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L’engagement de continuité envers l’organisation reste peu étudié dans la littérature, particulièrement en lien avec la santé mentale des employés. Suivant les principes de la théorie de la conservation des ressources, nous examinons la relation entre les deux dimensions de l’engagement de continuité, à savoir l’engagement par sacrifice perçu et l’engagement par manque d’alternatives, et deux indicateurs de santé : l’épuisement émotionnel et les symptômes dépressifs. De plus, l’étude contrôle pour l’effet des traits d’affectivité positive et négative et examine les effets modérateurs de ces traits, en lien avec la théorie broaden-and-build. Sur la base d’un large échantillon de répondants (n=1001), les analyses indiquent que l’engagement par sacrifice perçu et l’engagement par manque d’alternatives sont respectivement négativement et positivement liés à l’épuisement émotionnel et aux symptômes dépressifs. Également, l’affectivité positive accentue la relation négative de l’engagement par sacrifice perçu avec ces variables de santé. De façon surprenante, la relation entre l’engagement par sacrifice perçu et ces résultantes est plus négative lorsque l’affectivité négative est élevée. Enfin, l’affectivité négative accentue le lien positif entre l’engagement par manque d’alternatives et les symptômes dépressifs. Ces résultats sont discutés dans le contexte de la recherche sur l’engagement de continuité.

Diagnostic imaging using CT enterography, magnetic resonance enterography, and intestinal ultrasound are important tools in evaluating stricturing Crohn's disease. Definitions of strictures have been developed for CT enterography and magnetic resonance enterography. However, expert recommendations for definitions and treatment response of strictures on intestinal ultrasound are not available. The aim of this study was to standardise definitions, diagnosis, and treatment response criteria in small bowel stricturing Crohn's disease on intestinal ultrasound.

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Astrocytes are crucial to brain homeostasis, yet their changes along the spatiotemporal progression of Alzheimer’s disease (AD) neuropathology remain unexplored. Here we performed single-nucleus RNA sequencing of 628,943 astrocytes from five brain regions representing the stereotypical progression of AD pathology across 32 donors spanning the entire normal aging to severe AD continuum. We mapped out several unique astrocyte subclusters that exhibited varying responses to neuropathology across the AD-vulnerable neural network (spatial axis) or AD pathology stage (temporal axis). The proportion of homeostatic, intermediate and reactive astrocytes changed only along the spatial axis, whereas two other subclusters changed along the temporal axis. One of these, a trophic factor-rich subcluster, declined along pathology stages, whereas the other increased in the late stage but returned to baseline levels in the end stage, suggesting an exhausted response with chronic exposure to neuropathology. Our study underscores the complex dynamics of astrocytic responses in AD.

In recent decades, rare-isotope facilities have enabled the study of short-lived, neutron-rich nuclei. Their measured properties indicate that shell structure changes in the regime of unbalanced neutron-to-proton ratios compared with that of stable nuclei. In the so-called islands of inversion in the nuclear chart—around the neutron-rich nuclei 32Mg, 42Si and 64Cr, for example—the textbook shell model predicts spherical shapes due to the respective magic neutron numbers of 20, 28 and 40 of these nuclei. However, nuclei in these regions turn out to be deformed in their ground states. Another hallmark of these islands is shape coexistence, where a nucleus assumes different shapes with excitation energy. Here we present evidence for this phenomenon from the observation of an excited 0+state in 62Cr, two neutrons away from the heart of the island of inversion around neutron number N= 40. We use large-scale shell-model calculations to interpret the results, and we report extrapolations for the doubly magic nucleus 60Ca.

Mitochondrial genomic integrity is a key element of physiological processes and health. Changes in the half-life of the mitochondrial genome are implicated in the generation and accumulation of age-induced mitochondrial DNA (mtDNA) mutations, which are implicated in skeletal muscle aging and sarcopenia. There are conflicting data on the half-life of mtDNA, and there is limited information on how aging affects half-life in skeletal muscle. We hypothesized that skeletal muscle mtDNA synthesis rates would decrease with age in both female and male rats concomitant with changes in mtDNA integrity reflected in mtDNA copy number and mutation frequency. We measured mitochondrial genome half-life using stable isotope labeling over a period of 14 days and assessed mtDNA copy number and deletion mutation frequency using digital PCR in the quadriceps muscle of 9-month-old and 26-month-old male and female OKC-HET rats. We found a significant age-related increase in mtDNA half-life, from 132 days at 9 months to 216 days at 26 months of age in OKC-HET quadriceps. Concomitant with the increase in mtDNA half-life, we found an age-related increase in mtDNA deletion mutation frequency in both male and female rats. Notably, 26-month-old female rats had a lower mutation frequency than male rats, and there were no changes in mtDNA copy number with sex, age, or mitochondrial genotype. These data reveal several key findings: (1) mtDNA turnover in rat skeletal muscle decreases with age, (2) mtDNA half-lives in skeletal muscle are approximately an order of magnitude longer than what is reported for other tissues, and (3) muscle mtDNA turnover differs significantly from the turnover of other mitochondrial macromolecules including components of the mitochondrial nucleoid. These findings provide insight into the factors driving age-induced mtDNA mutation accumulation, which contribute to losses of mitochondrial genomic integrity and may play a role in skeletal muscle dysfunction.

Thirty-six years after the first edition of IEEE standard 982.1, Measures of the Software Aspects of Dependability, the third edition focuses on the measurement of in-service software dependability. This article explains how this new point of view evolved and shaped the third edition’s guidance for software dependability measurement.

Reading recent conference papers, journal articles, and the trade press articles one would think that power electronics consisted only of dual active bridge (DAB) converters, various types of multi-level converters, and modular multi-level converters (MMC). These are all important to power electronics. DABs are very useful. They can be designed for a wide range of power, offer isolation, offer a wide range of possible conversion ratios. Their ability to process power equally well between two or more power ports makes them very useful to interface between dc power buses and batteries.

This article explores the efforts to identify the birth family of John Joseph Cooney, who was adopted as an infant in Lawler, Iowa. The research uncovered clues suggesting that John Joseph may have had a brother named Philip O'Brien and that his father might have been named John Sullivan. Through genealogical research and DNA testing, connections were made to the O'Brien and Sullivan families, providing evidence for John Joseph's biological parents. The study highlights the power of DNA technology in complementing traditional genealogical research. [Extracted from the article]

Overexpression of the epidermal growth factor receptor family member HER3 (erbB3) has been implicated in several types of cancer and recently drugs targeting HER3 have shown promising clinical activity. In melanoma, HER3 overexpression has been linked to both metastasis formation and resistance to drug therapy in cell culture models. Here, we sought to characterise the expression of HER3 in 187 melanoma biopsies (149 cutaneous, 38 mucosal) using immunohistochemistry, as well as to analyse the association between HER3 expression and molecular, clinical and pathological variables. A subset of the cutaneous melanoma specimens was taken prior to treatment with immune checkpoint blockade therapy (pre-ICB) (n=79). HER3 expression (≥1+) was observed in 136 of 187 samples (∼73%). HER3 expression was found to be markedly lower in the mucosal melanomas, with 17 of the 38 tumours (∼45%) demonstrating no HER3 expression. In cutaneous melanomas, there was a negative association between HER3 expression and mutational load, a positive association with NRASmutational status, and a trend of negative association with PD-L1 expression. In the pre-ICB cohort, an association was found between high HER3 expression (≥2+) and overall survival after anti-PD-1-based immunotherapy. Overall, our results indicate that HER3 is a promising therapeutic avenue in cutaneous melanoma worthy of further clinical evaluation.

Lipid droplets (LDs) are crucial organelles for energy storage and lipid homeostasis. Autophagy of LDs is an important pathway for their catabolism, but the molecular mechanisms mediating LD degradation by selective autophagy (lipophagy) are unknown. Here we identify spartin as a receptor localizing to LDs and interacting with core autophagy machinery, and we show that spartin is required to deliver LDs to lysosomes for triglyceride mobilization. Mutations in SPART(encoding spartin) lead to Troyer syndrome, a form of complex hereditary spastic paraplegia1. Interfering with spartin function in cultured human neurons or murine brain neurons leads to LD and triglyceride accumulation. Our identification of spartin as a lipophagy receptor, thus, suggests that impaired LD turnover contributes to Troyer syndrome development.

The Ebola virus (EBOV) is a filamentous virus that acquires its lipid envelope from the plasma membrane of the host cell it infects. EBOV assembly and budding from the host cell plasma membrane are mediated by a peripheral protein, known as the matrix protein VP40. VP40 is a 326 amino acid protein with two domains that are loosely linked. The VP40 N-terminal domain (NTD) contains a hydrophobic α-helix, which mediates VP40 dimerization. The VP40 C-terminal domain has a cationic patch, which mediates interactions with anionic lipids and a hydrophobic region that mediates VP40 dimer–dimer interactions. The VP40 dimer is necessary for trafficking to the plasma membrane inner leaflet and interactions with anionic lipids to mediate the VP40 assembly and oligomerization. Despite significant structural information available on the VP40 dimer structure, little is known on how the VP40 dimer is stabilized and how residues outside the NTD hydrophobic portion of the α-helical dimer interface contribute to dimer stability. To better understand how VP40 dimer stability is maintained, we performed computational studies using per-residue energy decomposition and site saturation mutagenesis. These studies revealed a number of novel keystone residues for VP40 dimer stability just adjacent to the α-helical dimer interface as well as distant residues in the VP40 CTD that can stabilize the VP40 dimer form. Experimental studies with representative VP40 mutants in vitro and in cells were performed to test computational predictions that reveal residues that alter VP40 dimer stability. Taken together, these studies provide important biophysical insights into VP40 dimerization and may be useful in strategies to weaken or alter the VP40 dimer structure as a means of inhibiting the EBOV assembly.

AbstractThe temperature dependence of the partial heat capacity of the native protein structure in an aqueous solution has been analyzed. It is shown that the strictly linear temperature dependence is due to the contributions of the vibrational and conformational components, which indicates volume consistensy and the absence of conformational transitions up to the main two-state transition. The two-level structural and functional organization of the protein three-dimensional structure are considered in relation to the energy and conformational entropy properties in accordance with the principles of the organization of the protein macromolecule.Communicated by Ramaswamy H. Sarma

•Émicizumab a augmenté le coût de prise en charge des patients hémophiles A sévères sans inhibiteur.•Aucune différence de coût n’a été montrée concernant les injections de facteur VIII.•Le cout de prise en charge par émicizumab pourrait être diminué chez les patients jeunes.•Un horizon temporel allongé doit être utilisé pour corroborer les résultats.

Standard of care surgical treatment of cervical high-grade squamous intraepithelial lesions leads to substantial virological clearance but can be followed by recurrence, preterm birth, and complications including infection and bleeding.

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Surface plasmon resonance (SPR) has emerged as a powerful optical detection technique for studying the binding behaviour of immobilized ligands and analytes in solution. The technique makes it possible to measure interactions in real time with high sensitivity. Over the past two decades, SPR has become the gold standard for studying biomolecular interactions in biomedical research and drug discovery. The interactions that can be studied are diverse and include protein–protein, protein–small molecule, protein–nucleic acid, protein–carbohydrate, lipid–protein, hybrid systems of biomolecules and non-biological surfaces. SPR allows researchers to determine which molecules interact, how strongly they bind and inform experiments using mutants, truncations or other variations to probe specificity. This article summarizes the principle and experimental set-up and illustrates the utility of SPR using the example of lipid–protein interactions.

Cognitive radio (CR) is an emergent communication platform that offers solutions for spectrum scarcity issues. Cognitive radio networks (CRNs) will offer increased bandwidth to mobile consumers through wireless heterogeneous architectures and dynamic spectrum acquisition mechanisms. However, CRNs enforce challenges because of the fluctuating behaviour of the spectrum available and the diverse requirements for a varied range of applications. The functions of spectrum management can resolve those challenges to realize a new paradigm of the network. Secondary users (SUs) can opportunistically explore and employ the blank spaces present in licensed channels. This makes the SU evacuate the licensed channel and then switch to a vacant channel, when an incumbent primary user (PU) interferes with the channel, it causes degradation of SUs because of the frequent switching of channels. Also, the deafness problem is commonly seen in a CRN, where the QoS is critically affected due to the hidden interferences. This research proposes a Genetic Algorithm Optimized Fuzzy decision system for performing channel selection, channel switching, and spectrum allocation in a multi-channel multi-hop CRN. The proposed scheme acts as a decision support system (DSS), focusing on reducing the channel switching rate, hidden node interferences, and efficient spectrum allocation. Meta-heuristic genetic algorithm (GA) optimizes the parameters of the fuzzy decision system (FDS), for obtaining optimized decisions. The proposed DSS in the CR environment is simulated in the MATLAB platform and the results show improved performance concerning throughput and channel utilization.

Growing global demand for sustainable development places immense pressure on the construction industry to select and promote sustainable construction practices. The selection of sustainable construction practices is a challenging task, as there are numerous variables and uncertainties involved in the concept of sustainability and a consistent and widely accepted framework for assessment and evaluation seems to be lacking. Based on an extensive literature review on sustainability, sustainable construction was redefined and evaluation frameworks were identified for comparison. Furthermore, a conceptual framework is proposed by identifying specific indicators and criteria relating to the objectives of sustainable construction (sociocultural, economic, technical and environmental) to evaluate the sustainability of construction practices. Recommendations for the application of the proposed framework is also presented.

Considering the significant economic impact of SMEs and their proclivity towards collaborative strategies, SME coopetition remains under researched despite evidence of its distinctiveness. Drawing upon resource dependence theory, we develop and test a model that considers the role of strategic motivations, proactive or reactive, as determinants of the emphasis on mutual dependence in partner selection. We argue that coopetition is a unique avenue for constraint absorption that is particularly relevant in SMEs motivated by resource limitations and perceived market necessities. Further, we argue that SMEs with more traditional proactive strategic motivations are more likely to view coopetition as an avenue for market exploitation and thus less likely to select partners based on mutual dependence, particularly when engaging with less trusted partners. Our findings, based on the study of 104 firms in the automotive sector, generally support our arguments and suggest a number of implications for the continued study of SME coopetition.

High expression of PRAME (PReferentially expressed Antigen in MElanoma) and p53 (a proposed marker of desmoplastic melanoma) and low expression of 5-hydroxymethylcytosine (5-hmC) have each been reported in melanoma. However, their combined diagnostic utility for distinguishing melanomas, including uncommon variants, from histological mimics is unknown.