844 research outputs found
Overcoming Challenges to Continuous Integration in HPC
Continuous integration (CI) has become a ubiquitous practice in modern
software development, with major code hosting services offering free automation
on popular platforms. CI offers major benefits, as it enables detecting bugs in
code prior to committing changes. While high-performance computing (HPC)
research relies heavily on software, HPC machines are not considered "common"
platforms. This presents several challenges that hinder the adoption of CI in
HPC environments, making it difficult to maintain bug-free HPC projects, and
resulting in adverse effects on the research community. In this article, we
explore the challenges that impede HPC CI, such as hardware diversity,
security, isolation, administrative policies, and non-standard authentication,
environments, and job submission mechanisms. We propose several solutions that
could enhance the quality of HPC software and the experience of developers.
Implementing these solutions would require significant changes at HPC centers,
but if these changes are made, it would ultimately enable faster and better
science
Analytical Blowup Solutions to the Pressureless Navier-Stokes-Poisson Equations with Density-dependent Viscosity in R^N
We study the N-dimensional pressureless Navier--Stokes-Poisson equations with
density-dependent viscosity. With the extension of the blowup solutions for the
Euler-Poisson equations, the analytical blowup solutions,in radial symmetry, in
R^N are constructed.Comment: 12 Pages, more detail in the introduction to explain the validity of
the mode
Survival after Resection of Multiple Tumor Foci of Intrahepatic Cholangiocarcinoma
Background: Multiple tumor foci of intrahepatic cholangiocarcinoma (ICC) are often considered a contra-indication for resection. We sought to define long-term outcomes after resection of ICC in patients with multiple foci.
Methods: Patients who underwent resection for ICC between 1990 and 2017 were identified from 12 major HPB centers. Outcomes of patients with solitary lesions, multiple lesions (ML), and oligometastases (OM) were compared. OM were defined as extrahepatic metastases spread to a single organ.
Results: One thousand thirteen patients underwent resection of ICC. On final pathology, 185 patients (18.4%) had ML and 27 (2.7%) had OM. Median survival of patients with a solitary tumor was 43.2 months, while the median survival of patients with 2 tumors was 21.2 months; the median survival of patients with 3 or more tumors was 15.3 months (p < 0.001). Five-year survival was 43.3%, 28.0%, and 8.6%, respectively. The median survival of patients without OM was 37.8 months versus 14.9 months among patients with OM (p < 0.001); estimated 5-year survival was 39.3% and 10.6%, respectively. In multivariable analysis, the presence of two lesions was not an independent poor prognostic factor for OS (HR 1.19; 95%CI 0.90-1.57; p = 0.229). However, the presence of three or more tumors was an independent poor prognostic factor for OS (HR 1.97; 95%CI 1.48-2.64; p < 0.001).
Conclusion: Resection of multiple liver tumors for patients with ICC did not preclude 5-year survival: in particular, estimated 5-year OS for resection of two tumors was 28.0%.info:eu-repo/semantics/publishedVersio
Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination
Pseudohyperphosphorylation has differential effects on polymerization and function of tau isoforms
The microtubule-associated protein tau exists as six isoforms created through the splicing of the second, third, and tenth exons. The isoforms are classified by their number of N-terminal exons (0N, 1N or 2N) and by their number of microtubule-binding repeat regions (3R or 4R). Hyperphosphorylated isoforms accumulate in insoluble aggregates in Alzheimer’s disease and other tauopathies. These neurodegenerative diseases can be categorized based on the isoform content of the aggregates they contain. Hyperphosphorylated tau has the general characteristics of an upward electrophoretic shift, decreased microtubule binding, and an association with aggregation. Previously we have shown that a combination of seven pseudophosphorylation mutations at sites phosphorylated by GSK-3β, referred to as 7-Phos, induced several of these characteristics in full-length 2N4R tau and led to the formation of fewer but longer filaments. We sought to determine whether the same phosphorylation pattern could cause differential effects in the other tau isoforms, possibly through varied conformational effects. Using in vitro techniques, we examined the electrophoretic mobility, aggregation properties and microtubule stabilization of all isoforms and their pseudophosphorylated counterparts. We found that pseudophosphorylation affected each isoform, but in several cases certain isoforms were affected more than others. These results suggest that hyperphosphorylation of tau isoforms could play a major role in determining the isoform composition of tau aggregates in disease
Reduced antibody cross-reactivity following infection with B.1.1.7 than with parental SARS-CoV-2 strains
Background: The degree of heterotypic immunity induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains is a major determinant of the spread of emerging variants and the success of vaccination campaigns, but remains incompletely understood.
Methods: We examined the immunogenicity of SARS-CoV-2 variant B.1.1.7 (Alpha) that arose in the United Kingdom and spread globally. We determined titres of spike glycoprotein-binding antibodies and authentic virus neutralising antibodies induced by B.1.1.7 infection to infer homotypic and heterotypic immunity.
Results: Antibodies elicited by B.1.1.7 infection exhibited significantly reduced recognition and neutralisation of parental strains or of the South Africa variant B.1.351 (Beta) than of the infecting variant. The drop in cross-reactivity was significantly more pronounced following B.1.1.7 than parental strain infection.
Conclusions: The results indicate that heterotypic immunity induced by SARS-CoV-2 variants is asymmetric
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