Showing papers by "Université de Montréal published in 2006"
Proceedings Article•
04 Dec 2006TL;DR: These experiments confirm the hypothesis that the greedy layer-wise unsupervised training strategy mostly helps the optimization, by initializing weights in a region near a good local minimum, giving rise to internal distributed representations that are high-level abstractions of the input, bringing better generalization.
Abstract: Complexity theory of circuits strongly suggests that deep architectures can be much more efficient (sometimes exponentially) than shallow architectures, in terms of computational elements required to represent some functions. Deep multi-layer neural networks have many levels of non-linearities allowing them to compactly represent highly non-linear and highly-varying functions. However, until recently it was not clear how to train such deep networks, since gradient-based optimization starting from random initialization appears to often get stuck in poor solutions. Hinton et al. recently introduced a greedy layer-wise unsupervised learning algorithm for Deep Belief Networks (DBN), a generative model with many layers of hidden causal variables. In the context of the above optimization problem, we study this algorithm empirically and explore variants to better understand its success and extend it to cases where the inputs are continuous or where the structure of the input distribution is not revealing enough about the variable to be predicted in a supervised task. Our experiments also confirm the hypothesis that the greedy layer-wise unsupervised training strategy mostly helps the optimization, by initializing weights in a region near a good local minimum, giving rise to internal distributed representations that are high-level abstractions of the input, bringing better generalization.
4,385 citations
University of Pittsburgh1, Cedars-Sinai Medical Center2, Johns Hopkins University3, Johns Hopkins University School of Medicine4, Université de Montréal5, Broad Institute6, University of Toronto7, Harvard University8, University of Chicago9, McGill University10, North Shore-LIJ Health System11, Yale University12
TL;DR: A highly significant association is found between Crohn's disease and the IL23R gene on chromosome 1p31, which encodes a subunit of the receptor for the proinflammatory cytokine interleukin-23, which prioritize this signaling pathway as a therapeutic target in inflammatory bowel disease.
Abstract: The inflammatory bowel diseases Crohn's disease and ulcerative colitis are common, chronic disorders that cause abdominal pain, diarrhea, and gastrointestinal bleeding. To identify genetic factors that might contribute to these disorders, we performed a genome-wide association study. We found a highly significant association between Crohn's disease and the IL23R gene on chromosome 1p31, which encodes a subunit of the receptor for the proinflammatory cytokine interleukin-23. An uncommon coding variant (rs11209026, c.1142G>A, p.Arg381Gln) confers strong protection against Crohn's disease, and additional noncoding IL23R variants are independently associated. Replication studies confirmed IL23R associations in independent cohorts of patients with Crohn's disease or ulcerative colitis. These results and previous studies on the proinflammatory role of IL-23 prioritize this signaling pathway as a therapeutic target in inflammatory bowel disease.
2,937 citations
TL;DR: It is shown that variation partitioning as currently applied in canonical analysis is biased, and appropriate unbiased estimators are presented to consider so that comparisons between fractions or, eventually, between different canonical models are meaningful.
Abstract: Establishing relationships between species distributions and environmental characteristics is a major goal in the search for forces driving species distributions. Canonical ordinations such as redundancy analysis and canonical correspondence analysis are invaluable tools for modeling communities through environmental predictors. They provide the means for conducting direct explanatory analysis in which the association among species can be studied according to their common and unique relationships with the environmental variables and other sets of predictors of interest, such as spatial variables. Variation partitioning can then be used to test and determine the likelihood of these sets of predictors in explaining patterns in community structure. Although variation partitioning in canonical analysis is routinely used in ecological analysis, no effort has been reported in the literature to consider appropriate estimators so that comparisons between fractions or, eventually, between different canonical models are meaningful. In this paper, we show that variation partitioning as currently applied in canonical analysis is biased. We present appropriate unbiased estimators. In addition, we outline a statistical test to compare fractions in canonical analysis. The question addressed by the test is whether two fractions of variation are significantly different from each other. Such assessment provides an important step toward attaining an understanding of the factors patterning community structure. The test is shown to have correct Type I error rates and good power for both redundancy analysis and canonical correspondence analysis.
1,947 citations
TL;DR: In this paper, the authors evaluated the effect of rosuvastatin on coronary atheroma burden using intravascular ultrasound (IVUS) imaging. And they found that very intensive statin therapy could regress coronary atherosclerosis as determined by IVUS imaging.
Abstract: ContextPrior intravascular ultrasound (IVUS) trials have demonstrated slowing or halting of atherosclerosis progression with statin therapy but have not shown convincing evidence of regression using percent atheroma volume (PAV), the most rigorous IVUS measure of disease progression and regression.ObjectiveTo assess whether very intensive statin therapy could regress coronary atherosclerosis as determined by IVUS imaging.Design and SettingProspective, open-label blinded end-points trial (A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden [ASTEROID]) was performed at 53 community and tertiary care centers in the United States, Canada, Europe, and Australia. A motorized IVUS pullback was used to assess coronary atheroma burden at baseline and after 24 months of treatment. Each pair of baseline and follow-up IVUS assessments was analyzed in a blinded fashion.PatientsBetween November 2002 and October 2003, 507 patients had a baseline IVUS examination and received at least 1 dose of study drug. After 24 months, 349 patients had evaluable serial IVUS examinations.InterventionAll patients received intensive statin therapy with rosuvastatin, 40 mg/d.Main Outcome MeasuresTwo primary efficacy parameters were prespecified: the change in PAV and the change in nominal atheroma volume in the 10-mm subsegment with the greatest disease severity at baseline. A secondary efficacy variable, change in normalized total atheroma volume for the entire artery, was also prespecified.ResultsThe mean (SD) baseline low-density lipoprotein cholesterol (LDL-C) level of 130.4 (34.3) mg/dL declined to 60.8 (20.0) mg/dL, a mean reduction of 53.2% (P<.001). Mean (SD) high-density lipoprotein cholesterol (HDL-C) level at baseline was 43.1 (11.1) mg/dL, increasing to 49.0 (12.6) mg/dL, an increase of 14.7% (P<.001). The mean (SD) change in PAV for the entire vessel was −0.98% (3.15%), with a median of −0.79% (97.5% CI, −1.21% to −0.53%) (P<.001 vs baseline). The mean (SD) change in atheroma volume in the most diseased 10-mm subsegment was −6.1 (10.1) mm3, with a median of −5.6 mm3 (97.5% CI, −6.8 to −4.0 mm3) (P<.001 vs baseline). Change in total atheroma volume showed a 6.8% median reduction; with a mean (SD) reduction of −14.7 (25.7) mm3, with a median of −12.5 mm3 (95% CI, −15.1 to −10.5 mm3) (P<.001 vs baseline). Adverse events were infrequent and similar to other statin trials.ConclusionsVery high-intensity statin therapy using rosuvastatin 40 mg/d achieved an average LDL-C of 60.8 mg/dL and increased HDL-C by 14.7%, resulting in significant regression of atherosclerosis for all 3 prespecified IVUS measures of disease burden. Treatment to LDL-C levels below currently accepted guidelines, when accompanied by significant HDL-C increases, can regress atherosclerosis in coronary disease patients. Further studies are needed to determine the effect of the observed changes on clinical outcome.Trial RegistrationClinicalTrials.gov Identifier: NCT00240318Published online March 13, 2006 (doi:10.1001/jama.295.13.jpc60002).
1,913 citations
TL;DR: The OARSI cartilage OA histopathology grading system appears consistent and simple to apply as discussed by the authors, however, further studies are required to confirm the system's utility, as well as their reproducibility and validity.
1,813 citations
TL;DR: The Rome III child and adolescent criteria represent an evolution from Rome II and should prove useful for both clinicians and researchers dealing with childhood FGIDs.
1,676 citations
George M. Weinstock1, Gene E. Robinson2, Richard A. Gibbs1, Kim C. Worley1 +225 more•Institutions (55)
TL;DR: The genome sequence of the honeybee Apis mellifera is reported, suggesting a novel African origin for the species A. melliferA and insights into whether Africanized bees spread throughout the New World via hybridization or displacement.
Abstract: Here we report the genome sequence of the honeybee Apis mellifera, a key model for social behaviour and essential to global ecology through pollination. Compared with other sequenced insect genomes, the A. mellifera genome has high A+T and CpG contents, lacks major transposon families, evolves more slowly, and is more similar to vertebrates for circadian rhythm, RNA interference and DNA methylation genes, among others. Furthermore, A. mellifera has fewer genes for innate immunity, detoxification enzymes, cuticle-forming proteins and gustatory receptors, more genes for odorant receptors, and novel genes for nectar and pollen utilization, consistent with its ecology and social organization. Compared to Drosophila, genes in early developmental pathways differ in Apis, whereas similarities exist for functions that differ markedly, such as sex determination, brain function and behaviour. Population genetics suggests a novel African origin for the species A. mellifera and insights into whether Africanized bees spread throughout the New World via hybridization or displacement.
1,673 citations
TL;DR: The major focus of this Review is on the mechanisms of islet beta cell failure in the pathogenesis of obesity-associated type 2 diabetes (T2D).
Abstract: The major focus of this Review is on the mechanisms of islet beta cell failure in the pathogenesis of obesity-associated type 2 diabetes (T2D). As this demise occurs within the context of beta cell compensation for insulin resistance, consideration is also given to the mechanisms involved in the compensation process, including mechanisms for expansion of beta cell mass and for enhanced beta cell performance. The importance of genetic, intrauterine, and environmental factors in the determination of "susceptible" islets and overall risk for T2D is reviewed. The likely mechanisms of beta cell failure are discussed within the two broad categories: those with initiation and those with progression roles.
1,652 citations
TL;DR: The Principal Coordinates of Neighbors of Neighbor Matrices (PCNM) approach as discussed by the authors was proposed to create spatial predictors that can be easily incorporated into regression or canonical analysis models, providing a flexible tool especially when contrasted to the family of autoregressive models and trend surface analysis which are of common use in ecological and geographical analysis.
1,620 citations
TL;DR: An “Enhanced Perceptual Functioning” model encompassing the main differences between autistic and non-autistic social andnon-social perceptual processing is proposed, which may explain the autistic perceptual endophenotype.
Abstract: We propose an “Enhanced Perceptual Functioning” model encompassing the main differences between autistic and non-autistic social and non-social perceptual processing: locally oriented visual and auditory perception, enhanced low-level discrimination, use of a more posterior network in “complex” visual tasks, enhanced perception of first order static stimuli, diminished perception of complex movement, autonomy of low-level information processing toward higher-order operations, and differential relation between perception and general intelligence. Increased perceptual expertise may be implicated in the choice of special ability in savant autistics, and in the variability of apparent presentations within PDD (autism with and without typical speech, Asperger syndrome) in non-savant autistics. The overfunctioning of brain regions typically involved in primary perceptual functions may explain the autistic perceptual endophenotype.
1,572 citations
TL;DR: Blocking PD-1 engagement to its ligand (PD-L1) enhanced the capacity of HIV-specific CD8+ T cells to survive and proliferate and led to an increased production of cytokines and cytotoxic molecules in response to cognate antigen.
Abstract: The engagement of programmed death 1 (PD-1) to its ligands, PD-L1 and PD-L21,2,3,4, inhibits proliferation and cytokine production mediated by antibodies to CD3 (refs. 5,6,7). Blocking the PD-1–PD-L1 pathway in mice chronically infected with lymphocytic choriomeningitis virus restores the capacity of exhausted CD8+ T cells to undergo proliferation, cytokine production and cytotoxic activity and, consequently, results in reduced viral load8. During chronic HIV infection, HIV-specific CD8+ T cells are functionally impaired9,10,11, showing a reduced capacity to produce cytokines and effector molecules as well as an impaired capacity to proliferate12,13,14,15. Here, we found that PD-1 was upregulated on HIV-specific CD8+ T cells; PD-1 expression levels were significantly correlated both with viral load and with the reduced capacity for cytokine production and proliferation of HIV-specific CD8+ T cells. Notably, cytomegalovirus (CMV)-specific CD8+ T cells from the same donors did not upregulate PD-1 and maintained the production of high levels of cytokines. Blocking PD-1 engagement to its ligand (PD-L1) enhanced the capacity of HIV-specific CD8+ T cells to survive and proliferate and led to an increased production of cytokines and cytotoxic molecules in response to cognate antigen. The accumulation of HIV-specific dysfunctional CD8+ T cells in the infected host could prevent the renewal of a functionally competent HIV-specific CD8+ repertoire.
TL;DR: It is shown that phylogenetic analyses of the genome sequencing of the appendicularian Oikopleura dioica provide compelling evidence that tunicates, and not cephalochordates, represent the closest living relatives of vertebrates.
Abstract: Tunicates or urochordates (appendicularians, salps and sea squirts), cephalochordates (lancelets) and vertebrates (including lamprey and hagfish) constitute the three extant groups of chordate animals. Traditionally, cephalochordates are considered as the closest living relatives of vertebrates, with tunicates representing the earliest chordate lineage. This view is mainly justified by overall morphological similarities and an apparently increased complexity in cephalochordates and vertebrates relative to tunicates. Despite their critical importance for understanding the origins of vertebrates, phylogenetic studies of chordate relationships have provided equivocal results. Taking advantage of the genome sequencing of the appendicularian Oikopleura dioica, we assembled a phylogenomic data set of 146 nuclear genes (33,800 unambiguously aligned amino acids) from 14 deuterostomes and 24 other slowly evolving species as an outgroup. Here we show that phylogenetic analyses of this data set provide compelling evidence that tunicates, and not cephalochordates, represent the closest living relatives of vertebrates. Chordate monophyly remains uncertain because cephalochordates, albeit with a non-significant statistical support, surprisingly grouped with echinoderms, a hypothesis that needs to be tested with additional data. This new phylogenetic scheme prompts a reappraisal of both morphological and palaeontological data and has important implications for the interpretation of developmental and genomic studies in which tunicates and cephalochordates are used as model animals.
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TL;DR: The current understanding of pathogenesis, clinical features, diagnostic, and differential diagnostic approaches, and diagnostic algorithms and recommendations for management of Cushing's syndrome are reviewed.
Goddard Space Flight Center1, Université de Montréal2, Space Science Institute3, Herzberg Institute of Astrophysics4, European Space Agency5, École Polytechnique Fédérale de Lausanne6, Space Telescope Science Institute7, University of Arizona8, University of Exeter9, Max Planck Society10, NASA Headquarters11, Arizona State University12, UK Astronomy Technology Centre13
TL;DR: The James Webb Space Telescope (JWST) as discussed by the authors is a large (6.6 m), cold (<50 K), infrared-optimized space observatory that will be launched early in the next decade into orbit around the second Earth-Sun Lagrange point.
Abstract: The James Webb Space Telescope (JWST) is a large (6.6 m), cold (<50 K), infrared (IR)-optimized space observatory that will be launched early in the next decade into orbit around the second Earth–Sun Lagrange point. The observatory will have four instruments: a near-IR camera, a near-IR multiobject spectrograph, and a tunable filter imager will cover the wavelength range, 0.6 < ; < 5.0 μ m, while the mid-IR instrument will do both imaging and spectroscopy from 5.0 < ; < 29 μ m. The JWST science goals are divided into four themes. The key objective of The End of the Dark Ages: First Light and Reionization theme is to identify the first luminous sources to form and to determine the ionization history of the early universe. The key objective of The Assembly of Galaxies theme is to determine how galaxies and the dark matter, gas, stars, metals, morphological structures, and active nuclei within them evolved from the epoch of reionization to the present day. The key objective of The Birth of Stars and Protoplanetary Systems theme is to unravel the birth and early evolution of stars, from infall on to dust-enshrouded protostars to the genesis of planetary systems. The key objective of the Planetary Systems and the Origins of Life theme is to determine the physical and chemical properties of planetary systems including our own, and investigate the potential for the origins of life in those systems. Within these themes and objectives, we have derived representative astronomical observations. To enable these observations, JWST consists of a telescope, an instrument package, a spacecraft, and a sunshield. The telescope consists of 18 beryllium segments, some of which are deployed. The segments will be brought into optical alignment on-orbit through a process of periodic wavefront sensing and control. The instrument package contains the four science instruments and a fine guidance sensor. The spacecraft provides pointing, orbit maintenance, and communications. The sunshield provides passive thermal control. The JWST operations plan is based on that used for previous space observatories, and the majority of JWST observing time will be allocated to the international astronomical community through annual peer-reviewed proposal opportunities.
04 Dec 2006
TL;DR: These measures – Youden's index, likelihood, Discriminant power – are used in medical diagnosis and it is shown that they are interrelated, and they are applied to a case study from the field of electronic negotiations.
Abstract: Different evaluation measures assess different characteristics of machine learning algorithms. The empirical evaluation of algorithms and classifiers is a matter of on-going debate among researchers. Most measures in use today focus on a classifier's ability to identify classes correctly. We note other useful properties, such as failure avoidance or class discrimination, and we suggest measures to evaluate such properties. These measures – Youden's index, likelihood, Discriminant power – are used in medical diagnosis. We show that they are interrelated, and we apply them to a case study from the field of electronic negotiations. We also list other learning problems which may benefit from the application of these measures.
TL;DR: In this paper, the authors proposed an acquisition strategy and reduction pipeline for speckle attenuation and high contrast imaging is demonstrated to significantly get better detection limits with longer integration times at all angular separations.
Abstract: Angular differential imaging is a high-contrast imaging technique that reduces speckle noise from quasi-static optical aberrations and facilitates the detection of faint nearby companions. A sequence of images is acquired with an altitude/azimuth telescope, the instrument rotator being turned off. This keeps the instrument and telescope optics aligned, stabilizes the instrumental PSF and allows the field of view to rotate with respect to the instrument. For each image, a reference PSF obtained from other images of the sequence is subtracted. All residual images are then rotated to align the field and are median combined. Observed performances are reported for Gemini Altair/NIRI data. Inside the speckle dominated region of the PSF, it is shown that quasi-static PSF noise can be reduced by a factor {approx}5 for each image subtraction. The combination of all residuals then provides an additional gain of the order of the square root of the total number of images acquired. To our knowledge, this is the first time an acquisition strategy and reduction pipeline designed for speckle attenuation and high contrast imaging is demonstrated to significantly get better detection limits with longer integration times at all angular separations. A PSF noise attenuation of 100 was achieved from 2-hourmore » long sequences of images of Vega, reaching a 5-sigma contrast of 20 magnitudes for separations greater than 7''. This technique can be used with currently available instruments to search for {approx} 1 M{sub Jup} exoplanets with orbits of radii between 50 and 300 AU around nearby young stars. The possibility of combining the technique with other high-contrast imaging methods is briefly discussed.« less
TL;DR: Together these mechanisms contribute to the continuous dynamic adjustment of sensorimotor interactions, ensuring that the central program and feedback mechanisms are congruous during locomotion.
Abstract: Locomotion results from intricate dynamic interactions between a central program and feedback mechanisms. The central program relies fundamentally on a genetically determined spinal circuitry (central pattern generator) capable of generating the basic locomotor pattern and on various descending pathways that can trigger, stop, and steer locomotion. The feedback originates from muscles and skin afferents as well as from special senses (vision, audition, vestibular) and dynamically adapts the locomotor pattern to the requirements of the environment. The dynamic interactions are ensured by modulating transmission in locomotor pathways in a state- and phase-dependent manner. For instance, proprioceptive inputs from extensors can, during stance, adjust the timing and amplitude of muscle activities of the limbs to the speed of locomotion but be silenced during the opposite phase of the cycle. Similarly, skin afferents participate predominantly in the correction of limb and foot placement during stance on uneven terrain, but skin stimuli can evoke different types of responses depending on when they occur within the step cycle. Similarly, stimulation of descending pathways may affect the locomotor pattern in only certain phases of the step cycle. Section ii reviews dynamic sensorimotor interactions mainly through spinal pathways. Section iii describes how similar sensory inputs from the spinal or supraspinal levels can modify locomotion through descending pathways. The sensorimotor interactions occur obviously at several levels of the nervous system. Section iv summarizes presynaptic, interneuronal, and motoneuronal mechanisms that are common at these various levels. Together these mechanisms contribute to the continuous dynamic adjustment of sensorimotor interactions, ensuring that the central program and feedback mechanisms are congruous during locomotion.
Montreal General Hospital1, McGill University2, University of Pittsburgh3, SUNY Downstate Medical Center4, Toronto Western Hospital5, Johns Hopkins University School of Medicine6, University of Calgary7, University of Birmingham8, Hanyang University9, University College London10, NHS Lanarkshire11, Yeshiva University12, University of North Carolina at Chapel Hill13, Lund University14, University of Alabama at Birmingham15, Université de Montréal16, Dalhousie University17, University of British Columbia18, University of Western Ontario19, Royal University Hospital20, University of Manitoba21, Northwestern University22
TL;DR: The Lupus Survival Study Group data are reviewed and particularly the data from the State University of New York Health Science Center at Brooklyn, NY is reviewed.
Abstract: Objective. To examine mortality rates in the largest systemic lupus erythematosus (SLE) cohort ever assembled. Methods. Our sample was a multisite international SLE cohort (23 centers, 9,547 patients). Deaths were ascertained by vital statistics registry linkage. Standardized mortality ratio (SMR; ratio of deaths observed to deaths expected) estimates were calculated for-all deaths and by cause. The effects of sex, age, SLE duration, race, and calendar-year periods were determined. Results. The overall SMR was 2.4 (95% confidence interval 2.3-2.5). Particularly high mortality was seen for circulatory disease, infections, renal disease, non-Hodgkin's lymphoma, and lung cancer. The highest SMR estimates were seen in patient groups characterized by female sex, younger age, SLE duration < 1 year, or black/African American race. There was a dramatic decrease in total SMR estimates across calendar-year periods, which was demonstrable for specific causes including death due to infections and death due to renal disorders. However, the SMR due to circulatory diseases tended to increase slightly from the 1970s to the year 2001. Conclusion. Our data from a very large multicenter international cohort emphasize what has been demonstrated previously in smaller samples. These results highlight the increased mortality rate in SLE patients compared with the general population, and they suggest particular risk associated with female sex, younger age, shorter SLE duration, and black/African American race. The risk for certain types of deaths, primarily related to lupus activity (such as renal disease), has decreased over time, while the risk for deaths due to circulatory disease does not appear to have diminished. (Less)
TL;DR: It is demonstrated that OR83b heterodimerizes with conventional ORs early in the endomembrane system in OSNs, couples these complexes to the conserved ciliary trafficking pathway, and is essential to maintain the OR/OR83b complex within the sensory cilia, where odor signal transduction occurs.
Abstract: Drosophila olfactory sensory neurons (OSNs) each express two odorant receptors (ORs): a divergent member of the OR family and the highly conserved, broadly expressed receptor OR83b. OR83b is essential for olfaction in vivo and enhances OR function in vitro, but the molecular mechanism by which it acts is unknown. Here we demonstrate that OR83b heterodimerizes with conventional ORs early in the endomembrane system in OSNs, couples these complexes to the conserved ciliary trafficking pathway, and is essential to maintain the OR/OR83b complex within the sensory cilia, where odor signal transduction occurs. The OR/OR83b complex is necessary and sufficient to promote functional reconstitution of odor-evoked signaling in sensory neurons that normally respond only to carbon dioxide. Unexpectedly, unlike all known vertebrate and nematode chemosensory receptors, we find that Drosophila ORs and OR83b adopt a novel membrane topology with their N-termini and the most conserved loops in the cytoplasm. These loops mediate direct association of ORs with OR83b. Our results reveal that OR83b is a universal and integral part of the functional OR in Drosophila. This atypical heteromeric and topological design appears to be an insect-specific solution for odor recognition, making the OR/OR83b complex an attractive target for the development of highly selective insect repellents to disrupt olfactory-mediated host-seeking behaviors of insect disease vectors.
Broad Institute1, University of Oxford2, Wellcome Trust Sanger Institute3, Wellcome Trust Centre for Human Genetics4, Utrecht University5, Science Applications International Corporation6, Illumina7, Duke University8, Brigham and Women's Hospital9, University of Cambridge10, Harvard University11, Imperial College London12, Université de Montréal13, Montreal Heart Institute14
TL;DR: The analysis provides informative tag SNPs that capture much of the common variation in the MHC region and that could be used in disease association studies, and it provides new insight into the evolutionary dynamics and ancestral origins of the HLA loci and their haplotypes.
Abstract: The proteins encoded by the classical HLA class I and class II genes in the major histocompatibility complex (MHC) are highly polymorphic and are essential in self versus non-self immune recognition. HLA variation is a crucial determinant of transplant rejection and susceptibility to a large number of infectious and autoimmune diseases. Yet identification of causal variants is problematic owing to linkage disequilibrium that extends across multiple HLA and non-HLA genes in the MHC. We therefore set out to characterize the linkage disequilibrium patterns between the highly polymorphic HLA genes and background variation by typing the classical HLA genes and >7,500 common SNPs and deletion-insertion polymorphisms across four population samples. The analysis provides informative tag SNPs that capture much of the common variation in the MHC region and that could be used in disease association studies, and it provides new insight into the evolutionary dynamics and ancestral origins of the HLA loci and their haplotypes.
TL;DR: The results of this large, contemporary, multi-institutional series show that radical cystectomy and pelvic lymphadenectomy provide durable local control and disease specific survival in patients with localized invasive transitional cell carcinoma.
01 Jan 2006
TL;DR: This work proposes to fight the curse of dimensionality by learning a distributed representation for words which allows each training sentence to inform the model about an exponential number of semantically neighboring sentences, and incorporates this new language model into a state-of-the-art speech recognizer of conversational speech.
Abstract: A central goal of statistical language modeling is to learn the joint probability function of sequences of words in a language. This is intrinsically difficult because of the curse of dimensionality: a word sequence on which the model will be tested is likely to be different from all the word sequences seen during training. Traditional but very successful approaches based on n-grams obtain generalization by concatenating very short overlapping sequences seen in the training set. We propose to fight the curse of dimensionality by learning a distributed representation for words which allows each training sentence to inform the model about an exponential number of semantically neighboring sentences. Generalization is obtained because a sequence of words that has never been seen before gets high probability if it is made of words that are similar (in the sense of having a nearby representation) to words forming an already seen sentence. Training such large models (with millions of parameters) within a reasonable time is itself a significant challenge. We report on several methods to speed-up both training and probability computation, as well as comparative experiments to evaluate the improvements brought by these techniques. We finally describe the incorporation of this new language model into a state-of-the-art speech recognizer of conversational speech.
TL;DR: The results suggest that most children learned relatively well to inhibit PA by the end of childhood and that a minority failed to do so, and about one sixth of children exhibited an atypical developmental pattern reflected in more frequent and stable use of PA.
Abstract: The objectives of the study were to model the developmental trajectories of physical aggression (PA) from toddlerhood to pre-adolescence and to identify risk factors that distinguish typical (normative) from atypical developmental patterns. Ten cohorts of approximately 1,000 children (n = 10,658) drawn form a nationally representative (Canadian) sample were followed over 6 years. Using a group based trajectory approach, we identified three groups of children with distinct developmental trajectories between 2 and 11 years of age. One third of the children (31.1%) followed a low desisting trajectory, reflected in infrequent use of PA in toddlerhood and virtually no PA by pre-adolescence. The majority of children (52.2%) followed a moderate desisting trajectory, reflected in occasional use of PA in toddlerhood and infrequent use by pre-adolescence. One sixth of the children (16.6%) followed a high stable trajectory of PA. Multivariate logistic regression indicated that children in the high PA trajectory group were more likely to be boys (OR: 1.67; CI: 1.5–1.87), from low income families (OR: 1.4; CI; 1.27–1.67), from families where the mother had not completed high school (OR: 1.20; CI: 1.05–1.38) and who reported using hostile/ineffective parenting strategies (OR: 1.16; CI: 1.14–1.18). In sum, the results indicate that the typical developmental pattern of PA was one of occasional and declining use over time. However, about one sixth of children, mostly boys from disadvantaged families, exhibited an atypical developmental pattern reflected in more frequent and stable use of PA. The results suggest that most children learned relatively well to inhibit PA by the end of childhood and that a minority failed to do so. Family risks traditionally found to be associated with antisocial behaviors during adolescence appear to interfere with the socialization of PA during early and middle childhood.
TL;DR: Lamoureux and MacKerell as discussed by the authors used the SWM4-NDP model for negatively charged Drude particles and showed that it yields the correct liquid viscosity and free energy of hydration.
TL;DR: It is proposed that virulence in this organism is both multifactorial and combinatorial, the result of a pool of pathogenicity-related genes that interact in various combinations in different genetic backgrounds.
Abstract: Background: Pseudomonas aeruginosa is a ubiquitous environmental bacterium and an important opportunistic human pathogen. Generally, the acquisition of genes in the form of pathogenicity islands distinguishes pathogenic isolates from nonpathogens. We therefore sequenced a highly virulent strain of P. aeruginosa, PA14, and compared it with a previously sequenced (and less pathogenic) strain, PAO1, to identify novel virulence genes. Results: The PA14 and PAO1 genomes are remarkably similar, although PA14 has a slightly larger genome (6.5 megabses [Mb]) than does PAO1 (6.3 Mb). We identified 58 PA14 gene clusters that are absent in PAO1 to determine which of these genes, if any, contribute to its enhanced virulence in a Caenorhabditis elegans pathogenicity model. First, we tested 18 additional diverse strains in the C. elegans model and observed a wide range of pathogenic potential; however, genotyping these strains using a custom microarray showed that the presence of PA14 genes that are absent in PAO1 did not correlate with the virulence of these strains. Second, we utilized a full-genome nonredundant mutant library of PA14 to identify five genes (absent in PAO1) required for C. elegans killing. Surprisingly, although these five genes are present in many other P. aeruginosa strains, they do not correlate with virulence in C. elegans. Conclusion: Genes required for pathogenicity in one strain of P. aeruginosa are neither required for nor predictive of virulence in other strains. We therefore propose that virulence in this organism is both multifactorial and combinatorial, the result of a pool of pathogenicity-related genes that interact in various combinations in different genetic backgrounds.
TL;DR: The present review will focus on structure‐function relationships pertinent to understanding periodontal tissue breakdown and the repair ⁄ regeneration of affected structures.
Abstract: The periodontium, defined as those tissues supporting and investing the tooth, comprises root cementum, periodontal ligament, bone lining the tooth socket (alveolar bone), and that part of the gingiva facing the tooth (dentogingival junction). The widespread occurrence of periodontal diseases and the realization that lost tissues can be repaired and, perhaps, regenerated has generated considerable interest in the factors and cells regulating their formation and maintenance. It is important to understand that each of the periodontal components has its very specialized structure and that these structural characteristics directly define function. Indeed, proper functioning of the periodontium is only achieved through structural integrity and interaction between its components. In recent years, a number of detailed descriptions of the structural and compositional features of periodontal tissues have been published (3, 5‐7, 9, 15, 17, 46, 50, 56, 58, 61); we refer the reader to these for a comprehensive description of the development, formation, and structure of periodontal tissues. The present review will focus on structure‐function relationships pertinent to understanding periodontal tissue breakdown and the repair ⁄ regeneration of affected structures.
TL;DR: Patients infected with HCV genotype 1 and treated with peginterferon α‐2a/ribavirin sustained a RVR 24% of the time, which portends an 89% probability of a SVR after 24 weeks of treatment.
TL;DR: In this paper, four LEP collaborations, ALEPH, DELPHI, L3 and OPAL, have searched for the neutral Higgs bosons which are predicted by the minimal supersymmetric standard model (MSSM).
Abstract: The four LEP collaborations, ALEPH, DELPHI, L3 and OPAL, have searched for the neutral Higgs bosons which are predicted by the Minimal Supersymmetric standard model (MSSM). The data of the four collaborations are statistically combined and examined for their consistency with the background hypothesis and with a possible Higgs boson signal. The combined LEP data show no significant excess of events which would indicate the production of Higgs bosons. The search results are used to set upper bounds on the cross-sections of various Higgs-like event topologies. The results are interpreted within the MSSM in a number of “benchmark” models, including CP-conserving and CP-violating scenarios. These interpretations lead in all cases to large exclusions in the MSSM parameter space. Absolute limits are set on the parameter cosβ and, in some scenarios, on the masses of neutral Higgs bosons.
TL;DR: The main hepatic lesion induced by preoperative FU/oxaliplatin chemotherapy in patients with CLM is vascular and not steatosis, and the risk for other postoperative complications is related to the duration of preoperative chemotherapy administration.
Abstract: Purpose Preoperative chemotherapy for colorectal liver metastases (CLM) can produce histologic changes in the nontumor-bearing liver (NTBL) that may impact on surgical outcomes. Patients and Methods From a cohort of 303 patients treated for CLM with liver resection, 92 patients (75 received preoperative chemotherapy: group C+; and 17 were chemotherapy naive: group C−) were randomly selected for detailed pathologic analysis. Preoperative chemotherapy consisted of fluorouracil (FU)/leucovorin alone (23 patients, the majority chronomodulated) or in combination with oxaliplatin (52 patients, all chronomodulated). To determine associations between study factors, clinical and operative variables were compared with pathology data and surgical outcomes. Results Although clinical and operative factors were similarly distributed, C+ patients, compared with C− patients, were more likely to receive intraoperative RBC transfusions (mean units: 1.9 v 0.5, respectively; P = .03) and to have vascular abnormalities in the...
TL;DR: A review of the current state of the art in this area and also discusses likely future developments can be found in this paper, where the authors discuss areas in which significant advances are likely to be made or are needed.
Abstract: Environmental Context. The fate and behaviour of trace pollutants are very strongly modified, and usually dominated, by their physical and chemical interactions with naturally occurring aquatic colloids (defined as solid phase material with one dimension between 1 nm and 1 μm). This review summarises the area and key advances in the field of natural aquatic colloids, including technique development and quantification of colloidal structure and interactions with pollutants. The review also discusses areas in which significant advances are likely to be made or are needed and, as such, provides a framework for further work in the next few years. Abstract. Natural aquatic colloids are materials with one dimension between 1 nm and 1 μm. More informally defined, nanoparticles are materials with at least one dimension less than 100 nm. Both colloids and nanoparticles have significant effects on pollutant, nutrient, and pathogen chemistry, transport and bioavailability, and may themselves be bioavailable. Techniques for their fractionation, characterization and analysis have improved greatly in recent years. Although knowledge of their structure and environmental impact has also increased, it has not done so to the same degree and thus the field awaits the substantial application of new methodologies. This paper reviews the current state of the art in this area and also discusses likely future developments.