On the Divisibility of Trinomials by Maximum Weight Polynomials over F2

Divisibility of trinomials by given polynomials over finite fields has been studied and used to construct orthogonal arrays in recent literature. Dewar et al.\ (Des.\ Codes Cryptogr.\ 45:1-17, 2007) studied the division of trinomials by a given pentanomial over \F_2 to obtain the orthogonal arrays of strength at least 3, and finalized their paper with some open questions. One of these questions is concerned with generalizations to the polynomials with more than five terms. In this paper, we consider the divisibility of trinomials by a given maximum weight polynomial over \F_2 and apply the result to the construction of the orthogonal arrays of strength at least 3.Comment: 10 pages, 1 figur

Some properties of generalized self-reciprocal polynomials over finite fields

Numerous results on self-reciprocal polynomials over finite fields have been studied. In this paper we generalize some of these to a-self reciprocal polynomials defined in [4]. We consider some properties of the divisibility of a-reciprocal polynomials and characterize the parity of the number of irreducible factors for a-self reciprocal polynomials over finite fields of odd characteristic

Perlecan (HSPG2) promotes structural, contractile, and metabolic development of human cardiomyocytes

Perlecan (HSPG2), a heparan sulfate proteoglycan similar to agrin, is key for extracellular matrix (ECM) maturation and stabilization. Although crucial for cardiac development, its role remains elusive. We show that perlecan expression increases as cardiomyocytes mature in vivo and during human pluripotent stem cell differentiation to cardiomyocytes (hPSC-CMs). Perlecan-haploinsuffient hPSCs (HSPG2+/−) differentiate efficiently, but late-stage CMs have structural, contractile, metabolic, and ECM gene dysregulation. In keeping with this, late-stage HSPG2+/− hPSC-CMs have immature features, including reduced ⍺-actinin expression and increased glycolytic metabolism and proliferation. Moreover, perlecan-haploinsuffient engineered heart tissues have reduced tissue thickness and force generation. Conversely, hPSC-CMs grown on a perlecan-peptide substrate are enlarged and display increased nucleation, typical of hypertrophic growth. Together, perlecan appears to play the opposite role of agrin, promoting cellular maturation rather than hyperplasia and proliferation. Perlecan signaling is likely mediated via its binding to the dystroglycan complex. Targeting perlecan-dependent signaling may help reverse the phenotypic switch common to heart failure

Antileishmanial High-Throughput Drug Screening Reveals Drug Candidates with New Scaffolds

Drugs currently available for leishmaniasis treatment often show parasite resistance, highly toxic side effects and prohibitive costs commonly incompatible with patients from the tropical endemic countries. In this sense, there is an urgent need for new drugs as a treatment solution for this neglected disease. Here we show the development and implementation of an automated high-throughput viability screening assay for the discovery of new drugs against Leishmania. Assay validation was done with Leishmania promastigote forms, including the screening of 4,000 compounds with known pharmacological properties. In an attempt to find new compounds with leishmanicidal properties, 26,500 structurally diverse chemical compounds were screened. A cut-off of 70% growth inhibition in the primary screening led to the identification of 567 active compounds. Cellular toxicity and selectivity were responsible for the exclusion of 78% of the pre-selected compounds. The activity of the remaining 124 compounds was confirmed against the intramacrophagic amastigote form of the parasite. In vitro microsomal stability and cytochrome P450 (CYP) inhibition of the two most active compounds from this screening effort were assessed to obtain preliminary information on their metabolism in the host. The HTS approach employed here resulted in the discovery of two new antileishmanial compounds, bringing promising candidates to the leishmaniasis drug discovery pipeline

Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer

Summary Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886) we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralising antibody titres (NAbT) using a live virus microneutralization assay against wild-type (WT), Delta, Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titres and T cell responses after the fourth vaccine dose increases compared to those after the third vaccine dose. Patients who received B cell-depleting therapies within 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination

Author Correction: Scalable and robust SARS-CoV-2 testing in an academic center.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Criblage phénotypique d'une banque d'ARN interférents par microscopie haut-débit haut-contenu d'informations appliqué à l'identification de facteurs cellulaires impliqués dans la colonisation du pneumocyte par Mycobacterium tuberculosis

La psychopathologie de la tuberculose associée à l'épidémie de SIDA et l'apparition de bacilles multi - résistants et extrêmement - résistants conduisent à des situations d échecs thérapeutiques. Une meilleure compréhension des mécanismes moléculaires et cellulaires impliqués dans le processus de colonisation de l'organisme hôte par Mycobacteriun tuberculosis est nécessaire pour permettre des progrès radicaux en matière de lutte contre la tuberculose. M. tuberculosis a la capacité de coloniser différents types de cellules pulmonaires constituant ainsi des véritables réservoirs du bacille. Si la contribution du bacille intramacrophagique dans la pathogenèse est bien établie, en revanche, le processus de colonisation des cellules épithéliales par M. tuberculosis par microscopie haut débit haut contenu et l'avons appliqué au calibrage de 20 000 ARN interférents. Nous avons ainsi identifié 88 gènes candidats impliqués dans la réplication du bac. ARFGAP1 est un régulateur négatif de l'activation d'ARF1 qui est impliqué dans les système de trafic vésiculaire COPI et les voies de signalisation par la phospholipase D. L'ensemble de nos résultats ouvrent de nouvelles perspectives de recherche dans la signalisation intercellulaire de M. Tuberculosis. The current TB lengthy antibiotic therapy fails to be effective against multidrug and extremly resistant strains. To this end, improved understanding of the fundamental biology of this complex disease is needed to come up with radical advances in TB control. Pathology is intimately linked to the interplay between the host immune response and the persistence of the mycobacterium. In the lungs -the major affected organ- M. tuberculosis has a preferential tropism for alveolar macrophages, dendritic cells and type II alveolar pneumocytes. Whereas the colonization of macrophages by M. tuberculosis has been comprehensively studied, much less is knowm abaout that of lungs epithelial cells in which the bacillus penetrates but hardly replicates. To uncover key cellular genes involved in the invasion of M. tuberculosis in pneumocytes, we undertook a genome wide RNAi screening on the M. tuberculosis infected type II pneumocyte cell model A549. To do this we established a method relying on high content high troughput microscopy enabling the screening of a library of 20 000 RNAi and the selection and confirmation of the 88 RNAi hits. Among them, we carried out a more thorough study on ARFGAP1 for which silencing led to extensive bacterial internalization inside the epithelial cells followed by strong replication. We showed that in the context of out in vitro M. tuberculosis model of infection, ARFGAP1 negatively regulates ARF1, which impacts on vesicular trafficking, signaling through phospholipase D and actin remodeling. Altogether, our results reveal novel host pathways that are involved in the succesful intracellular colonization of the tubercle becillus.s.ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF