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Abstract This data descriptor presents a curated dataset for pathogen detection and identification (Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans) directly from whole-blood samples. The dataset was created using differential cell lysis combined with rapid extraction, digestion, and mass spectrometry-based proteomics. Our method offers a rapid diagnostic alternative to traditional culture, enabling timely disease management, such as sepsis. Highlighting our dataset’s uniqueness, it features a three-tier structure: Spectral Libraries of Pathogens for identifying peptide peaks for putative biomarkers; Spiked pathogen in blood MS data for biomarker panel optimization through varied concentration samples; and Parallel Reaction Monitoring (PRM) data from sepsis patients for validating our biomarker panel, achieving 83.3% sensitivity within seven hours without microbial enrichment culture. This dataset serves as a comprehensive reference for bioinformatic tool development and biomarker panel proposals, advancing microbial detection, antimicrobial resistance, and epidemiological studies.

RESUMO A amizade no trabalho tem se revelado um importante recurso social, representando um papel central na vida dos trabalhadores e que contribui para a promoção de ambientes laborais mais saudáveis. Com isso, uma lacuna referente à delimitação do escopo de pesquisa da amizade ainda está aberta. Assim, o objetivo do estudo consiste em identificar os benefícios e desafios da amizade no ambiente de trabalho com base na produção científica internacional, apresentando um panorama atual de pesquisas. Por meio de uma revisão sistemática da literatura, foi realizado um levantamento na base Web of Science, a qual retornou 36 artigos que compõem o corpus textual desta revisão. Os resultados revelaram como a temática evoluiu no decorrer dos últimos cinco anos, possibilitando identificar os principais benefícios e desafios da amizade para as organizações. Esta revisão apresenta um esforço seminal ao analisar o campo de estudos da amizade, em que identifica itinerários, benefícios e desafios, assim como faz um mapeamento do campo que impulsionou a construção de uma agenda por meio das lacunas encontradas. Espera-se, ainda, que os resultados aqui coligidos sirvam como um diagnóstico para que seja promovida uma gestão mais humanizada, pautada em laços de confiança e amizade.

Abstract Depression is associated with dysregulated circadian rhythms, but the role of intrinsic clocks in mood-controlling brain regions remains poorly understood. We found increased circadian negative loop and decreased positive clock regulators expression in the medial prefrontal cortex (mPFC) of a mouse model of depression, and a subsequent clock countermodulation by the rapid antidepressant ketamine. Selective Bmal1KO in CaMK2a excitatory neurons revealed that the functional mPFC clock is an essential factor for the development of a depression-like phenotype and ketamine effects. Per2 silencing in mPFC produced antidepressant-like effects, while REV-ERB agonism enhanced the depression-like phenotype and suppressed ketamine action. Pharmacological potentiation of clock positive modulator ROR elicited antidepressant-like effects, upregulating plasticity protein Homer1a, synaptic AMPA receptors expression and plasticity-related slow wave activity specifically in the mPFC. Our data demonstrate a critical role for mPFC molecular clock in regulating depression-like behavior and the therapeutic potential of clock pharmacological manipulations influencing glutamatergic-dependent plasticity.

Abstract A novel quantum-safe key encapsulation algorithm, called Multivariate Polynomial Public Key (MPPK), was recently proposed by Kuang, Perepechaenko, and Barbeau. Security of the MPPK key encapsulation mechanism does not rely on the prime factorization or discrete logarithm problems. It builds upon the NP-completeness of the modular Diophantine equation problem, for which there are no known efficient classical or quantum algorithms. Hence, it is resistant to known quantum computing attacks. The private key of MPPK comprises a pair of multivariate polynomials. In a companion paper, we analyzed the performance of MPPK when these polynomials are quadratic. The analysis highlighted the MPPK high decapsulation time. We found that, while maintaining the security strength, the polynomials can be linear. Considerable performance gains are obtained for the decapsulation process. In this article, we benchmark the linear case and compare the results with the previous quadratic case.

تم في هذه البحث دراسة وتحليل حقل التدفق والتكهف حول دفة NACA0018. تم في البداية إجراء الحسابات الرقمية باستخدام تقنية الـ CFD على الجناح الرافع الذي تم اختباره تجريبيا من قبل Gim 2013 [1] مع زوايا انحراف مختلفة للجناح. المقارنة بين النتائج الرقمية والنتائج التجريبية أظهرت دقة تقنية الـ CFD من إجراء مثل هذه الحسابات. تم استخدام معادلات الـ URANS (Unsteady RANS Averaged Navier Stocks Equation) والموديل الرياضي k-w SST لحل معادلات نافييه ستوكس الناظمة للجريانات المعقدة. بعد ذلك تم استخدام CFD من أجل حساب وتحليل التدفق حول بدن دفة السفينة KVLCC2 مع زوايا انحراف مختلفة وعند يم مختلفة لرقم فرود. أكدت نتائج هذه الدراسة على أن مع زوايا الانحراف الصفيرة للدفة 10 درجة، فإن التدفق حول بدن الدفة يبقى مستقرا ولا يتشكل تدفق عكسي خلف الدفة، في حين مع زوايا الانحراف الكبيرة تزداد مساحة التدفق العكسي خلف الدفة وبعد زاوية الانحراف 22.5 درجة تبدأ فعالية الدفة بالانخفاض. النتائج التي تم الحصول عليها تؤكد أم تشكل التكهف حول الدفة يرتبط بكل من زاوية الانحراف ورقم التكهف الحدي، حيث أن انخفاض قيمة رقم التكهف الحدي يزيد من احتمال تشكل التكهف بشكل كبير حول الدفة.

A atividade de levantamento de dados primários em ambiente escolar é um importante exercício a ser promovido cotidianamente, visto que os estudantes têm contato com metodologia de pesquisa sobre a realidade. Os conteúdos relacionados ao clima na Geografia e Biologia escolar podem estabelecer a relação entre os fenômenos climáticos e meteorológicos e sua influência no aprendizado dos estudantes. Dessa forma, a coleta de dados na prática, relacionada com os elementos físicos e sociais abordados na teoria, se coloca como importante no ensino das disciplinas. Neste sentido, objetivou-se levantar e analisar os índices pluviométricos e de temperaturas no município de Dores do Rio Preto, Espírito Santo, para mediar o processo de ensino e aprendizagem na escola. Durante o período de 24 meses (2019-2021), foram realizadas coletas de água pluvial. Para a coleta dos dados foi utilizada, um pluviômetro analógico e um termohigrômetro. Os resultados demonstraram que há variações relevantes durante os meses analisados. A abordagem do clima na educação básica contribuiu para significar os conteúdos, assim, os estudantes se mostraram mais interessados em estudar tais conteúdo. Neste sentido, o trabalho foi fundamental por relatar valores reais de precipitação e por permitir identificar as anomalias anuais da precipitação e temperatura.

Abstract High-pressure and ultra-high-pressure metamorphic terrains display an internal architecture consisting of a pile (or stack) of several coherent tectonic thrust sheets or units. Their identification is fundamental for understanding the scale and mechanisms active during subduction and exhumation of these crustal slices. This study investigates the geometry of the northern Dora-Maira Massif and the kinematics of the major tectonic boundaries, combining field and geochronological data. The tectonic stack of the northern Dora-Maira Massif comprises the following units. The lowermost unit (the Pinerolo Unit) is mainly characterized by Upper Carboniferous fluvio-lacustrine (meta-)sediments. The Pinerolo unit is overthrust by a pre-Carboniferous basement. The latter is subdivided in two tectonic units (the Chasteiran and Muret Units) with different Alpine metamorphism (ultra-high-pressure and high-pressure, respectively). The pre-Carboniferous basement of the Muret Unit is thicker than previously thought for two main reasons. Firstly, some paragneisses, traditionally assumed to be Carboniferous and/or Permian in age, display detrital zircon ages indicating a main source at about 600 Ma. Secondly, three samples of the Granero Orthogneiss, previously assumed to be a Permian intrusive body, have provided zircon U–Pb ages of 447 ± 1 Ma, 456 ± 2 Ma and 440 ± 2 Ma, indicating a late Ordovician or early Silurian age for the protoliths. The uppermost unit (the Serre Unit) comprises porphyritic (meta-) volcanic and volcaniclastic rocks dated to the Permian (271 ± 2 Ma), on top of which remnants of the Mesozoic cover is preserved. Detailed mapping of an area about 140 km2 shows that (i) the ultra-high pressure Chasteiran Unit is localized at the boundary between the Pinerolo and Muret Units, (ii) the Granero Orthogneiss may be considered as the mylonitic sole of the Muret Unit, characterized by a top-to-W sense of shear, and (iii) the contact between the Muret and Serre Units displays ductile-to brittle structures (La Fracho Shear Zone), indicating a top-to-the-NW displacement of the hangingwall with respect to the footwall. A final episode of brittle faulting, cutting across the nappe stack (the Trossieri Fault), indicates an extensional stage in the core of the Alpine belt, as previously documented in more external zones. This work provides a necessary and robust basis before an accurate discussion of processes acting during continental subduction of the Dora-Maira Massif may be understood.

Background and Aims: Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions influenced heavily by environmental factors. DNA methylation is a form of epigenetic regulation linking environmental stimuli to gene expression changes and inflammation. Here, we investigated how DNA methylation of the tumor necrosis factor (TNF) promoter differs between inflamed and uninflamed mucosa of IBD patients, including anti-TNF responders and nonresponders. Methods: We obtained mucosal biopsies from 200 participants (133 IBDs and 67 controls) and analyzed TNF promoter methylation using bisulfite sequencing, comparing inflamed with uninflamed segments, in addition to paired inflamed/uninflamed samples from individual patients. We conducted similar analyses on purified intestinal epithelial cells from bowel resections. We also compared TNF methylation levels of inflamed and uninflamed mucosa from a separate cohort of 15 anti-TNF responders and 17 nonresponders. Finally, we sequenced DNA methyltransferase genes to identify rare variants in IBD patients and functionally tested them using rescue experiments in a zebrafish genetic model of DNA methylation deficiency. Results: TNF promoter methylation levels were decreased in inflamed mucosa of IBD patients and correlated with disease severity. Isolated intestinal epithelial cells from inflamed tissue showed proportional decreases in TNF methylation. Anti-TNF nonresponders showed lower levels of TNF methylation than responders in uninflamed mucosa. Our sequencing analysis revealed 2 missense variants in DNA methyltransferase 1, 1 of which had reduced function in vivo. Conclusion: Our study reveals an association of TNF promoter hypomethylation with mucosal inflammation, suggesting that IBD patients may be particularly sensitive to inflammatory environmental insults affecting DNA methylation. Together, our analyses indicate that TNF promoter methylation analysis may aid in the characterization of IBD status and evaluation of anti-TNF therapy response.

La décentralisation représente une rupture radicale des gestions et des relations entre l’Etat et ses populations, suite à la mauvaise gouvernance de l’Etat unitaire qui détenait tous les pouvoirs. Elle consiste à faire reposer la gestion des Provinces et des Entités Territoriales Décentralisées sur l’autonomie fiscale, financière, administrative et politique. Alors que des dispositions pertinentes de la Constitution de la République du Congo déterminent la sphère d’action exclusive du pouvoir central et des provinces ainsi que la zone concurrente entre les deux échelons du pouvoir d’Etat, les provinces et les entités territoriales décentralisées peinent à décoller et à jouir de leur autonomie rattachée au statut juridique que leur consacre l’évolution du droit public positif congolais. Le constat qui est fait de manière générale et particulièrement en ce qui concerne la Ville de Kinshasa et ses ETD (24 Communes), est qu’on a l’impression d’être en face des Entités déconcentrées qui dépendent intimement du pouvoir central pour la Ville de Kinshasa et de cette dernière pour ses Entités territoriales décentralisées.

ObjectiveDue to its favorable outcome regarding late morbidity and mortality, thoracic endovascular repair (TEVAR) is becoming more popular for uncomplicated type B aortic dissection (TBAD). This study aimed to compare preemptive endovascular treatment and optimal medical treatment (OMT) and OMT alone in patients presenting uncomplicated TBAD with predictors of aortic progression.DesignRetrospective multicenter studyMethodsWe analyzed patients with uncomplicated TBAD and risk factors of progression in two French academic centers. Aortic events [defined as aortic-related (re)intervention or aortic-related death after initial hospitalization], postoperative complications, non-aortic events, and radiologic aortic progression and remodeling were recorded and analyzed. Analysis was performed on an intention-to-treat basis.ResultsBetween 2011 and 2021, preemptive endovascular procedures at the acute and early subacute phase (

Abstract Our laboratory has shown that calpain‐2 activation in the brain following acute injury is directly related to neuronal damage and the long‐term functional consequences of the injury, while calpain‐1 activation is generally neuroprotective and calpain‐1 deletion exacerbates neuronal injury. We have also shown that a relatively selective calpain‐2 inhibitor, referred to as C2I, enhanced long‐term potentiation and learning and memory, and provided neuroprotection in the controlled cortical impact (CCI) model of traumatic brain injury (TBI) in mice. Using molecular dynamic simulation and Site Identification by Ligand Competitive Saturation (SILCS) software, we generated about 130 analogs of C2I and tested them in a number of in vitro and in vivo assays. These led to the identification of two interesting compounds, NA‐112 and NA‐184. Further analyses indicated that NA‐184, (S)‐2‐(3‐benzylureido)‐N‐((R,S)‐1‐((3‐chloro‐2‐methoxybenzyl)amino)‐1,2‐dioxopentan‐3‐yl)‐4‐methylpentanamide, selectively and dose‐dependent inhibited calpain‐2 activity without evident inhibition of calpain‐1 at the tested concentrations in mouse brain tissues and human cell lines. Like NA‐112, NA‐184 inhibited TBI‐induced calpain‐2 activation and cell death in mice and rats, both male and females. Pharmacokinetic and pharmacodynamic analyses indicated that NA‐184 exhibited properties, including stability in plasma and liver and blood–brain barrier permeability, that make it a good clinical candidate for the treatment of TBI.

Osteoporosis after bariatric surgery is an increasing health concern as the rate of bariatric surgery has risen. In animal studies mimicking bariatric procedures, bone disease, together with decreased serum levels of Ca2+, Mg2+ and the gastric hormone Ghrelin were described. Ghrelin regulates metabolism by binding to and activating the growth hormone secretagogue receptor (GHSR) which is also expressed in the kidney. As calcium and magnesium are key components of bone, we tested the hypothesis that Ghrelin-deficiency contributes to osteoporosis via reduced upregulation of the renal calcium channel TRPV5 and the heteromeric magnesium channel TRPM6/7. We expressed GHSR with TRPV5 or TRPM6/7 channel in HEK293 cells and treated them with purified Ghrelin. Whole-cell current density was analyzed by patch-clamp recording. Nephron-specific gene expression was performed by tubular microdissection followed by qPCR in wild-type (WT) mice, and immunofluorescent imaging of GHSR-eGFP mice. Tubular magnesium homeostasis was analyzed in GHSR-null and WT mice at baseline and after caloric restriction. After Ghrelin exposure, whole-cell current density did not change for TRPV5 but increased for TRPM6/7 in a dose-dependent fashion. Applying the Ghrelin-mimetic (D-Trp7, Ala8,D-Phe10)-α-MSH (6–11) amide without and with the GHSR antagonist (D-Lys3)-GHRP6, we confirmed the stimulatory role of Ghrelin towards TRPM6/7. As GHSR initiates downstream signaling via protein kinase A (PKA), we found that the PKA inhibitor H89 abrogated TRPM6/7 stimulation by Ghrelin. Similarly, transfected Gαs, but not the Gαs mutant Q227L, nor Gαi2, Gαq, or Gα13 upregulated TRPM6/7 current density. In microdissected TALs and DCTs similar levels of GHSR mRNA were detected. In contrast, TRPM6 mRNA was expressed in the DCT and also detected in the TAL at 25% expression compared to DCT. Immunofluorescent studies using reporter GHSR-eGFP mice showed a strong eGFP signal in the TAL but surprisingly displayed no eGFP signal in the DCT. In 3-, 6-, and 9-month-old GHSR-null and WT mice, baseline serum magnesium was not significantly different, but 24-h urinary magnesium excretion was elevated in 9-month-old GHSR-null mice. In calorically restricted GHSR-null mice, we detected excess urinary magnesium excretion and reduced serum magnesium levels compared to WT mice. The kidneys from calorically restricted WT mice showed upregulated gene expression of magnesiotropic genes Hnf1b, Cldn-16, Cldn-19, Fxyd-2b, and Parvalbumin compared to GHSR-null mice. Our in vitro studies show that Ghrelin stimulates TRPM6/7 via GHSR and Gαs-PKA signaling. The murine studies are consistent with Ghrelin-GHSR signaling inducing reduced urinary magnesium excretion, particularly in calorically restricted mice when Ghrelin levels are elevated. This effect may be mediated by Ghrelin-upregulation of TRPM6 in the TAL and/or upregulation of other magnesiotropic genes. We postulate that rising Ghrelin levels with hunger contribute to increased renal Mg2+ reabsorption to compensate for lack of enteral Mg2+ uptake.

The targeted LC-MS/MS method has been widely applied for peptide quantification, offering sensibility, specificity, and reproducibility to the analysis. However, it requires the prior selection of targets, including the construction of a spectral library. Here, we present a dataset comprising peptide mass spectra for targeted LC-MS/MS method setup, applied to a set of human complement system proteins. Additionally, we selected a group of peptides and demonstrated their stability and reproducibility in quantification. This dataset is invaluable for studies aiming at the quantification of the complement system proteins by targeted LC-MS/MS, as it provides data for spectral library construction and a list of selected peptides.

Este estudo teve como objetivo caracterizar o estado da arte e identificar a estrutura conceitual subjacente sobre o fenômeno do humor no ambiente de trabalho. Para tanto, uma revisão sistemática da literatura foi realizada com uso da base de dados da Web of Science. Os resultados revelaram que a estrutura conceitual da temática é concebida por investigações dos tipos de humor, instrumento de medida, usos do humor e os seus efeitos para as organizações. Além disso, os principais usos do humor referem-se a: proteção contra supervisão abusiva, expressão da criatividade e pensamento crítico, comunicação direta e indireta a partir do sarcasmo, aliviar o estresse e tensões e incentivar o trabalho cooperativo. A partir dos itinerários de pesquisa, lacunas na literatura existente foram encontradas e que inspiraram a criação de uma agenda de pesquisa. Esta revisão apresenta um panorama que pode auxiliar gestores, trabalhadores e organizações a compreenderem a relevância estratégica do humor no contexto do trabalho. É esperado que a temática se torne pauta nas agendas de pesquisa no âmbito da Gestão de Pessoas e Comportamento Organizacional.

Abstract The rate of biological invasions is steadily increasing, with major ecological and economic impacts accounting for billions of dollars in damage as a result. One spectacular example is the western Atlantic invasion by lionfishes. In the Mediterranean Sea, invasions from the Red Sea via the Suez Canal (termed Lessepsian invasions) comprise more than 100 fish species, including a recent invasion by lionfish. In light of the devastating effects of lionfish in the Caribbean Sea, understanding the dynamics of Mediterranean lionfish invasion is crucial. The Lessepsian lionfish invasion started in 2012, and rapidly spread to the central Mediterranean. Here, we used thousands of RAD seq genomic markers to study the population dynamics of this invasion. While we did not find a reduction in genetic diversity between source (Red Sea) and invasive (Mediterranean) populations (i.e., bottleneck effects), we found evidence of population structure within the invasive range in the Mediterranean Sea. We found that loci that are potentially under selection may play an important role in invasion success (in particular, genes involved in osmoregulation and fin spine sizes). Genomic approaches proved powerful in examining the ecological and evolutionary patterns of successful invaders and may be used as tools to understand and potentially mitigate future invasions.

Single-cell CRISPR-based transcriptome screens are potent genetic tools for concomitantly assessing the expression profiles of cells targeted by a set of guides RNA (gRNA), and inferring target gene functions from the observed perturbations. However, due to various limitations, this approach lacks sensitivity in detecting weak perturbations and is essentially reliable when studying master regulators such as transcription factors. To overcome the challenge of detecting subtle gRNA induced transcriptomic perturbations and classifying the most responsive cells, we developed a new supervised autoencoder neural network method. Our Sparse supervised autoencoder (SSAE) neural network provides selection of both relevant features (genes) and actual perturbed cells. We applied this method on an in-house single-cell CRISPR-interference-based (CRISPRi) transcriptome screening (CROP-Seq) focusing on a subset of long non-coding RNAs (lncRNAs) regulated by hypoxia, a condition that promote tumor aggressiveness and drug resistance, in the context of lung adenocarcinoma (LUAD). The CROP-seq library of validated gRNA against a subset of lncRNAs and, as positive controls, HIF1A and HIF2A, the 2 main transcription factors of the hypoxic response, was transduced in A549 LUAD cells cultured in normoxia or exposed to hypoxic conditions during 3, 6 or 24 h. We first validated the SSAE approach on HIF1A and HIF2 by confirming the specific effect of their knock-down during the temporal switch of the hypoxic response. Next, the SSAE method was able to detect stable short hypoxia-dependent transcriptomic signatures induced by the knock-down of some lncRNAs candidates, outperforming previously published machine learning approaches. This proof of concept demonstrates the relevance of the SSAE approach for deciphering weak perturbations in single-cell transcriptomic data readout as part of CRISPR-based screening.

Abstract Angelman syndrome (AS) is a rare neurogenetic disorder caused by UBE3A deficiency and characterized by severe developmental delay, cognitive impairment, and motor dysfunction. In the present study, we performed RNA-seq on hippocampal samples from both wildtype (WT) and AS male mice, with or without contextual fear memory recall. There were 281 recall-associated differentially expressed genes (DEGs) in WT mice and 268 DEGs in AS mice, with 129 shared by the two genotypes. Gene ontology analysis showed that extracellular matrix and stimulation-induced response genes were prominently enriched in recall-associated DEGs in WT mice, while nuclear acid metabolism and tissue development genes were highly enriched in those from AS mice. Further analyses showed that the 129 shared DEGs belonged to nuclear acid metabolism and tissue development genes. Unique recall DEGs in WT mice were enriched in biological processes critical for synaptic plasticity and learning and memory, including the extracellular matrix network clustered around fibronectin 1 and collagens. In contrast, AS-specific DEGs were not enriched in any known pathways. These results suggest that memory recall in AS mice, while altering the transcriptome, fails to recruit memory-associated transcriptional programs, which could be responsible for the memory impairment in AS mice.

The steep and unstable terrain found on debris-covered glaciers, rock glaciers, talus slopes, moraines and other proglacial features often make terrestrial ground-penetrating radar (GPR) surveys unsafe or cost-prohibitive. To address these challenges, this research introduces a novel approach for studying buried ice using multi-low-frequency drone-based GPR. Monostatic antennas of 50, 100, and 200 MHz were flown along a transect spanning a debris-covered glacier and an ice–debris complex at Shár Shaw Tagà (Grizzly Creek) in southwest Yukon, Canada. The drone-based results were compared to manual GPR at two locations along the transect. The two manual segments were conducted using the same radar system in a bi-static mode and included common mid-point (CMP) surveys. Overall, the drone-based radar successfully identified buried ice and enabled estimation of ice body thickness. Notably, CMP results confirmed layer characteristics and enabled depths to be measured across the entire drone-based transect. Discrimination of detail across a range of depths was made possible by comparing the three low frequencies, highlighting the possibility of using this method for future investigations of debris thickness in addition to quantifying buried ice. This study confirms the effectiveness of drone-based GPR combined with manual CMP for surveying ice beneath previously inaccessible terrain.

Globally, groupers (Serranidae) are commercially important fish species. Hybridization within this family has been reported in captivity and natural environments, usually among congeneric species. However, intergeneric hybridization has been reported only occasionally. Given the commercial interest in these fish, artisanal or recreational fishermen easily notice “weird-looking” individuals. This is the case of an unidentified grouper noticed by a spearfisher in Lebanese Mediterranean waters. Visual comparisons raised the possibility that the observed specimen was a hybrid. Molecular analysis based on two mitochondrial and three nuclear markers was performed to investigate this potential hybrid’s affinity. The discordance of the phylogenetic gene trees of the mitochondrial and nuclear markers indicates that E. marginatus and M. rubra are potential parent species of a hybrid individual in our samples. The subsequent haploweb analysis based on the S7 nuclear marker reveals the affinity of the hybrid individual to both E. marginatus and M. rubra. In this specific hybridization case, the nuclear marker S7 emerges as a valuable diagnostic tool for species delineation and hybrid detection.

In 1984, Gary Lynch and Michel Baudry published in Science a novel biochemical hypothesis for learning and memory, in which they postulated that the calcium-dependent protease, calpain, played a critical role in regulating synaptic properties and the distribution of glutamate receptors, thereby participating in memory formation in hippocampus. Over the following 40 years, much work has been done to refine this hypothesis and to provide convincing arguments supporting what was viewed at the time as a simplistic view of synaptic biochemistry. We have now demonstrated that the two major calpain isoforms in the brain, calpain-1 and calpain-2, execute opposite functions in both synaptic plasticity/learning and memory and in neuroprotection/neurodegeneration. Thus, calpain-1 activation is required for triggering long-term potentiation (LTP) of synaptic transmission and learning of episodic memory, while calpain-2 activation limits the magnitude of LTP and the extent of learning. On the other hand, calpain-1 is neuroprotective while calpain-2 is neurodegenerative, and its prolonged activation following various types of brain insults leads to neurodegeneration. The signaling pathways responsible for these functions have been identified and involve local protein synthesis, cytoskeletal regulation, and regulation of glutamate receptors. Human families with mutations in calpain-1 have been reported to have impairment in motor and cognitive functions. Selective calpain-2 inhibitors have been synthesized and clinical studies to test their potential use to treat disorders associated with acute neuronal damage, such as traumatic brain injury, are being planned. This review will illustrate the long and difficult journey to validate a bold hypothesis.

Background and purpose: There is inconsistency in the literature regarding the relationship between increased birthweight and risk of developmental dysplasia of the hip (DDH). We aimed to investigate the correlation between birthweight and pubo-femoral distance (PFD), as well as Graf’s α angle in newborns undergoing hip ultrasound examination at 6 weeks of age. Patients and methods: Basic newborn characteristics and ultrasound measurements were retrospectively collected during a 1-year study period. We excluded multiple births, newborns born at less than 37 gestational weeks, and incomplete information. Simple and multiple linear regression analyses were performed to evaluate the correlation of birthweight and PFD, and, second, birthweight and α angles including a stratified regression analysis investigating the potential effect modification of sex. Results: 707 newborns (1,414 hips) were included. Mean birthweight was significantly higher for male newborns (P < 0.001). Increased birthweight was positively correlated to PFD values (crude coefficient 0.21, 95% confidence interval [CI] 0.10–0.32) and the correlation was still present after adjusting for sex, family history, and breech presentation (adjusted coefficient 0.18, CI 0.07–0.29). The stratified α angle model for the males was significant for both the crude coefficient (–0.73, CI –1.28 to –0.19) and the adjusted (–0.59, CI –1.15 to –0.03), and also for the females (crude coefficient –1.14, CI –1.98 to –0.31 and adjusted coefficient –1.15, CI –1.99 to –0.31). Conclusion: We found that increased birthweight positively correlated to PFD, and negatively correlated to α angle, but this was not of clinical significance.

Abstract While depression and chronic pain are frequently comorbid, underlying neuronal circuits and their psychopathological relevance remain poorly defined. Here we show in mice that hyperactivity of the neuronal pathway linking the basolateral amygdala to the anterior cingulate cortex is essential for chronic pain-induced depression. Moreover, activation of this pathway in naive male mice, in the absence of on-going pain, is sufficient to trigger depressive-like behaviors, as well as transcriptomic alterations that recapitulate core molecular features of depression in the human brain. These alterations notably impact gene modules related to myelination and the oligodendrocyte lineage. Among these, we show that Sema4a, which was significantly upregulated in both male mice and humans in the context of altered mood, is necessary for the emergence of emotional dysfunction. Overall, these results place the amygdalo-cingulate pathway at the core of pain and depression comorbidity, and unravel the role of Sema4a and impaired myelination in mood control.

Debris-covered glaciers are an important component of the mountain cryosphere and influence the hydrological contribution of glacierized basins to downstream rivers. This study examines the potential to make estimates of debris thickness, a critical variable to calculate the sub-debris melt, using ground-based thermal infrared radiometry (TIR) images. Over four days in August 2019, a ground-based, time-lapse TIR digital imaging radiometer recorded sequential thermal imagery of a debris-covered region of Peyto Glacier, Canadian Rockies, in conjunction with 44 manual excavations of debris thickness ranging from 10 to 110 cm, and concurrent meteorological observations. Inferring the correlation between measured debris thickness and TIR surface temperature as a base, the effectiveness of linear and exponential regression models for debris thickness estimation from surface temperature was explored. Optimal model performance (R2 of 0.7, RMSE of 10.3 cm) was obtained with a linear model applied to measurements taken on clear nights just before sunrise, but strong model performances were also obtained under complete cloud cover during daytime or nighttime with an exponential model. This work presents insights into the use of surface temperature and TIR observations to estimate debris thickness and gain knowledge of the state of debris-covered glacial ice and its potential hydrological contribution.

O florescimento no trabalho tem se mostrado como um campo promissor para pesquisas, pois está ligado às noções de bem-estar do indivíduo. Florescer remete ao entendimento de que os indivíduos no trabalho desfrutam da vida boa, alcançam o seu pleno desenvolvimento e apresentam maiores percepções de qualidade de vida. Com isso, o objetivo desta pesquisa consiste em analisar o panorama atual da produção científica internacional sobre florescimento no trabalho, propondo uma agenda de pesquisa. A partir de uma combinação entre revisão sistemática da literatura com análise bibliométrica, foram encontrados 42 artigos que versam sobre o florescimento do indivíduo no ambiente de trabalho. As análises se dividiram em indicadores bibliométricos e indicadores de conteúdo, podendo ser constatada uma evolução do campo a partir de 2005 e três clusters de tradições de pesquisa foram encontrados: florescimento e dimensões de bem-estar, bem-estar e engajamento no trabalho. Além disso, lacunas de pesquisas foram identificadas, o que permitiu o delineamento de uma agenda. Implicações teóricas e práticas são discutidas.

This paper presents the extension of the monolayer snow model of a semi-distributed hydrological model (HYDROTEL) to a multilayer model that considers snow to be a combination of ice and air, while accounting for freezing rain. For two stations in Yukon and one station in northern Quebec, Canada, the multilayer model achieves high performances during calibration periods yet similar to the those of the monolayer model, with KGEs of up to 0.9. However, it increases the KGE values by up to 0.2 during the validation periods. The multilayer model provides more accurate estimations of maximum SWE and total spring snowmelt dates. This is due to its increased sensitivity to thermal atmospheric conditions. Although the multilayer model improves the estimation of snow heights overall, it exhibits excessive snow densities during spring snowmelt. Future research should aim to refine the representation of snow densities to enhance the accuracy of the multilayer model. Nevertheless, this model has the potential to improve the simulation of spring snowmelt, addressing a common limitation of the monolayer model.

Chalcones are polyphenols that belong to the flavonoids family, known for their broad pharmacological properties. They have thus attracted the attention of chemists for their obtention and potential activities. In our study, a library of compounds from 2′-hydroxychalcone’s family was first synthesized. A one-step mechanochemical synthesis via Claisen–Schmidt condensation reaction under ball mill conditions was studied, first in a model reaction between a 5′-fluoro-2′-hydroxyacetophenone and 3,4-dimethoxybenzaldehyde. The reaction was optimized in terms of catalysts, ratio of reagents, reaction time, and influence of additives. Among all assays, we retained the best one, which gave the highest yield of 96% when operating in the presence of 1 + 1 eq. of substituted benzaldehyde and 2 eq. of KOH under two grinding cycles of 30 min. Thus, this protocol was adopted for the synthesis of the selected library of 2′-hydroxychalcones derivatives. The biological activities of 17 compounds were then assessed against Plasmodium falciparum, Leishmania donovani parasite development, as well as IGR-39 melanoma cell lines by inhibiting their viability and proliferation. Compounds 6 and 11 are the most potent against L. donovani, exhibiting IC50 values of 2.33 µM and 2.82 µM, respectively, better than the reference drug Miltefosine (3.66 µM). Compound 15 presented the most interesting antimalarial activity against the 3D7 strain, with IC50 = 3.21 µM. Finally, chalcone 12 gave the best result against IGR-39 melanoma cell lines, with an IC50 value of 12 µM better than the reference drug Dacarbazine (IC50 = 25 µM).

The silver-cheeked toadfish Lagocephalus sceleratus (Gmelin 1789), and to a lesser degree the orange spotted toadfish Torquigener hypselogeneion (Bleeker, 1852), pose threats to human health from physical attacks and poisonings in the Eastern Mediterranean Sea. This study reviewed human health-related impacts resulting from these pufferfish, compiling and assessing records from online sources, the peer-reviewed literature, medical records, personal interviews, and observations across the Eastern Mediterranean in the years 2004 to 2023. A total of 198 events impacting human health were documented: 28 records of physical attacks, at least 144 non-lethal poisoning episodes, and 27 human fatalities resulting from consumption. The majority of the reported incidences occurred in Syria, Türkiye, and Lebanon. Most physical attacks occurred in summer, while most poisoning events occurred during winter. The number of recorded incidents greatly increased after 2019, especially with regard to poisonings, yet whether this is related to greater media attention, or to increased fish abundance is unclear. This is the first comprehensive study to collate findings on attacks, poisonings and fatalities caused by these pufferfish in the Mediterranean Sea, and may help in improving national health policies. We urge the continuation of national campaigns to caution residents and tourists of these species’ high toxicities and potential aggressiveness.

Introdução/Objetivos: Sepse é a disfunção múltipla de órgãos causada pela resposta inflamatória irregular do corpo a uma infecção, incluída como prioridade em Saúde Pública pela Organização Mundial de Saúde. É a maior causa de mortes entre pacientes admitidos UTIs, o que é associado à falta de diagnóstico/tratamento eficiente em tempo adequado. O diagnóstico por hemocultura considerado padrão ouro na diagnose, demanda de 3 a 7 dias para o resultado final e baixa sensibilidade. Avanços têm sido realizados na identificação de patógenos a partir de hemocultura positiva, como automação dos testes fenotípicos e bioquímicos, testes moleculares e espectrometria de massas (MS) pela técnica MALDI-TOF, porém a dependência do cultivo prévio ocasiona importantes limitações, com aproximadamente 70% de resultados falso negativos e longo tempo necessário para o crescimento (1 a 5 dias ou mais). Neste estudo desenvolvemos uma prova de conceito para metodologia baseada em LC-MS/MS com o objetivo de monitorar íons de alta intensidade específicos para micro-organismos relacionados à sepse, diretamente de amostras de sangue total, sem a necessidade de cultivo microbiológico. Metodologia: O método que desenvolvemos tem como etapas metodológicas partindo de amostra de sangue total: lise diferencial de pH básico e lise celular ácida, extração/digestão rápida das proteínas do microrganismo e o uso da LC/ESI-MS/MS na análise/identificação dos peptídeos únicos discriminatórios de cada patógeno estudado. Resultados: Demonstramos a eficácia de nossa metodologia ao diagnosticar amostras infectadas com um ou mais dos seguintes patógenos: S. aureus, P. aeruginosa e C. albicans. Nosso método selecionou peptídeos discriminantes a partir dos dados gerados por LC-MS/MS que forneceram identificações corretas para todos os microrganismos mencionados acima com sensibilidade de 87,5% em sete horas e sem necessidade de enriquecimento em microcultura. Conclusão: Apresentamos um procedimento simples e rápido para a pré-seleção de um painel de peptídeos a ser usado para diagnóstico. A vantagem do nosso método é que podemos diagnosticar patógenos diretamente do sangue total, ao invés de passar pelo processo de cultura, configurando uma alternativa diagnóstica para sangue infecção. Prevemos também que nosso método será útil na identificação de fungos filamentosos e no diagnóstico de resistência antimicrobiana, em última análise, contribuindo para dados epidemiológicos.

Abstract Microneedling is a popular skin resurfacing and rejuvenation procedure. In order to develop better adjunct products for consumers, there is a scientific need to establish greater understanding of the mechanism in which microneedling stimulates regeneration within skin. The purpose of this study is to develop a physiologically relevant ex vivo tissue model which closely mimics the actual microneedling procedure to elucidate its mechanism of action. In this study, human ex vivo skin was subjected to microneedling treatment and cultured for 6 days. Histological analysis demonstrated that the ex vivo skin was able to heal from microneedling injury throughout the culture period. Microneedling treatment stimulated proliferation and barrier renewal of the skin. The procedure also increased the levels of inflammatory cytokines and angiogenic growth factors in a dynamic and time dependent fashion. The tissue demonstrated hallmark signs of epidermal regeneration through morphological and molecular changes after the treatment. This is one of the first works to date that utilizes microneedled ex vivo skin to demonstrate its regenerative behavior. Our model recapitulates the main features of the microneedling treatment and enables the evaluation of future cosmetic active ingredients used in conjunction with microneedling.

Abstract Background Presently, there is a wide variety of classification methods and deep neural network approaches in bioinformatics. Deep neural networks have proven their effectiveness for classification tasks, and have outperformed classical methods, but they suffer from a lack of interpretability. Therefore, these innovative methods are not appropriate for decision support systems in healthcare. Indeed, to allow clinicians to make informed and well thought out decisions, the algorithm should provide the main pieces of information used to compute the predicted diagnosis and/or prognosis, as well as a confidence score for this prediction. Methods Herein, we used a new supervised autoencoder (SAE) approach for classification of clinical metabolomic data. This new method has the advantage of providing a confidence score for each prediction thanks to a softmax classifier and a meaningful latent space visualization and to include a new efficient feature selection method, with a structured constraint, which allows for biologically interpretable results. Results Experimental results on three metabolomics datasets of clinical samples illustrate the effectiveness of our SAE and its confidence score. The supervised autoencoder provides an accurate localization of the patients in the latent space, and an efficient confidence score. Experiments show that the SAE outperforms classical methods (PLS-DA, Random Forests, SVM, and neural networks (NN)). Furthermore, the metabolites selected by the SAE were found to be biologically relevant. Conclusion In this paper, we describe a new efficient SAE method to support diagnostic or prognostic evaluation based on metabolomics analyses.

يهدف هذا البحث إلى دراسة تأثير الأجنحة الرفرافة Stern flaps على الأداء الهيدروديناميكي للقوارب السريعة، وذلك من خلال استخدام تقنية الـ CFD. لقد تم استخدام طريقة الـ URANS والموديل وبرنامج الـ ANSYS لحل معادلات نافييه ستوكس الناظمة للتدفق. كما وتم استخدام طريقة الـ VOF من أجل حل السطح الحر ودراسة التأثير المتبادل بين الماء والهواء. المقارنة بين النتائج الرقمية والنتائج التجريبية للمقاومة الكلية تظهر تطابق كبير بين النتائج وهذا يؤكد مدى دقة الـ CFD في حل هذا النوع من التدفقات.

Cet article est un témoignage sur les crises forestières et environnementales passées et actuelles. Les trois points de vue abordés portent sur la gestion des forêts publiques de l’ONF, sur les politiques publiques du ministère chargé de l’environnement et enfin sur la gestion familiale d’une forêt dans les Vosges. Messages clés La gestion d’une crise nécessite d’appréhender le temps. La gestion d’une crise nécessite des décisions. En forêt, les décisions doivent être prises à différents niveaux.

The synthesis and antiplasmodial evaluation of new hybrids combining the pharmacophore structures of artemisinin, ciprofloxacin or norfloxacin, and 7-chloroquinoline are reported in this study. The first step for all of the syntheses is the obtainment of key piperazine esters intermediates bearing the drugs ciprofloxacin and norfloxacin. Using these platforms, 18 final compounds were synthesized through a multistep procedure with overall yields ranging between 8 and 20%. All compounds were screened for their antiplasmodial activity against the chloroquine-resistant Plasmodium falciparum FcB1 strain. Compounds 20, 21, 22, and 28, bearing an artesunate fragment with ciprofloxacin, exhibited IC50 values in the range of 3.5–5.4 nM and excellent selectivity indices. Among the compounds bearing the artesunate moiety on the norfloxacin, two of them, 23 and 24, afforded IC50 values of 1.5 nM and 1.9 nM, respectively. They also showed excellent selectivity indices. The most potent compounds were also evaluated against the CQ-resistant Dd2 strain of Plasmodium falciparum, demonstrating that those compounds incorporating the artesunate fragment were the most potent. Finally, the combination of artesunate with either ciprofloxacin or norfloxacin moieties in a single molecular entity proved to substantially enhance the activity and selectivity when compared to the administration of the unconjugated counterparts artesunate/ciprofloxacin and artesunate/norfloxacin.

Abstract We propose a new quantum-safe digital signature algorithm called Multivariate Polynomial Public Key Digital Signature (MPPK/DS). The core of the algorithm is based on the modular arithmetic property that for a given element g, greater than equal to two, in a prime Galois field GF(p) and two multivariate polynomials P and Q, if P is equal to Q modulo p-1, then g to the power of P is equal to g to the power of Q modulo p. MPPK/DS is designed to withstand the key-only, chosen-message, and known-message attacks. Most importantly, making secret the element g disfavors quantum computers’ capability to solve the discrete logarithm problem. The security of the MPPK/DS algorithm stems from choosing a prime p associated with the field GF(p), such that p is a sum of a product of an odd prime number q multiplied with a power x of two and one. Given such a choice of a prime, choosing even coefficients of the publicly available polynomials makes it hard to find any private information modulo p-1. Moreover, it makes it exponentially hard to lift the solutions found modulo q to the ring of integers modulo p-1 by properly arranging x and q. However, finding private information modulo the components q and power x of two is an NP-hard problem since it involves solving multivariate equations over the chosen finite field. The time complexity of searching a private key from a public key or signatures is exponential over GF(p). The time complexity of perpetrating a spoofing attack is also exponential for a field GF(p). MPPK/DS can achieve all three NIST security levels with optimized choices of multivariate polynomials and the generalized safe prime p.

Abstract Nucleic acid polymers block the assembly of hepatitis B virus (HBV) subviral particles, effectively preventing hepatitis B surface antigen (HBsAg) replenishment in the circulation. Nucleic acid polymer (NAP)–based combination therapy of HBV infection or HBV/hepatitis D virus (HDV) co‐infection is accompanied by HBsAg clearance and seroconversion, HDV‐RNA clearance in co‐infection, and persistent functional cure of HBV (HBsAg < 0.05 IU/ml, HBV‐DNA target not dected, normal alanine aminotransferase) and persistent clearance of HDV RNA. An analysis of HBsAg isoform changes during quantitative HBsAg declines (qHBsAg), and subsequent treatment‐free follow‐up in the REP 301/REP 301‐LTF (HBV/HDV) and REP 401 (HBV) studies was conducted. HBsAg isoforms were analyzed from frozen serum samples using Abbott Research Use Only assays for HBsAg isoforms (large [L], medium [M], and total [T]). The relative change over time in small HBsAg relative to the other isoforms was inferred by the change in the ratio over time of T‐HBsAg to M‐HBsAg. HBsAg isoform declines followed qHBsAg declines in all participants. No HBsAg isoforms were detectable in any participants with functional cure. HBsAg declines > 2 log10 IU/ml from baseline were correlated with selective clearance of S‐HBsAg in 39 of 42 participants. Selective S‐HBsAg decline was absent in 9 of 10 participants with HBsAg decline < 2 log10 IU/ml from baseline. Mild qHBsAg rebound during follow‐up

Abstract Here we describe the structure, the high-pressure, low-temperature (HP-LT) metamorphism and tectonic evolution of the Briançonnais distal margin units from the south Western Alps. The studied area extends southwest of the Dora-Maira (U)HP basement units and east-southeast of the classical Briançonnais nappes. A new structural map accompanied by geological profiles shows the thrusting of the oceanic nappes (Monviso and Queyras units) onto the distal Briançonnais units (D1 and D2 late Eocene deformation phases) under blueschist-facies conditions. Subsequent deformation during the Early Oligocene (D3 deformation phase) took place under greenschist-facies conditions and was associated with back-folding and -thrusting in the units overlying the Dora-Maira massif and with exhumation related to normal reactivation of former thrusts within the latter massif. Two large cover units, detached from their former distal Briançonnais basement, are redefined as the Maira-Sampeyre and Val Grana Allochthons (shortly: Maira-Grana Allochthons = MGA) including, (i) the Val Maira-Sampeyre unit involving Lower and Middle Triassic formations, seemingly detached from the Dora-Maira units during the subduction process, and (ii) the Val Grana unit with Middle-Upper Triassic and Early-Middle Jurassic formations, which was probably detached from the Maira-Sampeyre unit and correlates with the “Prepiemonte units” known from the Ligurian Alps to the Swiss Prealps. Three major shear zones involving tectonic mélanges of oceanic and continental rocks at the base of the Val Grana, Maira-Sampeyre and Dronero units testify to an early phase of exhumation within the subduction channel in front of the Adria plate. We present a new metamorphic map based on published and new petrological data, including new thermometric data obtained by Raman spectroscopy of carbonaceous material (RSCM). The TRSCM values range from ~ 400 °C to > 500 °C, going from the most external Val Grana unit and overlying Queyras schists to the uppermost Dora-Maira unit. During the Late Triassic, the width of the Briançonnais s.l. domain can be restored at ~ 100 km, whereas it reached ~ 150 km after the Jurassic rifting. A significant, second rifting event affected the Briançonnais domain during the Late Cretaceous-Paleocene, forming the Longet-Alpet chaotic breccias, which deserve further investigations.

Abstract Epidermal growth factors (EGF) play a wide range of roles in embryogenesis, skin development, immune response homeostasis. They are involved in several pathologies as well, including several cancer types, psoriasis, chronic pain and chronic kidney disease. All members share the structural EGF domain, which is responsible for receptor interaction, thereby initiating transduction of signals. EGF growth factors have intense use in fundamental research and high potential for biotechnological applications. However, due to their structural organization with three disulfide bonds, recombinant production of these factors in prokaryotic systems is not straightforward. A significant fraction usually forms inclusion bodies. For the fraction remaining soluble, misfolding and incomplete disulfide bond formation may affect the amount of active factor in solution, which can compromise experimental conclusions and biotechnological applications. In this work, we describe a reliable procedure to produce seven human growth factors of the EGF family in Escherichia coli. Biophysical and stability analyses using limited proteolysis, light scattering, circular dichroism and nanoDSF show that the recombinant factors present folded and stable conformation. Cell proliferation and scratch healing assays confirmed that the recombinant factors are highly active at concentrations as low as 5 ng/ml.

Abstract Networked-Control Systems (NCSs), a type of cyber-physical systems, consist of tightly integrated computing, communication and control technologies. While being very flexible environments, they are vulnerable to computing and networking attacks. Recent NCSs hacking incidents had major impact. They call for more research on cyber-physical security. Fears about the use of quantum computing to break current cryptosystems make matters worse. While the quantum threat motivated the creation of new disciplines to handle the issue, such as post-quantum cryptography, other fields have overlooked the existence of quantum-enabled adversaries. This is the case of cyber-physical defense research, a distinct but complementary discipline to cyber-physical protection. Cyber-physical defense refers to the capability to detect and react in response to cyber-physical attacks. Concretely, it involves the integration of mechanisms to identify adverse events and prepare response plans, during and after incidents occur. In this paper, we assume that the eventually available quantum computer will provide an advantage to adversaries against defenders, unless they also adopt this technology. We envision the necessity for a paradigm shift, where an increase of adversarial resources because of quantum supremacy does not translate into a higher likelihood of disruptions. Consistently with current system design practices in other areas, such as the use of artificial intelligence for the reinforcement of attack detection tools, we outline a vision for next generation cyber-physical defense layers leveraging ideas from quantum computing and machine learning. Through an example, we show that defenders of NCSs can learn and improve their strategies to anticipate and recover from attacks.

The angular information of light lost in conventional images but preserved and stored in light-fields plays an instrumental role in many applications such as depth estimation, 3D reconstruction and post-capture refocusing. However, the limited angular resolution of light-field images due to the consumer hardware limitations is a major drawback in its widespread adoption. In this article, we present a novel deep learning-based light-field view synthesis method from a sparse set of input views. Our proposed method, an end-to-end trainable network, utilizes convolutional block attention modules to enhance the built-in depth image-based rendering. The proposed convolutional block attention module consists of two attention modules sequentially applied in the channel and spatial dimensions to focus the network on critical features. The proposed network architecture is a combination of three sub-networks, one for stereo feature extraction, another for disparity estimation, and the last for attention-based refinement. We present two schemes for the refinement network that perform equally well but differ in the number of parameters by 1.2% and execution time by 44%. Quantitative and qualitative results on four challenging real-world datasets show the superiority of the proposed method. Our proposed method shows considerable PSNR gains, around 1 dB compared to the state of the art and around 0.5 dB over our previous method LFVS-AM. In addition, ablation studies demonstrate the effectiveness of each module of the proposed method. Finally, the parallax edge precision-recall curve shows that our method better preserves parallax details.

RESUMO O objetivo deste trabalho consiste em analisar a influência dos antecedentes contextuais Confiança Interpessoal (CI) e Confiança Organizacional (CO) sobre os Comportamentos de Cidadania Organizacional (CCO). Por meio de uma survey. Foram investigados 988 trabalhadores do setor educacional pertencentes a treze organizações de ensino privadas do estado do Rio Grande do Sul, no ano de 2017. Os dados obtidos foram analisados com o apoio do software SPSS e AMOS, por meio da Modelagem de Equações Estruturais (MEE). Os principais resultados encontrados expõem a relação de influência da Confiança Interpessoal e Organizacional sobre os Comportamentos de Cidadania Organizacional. As reflexões que emergem com os achados desta pesquisa, sugerem que o contexto social assume um papel central no estímulo aos comportamentos cooperativos e discricionários nas organizações. Observou-se também, que foram empreendidos avanços ao trazer esta discussão para o campo das instituições do setor educacional, as quais exercem um papel social, político e econômico ímpar. Para os gestores em educação, uma maior compreensão dos antecedentes contextuais sobre o CCO pode contribuir para o desenvolvimento de comportamentos voltados à cooperação, por meio do maior envolvimento entre os indivíduos e apoio da instituição à participação e valorização das contribuições dos trabalhadores do setor.

تهدف هذه الدراسة إلى ابراز دور شكل مقدمة السفينة على سفن الدعم من خلال إجراء تعديل على شكل مقدمة السفينة باستخدام MAXSURF Modeler ودراسة المقاومات في المياه الهادئة باستخدام MAXSURF Resistance والمقاومات المضافة الناتجة عن الحركات التأرجحية أثناء الإبحار بالإضافة إلى إيجاد سعة استجابة السفينة للحركات الطولية والشاقولية باستخدام برنامج MAXSURF Motions

Children and adolescents with attentional-deficit/hyperactivity disorder (ADHD) present deficits in working memory (WM), but accounts for this phenomenon are still lacking. In this study, we used two variations of a complex-span task to test whether a specific WM mechanism, attentional refreshing, causes these deficits. Attentional refreshing is a maintenance strategy based on the sequential switch of attention between maintaining and processing information in WM. Its use is evidenced by a decrease in recall performance proportional to the distraction of attention away from the memoranda. In this study, we designed two experiments requiring children and adolescents with ADHD symptoms to maintain sequences of letters for subsequent recall, while performing a distracting task. In Experiment 1, the distracting task consisted of reading digits aloud. In Experiment 2, it consisted in making spatial judgements. The pace of the distracting tasks was varied to manipulate the level of attentional distraction. We observed that recall in ADHD participants was higher in the distracting conditions that give attention more opportunity to refresh letters. Moreover, ADHD participants had a similar recall performance to their age-matched typically developing peers. This study shows first evidence that individuals with ADHD can use attention to maintain verbal information in WM and calls for more research to understand their WM development.

Abstract Background Supervised classification methods have been used for many years for feature selection in metabolomics and other omics studies. We developed a novel primal-dual based classification method (PD-CR) that can perform classification with rejection and feature selection on high dimensional datasets. PD-CR projects data onto a low dimension space and performs classification by minimizing an appropriate quadratic cost. It simultaneously optimizes the selected features and the prediction accuracy with a new tailored, constrained primal-dual method. The primal-dual framework is general enough to encompass various robust losses and to allow for convergence analysis. Here, we compare PD-CR to three commonly used methods: partial least squares discriminant analysis (PLS-DA), random forests and support vector machines (SVM). We analyzed two metabolomics datasets: one urinary metabolomics dataset concerning lung cancer patients and healthy controls; and a metabolomics dataset obtained from frozen glial tumor samples with mutated isocitrate dehydrogenase (IDH) or wild-type IDH. Results PD-CR was more accurate than PLS-DA, Random Forests and SVM for classification using the 2 metabolomics datasets. It also selected biologically relevant metabolites. PD-CR has the advantage of providing a confidence score for each prediction, which can be used to perform classification with rejection. This substantially reduces the False Discovery Rate. Conclusion PD-CR is an accurate method for classification of metabolomics datasets which can outperform PLS-DA, Random Forests and SVM while selecting biologically relevant features. Furthermore the confidence score provided with PD-CR can be used to perform classification with rejection and reduce the false discovery rate.

Therapy with nucleic acid polymers (NAPs), tenofovir disoproxil fumarate (TDF), and pegylated interferon (pegIFN) achieve high rates of HBsAg loss/seroconversion and functional cure in chronic hepatitis B virus (HBV) infection. The role of hepatitis B surface antigen (HBsAg) seroconversion and inactivation of covalently closed circular DNA (cccDNA) in establishing functional cure were examined. Archived serum from the REP 401 study was analyzed using the Abbott ARCHITECT HBsAg NEXT assay (Chicago, IL), Abbott research use–only assays for HBsAg immune complexes (HBsAg ICs), circulating HBV RNA, and the Fujirebio assay for hepatitis B core‐related antigen (HBcrAg; Malvern, PA). HBsAg became < 0.005 IU/mL in 23 participants during NAP exposure, which persisted in all participants with functional cure. HBsAg IC declined during lead‐in TDF monotherapy and correlated with minor declines in HBsAg. Following the addition of NAPs and pegIFN, minor HBsAg IC increases (n = 13) or flares (n = 2) during therapy were not correlated with HBsAg decline, hepatitis B surface antibody (anti‐HBs) titers, or alanine aminotransferase. HBsAg IC universally declined during follow‐up in participants with virologic control or functional cure. Universal declines in HBV RNA and HBcrAg during TDF monotherapy continued with NAP + pegIFN regardless of therapeutic outcome. At the end of therapy, HBV RNA was undetectable in only 5 of 14 participants with functional cure but became undetectable after removal of therapy in all participants with functional cure. Undetectable HBV RNA at the end of therapy in 5 participants was followed by relapse to virologic control or viral rebound. Conclusion: Anti‐HBs‐independent mechanisms contribute to HBsAg clearance during NAP therapy. Inactivation of cccDNA does not predict functional cure following NAP‐based therapy; however, functional cure is accompanied by persistent inactivation of cccDNA. Persistent HBsAg loss with functional cure may also reflect reduction/clearance of integrated HBV DNA. Clinicaltrials.org number NCT02565719.

Abstract Trypanosoma cruzi—the causative agent of Chagas disease—like other kinetoplastids, relies mostly on post-transcriptional mechanisms for regulation of gene expression. However, trypanosomatids undergo drastic changes in nuclear architecture and chromatin structure along their complex life cycle which, combined with a remarkable set of reversible histone post-translational modifications, indicate that chromatin is also a target for control of gene expression and differentiation signals in these organisms. Chromatin-modifying enzymes have a direct impact on gene expression programs and DNA metabolism. In this work, we have investigated the function of T. cruzi histone deacetylase 4 (TcHDAC4). We show that, although TcHDAC4 is not essential for viability, metacyclic trypomastigote TcHDAC4 null mutants show a thin cell body and a round and less condensed nucleus located very close to the kinetoplast. Sixty-four acetylation sites were quantitatively evaluated, which revealed H2AT85ac, H4K10ac and H4K78ac as potential target sites of TcHDAC4. Gene expression analyses identified three chromosomes with overrepresented regions of differentially expressed genes in the TcHDAC4 knockout mutant compared with the wild type, showing clusters of either up or downregulated genes. The adjacent chromosomal location of some of these genes indicates that TcHDAC4 participates in gene expression regulation during T. cruzi differentiation.