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This study proposes a theoretical contribution to the problem of the various distortions affecting axisymmetric capillary bridges, due to gravity or to bending effects linked to the Gaussian curvature. We deduce a clear hierarchization of effects between various reference configurations and put in a prominent position an exact first integral for the Young–Laplace equations, classical or generalized. These relationships are taken advantage of to obtain the theoretical expression of the varying inter-particle force, quantified effects of flexural strength. Finally, we establish a generalization of the classical “gorge method” to calculate accurately the capillary force of a profile subjected to distorsion due to bending when the gravity effects are negligible or not taken into account.

The didactic object of these developments on differential geometry of curves and surfaces is to present fine and convenient mathematical strategies, adapted to the study of capillary bridges. The common thread is to be able to calculate accurately in any situation the bending stress over the free surface, represented mathematically by the integral of the Gaussian curvature over the surface (called the total curvature) involved in the generalized Young–Laplace equation. We prove in particular that the resultant of the bending energy is directly linked to the wetting angles at the contact line.

Sotiria Maria Iliopoulou,1 Stergios Tsartsalis,2 Stefan Kaiser,1,2 Philippe Millet,1,2 Benjamin B Tournier1,2 1Adult Psychiatry Division, Department of Psychiatry, Geneva University Hospitals (HUG), Geneva, 1225, Switzerland; 2Faculty of Medicine, University of Geneva, Geneva, 1204, SwitzerlandCorrespondence: Sotiria Maria Iliopoulou Rue de Lausanne 20bis, 1225 Chêne Bourg, Geneva, SwitzerlandTel +41766897182Fax +41223054599Email soil@hcuge.chAbstract: Schizophrenia is a complex disease whose pathophysiology is not yet fully understood. In addition to the long prevailing dopaminergic hypothesis, the evidence suggests that neuroinflammation plays a role in the pathophysiology of the disease. Recent studies using positron emission tomography (PET) that target a 18kDa translocator protein (TSPO) in activated microglial cells in an attempt to measure neuroinflammation in patients have shown a decrease or a lack of an increase in TSPO binding. Many biological and methodological considerations have been formulated to explain these findings. Although dopamine has been described as an immunomodulatory molecule, its potential role in neuroinflammation has not been explored in the aforementioned studies. In this review, we discuss the interactions between dopamine and neuroinflammation in psychotic states. Dopamine may inhibit neuroinflammation in activated microglia. Proinflammatory molecules released from microglia may decrease dopaminergic transmission. This could potentially explain why the levels of neuroinflammation in the brain of patients with schizophrenia seem to be unchanged or decreased compared to those in healthy subjects. However, most data are indirect and are derived from animal studies or from studies performed outside the field of schizophrenia. Further studies are needed to combine TSPO and dopamine imaging to study the association between microglial activation and dopamine system function.Keywords: microglia, inflammation, biomarker, neuroimaging, PET, translocator protein

Duhok City, developed rapidly in recent years, leading to an increase in the traffic volume on its streets which are not sufficient for this increase resulting in traffic congestion. Therefore, this paper studied the delay as an important measure of effectiveness at traffic signals. The delay was measured and predicted (for saturated and under saturated conditions) to help in solving some underestimation problems by using the transportation system management (TSM) techniques. Five signalized intersections on Barzani major street in Duhok city was chosen. Vehicle delay was measured in these intersections directly from field, then it was calculated using the time-dependent equations recommended by three different official manuals, Highway Capacity Manual (HCM2000), Canadian Capacity Guide (ITE1995) and Australian Capacity Guide (ARRB1995). After that comparisons between the results of each theoretical method and the field result was made. Finally, the regression analysis technique was used to establish different relationships between the delay data obtained from the field and each of the theoretical methods to find the best applicable model to predict the vehicle delay at signalized intersections in Duhok City. It was proved that the logarithmic relationship between field and theoretical results obtained from the Canadian Capacity Guide is the best

Abstract Background The α7 nicotinic acetylcholine receptor (α7 nAChR) negatively regulates the synthesis and release of pro-inflammatory cytokines by immune cells. Our previous studies showed that in encephalitogenic T cells, α7 nAChR expression is upregulated and that activation of the cholinergic system can attenuate experimental autoimmune encephalomyelitis (EAE). GAT107 is an allosteric agonist and positive allosteric modulator (ago-PAM) of α7 nAChR that can produce persistent activation of this receptor. Therefore, in the present study, we investigated the effect of GAT107 on neuroinflammation in EAE, the animal model used for the study of multiple sclerosis (MS) via α7 nAChR, and the inflammatory pathways involved. Methods EAE was induced by administration of myelin oligodendrocyte glycoprotein (MOG35–55) in C57BL/6 mice. EAE mice were treated with the ago-PAM GAT107 or a placebo for 9 days, starting from the day of EAE induction. Clinical assessment and immunological evaluation of immune cells and cytokine production was performed. Results Following activation of the α7 nAChR by GAT107 during EAE, disease severity was significantly reduced by 70% and was correlated with a reduction in the extent of neuroinflammation in the CNS. The treatment reduced encephalitogenic T cell proliferation and the production of pro-inflammatory cytokines, as well as increased the production of the anti-inflammatory cytokine IL-10. Furthermore, the expression of immune cell markers was altered by GAT107 treatment, which induced a significant reduction in macrophages, dendritic cells, and B cells, as well as a reduction in anti-MOG35–55 antibodies. Additionally, GAT107 was found to directly activate α7 nAChR in murine macrophage RAW264.7 cells and in human PBMCs derived from MS patients and healthy donors. Conclusions Our results show that GAT107 can be a useful molecule for harnessing the cholinergic anti-inflammatory pathway for long-lasting and wide-ranging modulation and downregulation of neuroinflammation in EAE.

Neuroendocrine neoplasms are most often found in the small intestine, rectum, appendix, and stomach. The colon, excluding the appendix and the cecum, is a rare location for these neoplasms and often gives rise to highly proliferative, poorly differentiated tumors with aggressive features and dismal prognosis. A 32-year-old male presents with a large cell neuroendocrine carcinoma arising from an unusual location, the descending colon. The patient's clinical and imaging characteristics resembles those seen in the much more common neoplasm, colonic adenocarcinoma. Computed tomography and In-111 octreotide scan are limited in diagnosing large cell neuroendocrine carcinoma. Pathologic correlation of a surgical specimen is required to make the correct diagnosis.

Humpback whales Megaptera novaeangliae were severely depleted by commercial whaling. Understanding key factors in their recovery is a crucial step for their conservation worldwide. In Oceania, the Chesterfield-Bellona archipelago was a primary whaling site in the 19th century, yet has been left almost unaffected by anthropogenic activities since. We present the results of the first multidisciplinary dedicated surveys in the archipelago assessing humpback whale populations 2 centuries post-whaling. We encountered 57 groups during 24 survey days (2016-2017), among which 35 whales were identified using photographs of natural markings (photo-ID), 38 using genotyping and 22 using both. Humpback whales were sparsely distributed (0.041 whales km-1): most sightings concentrated in shallow inner-reef waters and neighbouring offshore shallow banks. The recently created marine protected area covers most of the areas of high predicted habitat suitability and high residence time from satellite-tracked whales. Surprisingly for a breeding area, sex ratios skewed towards females (1:2.4), and 45% of females were with calf. Connectivity was established with the New Caledonia breeding area to the east (mtDNA FST = 0.001, p > 0.05, 12 photo-ID and 10 genotype matches) and with the Australian Great Barrier Reef breeding area to the west (mtDNA FST = 0.006, p > 0.05). Movement of satellite-tracked whales and photo-ID matches also suggest connections with the east Australian migratory corridor. This study confirms that humpback whales still inhabit the Chesterfield-Bellona archipelago 2 centuries post whaling, and that this pristine area potentially plays a role in facilitating migratory interchange among breeding grounds of the western South Pacific.

Stanford type A dissections usually require surgery because they are associated with high morbidity and mortality. However, there are situations where medical management becomes the definitive treatment. We report the successful medical management of a 16-month chronic type A aortic dissection in a 56-year-old male patient with a past surgical history of ascending aortic aneurysm repair. The dissection is unique because it is distal to the graft and does not extend into the main aortic branches. A review of a patient's surgical history and nonenhanced imaging studies is essential when a type A dissection is discovered. Ascending aortic grafts may preclude the most serious complications of type A dissections.

We propose in this article a model describing the dynamic of a system of adipocytes, structured by their sizes. This model takes into account the differentiation of a population of mesenchymal cells into preadipocytes and of preadipocytes into adipocytes; the differentiation rates depend on the mean adipocyte radius. The considered equations are therefore ordinary differential equations, coupled with an advection equation, the growth rate of which depends on food availability and on the total surface of adipocytes. Since this velocity is discontinuous, we need to introduce a convenient notion of solutions coming from Filippov theory. We are consequently able to determine the stationary solutions of the system, to prove the existence and uniqueness of solutions and to describe the asymptotic behavior of solutions in some simple cases. Finally, the parameters of the model are fitted thanks to some experimental data and numerical simulations are displayed; a spatial extension of the model is studied numerically.

Duhok City, developed rapidly in recent years, leading to an increase in the traffic volume on its streets which are not sufficient for this increase resulting in traffic congestion. Therefore, this paper studied the delay as an important measure of effectiveness at traffic signals. The delay was measured and predicted (for saturated and under saturated conditions) to help in solving some underestimation problems by using the transportation system management (TSM) techniques. Five signalized intersections on Barzani major street in Duhok city was chosen. Vehicle delay was measured in these intersections directly from field, then it was calculated using the time-dependent equations recommended by three different official manuals, Highway Capacity Manual (HCM2000), Canadian Capacity Guide (ITE1995) and Australian Capacity Guide (ARRB1995). After that comparisons between the results of each theoretical method and the field result was made. Finally, the regression analysis technique was used to establish different relationships between the delay data obtained from the field and each of the theoretical methods to find the best applicable model to predict the vehicle delay at signalized intersections in Duhok City. It was proved that the logarithmic relationship between field and theoretical results obtained from the Canadian Capacity Guide is the best

UNLABELLED: Infections caused by antimicrobial-resistant Escherichia coli are the leading cause of death attributed to antimicrobial resistance (AMR) worldwide, and the known AMR mechanisms involve a range of functional proteins. Here, we employed a pan-genome wide association study (GWAS) approach on over 1,000 E. coli isolates from sick dogs collected across the US and Canada and identified a strong statistical association (empirical P < 0.01) of AMR, involving a range of antibiotics to a group 1 capsular (CPS) gene cluster. This cluster included genes under relaxed selection pressure, had several loci missing, and had pseudogenes for other key loci. Furthermore, this cluster is widespread in E. coli and Klebsiella clinical isolates across multiple host species. Earlier studies demonstrated that the octameric CPS polysaccharide export protein Wza can transmit macrolide antibiotics into the E. coli periplasm. We suggest that the CPS in question, and its highly divergent Wza, functions as an antibiotic trap, preventing antimicrobial penetration. We also highlight the high diversity of lineages circulating in dogs across all regions studied, the overlap with human lineages, and regional prevalence of resistance to multiple antimicrobial classes. IMPORTANCE: Much of the human genomic epidemiology data available for E. coli mechanism discovery studies has been heavily biased toward shiga-toxin producing strains from humans and livestock. E. coli occupies many niches and produces a wide variety of other significant pathotypes, including some implicated in chronic disease. We hypothesized that since dogs tend to share similar strains with their owners and are treated with similar antibiotics, their pathogenic isolates will harbor unexplored AMR mechanisms of importance to humans as well as animals. By comparing over 1,000 genomes with in vitro antimicrobial susceptibility data from sick dogs across the US and Canada, we identified a strong multidrug resistance association with an operon that appears to have once conferred a type 1 capsule production system.

Summary: Tobacco smoking is a risk factor for several human diseases. Conversely, smoking also reduces the prevalence of Parkinson’s disease, whose hallmark is degeneration of substantia nigra dopaminergic neurons (DNs). We use C. elegans as a model to investigate whether tobacco-derived nicotine activates nicotinic acetylcholine receptors (nAChRs) to selectively protect DNs. Using this model, we demonstrate conserved functions of DN-expressed nAChRs. We find that DOP-2, a D3-receptor homolog; MCU-1, a mitochondrial calcium uniporter; PINK-1 (PTEN-induced kinase 1); and PDR-1 (Parkin) are required for nicotine-mediated protection of DNs. Together, our results support involvement of a calcium-modulated, mitochondrial stress-activated PINK1/Parkin-dependent pathway in nicotine-induced neuroprotection. This suggests that nicotine-selective protection of substantia nigra DNs is due to the confluence of two factors: first, their unique vulnerability to mitochondrial stress, which is mitigated by increased mitochondrial quality control due to PINK1 activation, and second, their specific expression of D3-receptors.

C. elegans PVD neurons are conserved for morphology, function and molecular determinants with mammalian polymodal nociceptors. Functions of polymodal nociceptors require activities of multiple ion channels and receptors including members of the TRP family. GTL-1, a member of the TRPM subclass of TRP channels, was previously shown to amplify PVD-mediated responses to optogenetic stimuli. Here we characterize effects of GTL-1 on PVD-mediated behavioral responses to noxious stimuli. We show that GTL-1 is required within PVD for the immediate and enduring response to thermal (cold) stimuli. But, find no significant reduction in percent animals responding to single or to repeated noxious mechanical stimuli. Nevertheless, PVD specific knockdown of gtl-1expression reduces the magnitude of responses to noxious mechanical stimuli. To understand GTL-1’s mechanism of action we expressed it in HEK293 cells. Our results show GTL-1-dependent currents induced by activation of a Gαq-coupled Designer Receptor Exclusively Activated by Designer Drugs (DREADD). In addition, using excised patches we show that GTL-1 can be activated by internal calcium. Our results are consistent with indirect, calcium dependent, activation of GTL-1 by noxious stimuli. This mechanism explains the GTL-1-dependent amplification of responses to multiple stimuli optogenetic and sensory in PVD.

Nicotinic acetylcholine receptors (nAChRs) are widely expressed in or on various cell types and have diverse functions. In immune cells nAChRs regulate proliferation, differentiation and cytokine release. Specifically, activation of the α7 nAChR reduces inflammation as part of the cholinergic anti-inflammatory pathway. Here we review numerous effects of α7 nAChR activation on immune cell function and differentiation. Further, we also describe evidence implicating this receptor and its chaperone RIC-3 in diseases of the central nervous system and in neuroinflammation, focusing on multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Deregulated neuroinflammation due to dysfunction of α7 nAChR provides one explanation for involvement of this receptor and of RIC-3 in neurodegenerative diseases. In this review, we also provide evidence implicating α7 nAChRs and RIC-3 in neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) involving neuroinflammation. Besides, we will describe the therapeutic implications of activating the cholinergic anti-inflammatory pathway for diseases involving neuroinflammation.

Entrepreneurial intention among university students may be conditioned by following training activities related to entrepreneurship during the course of their degree studies. There has clearly been an increase in the number of university graduates who become entrepreneurs, so it is necessary to determine the services that should be offered by the university as a platform to support university entrepreneurship. This research examines this issue through the use of statistical analyses. The main objective of this research is to determine the different types of entrepreneurial training offered to students and the services they think the university should establish as a platform to support entrepreneurship, thereby enabling a comparison of current and desired practices. The study determines whether access to training activities conditions the entrepreneurial intention of university students. Descriptive statistics have been used to conveniently present the information and to identify behavioral patterns of the variables analyzed. Data have thus been examined using frequency analysis, contingency tables and independence tests. The variables used in this survey are designed to represent the role of the university in fostering entrepreneurial culture and the intention among the university community to start their own business, having first extensively analyzed the concept of an entrepreneurial university

BackgroundSupporting patients to engage in (Web-based) self-management tools is increasingly gaining importance, but the engagement of health care professionals is lagging behind. This can partly be explained by resistance among health care professionals. ObjectiveThe aim of this study was to investigate drivers of resistance among oncology nurses toward Web-based self-management tools in cancer care. MethodsDrawing from previous research, combining clinical and marketing perspectives, and several variables and instruments, we developed the Resistance to Innovation model (RTI-model). The RTI-model distinguishes between passive and active resistance, which can be enhanced or reduced by functional drivers (incompatibility, complexity, lack of value, and risk) and psychological drivers (role ambiguity, social pressure from the institute, peers, and patients). Both types of drivers can be moderated by staff-, organization-, patient-, and environment-related factors. We executed a survey covering all components of the RTI-model on a cross-sectional sample of nurses working in oncology in the Netherlands. Structural equation modeling was used to test the full model, using a hierarchical approach. In total, 2500 nurses were approached, out of which 285 (11.40%) nurses responded. ResultsThe goodness of fit statistic of the uncorrected base model of the RTI-model (n=239) was acceptable (χ21=9.2; Comparative Fit Index=0.95; Tucker Lewis index=0.21; Root Mean Square Error of Approximation=0.19; Standardized Root Mean Square=0.016). In line with the RTI-model, we found that both passive and active resistance among oncology nurses toward (Web-based) self-management tools were driven by both functional and psychological drivers. Passive resistance toward Web-based self-management tools was enhanced by complexity, lack of value, and role ambiguity, and it was reduced by institutional social pressure. Active resistance was enhanced by complexity, lack of value, and social pressure from peers, and it was reduced by social pressure from the institute and patients. In contrast to what we expected, incompatibility with current routines was not a significant driver of either passive or active resistance. This study further showed that these drivers of resistance were moderated by expertise (P=.03), managerial support (P=.004), and influence from external stakeholders (government; P=.04). ConclusionsBoth passive and active resistance in oncology nurses toward Web-based self-management tools for patients with cancer are driven by functional and psychological drivers, which may be more or less strong, depending on expertise, managerial support, and governmental influence.

The year 2018 marked the 50th anniversary of the Mexico Olympic games, which represents the starting point of scientific research on hypoxic training. Since the original Live High Train High, many altitude/hypoxic training methods have been developed. The aim of the present review is to present the most recent method called Repeated Sprint training in Hypoxia (RSH). RSH is of unprecedented interest in the altitude training area with 25 studies published in the 5-year period following the pioneer article in 2013, and with only two studies that did not report any beneficial effects.Potential mechanisms include transcriptional factors involved in oxygen-signaling and oxygen-carrying capacity and mitochondrial metabolism enzymes, improved behavior of fasttwitch fibers notably via compensatory vasodilatation, improved vascular relaxation and greater microvascular oxygen delivery as well as faster rate of phosphocreatine resynthesis.In general, RSH leads to superior repeated-sprint ability (i.e., faster mean sprint times or higher power outputs associated witha better resistance to fatigue during a repeated-sprint test) in normoxic conditions. RSH where hypoxia is induced by voluntary hypoventilation at low lung volume (named VHL) may also improve repeated-sprint performance more than in normoxia. Practically, RSH benefits have been demonstrated for a large range of team- (rugby, football, LaCrosse, Australian Football, field hockey), endurance (cycling, track and field, cross-country ski), racket (tennis) or combat (Jiu-Jitsu) sports.KEY WORDS: Altitude, High-Intensity, Team-Sports, Performance, Hypoxia

Lipidomics has unveiled the intricate human lipidome, emphasizing the extensive diversity within lipid classes in mammalian tissues critical for cellular functions. This diversity poses a challenge in maintaining a delicate balance between adaptability to recurring physiological changes and overall stability. Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), linked to factors such as obesity and diabetes, stems from a compromise in the structural and functional stability of the liver within the complexities of lipid metabolism. This compromise inaccurately senses an increase in energy status, such as during fasting-feeding cycles or an upsurge in lipogenesis. Serum lipidomic studies have delineated three distinct metabolic phenotypes, or metabotypes in MASLD. MASLD-A is characterized by lower very low-density lipoprotein (VLDL) secretion and triglyceride (TG) levels, associated with a reduced risk of cardiovascular disease (CVD). In contrast, MASLD-C exhibits increased VLDL secretion and TG levels, correlating with elevated CVD risk. An intermediate subtype, with a blend of features, is designated as the MASLD-B metabotype. In this perspective, we examine into recent findings that show the multifaceted regulation of VLDL secretion by S-adenosylmethionine, the primary cellular methyl donor. Furthermore, we explore the differential CVD and hepatic cancer risk across MASLD metabotypes and discuss the context and potential paths forward to gear the findings from genetic studies towards a better understanding of the observed heterogeneity in MASLD.