Miracle-dz/UniFAR-FTUs huggingface dataset:
The anisotropic network model web server at 2015 (ANM 2.0)

Summary: The anisotropic network model (ANM) is one of the simplest yet powerful tools for exploring protein dynamics. Its main utility is to predict and visualize the collective motions of large complexes and assemblies near their equilibrium structures. The ANM server, introduced by us in 2006 helped making this tool more accessible to non-sophisticated users. We now provide a new version (ANM 2.0), which allows inclusion of nucleic acids and ligands in the network model and thus enables the investigation of the collective motions of protein–DNA/RNA and –ligand systems. The new version offers the flexibility of defining the system nodes and the interaction types and cutoffs. It also includes extensive improvements in hardware, software and graphical interfaces. Availability and implementation: ANM 2.0 is available at http://anm.csb. pitt.edu Contact: eran.eyal@sheba.health. gov.il, eyal.eran@gmail.com
Validation of the Dutch Eating Behavior Questionnaire (DEBQ) in a sample of Chinese adolescents

Abstract We sought to validate the Dutch Eating Behavior Questionnaire (DEBQ) in a sample of Chinese adolescents and investigate differences in eating behaviors among Chinese normal weight, overweight, and obese adolescents. Chinese middle and high school students completed the DEBQ, Eating Disorder Inventory-1, and the Self-Control Scale. Result showed that the DEBQ had good internal consistency, test–retest reliability and criterion validity. Furthermore, the obese and overweight adolescents scored significantly higher than normal weight adolescents on three subscales. The DEBQ is effective for assessing eating behaviors in Chinese adolescents.
Zeaxanthin Inhibits Hypoxia-Induced VEGF Secretion by RPE Cells through Decreased Protein Levels of Hypoxia-Inducible Factors-1α

Hypoxia is the most important stimulus leading to upregulation of VEGF in the retina and this is caused by accumulation of hypoxia-inducible factors-1α (HIF-1α) protein. The effects of zeaxanthin, a natural phytochemical, on the VEGF and HIF-1α expression in the primary culture of human retinal pigment epithelial (RPE) cells were studied. An in vitro RPE cell hypoxia model was established by placing cells under 1% oxygen pressure or by adding cobalt chloride (CoCl2) to the culture medium. RPE cells and conditioned media were collected from cultures treated with and without zeaxanthin under normoxic and hypoxic conditions. VEGF and HIF-1α protein and RNA levels were measured by ELISA kits and RT-PCR, respectively. Hypoxia caused a significant increase of VEGF expression and accumulation of HIF-1α in RPE cells. Zeaxanthin at 50–150 μM significantly inhibited the expression of VEGF and accumulation of HIF-1α protein caused by hypoxia but did not affect expression of VEGF and HIF-1α under normoxic conditions. This is the first report on the effect of zeaxanthin on VEGF and HIF-1α levels in cultured RPE cells and suggests that zeaxanthin may have potential value in the prevention and treatment of various retinal diseases associated with vascular leakage and neovascularization.
PEAK SHIFT DISCRIMINATION LEARNING AS A MECHANISM OF SIGNAL EVOLUTION

Abstract “Peak shift” is a behavioral response bias arising from discrimination learning in which animals display a directional, but limited, preference for or avoidance of unusual stimuli. Its hypothesized evolutionary relevance has been primarily in the realm of aposematic coloration and limited sexual dimorphism. Here, we develop a novel functional approach to peak shift, based on signal detection theory, which characterizes the response bias as arising from uncertainty about stimulus appearance, frequency, and quality. This approach allows the influence of peak shift to be generalized to the evolution of signals in a variety of domains and sensory modalities. The approach is illustrated with a bumblebee (Bombus impatiens) discrimination learning experiment. Bees exhibited peak shift while foraging in an artificial Batesian mimicry system. Changes in flower abundance, color distribution, and visitation reward induced bees to preferentially visit novel flower colors that reduced the risk of flower-type misidentification. Under conditions of signal uncertainty, peak shift results in visitation to rarer, but more easily distinguished, morphological variants of rewarding species in preference to their average morphology. Peak shift is a common and taxonomically wide-spread phenomenon. This example of the possible role of peak shift in signal evolution can be generalized to other systems in which a signal receiver learns to make choices in situations in which signal variation is linked to the sender's reproductive success.
Bayesian and GIS Mapping of Childhood Mortality in Rural Burkina Faso

Background: Various geographic information systems (GIS) are now widely used to map the distribution of diseases and mortality. However, the mapping of raw mortality rates has been found to be inappropriate since it does not account for the spatial heterogeneity of the population at risk. Bayesian techniques have therefore been suggested as a solution to the problem. Methods: Annual mortality rates for each of the 39 villages of the study area in the Kossi Province in northwest Burkina Faso were calculated using midyear populations of children under five. Two mapping techniques were then used. Firstly, the GIS software ArcView was used to map the crude mortality rates. Secondly, the data were smoothed by the method of empirical Bayes estimation. The geostatistical prediction method of Kriging was then used to spatially interpolate the data for successive years. Results: No spatial pattern is identifiable from the circles representing mortality rates drawn on the map using ArcView. The circles are scattered over the study area and comparing annual distributions between them is difficult. The maps produced by the Bayesian technique also do not show a clear spatial trend pattern. However, they indicate the tendency of villages in the northeastern region to produce higher incidence or risk values, confirming the results of an earlier study reporting a significant cluster of high childhood mortality in the same area. Discussion: Estimates of disease incidence/mortality should account for the difference in population density when drawing maps to reflect the distribution of risk. Raw mortality rates should be first multiplied by a factor, in our case 1000, before they are plotted by any GIS approach. The Bayesian smoothing technique addresses the issue of heterogeneity in the population at risk and it is therefore recommended for use in explorative mapping of disease/mortality. In this study, it is seen that the Bayesian method is helpful for visual identification of clustering in the northeastern part of the study region.
Chronic kidney disease progression in patients with autosomal dominant polycystic kidney disease

Correspondence: Nayara Panizo González Servicio de Nefrología. Hospital General Universitario Gregorio Marañón. Doctor Esquerdo, 28007, Madrid. Spain. nayara.panizo@salud.madrid. org Conclusions: Initial kidney function, proteinuria, renal size, hypercholesterolemia, hyperuricemia, and SBP are the factors that influence CKD progression in ADPKD. SBP and younger age at diagnosis are the only factors that maintain their independent predictive value in a multivariant analysis.
Perceived Cause, Environmental Factors, and Consequences of Falls in Adults with Cerebral Palsy: A Preliminary Mixed Methods Study

Objective. Describe perceived cause, environmental influences, and consequences of falls or near-falls in ambulant adults with cerebral palsy (CP). Methods. Adults with CP completed postal surveys and follow-up semistructured interviews. Surveys sought information on demographic data, self-nominated Gross Motor Function Classification Score (GMFCS-E&R), falls, and near-falls. Interviews gathered additional information on falls experiences, near-falls, and physical and psychosocial consequences. Results. Thirty-four adults with CP participated. Thirty-three participants reported at least one fall in the previous year. Twenty-six participants reported near-falls. Most commonly, falls occurred indoors, at home, and whilst engaged in nonhazardous ambulation. Adults with CP experienced adverse falls consequences, lower limb injuries predominant (37%), and descriptions of fear, embarrassment, powerlessness, and isolation. Discussion. Adults with CP may experience injurious falls. Further investigation into the impact of falls on health-related quality of life and effective remediation strategies is warranted to provide comprehensive falls prevention programs for this population.
Framing ‘fracking’: Exploring public perceptions of hydraulic fracturing in the United Kingdom

The prospect of fracking in the United Kingdom has been accompanied by significant public unease. We outline how the policy debate is being framed by UK institutional actors, finding evidence of a dominant discourse in which the policy approach is defined through a deficit model of public understanding of science and in which a technical approach to feasibility and safety is deemed as sufficient grounds for good policymaking. Deploying a deliberative focus group methodology with lay publics across different sites in the north of England, we find that these institutional framings are poorly aligned with participants’ responses. We find that unease regularly overflows the focus on safety and feasibility and cannot be satisfactorily explained by a lack of understanding on the part of participants. We find that scholarship from science and technology studies productively elucidates our participants’ largely sceptical positions, and orientates strategies for responding to them more effectively.
IS THE CURRENT LACK OF SOLAR ACTIVITY ONLY SKIN DEEP?

The Sun is a variable star whose magnetic activity and total irradiance vary on a timescale of approximately 11 years. The current activity minimum has attracted considerable interest because of its unusual duration and depth. This raises the question: what might be happening beneath the surface where the magnetic activity ultimately originates? The surface activity can be linked to the conditions in the solar interior by the observation and analysis of the frequencies of the Sun's natural seismic modes of oscillation—the p modes. These seismic frequencies respond to changes in activity and are probes of conditions within the Sun. The Birmingham Solar-Oscillations Network (BiSON) has made measurements of p-mode frequencies over the last three solar activity cycles, and so is in a unique position to explore the current unusual and extended solar minimum. We show that the BiSON data reveal significant variations of the p-mode frequencies during the current minimum. This is in marked contrast to the surface activity observations, which show little variation over the same period. The level of the minimum is significantly deeper in the p-mode frequencies than in the surface observations. We observe a quasi-biennial signal in the p-mode frequencies, which has not previously been observed at mid- and low-activity levels. The stark differences in the behavior of the frequencies and the surface activity measures point to activity-related processes occurring in the solar interior, which are yet to reach the surface, where they may be attenuated.
Self-perceived middle-distance race pace is faster in Advanced Footwear Technology spikes

Background Quantifying the potential benefits of advanced footwear technology (AFT) track shoes (i.e., “spikes”) in middle-distance events is challenging, because repeated maximal effort trials (as in sprinting) or aerobic running economy trials (as in long-distance running) are not feasible. Methods We introduce a novel approach to assess the benefits of AFT spikes, consisting of a series of 200 m runs at self-perceived middle-distance race pace with 10 min recovery and conducted four experiments to evaluate its validity, sensitivity, reproducibility, and utility. Results In experiment 1, participants ran 1.2% slower in spikes with 200 g added mass vs. control spikes, exactly equal to the known effects of shoe mass on running performance. In experiment 2, participants ran significantly faster in AFT prototype spikes vs. traditional spikes. In experiment 3, we compared two other AFT prototype spikes against traditional spikes, on three separate days. Group-level results were consistent across days, but our data indicates that at least two separate sessions are needed to evaluate individual responses. In experiment 4, participants ran significantly faster in two AFT spike models vs. traditional spikes (2.1% and 1.6%). Speed was similar between a third AFT spike model and the traditional spikes. These speed results were mirrored by changes in step length, as participants took significantly longer steps in the two faster AFT spike models (2.3% and 1.9%), while step length was similar between the other spikes. Conclusion Our novel, interval-based approach is a valid and reliable method to quantify differences between spikes at middle-distance running intensity.
Exploring ligands that target von Willebrand factor selectively under oxidizing conditions through docking and molecular dynamics simulations

The blood protein von Willebrand factor (VWF) is a large multimeric protein that, when activated, binds to blood platelets tethering them to the site of vascular injury initiating blood coagulation. This process is critical for the normal haemostatic response, but especially under inflammatory conditions it is thought to be a major player in pathological thrombus formation. For this reason, VWF has been the target for the development of anti-thrombotic therapeutics. However, it is challenging to prevent pathological thrombus formation while still allowing normal physiological blood coagulation as currently available anti-thrombotic therapeutics are known to cause unwanted bleeding in particular intracranial haemorrhage. This work explores the possibility of inhibiting VWF selectively under the inflammatory conditions present during pathological thrombus formation. In particular, the A2 domain of VWF is known to inhibit the neighboring A1 domain from binding to the platelet surface receptor GpIbα and this auto-inhibitory mechanism has been shown to be removed by oxidizing agents released during inflammation. Hence, finding drug molecules that bind at the interface between A1 and A2 only under oxidizing conditions could restore such auto-inhibitory mechanism. Here, by using a combination of computational docking, molecular dynamics simulations and free energy perturbation calculations, a ligand from the ZINC15 database was identified that binds at the A1A2 interface with the interaction being stronger under oxidizing conditions. The results provide a framework for the discovery of drug molecules that bind to a protein selectively in inflammatory conditions.
Enabling Task Parallelism in the CUDA Scheduler

General purpose computing on graphics processing units (GPUs) introduces the challenge of scheduling independent tasks on devices designed for data parallel or SPMD applications. This paper proposes an issue queue that merges workloads that would underutilize GPU processing resources such that they can be run concurrently on an NVIDIA GPU. Using kernels from microbenchmarks and two applications we show that throughput is increased in all cases where the GPU would have been underused by a single kernel. An exception is the case of memory-bound kernels, seen in a Nearest Neighbor application, for which the execution time still outperforms the same kernels executed serially by 12-20%. It can also be beneficial to choose a merged kernel that over-extends the GPU resources, as we show the worst case to be bounded by executing the kernels serially. This paper also provides an analysis of the latenc y penalty that can occur when two kernels with varying completion times are merged.
“They Did It”: The Effects of Emotionalized Blame Attribution in Populist Communication

How can we explain the persuasiveness of populist messages, and who are most susceptible to their effects? These questions remain largely unanswered in extant research. This study argues that populist messages are characterized by assigning blame to elites in an emotionalized way. As previous research pointed at the guiding influence of blame attributions and emotions on political attitudes, these message characteristics may explain populism’s persuasiveness. An experiment using a national sample (N = 721) was conducted to provide insights into the effects of and mechanisms underlying populist blame attribution with regard to the European and national levels of governance. The results show that emotionalized blame attributions influence both blame perceptions and populist attitudes. Identity attachment moderates these effects: Emotionalized blame attributions have the strongest effects for citizens with weaker identity attachments. These insights allow us to understand how populist messages affect which citizens.
Identifying immune signatures of common exposures through co-occurrence of T-cell receptors in tens of thousands of donors

Memory T cells are records of clonal expansion from prior immune exposures, such as infections, vaccines and chronic diseases like cancer. A subset of the receptors of these expanded T cells in a typical immune repertoire are highly public, i.e., present in many individuals exposed to the same exposure. For the most part, the exposures associated with these public T cells are unknown. To identify public T-cell receptor signatures of immune exposures, we mined the immunosequencing repertoires of tens of thousands of donors to define clusters of co-occurring T cells. We first built co-occurrence clusters of T cells responding to antigens presented by the same Human Leukocyte Antigen (HLA) and then combined those clusters across HLAs. Each cross-HLA cluster putatively represents the public T-cell signature of a single prevalent exposure. Using repertoires from donors with known serological status for 7 prevalent exposures (HSV-1, HSV-2, EBV, Parvovirus, Toxoplasma gondii, Cytomegalovirus and SARS-CoV-2), we identified a single T-cell cluster strongly associated with each exposure and used it to construct a highly sensitive and specific diagnostic model for the exposure. These T-cell clusters constitute the public immune responses to prevalent exposures, 7 known and many others unknown. By learning the exposure associations for more T-cell clusters, this approach could be used to derive a ledger of a person’s past and present immune exposures.
Adaptive chunking improves effective working memory capacity in a prefrontal cortex and basal ganglia circuit

How and why is working memory (WM) capacity limited? Traditional cognitive accounts focus either on limitations on the number or items that can be stored (slots models), or loss of precision with increasing load (resource models). Here we show that a neural network model of prefrontal cortex and basal ganglia can learn to reuse the same prefrontal populations to store multiple items, leading to resourcelike constraints within a slot-like system, and inducing a tradeoff between quantity and precision of information. Such “chunking” strategies are adapted as a function of reinforcement learning and WM task demands, mimicking human performance and normative models. Moreover, adaptive performance requires a dynamic range of dopaminergic signals to adjust striatal gating policies, providing a new interpretation of WM difficulties in patient populations such as Parkinson’s disease, ADHD and schizophrenia. These simulations also suggest a computational rather than anatomical limit to WM capacity.
Aging impacts basic auditory and timing processing

Deterioration in the peripheral and central auditory systems is common in older adults and often leads to hearing and speech comprehension difficulties. Even when hearing remains intact, electrophysiological data of older adults frequently exhibit altered neural responses across the auditory pathway, reflected in variability in the phase alignment of neural activity to speech sound onsets. However, it remains unclear whether speech processing challenges in older adults stem from more fundamental deficits in auditory and timing processing. Here, we investigated the efficiency of aging individuals in encoding temporal regularities in acoustic sequences and their ability to predict future events. We recorded EEG in older and young individuals listening to simple isochronous tone sequences. A comprehensive analysis pipeline evaluated the amplitude, latency, and variability of event-related responses (ERPs) to each tone onset along the auditory sequences. Spectral parametrization and Inter-Trial Phase Coherence (ITPC) analyses assessed how participants encoded the temporal regularity in the acoustic environment. Our findings indicate that aging individuals exhibit altered temporal processing and reduced capacity to generate and utilize temporal predictions to time-lock and adaptively suppress neural responses to predictable and repeated tones in auditory sequences. Given that deteriorations in these basic timing capacities may affect other higher-order cognitive processes (e.g., attention, perception, and action), our results underscore the need for future research examining the link between timing abilities and general cognition across the lifespan. Highligths Aging individuals (HO) show increased cortical excitability as compared to younger adults (HY); HO’s neural responses to fully predictable isochronous tones were larger and more variable than HY; HO showed reduced inter-trial phase coherence (ITPC) as compared to HY; The reduction in ITPC was associated with variability of event-related responses in HO; Altogether, results show altered auditory and timing processing in aging.
Rapid assessment of trachoma in Hainan Province, China: Validation of the new World Health Organization methodology

This study was undertaken to validate a WHO methodology for the rapid assessment of trachoma. Fourteen villages were chosen by random sampling in two counties in Hainan Province, China. For the rapid assessment, trichiasis patients were identified, 50 children ages 1–10 years were examined for active trachoma, and information was collected on community access to services and community risk factors. To validate the methodology, a prevalence survey was undertaken simultaneously in the same villages. For the prevalence survey, 2428 people from 1606 households in the 14 villages were chosen by random sampling. Very little active trachoma was found by either method, although the rates of trichiasis were more substantial. Ranking of the villages by the two methods for trichiasis was highly corre-lated (Spearman's correlation coefficient = 0.60, p = 0.02). For active trachoma, the Spearman's correlation coefficient for the ranking of villages by the two methods was 0.40 and not significant (p = 0.14), suggesting that a correlation this close may have been seen by chance alone. The observational data showed all the villages to be at risk of active trachoma (due to poor environmental hygiene conditions), suggesting that this aspect of the WHO methodology overestimates the risk for active trachoma. We conclude that, with the exception of the community assessment of risk, this rapid assessment methodology is a valid tool for the assessment of trichiasis and possibly of active trachoma in rural communities, although the level of active trachoma in this study was too low to effectively validate that aspect of the methodology.