Miracle-dz/UniFAR-FTUs huggingface dataset:
SNPnexus: a web database for functional annotation of newly discovered and public domain single nucleotide polymorphisms

Motivation: Design a new computational tool allowing scientists to functionally annotate newly discovered and public domain single nucleotide polymorphisms in order to help in prioritizing targets in further disease studies and large-scale genotyping projects. Summary: SNPnexus database provides functional annotation for both novel and public SNPs. Possible effects on the transcriptome and proteome levels are characterized and reported from five major annotation systems providing the most extensive information on alternative splicing. Additional information on HapMap genotype and allele frequency, overlaps with potential regulatory elements or structural variations as well as related genetic diseases can be also retrieved. The SNPnexus database has a user-friendly web interface, providing single or batch query options using SNP identifiers from dbSNP as well as genomic location on clones, contigs or chromosomes. Therefore, SNPnexus is the only database currently providing a complete set of functional annotations of SNPs in public databases and newly detected from sequencing projects. Hence, we describe SNPnexus, provide details of the query options, the annotation categories as well as biological examples of use. Availability: The SNPnexus database is freely available at http://www.snp-nexus.org. Contact: claude.chelala@cancer.org. uk
A comparison of the effects of medial prefrontal, cingulate cortex, and cingulum bundle lesions on tests of spatial memory: evidence of a double dissociation between frontal and cingulum bundle contributions

Rats were trained on an automated delayed nonmatching-to-position (DNMP) task. They then received cytotoxic lesions in either the medial prefrontal cortex (n = 13) or the cingulate and retrosplenial cortices (n = 8), or radiofrequency lesions in either the fornix (n = 6) or the cingulum bundle (n = 8). Twelve animals served as surgical controls. Only the fornical and medial prefrontal lesions disrupted DNMP performance, both groups showing a loss of accuracy and an increase in bias. The rats were then trained on a lever discrimination and reversal task, the medial prefrontal and fornical groups showing evidence of an increase in bias when compared with the cingulate cortex group. Finally, the rats were trained on a forced alternation task in a T- maze. Marked deficits were observed in the fornix and cingulum bundle groups, but the medial prefrontal and cingulate groups were unimpaired. The double dissociation between the effects of the prefrontal and cingulum bundle lesions highlights the very different nature of the two spatial tasks (DNMP and T-maze alternation), even though both involved a nonmatching rule. These findings may reflect the involvement of divergent outputs from the fornix-anterior thalamic pathway. One possibility is that anterior thalamic projections to the medial prefrontal cortex are concerned with processing egocentric information, while anterior thalamic projections to temporal regions via the cingulum bundle are concerned with allocentric information. The results also indicate that the effects of conventional lesions in the cingulate cortex and medial prefrontal cortex may be compromised by additional damage to the cingulum bundle.
Expression of Aldo-keto Reductase 1C23 in the Equine Corpus Luteum in Different Luteal Phases

Regression of the corpus luteum (CL) is characterized by a decay in progesterone (P4) production (functional luteolysis) and disappearance of luteal tissues (structural luteolysis). In mares, structural luteolysis is thought to be caused by apoptosis of luteal cells, but functional luteolysis is poorly understood. 20α-hydroxysteroid dehydrogenase (20α-HSD) catabolizes P4 into its biologically inactive form, 20α-hydroxyprogesterone (20α-OHP). In mares, aldo-keto reductase (AKR) 1C23, which is a member of the AKR superfamily, has 20α-HSD activity. To clarify whether AKR1C23 is associated with functional luteolysis in mares, we investigated the expression of AKR1C23 in the CL in different luteal phases. The luteal P4 concentration and levels of 3β-hydroxysteroid dehydrogenase (3β-HSD) mRNA were higher in the mid luteal phase than in the late and regressed luteal phases (P<0.05), but the level of 3β-HSD protein was higher in the late luteal phase than in the regressed luteal phase (P<0.05). The luteal 20α-OHP concentration and the level of AKR1C23 mRNA were higher in the late luteal phase than in the early and mid luteal phases (P<0.05), and the level of AKR1C23 protein was also highest in the late luteal phase. Taken together, these findings suggest that metabolism of P4 by AKR1C23 is one of the processes contributing to functional luteolysis in mares.
Learning and Invariance in a Family of Hierarchical Kernels

Understanding invariance and discrimination properties of hierarchical models is arguably the key to understanding how and why such models, of which the the mammalian visual system is one instance, can lead to good generalization properties and reduce the sample complexity of a given learning task. In this paper we explore invariance to transformation and the role of layerwise embeddings within an abstract framework of hierarchical kernels motivated by the visual cortex. Here a novel form of invariance is induced by propagating the effect of locally defined, invariant kernels throughout a hierarchy. We study this notion of invariance empirically. We then present an extension of the abstract hierarchical modeling framework to incorporate layer-wise embeddings, which we demonstrate can lead to improved generalization and scalable algorithms. Finally we analyze experimentally sample complexity properties as a function of architectural parameters.
B Cell-Intrinsic Role for IRF5 in TLR9/BCR-Induced Human B Cell Activation, Proliferation, and Plasmablast Differentiation

Upon recognition of antigen, B cells undergo rapid proliferation followed by differentiation to specialized antibody secreting cells (ASCs). During this transition, B cells are reliant upon a multilayer transcription factor network to achieve a dramatic remodeling of the B cell transcriptional landscape. Increased levels of ASCs are often seen in autoimmune diseases and it is believed that altered expression of regulatory transcription factors play a role in this imbalance. The transcription factor interferon regulatory factor 5 (IRF5) is one such candidate as polymorphisms in IRF5 associate with risk of numerous autoimmune diseases and correlate with elevated IRF5 expression. IRF5 genetic risk has been widely replicated in systemic lupus erythematosus (SLE), and loss of Irf5 ameliorates disease in murine lupus models, in part, through the lack of pathogenic autoantibody secretion. It remains unclear, however, whether IRF5 is contributing to autoantibody production through a B cell-intrinsic function. To date, IRF5 function in healthy human B cells has not been characterized. Using human primary naive B cells, we define a critical intrinsic role for IRF5 in B cell activation, proliferation, and plasmablast differentiation. Targeted IRF5 knockdown resulted in significant immunoglobulin (Ig) D retention, reduced proliferation, plasmablast differentiation, and IgG secretion. The observed decreases were due to impaired B cell activation and clonal expansion. Distinct from murine studies, we identify and confirm new IRF5 target genes, IRF4, ERK1, and MYC, and pathways that mediate IRF5 B cell-intrinsic function. Together, these results identify IRF5 as an early regulator of human B cell activation and provide the first dataset in human primary B cells to map IRF5 dysfunction in SLE.
Loudness measurement of human utterance to a robot in noisy environment

In order to understand utterance based human-robot interation, and to develop such a system, this paper initially analyzes how loud humans speak in a noisy environment. Experiments were conducted to measure how loud humans speak with 1) different noise levels, 2) different number of sound sources, 3) different sound sources, and 4) different distances to a robot. Synchronized sound sources add noise to the auditory scene, and resultant utterances are recorded and compared to a previously recorded noiseless utterance. From experiments, we understand that humans generate basically the same level of sound pressure level at his/her location irrespective of distance and background noise. More precisely, there is a band according to a distance, and also according to sound sources that is including language pronounce. According to this understanding, we developed an online spoken command recognition system for a mobile robot. System consists of two key componenets: 1) Low side-lobe microphone array that works as omini-directional telescopic microphone, and 2) DSBF combined with FBS method for sound source localization and segmentation. Caller location and segmented sound stream are calculated, and then the segmented sound stream is sent to voice recognition system. The system works with at most five sound sources at the same time with about at most 18[dB] sound pressure differences. Experimental results with the modile robot are also shown.
Peptidoglycan Up-Regulates CXCL8 Expression via Multiple Pathways in Monocytes/Macrophages

Peptidoglycan (PG), the gram positive bacterial pathogen-associated molecular patterns (PAMP), is detected in a high proportion in macrophage-rich atheromatous regions, and expression of chemokine CXCL8, which triggers monocyte arrest on early atherosclerotic endothelium, is elevated in monocytes/macrophages in human atherosclerotic lesion. The aim of this study was to investigate whether PG induced CXCL8 expression in the cell type and to determine cellular signaling pathways involved in that process. Exposure of THP-1 cell, human monocyte/macrophage cell line, to PG not only enhanced CXCL8 release but also profoundly induced il8 gene transcription. PG-induced release of CXCL8 and induction of il8 gene transcription were blocked by OxPAPC, an inhibitor of TLR-2/4 and TLR4, but not by polymyxin B, an inhibitor of LPS. PG-mediated CXCL8 release was significantly attenuated by inhibitors of PI3K-Akt-mTOR pathways. PKC inhibitors, MAPK inhibitors, and ROS quenchers also significantly attenuated expression of CXCL8. The present study proposes that PG contributes to inflammatory reaction and progression of atherosclerosis by inducing CXCL8 expression in monocytes/macrophages, and that TLR-2, PI3K-Akt-mTOR, PKC, ROS, and MAPK are actively involved in the process.
Fast Measurement of Dielectric Loss Angle With Time-Domain Quasi-Synchronous Algorithm

Fast Fourier transform (FFT) algorithm inevitably suffers from spectral leakage and picket-fence effect under asynchronous sampling and nonintegral period truncation. So the FFT-based dielectric loss angle (DLA) measurement needs window functions and spectral lines interpolation algorithm, which requires massive sampled data and high computational cost. Therefore, this paper proposes a DLA measurement method on the basis of time-domain quasi-synchronous sampling technique to achieve fast measurement and high accuracy. First, the fundamental frequencies of the original voltage and current sampled signals were estimated accurately with the time-domain Newton interpolation algorithm. Then, the quasi-synchronous sampled sequences (QSSA) of the original asynchronous sampled signals were reconstructed using cubic spline interpolation algorithm. Finally, the DLA was calculated according to the equivalent circuit model and frequency-domain analysis of voltage and current QSSA based on FFT. The proposed method in this paper can perfectly restrain spectral leakage and picket-fence effect without window functions and spectral lines interpolation algorithm. The results of simulation and the implementation on the embedded system have confirmed the effectiveness of the proposed algorithm in this paper with less sampled data and lower computational cost.
Tangled and drowned: a global review of penguin bycatch in fisheries

Penguins are the most threatened group of seabirds after albatrosses. Although penguins are regularly captured in fishing gear, the threat to penguins as a group has not yet been assessed. We reviewed both published and grey literature to identify the fishing gear types that penguins are most frequently recorded in, the most impacted species and, for these susceptible species, the relative importance of bycatch compared to other threats. While quantitative estimates of overall bycatch levels are difficult to obtain, this review highlights that, of the world’s 18 species of penguins, 14 have been recorded as bycatch in fishing gear and that gillnets, and to a lesser extent trawls, are the gear types that pose the greatest threats to penguins. Bycatch is currently of greatest concern for yellow-eyed Megadyptes antipodes (Endangered), Humboldt Spheniscus humboldti (Vulnerable) and Magellanic Spheniscus magellanicus penguins (Near Threatened). Penguins face many threats; reducing bycatch mortality in fishing gear will greatly enhance the resilience of penguin populations to threats from habitat loss and climate change that are more difficult to address in the short term. Additional data are required to quantify the true extent of penguin bycatch, particularly for the most susceptible species. In the meantime, it is crucially important to manage the fisheries operating within known penguin foraging areas to reduce the risks to this already threatened group of seabirds.
Distributed, real-time bayesian learning in online services

The last ten years have seen a tremendous growth in Internet-based online services such as search, advertising, gaming and social networking. Today, it is important to analyze large collections of user interaction data as a first step in building predictive models for these services as well as learn these models in real-time. One of the biggest challenges in this setting is scale: not only does the sheer scale of data necessitate parallel processing but it also necessitates distributed models; with over 900 million active users at Facebook, any user-specific sets of features in a linear or non-linear model yields models of a size bigger than can be stored in a single system. In this talk, I will give a hands-on introduction to one of the most versatile tools for handling large collections of data with distributed probabilistic models: the sum-product algorithm for approximate message passing in factor graphs. I will discuss the application of this algorithm for the specific case of generalized linear models and outline the challenges of both approximate and distributed message passing including an in-depth discussion of expectation propagation and Map-Reduce.
Struggling toward reward: Recent experience of anhedonia interacts with motivation to predict reward pursuit in the face of a stressful manipulation

Anhedonia, or the loss of interest and/or pleasure, is a core symptom of depression. Individuals experiencing anhedonia have difficulty motivating themselves to pursue rewarding stimuli, which can result in dysfunction. Action orientation is a motivational factor that might interact with anhedonia to potentially buffer against this dysfunction, as action-oriented individuals upregulate positive affect to quickly motivate themselves to complete goals in the face of stress. The Effort-Expenditure for Rewards Task (EEfRT) is a promising new method for examining differences in motivation in individuals experiencing anhedonia. In the EEfRT, participants choose either easier tasks associated with smaller monetary rewards or harder tasks associated with larger monetary rewards. We examined the relationship between action orientation and EEfRT performance following a negative mood induction in a sample with varying levels of anhedonia. There were two competing hypotheses: (1) action orientation would act as a buffer against anhedonia such that action-oriented individuals, regardless of anhedonic symptoms, would be motivated to pursue greater rewards despite stress, or (2) anhedonia would act as a debilitating factor such that individuals with elevated anhedonic symptoms, regardless of action orientation, would not pursue greater rewards. We examined these hypotheses via Generalized Estimating Equations and found an interaction between anhedonia and action orientation. At low levels of anhedonia, action orientation was associated with effort for reward, but this relationship was not present at high levels of anhedonia. Thus, at low levels of anhedonia, action orientation acted as a buffer against stress, but at high levels, anhedonia debilitated action orientation so that it was no longer a promotive factor.
Efficacy and tolerability of the fixed combination of brinzolamide 1% and timolol 0.5% in daily practice

Introduction: The purpose of this study was to document the efficacy and tolerability of the new fixed-combination (FC) brinzolamide 1%/timolol 0.5% as used in daily practice throughout Germany. Methods: An open-label, multicenter, observational study of patients was performed that evaluated the transition from prior medication to brinzolamide/timolol FC for the reduction of intraocular pressure (IOP). Ophthalmologists measured IOP at baseline and 4–6 weeks after transition and assessed their satisfaction with brinzolamide/timolol FC. Patients assessed the tolerability of both their previous and new regimens, judged their satisfaction with brinzolamide/timolol, and reported their preference between their previous and new regimens. Patients transitioning from other FC products to brinzolamide/timolol FC were analyzed separately. Results: Data from 14,025 patients from 1161 centers were analyzed. Four to 6 weeks after transition to brinzolamide/timolol, patients experienced a mean IOP decrease of 3.9 ± 4.3 mm Hg (P < 0.0001). All of the predefined patient subgroups (grouped by previous therapy) demonstrated a significant mean IOP reduction following transition to brinzolamide/timolol (P < 0.0001). Patients judged brinzolamide/timolol tolerability more positively than they did their previous therapies (87.2% vs 53.7% favorable assessments) and reported a high satisfaction rating with brinzolamide/timolol (93.4%). Brinzolamide/timolol was preferred over previous therapy at a ratio of almost 9:1. Patients who transitioned from dorzolamide/timolol to brinzolamide/timolol (n = 2937) demonstrated a significant decrease in mean IOP (P < 0.0001), rated brinzolamide/timolol more tolerable than dorzolamide/timolol (88.9% vs 28.9%), and preferred brinzolamide/timolol at a ratio of more than 9:1. Patients who transitioned from brimonidine/timolol (n = 209) demonstrated a significant decrease in mean IOP (P < 0.0001), rated brinzolamide/timolol more tolerable (86.5% vs 32.1%), and preferred brinzolamide/timolol at a ratio of 11.5:1. Conclusions: The FC brinzolamide 1%/timolol 0.5% produced better IOP control than all previous therapies analyzed and demonstrated favorable tolerability and a high satisfaction rating, resulting in a strong patient preference for brinzolamide/timolol over previous therapies.
Predictors of treatment outcome in modular cognitive therapy for obsessive–compulsive disorder

Background: The present study sought to identify predictors of outcome for a comprehensive cognitive therapy (CT) developed for patients with obsessive–compulsive disorder (OCD). Methods: Treatment was delivered over 22 sessions and included standard CT methods, as well as specific strategies designed for subtypes of OCD including religious, sexual, and other obsessions. This study of 39 participants assigned to CT examined predictors of outcomes assessed on the Yale‐Brown Obsessive Compulsive Scale. A variety of baseline symptom variables were examined as well as treatment expectancy and motivation. Results: Findings indicated that participants who perceived themselves as having more severe OCD at baseline remained in treatment but more severe symptoms were marginally associated with worse outcome for those who completed therapy. Depressed and anxious mood did not predict post‐test outcome, but more Axis I comorbid diagnoses (mainly major depression and anxiety disorders), predicted more improvement, as did the presence of sexual (but not religious) OCD symptoms, and stronger motivation (but not expectancy). A small rebound in OCD symptoms at 1‐year follow‐up was significantly predicted by higher scores on personality traits, especially for schizotypal (but not obsessive–compulsive personality) traits. Conclusions: Longer treatment may be needed for those with more severe symptoms at the outset. CT may have positive effects not only on OCD symptoms but also on comorbid depressive and anxious disorders and associated underlying core beliefs. Findings are discussed in light of study limitations and research on other predictors. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.
Trophic factors and cell therapy to stimulate brain repair after ischaemic stroke

Brain repair involves a compendium of natural mechanisms that are activated following stroke. From a therapeutic viewpoint, reparative therapies that encourage cerebral plasticity are needed. In the last years, it has been demonstrated that modulatory treatments for brain repair such as trophic factor‐ and stem cell‐based therapies can promote neurogenesis, gliogenesis, oligodendrogenesis, synaptogenesis and angiogenesis, all of which having a beneficial impact on infarct volume, cell death and, finally, and most importantly, on the functional recovery. However, even when promising results have been obtained in a wide range of experimental animal models and conditions these preliminary results have not yet demonstrated their clinical efficacy. Here, we focus on brain repair modulatory treatments for ischaemic stroke, that use trophic factors, drugs with trophic effects and stem cell therapy. Important and still unanswered questions for translational research ranging from experimental animal models to recent and ongoing clinical trials are reviewed here.
Demographic features, BMPR2 status and outcomes in distal chronic thromboembolic pulmonary hypertension

Background: Although pulmonary endarterectomy (PEA) is potentially curative in chronic thromboembolic pulmonary hypertension (CTEPH), some patients have distally distributed disease that is not amenable to surgery. The aetiology and characteristics of this patient group are currently not well understood. Objectives: This study compares the baseline demographic features and outcomes in subjects with distal CTEPH, those with proximal CTEPH and those with idiopathic pulmonary arterial hypertension (IPAH) to determine whether these conditions represent separate entities or whether they exist along the same spectrum of disease. Methods: The medical history, clinical characteristics, bone morphogenetic protein receptor type II (BMPR2) mutation status and outcomes of 96 subjects with IPAH, 35 with distal CTEPH and 68 with proximal CTEPH referred to a single specialist centre between 1994 and 2005 were reviewed. Results: There were significant differences between the distal CTEPH, proximal CTEPH and IPAH groups in age (55.9 years vs 54.8 years vs 46.2 years, p<0.001), proportion who were male (43% vs 69% vs 29%, p<0.001), previous deep vein thrombosis (28.6% vs 30.9% vs 3.1%, p<0.001), positive BMPR2 status (0% vs 0% vs 15%, p = 0.018), mean pulmonary artery pressure (47.3 mm Hg vs 45.4 mm Hg vs 54.8 mm Hg, p<0.001) and total pulmonary resistance (12.9 WU vs 12.4 WU vs 18.1 WU, p<0.001). Patients with distal CTEPH and those with IPAH were managed similarly and had comparable survival characteristics (1 year survival 77% vs 86%; 3 year survival 53% vs 60%; p = 0.68). Conclusions: Patients with distal CTEPH share certain demographic features with patients with proximal CTEPH that not only indicate a common aetiology but also help to differentiate them from patients with IPAH. Despite more favourable haemodynamic parameters in those with distal CTEPH, patients in this group had a poor long-term outcome which was similar to that of patients with IPAH.