Optimization Coaching for JavaScript

The performance of dynamic object-oriented programming languages such as JavaScript depends heavily on highly optimizing just-in-time compilers. Such compilers, like all compilers, can silently fall back to generating conservative, low-performance code during optimization. As a result, programmers may inadvertently cause performance issues on users\u27 systems by making seemingly inoffensive changes to programs. This paper shows how to solve the problem of silent optimization failures. It specifically explains how to create a so-called optimization coach for an object-oriented just-in-time-compiled programming language. The development and evaluation build on the SpiderMonkey JavaScript engine, but the results should generalize to a variety of similar platforms

Optimization Coaching for JavaScript (Artifact)

This artifact is based on our prototype optimization coach for the SpiderMonkey (https://developer.mozilla.org/en-US/docs/Mozilla/Projects/SpiderMonkey) JavaScript engine. An optimization coach is a performance tool that aims to provide programmers with insight into how their compiler optimizes their programs and to help them better harness the optimization process. It does so by reporting optimization near misses, i.e., reports of optimizations that the compiler did not apply, but could apply if the program were to be modified slightly. This artifact provides the necessary environment, programs and data to repeat our experiments, and to allow readers to run our tool on JavaScript programs of their choic

Développement d'outils de sélection génomique assistée par marqueurs pour la lutte au nématode à kyste du soja

La culture du soja (Glycine max (L.) Merr.) a connu une forte expansion au Canada surtout grâce au développement de lignées à maturité hâtive facilitant sa culture plus au nord. En parallèle le nématode à kyste du soja (NKS ; Heterodera glycines Ichinohe), parasite du soja, est devenu le premier ravageur du soja mondialement et il s’installe progressivement au Canada. L’utilisation de cultivars résistants demeure le moyen le plus efficace pour réduire les pertes associées au NKS. Cependant une seule source de résistance a été largement exploitée en Amérique, soit l’accession PI 88788. Son utilisation intensive a exercé une forte pression de sélection sur le NKS pouvant maintenant surmonter cette résistance presque partout aux États-Unis. De plus PI 88788 présente une maturité très tardive la rendant mal adaptée aux régions canadiennes. Cette étude visait à déterminer les régions génomiques conférant la résistance au NKS chez la variété de soja Suzuhime (PI 494182) laquelle affiche une grande résistance au NKS et la maturité la plus hâtive parmi les accessions résistantes. Pour ce faire 149 lignées issues d’un croisement entre la variété Costaud (haut rendement, maturité hâtive, mais sensible au NKS) et Suzuhime ont été génotypées et évaluées pour leur résistance au NKS permettant de réaliser une analyse QTL (« quantitive trait loci ») et ainsi identifier les locus de résistance. Ces lignées ont aussi été évaluées pour certains caractères agronomiques dans le but de déterminer l’impact de la sélection des allèles de résistance sur les performances agronomiques. Finalement, grâce au reséquençage de PI 494182 et Costaud, nous avons identifié les allèles en présence pour certains gènes de résistance connus. Ce travail permettra d’identifier des marqueurs génétiques de résistance au NKS et ainsi faciliter le développement de cultivars combinant maturité hâtive, rendement élevé et résistance au NKS

Migratory Typing: Ten Years Later

In this day and age, many developers work on large, untyped code repositories. Even if they are the creators of the code, they notice that they have to figure out the equivalent of method signatures every time they work on old code. This step is time consuming and error prone. Ten years ago, the two lead authors outlined a linguistic solution to this problem. Specifically they proposed the creation of typed twins for untyped programming languages so that developers could migrate scripts from the untyped world to a typed one in an incremental manner. Their programmatic paper also spelled out three guiding design principles concerning the acceptance of grown idioms, the soundness of mixed-typed programs, and the units of migration. This paper revisits this idea of a migratory type system as implemented for Racket. It explains how the design principles have been used to produce the Typed Racket twin and presents an assessment of the project\u27s status, highlighting successes and failures

The measurement of ancestral roots with genealogical data

This study presents a new method to measure the depth of ancestral roots in a population. This method sheds light on the migratory movements which led to present-day population distribution across space. The method was applied to a dataset of 5,100 ascending genealogies from seventeen regions of the province of Quebec (Canada). Dates of marriage of the earliest ancestors married in the same region as their descendants were used to measure the age of individual ancestral roots. The average regional ages vary between 16 and 157 years, while some individual roots reach as far back as 300 years in the same region. The proposed method can be useful for assessing how deeply rooted a contemporary population is at a local, regional or other geographical level

Portrait of blood-derived extracellular vesicles in patients with Parkinson's disease.

The production of extracellular vesicles (EV) is a ubiquitous feature of eukaryotic cells but pathological events can affect their formation and constituents. We sought to characterize the nature, profile and protein signature of EV in the plasma of Parkinson's disease (PD) patients and how they correlate to clinical measures of the disease. EV were initially collected from cohorts of PD (n = 60; Controls, n = 37) and Huntington's disease (HD) patients (Pre-manifest, n = 11; manifest, n = 52; Controls, n = 55) - for comparative purposes in individuals with another chronic neurodegenerative condition - and exhaustively analyzed using flow cytometry, electron microscopy and proteomics. We then collected 42 samples from an additional independent cohort of PD patients to confirm our initial results. Through a series of iterative steps, we optimized an approach for defining the EV signature in PD. We found that the number of EV derived specifically from erythrocytes segregated with UPDRS scores corresponding to different disease stages. Proteomic analysis further revealed that there is a specific signature of proteins that could reliably differentiate control subjects from mild and moderate PD patients. Taken together, we have developed/identified an EV blood-based assay that has the potential to be used as a biomarker for PD

Broad-Spectrum Matrix Metalloproteinase Inhibition Curbs Inflammation and Liver Injury but Aggravates Experimental Liver Fibrosis in Mice

Background Liver fibrosis is characterized by excessive synthesis of extracellular matrix proteins, which prevails over their enzymatic degradation, primarily by matrix metalloproteinases (MMPs). The effect of pharmacological MMP inhibition on fibrogenesis, however, is largely unexplored. Inflammation is considered a prerequisite and important co-contributor to fibrosis and is, in part, mediated by tumor necrosis factor (TNF)-α-converting enzyme (TACE). We hypothesized that treatment with a broad-spectrum MMP and TACE-inhibitor (Marimastat) would ameliorate injury and inflammation, leading to decreased fibrogenesis during repeated hepatotoxin-induced liver injury.Methodology/Principal Findings Liver fibrosis was induced in mice by repeated carbon tetrachloride (CCl4) administration, during which the mice received either Marimastat or vehicle twice daily. A single dose of CCl4was administered to investigate acute liver injury in mice pretreated with Marimastat, mice deficient in Mmp9, or mice deficient in both TNF-α receptors. Liver injury was quantified by alanine aminotransferase (ALT) levels and confirmed by histology. Hepatic collagen was determined as hydroxyproline, and expression of fibrogenesis and fibrolysis-related transcripts was determined by quantitative reverse-transcription polymerase chain reaction. Marimastat-treated animals demonstrated significantly attenuated liver injury and inflammation but a 25% increase in collagen deposition. Transcripts related to fibrogenesis were significantly less upregulated compared to vehicle-treated animals, while MMP expression and activity analysis revealed efficient pharmacologic MMP-inhibition and decreased fibrolysis following Marimastat treatment. Marimastat pre-treatment significantly attenuated liver injury following acute CCl4-administration, whereas Mmp9 deficient animals demonstrated no protection. Mice deficient in both TNF-α receptors exhibited an 80% reduction of serum ALT, confirming the hepatoprotective effects of Marimastat via the TNF-signaling pathway.Conclusions/Significance Inhibition of MMP and TACE activity with Marimastat during chronic CCl4administration counterbalanced any beneficial anti-inflammatory effect, resulting in a positive balance of collagen deposition. Since effective inhibition of MMPs accelerates fibrosis progression, MMP inhibitors should be used with caution in patients with chronic liver diseases