Fast and Rigorous Computation of Gene and Pathway Scores from SNP-Based Summary Statistics.

Integrating single nucleotide polymorphism (SNP) p-values from genome-wide association studies (GWAS) across genes and pathways is a strategy to improve statistical power and gain biological insight. Here, we present Pascal (Pathway scoring algorithm), a powerful tool for computing gene and pathway scores from SNP-phenotype association summary statistics. For gene score computation, we implemented analytic and efficient numerical solutions to calculate test statistics. We examined in particular the sum and the maximum of chi-squared statistics, which measure the strongest and the average association signals per gene, respectively. For pathway scoring, we use a modified Fisher method, which offers not only significant power improvement over more traditional enrichment strategies, but also eliminates the problem of arbitrary threshold selection inherent in any binary membership based pathway enrichment approach. We demonstrate the marked increase in power by analyzing summary statistics from dozens of large meta-studies for various traits. Our extensive testing indicates that our method not only excels in rigorous type I error control, but also results in more biologically meaningful discoveries.

Monte Carlo derivation of filtered tungsten anode X-ray spectra for dose computation in digital mammography

Abstract Objective: Derive filtered tungsten X-ray spectra used in digital mammography systems by means of Monte Carlo simulations. Materials and Methods: Filtered spectra for rhodium filter were obtained for tube potentials between 26 and 32 kV. The half-value layer (HVL) of simulated filtered spectra were compared with those obtained experimentally with a solid state detector Unfors model 8202031-H Xi R/F & MAM Detector Platinum and 8201023-C Xi Base unit Platinum Plus w mAs in a Hologic Selenia Dimensions system using a direct radiography mode. Results: Calculated HVL values showed good agreement as compared with those obtained experimentally. The greatest relative difference between the Monte Carlo calculated HVL values and experimental HVL values was 4%. Conclusion: The results show that the filtered tungsten anode X-ray spectra and the EGSnrc Monte Carlo code can be used for mean glandular dose determination in mammography.

Anàlisi energètic de deformació incremental de xapa en materials polimèrics

Existeixen diversos estudis que avaluen el consum energètic derivat del procés de producció deISF (Incremental Sheet Forming), principalment per materials metàl•lics. Per tant, l’objectiu d’aquest projecte ésdeterminar el consum energètic en la conformació de materials plàstics en aquest procés.S’estudiarà el consum energètic mesurant l’energia elèctrica necessària per al procés, utilitzantdiferents paràmetres i estratègies de fabricació, com poden ser diferents materialspolimèrics, trajectòries variades de conformat, diferents velocitats d’avanç i rotació i diferentsgeometries.Un cop analitzat el consum energètic derivat de la fabricació amb ISF es valorarà l’impacteambiental que provoca aquesta tecnologia

Optimizing Customer Energy Invoice Calculation with Parallel Computation

Diplomityön tarkoituksena on optimoida asiakkaiden sähkölaskun laskeminen hajautetun laskennan avulla. Älykkäiden etäluettavien energiamittareiden tullessa jokaiseen kotitalouteen, energiayhtiöt velvoitetaan laskemaan asiakkaiden sähkölaskut tuntiperusteiseen mittaustietoon perustuen. Kasvava tiedonmäärä lisää myös tarvittavien laskutehtävien määrää. Työssä arvioidaan vaihtoehtoja hajautetun laskennan toteuttamiseksi ja luodaan tarkempi katsaus pilvilaskennan mahdollisuuksiin. Lisäksi ajettiin simulaatioita, joiden avulla arvioitiin rinnakkaislaskennan ja peräkkäislaskennan eroja. Sähkölaskujen oikeinlaskemisen tueksi kehitettiin mittauspuu-algoritmi.

Potential and Challenges of Analog Reconfigurable Computation in Modern and Future CMOS

In this work, the feasibility of the floating-gate technology in analog computing platforms in a scaled down general-purpose CMOS technology is considered. When the technology is scaled down the performance of analog circuits tends to get worse because the process parameters are optimized for digital transistors and the scaling involves the reduction of supply voltages. Generally, the challenge in analog circuit design is that all salient design metrics such as power, area, bandwidth and accuracy are interrelated. Furthermore, poor flexibility, i.e. lack of reconfigurability, the reuse of IP etc., can be considered the most severe weakness of analog hardware. On this account, digital calibration schemes are often required for improved performance or yield enhancement, whereas high flexibility/reconfigurability can not be easily achieved. Here, it is discussed whether it is possible to work around these obstacles by using floating-gate transistors (FGTs), and analyze problems associated with the practical implementation. FGT technology is attractive because it is electrically programmable and also features a charge-based built-in non-volatile memory. Apart from being ideal for canceling the circuit non-idealities due to process variations, the FGTs can also be used as computational or adaptive elements in analog circuits. The nominal gate oxide thickness in the deep sub-micron (DSM) processes is too thin to support robust charge retention and consequently the FGT becomes leaky. In principle, non-leaky FGTs can be implemented in a scaled down process without any special masks by using “double”-oxide transistors intended for providing devices that operate with higher supply voltages than general purpose devices. However, in practice the technology scaling poses several challenges which are addressed in this thesis. To provide a sufficiently wide-ranging survey, six prototype chips with varying complexity were implemented in four different DSM process nodes and investigated from this perspective. The focus is on non-leaky FGTs, but the presented autozeroing floating-gate amplifier (AFGA) demonstrates that leaky FGTs may also find a use. The simplest test structures contain only a few transistors, whereas the most complex experimental chip is an implementation of a spiking neural network (SNN) which comprises thousands of active and passive devices. More precisely, it is a fully connected (256 FGT synapses) two-layer spiking neural network (SNN), where the adaptive properties of FGT are taken advantage of. A compact realization of Spike Timing Dependent Plasticity (STDP) within the SNN is one of the key contributions of this thesis. Finally, the considerations in this thesis extend beyond CMOS to emerging nanodevices. To this end, one promising emerging nanoscale circuit element - memristor - is reviewed and its applicability for analog processing is considered. Furthermore, it is discussed how the FGT technology can be used to prototype computation paradigms compatible with these emerging two-terminal nanoscale devices in a mature and widely available CMOS technology.

Relationship between work rate and oxygen uptake in mitochondrial myopathy during ramp-incremental exercise

We determined the response characteristics and functional correlates of the dynamic relationship between the rate (Δ) of oxygen consumption ( O2) and the applied power output (work rate = WR) during ramp-incremental exercise in patients with mitochondrial myopathy (MM). Fourteen patients (7 males, age 35.4 ± 10.8 years) with biopsy-proven MM and 10 sedentary controls (6 males, age 29.0 ± 7.8 years) took a ramp-incremental cycle ergometer test for the determination of the O2 on-exercise mean response time (MRT) and the gas exchange threshold (GET). The ΔO2/ΔWR slope was calculated up to GET (S1), above GET (S2) and over the entire linear portion of the response (S T). Knee muscle endurance was measured by isokinetic dynamometry. As expected, peak O2 and muscle performance were lower in patients than controls (P < 0.05). Patients had significantly lower ΔO2/ΔWR than controls, especially the S2 component (6.8 ± 1.5 vs 10.3 ± 0.6 mL·min-1·W-1, respectively; P < 0.001). There were significant relationships between ΔO2/ΔWR (S T) and muscle endurance, MRT-O2, GET and peak O2 in MM patients (P < 0.05). In fact, all patients with ΔO2/ΔWR below 8 mL·min-1·W-1 had severely reduced peak O2 values (<60% predicted). Moreover, patients with higher cardiopulmonary stresses during exercise (e.g., higher Δ ventilation/carbon dioxide output and Δ heart rate/ΔO2) had lower ΔO2/ΔWR (P < 0.05). In conclusion, a readily available, effort-independent index of aerobic dysfunction during dynamic exercise (ΔO2/ΔWR) is typically reduced in patients with MM, being related to increased functional impairment and higher cardiopulmonary stress.

Reliability and validity of heart rate variability threshold assessment during an incremental shuttle-walk test in middle-aged and older adults

Studies on the assessment of heart rate variability threshold (HRVT) during walking are scarce. We determined the reliability and validity of HRVT assessment during the incremental shuttle walk test (ISWT) in healthy subjects. Thirty-one participants aged 57 ± 9 years (17 females) performed 3 ISWTs. During the 1st and 2nd ISWTs, instantaneous heart rate variability was calculated every 30 s and HRVT was measured. Walking velocity at HRVT in these tests (WV-HRVT1 and WV-HRVT2) was registered. During the 3rd ISWT, physiological responses were assessed. The ventilatory equivalents were used to determine ventilatory threshold (VT) and the WV at VT (WV-VT) was recorded. The difference between WV-HRVT1 and WV-HRVT2 was not statistically significant (median and interquartile range = 4.8; 4.8 to 5.4 vs4.8; 4.2 to 5.4 km/h); the correlation between WV-HRVT1 and WV-HRVT2 was significant (r = 0.84); the intraclass correlation coefficient was high (0.92; 0.82 to 0.96), and the agreement was acceptable (-0.08 km/h; -0.92 to 0.87). The difference between WV-VT and WV-HRVT2 was not statistically significant (4.8; 4.8 to 5.4 vs 4.8; 4.2 to 5.4 km/h) and the agreement was acceptable (0.04 km/h; -1.28 to 1.36). HRVT assessment during walking is a reliable measure and permits the estimation of VT in adults. We suggest the use of the ISWT for the assessment of exercise capacity in middle-aged and older adults.

Energy system contribution in a maximal incremental test: correlations with pacing and overall performance in a 10-km running trial

This study aimed to verify the association between the contribution of energy systems during an incremental exercise test (IET), pacing, and performance during a 10-km running time trial. Thirteen male recreational runners completed an incremental exercise test on a treadmill to determine the respiratory compensation point (RCP), maximal oxygen uptake (V˙O2max), peak treadmill speed (PTS), and energy systems contribution; and a 10-km running time trial (T10-km) to determine endurance performance. The fractions of the aerobic (WAER) and glycolytic (WGLYCOL) contributions were calculated for each stage based on the oxygen uptake and the oxygen energy equivalents derived by blood lactate accumulation, respectively. Total metabolic demand (WTOTAL) was the sum of these two energy systems. Endurance performance during the T10-km was moderately correlated with RCP, V˙O2maxand PTS (P<@0.05), and moderate-to-highly correlated with WAER, WGLYCOL, and WTOTAL (P<0.05). In addition, WAER, WGLYCOL, and WTOTAL were also significantly correlated with running speed in the middle (P<0.01) and final (P<0.01) sections of the T10-km. These findings suggest that the assessment of energy contribution during IET is potentially useful as an alternative variable in the evaluation of endurance runners, especially because of its relationship with specific parts of a long-distance race.

Computation and Analysis of Multiple Structural-Change Models

In a recent paper, Bai and Perron (1998) considered theoretical issues related to the limiting distribution of estimators and test statistics in the linear model with multiple structural changes. In this companion paper, we consider practical issues for the empirical applications of the procedures. We first address the problem of estimation of the break dates and present an efficient algorithm to obtain global minimizers of the sum of squared residuals. This algorithm is based on the principle of dynamic programming and requires at most least-squares operations of order O(T 2) for any number of breaks. Our method can be applied to both pure and partial structural-change models. Secondly, we consider the problem of forming confidence intervals for the break dates under various hypotheses about the structure of the data and the errors across segments. Third, we address the issue of testing for structural changes under very general conditions on the data and the errors. Fourth, we address the issue of estimating the number of breaks. We present simulation results pertaining to the behavior of the estimators and tests in finite samples. Finally, a few empirical applications are presented to illustrate the usefulness of the procedures. All methods discussed are implemented in a GAUSS program available upon request for non-profit academic use.

Examining the incremental validity of psychopathy versus antisocial personality disorder in understanding patterns of criminal behavior

La psychopathie et le trouble de personnalité antisociale sont deux syndromes reliés qui ont été identifiés comme prédicteurs importants de comportements violents et de criminalité. Cependant, la recherche indique que les facteurs de la psychopathie centrés sur la personnalité ne sont pas des prédicteurs fiables de récidive violente chez les personnes atteintes de maladies mentales. Toutefois, peu d’études se sont centrées sur l’identification des facteurs associés au patron des antécédents criminels. Les 96 hommes de l’étude ont été déclarés non criminellement responsables en raison de troubles mentaux. Ils ont été évalués quant au trouble de la personnalité antisociale ainsi qu’à la psychopathie. Les dossiers criminels de la Gendarmerie Royale du Canada ont également été consultés afin de reconstituer l’histoire criminelle. Les résultats suggèrent que ni les traits de personnalité antisociaux, ni les facteurs de la psychopathie ne démontrent une validité prédictive incrémentielle les uns sur les autres quant au nombre ou à la sévérité des délits. La présence d’un grand nombre de traits antisociaux est associée à un plus grand nombre et à une plus importante sévérité d’actes criminels non-violents. Les résultats sont discutés en termes de l’utilité d’une classification du trouble de personnalité antisociale, et de la pertinence du construit de la psychopathie pour les personnes atteintes de maladies mentales graves.

Categorical quantum computation

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

Reliable computation for geometric models

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal