De la fusion du génie logiciel et d'une bibliothèque à source ouverte pour la modélisation/simulation de processus matériel et logiciel

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Modulation des radeaux lipidiques et des propriétés de fusion des phagosomes par le lipophosphoglycane du parasite intracellulaire Leishmania donovani

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Étude des GTPases potentiellement responsables de la fusion du réticulum endoplasmique

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

The relationship between fusion, suppression, and diplopia in amblyopia

Purpose: Traditionally, it has been thought that no binocular combination occurs in amblyopia. However, there is a growing body of evidence that there are intact binocular mechanisms in amblyopia rendered inactive under normal viewing conditions due to imbalanced monocular inputs. Georgeson and Wallis (2014) recently introduced a novel method to investigate fusion, suppression and diplopia in normal population. We have modified this method to assess binocular interactions in amblyopia. Methods: Ten amblyopic and ten control subjects viewed briefly-presented (200 ms) pairs of dichoptically separated horizontal Gaussian blurred edges. Subjects reported one central edge, one offset edge, or a double edge as the vertical disparity was manipulated. The experiment was conducted at a range of spatial scales (blur widths of 4, 8, 16, and 32 arc min) and contrasts. Our model, based Georgeson and Wallis (2014), converted subjects’ responses into probabilities of fusion, suppression, and diplopia. Results: When the normal participants were presented equal contrast to each eye the probability of fusion gradually decreased with increasing disparity, as the probability of diplopia gradually increased. In only a small proportion of the trials, normal participants experienced suppression. The pattern was consistent across all edge blurs. Interestingly, the majority of amblyopes had a comparable pattern of fusion, i.e. decreasing probability with increasing disparity. However, with increasing disparity the amblyopes tended to suppress the amblyopic eye, experiencing diplopia only in a small proportion of trials particularly at large blurs. Increasing the interocular contrast offset favouring the amblyopic eye normalized the pattern of data in a way similar to normal participants. There were some interesting exceptions: strong suppressors for which our contrast range was inadequate and one case in which diplopia dominated. Conclusions: This task is suitable for assessing binocular interactions in amblyopic participants and providing a way to quantify the relationship between fusion, suppression and diplopia. In agreement with previous studies, our data indicate the presence of binocular mechanisms in amblyopia. A contrast offset favouring the amblyopic eye normalizes the measured binocular interactions in the amblyopic visual system.

De la fusion du génie logiciel et d'une bibliothèque à source ouverte pour la modélisation/simulation de processus matériel et logiciel

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Modulation des radeaux lipidiques et des propriétés de fusion des phagosomes par le lipophosphoglycane du parasite intracellulaire Leishmania donovani

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Étude des GTPases potentiellement responsables de la fusion du réticulum endoplasmique

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

IMPROVING THE PERFORMANCE OF DATABASE-CENTRIC APPLICATIONS THROUGH PROGRAM ANALYSIS

Modern software applications are becoming more dependent on database management systems (DBMSs). DBMSs are usually used as black boxes by software developers. For example, Object-Relational Mapping (ORM) is one of the most popular database abstraction approaches that developers use nowadays. Using ORM, objects in Object-Oriented languages are mapped to records in the database, and object manipulations are automatically translated to SQL queries. As a result of such conceptual abstraction, developers do not need deep knowledge of databases; however, all too often this abstraction leads to inefficient and incorrect database access code. Thus, this thesis proposes a series of approaches to improve the performance of database-centric software applications that are implemented using ORM. Our approaches focus on troubleshooting and detecting inefficient (i.e., performance problems) database accesses in the source code, and we rank the detected problems based on their severity. We first conduct an empirical study on the maintenance of ORM code in both open source and industrial applications. We find that ORM performance-related configurations are rarely tuned in practice, and there is a need for tools that can help improve/tune the performance of ORM-based applications. Thus, we propose approaches along two dimensions to help developers improve the performance of ORM-based applications: 1) helping developers write more performant ORM code; and 2) helping developers configure ORM configurations. To provide tooling support to developers, we first propose static analysis approaches to detect performance anti-patterns in the source code. We automatically rank the detected anti-pattern instances according to their performance impacts. Our study finds that by resolving the detected anti-patterns, the application performance can be improved by 34% on average. We then discuss our experience and lessons learned when integrating our anti-pattern detection tool into industrial practice. We hope our experience can help improve the industrial adoption of future research tools. However, as static analysis approaches are prone to false positives and lack runtime information, we also propose dynamic analysis approaches to further help developers improve the performance of their database access code. We propose automated approaches to detect redundant data access anti-patterns in the database access code, and our study finds that resolving such redundant data access anti-patterns can improve application performance by an average of 17%. Finally, we propose an automated approach to tune performance-related ORM configurations using both static and dynamic analysis. Our study shows that our approach can help improve application throughput by 27--138%. Through our case studies on real-world applications, we show that all of our proposed approaches can provide valuable support to developers and help improve application performance significantly.

EGFR interacts with the fusion protein of respiratory syncytial virus strain 2-20 and mediates infection and mucin expression.

Respiratory syncytial virus (RSV) is the major cause of viral lower respiratory tract illness in children. In contrast to the RSV prototypic strain A2, clinical isolate RSV 2-20 induces airway mucin expression in mice, a clinically relevant phenotype dependent on the fusion (F) protein of the RSV strain. Epidermal growth factor receptor (EGFR) plays a role in airway mucin expression in other systems; therefore we hypothesized that the RSV 2-20 F protein stimulates EGFR signaling. Infection of cells with chimeric strains RSV A2-2-20F and A2-2-20GF or over-expression of 2-20 F protein resulted in greater phosphorylation of EGFR than infection with RSV A2 or over-expression of A2 F, respectively. Chemical inhibition of EGFR signaling or knockdown of EGFR resulted in diminished infectivity of RSV A2-2-20F but not RSV A2. Over-expression of EGFR enhanced the fusion activity of 2-20 F protein in trans. EGFR co-immunoprecipitated most efficiently with RSV F proteins derived from “mucogenic” strains. RSV 2-20 F and EGFR co-localized in H292 cells, and A2-2-20GF-induced MUC5AC expression was ablated by EGFR inhibitors in these cells. Treatment of BALB/c mice with the EGFR inhibitor erlotinib significantly reduced the amount of RSV A2-2-20F-induced airway mucin expression. Our results demonstrate that RSV F interacts with EGFR in a strain-specific manner, EGFR is a co-factor for infection, and EGFR plays a role in RSV-induced mucin expression, suggesting EGFR is a potential target for RSV disease.

Numerical study of neutron beam divergence in a beam-fusion scenario employing laser driven ions

The most established route to create a laser-based neutron source is by employing laser accelerated, low atomic-number ions in fusion reactions. In addition to the high reaction cross-sections at moderate energies of the projectile ions, the anisotropy in neutron emission is another important feature of beam-fusion reactions. Using a simple numerical model based on neutron generation in a pitcher–catcher scenario, anisotropy in neutron emission was studied for the deuterium–deuterium fusion reaction. Simulation results are consistent with the narrow-divergence ( ∼ 70 ° full width at half maximum) neutron beam recently served in an experiment employing multi-MeV deuteron beams of narrow divergence (up to 30° FWHM, depending on the ion energy) accelerated by a sub-petawatt laser pulse from thin deuterated plastic foils via the Target Normal Sheath Acceleration mechanism. By varying the input ion beam parameters, simulations show that a further improvement in the neutron beam directionality (i.e. reduction in the beam divergence) can be obtained by increasing the projectile ion beam temperature and cut-off energy, as expected from interactions employing higher power lasers at upcoming facilities.