Showing papers by "Université de Montréal published in 2009"

Learning Deep Architectures for AI

Abstract: Can machine learning deliver AI? Theoretical results, inspiration from the brain and cognition, as well as machine learning experiments suggest that in order to learn the kind of complicated functions that can represent high-level abstractions (e.g. in vision, language, and other AI-level tasks), one would need deep architectures. Deep architectures are composed of multiple levels of non-linear operations, such as in neural nets with many hidden layers, graphical models with many levels of latent variables, or in complicated propositional formulae re-using many sub-formulae. Each level of the architecture represents features at a different level of abstraction, defined as a composition of lower-level features. Searching the parameter space of deep architectures is a difficult task, but new algorithms have been discovered and a new sub-area has emerged in the machine learning community since 2006, following these discoveries. Learning algorithms such as those for Deep Belief Networks and other related unsupervised learning algorithms have recently been proposed to train deep architectures, yielding exciting results and beating the state-of-the-art in certain areas. Learning Deep Architectures for AI discusses the motivations for and principles of learning algorithms for deep architectures. By analyzing and comparing recent results with different learning algorithms for deep architectures, explanations for their success are proposed and discussed, highlighting challenges and suggesting avenues for future explorations in this area.

Effects of stress throughout the lifespan on the brain, behaviour and cognition

Abstract: Chronic exposure to stress hormones, whether it occurs during the prenatal period, infancy, childhood, adolescence, adulthood or aging, has an impact on brain structures involved in cognition and mental health. However, the specific effects on the brain, behaviour and cognition emerge as a function of the timing and the duration of the exposure, and some also depend on the interaction between gene effects and previous exposure to environmental adversity. Advances in animal and human studies have made it possible to synthesize these findings, and in this Review a model is developed to explain why different disorders emerge in individuals exposed to stress at different times in their lives.

A systematic analysis of performance measures for classification tasks

Abstract: This paper presents a systematic analysis of twenty four performance measures used in the complete spectrum of Machine Learning classification tasks, i.e., binary, multi-class, multi-labelled, and hierarchical. For each classification task, the study relates a set of changes in a confusion matrix to specific characteristics of data. Then the analysis concentrates on the type of changes to a confusion matrix that do not change a measure, therefore, preserve a classifier's evaluation (measure invariance). The result is the measure invariance taxonomy with respect to all relevant label distribution changes in a classification problem. This formal analysis is supported by examples of applications where invariance properties of measures lead to a more reliable evaluation of classifiers. Text classification supplements the discussion with several case studies.

Associations between species and groups of sites: indices and statistical inference

Abstract: Ecologists often face the task of studying the association between single species and one or several groups of sites representing habitat types, community types, or other categories. Besides characterizing the ecological preference of the species, the strength of the association usually presents a lot of interest for conservation biology, landscape mapping and management, and natural reserve design, among other applications. The indices most frequently employed to assess these relationships are the phi coefficient of association and the indicator value index (IndVal). We compare these two approaches by putting them into a broader framework of related measures, which includes several new indices. We present permutation tests to assess the statistical significance of species-site group associations and bootstrap methods for obtaining confidence intervals. Correlation measures, such as the phi coefficient, are more context-dependent than indicator values but allow focusing on the preference of the species. In contrast, the two components of an indicator value index directly assess the value of the species as a bioindicator because they can be interpreted as its positive predictive value and sensitivity. Ecologists should select the most appropriate index of association strength according to their objective and then compute confidence intervals to determine the precision of the estimate.

Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis.

Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal degenerative motor neuron disorder Ten percent of cases are inherited; most involve unidentified genes We report here 13 mutations in the fused in sarcoma/translated in liposarcoma (FUS/TLS) gene on chromosome 16 that were specific for familial ALS The FUS/TLS protein binds to RNA, functions in diverse processes, and is normally located predominantly in the nucleus In contrast, the mutant forms of FUS/TLS accumulated in the cytoplasm of neurons, a pathology that is similar to that of the gene TAR DNA-binding protein 43 (TDP43), whose mutations also cause ALS Neuronal cytoplasmic protein aggregation and defective RNA metabolism thus appear to be common pathogenic mechanisms involved in ALS and possibly in other neurodegenerative disorders

HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation

Abstract: HIV persists in a reservoir of latently infected CD4+ T cells in individuals treated with highly active antiretroviral therapy (HAART). Here we identify central memory (TCM) and transitional memory (TTM) CD4+ T cells as the major cellular reservoirs for HIV and find that viral persistence is ensured by two different mechanisms. HIV primarily persists in TCM cells in subjects showing reconstitution of the CD4+ compartment upon HAART. This reservoir is maintained through T cell survival and low-level antigen-driven proliferation and is slowly depleted with time. In contrast, proviral DNA is preferentially detected in TTM cells from aviremic individuals with low CD4+ counts and higher amounts of interleukin-7–mediated homeostatic proliferation, a mechanism that ensures the persistence of these cells. Our results suggest that viral eradication might be achieved through the combined use of strategic interventions targeting viral replication and, as in cancer, drugs that interfere with the self renewal and persistence of proliferating memory T cells.

FactSage thermochemical software and databases - recent developments

Abstract: FactSage® was introduced in 2001 as the fusion of the F*A*C*T/FACT-Win and ChemSage thermochemical packages. The FactSage package runs on a PC operating under Microsoft Windows® and consists of a series of information, database, calculation and manipulation modules that enable one to access and manipulate pure substances and solution databases. With the various modules one can perform a wide variety of thermochemical calculations and generate tables, graphs and figures of interest to chemical and physical metallurgists, chemical engineers, corrosion engineers, inorganic chemists, geochemists, ceramists, electrochemists, environmentalists, etc. This paper presents a summary of the recent developments in the FactSage thermochemical software and databases. In the article, emphasis is placed on the new databases and the calculation and manipulation of phase diagrams and complex phase equilibria.

PhyloBayes 3

Abstract: Motivation: A variety of probabilistic models describing the evolution of DNA or protein sequences have been proposed for phylogenetic reconstruction or for molecular dating. However, there still lacks a common implementation allowing one to freely combine these independent features, so as to test their ability to jointly improve phylogenetic and dating accuracy. Results: We propose a software package, PhyloBayes 3, which can be used for conducting Bayesian phylogenetic reconstruction and molecular dating analyses, using a large variety of amino acid replacement and nucleotide substitution models, including empirical mixtures or non-parametric models, as well as alternative clock relaxation processes. Availability: PhyloBayes is freely available from our web site http://www.phylobayes.org. It works under Linux, Mac OsX and Windows operating systems. Contact: nicolas.lartillot@umontreal.ca Supplementary information:Supplementary data are available at Bioinformatics online.

A Sensitive Cardiac Troponin T Assay in Stable Coronary Artery Disease

Abstract: Background In most patients with stable coronary artery disease, plasma cardiac troponin T levels are below the limit of detection for the conventional assay. The distribution and determinants of very low circulating troponin T levels, as well as their association with cardiovascular events, in such patients are unknown. Methods We used a new, high-sensitivity assay to determine the concentration of cardiac troponin T in plasma samples from 3679 patients with stable coronary artery disease and preserved left ventricular function. Results of the assay were analyzed in relation to the incidence of cardiovascular events during a median follow-up period of 5.2 years. Results With the highly sensitive assay, concentrations of cardiac troponin T were at or above the limit of detection (0.001 μg per liter) in 3593 patients (97.7%) and at or above the 99th percentile for apparently healthy subjects (0.0133 μg per liter) in 407 patients (11.1%). After adjustment for other independent prognostic indicators, there w...

The SECOQC quantum key distribution network in Vienna

Abstract: In this paper, we present the quantum key distribution (QKD) network designed and implemented by the European project SEcure COmmunication based on Quantum Cryptography (SECOQC) (2004?2008), unifying the efforts of 41 research and industrial organizations. The paper summarizes the SECOQC approach to QKD networks with a focus on the trusted repeater paradigm. It discusses the architecture and functionality of the SECOQC trusted repeater prototype, which has been put into operation in Vienna in 2008 and publicly demonstrated in the framework of a SECOQC QKD conference held from October 8 to 10, 2008. The demonstration involved one-time pad encrypted telephone communication, a secure (AES encryption protected) video-conference with all deployed nodes and a number of rerouting experiments, highlighting basic mechanisms of the SECOQC network functionality.The paper gives an overview of the eight point-to-point network links in the prototype and their underlying technology: three plug and play systems by id Quantique, a one way weak pulse system from Toshiba Research in the UK, a coherent one-way system by GAP Optique with the participation of id Quantique and the AIT Austrian Institute of Technology (formerly ARC), an entangled photons system by the University of Vienna and the AIT, a continuous-variables system by Centre National de la Recherche Scientifique (CNRS) and THALES Research and Technology with the participation of Universit? Libre de Bruxelles, and a free space link by the Ludwig Maximillians University in Munich connecting two nodes situated in adjacent buildings (line of sight 80?m). The average link length is between 20 and 30?km, the longest link being 83?km.The paper presents the architecture and functionality of the principal networking agent?the SECOQC node module, which enables the authentic classical communication required for key distillation, manages the generated key material, determines a communication path between any destinations in the network, and realizes end-to-end secure transport of key material between these destinations.The paper also illustrates the operation of the network in a number of typical exploitation regimes and gives an initial estimate of the network transmission capacity, defined as the maximum amount of key that can be exchanged, or alternatively the amount of information that can be transmitted with information theoretic security, between two arbitrary nodes.

Albuminuria and Kidney Function Independently Predict Cardiovascular and Renal Outcomes in Diabetes

Abstract: There are limited data regarding whether albuminuria and reduced estimated GFR (eGFR) are separate and independent risk factors for cardiovascular and renal events among individuals with type 2 diabetes. The Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study examined the effects of routine BP lowering on adverse outcomes in type 2 diabetes. We investigated the effects of urinary albumin-to-creatinine ratio (UACR) and eGFR on the risk for cardiovascular and renal events in 10,640 patients with available data. During an average 4.3-yr follow-up, 938 (8.8%) patients experienced a cardiovascular event and 107 (1.0%) experienced a renal event. The multivariable-adjusted hazard ratio for cardiovascular events was 2.48 (95% confidence interval 1.74 to 3.52) for every 10-fold increase in baseline UACR and 2.20 (95% confidence interval 1.09 to 4.43) for every halving of baseline eGFR, after adjustment for regression dilution. There was no evidence of interaction between the effects of higher UACR and lower eGFR. Patients with both UACR >300 mg/g and eGFR <60 ml/min per 1.73 m(2) at baseline had a 3.2-fold higher risk for cardiovascular events and a 22.2-fold higher risk for renal events, compared with patients with neither of these risk factors. In conclusion, high albuminuria and low eGFR are independent risk factors for cardiovascular and renal events among patients with type 2 diabetes.

Frequency and Evolution of Azole Resistance in Aspergillus fumigatus Associated with Treatment Failure

Abstract: Azoles are the mainstay of oral therapy for aspergillosis. Azole resistance in Aspergillus has been reported infrequently. The first resistant isolate was detected in 1999 in Manchester, UK. In a clinical collection of 519 A. fumigatus isolates, the frequency of itraconazole resistance was 5%, a significant increase since 2004 (p<0.001). Of the 34 itraconazole-resistant isolates we studied, 65% (22) were cross-resistant to voriconazole and 74% (25) were cross-resistant to posaconazole. Thirteen of 14 evaluable patients in our study had prior azole exposure; 8 infections failed therapy (progressed), and 5 failed to improve (remained stable). Eighteen amino acid alterations were found in the target enzyme, Cyp51A, 4 of which were novel. A population genetic analysis of microsatellites showed the existence of resistant mutants that evolved from originally susceptible strains, different cyp51A mutations in the same strain, and microalterations in microsatellite repeat number. Azole resistance in A. fumigatus is an emerging problem and may develop during azole therapy.

Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial.

Abstract: Context Coronary artery disease (CAD) is the major cause of mortality and morbidity in patients with type 2 diabetes. But the utility of screening patients with type 2 diabetes for asymptomatic CAD is controversial. Objective To assess whether routine screening for CAD identifies patients with type 2 diabetes as being at high cardiac risk and whether it affects their cardiac outcomes. Design, Setting, and Patients The Detection of Ischemia in Asymptomatic Diabetics (DIAD) study is a randomized controlled trial in which 1123 participants with type 2 diabetes and no symptoms of CAD were randomly assigned to be screened with adenosine-stress radionuclide myocardial perfusion imaging (MPI) or not to be screened. Participants were recruited from diabetes clinics and practices and prospectively followed up from August 2000 to September 2007. Main Outcome Measure Cardiac death or nonfatal myocardial infarction (MI). Results The cumulative cardiac event rate was 2.9% over a mean (SD) follow-up of 4.8 (0.9) years for an average of 0.6% per year. Seven nonfatal MIs and 8 cardiac deaths (2.7%) occurred among the screened group and 10 nonfatal MIs and 7 cardiac deaths (3.0%) among the not-screened group (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.44-1.88; P = .73). Of those in the screened group, 409 participants with normal results and 50 with small MPI defects had lower event rates than the 33 with moderate or large MPI defects; 0.4% per year vs 2.4% per year (HR, 6.3; 95% CI, 1.9-20.1; P = .001). Nevertheless, the positive predictive value of having moderate or large MPI defects was only 12%. The overall rate of coronary revascularization was low in both groups: 31 (5.5%) in the screened group and 44 (7.8%) in the unscreened group (HR, 0.71; 95% CI, 0.45-1.1; P = .14). During the course of study there was a significant and equivalent increase in primary medical prevention in both groups. Conclusion In this contemporary study population of patients with diabetes, the cardiac event rates were low and were not significantly reduced by MPI screening for myocardial ischemia over 4.8 years. Trial Registration clinicaltrials.gov Identifier: NCT00769275

Coronary Bypass Surgery with or without Surgical Ventricular Reconstruction

Abstract: Background Surgical ventricular reconstruction is a specific procedure designed to reduce left ventricular volume in patients with heart failure caused by coronary artery disease. We conducted a trial to address the question of whether surgical ventricular reconstruction added to coronary-artery bypass grafting (CABG) would decrease the rate of death or hospitalization for cardiac causes, as compared with CABG alone. Methods Between September 2002 and January 2006, a total of 1000 patients with an ejection fraction of 35% or less, coronary artery disease that was amenable to CABG, and dominant anterior left ventricular dysfunction that was amenable to surgical ventricular reconstruction were randomly assigned to undergo either CABG alone (499 patients) or CABG with surgical ventricular reconstruction (501 patients). The primary outcome was a composite of death from any cause and hospitalization for cardiac causes. The median follow-up was 48 months. Results Surgical ventricular reconstruction reduced the end-systolic volume index by 19%, as compared with a reduction of 6% with CABG alone. Cardiac symptoms and exercise tolerance improved from baseline to a similar degree in the two study groups. However, no significant difference was observed in the primary outcome, which occurred in 292 patients (59%) who were assigned to undergo CABG alone and in 289 patients (58%) who were assigned to undergo CABG with surgical ventricular reconstruction (hazard ratio for the combined approach, 0.99; 95% confidence interval, 0.84 to 1.17; P = 0.90). Conclusions Adding surgical ventricular reconstruction to CABG reduced the left ventricular volume, as compared with CABG alone. However, this anatomical change was not associated with a greater improvement in symptoms or exercise tolerance or with a reduction in the rate of death or hospitalization for cardiac causes. (ClinicalTrials. gov number, NCT00023595.)

Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop.

Abstract: Background: At the Third International Workshop on Asymptomatic Primary Hyperparathyroidism (PHPT) in May 2008, recent data on the disease were reviewed. We present the results of a literature review on issues arising from the clinical presentation and natural history of PHPT. Methods: Questions were developed by the International Task Force on PHPT. A comprehensive literature search for relevant studies was reviewed, and the questions of the International Task Force were addressed by the Consensus Panel. Conclusions: 1) Data on the extent and nature of cardiovascular involvement in those with mild disease are too limited to provide a complete picture. 2) Patients with mild PHPT have neuropsychological complaints. Although some symptoms may improve with surgery, available data remain inconsistent on their precise nature and reversibility. 3) Surgery leads to long-term gains in spine, hip, and radius bone mineral density (BMD). Because some patients have early disease progression and others lose BMD after ...

A genome-wide linkage and association scan reveals novel loci for autism

Abstract: Although autism is a highly heritable neurodevelopmental disorder, attempts to identify specific susceptibility genes have thus far met with limited success. Genome-wide association studies using half a million or more markers, particularly those with very large sample sizes achieved through meta-analysis, have shown great success in mapping genes for other complex genetic traits. Consequently, we initiated a linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms (SNPs) in a common set of 1,031 multiplex autism families (1,553 affected offspring). We identified regions of suggestive and significant linkage on chromosomes 6q27 and 20p13, respectively. Initial analysis did not yield genome-wide significant associations; however, genotyping of top hits in additional families revealed an SNP on chromosome 5p15 (between SEMA5A and TAS2R1) that was significantly associated with autism (P = 2 x 10(-7)). We also demonstrated that expression of SEMA5A is reduced in brains from autistic patients, further implicating SEMA5A as an autism susceptibility gene. The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants.

Characterizing Manufactured Nanoparticles in the Environment: Multimethod Determination of Particle Sizes

Abstract: Sizes of stabilized (24 h) nanoparticle suspensions were determined using several state-of-the-art analytical techniques (transmission electron microscopy; atomic force microscopy; dynamic light scattering; fluorescence correlation spectroscopy; nanoparticle tracking analysis; flow field flow fractionation). Theoretical and analytical considerations were evaluated, results were compared, and the advantages and limitations of the techniques were discussed. No "ideal" technique was found for characterizing manufactured nanoparticles in an environmental context as each technique had its own advantages and limitations.

Partitioning beta diversity in a subtropical broad-leaved forest of China

Abstract: The classical environmental control model assumes that species distribution is determined by the spatial variation of underlying habitat conditions. This niche-based model has recently been challenged by the neutral theory of biodiversity which assumes that ecological drift is a key process regulating species coexistence. Understanding the mechanisms that maintain biodiversity in communities critically depends on our ability to decompose the variation of diversity into the contributions of different processes affecting it. Here we investigated the effects of pure habitat, pure spatial, and spatially structured habitat processes on the distributions of species richness and species composition in a recently established 24-ha stem-mapping plot in the subtropical evergreen broad-leaved forest of Gutianshan National Nature Reserve in East China. We used the new spatial analysis method of principal coordinates of neighbor matrices (PCNM) to disentangle the contributions of these processes. The results showed that (1) habitat and space jointly explained approximately 53% of the variation in richness and approximately 65% of the variation in species composition, depending on the scale (sampling unit size); (2) tree diversity (richness and composition) in the Gutianshan forest was dominantly controlled by spatially structured habitat (24%) and habitat-independent spatial component (29%); the spatially independent habitat contributed a negligible effect (6%); (3) distributions of richness and species composition were strongly affected by altitude and terrain convexity, while the effects of slope and aspect were weak; (4) the spatial distribution of diversity in the forest was dominated by broad-scaled spatial variation; (5) environmental control on the one hand and unexplained spatial variation on the other (unmeasured environmental variables and neutral processes) corresponded to spatial structures with different scales in the Gutianshan forest plot; and (6) five habitat types were recognized; a few species were statistically significant indicators of three of these habitats, whereas two habitats had no significant indicator species. The results suggest that the diversity of the forest is equally governed by environmental control (30%) and neutral processes (29%). In the fine-scale analysis (10 x 10 m cells), neutral processes dominated (43%) over environmental control (20%).

Investing in early human development: timing and economic efficiency.

Abstract: Policy discussions to ameliorate socioeconomic (SES) inequalities are increasingly focused on investments in early childhood. Yet such interventions are costly to implement, and clear evidence on the optimal time to intervene to yield a high economic and social return in the future is meagre. The majority of successful early childhood interventions start in the preschool years. However socioeconomic gradients in cognitive skills, socio-emotional functioning and health can be observed by age three, suggesting that preventative programmes starting earlier in childhood may be even more effective. We discuss the optimal timing of early childhood intervention with reference to recent research in developmental neuroscience. We motivate the need for early intervention by providing an overview of the impact of adverse risk factors during the antenatal and early childhood periods on outcomes later in life. We provide a brief review of the economic rationale for investing early in life and propose the “antenatal investment hypothesis”. We conclude by discussing a suite of new European interventions that will inform this optimal timing debate.

Increased Expression of IL-33 in Severe Asthma: Evidence of Expression by Airway Smooth Muscle Cells

Abstract: IL-33, a new member of the IL-1 cytokine family, promotes Th2 inflammation, but evidence on the implications of this cytokine in asthma is lacking IL-33 would be mainly expressed by structural cells, but whether proinflammatory cytokines modulate its expression in airway smooth muscle cells (ASMC) is unknown Endobronchial biopsies were obtained from adults with mild (n = 8), moderate (n = 8), severe (n = 9), asthma and from control subjects (n = 5) Immunocytochemistry, laser-capture microdissection, reverse transcriptase, and real-time quantitative PCR were used for determining IL-33 expression in the lung tissues ASMC isolated from resected lung specimens were cultured with proinflammatory cytokines and with dexamethasone IL-33 expression by ASMC was determined by PCR, ELISA, and Western blotting Higher levels of IL-33 transcripts are detected in biopsies from asthmatic compared with control subjects, and especially in subjects with severe asthma ASMC show IL-33 expression at both protein and mRNA levels IL-33 and TNF-alpha transcript levels correlate in the lung tissues, and TNF-alpha up-regulates IL-33 expression by cultured ASMC in a time- and dose-dependent manner IFN-gamma also increases IL-33 expression and shows synergistic effect with TNF-alpha Dexamethasone fails to abolish TNF-alpha-induced IL-33 up-regulation IL-33 expression increases in bronchial biopsies from subjects with asthma compared with controls, as well as subjects with asthma severity ASMC are a source of the IL-33 cytokine Our data propose IL-33 as a novel inflammatory marker of severe and refractory asthma