Miracle-dz/UniFAR-FTUs huggingface dataset:
Direct actin binding to A- and B-type lamin tails and actin filament bundling by the lamin A tail

Nuclear intermediate filament networks formed by A- and B-type lamins are major components of the nucleoskeleton. Lamins have growing links to human physiology and disease including Emery-Dreifuss muscular dystrophy (EDMD), lipodystrophy, cardiomyopathy, neuropathy, cerebellar disorders and segmental accelerated ‘aging’ syndromes. How lamins interact with other nucleoskeletal components, and even the identities of these other components, are open questions. Previous studies suggested lamins might bind actin. We report that the recombinant C- terminal tail domain of human A- and B-type lamins binds directly to purified actin in high- speed pelleting assays. This interaction maps to a conserved Actin Binding site (AB-1) comprising lamin A residues 461-536 in the Ig-fold domain, which are 54% identical in lamin B1. Two EDMD-causing missense mutations (R527P and L530P) in lamin A that are predicted to disrupt the Ig-fold, each reduced F-actin binding by ~66%, whereas the surface-exposed lipodystrophy-causing R482Q mutation had no significant effect. The lamin A tail was unique among lamins in having a second actin-binding site (AB-2). This second site was mapped to lamin A tail residues 564-608, based on actin-binding results for the lamin C tail and internal deletions in the lamin A tail that cause Hutchinson-Gilford Progeria Syndrome (Δ35, Δ50) or restrictive dermopathy (Δ90). Supporting the presence of two actin-binding sites, recombinant precursor (unmodified) and mature lamin A tails (not C or B1 tails) each bundled F-actin in vitro: furthermore F-actin bundling was reduced 25-40% by the R527P, L530P, Δ35 and Δ50 mutations, and was abolished by Δ90. Unexpectedly, the mature lamin A tail bound F-actin significantly more efficiently than did the prelamin A tail; this suggested unmodified residues 647-664, unique to prelamin A, might auto-inhibit binding to actin (and potentially other partners). These biochemical results suggest direct mechanisms by which lamins, particularly lamin A, might impact the concentration of free actin in the nucleus or pathways including transcription, nuclear export, chromatin remodeling, chromatin movement and nuclear assembly that require nuclear myosin 1c and polymerizable actin.
Two Transport Systems for Tetracycline in Sensitive Escherichia coli: Critical Role for an Initial Rapid Uptake System Insensitive to Energy Inhibitors

Escherichia coli sensitivity to tetracycline involves transport and accumulation of the antibiotic within the cell by two different uptake systems: an initial rapid uptake, which occurs over the initial 6 min of contact of the cell with tetracycline, and a slower uptake system, which continues indefinitely and whose rate of uptake is 1/10 that of the rapid system. Only the slow uptake system is blocked by inhibitors of energy-driven systems; it appears to be particularly dependent upon energy from oxidative phosphorylation. Although both uptake systems lead to accumulation of intracellular tetracycline and contribute to the cell's sensitivity, the rapid uptake system appears to be the more important. While these studies confirm active transport of tetracycline into the cell, they demonstrate that a critical uptake system which appears insensitive to metabolic inhibitors occurs initially.
Energy management of a multi-agent based multi-microgrid system

This paper presents a model-based optimization algorithm for short-term energy trading in a multi-microgrid system. The multi-microgrid system has a hierarchical design architecture which is based on the Multi-Agent System (MAS) concept. Mixed-integer linear programming (MILP) which takes into consideration multiple constraints is used to obtain the optimum amount of power that will be generated, sold, or stored for the Energy Management System (EMS) of the multi-microgrid system at different time intervals. By using the proposed optimization algorithm, the EMS will ensure that power balance in the multi-microgrid system is achieved through energy trading between different interconnecting microgrids. The proposed optimization algorithm and hierarchical multi-microgrid system design architecture have the capability to ensure that the multi-microgrid system operates in a coordinated and economic manner. The design concept is demonstrated through different test case scenarios and the results obtained are discussed.
Estimating coupling directions in the cardiorespiratory system using recurrence properties

The asymmetry of coupling between complex systems can be studied by conditional probabilities of recurrence, which can be estimated by joint recurrence plots. This approach is applied for the first time on experimental data: time series of the human cardiorespiratory system in order to investigate the couplings between heart rate, mean arterial blood pressure and respiration. We find that the respiratory system couples towards the heart rate, and the heart rate towards the mean arterial blood pressure. However, our analysis could not detect a clear coupling direction between the mean arterial blood pressure and respiration.
Assessment of the allelopathic effects of seeds and seedlings of rotational crops and ryegrass

Allelopathic effects were evaluated for a series of rotational crops, namely barley, canola, wheat, lupine, medic, lucerne (alfalfa) and ryegrass in laboratory studies. This followed on a field assessment of these crops to identify inter-species phytotoxic effects. Two different experiments to determine phytotoxicity effects of seed and seedling leachates were conducted under controlled conditions. The first experiment was set up in the laboratory to observe the mutual effect of seed leachates from the plant series. The second experiment was conducted in the laboratory to study the effect of seedling leachates from all the plants in the series on germination and early development of all other species. The phytotoxic activity observed for lupine and medic under controlled conditions, corresponds to results obtained in the field and confirms that these leguminous crops could be considered as living or terminated mulches for weed suppression. Crop mixtures containing legumes may provide weed suppression which would reduce dependency on herbicides that are associated with the development of weed resistance. Key words: Cumulative germination, inhibition, stimulation, phytotoxic leachates.
Persistent impacts of West Nile virus on North American bird populations

Significance Since its introduction to North America, West Nile virus (WNV) has impacted the health of both human and wildlife populations, but the extent of the burden across host species remains poorly understood. Using extensive mark-recapture data from 49 species spanning nearly two decades, combined with recently developed models of WNV risk, we estimated the impacts of this emergent disease on avian populations. We show that WNV has had significant negative effects on survival of 47% of bird species examined. We provide the first in-depth picture of the extent, duration, and phylogenetic signal of WNV impacts on bird populations. Our results suggest that introduced infectious diseases can have significant persistent effects on populations long after initial concerns have waned. Since its introduction to North America in 1999, West Nile virus (WNV) has had devastating impacts on native host populations, but to date these impacts have been difficult to measure. Using a continental-scale dataset comprised of a quarter-million birds captured over nearly two decades and a recently developed model of WNV risk, we estimated the impact of this emergent disease on the survival of avian populations. We find that populations were negatively affected by WNV in 23 of the 49 species studied (47%). We distinguished two groups of species: those for which WNV negatively impacted survival only during initial spread of the disease (n = 11), and those that show no signs of recovery since disease introduction (n = 12). Results provide a novel example of the taxonomic breadth and persistent impacts of this wildlife disease on a continental scale. Phylogenetic analyses further identify groups (New World sparrows, finches, and vireos) disproportionally affected by temporary or persistent WNV effects, suggesting an evolutionary dimension of disease risk. Identifying the factors affecting the persistence of a disease across host species is critical to mitigating its effects, particularly in a world marked by rapid anthropogenic change.
Evaluation of the Ultrasensitive Roche Amplicor HIV-1 Monitor Assay for Quantitation of Human Immunodeficiency Virus Type 1 RNA

ABSTRACT The ultrasensitive Amplicor HIV-1 Monitor test (Roche Diagnostic Systems) was evaluated for precision, linearity, and sensitivity and was compared to the standard Amplicor assay. The ultrasensitive assay reliably quantified samples in the range from 50 to 50,000 human immunodeficiency virus type 1 RNA copies/ml with acceptable correlation with the standard Amplicor test.
Automatic Detection of ADHD and ASD from Expressive Behaviour in RGBD Data

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are neurodevelopmental conditions which impact on a significant number of children and adults. Currently, the diagnosis of such disorders is done by experts who employ standard questionnaires and look for certain behavioural markers through manual observation. Such methods for their diagnosis are not only subjective, difficult to repeat, and costly but also extremely time consuming. In this work, we present a novel methodology to aid diagnostic predictions about the presence/absence of ADHD and ASD by automatic visual analysis of a persons behaviour. To do so, we conduct the questionnaires in a computer-mediated way while recording participants with modern RGBD (Colour+Depth) sensors. In contrast to previous automatic approaches which have focussed only on detecting certain behavioural markers, our approach provides a fully automatic end-to-end system to directly predict ADHD and ASD in adults. Using state of the art facial expression analysis based on Dynamic Deep Learning and 3D analysis of behaviour, we attain classification rates of 96% for Controls vs Condition (ADHD/ASD) groups and 94% for Comorbid (ADHD+ASD) vs ASD only group. We show that our system is a potentially useful time saving contribution to the clinical diagnosis of ADHD and ASD.
Multivariate inference of pathway activity in host immunity and response to therapeutics

Developing a quantitative view of how biological pathways are regulated in response to environmental factors is central for understanding of disease phenotypes. We present a computational framework, named Multivariate Inference of Pathway Activity (MIPA), which quantifies degree of activity induced in a biological pathway by computing five distinct measures from transcriptomic profiles of its member genes. Statistical significance of inferred activity is examined using multiple independent self-contained tests followed by a competitive analysis. The method incorporates a new algorithm to identify a subset of genes that may regulate the extent of activity induced in a pathway. We present an in-depth evaluation of specificity, robustness, and reproducibility of our method. We benchmarked MIPA's false positive rate at less than 1%. Using transcriptomic profiles representing distinct physiological and disease states, we illustrate applicability of our method in (i) identifying gene–gene interactions in autophagy-dependent response to Salmonella infection, (ii) uncovering gene–environment interactions in host response to bacterial and viral pathogens and (iii) identifying driver genes and processes that contribute to wound healing and response to anti-TNFα therapy. We provide relevant experimental validation that corroborates the accuracy and advantage of our method.
The benefits and risks of testosterone replacement therapy: a review

Increased longevity and population aging will increase the number of men with late onset hypogonadism. It is a common condition, but often underdiagnosed and undertreated. The indication of testosterone-replacement therapy (TRT) treatment requires the presence of low testosterone level, and symptoms and signs of hypogonadism. Although controversy remains regarding indications for testosterone supplementation in aging men due to lack of large-scale, long-term studies assessing the benefits and risks of testosterone-replacement therapy in men, reports indicate that TRT may produce a wide range of benefits for men with hypogonadism that include improvement in libido and sexual function, bone density, muscle mass, body composition, mood, erythropoiesis, cognition, quality of life and cardiovascular disease. Perhaps the most controversial area is the issue of risk, especially possible stimulation of prostate cancer by testosterone, even though no evidence to support this risk exists. Other possible risks include worsening symptoms of benign prostatic hypertrophy, liver toxicity, hyperviscosity, erythrocytosis, worsening untreated sleep apnea or severe heart failure. Despite this controversy, testosterone supplementation in the United States has increased substantially over the past several years. The physician should discuss with the patient the potential benefits and risks of TRT. The purpose of this review is to discuss what is known and not known regarding the benefits and risks of TRT.
Immune Selection and Within-Host Competition Can Structure the Repertoire of Variant Surface Antigens in Plasmodium falciparum - A Mathematical Model

Background The evolutionary mechanisms structuring the expression pattern of variant surface antigen (VSA) families that allow pathogens to evade immune responses and establish chronic and repeated infections pose major challenges to theoretical research. In Plasmodium falciparum, the best-studied VSA family is erythrocyte membrane protein 1 (PfEMP1). Each parasite genome encodes about 60 PfEMP1 variants, which are important virulence factors and major targets of host antibody responses. Transcriptional switching is the basis of clonal PfEMP1 variation and immune evasion. A relatively conserved subset of PfEMP1 variants tends to dominate in non-immune patients and in patients with severe malaria, while more diverse subsets relate to uncomplicated infection and higher levels of pre-existing protective immunity. Methodology/Principal Findings Here, we use the available molecular and serological evidence regarding VSAs, in particular PfEMP1, to formulate a mathematical model of the evolutionary mechanisms shaping VSA organization and expression patterns. The model integrates the transmission dynamics between hosts and the competitive interactions within hosts, based on the hypothesis that the VSAs can be organized into so-called dominance blocks, which characterize their competitive potential. The model reproduces immunological trends observed in field data, and predicts an evolutionary stable balance between inter-clonally conserved dominance blocks that are highly competitive within-host and diverse blocks that are favoured by immune selection at the population level. Conclusions/Significance The application of a monotonic dominance profile to VSAs encoded by a gene family generates two opposing selective forces and, consequently, two distinct clusters of genes emerge in adaptation to naïve and partially immune hosts, respectively.
Stochastic Simulation of Delay-Induced Circadian Rhythms in Drosophila

Circadian rhythms are ubiquitous in all eukaryotes and some prokaryotes. Several computational models with or without time delays have been developed for circadian rhythms. Exact stochastic simulations have been carried out for several models without time delays, but no exact stochastic simulation has been done for models with delays. In this paper, we proposed a detailed and a reduced stochastic model with delays for circadian rhythms in Drosophila based on two deterministic models of Smolen et al. and employed exact stochastic simulation to simulate circadian oscillations. Our simulations showed that both models can produce sustained oscillations and that the oscillation is robust to noise in the sense that there is very little variability in oscillation period although there are significant random fluctuations in oscillation peeks. Moreover, although average time delays are essential to simulation of oscillation, random changes in time delays within certain range around fixed average time delay cause little variability in the oscillation period. Our simulation results also showed that both models are robust to parameter variations and that oscillation can be entrained by light/dark circles. Our simulations further demonstrated that within a reasonable range around the experimental result, the rates that dclock and per promoters switch back and forth between activated and repressed sites have little impact on oscillation period.
LMS rules and the inverse base-rate effect: Comment on Gluck and Bower (1988).

(}luck and Bower (1988) suggestmi that through the use of the Rescorla-Wagner learning rule, a connectionist network might be ~ble to model the inverse base-rate phenomenon found by Medin and Edelson (1988). I prove that a network of the type that they proposed does not capture this effect. However, one can also prove that with additional assumptions about the encoding of features, the Rescorla-Wagner learning rule can be made to model the inverse baserate effect. The importance of these assumptions and an outline of how they might be tested are then discussed. Gluck and Bower (1988) recently showed how a version of the Rescorla-Wagner learning rule (a variant of the least mean squared [LMS] error correction rule) could be used to predict human behavior in a category-learning task. At the end of their article, they theorized that this rule might be able to account for subjects' incorrect use of base-rate information found in a set of experiments by Medin and Edelson (1988). The inverse base-rate phenomenon (Medin & Edelson, 1988) is a surprising and counterintuitive effect shown by subjects in category-learning experiments in which the frequency of presentation of the categories is varied. Table 1 illustrates a simple case: Subjects are presented ~h exemplars for each of two categories. In the simple case, these categories have one common feature (A) and one distinctive feature (B or C). When one category is presented more frequently than the other, an interesting pattern or responses results. If subjects • are given the common feature and asked which category is more likely to be described by this feature, subjects respond with the more frequently presented category. If either of the distinctive features is presented during testing, the appropriate category is selected. However, ifboth of the distinctive features are presented together, the subject is more likely to select the less frequently presented category, responding in opposition to the base-rate information. Medin and Edelson (1988) discussed the possibility that the inverse base-rate effect stems from a competition between features. In a context in which the categories are diseases and the features are symptoms, they stated that
Reproducibility of histopathological diagnosis in poorly differentiated NSCLC: an international multiobserver study.

Journal of Thoracic Oncology ® • Volume 9, Number 9, September 2014 Introduction: The 2004 World Health Organization classification of lung cancer contained three major forms of non–small-cell lung cancer: squamous cell carcinoma (SqCC), adenocarcinoma (AdC), and large cell carcinoma. The goal of this study was first, to assess the reproducibility of a set of histopathological features for SqCC in relation to other poorly differentiated non–small-cell lung cancers and second, to assess the value of immunohistochemistry in improving the diagnosis. Methods: Resection specimens (n = 37) with SqCC, large cell carcinoma, basaloid carcinoma, sarcomatoid carcinoma, lymphoepithelial-like carcinoma, and solid AdC, were contributed by the participating pathologists. Hematoxylin and eosin (H&E) stained slides were digitized. The diagnoses were evaluated in two ways. First, the histological criteria were evaluated and the (differential) diagnosis on H&E alone was scored. Second, the added value of additional stains to make an integrated diagnosis was examined. Results: The histologic criteria defining SqCC were consistently used, but in poorly differentiated cases they were infrequently present, rendering the diagnosis more difficult. Kappa scores on H&E alone were for SqCC 0.46, large cell carcinoma 0.25, basaloid carcinoma 0.27, sarcomatoid carcinoma 0.52, lymphoepithelial-like carcinoma 0.56, and solid AdC 0.21. The κ score improved with the use of additional stains for SqCC (combined with basaloid carcinoma) to 0.57, for solid AdC to 0.63. Conclusion: The histologic criteria that may be used in the differential diagnosis of poorly differentiated lung cancer were more precisely refined. Furthermore, additional stains improved the reproducibility of histological diagnosis of SqCC and AdC, uncovering information that was not present in routine H&E stained slides.
A hybrid GP/GA approach for co-evolving controllers and robot bodies to achieve fitness-specified tasks

Evolutionary approaches have been advocated to automate robot design. Some research work has shown the success of evolving controllers for the robots by genetic approaches. As we can observe, however, not only the controller but also the robot body itself can affect the behavior of the robot in a robot system. We develop a hybrid GP/GA approach to evolve both controllers and robot bodies to achieve behavior-specified tasks. In order to assess the performance of the developed approach, it is used to evolve a simulated agent, with its own controller and body, to do obstacle avoidance in the simulated environment. Experimental results show the promise of this work. In addition, the importance of co-evolving controllers and robot bodies is analyzed and discussed.
Corpus statistics approaches to discriminating among near-synonyms

Near-synonyms are words that mean approximately the same thing, and which tend to be assigned to the same leaf in ontologies such as WordNet. However, they can differ from each other subtly in both meaning and usage—consider the pair of near-synonyms frugal and stingy— and therefore choosing the appropriate near-synonym for a given context is not a trivial problem. Early work on near-synonyms was that of Edmonds (1997). Edmonds reported an experiment attempting to predict which of a set of near-synonyms would be used in a given context using lexical co-occurrence networks. The conclusion of this work was that corpus statistics approaches did not appear to work well for this type of problem and led instead to the development of machine learning approaches over lexical resources such as Choose the Right Word (Hayakawa, 1994). Our hypothesis is that some kind of corpus statistics approach may still be effective in some situations: particularly if the nearsynonyms differ in sentiment from each other. Intuition based on work in sentiment analysis suggests that if the distribution of words embodying some characteristic of sentiment can predict the overall sentiment or attitude of a document, perhaps these same words can predict the choice of an individual ‘attitudinal’ nearsynonym given its context, while this is not necessarily true for other types of nearsynonym. This would again open up problems involving this type of near-synonym to corpus statistics methods. As a first step, then, we investigate whether attitudinal near-synonyms are more likely to be successfully predicted by a corpus statistics method than other types. In this paper we present a larger-scale experiment based on Edmonds (1997), and show that attitudinal near-synonyms can in fact be predicted more accurately using corpus statistics methods.