuous integration tool chains (tools to help the scientific community adopting such practise is really needed and would increase the value of the proposed framework). Provide reference ti EDAC-SPH gitlab earlier in the paper (maybe reworking the paper ordering in line with comment 1.) . Open-source release: The code of the framework, and the code corresponding to the EDAC-SPH are both available online. However, it may be good to state that the code is under BSD license (reading the license file it seems to be the case) [concerning the publication code on gitlab, I am not sure what is the licensing practice in such scenario, but it may be good to also provide the license]. Finally the author may want to look into packaging their framework. This work will be of clear interest to CiSE readership and fit perfectly the requirements and objectives of the reproducible research track. The manuscript should be accepted after minor revisions.

SummaryThis is the editor's review of manuscript CiSESI-2018-02-0013, submitted to Computing in Science & Engineering, Reproducible Research Track: "automan: a Python-based, automation framework for numerical computing"  \citep{p2018b}.We received two peer-review reports for this manuscript, and the reviewers were: Thomas Pasquier and Olivier Mesnard. Both reviewers recommended that the manuscript be accepted with a minor revision, and I agree. Reviewer 1 comments on software-engineering aspects: he asks if automan could be combined with continuous integration tool chains. He also asks to state plainly the license of automan—from the LICENSE.txt file in the GitHub repository, it looks like it’s under BSD3, but you could state this in the README and in the paper. Reviewer 2 acted as Reproducibility Reviewer. He inspected the code repository of automan, installed it, and tested it with a fabricated problem. He also provides several minor suggestions in his open report \citep{o2018}.Editor's reviewOne issue that the author needs to correct is the terminology. The CiSE RR Track adopted a set terminology that we request authors to consistently apply. See the Call for Papers \citep{g2018}.Citing from there:Reproducible research is defined as research in which authors provide all the necessary data and the computer codes to run the analysis again, re-creating the results. Replication, on the other hand, is defined as arriving at the same scientific findings as another study, collecting new data (possibly with different methods), and completing new analyses.Throughout the manuscript, the author is using “repeatability” and “repeating” in place of “reproducibility” and “reproducing.” Conflicting terminology is a source of confusion in the field, and the CiSE RR editors want consistent usage in the magazine.I also recommend reading: “Re-run, Repeat, Reproduce, Reuse, Replicate…” \citep{Benureau_2018}AbstractCiSE articles don’t normally carry a standard abstract. Instead, a short “blurb” appears under the title, usually about three sentences long, to pull focus. Please edit the abstract down, in line with this style. Here's a starting point for your editing (or simply re-use this, if you like it):Automating computational workflows leads to more reproducible research. The Python tool automan assembles a suite of long-running computations, deploys them to your computational resources, and produces final plots from output data, all with a single command.Introduction and DiscussionIn the Introduction, you say “What is perhaps more important is that we discovered that [reproducibility] can be very profitable to the researcher.” The paper then goes into the design details and explains the usage of automan in section 3, and you wrap up with a summary in the first paragraph of section 4 (Discussion). Towards the end, the Discussion explains how automan helped you manage a series of about 75 computational experiments with SPH schemes. But I miss here a stronger, more persuasive statement about how automan expedited and ensured quality of the research (it doesn’t help that the paragraph in question is plagued with passive phrases). I would like it if you re-wrote this passage to reveal more about your own experience, and how you benefitted from the tool you created. Convince your readers here that the initial overhead of setting up automan for their simulation-based workflow will pay off!Editorial / style requestsThe manuscript is well written, overall, but a few small improvements would polish it further. In CiSE, we aim for a more readable style than typical scholarly literature. In line with that, I want to encourage you to especially look at whether any passive constructions are strictly necessary, and look to remove syntactic-expletive phrases like “there are,” if you can, as well as superfluous adverbs and superlatives (e.g., clearly, very).Examples:First sentence! “It is well known that…” You can easily remove that, and combine the first two sentences: “Reproducibility is a cornerstone in all science fields, and is vitally important in computational science.”p. 1, l. 39: “Unfortunately, there are not many immediate or direct incentives for a researcher to invest time…” >> “Unfortunately, researchers have few immediate or direct incentives to invest time…”p. 1, l. 41: “there can be significant challenges involved in [reproducing] and replicating numerical experiments” >> “reproducing and replicating numerical experiments involves serious challenges” (or another adjective, but don’t use “significant” unless you mean statistically significant, to avoid misunderstanding).p. 1, l. 45: “we believe this is a very important step in facilitating reproducible research” >> This step is important for facilitating reproducible research” (the terminology here is consistent with CiSE usage).p. 1, l. 46: “The approach used in our automation framework is fairly general” >> “Our automation framework typifies a general approach”p. 1, .. 49: “[reproducibility] can be very profitable to the researcher” (remove “very”)p. 1, l. 51: “It is our hope that” >> “We hope that"— The fact that we can pick several examples from just the first two paragraphs shows that you could polish the manuscript by combing through the text looking for just these patterns. I expect about a 5–10% reduction in word count from this exercise!p. 10, l. 40: Bad sentence: “It is important to note again that the commands that are executed such that one may configure the directory in which they will generate output using a command line argument.” Typos:Title: you don’t need the comma.p. 1, l. 38: “some of [the] most important articles” (missing “the”)p. 3, l. 21: capitalize DockerSoftware AppendixAs indicated in the Call for Papers: “articles will include an appendix reporting on the software engineering and data management practices followed by the authors.” Please add a description to that effect, in the form of a brief Appendix.Extended AcknowledgementIn the short statement on "Peer review in the CiSE RR Track" \citep{Barba}, we describe our ambitions for opening up the peer-review process in this track. Your reviewers opted in to open identity and open reports. We ask that you recognize reviewers by name in an extended acknowledgements section, briefly stating their contribution to your paper. You can cite the open reports with the URL or DOI, in each case.ReferencesPlease provide DOIs wherever possible for all references.For Ref. [1], please add DOI of the PDF version of this blog post, published on Figshare (10.6084/m9.figshare.4879928.v1).For Ref. [8], please update the citation, as needed.

Three novel treatments for bacterial diseases show high bactericidal effects, giving hope to a future without antibiotics. As antibiotic resistance continues to threaten global health, and with the progress of antibiotic discovery having slowed down dramatically in recent years, the demand for alternative methods of treating the ever-growing list of bacterial diseases has become increasingly urgent. In a paper published in Biorxiv in the last quarter of 2015, Kim & Gaitas [1] explore three novel methods of eliminating Staphylococcus aureus from blood in vitro. These involve capturing pathogens using an antibody-coated tube, killing pathogens using near infrared light, and killing pathogens using ultraviolet light. The authors investigate the viability of these antibiotic-free techniques as options for the treatment of S. aureus infections and address limitations and future research to improve and expand the application of these methodologies to other bacterial diseases. Fig 1 illustrates the experimental setup. Staphylococcus aureus is a bacterium responsible for a wide range of diseases including food poisoning and skin and bone infections. Penicillin, which was used to treat S. aureus, was quickly rendered useless as the bacterium evolved to produce penicillinase, an enzyme that breaks the penicillin molecule apart. As a result, penicillinase-resistant antibiotics such as methicillin and oxacillin were developed. Widespread use of these antibiotics led to the emergence of new strains of the bacterium, methicillin-resistant S. aureus (MRSA) and oxacillin-resistant S. aureus (ORSA).

Review the manuscript CiSESI-2018-02-0013 for _Computing in Science & Engineering_: _"automan: a Python-based, automation framework for numerical computing"_ (Ramachandran, 2018). The manuscript describes an open-source Python-based library, called automan, to automate scientific computational workflow. automan is open-source with a permissive license (BSD 3-clause), hosted on GitHub (developing the code in the open under a version-control system). The manuscript was made available on arXiv (https://arxiv.org/abs/1712.04786) before submission to CiSE and serves as API documentation for the Python package. The main purpose of automan is to automate a computational research manuscript: it provides a Python framework to assemble and run simulations (on local or distributed machines) and to generate figures from the data produced by those simulations. With automan, a user has the possibility to re-create all figures used in a research paper with one command line (as envisioned by ). The content of the manuscript perfectly fits into the types of submission sought by the RR track of CiSE (). The author gives an extensive review of already existing frameworks to automate workflows, leading to a clear explanation on the need for a new tool such as automan. As mentioned in the manuscript, automan has already been used by the author to automate the generation of the figures in an other manuscript (under review) that compares different Smoothed Particle Hydrodynamics schemes (to simulate incompressible fluid flow problems). The examples provided in the manuscript are well detailed such that it is easy for the users to adopt automan for their own workflow. As part of the review for the manuscript, I successfully installed automan and created a toy problem to test the features of the package. I used an in-house two-dimensional panel-method code (written in Python) to compute and compare the surface pressure coefficient on a series of NACA airfoils are different angles of attack. automan is modular enough such that I did not have to re-run the simulations if I was only creating/tweaking the post-processing code to create figures. When needed, I was also able to re-run only specific simulations (and not the entire batch). I created a public GitHub repository (https://github.com/mesnardo/automan-example) that contains the input files and Python scripts used to test automan. Finally, I would like to point out that automan helps users to make their computational workflow reproducible, but does not guarantee numerical reproducibility of the results. As mentioned by the author, automan does not capture the working environment (software versions, dependencies, etc.) The manuscript should be ACCEPTED AFTER MINOR REVISIONS. Following is a list of suggestions/modifications the author should address: 1. I think the author should favor the term "reproducibility" instead of "repeatability". The meanings of "reproducibility" and "replication" are clearly defined in the highly cited paper from . To add more clarity, the author could recall the definition the "reproducibility" and "reproducible workflow" in the introduction section. 2. As mentioned by the author in the discussion section, automan is a "very young package". Thus, it is very likely that the core of the package and/or the API will change in the future. Therefore, the author should mention the release version of automan on which the manuscript is based. 3. (p.1, l.47) Could the author add in the introduction the license under which the code is being developed and released (BSD 3-clause license)? 4. (p.3, l.31) The term "exactly similar" is too strong to describe a re-implementation of a feature that already exists in luigi. Maybe the author could remove the word "exactly". 5. (p.13, l.12) Small typo ("elgant" -> "elegant"). 6. (p.7, l.53; l.26 in Listing 1) I think the name of the method is make_output_dir, instead of make_output_directory. 7. (p.9, l.5) It was not clear to me which folders or directories I should delete to re-run a completed simulation. It would be interesting to add a command-line instruction as an example. 8. Although this is probably outside the scope for this submission, the developer could use a tool, such as Doxygen or Sphinx, to write the API documentation.