bluuebunny/crossref_metadata_2025 huggingface dataset:
Transfer learning for biomedical named entity recognition with neural networks
Authors: Giorgi John M , Bader Gary D
Published: May 2018

Motivation

The explosive increase of biomedical literature has made information extraction an increasingly important tool for biomedical research. A fundamental task is the recognition of biomedical named entities in text (BNER) such as genes/proteins, diseases and species. Recently, a domain-independent method based on deep learning and statistical word embeddings, called long short-term memory network-conditional random field (LSTM-CRF), has been shown to outperform state-of-the-art entity-specific BNER tools. However, this method is dependent on gold-standard corpora (GSCs) consisting of hand-labeled entities, which tend to be small but highly reliable. An alternative to GSCs are silver-standard corpora (SSCs), which are generated by harmonizing the annotations made by several automatic annotation systems. SSCs typically contain more noise than GSCs but have the advantage of containing many more training examples. Ideally, these corpora could be combined to achieve the benefits of both, which is an opportunity for transfer learning. In this work, we analyze to what extent transfer learning improves upon state-of-the-art results for BNER.

Results

We demonstrate that transferring a deep neural network (DNN) trained on a large, noisy SSC to a smaller, but more reliable GSC significantly improves upon state-of-the-art results for BNER. Compared to a state-of-the-art baseline evaluated on 23 GSCs covering four different entity classes, transfer learning results in an average reduction in error of approximately 11%. We found transfer learning to be especially beneficial for target datasets with a small number of labels (approximately 6000 or less).

Availability and implementation

Source code for the LSTM-CRF is available at https://github.com/Franck-Dernoncourt/NeuroNER/ and links to the corpora are available at https://github.com/BaderLab/Transfer-Learning-BNER-Bioinformatics-2018/.

Supplementary information

Supplementary data are available at Bioinformatics online.
ACPred-FL: a sequence-based predictor using effective feature representation to improve the prediction of anti-cancer peptides
Authors: Wei Leyi , Zhou Chen , Chen Huangrong , Song Jiangning , Su Ran
Published: May 2018

Motivation

Anti-cancer peptides (ACPs) have recently emerged as promising therapeutic agents for cancer treatment. Due to the avalanche of protein sequence data in the post-genomic era, there is an urgent need to develop automated computational methods to enable fast and accurate identification of novel ACPs within the vast number of candidate proteins and peptides.

Results

To address this, we propose a novel predictor named Anti-Cancer peptide Predictor with Feature representation Learning (ACPred-FL) for accurate prediction of ACPs based on sequence information. More specifically, we develop an effective feature representation learning model, with which we can extract and learn a set of informative features from a pool of support vector machine-based models trained using sequence-based feature descriptors. By doing so, the class label information of data samples is fully utilized. To improve the feature representation, we further employ a two-step feature selection technique, resulting in a most informative five-dimensional feature vector for the final peptide representation. Experimental results show that such five features provide the most discriminative power for identifying ACPs than currently available feature descriptors, highlighting the effectiveness of the proposed feature representation learning approach. The developed ACPred-FL method significantly outperforms state-of-the-art methods.

Availability and implementation

The web-server of ACPred-FL is available at http://server.malab.cn/ACPred-FL.

Supplementary information

Supplementary data are available at Bioinformatics online.
Quantitative Three-Dimensional Reconstructions of Excitatory Synaptic Boutons in Layer 5 of the Adult Human Temporal Lobe Neocortex: A Fine-Scale Electron Microscopic Analysis
Authors: Yakoubi Rachida , Rollenhagen Astrid , von Lehe Marec , Shao Yachao , Sätzler Kurt , Lübke Joachim H R
Published: May 2018

Studies of synapses are available for different brain regions of several animal species including non-human primates, but comparatively little is known about their quantitative morphology in humans. Here, synaptic boutons in Layer 5 (L5) of the human temporal lobe (TL) neocortex were investigated in biopsy tissue, using fine-scale electron microscopy, and quantitative three-dimensional reconstructions. The size and organization of the presynaptic active zones (PreAZs), postsynaptic densities (PSDs), and that of the 3 distinct pools of synaptic vesicles (SVs) were particularly analyzed. L5 synaptic boutons were medium-sized (~6 μm2) with a single but relatively large PreAZ (~0.3 μm2). They contained a total of ~1500 SVs/bouton, ~20 constituting the putative readily releasable pool (RRP), ~180 the recycling pool (RP), and the remainder, the resting pool. The PreAZs, PSDs, and vesicle pools are ~3-fold larger than those of CNS synapses in other species. Astrocytic processes reached the synaptic cleft and may regulate the glutamate concentration. Profound differences exist between synapses in human TL neocortex and those described in various species, particularly in the size and geometry of PreAZs and PSDs, the large RRP/RP, and the astrocytic ensheathment suggesting high synaptic efficacy, strength, and modulation of synaptic transmission at human synapses.
Runge–Kutta convolution coercivity and its use for time-dependent boundary integral equations
Authors: Banjai Lehel , Lubich Christian
Published: May 2018

A coercivity property of temporal convolution operators is an essential tool in the analysis of time-dependent boundary integral equations and their space and time discretizations. It is known that this coercivity property is inherited by convolution quadrature time discretization based on A-stable multistep methods, which are of order at most 2. Here we study the question as to which Runge–Kutta-based convolution quadrature methods inherit the convolution coercivity property. It is shown that this holds without any restriction for the third-order Radau IIA method, and on permitting a shift in the Laplace domain variable, this holds for all algebraically stable Runge–Kutta methods and hence for methods of arbitrary order. As an illustration the discrete convolution coercivity is used to analyse the stability and convergence properties of the time discretization of a nonlinear boundary integral equation that originates from a nonlinear scattering problem for the linear wave equation. Numerical experiments illustrate the error behaviour of the Runge–Kutta convolution quadrature time discretization.
Regulation and role of the transcription factor IRF5 in innate immune responses and systemic lupus erythematosus
Authors: Ban Tatsuma , Sato Go R , Tamura Tomohiko
Published: May 2018

The transcription factor interferon regulatory factor-5 (IRF5) plays an important role in innate immune responses via the TLR-MyD88 (Toll-like receptor - myeloid differentiation primary response 88) pathway. IRF5 is also involved in the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE). Recent studies have identified new regulators, both positive and negative, which act on IRF5 activation events in the TLR-MyD88 pathway such as post-translational modifications, dimerization and nuclear translocation. A model of the causal relationship between IRF5 activation and SLE pathogenesis proposes that a loss of the negative regulation of IRF5 causes its hyperactivation, resulting in hyperproduction of type I interferons and other cytokines, and ultimately in the development of SLE. Importantly, to our knowledge, all murine models of SLE studied thus far have shown that IRF5 is required for the pathogenesis of SLE-like diseases. During the development of SLE-like diseases, IRF5 plays key roles in various cell types, including dendritic cells and B cells. It is noteworthy that the onset of SLE-like diseases can be inhibited by reducing the activity or amount of IRF5 by half. Therefore, IRF5 is an important therapeutic target of SLE, and selective suppression of its activity and expression may potentially lead to the development of new therapies.
National or political cake? The political economy of intergovernmental transfers in Nigeria
Authors: Maystadt Jean-François , Salihu Muhammad-Kabir
Published: May 2018

Rule-based intergovernmental transfers are often presented as the panacea to avoid the manipulation of transfers for political motives. We question that assertion in the case of Nigeria, where these transfers are highly dependent on natural resources and likely to be subject to elite capture. In this article, we use oil windfalls as a source of exogenous variation in the political discretion an incumbent government can exert in rule-based transfers. Exploiting within-state variation between 2007 and 2015 in Nigeria, an increase in VAT transfers induced by higher oil windfalls is found to improve the electoral fortune of an incumbent government. Our results question the promotion of rule-based transfers as a one-fits-all institutional solution in resource-abundant countries with relatively weak institutions.
Marketing Exposure Recall is Associated With Past 30-Day Single, Dual, Polytobacco Use Among US Adolescents
Authors: Mantey Dale S , Creamer MeLisa R , Pasch Keryn E , Perry Cheryl L
Published: May 2018

Introduction

This study assesses the relationship between tobacco/e-cigarette marketing exposure and single, dual, and polytobacco product use, among adolescents. Given the increased use of noncigarette tobacco products (eg, cigars, e-cigarettes, hookah) among youth, it is imperative to understand if marketing exposure is associated with dual and polytobacco product use.

Methods

Data were obtained from the 2014 National Youth Tobacco Survey and weighted to be representative of US middle and high school students. Multivariable multinomial logistic regression models were used to assess the relationships between product marketing (via internet, print, retail, and TV/movies) and past 30-day single, dual, and poly (three or more) tobacco product use. Three analyses were conducted using different categories as referent groups to allow for comprehensive examination of the relationships between all groups.

Results

Marketing exposure was significantly correlated with a greater risk of single, dual, and polytobacco product use relative to nonusers. Relative to single product users, product marketing exposure was significantly correlated with a greater relative risk of dual and polytobacco use. There was no statistical difference in the association of marketing exposure between dual and polytobacco use, in any model.

Conclusion

A positive relationship between tobacco product marketing exposure and number of tobacco products used was observed. The magnitude of the relationship grew from single product to dual/poly use. Restrictions of marketing of all tobacco products, similar to cigarettes, particularly in the retail setting, should be considered.

Implications

This study has two primary public health implications. First, self-reported exposure to tobacco/e-cigarette marketing is widespread among adolescents of all tobacco product categories. Second, this widespread exposure to tobacco/e-cigarette marketing appears to not only be correlated with use of a single tobacco product (eg, cigarettes, e-cigarettes), but also multiple tobacco products. While longitudinal studies are needed to further investigate the relationships observed in this study, findings justify further study given the known relationship between tobacco marketing exposure and subsequent cigarette use.
Patient features and survival of pediatric aplastic anemia in the USA: a large institution experience
Authors: Hossain M J , Xie S
Published: May 2018

Background

We performed the first epidemiologic investigation to examine association of demographics and clinical characteristics at diagnosis, as well as health care expense coverage, with survival of US children with aplastic anemia (AA).

Methods

We obtained electronic medical record data of 1140 children aged 0–19 years diagnosed with AA followed at a pediatric health system between 2004 and 2014. Kaplan–Meier curve and Cox proportional hazards regressions were used.

Results

Self-pay patients had a mortality risk five times higher than that of those insured by publicly funded insurance (hazards ratio, 95% CI: 6.0, 3.7–9.8). Other features associated with higher mortality risk include pancytopenia (hazards ratio, referent: 4.2, constitutional AA); underweight (2.0, normal-weight); platelet count <50 × 109/l (1.3, ≥50 × 109/l); male sex (1.3, female); and ages at diagnosis 6–11, 11–16 and 16–19 years (1.6, 1.9, 2.3, 1–3 years), respectively.

Conclusions

Self-pay was the strongest prognostic factor for pediatric AA mortality. Older age, pancytopenia, underweight, male sex and lower platelet count were also associated with increased risk of mortality. These findings may be useful for providers, researchers and policymakers to ensure effective health care delivery to this population and to motivate future etiologic research and establishment of a surveillance registry.
Viral Metagenomic-Based Screening of Sugarcane from Florida Reveals Occurrence of Six Sugarcane-Infecting Viruses and High Prevalence ofSugarcane yellow leaf virus
Authors: Filloux D. , Fernandez E. , Comstock J. C. , Mollov D. , Roumagnac P. , Rott P.
Published: May 2018

A viral metagenomics study of the sugarcane virome in Florida was carried out in 2013 to 2014 to analyze occurrence of known and potentially new viruses. In total, 214 sugarcane leaf samples were collected from different commercial sugarcane (Saccharum interspecific hybrids) fields in Florida and from other Saccharum and related species taken from two local germplasm collections. Virion-associated nucleic acids (VANA) metagenomics was used for detection and identification of viruses present within the collected leaf samples. VANA sequence reads were obtained for 204 leaf samples and all four previously reported sugarcane viruses occurring in Florida were detected: Sugarcane yellow leaf virus (SCYLV, 150 infected samples out of 204), Sugarcane mosaic virus (1 of 204), Sugarcane mild mosaic virus (13 of 204), and Sugarcane bacilliform virus (54 of 204). High prevalence of SCYLV in Florida commercial fields and germplasm collections was confirmed by reverse-transcription polymerase chain reaction. Sequence analyses revealed the presence of SCYLV isolates belonging to two different phylogenetic clades (I and II), including a new genotype of this virus. This viral metagenomics approach also resulted in the detection of a new sugarcane-infecting mastrevirus (recently described and named Sugarcane striate virus), and two potential new viruses in the genera Chrysovirus and Umbravirus.
Fine Endmesolithic Fish Caviar Meal Discovered by Proteomics of Foodcrusts
Authors: Shevchenko Anna , Schuhmann Andrea , Wetzel Günter
Published: May 2018

The role of aquatic resources in ancient economies and paleodiet is important for understanding the evolution of prehistorical societies. However, conventional archaeometric approaches lack organismal specificity, are affected by abundant environmental contaminants and do not elucidate food processing recipes. We performed proteomics analysis of charred organic deposits adhered on early ceramics from Mesolithic-Neolithic inland site Friesack 4 (Brandenburg, Germany). Proteomics of foodcrust from a vessel attributed to Endmesolithic pottery identified fine carp roe meal and revealed details of a prehistorical culinary recipe. We propose that Endmesolithic occupants of Friesack at the end of the 5thmillennium BC utilized fish as a food reserve and adopted delayed-return subsistence strategy. These data contribute to better understanding of the dietary context of Neolithic transition in European inland.
Potential combined pro-cognitive, anxiolytic and antidepressant properties of novel GABAA receptor positive modulators with preferential efficacy at the α5-subunit
Authors: Prevot Thomas D. , Li Guanguan , Vidojevic Aleksandra , Misquitta Keith A. , Fee Corey , Santrac Anja , Knutson Daniel E. , Stephen Michael R. , Kodali Revathi , Zahn Nicolas M. , Arnold Leggy A. , Scholze Petra , Fisher Janet L. , Marković Bojan D. , Banasr Mounira , Cook Jim , Savic Miroslav , Sibille Etienne
Published: May 2018

Altered γ-aminobutyric acid (GABA) function is consistently reported in psychiatric disorders, normal aging and neurodegenerative disorders, and reduced function of somatostatin - expressing GABA interneurons is associated with both mood and cognitive symptoms. Somatostatin-neurons signal in part through α5-subunit containing GABAA receptors (α5-GABAA-Rs) which are localized in brain regions implicated in emotion and cognition. We hypothesize that enhancing α5-GABAA-R activity has therapeutic potential for both mood and cognitive symptoms in stress-based and aging rodent models.

We synthesized four novel imidazobenzodiazepine (IBZD) amide ligands, tested them for positive allosteric modulation at α5-GABAA-R (α5-PAM), pharmacokinetic properties, and for anxiolytic and antidepressant activities in adult mice. Pro-cognitive activity was tested in adult mice submitted to chronic stress and in old mice. Diazepam (DZP), with broad PAM activity at GABAA-Rs, was used as a control.

Three novel IBZD amide ligands (GL-II-73, GL-II-74 and GL-II-75) demonstrated adequate brain penetration, affinity and α5-PAM activity, and metabolic stability for in vivo studies. GL-II-73/74/75 showed significant anxiolytic and antidepressant efficacies in adult mice. GL-II-73 and GL-II-75 significantly reversed cognitive deficits induced by stress or occurring throughout normal aging. This activity was maintained after sub-chronic administration for GL-II-73. In contrast DZP displayed anxiolytic but no antidepressant or pro-cognitive activities.

We demonstrate for the first time the potential for combined anxiolytic, antidepressant and pro-cognitive therapeutic, mediated by newly designed IBDZ amide ligands with efficacy at α5-GABAA-Rs. These results suggest a novel therapeutic approach targeting both mood and cognitive symptoms in depression and/or aging.
Assessment and Optimization of Collective Variables for Protein Conformational Landscape: GB1 β-hairpin as a Case Study
Authors: Ahalawat Navjeet , Mondal Jagannath
Published: May 2018

Collective variables (CV), when chosen judiciously, can play an important role in recognizing rate-limiting processes and rare events in any biomolecular systems. However, high dimensionality and inherent complexities associated with such biochemical systems render the identification of an optimal CV a challenging task, which in turn precludes the elucidation of underlying conformational landscape in sufficient details. In this context, a relevant model system is presented by 16residue, β hairpin of GB1 protein. Despite being the target of numerous theoretical and computational studies for understanding the protein folding, the set of CVs optimally characterizing the conformational landscape of, β hairpin of GB1 protein has remained elusive, resulting in a lack of consensus on its folding mechanism. Here we address this by proposing a pair of optimal CVs which can resolve the underlying free energy landscape of GB1 hairpin quite efficiently. Expressed as a linear combination of a number of traditional CVs, the optimal CV for this system is derived by employing recently introduced Timestructured Independent Component Analysis (TICA) approach on a large number of independent unbiased simulations. By projecting the replica-exchange simulated trajectories along these pair of optimized CVs, the resulting free energy landscape of this system are able to resolve four distinct wellseparated metastable states encompassing the extensive ensembles of folded,unfolded and molten globule states. Importantly, the optimized CVs were found to be capable of automatically recovering a novel partial helical state of this protein, without needing to explicitly invoke helicity as a constituent CV. Furthermore, a quantitative sensitivity analysis of each constituent in the optimized CV provided key insights on the relative contributions of the constituent CVs in the overall free energy landscapes. Finally, the kinetic pathways con necting these metastable states, constructed using a Markov State Model, provide an optimum description of underlying folding mechanism of the peptide. Taken together, this work oers a quantitatively robust approach towards comprehensive mapping of the underlying folding landscape of a quintessential model system along its optimized collective variables.
VARAN-GIE: Curation of Genomic Interval Sets
Authors: Popitsch Niko
Published: May 2018

Genomic interval sets are fundamental elements of genome annotation and are the output of countless bioinformatics applications. Nevertheless, tool support for the manual curation of these data is currently limited. We developed VARAN-GIE, an extension of the popular Integrative Genomics Viewer (IGV) that adds functionality to edit, annotate and merge genomic interval sets. Data can easily be shared with other users and imported/exported from/to multiple common data formats. VARAN-GIE binary releases, source-code, user guides and tutorials are available at https://github.com/popitsch/varan-gie/
Driving the expression of theSalmonella entericasv Typhimurium flagellum usingflhDCfromEscherichia coliresults in key regulatory and cellular differences
Authors: Albanna Ayman , Sim Martin , Hoskisson Paul A , Gillespie Colin , Rao Christopher V. , Aldridge Phillip
Published: May 2018

The flagellar systems ofEscherichia coliandSalmonella entericaexhibit a significant level of genetic and functional synteny. Both systems are controlled by the flagellar specific master regulator FlhD4C2. Since the early days of genetic analyses of flagellar systems it has been known thatE. coli flhDCcan complement a ΔflhDCmutant inS. enterica. The genomic revolution has identified how genetic changes to transcription factors and / or DNA binding sites can impact the phenotypic outcome across related species. We were therefore interested in asking: using modern tools to interrogate flagellar gene expression and assembly, what would the impact be of replacing theflhDCcoding sequences inS. entericafor theE. coligenes at theflhDC S. enterciachromosomal locus? We show that even though all strains created are motile, flagellar gene expression is measurably lower whenflhDCECare present. These changes can be attributed to the impact of FlhD4C2DNA recognition and the protein-protein interactions required to generate a stable FlhD4C2complex. Furthermore, our data suggests that inE. colithe internal flagellar FliT regulatory feedback loop has a marked difference with respect to output of the flagellar systems. We argue due diligence is required in making assumptions based on heterologous expression of regulators and that even systems showing significant synteny may not behave in exactly the same manner.
Phosphatidylinositol 5 phosphate 4-kinase regulates plasma-membrane PIP3 turnover and insulin sensitivity in Drosophila
Authors: Sharma Sanjeev , Mathre Swarna , Visvanathan Sanjeev , Shinde Dhananjay , Raghu Padinjat
Published: May 2018

Phosphatidylinositol-3,4,5-trisphosphate (PIP3) generation at the plasma membrane is a key event during activation of receptor tyrosine kinases such as the insulin receptor and is critical for normal growth and metabolism. The lipid kinases and phosphatases regulating PIP3 levels are described but mechanisms controlling their activity remain unclear. We report that in Drosophila, phosphatidylinositol 5 phosphate 4-kinase (PIP4K) function at the plasma membrane is required for normal PIP3 levels during insulin receptor activation. Depletion of PIP4K increases PIP3 levels and augments sensitivity to insulin through enhanced Class I phosphoinositide 3-kinase (PI3K) activity. Animals lacking PIP4K show enhanced insulin signalling dependent phenotypes in vivo and are resistant to the metabolic consequences of a high-sugar diet, highlighting the importance of PIP4K in normal metabolism and development. Thus, PIP4KS are key regulators of receptor tyrosine kinase signalling with implications for growth factor dependent processes including tumour growth, T-cell activation and metabolism.
Ethanol-Mediated Compaction and Crosslinking Enhance Mechanical Properties and Degradation Resistance While Maintaining Cytocompatibility of a Nucleus Pulposus Scaffold
Authors: Walters Joshua D. , Gill Sanjitpal S. , Mercuri Jeremy J.
Published: May 2018

Intervertebral disc degeneration is a complex, cell-mediated process originating in the nucleus pulposus (NP) and is associated with extracellular matrix catabolism leading to disc height loss and impaired spine kinematics. Previously, we developed an acellular bovine NP (ABNP) for NP replacement that emulated human NP matrix composition and supported cell seeding; however, its mechanical properties were lower than those reported for human NP. To address this, we investigated ethanol-mediated compaction and crosslinking to enhance the ABNP’s dynamic mechanical properties and degradation resistance while maintaining its cytocompatibility. First, volumetric and mechanical effects of compaction only were confirmed by evaluating scaffolds after various immersion times in buffered 28% ethanol. It was found that compaction reached equilibrium at ∼30% compaction after 45 min, and dynamic mechanical properties significantly increased 2-6x after 120 min of submersion. This was incorporated into a crosslinking treatment, through which scaffolds were subjected to 120 min pre-compaction in buffered 28% ethanol prior to carbodiimide crosslinking. Their dynamic mechanical properties were evaluated before and after accelerated degradation by ADAMTS-5 or MMP-13. Cytocompatibility was determined by seeding stem cells onto scaffolds and evaluating viability through metabolic activity and fluorescent staining. Compacted and crosslinked scaffolds showed significant increases in DMA properties without detrimentally altering their cytocompatibility, and these mechanical gains were maintained following enzymatic exposure.
Inductive reasoning differs between taxonomic and thematic contexts: Electrophysiological evidence
Authors: Liu Fangfang , Han Jiahui , Zhang Lingcong , Li Fuhong
Published: May 2018

Inductive reasoning can be performed in different contexts, but it is unclear whether the neural mechanism of inductive reasoning performed in a thematic context (e.g., panda has x, so bamboo has x) is the same as that performed in a taxonomic context (e.g., panda has x, so bear has x). In the present study, participants were required to judge whether a conclusion was acceptable or not based on its premise, for which the taxonomic or thematic distances between premise and conclusion objects were either far or near. The ERP results indicated that the effect of reasoning context (taxonomic vs. thematic) was initially observed in the P2 component; while the distance effect (far vs. near) was observed in N400 and late components. Moreover, the distance effect on thematic-based inductive reasoning was found in the frontal and frontal-central brain regions, while the distance effect in taxonomic-based inductive reasoning conditions was found in the central-parietal and parietal regions. These results support the view that inductive reasoning is performed differently under different semantic contexts.
Evaluation of a guideline developed to reduce HIV-related stigma and discrimination in healthcare settings and establishing consensus
Authors: Feyissa Garumma Tolu , Lockwood Craig , Woldie Mirkuzie , Munn Zachary
Published: May 2018

Background

Developing guidelines and policies is critical to address HIV-related stigma and discrimination (SAD) in healthcare settings. To this end, a multidisciplinary panel developed a guideline to reduce SAD. This project evaluated the appropriateness of implementing the guideline in the Ethiopian context.

Methods

A consensus of the expert panel was established through a Delphi technique which was followed by a panel meeting. Initial tentative recommendations were distributed to experts through e-mails to be evaluated using the modified guideline implementability appraisal (GLIA) v.2.0 checklist.

Results

In the first round of the Delphi survey, all (13) panel members evaluated the guideline. The overall score for the general domain of the modified GLIA checklist was 96.56%. The scores for individual recommendations ranged from 68.33% to 92.76%. Maximum and minimum scores were attained for measurability (97.71%) and flexibility (59.77%) domains respectively. Percentages mean score lower than 75% was obtained for flexibility and validity domains. Participants suggested that additional tools and training should be added to the guideline. In the second round of the survey, all the recommendations received endorsement with scores above 75%. Maximum and minimum scores were attained for measurability (100%) and flexibility (86.88%) domains respectively. During the panel meeting, issues of responsibility for implementing the guideline were discussed.

Conclusion

The project evaluated implementability of a guideline developed to reduce HIV-related SAD in healthcare settings. The Delphi survey was followed by a half-day meeting that helped in further clarification of points.
Mutation load dynamics during environmentally-driven range shifts
Authors: Gilbert Kimberly J. , Peischl Stephan , Excoffier Laurent
Published: May 2018

The fitness of spatially expanding species has been shown to decrease over time and space, but specialist species tracking their changing environment and shifting their range accordingly have been little studied. We use individual-based simulations and analytical modeling to compare the impact of range expansions and range shifts on genetic diversity and fitness loss, as well as the ability to recover fitness after either a shift or expansion. We find that the speed of a shift has a strong impact on fitness evolution. Fastest shifts show the strongest fitness loss per generation, but intermediate shift speeds lead to the strongest fitness loss per geographic distance. Range shifting species lose fitness more slowly through time than expanding species, however, their fitness compared at equivalent geographic distances spread can be considerably lower. These counter-intuitive results arise from the combination of time over which selection acts and mutations enter the system. Range shifts also exhibit reduced fitness recovery after a geographic shift and may result in extinction, whereas range expansions can persist from the core of the species range. The complexity of range expansions and range shifts highlights the potential for severe consequences of environmental change on species survival.

Author Summary

As environments change through time across the globe, species must adapt or relocate to survive. Specialized species must track the specific moving environments to which they are adapted, as compared to generalists which can spread widely. During colonization of new habitat, individuals can accumulate deleterious alleles through repeated bottlenecks. We show through simulation and analytic modeling that the process by which these alleles accumulate changes depending upon the speed at which populations spread over a landscape. This is due to the increased efficacy of selection against deleterious variants at slow speeds of range shifts and decreased input of mutations at faster speeds of range shifts. Under some selective circumstances, shifting of a species range leads to extinction of the entire population. This suggests that the rate of environmental change across the globe will play a large role in the survival of specialist species as compared to more generalist species.
Analysis of the transcriptional logic governing differential spatial expression in Hh target genes
Authors: Cambón Manuel , Sánchez Óscar
Published: May 2018

This work provides theoretical tools to analyse the transcriptional effects of certain biochemical mechanisms (i.e. affinity and cooperativity) that have been proposed in previous literature to explain the differential spatial expression of Hedgehog target genes involved inDrosophiladevelopment. Specifically we have focused on the expression ofdecapentaplegicandpatched. The transcription of these genes is believed to be controlled by opposing gradients of the activator and repressor forms of the transcription factor Cubitus interruptus (Ci). This study is based on a thermodynamic approach, which provides expression rates for these genes. These expression rates are controlled by transcription factors which are competing and cooperating for common binding sites. We have made mathematical representations of the different expression rates which depend on multiple factors and variables. The expressions obtained with the model have been refined to produce simpler equivalent formulae which allow for their mathematical analysis. Thanks to this, we can evaluate the correlation between the different interactions involved in transcription and the biological features observed at tissular level. These mathematical models can be applied to other morphogenes to help understand the complex transcriptional logic of opposing activator and repressor gradients.

Author summary

Morphogenic differentiation is a complex process that involves emission, reception and cellular response to different signals. It is well known that the same morphogenic signal can give rise to different cellular transcriptional responses that usually depend, among other factors, on transcription factors. In concordance with the activator threshold model, classically it has been distinguished between high and low threshold target genes in order to explain how cells receiving the same signal can activate different genes. However, in particular cases where the transcription is controlled by two opposing transcription factors, it has been tested that this logic is not valid. This motivates the necessity for describing new theoretical models in order to understand better these cellular responses. By a theoretical analysis we have deduced different versions of transcriptional logic that are significantly determined by how the opposing transcription factors cooperate between them in the transcription process. We have also tested these different scenarios focussing on the Drosophila Hh target genes, and we have reproduced similar conclusions to the ones obtained by other methodologies.
Estimating heterogeneous treatment effects by balancing heterogeneity and fitness
Authors: Zhang Weijia , Le Thuc , Liu Lin , Li Jiuyong
Published: May 2018

Estimating heterogeneous treatment effects is an important problem in many medical and biological applications since treatments may have different effects on the prognoses of different patients. Recently, several recursive partitioning methods have been proposed to identify the subgroups that with different responds to a treatment, and they rely on a fitness criterion to minimize the error between the estimated treatment effects and the unobservable true effects. In this paper, we propose that a heterogeneity criterion, which maximizes the differences of treatment effects among the subgroups, also needs to be considered. Moreover, we show that better performances can be achieved when the fitness and the heterogeneous criteria are considered simultaneously. Selecting the optimal splitting points then becomes a multi-objective problem; however, a solution that achieves optimal in both aspects are often not available. To solve this problem, we propose a multi-objective splitting procedure to balance both criteria. The proposed procedure is computationally efficient and fits naturally into the existing recursive partitioning framework. Experimental results show that the proposed multi-objective approach performs consistently better than existing ones.

Author summary

The effects of a treatment are often not the same for different individuals with different gene expressions. Learning to predict the heterogeneous treatment effects from clinical and expression data is an important step towards personalized medical treatment. Existing computational methods are not ideal for the task because they do not address the interpretability of the model and do not consider the limited sample sizes in biological and medical applications. Our method addresses these issues and achieves superior performance in analyzing the treatment effects of radiotherapy on breast cancer patients.
Unbiased dynamic characterization of RNA-protein interactions by OOPS
Authors: Queiroz Rayner M. L. , Smith Tom , Villanueva Eneko , Monti Mie , Pizzinga Mariavittoria , Marti-Solano Maria , Mirea Dan-Mircea , Ramakrishna Manasa , Harvey Robert F. , Dezi Veronica , Degroeve Sven , Martens Lennart , Thomas Gavin H. , Willis Anne E. , Lilley Kathryn S.
Published: May 2018

Current methods for the identification of RNA–protein interactions require a quantity and quality of sample that hinders their application, especially for dynamic biological systems or when sample material is limiting. Here, we present a new approach to enrich RNA-Binding Proteins (RBPs): Orthogonal Organic Phase Separation (OOPS), which is compatible with downstream proteomics and RNA sequencing. OOPS enables recovery of RBPs and free protein, or protein-bound RNA and free RNA, from a single sample in an unbiased manner. By applying OOPS to human cell lines, we extract the majority of known RBPs, and importantly identify additional novel RBPs, including those from previously under-represented cellular compartments. The high yield and unbiased nature of OOPS facilitates its application in both dynamic and inaccessible systems. Thus, we have identified changes in RNA-protein interactions in mammalian cells following nocodazole cell-cycle arrest, and defined the first bacterial RNA-interactome. Overall, OOPS provides an easy-to-use and flexible technique that opens new opportunities to characterize RNA-protein interactions and explore their dynamic behaviour.
Deep feature selection for Identification of Essential Proteins of Learning and Memory in Mouse Model of Down Syndrome
Authors: Abdeldayem Sara S. , Elhefnawi Mahmoud M.
Published: May 2018

Down syndrome is a chromosomal abnormality related to intellectual disabilities that affects 0.1% of live births worldwide. It occurs when an individual has a full or partial extra copy of chromosome 21. This chromosome trisomy results in the overexpression of genes that is believed to be sufficient to interfere normal pathways and normal responses to stimulation, causing learning and memory deficiency. Therefore, by studying these proteins and the disturbance in pathways that are involved in learning and memory, we can consider drugs that would correct the observed perturbations, and therefore assist in enhancing the memory and learning. Here, from genes based on an earlier study that identified 77 proteins differentially expressed in normal and trisomic wild mice exposed to context fear conditioning (CFC), we provide a quantitative protein selection based on different feature selection techniques to select the most important proteins related to learning and memory. These techniques include Fisher score, Chi score, and correlation-based subset. In addition, a deep feature selection is utilized to extract high order proteins using deep neural networks. Three main experiments are carried out:studying the control mice’s response, studying the trisomy mice’s response, and studying the control-trisomy mice’s response. In each experiment, support vector machine classifier is used to assess these selected proteins ability to distinguish between learned and not-learned mice to the fear conditioning event. By applying the deep feature selection, fifteen proteins were selected in control mice, nine in trisomy mice, and seven in control-trisomy mice achieving distinguishing accuracies of 93%, 99%, 84% respectively compared to 74%, 78%, and 71% average accuracies of other selection methods. Some of these proteins have important biological function in learning such as CaNA, NUMb, and NOS.
An Event-related Potential Comparison of Facial Expression Processing between Cartoon and Real Faces
Authors: Zhao Jiayin , Wang Yifang , An Licong
Published: May 2018

Faces play important roles in the social lives of humans. In addition to real faces, people also encounter numerous cartoon faces in daily life. These cartoon faces convey basic emotional states through facial expressions. Using a behavioral research methodology and event-related potentials (ERPs), we conducted a facial expression recognition experiment with 17 university students to compare the processing of cartoon faces with that of real faces. This study used face type (real vs. cartoon) and participant gender (male vs. female) as independent variables. Reaction time, recognition accuracy, and the amplitudes and latencies of emotion processing-related ERP components such as N170, vertex positive potential (VPP), and late positive potential (LPP) were used as dependent variables. The ERP results revealed that cartoon faces caused larger N170 and VPP amplitudes as well as a briefer N170 latency than did real faces; that real faces induced larger LPP amplitudes than did cartoon faces; and that angry faces induced larger LPP amplitudes than did happy faces. In addition, the results showed a significant difference in the brain regions associated with face processing as reflected in a right hemispheric advantage. The behavioral results showed that the reaction times for happy faces were shorter than those for angry faces; that females showed a higher facial expression recognition accuracy than did males; and that males showed a higher recognition accuracy for angry faces than happy faces. These results demonstrate differences in facial expression recognition and neurological processing between cartoon faces and real faces among adults. Cartoon faces showed a higher processing intensity and speed than real faces during the early processing stage. However, more attentional resources were allocated for real faces during the late processing stage.
Generalized resolution matrix for neutron spin-echo three-axis spectrometers
Authors: Groitl Felix , Keller Thomas , Habicht Klaus
Published: May 2018

This article describes the energy resolution of spin-echo three-axis spectrometers (SE-TASs) by a compact matrix formalism. SE-TASs allow one to measure the line widths of elementary excitations in crystals, such as phonons and magnons, with an energy resolution in the µeV range. The resolution matrices derived here generalize prior work: (i) the formalism works for all crystal structures; (ii) spectrometer detuning effects are included; these arise typically from inaccurate knowledge of the excitation energy and group velocity; (iii) components of the gradient vector of the dispersion surface dω/dq perpendicular to the scattering plane are properly treated; (iv) the curvature of the dispersion surface is easily calculated in reciprocal units; (v) the formalism permits analysis of spin-echo signals resulting from multiple excitation modes within the three-axis spectrometer resolution ellipsoid.
Size–strain separation in diffraction line profile analysis
Authors: Scardi P. , Ermrich M. , Fitch A. , Huang E-Wen , Jardin R. , Kuzel R. , Leineweber A. , Mendoza Cuevas A. , Misture S. T. , Rebuffi L. , Schimpf Christian
Published: May 2018

Separation of size and strain effects on diffraction line profiles has been studied in a round robin involving laboratory instruments and synchrotron radiation beamlines operating with different radiation, optics, detectors and experimental configurations. The studied sample, an extensively ball milled iron alloy powder, provides an ideal test case, as domain size broadening and strain broadening are of comparable size. The high energy available at some synchrotron radiation beamlines provides the best conditions for an accurate analysis of the line profiles, as the size–strain separation clearly benefits from a large number of Bragg peaks in the pattern; high counts, reliable intensity values in low-absorption conditions, smooth background and data collection at different temperatures also support the possibility to include diffuse scattering in the analysis, for the most reliable assessment of the line broadening effect. However, results of the round robin show that good quality information on domain size distribution and microstrain can also be obtained using standard laboratory equipment, even when patterns include relatively few Bragg peaks, provided that the data are of good quality in terms of high counts and low and smooth background.
Neutron scattering length determination by means of total scattering
Authors: Hannon Alex C. , Gibbs Alexandra S. , Takagi Hidenori
Published: May 2018

A new method for the measurement of bound coherent neutron scattering lengths is reported. It is shown that a relative measurement of the neutron scattering length, {\overline b}, of an element can be made by analysis of the neutron correlation function of a suitable oxide crystal powder. For this analysis, it is essential to take into account the average density contribution to the correlation function, as well as the contributions arising from distances between atoms in the crystal. The method is demonstrated and verified by analysis of the neutron correlation function for the corundum form of Al2O3, yielding a value {\overline b} = 3.44 (1) fm for Al, in good agreement with the literature. The method is then applied to the isotopes of iridium, for which the values of the scattering lengths were unknown, and which are difficult to investigate by other methods owing to the large cross sections for the absorption of neutrons. The neutron correlation function of a sample of Sr2IrO4 enriched in 193Ir is used to determine values {\overline b} = 9.71 (18) fm and {\overline b} = 12.1 (9) fm for 193Ir and 191Ir, respectively, and these are consistent with the tabulated scattering length and cross sections of natural Ir. These values are of potential application for obtaining improved neutron diffraction results on iridates by the use of samples enriched in 193Ir, so that the severe absorption problems associated with 191Ir are avoided. Rietveld refinement of the neutron diffraction pattern of isotopically enriched Sr2IrO4 is used to yield a similar result for Ir. However, in practice the Rietveld result is shown to be less reliable because of correlation between the parameters of the fit.
A call for a round robin study of XAFS stability and platform dependence at synchrotron beamlines on well defined samples
Authors: Chantler Christopher T. , Bunker Bruce A. , Abe Hitoshi , Kimura Masao , Newville Matthew , Welter Edmund
Published: May 2018

Round robin studies have been used across fields of science for quality control testing and to investigate laboratory dependencies and cross-platform inconsistencies as well as to drive forward the improvement of understanding of experimental systems, systematic effects and theoretical limitations. Here, following the Q2XAFS Workshop and Satellite to IUCr Congress 2017 on `Data Acquisition, Treatment, Storage – quality assurance in XAFS spectroscopy', a mechanism is suggested for a suitable study across XAFS (X-ray absorption fine-structure) beamlines and facilities, to enable each beamline to cross-calibrate, provide representative test data, and to enable collaborative cross-facility activities to be more productive.