Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of the β cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes

Type 1 diabetes is an autoimmune disease in which autoreactive T cells attack and destroy the insulin-producing pancreatic β cells. CD8+ T cells are essential for this β cell destruction, yet their specific antigenic targets are largely unknown. Here, we reveal that the autoantigen targeted by a prevalent population of pathogenic CD8+ T cells in nonobese diabetic mice is islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). Through tetramer technology, IGRP-reactive T cells are readily detected in islets and peripheral blood directly ex vivo. The human IGRP gene maps to a diabetes susceptibility locus, suggesting that IGRP also may be an antigen for pathogenic T cells in human type 1 diabetes and, thus, a new, potential target for diagnostic and therapeutic approaches.
Nonuniform traffic in the Manhattan Street network

A network operating with deflection routing and nonuniform traffic is considered. In addition, each communication link may be characterized by an arbitrary but known propagation delay. A study is made of three distinct contention resolution rules, focusing on one which gives priority to those packets that have been in the network longest. Independence approximations are used to describe the distribution of packet arrivals at each node. A recursive equation is written for each node and used to derive approximate steady-state packet delay distributions. Examples are presented and the independence assumption is discussed. <<ETX>>
DNA Replication Initiates at Different Sites in Early and Late S Phase within Human Ribosomal RNA Genes

Metazoan replication origins often contain multiple potential initiation sites, and the selection of whichof the potential sites are used appears to be dependent upon multiple factors, including the state ofdifferentiation, cell metabolism, and local transcriptional activity. Numerous studies have shown that areplication origin exists within the nontranscribed spacer region of the human ribosomal RNA gene. Wehere analyze nascent leading strand DNA from S phase human lymphoid cells, and find that while themajority of rDNA replicates in mid- and late S phase and preferentially initiates replication 6 kbp fromthe transcription start site, in very early S phase the preferred initiation site is much closer to thetranscription start site and may involve rDNA promoter sequences. This early site is coincident with aminimum GC skew value, diagnostic for replication origins in bacteria and yeast. These results suggestthat replication timing can influence initiation site selection. The timing and nucleolar localization ofrDNA further suggest that this site likely participates in the small number of perinucleolar initiation fociobserved in very early S phase cells that represent the beginning of cellular DNA replication.
Random CNFs are Hard for Cutting Planes

The random k-SAT model is the most important and well-studied distribution over k-SAT instances. It is closely connected to statistical physics; it is used as a testbench for satisfiability algorithms, and average-case hardness over this distribution has also been linked to hardness of approximation via Feige's hypothesis. We prove that any Cutting Planes refutation for random k-SAT requires exponential size, for k that is logarithmic in the number of variables, in the (interesting) regime where the number of clauses guarantees that the formula is unsatisfiable with high probability.
TOWARDS SOCIAL MEDIA MINING : TWITTEROBSERVATORY

This paper presents an approach to social media mining based on a pipeline that implements observing, enriching, storing, modeling and presentation techniques. While social media mining solutions have been used for information extraction and sentiment identification about certain topics, applying social media for modeling and nowcasting is a promising new research direction. A novel tool TwitterObservatory that allows observing, searching, analyzing and presenting social media is introduced as a part of the research. Illustrative examples of using the proposed pipeline show how the TwitterObservatory implementing the pipeline can support the user in interaction with the social media data.
Using Situational Crime Prevention Theory to Explain the Effectiveness of Information Systems Security

Information is an intangible organizational asset of enormous value in the information age. Information systems (IS) security technologies play an important role in protecting that information from unauthorized disclosure, modification, and use. As such, the factors that influence the effectiveness of IS security strategies need to be understood. The existing theory base for studying IS security effectiveness is limited to three major perspectives since the mid-1980s: Straub’s extension of general deterrence theory (1987, 1990); an argument for balanced technical, formal, and informal controls by Dhillon and colleagues (1999, 2001, 2004); and various hacker motivation taxonomies developed during the 1980’s and 1990’s. Our goal is to expand the range of the theoretical lens that can be used to understand IS security effectiveness. Towards this goal, we examine the appropriateness of extending situational crime prevention theory, a theory developed in the criminal justice domain to address physical crime, to the digital realm. Our conceptual analysis suggests that situational crime prevention theory may offer new insights into improving IS security effectiveness by reducing the criminal’s anticipated rewards from the crime.
Docosahexaenoic acid‐supplementation prior to fasting prevents muscle atrophy in mice

Muscle wasting prevails in numerous diseases (e.g. diabetes, cardiovascular and kidney diseases, COPD,…) and increases healthcare costs. A major clinical issue is to devise new strategies preventing muscle wasting. We hypothesized that 8‐week docosahexaenoic acid (DHA) supplementation prior to fasting may preserve muscle mass in vivo.
Pivotbrowser: a tag-space image searching prototype

We propose a novel iterative searching and refining prototype for tagged images. This prototype, named PivotBrowser, captures semantically similar tag sets in a structure called pivot. By constructing a pivot for a textual query, PivotBrowser first selects candidate images possibly relevant to the query. The tags contained in these candidate images are then selected in terms of their tag relevances to the pivot. The shortlisted tags are clustered and one of the tag clusters is used to select the results from the candidate images. Ranking of the images in each partition is based on their relevance to the tag cluster. With the guidance of the tag clusters presented, a user is able to perform searching and iterative query refinement.
Domains Responsible for Constitutive and Ca2+-Dependent Interactions between Calmodulin and Small Conductance Ca2+-Activated Potassium Channels

Small conductance Ca2+-activated potassium channels (SK channels) are coassembled complexes of pore-forming SK α subunits and calmodulin. We proposed a model for channel activation in which Ca2+ binding to calmodulin induces conformational rearrangements in calmodulin and the α subunits that result in channel gating. We now report fluorescence measurements that indicate conformational changes in the α subunit after calmodulin binding and Ca2+ binding to the α subunit–calmodulin complex. Two-hybrid experiments showed that the Ca2+-independent interaction of calmodulin with the α subunits requires only the C-terminal domain of calmodulin and is mediated by two noncontiguous subregions; the ability of the E-F hands to bind Ca2+ is not required. Although SK α subunits lack a consensus calmodulin-binding motif, mutagenesis experiments identified two positively charged residues required for Ca2+-independent interactions with calmodulin. Electrophysiological recordings of SK2 channels in membrane patches from oocytes coexpressing mutant calmodulins revealed that channel gating is mediated by Ca2+ binding to the first and second E-F hand motifs in the N-terminal domain of calmodulin. Taken together, the results support a calmodulin- and Ca2+-calmodulin-dependent conformational change in the channel α subunits, in which different domains of calmodulin are responsible for Ca2+-dependent and Ca2+-independent interactions. In addition, calmodulin is associated with each α subunit and must bind at least one Ca2+ ion for channel gating. Based on these results, a state model for Ca2+ gating was developed that simulates alterations in SK channel Ca2+sensitivity and cooperativity associated with mutations in CaM.
Clarification Dialogues as Measure to Increase Robustness in a Spoken Dialogue System

A number of methods are implemented in the face-to-face translation system Verbmobil to improve its robustness. In this paper, we describe clarification dialogues as one method to deal with incomplete or inconsistent information. Currently, three types of clarification dialogues are realized: subdialogues concerning phonological ambiguities, unknown words and semantic inconsistencies. For each clarification type we discuss the detection of situations and system states which lead to their initialization and explain the information flow during processing.
Mice with a naturally occurring DISC1 mutation display a broad spectrum of behaviors associated to psychiatric disorders

Disrupted in schizophrenia-1 (DISC1) gene is associated with several neuropsychiatric disorders as it is disrupted by a balanced translocation involving chromosomes 1 and 11 in a large Scottish pedigree with high prevalence of schizophrenia, bipolar disorder and major depression. Since its identification, several mouse models with DISC1 genetic modifications have been generated using different approaches. Interestingly, a natural deletion of 25bp in the 129 mouse strain alters the DISC1 gene reading frame leading to a premature stop codon very close to the gene breakpoint in the mutant allele of the Scottish family. In the present study we confirmed that the 129DISC1Del mutation results in reduced level of full length DISC1 in hippocampus of heterozygous mice and we have characterized the behavioral consequences of heterozygous 129DISC1Del mutation in a mixed B6129 genetic background. We found alterations in spontaneous locomotor activity (hyperactivity in males and hypoactivity in females), deficits in pre-pulse inhibition (PPI) and also increased despair behavior in heterozygous 129DISC1Del mice, thus reproducing typical behaviors associated to psychiatric disorders. Since this mouse strain is widely and commercially available, we propose it as an amenable tool to study DISC1-related biochemical alterations and psychiatric behaviors.
Deriving a Mutation Index of Carcinogenicity Using Protein Structure and Protein Interfaces

With the advent of Next Generation Sequencing the identification of mutations in the genomes of healthy and diseased tissues has become commonplace. While much progress has been made to elucidate the aetiology of disease processes in cancer, the contributions to disease that many individual mutations make remain to be characterised and their downstream consequences on cancer phenotypes remain to be understood. Missense mutations commonly occur in cancers and their consequences remain challenging to predict. However, this knowledge is becoming more vital, for both assessing disease progression and for stratifying drug treatment regimes. Coupled with structural data, comprehensive genomic databases of mutations such as the 1000 Genomes project and COSMIC give an opportunity to investigate general principles of how cancer mutations disrupt proteins and their interactions at the molecular and network level. We describe a comprehensive comparison of cancer and neutral missense mutations; by combining features derived from structural and interface properties we have developed a carcinogenicity predictor, InCa (Index of Carcinogenicity). Upon comparison with other methods, we observe that InCa can predict mutations that might not be detected by other methods. We also discuss general limitations shared by all predictors that attempt to predict driver mutations and discuss how this could impact high-throughput predictions. A web interface to a server implementation is publicly available at http://inca.icr. ac.uk/.
Dynamic Resource Allocation with Imperfect Channel Sensing –Heterogeneous Services in Cognitive Radio Network

In cognitive radio networks (CRN), resource should dynamically be assigned to the users with respect to sensed radio atmospheres. Many works has been done for dynamic allocation but it is not practically easy because the secondary network is very difficult to know the right knowledge of dynamic radio atmospheres in CRN. In this object we study the different methods of dynamic resource allocation in CRN for diverse services. We proposed the joint power and channel allocation problem using the discrete stochastic optimization method. The simulation result provided significant improvements of effectiveness of the proposed system.
Sense of agency is related to gamma band coupling in an inferior parietal-preSMA circuitry

In the present study we tested whether sense of agency (SoA) is reflected by changes in coupling between right medio-frontal/supplementary motor area (SMA) and inferior parietal cortex (IPC). Twelve healthy adult volunteers participated in the study. They performed a variation of a line-drawing task (Nielsen, 1963; Fourneret and Jeannerod, 1998), in which they moved a cursor on a digital tablet with their right hand without seeing the hand. Visual feedback displayed on a computer monitor was either in correspondence with or deviated from the actual movement. This made participants uncertain as to the agent of the movement and they reported SoA in approximately 50% of trials when the movement was computer-generated. We tested whether IPC-preSMA coupling was associated with SoA, using dynamic causal modeling (DCM) for induced responses (Chen et al., 2008; Herz et al., 2012). Nine different DCMs were constructed for the early and late phases of the task, respectively. All models included two regions: a superior medial gyrus (preSMA) region and a right supramarginal gyrus (IPC) region. Bayesian models selection (Stephan et al., 2009) favored a model with input to IPC and modulation of the forward connection to SMA in the late task phase, and a model with input to preSMA and modulation of the backward connection was favored for the early task phase. The analysis shows that IPC source activity in the 50–60 Hz range modulated preSMA source activity in the 40–70 Hz range in the presence of SoA compared with no SoA in the late task phase, but the test of the early task phase did not reveal any differences between presence and absence of SoA. We show that SoA is associated with a directionally specific between frequencies coupling from IPC to preSMA in the higher gamma (ɣ) band in the late task phase. This suggests that SoA is a retrospective perception, which is highly dependent on interpretation of the outcome of the performed action.
Le psychologique et le religieux

Depuis Freud, les recherches psychologiques se sont développées en écartant des concepts nécessaires à la reconnaissance de l'interpénétration du psychologique et du religieux dans la dynamique des personnes. L'étude des questions religieuses oblige donc à un dépassement quant aux présupposés philosophiques et méthodologiques de ces recherches. Ce dépassement, l'auteure propose de le faire en référant à l'approche expérientielle phénoménologico-ontologique élaborée par J. Croteau (1981) comme arrière-fond scientifico-philosophique dans lequel peuvent s'inscrire les concepts de l'être et de volonté et leur rôle dans le développement de la personnalité. Elle propose alors d'articuler le rapport du psychologique et du religieux en référant aux concepts de base du modèle de la Valeur fondamentale d'Yvon Saint-Arnaud, sous l'angle de la dynamique psychospirituelle ou psychoreligieuse des personnes.
Biomarkers of Lead Exposure and DNA Methylation within Retrotransposons

Background DNA methylation is an epigenetic mark that regulates gene expression. Changes in DNA methylation within white blood cells may result from cumulative exposure to environmental metals such as lead. Bone lead, a marker of cumulative exposure, may therefore better predict DNA methylation than does blood lead. Objective In this study we compared associations between lead biomarkers and DNA methylation. Methods We measured global methylation in participants of the Normative Aging Study (all men) who had archived DNA samples. We measured patella and tibia lead levels by K-X-Ray fluorescence and blood lead by atomic absorption spectrophotometry. DNA samples from blood were used to determine global methylation averages within CpG islands of long interspersed nuclear elements-1 (LINE-1) and Alu retrotransposons. A mixed-effects model using repeated measures of Alu or LINE-1 as the dependent variable and blood/bone lead (tibia or patella in separate models) as the primary exposure marker was fit to the data. Results Overall mean global methylation (± SD) was 26.3 ± 1.0 as measured by Alu and 76.8 ± 1.9 as measured by LINE-1. In the mixed-effects model, patella lead levels were inversely associated with LINE-1 (β = −0.25; p < 0.01) but not Alu (β = −0.03; p = 0.4). Tibia lead and blood lead did not predict global methylation for either Alu or LINE-1. Conclusion Patella lead levels predicted reduced global DNA methylation within LINE-1 elements. The association between lead exposure and LINE-1 DNA methylation may have implications for the mechanisms of action of lead on health outcomes, and also suggests that changes in DNA methylation may represent a biomarker of past lead exposure.
All-Digital Transmitter With a Mixed-Domain Combination Filter

In this brief, we present a new reconfigurable filtering technique for all-digital transmitters using signal interference and cancellation. The proposed method allows the change of some filtering characteristics digitally. This technique is used to reduce the quantization noise from the all-digital transmitter's output, reducing the analog output filter requirements. Without a narrow band filter, a greater degree of flexibility for the transmitter's carrier frequency and bandwidth is attained, improving its suitability for multiband and multistandard operation. The results show the quantization noise reduction without an output analog filter, contributing to an increase of the transmitter's coding efficiency up to more than 95%.
Prevalence and Interpretation of Recent Trends in Rates of Pervasive Developmental Disorders

The aims of this article are to provide an up-to-date review of the methodological features and substantive results of published epidemiological surveys of the prevalence of pervasive developmental disorders (PDD). This article updates previous reviews (1, 2) with the inclusion of new studies made available since then. The specific questions addressed inthis article are: a) how are cases of PDD defined and identified in epidemiological surveys? ; b) what are the best estimates for the prevalence of autism and related pervasive developmental disorders considering the methodological implications of the surveys, and c) what interpretation can be given to time trends observed in prevalence rates of PDDs given the hypothesized secular increase in PDDs?
What Should be the Primary Treatment in Atrial Fibrillation: Ventricular Rate Control or Sinus Rhythm Control with Long-term Anticoagulation?

Recent trials have favoured ventricular rate control in atrial fibrillation (AF) management, however the present study investigated whether the restoration and maintenance of sinus rhythm with long-term anticoagulation therapy was superior in terms of embolic events and death in 534 patients with an AF duration > 48 h. Patients were randomized and received sinus rhythm control with either aspirin (group 1) or warfarin (group 2), or they were given ventricular rate control (group 3). Cardioversion to sinus rhythm was attempted in 425 patients and was successful in 387 (91.1%) of them. After 3 years' follow-up there were 12, two and 15 embolic events in groups 1, 2 and 3 respectively (significant difference between groups 1 and 2, and 2 and 3) and overall mortalities were four, two and 12, respectively (significant difference between groups 2 and 3). It is concluded that patients with an AF duration > 48 h might benefit considerably from sinus rhythm restoration and long-term warfarin therapy in terms of embolic events and mortality.
Effects of Antiretroviral Therapy on Autonomic Function in Early HIV Infection: A Preliminary Report

Background: A prospective study was conducted in human immunodeficiency virus (HIV)-infected patients as they undergo alterations in their antiretroviral therapy (ART) to determine the effect of ART on autonomic function. Methods: HIV-infected subjects who were either 1) naïve to ART and initiating ART, or 2) receiving ART and in HIV virologic failure for at least 4 months and were about to switch ART were enrolled in this study. Autonomic function assessment (cardiovagal, adrenergic, and sudomotor tests) was performed prior to and 4 months after initiating the new ART. Changes in clinical autonomic symptoms and virologic assessment were assessed. Results: Twelve subjects completed the study: 92% male; median age (Q1, Q3) was 41.0 (28.0, 48.2) years; and 50% White/Non-Hispanic. Seventy-five percent were ART naïve while 25% were failing their ART regimen. The median CD4 count was 336.5 (245.3, 372.3) cells/mm3. All subjects achieved an undetectable HIV viral load by the 4-month follow-up visit. The majority of naïve subjects were started on an ART regimen of tenofovir / emtricitabine / efavirenz. There were no significant differences in autonomic function assessment, as measured by cardiovagal, adrenergic, and sudomotor tests, with regards to ART initiation. Conclusion: This is the first study to examine the effects of initiating ART on autonomic function in early HIV infection. This study found no appreciable differences of ART on the autonomic nervous system when ART is initiated early in the course of HIV disease. ART may not contribute to short-term changes in autonomic function.
Turning emergency plans into executable artifacts

On the way to the improvement of Emergency Plans, we show how a structured specification of the response procedures allows transforming static plans into dynamic, executable entities that can drive the way different actors participate in crisis responses. Additionally, the execution of plans requires the definition of information access mechanisms allowing execution engines to provide an actor with all the information resources he or she needs to accomplish a response task. We describe work in progress to improve the SAGA's Plan definition Module and Plan Execution Engine to support information-rich plan execution.