Miracle-dz/UniFAR-FTUs huggingface dataset:
Recognition of Unknown Conserved Alternatively Spliced Exons

The split structure of most mammalian protein-coding genes allows for the potential to produce multiple different mRNA and protein isoforms from a single gene locus through the process of alternative splicing (AS). We propose a computational approach called UNCOVER based on a pair hidden Markov model to discover conserved coding exonic sequences subject to AS that have so far gone undetected. Applying UNCOVER to orthologous introns of known human and mouse genes predicts skipped exons or retained introns present in both species, while discriminating them from conserved noncoding sequences. The accuracy of the model is evaluated on a curated set of genes with known conserved AS events. The prediction of skipped exons in the ~1% of the human genome represented by the ENCODE regions leads to more than 50 new exon candidates. Five novel predicted AS exons were validated by RT-PCR and sequencing analysis of 15 introns with strong UNCOVER predictions and lacking EST evidence. These results imply that a considerable number of conserved exonic sequences and associated isoforms are still completely missing from the current annotation of known genes. UNCOVER also identifies a small number of candidates for conserved intron retention.
Open Text Semantic Parsing Using FrameNet and WordNet

This paper describes a rule-based semantic parser that relies on a frame dataset (FrameNet), and a semantic network (WordNet), to identify semantic relations between words in open text, as well as shallow semantic features associated with concepts in the text. Parsing semantic structures allows semantic units and constituents to be accessed and processed in a more meaningful way than syntactic parsing, moving the automation of understanding natural language text to a higher level.
Flavonoids and Insulin-Resistance: From Molecular Evidences to Clinical Trials

Insulin-resistance is one of the main factors responsible for the onset and progression of Metabolic Syndrome (MetS). Among all polyphenols, the effects of flavonoids and their main food sources on insulin sensitivity have been widely evaluated in molecular and clinical studies. The aim of this review is to analyse the data observed in vitro, in vivo and in clinical trials concerning the effects of flavonoids on insulin resistance and to determine the molecular mechanisms with which flavonoids interact with insulin signaling.
Visual census, photographic records and the trial of a video network provide first evidence of the elusive Sicyopterus cynocephalus in Australia

Opportunistic encounters with an elusive large-bodied sicydiine goby in a single plunge pool led us to photograph and deploy three video cameras to detect individuals in that pool. Subsequently, a catchment-wide search indicated that the species, eventually identified as Sicyopterus cynocephalus, was confined to the single pool where it was originally detected. A network of ten video cameras was then deployed to estimate the number of individuals of that species and of a congener, S. lagocephalus, by non-destructive means. This study provides the first record of S. cynocephalus in Australia, and showcases the synergy of active snorkel searches and a remote camera network in counting individuals of two sympatric species of Sicyopterus.
A Gradient-Based Implicit Blend Preprint

OLIVIER GOURMEL IRIT, Université de Toulouse, CNRS, France and LOIC BARTHE IRIT, Université de Toulouse, CNRS, France and MARIE-PAULE CANI Laboratoire Jean Kuntzmann, Grenoble Universités, CNRS, INRIA Grenoble, France and BRIAN WYVILL Department of Computer Science, University of Victoria, Canada and ADRIEN BERNHARDT Laboratoire Jean Kuntzmann, Grenoble Universités, CNRS, INRIA Grenoble, France and MATHIAS PAULIN IRIT, Université de Toulouse, CNRS, France and HERBERT GRASBERGER Department of Computer Science, University of Victoria, Canada
Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates.

PURPOSE Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, may suppress antitumor immunity. This phase I study sought to determine the safety and tolerability of anti-PD-1 blockade in patients with treatment-refractory solid tumors and to preliminarily assess antitumor activity, pharmacodynamics, and immunologic correlates. PATIENTS AND METHODS Thirty-nine patients with advanced metastatic melanoma, colorectal cancer (CRC), castrate-resistant prostate cancer, non-small-cell lung cancer (NSCLC), or renal cell carcinoma (RCC) received a single intravenous infusion of anti-PD-1 (MDX-1106) in dose-escalating six-patient cohorts at 0.3, 1, 3, or 10 mg/kg, followed by a 15-patient expansion cohort at 10 mg/kg. Patients with evidence of clinical benefit at 3 months were eligible for repeated therapy. RESULTS Anti-PD-1 was well tolerated: one serious adverse event, inflammatory colitis, was observed in a patient with melanoma who received five doses at 1 mg/kg. One durable complete response (CRC) and two partial responses (PRs; melanoma, RCC) were seen. Two additional patients (melanoma, NSCLC) had significant lesional tumor regressions not meeting PR criteria. The serum half-life of anti-PD-1 was 12 to 20 days. However, pharmacodynamics indicated a sustained mean occupancy of > 70% of PD-1 molecules on circulating T cells > or = 2 months following infusion, regardless of dose. In nine patients examined, tumor cell surface B7-H1 expression appeared to correlate with the likelihood of response to treatment. CONCLUSION Blocking the PD-1 immune checkpoint with intermittent antibody dosing is well tolerated and associated with evidence of antitumor activity. Exploration of alternative dosing regimens and combinatorial therapies with vaccines, targeted therapies, and/or other checkpoint inhibitors is warranted.
Wireless sensor networks for emergency navigation

In an emergency, wireless network sensors combined with a navigation algorithm could help safely guide people to a building exit while helping them avoid hazardous areas. We propose a distributed navigation algorithm for emergency situations. At normal time, sensors monitor the environment. When the sensors detect emergency events, our protocol quickly separates hazardous areas from safe areas, and the sensors establish escape paths. Simulation and implementation results show that our scheme achieves navigation safety and quick convergence of the navigation directions. We based our protocol on the temporally ordered routing algorithm for mobile ad hoc networks. TORA assigns mobile nodes temporally ordered sequence numbers to support multipath routing from a source to a specific destination node
Using Latent Variable Mixture Modeling to Understand Trauma-Related Outcomes in Undergraduate Women

Abstract Posttraumatic stress disorder (PTSD) and sexual functioning problems often co-occur after trauma. Researchers have linked certain factors (e.g., depression, relationship satisfaction) to PTSD and sexual functioning, but it is unclear how these variables interact. Adult undergraduate female trauma survivors (N = 280) completed self-report measures via an online survey. Latent variable mixture modeling generated four groups that differed in terms of their PTSD symptom severity, sexual functioning, sexual pain, relationship status, and relationship functioning. ANOVAs explored group differences. Classes were not differentiated by trauma, relationship satisfaction, or drug use. Results highlight the complex relations between sexual functioning and post-trauma symptomology.
Assessment of risk for asthma initiation and cancer and heart disease deaths among patrons and servers due to secondhand smoke exposure in restaurants and bars

Background Despite efforts to reduce exposure to secondhand smoke (SHS), only 5% of the world's population enjoy smoke-free restaurants and bars. Methods Lifetime excess risk (LER) of cancer death, ischaemic heart disease (IHD) death and asthma initiation among non-smoking restaurant and bar servers and patrons in Minnesota and the US were estimated using weighted field measurements of SHS constituents in Minnesota, existing data on tobacco use and multiple dose-response models. Results A continuous approach estimated a LER of lung cancer death (LCD) of 18×10−6(95% CI 13 to 23×10−6) for patrons visiting only designated non-smoking sections, 80×10−6(95% CI 66 to 95×10−6) for patrons visiting only smoking venues/sections and 802×10−6(95% CI 658 to 936×10−6) for servers in smoking-permitted venues. An attributable-risk (exposed/non-exposed) approach estimated a similar LER of LCD, a LER of IHD death about 10−2 for non-smokers with average SHS exposure from all sources and a LER of asthma initiation about 5% for servers with SHS exposure at work only. These risks correspond to 214 LCDs and 3001 IHD deaths among the general non-smoking population and 1420 new asthma cases among non-smoking servers in the US each year due to SHS exposure in restaurants and bars alone. Conclusions Health risks for patrons and servers from SHS exposure in restaurants and bars alone are well above the acceptable level. Restaurants and bars should be a priority for governments’ effort to create smoke-free environments and should not be exempt from smoking bans.
Expression and Function of Transient Receptor Potential Ankyrin 1 Ion Channels in the Caudal Nucleus of the Solitary Tract

The nucleus of the solitary tract (NTS) receives visceral information via the solitary tract (ST) that comprises the sensory components of the cranial nerves VII, IX and X. The Transient Receptor Potential Ankyrin 1 (TRPA1) ion channels are non-selective cation channels that are expressed primarily in pain-related sensory neurons and nerve fibers. Thus, TRPA1 expressed in the primary sensory afferents may modulate the function of second order NTS neurons. This hypothesis was tested and confirmed in the present study using acute brainstem slices and caudal NTS neurons by RT-PCR, immunostaining and patch-clamp electrophysiology. The expression of TRPA1 was detected in presynaptic locations, but not the somata of caudal NTS neurons that did not express TRPA1 mRNA or proteins. Moreover, caudal NTS neurons did not show somatodendritic responsiveness to TRPA1 agonists, while TRPA1 immunostaining was detected only in the afferent fibers. Electrophysiological recordings detected activation of presynaptic TRPA1 in glutamatergic terminals synapsing on caudal NTS neurons evidenced by the enhanced glutamatergic synaptic neurotransmission in the presence of TRPA1 agonists. The requirement of TRPA1 for modulation of spontaneous synaptic activity was confirmed using TRPA1 knockout mice where TRPA1 agonists failed to alter synaptic efficacy. Thus, this study provides the first evidence of the TRPA1-dependent modulation of the primary afferent inputs to the caudal NTS. These results suggest that the second order caudal NTS neurons act as a TRPA1-dependent interface for visceral noxious-innocuous integration at the level of the caudal brainstem.
On radiating-zone boundaries of short, /spl lambda//2, and /spl lambda/ dipoles

This article presents a critical analysis of the classical definitions of the radiation regions for the particular case of short, /spl lambda//2, or /spl lambda/ dipole antennas, regions which we have revisited. We worked out a definition of radiation zones from consistent criteria directly linked with radiation characteristics: radiated field, wavefront, wave impedance, and radiated power. The "far-field zone" boundary is then defined as the distance beyond which the radiated wave is spherical and the radial component of the fields is negligible compared to the transverse component. Next, we consider the "near-field-reactive or very-near-field zone" to be the region wherein the wave impedance is different from Z/sub 0/ =120/spl pi/, and wherein the reactive power is not negligible when compared to the active power. In this paper, the short dipole case is first studied. Dipoles of length up to /spl lambda/ are also treated, considering diameters from 0 up to /spl lambda//20. The results obtained lead us to accurately set the boundaries of the radiation zones of dipoles without the need for the restrictive hypotheses of the classical definitions.
A video compression case study on a reconfigurable VLIW architecture

In this paper, we investigate the benefits of a flexible, application-specific instruction set by adding a run-time Reconfigurable Functional Unit (RFU) to a VLIW processor. Preliminary results on the motion estimation stage in an MPEG4 video encoder are presented. With the RFU modeled at functional level and under realistic assumptions on execution latency, technology scaling and reconfiguration penalty, we explore different RFU instructions at fine-grain (instruction-level) and coarse-grain (loop-level) granularity to speedup the application execution. The memory bandwidth bottleneck, typical for streaming applications, is alleviated through the combined adoption of custom prefetch pattern instructions and an extent of local memory. Performance evaluations indicate that up to an 8/spl times/ improvement with loop-level optimizations can be achieved under various architectural assumptions.
Technologies Systems and Conventional Systems: Requirements for Co-ordinating Multiple Agents for Diagnostic Decisions

This paper describes the development of an integrated intelligent (expert) system and conventional information system to support decision making of a diagnostic decision in a multi-agent environment. It argues that many a priori requirements for the information system can be elicited by accounting for the specific nature of the diagnostic decision and for the single/multiple-actor environment. This finding is generalized to a framework that indicates that a priori requirements take into account the basic theories on which the information system supporting the decision task is ultimately based. In particular, attention is focused on the nature of the task (e.g. diagnostic), whether the application is for a single- or multiple-agent situation and the nature of the multi-agent structure (e.g. product or functional form of organization).
Correlating user activity with system data for fast detection and diagnosis of system outages

Human error has been identified one of the major factors behind system outages and network downtime in a number of previous research papers and surveys. Gartner statistics show that almost 40% of unplanned application downtime is caused due to operator errors such as unintentional changes to network configuration resulting in a network outage, patch installations, service restart,etc. Yet, system admin activities on production IT systems are rarely properly logged and monitored. Existing tools to track user activities either produce too much information without any hints of a potential outage scenario or too little information to be useful in a meaningful way. In this paper, we describe the design and implementation of iTrack a framework for monitoring user activities and correlating them with system data for fast detection and diagnosis of service outages. iTrack makes use of commonly available native monitoring and diagnostic utilities on operating systems to monitor systems events as well as system admin activity, correlates these two sets of information and categorizes the activity as potentially abnormal or harmful based on their impact on the system in terms of file system, network and memory activities. Our results confirm that iTrack overhead in terms of CPU time, activity completion time and data generated is within the tolerance range of most production systems. In cases, where the overhead was found to be unacceptable, we detect the underlying cause and provide solutions which improve performance by up to 20% to 90%, in terms of managed sever and iTrack server CPU utilization, respectively and by up to 2 times in terms of completion time of certain system admin activities on the managed server.
Gender Based Within-Household Inequality in Childhood Immunization in India: Changes over Time and across Regions

Background and Objectives Despite India's substantial economic growth in the past two decades, girls in India are discriminated against in access to preventive healthcare including immunizations. Surprisingly, no study has assessed the contribution of gender based within-household discrimination to the overall inequality in immunization status of Indian children. This study therefore has two objectives: to estimate the gender based within-household inequality (GWHI) in immunization status of Indian children and to examine the inter-regional and inter-temporal variations in the GWHI. Data and Methods The present study used households with a pair of male-female siblings (aged 1–5 years) from two rounds of National Family Health Survey (NFHS, 1992–93 and 2005–06). The overall inequality in the immunization status (after controlling for age and birth order) of children was decomposed into within-households and between-households components using Mean log deviation to obtain the GWHI component. The analysis was conducted at the all-India level as well as for six specified geographical regions and at two time points (1992–93 and 2005–06). Household fixed-effects models for immunization status of children were also estimated. Results and Conclusions Findings from household fixed effects analysis indicated that the immunization scores of girls were significantly lower than that of boys. The inequality decompositions revealed that, at the all-India level, the absolute level of GWHI in immunization status decreased from 0.035 in 1992–93 to 0.023 in 2005–06. However, as a percentage of total inequality, it increased marginally (15.5% to 16.5%). In absolute terms, GWHI decreased in all the regions except in the North-East. But, as a percentage of total inequality it increased in the North-Eastern, Western and Southern regions. The main conclusions are the following: GWHI contributes substantially to the overall inequality in immunization status of Indian children; and though the overall inequality in immunization status declined in all the regions, the changes in GWHI were mixed.
A robust nonlinear semi-active control for base seismically-isolated structures

This paper proposes a robust nonlinear semi-active control for base seismically-isolated structures. The control is based upon an extension of works of Leitmann et al. on the stabilization of nonlinear systems with uncertain models. For usual models of structure dynamics it is shown that applying a specific control law drives the state variables into a ball of specified radius in finite time. The radius of the ball may be arbitrarily chosen as long as it is not lower than a limiting value. In addition, estimates of this limiting ball radius is provided. The time to reach the ball is also provided. The semi-active control thus provides the control designer with interesting design parameters. The efficacy of proposed semi-active control is illustrated by its application to simple models of structures focusing in particular to the attenuation of excitation transmitted from floor to equipment mounted on them.
Assesment of artificial caries lesions through scanning electron microscopy and cross-sectional microhardness test.

AIMS To assess through scanning electron microscopy (SEM) and cross-sectional microhardness (CSMH) test whether the methodology exposed in this experiment can be used to produce artificial active white spot lesions (AAWSLs) on smooth unabraded human dental enamel. MATERIALS AND METHODS Ten human permanent molars were used in this experiment. One section of each tooth was double coated with nail varnish except for a limited central area sized 2.5 mm × 1 mm (2.5 mm 2 ). Each specimen was individually exposed to 10.4 ml of a demineralizing solution at pH 5.0, during 42 days (37°C) without agitation. Samples were sectioned in the center of the AAWSL and one half was analyzed in SEM and the other half was subjected to CSMH. Descriptive statistics was performed to determine mean depth of the lesion. RESULTS The mean depth of AAWSL was 100 μm (s.d. =12.1) and a white dull rough surface could be detected by the unaided eye. SEM images demonstrated that although some surface areas of the lesion appeared to be relatively intact, erosion was present. A prismatic pattern of dissolution was observed in all samples with an enlargement of the prism sheaths and some samples had also sites of destruction of prism cores. CONCLUSION This methodology can be used to induce AAWSLs in human dental enamel but surface erosion has to be taken into account when performing CSMH test.
Reduced-intensity conditioning compared with conventional allogeneic stem-cell transplantation in relapsed or refractory Hodgkin's lymphoma: an analysis from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.

PURPOSE To compare the clinical outcome in terms of nonrelapse mortality (NRM), relapse rate (RR), overall survival (OS), and progression-free survival (PFS) in patients with relapsed Hodgkin's lymphoma (HL) treated with reduced-intensity conditioning (RIC) or myeloablative conditioning followed by allogeneic stem-cell transplantation (alloSCT). PATIENTS AND METHODS A total of 168 patients with HL undergoing a first alloSCT (RIC, n = 89; myeloablative conditioning, n = 79) between January 1997 and December 2001 and registered in the European Group for Blood and Marrow Transplantation database were analyzed. RESULTS NRM was significantly decreased in the RIC group (hazard ratio [HR], 2.85; 95% CI, 1.62 to 5.02; P < .001). OS was better in the RIC group (HR, 2.05; 95% CI, 1.27 to 3.29; P = .04) and there was a trend for better PFS in the RIC group (HR, 1.53; 95% CI, 0.97 to 2.40; P = .07). RR was higher in the RIC group in univariate but not in multivariate analysis. The development of chronic graft-versus-host disease (GVHD) significantly decreased the incidence of relapse, which translated into a trend for a better PFS. CONCLUSION The lower incidence of NRM in the RIC group is encouraging, particularly because these patients experienced adverse pretransplantation characteristics more frequently. This analysis also indicates the existence of a graft-versus-HL effect correlated to the development of GVHD. Additional efforts to reduce the high RR seen in both groups of patients will be necessary to improve the modest PFS (31% v 27%) and OS (59% v 36%) for patients prepared with RIC or myeloablative conditioning.
Anti-CD 3 Antibody Induces IL-10-producing CD 4 + CD 25 + Regulatory T Cells , Which Suppress T Cell Response in Rheumatoid Arthritis Patients

Background: Regulatory T cells (Tregs) have been investigated intensively for some decades. These cells regulate the immune system, prevent overactivated immune responses and can be used therapeutically. For rheumatoid arthritis (RA), understanding the functions and status of Tregs is an important step for understanding immune regulation in this autoimmune disease. Methods: We investigated the percentages, phenotypes and suppressive functions of CD4 CD25 Tregs in peripheral blood (PB) of patients with RA. Results: The percentages were higher in the patients (n=12) than in healthy controls (n=10), and the cells expressed the CD45RB, CTLA-4 and CCR7 phenotypes. We also investigated the expression of Foxp3 and secretion of interleukin (IL)-10 induced CD4CD25 Tcells by anti-CD3 antibody treatment. A suppressive function of the patients' cells was shown through coculture with CD4+CD25󰠏 T cells in vitro. Conclusion: We suggest that, despite their increased numbers and suppressive function, they manage the ongoing inflammation ineffectively. It might be possible to apply IL-10 to induce the proliferation of IL-10-producing Tregs as therapy for RA. (Immune Network 2007;7(3):124-132)