4,865 Matching Annotations
  1. Jun 2022
    1. Evaluation Summary:

      The manuscript will be of interest to a broad audience in structural biology, biochemistry, and enzymology. The work demonstrates the use of a cutting-edge approach in protein crystallography to investigate and visualize the complex mechanism of an enzyme, the paradigm being Mn-dependent ribonucleotide reductase R2b in complex with flavin-bound NrdI at different redox states. The work is timely and has implications for future investigation of complex biochemical processes.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    1. Evaluation Summary:

      Using an impressive experimental design, Tang et al. analyzed the effects of intraspecific (genetic) and interspecific (species) diversity in ecosystem processes carried out by forest communities. The results show that both species and genotype diversity influence productivity via changes in overall functional diversity, herbivory, and soil fungal diversity. This study will be important to ecologists and environmentalists interested in ecosystem processes and restoration efforts.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    1. Evaluation Summary:

      The manuscript shows an important role for Cav2.3 channels in SNI-mediated allodynia and firing properties of PV-expressing APT neurons. Mechanisms that underlie adaptations in chronic pain models are extremely important for the development of novel therapeutics for chronic pain and this could be a significant contribution in that regard. However, the discussion asserts that these studies are the "first direct evidence that supra-spinal Cav3.2 channels play a fundamental role in pain pathophysiology." This is an overstatement as Chen and colleagues examined the role of these channels in the anterior cingulate cortex in CCI-mediated neuropathic pain (Shen, et al., 2015, Molecular Pain).

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      Ribeiro M et al investigate the ability of a novel bispecific CD19-CD47 antibody to enhance the cell mediated killing mediated by existing drug combinations - anti-CD20 plus PIK3d/CK1E inhibitor. The novelty of this study is the restriction to CD19 positive lymphoma cells, thus potentially avoiding toxicity to non-lymphoma lineages, and the gene expression profiling to identify up regulation of GPR183 after combined treatment of CD19/47 plus CD20/PI3K/CK1E vs CD19/47 alone. Genetic and drug studies suggest that GPR183 is essential for the full activity of the triplet drug combination.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

    1. Evaluation summary:

      This study investigates the neural basis of the hidden causal structure between visual and proprioceptive signals in the primate premotor and parietal circuit during reaching tasks executed in a virtual reality environment, where information between the two modalities can be dissociated. Modelling is used to characterize the proprioceptive drift of the monkeys when integrating bimodal information. The key novel result is that premotor neurons represent the integration of bimodal information for small disparities and the segregation for large disparities between the proprioceptive and visual information, while parietal cells show reaching tuning changes that support the updating sensory uncertainty between tasks. Overall, the experiments are technically sound, and the conclusions are mostly well supported. However, a simpler framing of the paper could make the main message easier to grasp, the analysis of Bayesian models seems to lack major details, the statistical reporting is below standard, and a large part of the extensive literature on the role of premotor and parietal cortex in visuomotor behavior is lacking.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This paper suggests that assembly of CaV2.3 with b2a/b2e splice variants confers biophysical properties that enable these channels to contribute to calcium-dependent pacemaking in dopaminergic neurons. The findings could have implications for why these neurons are vulnerable to degeneration in Parkinson's disease. The work will be of interest to ion channel biophysicists and neuroscientists.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    1. Evaluation Summary:

      The authors use a comparative genomics approach to predict gene function, in particular genes that have a role in eye development. After identifying the convergent loss of SERPINE3 with vision loss across mammals, the authors confirmed its involvement in eye development by characterizing zebrafish knockouts. This work highlights the power of comparative genomics to generate hypotheses that can be experimentally validated. This work is relevant to a broad audience interested in evolution and adaptation as well as for those studying eye development and eye pathologies.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

    1. Evaluation Summary:

      The authors provide evidence suggesting the gene expression profile of a specific subset of dendritic cells define features of specific forms of non-infectious uveitis. This work suggests specific pathways in these cells that may have mechanistic import in inflammatory eye disease. This manuscript is of interested to immunologists studying autoimmunity and ocular immunity. While the paper is largely descriptive, the data it presents should serve as a valuable resource for generating hypotheses about the pathogenesis of ocular autoimmune disease.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This article proposes methodology and accompanying software for robustly fitting dose-response curves where response is a number between 0 and 1. When response is transformed using the common logistic transformation, values close to 0 or 1 become large in magnitude, unduly influencing the fitted curve after back-transformation and introducing bias in the estimate of certain parameters. The proposed approach, called Robust and Efficient Assessment of Potency, is less perturbed by these extreme measurements.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This paper combines new and previously generated data on hand preference to show that hand preference strength, but not direction, is predicted by ecology and phylogeny across primates. By drawing on the most expansive data set to date on experimentally determined hand preference, it calls existing hypotheses on the evolution of hand preference into question and shows that the strength of lateralization in humans is uniquely extreme. Its results are of interest to evolutionary anthropologists, primatologists, and evolutionary morphologists. However, concerns about intraspecific variation and the accuracy of handedness estimates for poorly sampled species are incompletely addressed by the manuscript in its current form.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

    1. Evaluation Summary:

      The authors of this manuscript, which is of interest to the cancer community, identify the chromatin regulator WDR5 as a possible new drug target in triple negative breast cancer. Targeted therapeutics for this patient population are of high scientific and clinical interest, and the authors provide a compelling case that co-targeting WDR5 along with mTOR provides a promising new therapeutic strategy.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

    1. Evaluation Summary:

      This manuscript provides a detailed structural and biophysical characterization of several complexes of the p52 homodimer of NF kB and different DNA binding sites. The main topic is the investigation of why the central base pair(s) have a strong influence on the transcriptional activity of the homodimer. The authors correlate structural changes with measurements of kinetic on and off rates to develop a model that explains the differences in activity. The paper is of interest to all working on understanding how transcriptional activity is regulated.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      The long non-coding RNA HOTAIR has been widely reported to be overexpressed in many cancers, including breast cancer, and is strongly associated with disease progression and poor patient outcomes. A valuable new mouse model was developed for studying the functional effects of overexpressing HOTAIR and the mechanism of action of HOTAIR and used to demonstrate overexpression of HOTAIR promoted breast cancer metastasis to the lung. The mouse model and the conclusions will be of interest to researchers interested in improving treatment for breast cancer.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This paper proposes that specializations in the outer hair cells' biophysical properties along the cochlea may allow them to amplify the reduced receptor potentials in a manner sufficient to explain all present experimental results. Moreover, the filtering provided by the hair cells may be beneficial for hearing soft high-frequency sounds because it decreases noise and harmonic distortions. Importantly, the amplitude of the relevant motions, even with the low-pass-filtered attenuation, are as large as those measured in the high frequency regions of the cochlea. The authors provide insights and suggestions but the paper lacks strong supportive experimental data to definitively resolve the claimed "apparent" membrane time constant conundrum.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      The manuscript describes several optimizations of classic DNA reporter constructs to monitor closely the dynamics of Wnt/β-catenin signalling during development using transgenic avian lines. As Wnt signalling pathway is essential in the homeostasis of vertebrate and invertebrate organisms, a robust tool to analyse finely the dynamics of Wnt/β-catenin pathway is of broad interest for the biology/biomedicine scientific communities.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    1. Evaluation Summary:

      The authors describe the reconstitution of axonemal bending using polymerized microtubules, purified outer-arm dyneins, and synthesized DNA origami to cross-link two microtubules. The work is of interest for the field as it shows that bidirectional sliding and bending of microtubules can be generated by a minimal set of elements.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This manuscript describes a fluorospot-based assay as a model for a methodical, step-wise and rigorous approach - that combines multiple reagents in a complex system - to study the cross-reactivity of antibody to polymorphic antigens using the malaria vaccine candidate, VAR2CSA, as a model. The authors apply monoclonal antibodies and the corresponding B cells to validate their multiplexed assay before testing small number of samples from malaria exposed donors in a pilot application of the assay. The data support the conclusions. This information will attract the attention of immunologists and vaccinologists, who are primarily but not exclusively, involved in research on malaria.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their name with the authors.)

    1. Evaluation Summary:

      The authors have engineered an anti-CD73 chimeric antigen receptor (CAR) that they express in NK cells to counteract tumors bearing CD73, which contributes to the generation of immunosuppressive adenosine in the tumor microenvironment. This is a promising approach for a new anti-cancer immunotherapy and will be of interest to oncologists and cancer immunologists. The CAR-bearing NK cells show slightly enhanced tumor killing in vitro, but preliminary data show more promising results in mice. This could be due to the CD73 CAR blocking catalytic activity in the tumor microenvironment more effectively than directly promoting cytotoxicity responses.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    1. Evaluation Summary:

      The authors report that neurons in V1 and V4 provide multiplex information of simultaneously presented objects. A combination of multi-single unit recordings, statistical modelling of neuronal responses and neuronal correlations analyses argues in favor of their claims. Pairs of neurons having similar object preferences tended to be positively correlated when both objects were presented, while pairs of neurons having different objects preferences tended to be negatively correlated. These patterns and others suggest that information about the two objects is multiplexed in time. There are, however, some unclear points that deserve discussion and further analysis that could more strongly support the claims.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This paper will be of interest to readers interested ligand-gated ion channels and their evolution. The authors show that ancestral AChR beta subunits reconstructed phylogenetically can form homomeric channels that open spontaneously. The work expands our understanding of agonist-independent AChR gating and highlights intriguing aspects of AChR evolution.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      Replication Factor C (RFC) is known to play a role in both DNA replication and DNA repair by loading a protein clamp called PCNA onto DNA junctions with a 3'-recessed end. The current paper elegantly demonstrates that RFC has a second DNA binding site that recognizes a single strand-double strand DNA with a 5'-recessed junction. The paper reports a series of interesting structures and confirms binding to both short gapped DNA and nicked DNA by RFC, causing local unwinding DNA at the ssDNA/dsDNA junctions. The paper, which is of interest to colleagues studying DNA replication and repair, should be improved through a few clarifications.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      Hart et al show that loss of mitochondrial complex I rescues succinate dehydrogenase deficient (SDH) cells. The experiments are well performed and the phenotype is potentially very interesting to researchers of cancer metabolism. The authors propose that rescue of SDH deficiency by complex I inhibition is caused by an increase in mitochondrial NADH which leads to a restoration of aspartate levels, which in turn rescues proliferation. To support the model, the authors do demonstrate that there are possible correlations of this phenotype to restored aspartate biosynthesis. However, they do not unambiguously establish a mechanism that fully defines how complex I inhibition rescues the proliferation of SDH deficient cells.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

    1. Evaluation Summary:

      The authors provide novel evidence that semaphorin signaling (SEMA3F) is engaged in the vascular endothelium and smooth muscle to confer atheroprotection. They show that SEMA3F reduces the activity of key enzyme Phosphoinositide 3-kinase to decrease smooth muscle cell proliferation, migration, and phenotype switching, which contributes to atheroprotection. The study has significant translational potential and yields a new therapeutic target.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    1. Evaluation Summary:

      Mahalingam et al. report on a new software suite, ASAP, the assembly stitching and alignment pipeline, capable of montaging and aligning serial sections at a speed leading to total time shorter than image acquisition time. The software applies to both electron microscopy and array tomography, and more generally to any data set consisting of collections of 2D images in need of in-section montaging and cross-section registration. The result is a coarsely registered volume, ready for refining with existing software suits such as SEAMLESS by Macrina et al. (2021) towards subsequent processing, such as image segmentation and neuronal arbor reconstruction for cellular connectomics. This paper will be of special interest to researchers within the field of connectomics, but also to the broad class of scientists who perform large-scale microscopy. The establishment of fast, reliable and scalable image alignment software to process the millions of images produced by modern microscopes at the same speed as they are acquired is key to accelerate research in neuroscience and other fields. The key claims of the manuscript are well supported by the data, and the approaches used are thoughtful and rigorous.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      Using mass spectrometry, Crawford et al. identify aspartate aminotransferase 2 (Aat2) as a protein whose polysome-association is increased under oxidative stress in yeast. Aat2 deletion sensitizes yeast to oxidative stress, which is paralleled by an aberrantly elevated integrated stress response, although polysome-association of Aat2 and its effect on oxidative stress response are independent of its aminotransferase activity. This provides evidence that metabolic enzymes may "moonlight" as post-transcriptional regulators. The study will appeal to experts in the fields of biochemistry, genetics, cellular and molecular biology. The presented data mostly support the authors' conclusions, but there are a few technical issues that should be addressed. These include corroborating Aat2:ribosome association and characterizing the effects of non-catalytic Aat2 mutants on the integrated stress response.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer 3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      Ivica et al. provide both functional and structural characterization of a relatively unstudied glycine receptor agonist that is structurally in between a full and partial agonist. The combination of cryogenic electron microscopy and electrophysiological approaches allows for complementary structural and functional investigations into the criteria that determine ligand efficacy at the glycine receptor. This manuscript will be of interest to both biophysical and pharmacological investigations of ligand-gated ion channels.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This paper is of broad interest to investigators studying the function and regulation of protein scaffolds, dynamic protein structure, and the regulation of the postsynaptic density at excitatory synapses. The authors develop an integrated approach using fluorescence-based biochemical methods, disulfide mapping, and discrete molecular dynamic simulations to study the dynamic supertertiary conformation of the synaptic scaffold protein PSD95.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This paper introduces Neuroscout, a new web-based platform for the analysis of fMRI data with a particular focus on naturalistic stimuli. It describes a new tool that will potentially be of great use to the neuroimaging community, and whose development is already quite mature and has a number of datasets ready to use online. Neuroscout as a tool will be of particular interest to neuroimagers and cognitive neuroscientists, but the conclusions drawn using the tool should be of interest to neuroscientists more broadly.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      A pathogen's generation interval directly affects estimates of its transmissibility (R), and the period of self-isolation or quarantine needed to prevent transmission. This study shows that the unmitigated generation interval of the original variant of SARS-CoV-2 is several days longer than previously estimated and that interventions have substantially decreased the effective generation interval. These findings improve our ability to model counterfactual intervention-free scenarios. Overall technically sound analyses support the conclusions, and extensive sensitivity analyses show that the findings are robust. However, sampling or ascertainment bias in this relatively small pre-intervention dataset or biased inputs could affect the accuracy of the reported estimates.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This manuscript describes randomly generated small proteins of <50 amino acids that can rescue the growth of an auxotrophic mutant of Escherichia coli. The authors suggest that these proteins function by binding specifically to a regulatory element in the 5' UTR of the his operon RNA, altering RNA structure to increase expression. The study suggests that functional small proteins can evolve de novo and that newly evolved small proteins can function as regulators by binding RNA. This is an exciting idea, but the suggested mechanism involving the binding of the small proteins to RNA requires additional experimental support.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This manuscript could be of interest to physicians and researchers in the field of vascular anomalies. The cohort of patients with lymphatic malformations is reasonably sized (n=30) and the claims made by the authors are supported by the data as well as by current knowledge in the field.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This manuscript analyzes human blastocysts from in vitro fertilization for three subjects (a total of 55 blastocysts), demonstrating transmission of mosaic mutations at close to expected frequencies. These studies are the first of their kind and of translational relevance for the field of clinical genetics and prenatal genetic testing, with the potential to contribute to strategies to reduce genetic disease risk in future offspring.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This interesting study identifies why or how the integrated stress response pathway regulates cell recovery upon proteotoxic stress, which is especially interesting in cancer cells resistant to proteasome inhibitors. The authors conclude that translation initiation of mRNAs encoding microtubule cytoskeleton, centrosome and ATF5 proteins is necessary to recover from proteotoxic stress. This paper will make a strong contribution to the literature.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    1. Evaluation Summary:

      Wang et al., present a thorough analysis of specific neuronal lineages in the early larval ventral nervous system with the objective to relate the birth order to circuit connectivity and function. The stated key findings of the work are (1) the identification of sharp temporal cohort divisions for the lineages under investigation, (2) synapse formation between neurons of different lineages and temporal cohorts, and (3) the observation that output neurons in this instance are born prior to input neurons. The study raises the question of to what extent these findings can be generalized.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This manuscript is one of the first broad epigenetic analyses in lung development and will be of interest to not only lung biologists but also to the field of epithelial developmental biology. Using paired transcriptomic and epigenetic data, they have uncovered a vast repertoire of signaling mechanisms underlying lung development. These findings have opened up the field's opportunities to understand and study novel pathways and have further defined a role for PI3 kinase signaling in lung development.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    1. Evaluation Summary:

      Clement and colleagues describe and illustrate the endocasts of six Palaeozoic lungfish genera from superb 3D fossil material, which are very informative for the understanding of brain evolution of lungfishes, the extant sister group to land vertebrates. Rendering important anatomical details regarding brain evolution in lungfishes, and sarcopterygians in general, this work will be of broad interest to zoologists, including vertebrate paleontologists and neuroanatomists.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      Giant dsDNA viruses, with genomes in excess of 1Mb that encode more than a thousand genes, were only recently discovered and their study offers new opportunities to understand life's evolved mechanisms. In this manuscript, Villalta and colleagues report results on one of the most complex known viruses, the Mimivirus. Its genome is compacted into magnificent fibers comprising apparently repurposed GMC-type oxidoreductase paralogs assembled as a helical coat around genomic dsDNA. Cryo-EM and cryo-ET image analysis yielded a structural model of the fiber in multiple states. The authors also provide some evidence that additional viral enzymes, including RNA polymerases, exist within the fiber assemblies. Pending the resolution of certain issues that emerged in peer review, the study will be of broad interest to biologists.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      The paper would be of interest to neuroscientists and clinician scientists interested in better understanding the mechanism of deep brain stimulation (DBS) in the treatment of Parkinson's disease. Using a combination of electrical artifact-free calcium imaging and electrical stimulation, it probes the effects of stimulation on the neural dynamics of basal ganglia structures that correlate with motor improvement. The key claims are well supported with a convincing discussion of the caveats of the methods used.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      McGregor et al. establish a new reinforcement learning paradigm for songbirds, where instead of auditory feedback (white noise) they use mild cutaneous electrical stimulation as a reinforcer. Their data shows that this somatosensory stimulus can aversively drive pitch changes of a targeted syllable in similar manners as an auditory stimulus does. They further show that the anterior forebrain pathway (AFP) and dopaminergic projections to the AFP are necessary for this non-auditory vocal learning by electrolytically lesioning the output nucleus of the AFP and by depleting dopaminergic input to Area X. Their analysis is rigorous and their data convincingly show shared mechanisms for vocal reinforcement learning using white noise (auditory) or cutaneous electrical stimulation (non-auditory).

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      Aida et al use a combination of novel experimental measurements and data processing to wrangle the complexity of bacterial growth for different media conditions. This study represents a clear example tackling the complexity of biological systems from the condition sides (~13,000 growth curves were measured) influencing the growth of a well-defined single specie of bacterium and with a reasonable first pass at data processing. The findings are ultimately simple (with essentially 3 conditions accounting all variability in the system) and easily interpretable.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This study provides novel evidence that a dopamine D2 receptor antagonist enhances model-based control of behavior, whereas blocking opioid receptors has no effect on the trade-off between habitual responding and goal-directed planning. These conclusions are based on compelling behavioral and computational modeling data and will be of interest to cognitive neuroscientists and computational psychiatrists.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    1. Evaluation Summary:

      In this paper, the authors find a link between the emergence of functional connectivity (FC) and changes in regional Cerebral Blood Flow (rCBF) in human infancy from birth to 24 months of age, which will be of interest to the increasing field investigating how the establishment of the brain's functional organization is linked to neurodevelopmental and psychiatric conditions. The data quality and complementarity are impressive for infants over this developmental period (0-2 years). Most of the key claims of the manuscript are well supported by the data. However, the relatively sparse sample and cross-sectional nature does limit interpretation.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This manuscript will be of interest to developmental biologists and pediatric cardiologists. Addressing the role of NR2F transcription factors in the fish heart, it provides novel insight into atrial chamber patterning and the formation of pacemaker cells. High-quality data are presented supporting the novel finding of a requirement of nr2f1a for restricting the production of pacemaker cells. Yet, data are currently not conclusive in claiming transdifferentiation of atrial cells in the mutants.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This is an interesting report using computational tools and large amounts of prospective samples from clinical trials to identify different signatures. Using data collected early in the infection in outpatients, the authors aim to identify a set of plasma proteins that can predict a number of outcomes, including disease progression, control of viral shedding, and the onset of antibodies during COVID-19. This study adds to the understanding of the host immune response against COVID-19, as well as the potential of computational tools for the molecular taxonomy of immune responses.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    1. Evaluation Summary:

      This study applies super-resolution imaging to the distribution of Ca2+ release channels before and after adrenergic stimulation. They make comparisons between healthy and failing cardiomyocytes. The results are specifically applicable to the understanding of contractile function in cardiac failure.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    1. Evaluation Summary:

      Bistable visual perception offers a unique window to study how perception arises and changes via an interaction between bottom-up and top-down processes. In three Magnetoencephalography (MEG) experiments with advanced neural state space analysis, this study demonstrates that two key aspects of bistable visual perception - perceptual content and perceptual stability - are mediated by slow cortical potential (SCP) and alpha-beta-band neural oscillations, respectively. The findings would be interesting for many fields, such as perception, consciousness, and attention.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    1. Evaluation Summary:

      This is a well-designed study that will be of interest to cognitive neuroscientists studying event perception and memory, particularly those interested in naturalistic paradigms. The main contribution is in growing our understanding of how interpretational differences of events are reflected in differences in neural representations of those events. While the presented results are convincing, it remains somewhat unclear what processes drive the observed effects, and thus what the role of the implicated brain regions is in memory updating.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This manuscript presents a combination of in vivo recording and optogenetic experiments that together with modeling brings a significant message: inhibition is functionally present in the newborn frontal cortex having major effects in EEG dynamics. The work challenges the view on the switch in GABAergic excitation to inhibition and extends phenomenological observations to human infant EEG data.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This paper combines evolution experiments with genomic analysis of environmental samples to study the evolution of colistin resistance in E. coli. It highlights the importance of pre-existing genomic variations in clinical strains in driving the evolution of antibiotic resistance. The results presented here are relevant for clinical and non-clinical microbiologists studying antibiotic resistance to last-resort drugs like colistin. The design of the research is simple and elegant, and the genomic data analysis connects the in vitro findings to the real world. However, the authors could better align the experimental and clinical data, and better clarify their experimental design choices.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their name with the authors.)

    1. Evaluation Summary:

      Vaccines are a major influenza control strategy in swine, but perform sub-optimally and are under-utilized. The manuscript describes a detailed genetic characterization of influenza virus variants in vaccinated versus unvaccinated pigs. The results indicate that viral reassortment, which is an important process yielding new strange of importance to man and animals, may be less common in pigs that have been vaccinated against influenza.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This is a systematic review by meta-analysis about the effect of calcium supplementation on bone health in people under 35 years old. The authors found that calcium supplementation can significantly improve BMD and BMC in young people. Moreover, a better effect of calcium supplementation was shown in people who are at the plateau of their PBM. A unique feature of this study is that it focused on people at the age before achieving PBM or age at the plateau of PBM, which is different from previous studies that mainly focused on the elderly or children.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    1. Evaluation Summary:

      This paper describes a new dotplot-based approach for analyzing Low Complexity Regions (LCRs) in proteins. The work is validated against a single protein, compared to existing methods, and applied to the proteomes of several model systems. The work aims to show links between specific LCRs and biological function and subcellular location, and study conservation in LCRs amongst higher species.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

    1. Evaluation Summary:

      Jia et al. present an exciting machine learning framework named "Selfee" for unsupervised and objective analysis of animal behavior that should draw broad interest from researchers studying quantitative animal behavior. However, there are some unresolved issues for establishing credibility of the method that needs to be addressed.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      The manuscript reports results of a combined experimental and numerical investigation of magnetotactic bacteria in strong spatial confinement and under the influence of an external magnetic field. Single cells are trapped in micrometer-sized microfluidic chambers. A variety of trajectories are found, which depend on the chamber size and the strength of the magnetic field. A detailed understanding of swimming in simple controlled confinement is essential to predict the behavior of motile microorganisms in the complex environments of their natural habitat.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    1. Evaluation Summary:

      This work offers a simple explanation to a fundamental question in cell biology: what dictates the volume of a cell and of its nucleus, focusing on yeast cells. The central message is that all this can be explained by an osmotic equilibrium, using the classical Van't Hoff's Law. The novelty resides in an effort to provide actual numbers experimentally.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This manuscript by Kosillo and colleagues presents a series of carefully carried out experiments evaluating the impact of perturbing the mTORC1 and mTORC2 protein complexes selectively in mouse dopamine neurons. By utilizing dopamine neuron-specific Raptor and Rictor cKO mice, this paper elucidated which of these mTOR complexes are responsible for the regulation of dopamine neuronal functions, revealing the importance of mTORC1/2 signaling for the structure and function of dopamine neurons. This paper provided comprehensive data including structural, physiological, and biochemical alterations by genetic deletion of Raptor/Rictor in dopamine neurons.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This paper is of broad interest to researchers studying chromosome structure. Using a powerful reconstitution system, the authors dissect the function of the chromosome organising complex, condensin II. Several findings, if supported by some additional analyses, are surprising and thus have the potential to fuel further mechanistic studies of condensin function.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

    1. Evaluation Summary:

      This study describes the correlations between different membrane properties and the size of the soma of spinal alpha-motoneurons (MNs) using data from 40 experimental in vivo studies. The authors have distilled decades of research on motoneuron properties into a set of mathematical relationships that can guide both experimentalists and modelers interested in developing realistic models of populations of motoneurons. The key result is a complete table of the empirical relationships between the anatomical and physiological properties of MNs. Overall, the dataset approach is interesting, although a detailed analysis of the variability within and between datasets is urgently needed. In addition, a simpler framing of the paper could make the main message easier to grasp.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      Kang et al. studied the role of cystathionine beta-synthase , an enzyme involved in homocysteine catabolism, in the senescent state imposed by oncogenic Akt. They find that this enzyme facilitates the acquisition of features of senescence, and is frequently silenced in tumors, whereas re-expressing it reduces cell proliferation. This manuscript is potentially of interest to cancer biologists, particularly those studying oncogene-induced senescence and mechanisms of senescence escape in cancers.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This work seeks to resolve questions surrounding "unexplained variability in functional recovery" after experimental spinal cord injury in mice using virus-based retrograde tracing from cervical, thoracic and lumbar spinal cord injection sites, tissue clearing and cutting-edge imaging, to develop a supraspinal connectome or map of neurons in the brain that project to the spinal cord. They apply their methods to understand the differences in the connections between the brain and the cervical or lumbar spinal cord and to compare the connectome from intact mice to those of mice with mild, moderate and severe spinal cord injuries. This work will be of interest to neuroscientists interested in tissue clearing, viral labelling, and its applications to spinal cord injury.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This paper very nicely tackles a methodological problem in aligning different types of datasets (EM and light microscopy) to image embryonic nervous system development in the nematode C.elegans. The paper is important not just from a methodological standpoint, but also provides novel insights into nervous system development that will be of general interest to the reader. The latter deserves more attention in the manuscript.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This paper will be of great interest to the field of developmental neuroscience and social communication. The authors identified prenatal sensorimotor vocal precursors by detecting rhythmic orofacial movements related to vocalizations. These findings will provide new insights into the development of vocal behavior in primates. The data acquired by a highly quantitative approach support the major claims of the paper.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

    1. Evaluation Summary:

      The manuscript has the potential to transform the field of sensory transduction and gene regulation in the Vibrio genus by uncovering a previously undescribed enhancer binding protein and its role in the regulation of quorum sensing and physiology in the Vibrio - squid symbiosis. However, in its present form, several experiments are required to support the claims of the manuscript.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    1. Evaluation Summary:

      Guimaraes et al address the origin of the macrophage increase in sensory ganglia after peripheral nerve injury. The authors show that there is no major influx by blood-derived monocytes into ganglia after injury and that resident macrophages proliferate, which is dependent on CX3CR1 signaling. Overall the work is clear and sound and should be of interest to immunologists and neurobiologists.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 and Reviewer #3 agreed to share their names with the authors.)

    1. Evaluation Summary:

      The paper provides information about the relative importance of the type I and type III interferon-driven gene expression and anti-viral responses, particularly focused on the role of the Intestinal microbiota to maintain background levels of type III (interferon lambda) signaling. Type III-driven gene expression is highly discontinuous in the epithelial layer and mainly at the villous tips with consequent effects on the kinetics of rotavirus model infections.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript.The reviewers remained anonymous to the authors.)

    1. Evaluation Summary:

      The mechanisms that control cholesterol movement from the plasma membrane (PM) to the endoplasmic reticulum (ER) remain poorly understood. Here, Ogasawara and Ueda propose an intriguing mechanism whereby ABCA1, a membrane protein, moves cholesterol from the inner to the outer leaflet of the PM to keep the cholesterol away from intracellular Aster proteins that move cholesterol to the ER. When cholesterol builds up beyond a threshold, it accumulates on the inner leaflet and is transported to ER by Asters. If strengthened by the analysis of the endogenous ABCA1 and more physiological cholesterol manipulation, this work will be of significant interest to scientists studying lipid metabolism and transport.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their name with the authors.)

    1. Evaluation Summary:

      Eckstein and colleagues take a within-participant approach to answer two critical questions in the field of human reinforcement learning: to what extent do estimated computational model parameters generalize across different tasks and can their meaning be interpreted in the same way in different task contexts? The authors find that inferred parameters show moderate to little generalizability across tasks, and that their interpretation strongly depends on task context. Support for these claims could be further strengthened through additional simulations and by providing greater methodological detail.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This manuscript will be of interest to cell and developmental biologists and neuroscientists. It addresses the question of how the number of connecting neurons in a circuit is matched whilst maintaining topography. It shows that non-autonomous control of neuronal number involves a relay mechanism through two distinct glial cell types, enabling the specification of distinct neuronal classes.

      This manuscript was co-submitted with: https://www.biorxiv.org/content/10.1101/2022.02.21.481306v1

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    1. Evaluation Summary:

      In this elegant genetic study, Bailon-Zambrano and colleagues draw on classical genetic concepts to address the clinically pertinent question of how genetic variants in the same gene can yield wildly different phenotypes in different individuals. From their case study they conclude that a major contributor is variation in paralog expression. The question addressed is of great interest to evolutionary and developmental biologists in general and to those studying the evolution of developmental mechanisms in particular.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript.The reviewers remained anonymous to the authors.)

  2. May 2022
    1. Evaluation Summary:

      Beginning with transcriptome data, Rhodes et al. identify a new family of peptides with signalling function called CTNIP in the model plant Arabidopsis thaliana. They use an elegant biochemical capture approach to pinpoint the SERK-dependent LRR receptor kinase HSL3 as the only receptor for these peptides. They provide convincing genetic and biochemical evidence that HSL3 binds CTNIP and that CTNIP perception triggers HSL3-dependent cytoplasmic calcium influx, ROS production and transcriptional changes. Furthermore, they provide initial evidence that the CTNIP-HSL3 module may participate in regulating root growth.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    1. Evaluation Summary:

      Wang and colleagues report that the expression of Piezo1 (an ion channel and mechanical sensor) is upregulated on dendritic cells (DC) under conditions of inflammation/high environmental stiffness resulting in DC activation, maturation, and skewing in DC functional polarity and metabolism. They show that Piezo1 knockout results in faster tumor progression and accumulation of more regulatory T cells, and that Smad3 and STAT4 are involved in DC-mediated differentiation of Th1 and Treg. Overall this represents a mechanistic advance in our understanding of DC biology as it relates to cancer and other human pathologies.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This is a useful study employing a well-established one-pawed reaching/grasping paradigm for fine-motor skill learning to assess if learning is associated with cortical structural changes as assessed by longitudinal MRI measurements in mice. The authors report a non-linear time course of MRI signal changes representing a decrease in grey matter and an increase in white matter volumes in the cerebral cortex and other regions. The authors ascribe these changes to increased myelination, a conclusion that is supported by quantitative immunolabelling for the myelin protein MBP. These results represent an interesting addition to the literature around myelination changes associated with learning/activity (adaptive myelination). Additional histological analysis of changes in myelination would bolster support for the authors' conclusions.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    1. Evaluation Summary:

      Cuticles are specialized extracellular matrices that cover the bodies of ecdysozoans, which make up 85% of all animals. How cuticles are formed is very poorly understood, in particular in light of the fact that cuticles are shed and regrown as animals grow. The authors present a comprehensively and carefully curated resource of the components of the pharyngeal cuticle of C. elegans and provide a spatio-temporal framework to understand cuticle assembly. In doing so, the authors propose a function for a large class of intrinsically disordered proteins (IDPs). The significance of this work is high because our understanding of both cuticle formation and of IDPs is poor.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    1. Evaluation Summary:

      This manuscript reports a striking finding, which should be of interest to cell biologists and biophysicists. The authors use an innovative approach to recruit clathrin to mitochondrial membranes and observe the budding and fission of clathrin-coated vesicles. The study leads to a much clearer view of how the clathrin lattice functions in endocytosis.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    1. Evaluation Summary:

      The authors investigated the structure of phosphoribosyl pyrophosphate (PRPP) synthase (PRPPS) from Escherichia coli, a highly conserved enzyme from bacteria to mammals that catalyzes the synthesis of a key common compound for several metabolic pathways. Combining structural data with mutagenesis and activity assays, they demonstrate that the enzyme is regulated differently by allosteric effectors when assembled into one filament form or the other. The strength of the manuscript is the high-quality cryo-EM data, which allows the reconstruction of two different filament forms bound to different ligands.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    1. Evaluation Summary:

      This paper uses an impressively rich dataset (obtained and curated by the authors) to compare the structural brain connectomes of many animals spanning 6 taxonomic orders. The approach is innovative and relies on graph theoretical measures to describe the connectivity, which means it can be done without the need to spatially/functionally match the brains. The authors find that there is more variability between than within order. They attribute this effect to changes in local connectivity features, whereas global patterns are preserved. The approach can potentially be a useful way to study phylogeny and brain evolution.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This paper presents an exciting new automated package to investigate the hippocampal organization in new ways. As such, this package will be equally interesting for the fundamental basic and clinical neurosciences.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

    1. Evaluation Summary:

      The study shows that the LXRbeta - NCOR1 axis restricts the terminal differentiation of Treg cells into effector Tregs. It also suggests that, in addition to an impact on effector Treg differentiation, loss of NCOR1 leads to impaired suppression function in Treg cells. The results may contribute to our understanding of Treg cell differentiation and function.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    1. Evaluation Summary:

      There are various ways in which self-fertility has arisen in the fungal kingdom. This study describes a novel form of self-fertility that evolved in a species closely related to the Cryptococcus species causing serious human lung disease, in which sexual development is achieved by self signaling of a cognate pheromone and pheromone receptor pair. Through a combination of high-quality genomic analysis and experimental gene expression and manipulation work, the study adds to our understanding of the evolution and flexibility of fungal breeding systems. This work will be of interest to colleagues studying fungi as well as mating systems in any eukaryote.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    1. Evaluation Summary:

      The authors present a study on the cohesion maintenance of E.coli during collective migration in a self-generated gradient. They performed experiments and complemented the study with a predictive model and simulation to understand how bacteria with different phenotype are able to move as a cohesive group and how the individual bacterium defines its own position within the group. Particularly interesting aspects of the study are the use of titration of behavior with chemoreceptor abundance and the use of potential wells to model the attraction of bacteria to the center of their cohesive group. This approach will be of interest to physicists and biologists interested in collective motility and migration.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript.The reviewers remained anonymous to the authors.)

    1. Evaluation Summary:

      In the present study Pal and colleagues provide evidence that hydrogen sulfide (H2S) inhibits HIV replication and reactivation by a variety of mechanisms including inhibition of NF-kB and and recruitment of the epigenetic silencer, YY1, to the HIV promoter. They further report that H2S helps to maintaining mitochondrial bioenergetics and redox homeostasis and suggest that inclusion of an H2S donor in current ART regimens may help to achieve a functional HIV-1 cure.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    1. Evaluation Summary:

      This paper will be of interest to scientists who use imaging approaches to study cellular metabolism. It presents a new coarse-grained model for inferring mitochondrial NADH oxidation from NAD(P)H fluorescence lifetime imaging in mouse oocytes. The modeling is thoughtfully and clearly presented, but the validity of some key assumptions of the model and the overall generalizability of the method to other cell types could be strengthened.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 and Reviewer #3 agreed to share their names with the authors.)

  3. Apr 2022
    1. As Hutchisson shares, it ignores the fact that people bring their “whole selves” to work, and in doing so they bring “life to the vision and purpose” of the workplace. I couldn’t agree more. We’re incredibly unique and come from all walks of life. And in this age, we’re seeing job candidates more purposefully seeking employment with companies that align with their moral code and values as individuals.

      Sum: The term in itself may be indeed not the best to describe what corporate social responsibility actually accounts for, and thus a change to human social responsibility would be better placed because of what CSR actually encompasses.

    1. Will be executed right after outermost transaction have been successfully committed and data become available to other DBMS clients.

      Very good, pithy summary. Worth 100 words.

      The first half was good enough. But the addition of "and data become available to other DBMS clients" makes it real-world and makes it clear why it (the first part) even matters.

  4. Mar 2022
    1. We have several ways to deal with partial functions. A straightforward approach is to restrict the domain so that it is clear the function cannot be legitimately used on some inputs. The specification rules out bad inputs with a requires clause establishing when the function may be called. This clause is also called a precondition because it describes a condition that must hold before the function is called

      A "requires clause" is a precondition declaring the sub-set of input values that are not restricted by the type on which the function is defined (e.g. x >= 0, if x : int)

    2. How might we specify sqr, a square-root function? First, we need to describe its result. We will call this description the returns clause because it is a part of the specification that describes the result of a function call. It is also known as a postcondition: it describes a condition that holds after the function is called. Here is an example of a returns clause:

      The "return clause" is a postcondition declaring what is the result of the function; including domain-specific properties of the result (e.g. accuracy of approximative operations).

    1. that chronically ill patients have such low quality of life anyway that they aren’t worth protecting

      Some people have this idea that if your sick, it's ok if you die because you are probably not living anyway.

    2. One reason Bernstein said she included her picture is that she looks healthy and young, contrary to images that people may have in their minds

      She is pointing out that "Hey, I'm sick but I don't look sick".

    3. Now thousands of people have shared their own stories about living through the pandemic with chronic illness — and about coping with remarks from media personalities and even health officials that minimize the human toll of COVID-19 because deaths and hospitalizations disproportionately affect people who are old or have underlying medical conditions.

      Comments made by Media, and Health Officials was minimizing the COVID-19 deaths and illnesses because most or some of those affected were older or had comorbidities.

    4. “What I was seeing in the hospital and ... the patients that I was caring for and the families, and then my own personal experience ... was kind of in conflict with a lot of the things I was reading in the news, on Twitter and actually hearing from friends, about the pandemic being over and about omicron being mild and no big deal,” Bernstein said in a news conference this week.

      What was being said in the New and Media were not matching up with what Dr. Bernstein was seeing and experiencing with her patients. COVID-19 wasn't over, and it wasn't mild, and it was a big deal.

  5. Feb 2022
    1. This article focuses on the concept of "mental" and what exactly mental disorders are. This can be considered habits that become reflexes or something that is learned or even a condition that is not "outgrown" from childhood. Not all reactions are voluntary and the idea of the "mind" can not be boiled down to a single explanation since the science is continually changing. Terminology is not understood across the board because scientist, especially across different fields, cannot agree on a single definition. Because habits can be learned though training, there is a possibly for them to be unlearned over a period of time - this is where the importance of a therapist, psychiatrist, counsoler, or psychopathologist comes into paly.

  6. Jan 2022
  7. Dec 2021
    1. Summary of evaluation: The eight white clergymen who wrote this letter to civil rights leaders missed an opportunity by not using the Rogerian structure. Classical oration left their audience feeling not heard and not understood. This combined with only first-hand qualitative evidence and several insulting logical fallacies makes for a letter just asking for Martin Luther King's scathing response.

  8. Nov 2021
    1. And racial discrimination doesn’t exist just within the military rank-and-file.

      This is show that discrimination not just in one place, it's everywhere like the Army, Air Force and Navy for example.

    2. we initially experience racism or discrimination in the military, we feel blindsided

      They are talking about how them feel when they get discriminated and what they believe.

      • why we need ControlValueAccessor
      • how it's used inside Auglar
      • how to wrap a 3rd widget into an Angular component and
      • setup communication with a parent component using the standard input/output mechanism
      • how to implement ControlValueAccessor that introducs a new communication mechanism specifically for Augular forms
  9. Oct 2021
    1. ual, this study examines the relationship of the extent of power concentration to urban renewal success. The ratio of managers, proprietors, and officials to the employed labor force measures the concentration of power, and success in urban renewal is represented by arrival of cities at the execution stage in that pro- gram. The relationship is found to be statistically significant and remains so under a series of controlled observations

      Quant study that examines the concentration of community power on the success of urban renewal projects.

    Tags

    Annotators

  10. Sep 2021
    1. The City Sustainable: Three Thoughts on “Green Cities, Growing Cities, Just Cities”

      Planners considering social equity, the economy and nature in sustainable development plans have the opportunity to add other dimensions to the mix.

      Prior to Campbell and the sustainable development paradigm, planning was about improving sanitation and improving determinants of health in communities.

    Tags

    Annotators

    1. Cities, Growing Cities”

      Article examines Campbell's seminal article's affect on research paradigms on planning and notes that the planners as well as planning researchers have a long way to go in order to put into balance the triad of social, economic, and ecological concerns in order to achieve true sustainable development.

    Tags

    Annotators

  11. Aug 2021
    1. HyDrop: droplet-based scATAC-seq and scRNA-seq using dissolvable hydrogel beads

      Data Discovery/Status Report

      Click Here for full report

      Summary of datasets and Open Science materials associated with article:

      • 15 Protocols
      • 27 Datasets
      • 16 Code
      • 13 Reagents/Materials/Lab Resources

      18 Tabular Data Dataset(s)

      • 15 "Tabular Data"
      • 2 "Assay"
      • 1 "Fluorometry"

      5 Image Dataset(s)

      • 1 "Image"
      • 3 "Microscopy"
      • 1 "Photography"

      4 Genetic Data Dataset(s)

      • 2 "Sequence Alignment"
      • 2 "High-Throughput Nucleotide Sequencing"
  12. Jul 2021
    1. Nick Holliman. (2021, May 30). @anthonybmasters @d_spiegel A quick visual summary of data on this week’s article by @anthonybmasters & @d_spiegel The outlook is uncertain, although we have survived a variant once already (B.1.1.7). The data on the effect of variants is analysed as fast as it (reliably) arrives. Https://t.co/vOKmCxYMGT https://t.co/3ZeJJTdRs3 [Tweet]. @binocularity. https://twitter.com/binocularity/status/1398957348492918784

  13. May 2021
  14. Apr 2021
  15. Mar 2021
  16. Feb 2021
    1. That’s it, plain and simple. But if you want the legalese version, dive into it here.
    2. What we do collect:The translated words you encounter so that we know what words you are exposed to and can serve up appropriate vocabulary quizzes.Any vocabulary quizzes you see and the results of those quizzes so that we can keep track of how well you know each vocabulary concept.Anonymized (not linked to anyone's particular account) web page URLs, whether translations show up on them, and whether any bugs or errors occur on those pages so that we can better detect any broad issues affecting our user base.
    1. Objective: Some gambling product messages are designed to inform gamblers about the long-run cost of gambling, e.g., “this game has an average percentage payout of 90%.” This message is in the “return-to-player” format and is meant to convey that for every £100 bet about £90 will be paid out in prizes. Some previous research has found that restating this information in the “house-edge” format, e.g., “this game keeps 10% of all money bet on average”, is better understood by gamblers and reduces gamblers’ perceived chances of winning. Here we additionally test another potential risk communication improvement: a “volatility statement” highlighting that return-to-player and house-edge percentages are long-run statistical averages, which may not be experienced in any short period of gambling. Method: Gambling information format and volatility statement presence were manipulated in an online experiment involving 2,025 UK gamblers. Results: The house-edge format and the presence of volatility statements both additively reduced gamblers’ perceived chances of winning. In terms of gamblers’ understanding, house-edge messages were understood the best, but no consistent effect of volatility statements was observed. Conclusions: The return-to-player gambling messages in current widespread use can be improved by switching to the house-edge format and via the addition of a volatility statement.
      1. Download Office Deployment Tool. Double-click to extract.
      2. Generate an XML in Office Customization Tool.
      3. Merge it with the unpacked configuration-Office365-x64.xml
      4. Run it
      .\setup.exe /configure configuration-Office365-x64.xml
      
    1. Using details/summary for dropdown nav menu without requiring any JavaScript

    2. in this post, we’ll look at how to use this as the basis for an accessible dropdown navigation element that can be opened equally well by keyboard users tabbing through the page, and mouse users hovering on the nav item
    3. The HTML details element comes with a surprise – in most browsers it has the ability to hide and show content with no additional JavaScript or CSS whatsoever. Here’s a little bit about how it works. details has with a child called summary, and when a page first loads, the summary is the only part of the element that’s visible, along with a triangle that browsers display by default, to suggest the expandable nature of the content. Interacting with the summary element, by clicking or using the keyboard, will make the rest of the details element visible and add an open attribute to the details element itself.
    1. In this commentary, we argue that Fried's article, "Lack of theory building and testing impedes progress in the factor and network literature," provides a number of insights that will be very useful for psychologists, but also that he is wishing for psychology to focus on a kind of theory that it cannot generally be expected to produce at this time. As we will explain, Fried asks too much of our models and our theories. In part, this stems from a failure to consistently heed his own warnings about the limitations of statistical models, but it also reflects an overestimation of the kind of evidence and reasoning necessary to develop and test theory. We too believe that psychological research on individual differences should pay attention to theory, but we are more optimistic than Fried about the progress that can be made through a focus on the kind of theory that psychology is actually capable of producing. In order to justify our optimism, we first develop our perspective on the nature of latent variables and then consider how individual-difference researchers should approach theory that has the potential to explain them.
  17. Jan 2021
    1. Path parameters:

      • Identify a resource uniquely

      Request body:

      • Send and receive data via the REST API, often specifically to upload data.
      • Needs to adhere to REST API principles to be RESTful. Therefore for POST/PUT, needs to send the whole resource in the body.

      Query:

      • Mainly used for filtering. If you send a query asking for a large number of resources, use query parameters to filter the set of resources that you want. Example: You send a request to api/pictures/category/cat. You will now get all pictures with cats which could be millions. You can put in the query more specific parameters to clarify your request, such as: api/pictures/category/cat?color=black&breed=korat. Now you will get the subset of pictures of cats which havethe color black and are korat cats.
  18. Dec 2020
    1. Monte Carlo Dropout boils down to training a neural network with the regular dropout and keeping it switched on at inference time. This way, we can generate multiple different predictions for each instance.

      .

    1. SWA uses a modified learning rate schedule so that SGD continues to explore the set of high-performing networks instead of simply converging to a single solution. For example, we can use the standard decaying learning rate strategy for the first 75% of training time, and then set the learning rate to a reasonably high constant value for the remaining 25% of the time (see the Figure 2 below). The second ingredient is to average the weights of the networks traversed by SGD. For example, we can maintain a running average of the weights obtained in the end of every epoch within the last 25% of training time (
      1. we train enough to get to a good area in the loss function.
      2. We have a high learning rate(but not too high) so we can explore our surroundings and stumble upon nearby high performing minima. We periodically save the weights(every x epochs)
      3. We average the weights . As a result, the averaged weights will be centered around the loss. See left picture below

  19. Nov 2020
  20. Oct 2020
    1. The perfect breath is this: Breathe in for about 5.5 seconds, then exhale for 5.5 seconds. That’s 5.5 breaths a minute for a total of about 5.5 liters of air. You can practice this perfect breathing for a few minutes, or a few hours. There is no such thing as having too much peak efficiency in your body.

      The perfect breath is 5.5 seconds of breathing in and 5.5 seconds of breathing out.

    2. Breathing less offered huge benefits. If athletes kept at it for several weeks, their muscles adapted to tolerate more lactate accumulation, which allowed their bodies to pull more energy during states of heavy anaerobic stress, and, as a result, train harder and longer. All of them claimed to have gained a boost in performance and blunted the symptoms of respiratory problems, simply by decreasing the volume of air in their lungs and increasing the carbon dioxide in their bodies.

      Breathing less can increase toleration to lactate accumulation. This is because of increase tolerance to CO2

    1. Many black business owners blamed the problem on lowerclass peoples’ affliction with the “white man’s psychology,” namely, that migrantshad been brainwashed into thinking they had to shop in a white-owned store, eitherbecause whites would punish them if they didn’t or because white stores were nec-essarily higher quality than black ones.48Whether this was the case or not, therewere several other things complicating black consumers’ willingness to shop inblack-owned businesses.

      Breakout Group 02: The evidence above demonstrates the "integration of rural Southern culture into urban African American consciousness" where foodways are a "natural vehicle for the expression…of freedom" because it shows the complication within the black community. Where an expression of freedom is an African American having a grocery store. One would think that the Black owned grocery store would be successful due to "black authenticity" but many Black people feared blacklash from White people for even attempting to be independent but also because many Black people were brainwashed to believe that the white businesses have better quality products over the black owned business.

    1. A JavaScript DOM model supporting element creation, diff computation and patch operations for efficient re-rendering
    1. That is, we envision a cuisine and an attendant lifestyle that is more au-thentic and less stressful, more "natural," than the world in which we live.

      ~Group 4~ Anne Meneley is discussing how olive oil is becoming an increasingly more sought after ingredient because of its praise as a natural ingredient. Though olive oil is seen as a traditional and authentic ingredient, due to media, it is an industrialized product and is only widespread because of that- despite the misconceptions to make people think otherwise. There are many reoccuring themes within the article such as distinction, naturalness, processed, and industrialization to name a few. The quote that is highlighted connects to themes because people truly seem to worship this idea of being and living naturally. The idea of being natural also includes eating naturally and there's this distinction between people who live naturally and who don't. People who idolizes this natural lifestyle seem to think they are being authentic when they are failing to realize that transformations and growth are necessary. Meneley seems to want the reader to think about what industrialization and processed foods mean exactly.

    1. Graeber has a great deal more to say about money and its unique capacityto store value, and also about the ideology of the market with its highlyindividuated notion of human desires (e.g. 2001: 257). His analysis opensup an intriguing question. If in market societies money is a measure, amedium and above all an end in itself (2001: 66) and value-for-moneydominates what we conventionally call the economy, how do other valuescoexist with this monetarized realm and its rationality of quantificationand self-interest? Graeber points out that, in our view of society, marketprinciples can be balanced by family values and altruistic charity (2001:257), but he views these as just ‘two sides of the same false coin’

      In this capitalistic society money makes the world go round. Graeber has a pessimistic view in regards to the idea that family and altruism can balance out greed because he believes that they are in direct conflict to capitalism. Graeber expands further on his thoughts

  21. Sep 2020
    1. As a general rule, I would recommend reading the article in it's entirety. With that said, if you wish to "cut to the chase", I have summarized my findings at the end ... feel free to jump ahead to the Summary!
    1. Tuples are a sequence of values which can be of any of any type. The key difference between list and tuple is tuples are immutable.Tuples uses built in function like zip,etc.

    2. Chapter 11Dictionaries

      Dictionaries are like lists and values in dictionaries can be of any type. Every Value is mapped to an key jointly called as key value pair. Dictionaries have various built in functions like invert,etc. In Dictionaries, global variables can be created which can be accessed in function of the program.

    3. Lists are sequence of values which are mutable. Lists have many built in methods to perform variety of operations like append,sort,expand,etc. Lists can perform many operations with each other in different ways.

    4. Strings are list of characters which are immutable. Strings have many built in methods to perform variety of operations like lower case to upper case,finding of a characters in a string,etc. Strings are comparable with each other in many different ways.

    5. Chapter 12Tuples

      tuples is a sequence of values this can be anytype and they are indexed by integers and tuples are immutable in().operations like addition ,multiplication works on tuples.they can return multiple values. Tuples are immutable which means you cannot update or change the values of tuple elements. An operation that collects multiple arguments into a tuple is known as gather. an operation that makes a sequence behaves like multiple arguments is known as scatter. .And the tuples we cannot modify the values. and we can assign the values to the tuples.

    6. Chapter 10Lists

      like a strings here lists is a sequence of values in a list that may be any type this values in a list are called elements and list can have different data types Strings are need to be given in single or double codes.And also Strings are immutable which means a string cannot be updated.And another important topic from strings is Slicing of a string which means we can obtain the substring from the given string by following a syntax.

    7. Chapter 8Strings

      strings is a sequence of characters you can acess the characters at once in bracket opertater ,fruit ='banana' String should be given in single or double codes.Strings are immutable.once we create a string we cannot make any changes in them .We declare strings using square brackets.A segment of a string is called a slice.Many built in functions can be used len(),upper(),lower(),etc.We can use len() function to find length of a string.We can even compare two strings==(equal).The expression in brackets

    8. Tuples are sequence of values. Tuples are immutable. Bracket operator indexes an element,slice,relational operators which work on lists aslo work on tuples. Built-in function divmod takes two arguments and returns a tuple of two values as quotient and remainder. If you have a sequence of values you can use * operator to pass it to asunction as multiplue arguments. Operation that collects multiple arguments into a tuple is known as 'gather'. Operation which makes a sequence behave like multiple arguments is called 'scatter'. Zip is a built-in function in the lists and tuples takes two or more sequences and interleaves them.If the sequences are not of same length, the result has the length of the shorter one. Tuples has built-in funtions sorted and reversed as it does not provide methods like sort an reverse which work as the same.

    9. =>Dictionary is like a list , contains a collection of indices , called keys and their corresponding values. *Mapping : A dictionary represents a route/map from keys to values. The elements of a dictionary are never indexed with integers Python dictionaries use a data structure called a hashtable =>There are 3 ways to count how many times a letter appears and the best way is implementing through dictionaries Dictionaries have a method called "get" that takes a key and a default value. =>Traverses the keys of the dictionary is possible by us ing dictionary in a for statement. =>Lookup : The operation lookup means finding the corresponding value of a key in dictionary i.e., by value v = d[k]. Reverse lookup is nothing but finding the corresponding key of a value. The raise statement causes an exception; in<br> this case it causes a LookupError. You can provide a detailed error message as<br> an optional argument , when you raise an<br> exception. A reverse lookup is much slower than a forward lookup. =>Lists can be values in a dictionary, but they cannot be keys. In the inverted dictionary there are several hits's of having same vales which are in "List" see below example

                      *      hist = histogram('parrot')
                                >>> hist
                                {'a' :1,'p':1,'r':2,'t':1,'o':1}
                                >>>inverse = invert_dict(hist)
                                >>>inverse
                                {1:   ['a','p','t','o'],  2:  ['r']}
             **A hash is a function that takes a value and 
                returns an integer.
             **if the keys are mutable, like lists, the dictionary 
                wouldn’t work correctly.
      

      =>A previously computed value that is stored for later use is called a memo. =>If a global variable refers to a mutable value, you can modify the value without declaring the variable: =>There are four types of debugging Scale down the input Check summaries and types Write self-checks Format the output

    10. A tuple is a sequence of values. The values can be any type, and they are indexed byintegers, so in that respect tuples are a lot like lists. The important difference is that tuplesare immutable
      • A tuple is a sequence of values. The values can be any type, and they are indexed by integers, so in that respect tuples are a lot like lists. The important difference is that tuples are immutable.
      • Strictly speaking, a function can only return one value, but if the value is a tuple, the effect is the same as returning multiple values.
      • Dictionaries have a method called items that returns a sequence of tuples, where each tuple is a key-value pair.
      • zip object:The result of calling a built-in function zip; an object that iterates through a sequence of tuples
      • .iterator:An object that can iterate through a sequence, but which does not provide list operators and methods.
      • data structure:A collection of related values, often organized in lists, dictionaries, tuples,
      • A dictionary is also like a list where in list only one type of variables need to be and in dictionaries there can be almost any type in one set.
      • A dictionary contains a collection of indices which are called keys and keep any values.
      • In dictionary we use curly brackets and in lists we use square brackets.
      • In a dictionary we can use for loop and it traverse the keys of dictionary.
      • In a dictionary another name for a ey value is pair.
      • Implementation a way of performing a computation.
      • HASHTABLE-The algorithm used to implement python dictionaries.
      • . list means it is a sequence of values.
      • .In a list we can store any type of values not like strings.
      • A list can be created easily by storing the values in square brackets.
      • We can do different types of operations in list like we can do concatenation.
      • List indices work the same way as string indices: 1-any integer expression can be used as an index. 2-if you try to read or write a element that does nt exist,you get an index error.
      • List slices ,list are mutable
      • in list to delete any type of variables we can use del,pop,remove.
      • The association of a variable with an object is called a reference.
      • MAP-a processing pattern that traverse a sequence and performs an operation on each element.
      • With lists we can perform different types of operations.
      • A String is a sequence of character.you can access the character using bracket operator.
      • In string the expression in brackets is called index it calculates the character from 0.
      • In index we can do operations and if it is not in integer it gives you error.
      • Len means it is a built in function that returns the number of characters in the string.
      • A lot of computations involve processing a string and while doing it will do from beginning with each and every string.it is known as traversal wit for loop in string.
      • String slice means we can divide a word into two and we can do concatenation.
      • In string we cannot use some operators we can only use some operators like in, as,etc.
      • . String is immutable we cannot change .
      1. Strings are not like integers, floats, and booleans.
      2. A string is asequence, which means it isan ordered collection of other values.
      3. A string is a sequence of characters.
      4. len is a built-in function that returns the number of characters in a string.
      5. A segment of a string is called aslice.
      6. Strings provide methods that perform a variety of useful operations.
      7. A method is similarto a function—it takes arguments and returns a value—but the syntax is different.
    11. 10ListsThis

      List List is a collection of values which is ordered and changeable. Allows duplicate members. Nested list is possible ( list containing one more list). They are mutable means no fixed elements.List slices are possible with index numbers (0:2) .Operations used in list -- ' + ' concatenates the list, ' * ' repeats a list a given number of times. Aliasing -- variable's value is assigned to another variable. List methods -- append() , extend() , sort() , map() , split() , etc

    12. 8StringsStrings

      Strings A string is a finite sequence an alphabet. Each sub string is called by there index. Strings are immutable which mean they cannot be edited or changed. To access characters in the String, method of slicing is used. Slicing in a String is done by using a Slicing operator (colon,: ). Built in functions -- upper(), lower(), replace(),type(), etc. Operators:+, *, in, not in..etc.Comparison and debugging of strings is possible.

    13. What I have learnt from chapter-10(Lists): List is similar to array. List is a most versatile datatype available in python which can be written as a list of comma-separates values (items) between square brackets. Important thing about a list is that items in a list need not be of the same type. List is a sequence of values like integers , floating numbers , strings, etc called as elements and they are mutable. List methods are append() , extend() , sort() , map() , split() , etc and Operations on lists are ' + '.

    14. What I have learnt from chapter-8(Strings) : Strings are sequence of characters. Strings are immutable. Strings can be accessed by square bracket operator. There are some builtin functions in strings.they are: upper(),lower(),find(),len() etc.. I got to know about applying sequence and comparing string(=,>,<). We can learn indexing and slicing of a string in this chapter.

    15. Lists

      I have learnt these things about list: Lists are also sequence data types as strings but it can store heterogeneous data. list are also zero index based . List can be traversed using for loop . Lists are mutable unlike strings. Any operations made on lists , modifies it in place. Slicing can also be performed same as strings The plus operator concatenates two lists and comparison operators compares two lists element by element same as strings. Various built in methods of lists such as len,count,sort,append,extend etc are there. split method splits string into list and join method return a string of elements of list. Got to know about aliasing and many more.

    16. Lists

      LISTS: • Sequence of values just like strings • Values in the list are called elements or items • A list can contain a list within itself and is called nested list • Lists are mutable • In operator can be used in the same way as strings Map: - it’s a function that acts onto each of the elements in a sequence Reduce:-an operation which combines sequence of characters into a single value Filter:-an operation which acts upon few elements of the list ***If two objects are identical they are also equivalent but if they are equivalent, they are not necessarily identical

    17. Strings

      STRINGS: • Sequence of characters • Index tells us which character in the sequence we want • Index must only be integers or else we will get Type Error • We can use the len() to get the length of the string • We can iterate through the strings in two different ways o for i in range(len(string): print(string[i]) o for i in string: print(i) • The in operator can be used to check whether a substring is present in the given string • Strings can be sliced and is Counterintuitive • Strings are immutable in nature

    18. Strings

      A string is a sequence of characters that are assigned or declared to a variable within quotes.They are immutable i.e. we can't make any further changes to the string once they are assigned.The elements in the string can be accessed through index. I have learnt about many built-in functions like len(),split(),upper(),lower(),find() ,etc...

    19. Strings

      I have learnt these things about strings: strings are sequence of characters and zero-index based. A char in a string can be accessed by using []. A string can be traversed using for loop. Strings can be sliced to get a piece of string. Various built in methods area available such as len,find,lower,upper,capitalize,isalpha,isnumeric etc.

      • operator concats two strings. comparison operaors compares teo strings lexicographically. Most importantly strings are immutable i.e once created they can't be modified.
  22. Jul 2020
  23. Jun 2020
  24. May 2020
    1. We group a description of and about personal data (such as a Cookie or IP Address), the purpose of its collection (such as Analytics or Advertising) and the providers (such as Google or even your own website) into what we call services. Each service corresponds to a portion of a privacy policy, and provides all the relevant information to the end users of your website.
  25. Apr 2020
    1. e submit that the use of a crystallographic primary screenfollowed by rapid poised chemistry to generate a follow-uplibrary offers a new, powerful method in hit discovery and leadseries selectio

      method summary: crystallography as primary screen, followd by rapid poised chemistry

    Tags

    Annotators

    1. Hypothesis already deals with minor changes to a document thanks to our fuzzy anchoring algorithm, which can cleverly locate the original annotated selection even if it or its surrounding context has changed slightly or been moved around.

      Summary: Small changes in the document should be okay.

    1. Misinformation can amplify humanity's greatest challenges. A salient recent example of this is the COVID-19 pandemic, which has bred a multitude of falsehoods even as truth has increasingly become a matter of life-and-death. Here we investigate why people believe and spread false (and true) news content about COVID-19, and test an intervention intended to increase the truthfulness of the content people share on social media. Across two studies with over 1,600 participants (quota-matched to the American public on age, gender, ethnicity and geographic region), we find support for the idea that people share false claims about COVID-19 in part because they simply fail to think sufficiently about whether or not content is accurate when deciding what to share. In Study 1, participants were far worse at discerning between true and false content when deciding what they would share on social media relative to when they are asked directly about accuracy. Furthermore, participants who engaged in more analytic thinking and had greater science knowledge were more discerning in their belief and sharing. In Study 2, we found that a simple accuracy reminder at the beginning of the study – i.e., asking people to judge the accuracy of a non-COVID-19-related headline – more than doubled the level of truth discernment in participants’ sharing intentions. In the control, participants were equally like to say they would share false versus true headlines at COVID-19 whereas, in the treatment, sharing of true headlines was significantly higher than false headlines. Our results – which mirror those found previously for political fake news – suggest that nudging people to think about accuracy is a simple way to improve choices about what to share on social media. Accuracy nudges are straightforward for social media platforms to implement on top of the other approaches they are currently employing, and could have an immediate positive impact on stemming the tide of misinformation about the COVID-19 outbreak.
    1. There is an obvious concern globally regarding the fact about the emerging coronavirus 2019 novel coronavirus (2019‐nCoV) as a worldwide public health threat. As the outbreak of COVID‐19 causes by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) progresses within China and beyond, rapidly available epidemiological data are needed to guide strategies for situational awareness and intervention. The recent outbreak of pneumonia in Wuhan, China, caused by the SARS‐CoV‐2 emphasizes the importance of analyzing the epidemiological data of this novel virus and predicting their risks of infecting people all around the globe. In this study, we present an effort to compile and analyze epidemiological outbreak information on COVID‐19 based on the several open datasets on 2019‐nCoV provided by the Johns Hopkins University, World Health Organization, Chinese Center for Disease Control and Prevention, National Health Commission, and DXY. An exploratory data analysis with visualizations has been made to understand the number of different cases reported (confirmed, death, and recovered) in different provinces of China and outside of China. Overall, at the outset of an outbreak like this, it is highly important to readily provide information to begin the evaluation necessary to understand the risks and begin containment activities.
  26. Mar 2020
    1. A koala bear isn’t actually a bear, it’s a marsupial. Whales aren’t fish, they’re mammals. Tomatoes aren’t vegetables, they’re fruit. Almost nothing is actually a nut. Peanuts, Brazil nuts, cashews, walnuts, pecans and almonds: none of them are really nuts (for the record, peanuts are legumes, Brazils and cashews are seeds, and the others are all drupes). Hazelnuts and chestnuts are the exception: they are the elite, the “true” nuts.

      When using everyday-English, we follow a different classification system than in Biology.

  27. Feb 2020
    1. Nix is a purely functional package manager. This means that it treats packages like values in purely functional programming languages such as Haskell — they are built by functions that don’t have side-effects, and they never change after they have been built.
    1. The ethical principle that I chose to do was Cultural Relativism. This part in this article indicates that a vast majority of jobs need to think in the cultural relativism approach. Since the impact of globalization, the diversity context in society, workplaces and schools force us to face some discrimination that should not appeared. People are used to evaluate other cultural basing on their own background, if they are not familiar with other culture. Judging other cultural objects on your own norms and beliefs can be a negative behavior against people who are different from you. In this case, we should think in cultural relativism method. We should try to understand other cultural practices in their own context. It would be better to create a harmonious society.

    2. I chose the principle of utilitarianism. I found this rather interesting because I feel that at first it sounds really good because you focus on doing what's best for the majority of people. You focus on what brings them happiness. However, as you think more deeply about it, utilitarianism has very blurry lines about what's good or not because they only have the one principle of making the majority of people happy, which can become an ethical problem if the majority of people want something that is not considered particularly good.

    3. The ethical principle that I have chosen is Eminent Domain vs. Rights of the Land Owner. Eminent Domain is the government's power to acquire private property against the will of the property owner as long as that land is necessary for public use. There are many examples of eminent domain throughout history and some cases of eminent domain have even made it to the Supreme Court. Eminent Domain challenges the Fifth Amendment of the United States Constitution, which guarantees Americans the right to own private property. Eminent Domain does state that the land owner will be fairly compensated, but private property owner often times do not want to sell in the first place. As long as the eminent domain is justified for "public use" the government may seize any private property that it needs to.

    4. The ethical principle I am interested in, utilitarianism, originated back in the 18th and 19th centuries from a guy named Jeremy Bentham, James Mill, and his son John Stuart Mill. As Catherine Rainbow from Davidson College states, the main focus of utilitarianism is that the most ethical decision is the one that yields the greatest benefit to the greatest number of people. To me I think that is a fun topic to think about because if a lot of people focused on this ethical strategy the world would be a lot less selfish and more selfless. The main flaw is that the predictions someone may make about a certain issue may not actually be for the greatest good as time passes along.

    5. The ethical principle that I chose to do was Utilitarianism vs. Justice : Allocation of limited resources. This section talks about how things can be Justice or utilitarianism in life or dead situations. Justice Oliver Holmes argued that everything should be justice and equal no matter what everyone should get the same shot at life. Some examples was that was given from this excerpt was about kidney and organ donors and people on the waiting list to get them. Holmes is basically saying it should be an equal draw to get a kidney an example would be everyone putting their name in a bucket and someone randomly draws out a name everyone had an equal chance to get the kidney. On the flip side utilitarianism is saying the people that needs it the most needs to get it based off severity to get it. I personally would say I'm Utilitarianism because I believe the people that need something the most in life or death situations should get what is needed.

    6. The book Ethics of Emerging Technologies: Scientific Facts and Moral Challenges explains the different types of ethical principles, and uses situations to analyze them. The principal that intrigued me the most was Utilitarianism. I thought this theory was the most interesting because of the way in which it competes against every other theory in some way. When I originally learned about this theory I thought it was doing the greatest good for the greatest number, but I learned there was more behind it. A big part of Utilitarianism revolves around consequences and understanding what they will be based on your action. Utilitarianism is different than many theories because in some circumstances, it is better for the greatest number of people to do a specific action than doing what your specific duty is, or what justice says is fair for everyone. I believe that Utilitarianism introduces a quality of realism, because it requires understanding the consequences and knowing you will not be able to make everyone happy with your action.

    1. Exchange value

      Exchange value appears as the property of a commodity that is exchangeable for other commodities. It also presupposes societies who produce commodities and exchange them. While all societies have things with use values, exchange value is relative to a specific time and place.

      Additionally, exchanging commodities must also presupposes a way to determine proportionality between different commodities, so that they can be exchanged in the first place.

      Exchange therefore requires some other measure that stands above the two commodities meant to be exchanged. If there were no ways in which iron and corn were found similar to a society, for example, then we would not exchange them and they would have no exchange value.

      Marx will contend that what each commodity must contain crystalized within it is value (formally) and that the substance of value is labor (viz. the common factor of both iron and corn is labor). Marx will call this kind of labor abstract labor.

    2. Section 1. The Two Factors of a Commodity, Use-Value and Value

      Marx's analysis of a capitalist system begins by postulating that it's fundamentally composed of units called commodities.

      In the capitalist system commodities have two features.

      1. They are produced

      2. They are produced by capitalists

      Capitalists produce commodities by employing workers to produce them.

      In this section, Marx begins his analysis of the first feature of the capitalist system (viz. that it is commodity producing). Workers and capitalists will not appear in Marx's analysis for several more chapters.

  28. Dec 2019
    1. When a javascript module is prepared for use on a client there are two major concerns: certain features are already provided by the client, and certain features are not available. Features provided by a client can include http requests, websockets, dom manipulation. Features not available would include tcp sockets, system disk IO.
  29. Aug 2019
    1. Prelude to Plant Form and Physiology

      The reading discusses the importance and value of plants and photosynthesis to our everyday lives. Although plants are broken down into a plethora of categories, they all behave very similarly (using photosynthesis to obtain nutrients) and share the same basic structure (consist of roots, stems and leaves).

  30. Jun 2019
    1. I find Act Utilitarianism very interesting because it places the morality of an action on the result rather than the actions that lead up to the result. The author gives many examples of conflicts people who ascribe to Act Utilitarianism may face because they do not adhere to a code of ethics. Rather, they have one ethical principle that they aim to achieve. This guiding principle is to make decisions that lead to the most amount of good for the most amount of people. The author uses a tax example, saying, it is most Act Utilitarian to tax people proportionally based on wealth rather than tax everyone the same rate. This is to ensure that each taxed individual is paying their fair share. While this seems like a simple ethical model to follow, it does raise some issues. Mainly, that it does not define what good is. Therefore, Act Utilitarianism requires its followers to make decisions in pursuit of something that is unclear. #summary

    2. The ethical principal that I choose is Justice Ethic, the author talks about how it is important that everyone is treated equally. Such as tax, responsibility, benefit, obligation etc. Which it is becoming a social issue today and changing this situation is a challenge for us. Because people tend to treat people similar to themselves equally and people different to them poorly. This makes people want to treat people nicely, so they can get the same treatment in return. The issue today is, people don't feel they are being treated equally. Justice is a valuable tool to show the right way of the moral and philosophy in society. It makes making decisions a lot easier.

    3. The ethical principle that I chose to do was Rules of Ethics. This section talked about in the 16th century Hobbes believed that peoples individual liberties lead to their selfish decisions. Hobbes felt that civilization was all based on the fear of death and the will to be in power. He felt that people should have construction and commonwealth and people should should have the final word to be able to keep the peace this has been seen in may cultures to be unacceptable.

  31. May 2019
    1. Key ideas: rebel culture; black metal; bending rules; combining ideas; AND brewers grounded in education/tradition