Miracle-dz/UniFAR-FTUs huggingface dataset:
The emergence of vampire bat rabies in Uruguay within a historical context

Abstract Pathogen spillover from wildlife to humans or domestic animals requires a series of conditions to align with space and time. Comparing these conditions between times and locations where spillover does and does not occur presents opportunities to understand the factors that shape spillover risk. Bovine rabies transmitted by vampire bats was first confirmed in 1911 and has since been detected across the distribution of vampire bats. However, Uruguay is an exception. Uruguay was free of bovine rabies until 2007, despite high-cattle densities, the presence of vampire bats and a strong surveillance system. To explore why Uruguay was free of bovine rabies until recently, we review the historic literature and reconstruct the conditions that would allow rabies invasion into Uruguay. We used available historical records on the abundance of livestock and wildlife, the vampire bat distribution and occurrence of rabies outbreaks, as well as environmental modifications, to propose four alternative hypotheses to explain rabies virus emergence and spillover: bat movement, viral invasion, surveillance failure and environmental changes. While future statistical modelling efforts will be required to disentangle these hypotheses, we here show how a detailed historical analysis can be used to generate testable predictions for the conditions leading to pathogen spillover.
Recurrent Neural Networks With External Addressable Long-Term and Working Memory for Learning Long-Term Dependences

Learning long-term dependences (LTDs) with recurrent neural networks (RNNs) is challenging due to their limited internal memories. In this paper, we propose a new external memory architecture for RNNs called an external addressable long-term and working memory (EALWM)-augmented RNN. This architecture has two distinct advantages over existing neural external memory architectures, namely the division of the external memory into two parts—long-term memory and working memory—with both addressable and the capability to learn LTDs without suffering from vanishing gradients with necessary assumptions. The experimental results on algorithm learning, language modeling, and question answering demonstrate that the proposed neural memory architecture is promising for practical applications.
Journal of Reproduction and Development

Calving is a critical but stressful event required for milk production in dairy cows. In the present study, we investigated the immune status of peripheral blood mononuclear cells (PBMCs) isolated from periparturient cows to better understand and, thus, possibly prevent stress during the periparturient period. To evaluate the immune response of PBMCs, we assessed their proliferation with or without a mitogen (concanavalin A, ConA). Blood samples were collected 24 h before and after calving and 1 week after calving. The proliferation of non-treated cells remained unchanged throughout the examination period. The immune response of PBMCs isolated from the cows before calving was relatively low, even after ConA stimulation; however, the immune response of PBMCs collected at both time points after calving was significantly higher than those of non-stimulated controls. Next, we examined the expression patterns of T cell related and inflammatory cytokine genes in PBMCs. We found that the mRNA expression levels of both CD4 and CD8 showed decreasing trends after calving. The expression of the Th1 cell marker gene IFNG also decreased after calving. The mRNA expression level of the inflammatory cytokine gene TNFA increased after parturition. Overall, our results suggest that the PBMC immune response was weakened in cows before delivery and part of the expression of the immune cell-related genes in these cells is altered 24 h before and after calving.
Physiological synchrony in psychotherapy sessions

Abstract Objective: In this proof-of-principle study, a convenience sample of 55 dyadic psychotherapy sessions conducted by one therapist was analyzed. This study aimed at exploring physiological synchrony in naturalistic psychotherapy sessions and the association of such synchrony with self-report ratings. Methods: The electrocardiograms and respiration behavior of both therapist and client were monitored simultaneously. Four clients were included, and session outcome was documented by session reports in two clients. From electrocardiograms, heart rate and heart rate variability were derived in consecutive 15-second intervals throughout sessions. Entire sessions (average duration, 51 min) were assessed for physiological synchrony of therapist’s and client’s respiration, electrocardiogram, heart rate, and heart rate variability. Two methods of synchrony computation were applied to the time series: windowed cross-correlation and correlation of local slopes (concordance). Both methods included surrogate controls using segment-wise shuffling. Results: Significant synchrony of three measures, but not of electrocardiograms, was present in this dataset. In regression models, we found associations between synchronies and alliance ratings, and further self-report variables. Conclusions: Results support the existence of physiological synchrony in this collection of psychotherapy sessions, which speaks for the sympathetic and parasympathetic coupling between this therapist and her clients and its link with ratings of the therapy process. The feasibility of deriving signatures of synchrony of physiological signals with the described methodology was corroborated. The findings now await generalization by further research.
Toll-Like Receptor 2-Mediated Signaling Requirements for Francisella tularensis Live Vaccine Strain Infection of Murine Macrophages

ABSTRACT Francisella tularensis, an aerobic, non-spore-forming, gram-negative coccobacillus, is the causative agent of tularemia. We reported previously that F. tularensis live vaccine strain (LVS) elicited strong, dose-dependent NF-κB reporter activity in Toll-like receptor 2 (TLR2)-expressing HEK293T cells and proinflammatory gene expression in primary murine macrophages. Herein, we report that F. tularensis LVS-induced murine macrophage proinflammatory cytokine gene and protein expression are overwhelmingly TLR2 dependent, as evidenced by the abrogated responses of TLR2−/− macrophages. F. tularensis LVS infection also increased expression of TLR2 both in vitro, in mouse macrophages, and in vivo, in livers from F. tularensis LVS-infected mice. Colocalization of intracellular F. tularensis LVS, TLR2, and MyD88 was visualized by confocal microscopy. Signaling was abrogated if the F. tularensis LVS organisms were heat or formalin killed or treated with chloramphenicol, indicating that the TLR2 agonist activity is dependent on new bacterial protein synthesis. F. tularensis LVS replicates in macrophages; however, bacterial replication was not required for TLR2 signaling because LVSΔguaA, an F. tularensis LVS guanine auxotroph that fails to replicate in the absence of exogenous guanine, activated NF-κB in TLR2-transfected HEK293T cells and induced cytokine expression in wild-type macrophages comparably to wild-type F. tularensis LVS. Collectively, these data indicate that the primary macrophage response to F. tularensis LVS is overwhelmingly TLR2 dependent, requires de novo bacterial protein synthesis, and is independent of intracellular F. tularensis replication.
HY5 Interacts with the Histone Deacetylase HDA15 to Repress Hypocotyl Cell Elongation in Photomorphogenesis1[OPEN]

HY5 interacts with HDA15 to form a key transcription regulatory node involved in repressing hypocotyl cell elongation-related genes and promoting photomorphogenesis in Arabidopsis seedlings. Photomorphogenesis is a critical plant developmental process that involves light-mediated transcriptome and histone modification changes. The transcription factor ELONGATED HYPOCOTYL5 (HY5) acts downstream of multiple families of photoreceptors to promote photomorphogenesis by regulating the expression of light-responsive genes. However, the molecular mechanism for HY5-mediated transcriptional regulation remains largely unclear. Here, we demonstrated that HY5 directly interacts with a Reduced Potassium Dependence3/Histone Deacetylase1 (HDA1)-type histone deacetylase, HDA15, both in vitro and in vivo. Phenotypic analysis revealed that HDA15 is a negative regulator of hypocotyl cell elongation under both red and far-red light conditions in Arabidopsis (Arabidopsis thaliana) seedlings. The enzymatic activity of HDA15 is required for inhibition of hypocotyl elongation. Furthermore, HDA15 and HY5 act interdependently in the repression of hypocotyl cell elongation in photomorphogenesis. Genome-wide transcriptome analysis revealed that HDA15 and HY5 corepress the transcription of a subset of cell wall organization and auxin signaling-related genes. In addition, HDA15 is required for the function of HY5 in the repression of genes related to hypocotyl cell elongation in Arabidopsis seedlings. Moreover, HY5 recruits HDA15 to the promoters of target genes and represses gene expression by decreasing the levels of histone H4 acetylation in a light-dependent manner. Our study revealed a key transcription regulatory node in which HY5 interacts with HDA15 involved in repressing hypocotyl cell elongation to promote photomorphogenesis.
A Recombinant Modified Vaccinia Ankara Vaccine Encoding Epstein–Barr Virus (EBV) Target Antigens: A Phase I Trial in UK Patients with EBV-Positive Cancer

Purpose: Epstein–Barr virus (EBV) is associated with several cancers in which the tumor cells express EBV antigens EBNA1 and LMP2. A therapeutic vaccine comprising a recombinant vaccinia virus, MVA-EL, was designed to boost immunity to these tumor antigens. A phase I trial was conducted to demonstrate the safety and immunogenicity of MVA-EL across a range of doses. Experimental Design: Sixteen patients in the United Kingdom (UK) with EBV-positive nasopharyngeal carcinoma (NPC) received three intradermal vaccinations of MVA-EL at 3-weekly intervals at dose levels between 5 × 107 and 5 × 108 plaque-forming units (pfu). Blood samples were taken at screening, after each vaccine cycle, and during the post-vaccination period. T-cell responses were measured using IFNγ ELISpot assays with overlapping EBNA1/LMP2 peptide mixes or HLA-matched epitope peptides. Polychromatic flow cytometry was used to characterize functionally responsive T-cell populations. Results: Vaccination was generally well tolerated. Immunity increased after vaccination to at least one antigen in 8 of 14 patients (7/14, EBNA1; 6/14, LMP2), including recognition of epitopes that vary between EBV strains associated with different ethnic groups. Immunophenotypic analysis revealed that vaccination induced differentiation and functional diversification of responsive T-cell populations specific for EBNA1 and LMP2 within the CD4 and CD8 compartments, respectively. Conclusions: MVA-EL is safe and immunogenic across diverse ethnicities and thus suitable for use in trials against different EBV-positive cancers globally as well as in South-East Asia where NPC is most common. The highest dose (5 × 108 pfu) is recommended for investigation in current phase IB and II trials. Clin Cancer Res; 20(19); 5009–22. ©2014 AACR.
Formation of 3‐hydroxyglutaric acid in glutaric aciduria type I: in vitro participation of medium chain acyl‐CoA dehydrogenase

3‐Hydroxyglutaric acid (3‐OH‐GA) in urine has been identified as the most reliable diagnostic marker for glutaric aciduria type I (GA I). We showed that hydratation of glutaconyl‐CoA to 3‐hydroxyglutaryl‐CoA, which is subsequently hydrolyzed to 3‐OH‐GA, is efficiently catalyzed by 3‐methylglutaconyl‐CoA hydratase (3‐MGH). We have now investigated whether mitochondrial acyl‐CoA‐dehydrogenases can convert glutaryl‐CoA to glutaconyl‐CoA. Short‐chain acyl‐CoA dehydrogenase (SCAD), medium‐chain acyl‐CoA dehydrogenase (MCAD), and long‐chain acyl‐CoA dehydrogenase (LCAD) accepted glutaryl‐CoA as a substrate. The highest kcat of glutaryl‐CoA was found for MCAD (0.12 ± 0.01 second−1) and was about 26‐fold and 52‐fold higher than those of LCAD and SCAD, respectively. The turnover of MCAD for glutaryl‐CoA was about 1.5% of that of its natural substrate octanoyl‐CoA. Despite high Km (above 600 μM) and low turnover rate, the oxidation of glutaryl‐CoA by MCAD in combination with 3‐MGH could explain the urinary concentration of 3‐OH‐GA in GA I patients.
Enclomiphene citrate: A treatment that maintains fertility in men with secondary hypogonadism

ABSTRACT Introduction: Hypogonadism is an important issue among the male population. Treatments such as exogenous testosterone have become very popular. One of the adverse effects of testosterone is its suppression of fertility. This has lead to the use of alternative therapies such as selective estrogen receptor modulators (SERMs) that aim to correct hypogonadism without reducing fertility. Areas covered: The SERM, clomiphene citrate, which is approved by the FDA for the treatment of ovarian dysfunction, has been shown to have beneficial effects on male hypogonadism. Clomiphene citrate exists as a mixture of both the cis-isomer (zuclomiphene) and the trans-isomer (enclomiphene). The literature has suggested that most of the beneficial effects of clomiphene are due to the trans-isomer enclomiphene. Zuclomiphene contributes little to the intended outcomes. The purpose of this drug profile is to examine the available literature on the trans-isomer enclomiphene. Expert opinion: Enclomiphene has been shown to increase testosterone levels while stimulating FSH and LH production. Initial studies demonstrated that enclomiphene maintains the androgenic benefit of clomiphene citrate without the undesirable effects attributable to zuclomiphene. This article reviews the difficulties associated with the FDA approval of a new molecular entity related to the treatment of hypogonadism.
Otolith Function Assessed with the Subjective Postural Horizontal and Standardised Stance and Gait Tasks

If otolith function is essential to maintain upright standing while moving along slanted or uneven surfaces, subjects with an otolith deficit should have difficulty judging whether the inclination of the surface on which they are standing is tilted or not. We tested this judgement and compared it with the ability to control trunk sway during standardised stance and gait tests. Thirteen patients with unilateral vestibular nerve neurectomy at least 6 months prior to testing and 39 age-matched controls were asked to move a dynamic posturography platform on which they were standing back to their subjective ‘horizontal’ position after the platform had been slowly tilted at 0.4°/s to 5° in 8 different directions. Normal subjects left the platform deviated in pitch (forwards-backwards) at about 0.7° on describing the platform as levelled off for all directions of tilt. Patients showed larger deviations of about 1.3° in pitch with significant differences for forward right tilt (1.58 ± 0.73° compared to 0.73 ± 0.11° for normals; mean and SEM) and for forward left. Roll (lateral) deviations were about 0.4° for normals and 0.5° larger for the patients (for example, for backward left, 1.13 ± 0.24° compared to 0.4 ± 0.07° in normals). Except for a tendency towards greater deviations to the lesion side of patients with eyes closed, no differences were noted between tests under eyes open and closed conditions. However, for backward and roll tilts patients needed to steady themselves first by grasping a handrail when tested with eyes closed. Stance tests on foam showed increases in roll and pitch trunk sway with respect to controls. Patients had significantly larger trunk roll sway deviations during 1-legged stance tests and during gait trials. For stance trials, the patients lost their balance control prior to the end of the standard 20-second recording time. We conclude that a unilateral loss of otolith inputs due to nerve resection permanently impairs the ability to judge whether the support surface is horizontal, and leads to excessive trunk sway when standing on a compliant surface as well as excessive trunk roll sway during gait.
Effect of Exposure to 2.5 μm Indoor Particulate Matter on Adult Lung Function in Jakarta

Objectives Lung function impairment due to exposure to indoor air pollution of particulate matter size 2.5 micrometers (PM2.5) is not well documented in Jakarta. Methods To assess whether there is an association between indoor PM2.5 concentration and lung function impairment among the adult population, a cross-sectional design was implemented. There were 109 adults selected aged between 20 years and 65 years from the Pulo Gadung industrial area, East Jakarta. Association and logistic regression analysis were implemented for statistical analysis of the data. Results The average exposure to indoor PM2.5 was 308 μg/m3. There were 38.5% of participants that had lung function impairment. PM2.5 concentration was found to be associated with lung function impairment among the adult population living in Pulo Gadung industrial area after controlling for gender, duration of exposure, ventilation, smoking status, and humidity. Conclusion The results of this study suggest that PM2.5 concentrations in the Pulo Gadung industrial area may be the main contributor to the impairment of lung function for adults living in the surrounding residential area.
A nonlinear non-probabilistic spot interest rate model

We show how to use ‘uncertainty’ in place of the more traditional Brownian ‘randomness’ to model a short–term interest rate. The advantage of this model is principally that it is difficult to show statistically that it is wrong. We discuss the pros and cons of the model and show how to price and hedge various contracts.
Part-of-Speech Tagging with a Symbolic Full Parser: Using the TIGER Treebank to Evaluate Fips

In this paper, we introduce the German version of the multilingual Fips parsing system. We focus on the evaluation of its part-of-speech tagging component with the help of the TIGER treebank. We explain how Fips can be adapted to the tagset used by TIGER and report first results of this study: currently, 87% of words are tagged correctly. We also discuss some common errors and explore a possible extension of this study to parsing.
Low complexity covariance-based DOA estimation algorithm

The aim of this work is to present an alternative method for estimating the direction-of-arrival (DoA), that is, the incoming angle, of a signal impinging on an antenna array. The proposed method is similar to ESPRIT (estimation of signal parameters via rotational invariance techniques) algorithm, which is the most widely used technique for this application. The new algorithm exploits the structural similarities between ESPRIT and the Tong-Xu-Kailath method for blind channel equalization. The result is an ESPRIT-like algorithm for DoA estimation with substantially reduced computational complexity. Simulation results are included to verify the properties and performance of the new covariance-based DoA algorithm, in comparison to ESPRIT and to the theoretical Cramer-Rao lower bound.
Utilization of glycerophosphodiesters by Staphylococcus aureus

The facultative pathogen Staphylococcus aureus colonizes the human anterior nares and causes infections of various organ systems. Which carbon, energy, and phosphate sources can be utilized by S. aureus in nutrient‐poor habitats has remained largely unknown. We describe that S. aureus secretes a glycerophosphodiesterase (glycerophosphodiester phosphodiesterase, EC 3.1.4.46), GlpQ, degrading the glycerophosphodiester (GPD) head groups of phospholipids such as human phosphatidylcholine (GroPC). Deletion of glpQ completely abolished the GroPC‐degrading activity in S. aureus culture supernatants. GroPC has been detected in human tissues and body fluids probably as a result of phospholipid remodelling and degradation. Notably, GroPC promoted S. aureus growth under carbon‐ and phosphate‐limiting conditions in a GlpQ‐dependent manner indicating that GlpQ permits S. aureus to utilize GPD‐derived glycerol‐3‐phosphate as a carbon and phosphate sources. Thus, S. aureus can use a broader spectrum of nutrients than previously thought which underscores its capacity to adapt to the highly variable and nutrient‐poor surroundings.
A Review of Machine Learning based Anomaly Detection Techniques

Intrusion detection is so much popular since the last two decades where intrusion is attempted to break into or misuse the system. It is mainly of two types based on the intrusions, first is Misuse or signature based detection and the other is Anomaly detection. In this paper Machine learning based methods which are one of the types of Anomaly detection techniques is discussed.
Cohort profile: the Cambridge City over-75s Cohort (CC75C).

The Cambridge City over-75s Cohort (CC75C), one of the largest and longest-running population-based studies of the oldest old, is celebrating its 21st birthday. Its origins and subsequent evolution into one of the UK's key ageing cohort studies lie in the collaboration of many distinguished researchers, and its ongoing importance owes much to the invaluable contribution made by its many committed participants.
Three-robot minimax travel-distance optimal formation

Multi-robot formation problem has received increasing attention due to its wide applications such as surveillances and various services. To illustrate a novel framework on optimal multi-robot formation given in our previous work, which aims to answer the long-term ignored fundamental problem of describing the formation and clarifying optimal formation rigorously in a mathematical manner, as a preliminary case study, various cases of the simplest optimal line formation of three robots, i.e. minimax travel-distance line formation problems, where each robot admits to move with the same constant speed along any chosen direction and the three-robot team aims to row on a straight line with the minimum maximal travel distance, are investigated in this note. Such problems look like very easy to resolve, however, to our surprise, mathematical results for these cases established with geometric analysis and inequalities have shown the non-trivialness of the most simple optimal line formation problem. Extensive simulations have also been conducted and briefly reported in this contribution, and these experimental results are found to coincide with the established theoretical results.
An Ambulatory Method of Identifying Anterior Cruciate Ligament Reconstructed Gait Patterns

The use of inertial sensors to characterize pathological gait has traditionally been based on the calculation of temporal and spatial gait variables from inertial sensor data. This approach has proved successful in the identification of gait deviations in populations where substantial differences from normal gait patterns exist; such as in Parkinsonian gait. However, it is not currently clear if this approach could identify more subtle gait deviations, such as those associated with musculoskeletal injury. This study investigates whether additional analysis of inertial sensor data, based on quantification of gyroscope features of interest, would provide further discriminant capability in this regard. The tested cohort consisted of a group of anterior cruciate ligament reconstructed (ACL-R) females and a group of non-injured female controls, each performed ten walking trials. Gait performance was measured simultaneously using inertial sensors and an optoelectronic marker based system. The ACL-R group displayed kinematic and kinetic deviations from the control group, but no temporal or spatial deviations. This study demonstrates that quantification of gyroscope features can successfully identify changes associated with ACL-R gait, which was not possible using spatial or temporal variables. This finding may also have a role in other clinical applications where small gait deviations exist.