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  • Open Access English
    Authors: 
    Saleh Ali Alrebish; Mohamed H. Taha; Mohamed H. Ahmed; Mohamed Elhassan Abdalla;
    Publisher: Taylor & Francis

    ABSTRACT Background: The College of Medicine at Qassim University (COMQU) was founded in 2001 as a problem-based learning and community-oriented medical school in order to strengthen the health system not only in the Qassim region but also in the whole of Saudi Arabia. The aim of the current study was to assess whether the COMQU is a socially accountable medical school and the steps taken to achieve that target. Materials and methods: The study used the social accountability grid published by the World Health Organization (WHO) as a framework to assess the social accountability efforts in the context of three functions of medical schools: education, service and research. Data were collected through the analysis of college documents (2001–2017) and interviews with key informants. Results: The COMQU shows compliance towards social accountability in the three domains of the grid. The indicators related to the education domain demonstrate more compliance than those of research and community service in the grid. Conclusion: The COMQU is based on community-oriented medical education (COME) with strong commitment towards social accountability (socially responsible going towards social responsiveness). More research is needed in order to pave the way to achieve social accountability status. Abbreviations: COMQU: College of Medicine at Qassim University; COME: Community-oriented medical education; WHO: The World Health Organization; MOH: Ministry of Health; SCFHS: Saudi Commission of Health Specialties; PHC: Primary Health Care; HYMS: Hull York Medical School; WFME: World Federation for Medical Education; NCAAA: National Commission for Academic Accreditation and Assessment

  • Publication . Article . Other literature type . Preprint . 2022
    Open Access English
    Authors: 
    Laura Sberna; Stanislav Babak; Sylvain Marsat; Andrea Caputo; Giulia Cusin; Alexandre Toubiana; Enrico Barausse; Chiara Caprini; Tito Dal Canton; Alberto Sesana; +1 more
    Project: EC | GRU (101007855), EC | LDMThExp (682676), EC | GRAMS (815673), EC | B Massive (818691)

    Binaries of relatively massive black holes like GW190521 have been proposed to form in dense gas environments, such as the disks of Active Galactic Nuclei (AGNs), and they might be associated with transient electromagnetic counterparts. The interactions of this putative environment with the binary could leave a significant imprint at the low gravitational wave frequencies observable with the Laser Interferometer Space Antenna (LISA). We show that LISA will be able to detect up to ten GW190521-like black hole binaries, with sky position errors $\lesssim1$ deg$^2$. Moreover, it will measure directly various effects due to the orbital motion around the supermassive black hole at the center of the AGN, especially the Doppler modulation and the Shapiro time delay. Thanks to a careful treatment of their frequency domain signal, we were able to perform the full parameter estimation of Doppler and Shapiro-modulated binaries as seen by LISA. We find that the Doppler and Shapiro effects will allow for measuring the AGN parameters (radius and inclination of the orbit around the AGN, central black hole mass) with up to percent-level precision. Properly modeling these low-frequency environmental effects is crucial to determine the binary formation history, as well as to avoid biases in the reconstruction of the source parameters and in tests of general relativity with gravitational waves. 13+4 pages, 7+1 figures v3: corrected typo in Fig 5

  • Open Access English
    Authors: 
    Irene Jiménez Guerrero; Francisco Pérez-Montaño; Gustavo Mateus da Silva; Naama Wagner; Dafna Shkedy; Mei Zhao; Lorena Pizarro; Maya Bar; Ron Walcott; Guido Sessa; +2 more
    Publisher: Cold Spring Harbor Laboratory

    AbstractMany Gram-negative plant and animal pathogenic bacteria employ a type III secretion system (T3SS) to secrete protein effectors into the cells of their hosts and promote disease. The plant pathogen Acidovorax citrulli requires a functional T3SS for pathogenicity. As with Xanthomonas and Ralstonia spp., an AraC-type transcriptional regulator, HrpX, regulates expression of genes encoding T3SS components and type III-secreted effectors (T3Es) in A. citrulli. A previous study reported eleven T3E genes in this pathogen, based on the annotation of a sequenced strain. We hypothesized that this was an underestimation. Guided by this hypothesis, we aimed at uncovering the T3E arsenal of the A. citrulli model strain, M6. We carried out a thorough sequence analysis searching for similarity to known T3Es from other bacteria. This analysis revealed 51 A. citrulli genes whose products are similar to known T3Es. Further, we combined machine learning and transcriptomics to identify novel T3Es. The machine learning approach ranked all A. citrulli M6 genes according to their propensity to encode T3Es. RNA-Seq revealed differential gene expression between wild-type M6 and a mutant defective in HrpX. Data combined from these approaches led to the identification of seven novel T3E candidates, that were further validated using a T3SS-dependent translocation assay. These T3E genes encode hypothetical proteins, do not show any similarity to known effectors from other bacteria, and seem to be restricted to plant pathogenic Acidovorax species. Transient expression in Nicotiana benthamiana revealed that two of these T3Es localize to the cell nucleus and one interacts with the endoplasmic reticulum. This study not only uncovered the arsenal of T3Es of an important pathogen, but it also places A. citrulli among the “richest” bacterial pathogens in terms of T3E cargo. It also revealed novel T3Es that appear to be involved in the pathoadaptive evolution of plant pathogenic Acidovorax species.Author summaryAcidovorax citrulli is a Gram-negative bacterium that causes bacterial fruit blotch (BFB) disease of cucurbits. This disease represents a serious threat to cucurbit crop production worldwide. Despite the agricultural importance of BFB, the knowledge about basic aspects of A. citrulli-plant interactions is rather limited. As many Gram-negative plant and animal pathogenic bacteria, A. citrulli employs a complex secretion system, named type III secretion system, to deliver protein virulence effectors into the host cells. In this work we aimed at uncovering the arsenal of type III-secreted effectors (T3Es) of this pathogen by combination of bioinformatics and experimental approaches. We found that this bacterium possesses at least 51 genes that are similar to T3E genes from other pathogenic bacteria. In addition, our study revealed seven novel T3Es that seem to occur only in A. citrulli strains and in other plant pathogenic Acidovorax species. We found that two of these T3Es localize to the plant cell nucleus while one partially interacts with the endoplasmic reticulum. Further characterization of the novel T3Es identified in this study may uncover new host targets of pathogen effectors and new mechanisms by which pathogenic bacteria manipulate their hosts.

  • Open Access English
    Authors: 
    Tonametl Sanchez; Andrey Polyakov; Emilia Fridman; Laurentiu Hetel;
    Publisher: HAL CCSD
    Country: France
    Project: ANR | DIGITSLID (ANR-18-CE40-0008)

    In this paper, we propose a state-dependent switching controller for multiple-input multiple-output (MIMO) bilinear systems with constant delays in both the state and the input. The control input is assumed to be restricted to take only a finite number of values. The stability analysis of the closed loop is based on a Lyapunov–Krasovskii functional, and the design is reduced to solve a system of linear matrix inequalities. The controller can be designed by considering (state) delay-dependent or delay-independent conditions.

  • Open Access English
    Authors: 
    Jiarui Liu; André Pellerin; Gilad Antler; Gareth Izon; Alyssa Findlay; Hans Røy; Shuhei Ono; Sabine Kasten; Alexandra V. Turchyn; Bo Barker Jørgensen;
    Country: Denmark

    Sediment-hosted marine sulfur cycling has played a significant role in regulating Earth's surface chemistry over our planet's history. Microbially-mediated reactions involving sulfur are often accompanied by sulfur isotope fractionation that, in turn, is captured by sulfate and sulfide minerals, providing the opportunity to track changes in the microbial utilization of sulfur and thus the marine sulfur cycle. Studying sulfur diagenesis within the Bornholm Basin, Baltic Sea, we explore the interplay between carbon, sulfur and iron, focusing on the fate of sulfur and the dynamics of the sulfur and oxygen isotopic response as a function of the varying thickness of the organic carbon-rich Holocene Mud Layer (HML) across the basin. Using a one-dimensional reaction-transport model, porewater sulfate and sulfide profiles were used to calculate net sulfate reduction rates (SRR) and net sulfide production rates, respectively. These calculations suggest a positive relationship between the thickness of the HML and net rates of sulfate reduction and sulfide production. Given that ascending sulfide is enriched in 34S relative to that produced in-situ, a heightened sulfide flux promotes spatially variable precipitation of 34S-enriched pyrite (δ34S ≈ −10‰) close to the sediment–water interface. Modeling results indicate that this isotopically “heavy” sulfide is formed as a consequence of mixing between ascending sulfide (up to +6.3‰) and that produced in-situ (ca. −40‰). Further, we show that the sulfur and oxygen isotopic composition of porewater sulfate is controlled by the net SRR: when the net SRR is high (i.e., in sulfide-replete settings) the downcore increase in δ18OSO4 is dampened relative to increase in δ34SSO4, whereas when net SRR is low (i.e., in iron-rich parts of the basin) downcore δ18OSO4 values increase while δ34SSO4 values remain invariant. We conclude that sedimentation rates and open system diffusion strongly influence the distribution of sulfur species and their sulfur isotopic composition, as well as the oxygen isotopic composition of sulfate, through the interaction between iron, sulfur and methane. This work highlights the importance of considering diffusion to better understand open system diagenesis and the δ34S signatures of sulfate and sulfide in both modern settings and ancient rocks.

  • Open Access English
    Authors: 
    O.B. Kostyuk; Bogdan Dzundza; Ya.S. Yavorsky; Zinovy Dashevsky;
    Publisher: Vasyl Stefanyk Precarpathian National University

    Thermal detectors find a significant niche in the market of modern sensors. Bi2T3 and PbTe semiconductors are effective thermoelectrics and excellent candidates for different applications. In the present work, a technology for fabrication of p-Bi0.5Sb1.5Te3 and n-PbTe films with the high thermoelectric efficiency on thin flexible polyimide substrate has been developed. The preparation of films was performed by flash evaporation method. The high sensitivity of the devices is due to the high Seebeck coefficient of 200 mV/K and reduction of thermal conductivity of thin thermoelectric film from the bulk value. The devices operate in the Johnson-Nyquist noise limit of the thermocouple. The performance enables fast and sensitive detection of low levels of thermal power and infrared radiation at room temperature.

  • Publication . Article . Other literature type . 2020
    Open Access English
    Authors: 
    Dror Dicker; Silvia Bettini; Nathalie Farpour-Lambert; Gema Frühbeck; Rachel Golan; Gijs H. Goossens; Jason C.G. Halford; Grace O'Malley; Dana Müllerová; Ximena Ramos Salas; +5 more
    Countries: United Kingdom, Switzerland, Turkey, Turkey, Netherlands, Netherlands, United Kingdom

    WOS:000577671800010 PubMed ID: 32659766 The World Health Organization declared COVID-19, the infectious disease caused by the coronavirus SARS-CoV-2, a pandemic on March 12, 2020. COVID-19 is causing massive health problems and economic suffering around the world. The European Association for the Study of Obesity (EASO) promptly recognised the impact that the outbreak could have on people with obesity. On one side, emerging data suggest that obesity represents a risk factor for a more serious and complicated course of COVID-19 in adults. On the other side, the health emergency caused by the outbreak diverts attention from the prevention and care of non-communicable chronic diseases to communicable diseases. This might be particularly true for obesity, a chronic and relapsing disease frequently neglected and linked to significant bias and stigmatization. The Obesity Management Task Force (OMTF) of EASO contributes in this paper to highlighting the key aspects of these two sides of the coin and suggests some specific actions.

  • Open Access English
    Authors: 
    Gal Dalal; Balázs Szörényi; Gugan Thoppe;
    Project: NSF | RoL: FELS: RAISE: Does ev... (1840223)

    Policy evaluation in reinforcement learning is often conducted using two-timescale stochastic approximation, which results in various gradient temporal difference methods such as GTD(0), GTD2, and TDC. Here, we provide convergence rate bounds for this suite of algorithms. Algorithms such as these have two iterates, $\theta_n$ and $w_n,$ which are updated using two distinct stepsize sequences, $\alpha_n$ and $\beta_n,$ respectively. Assuming $\alpha_n = n^{-\alpha}$ and $\beta_n = n^{-\beta}$ with $1 > \alpha > \beta > 0,$ we show that, with high probability, the two iterates converge to their respective solutions $\theta^*$ and $w^*$ at rates given by $\|\theta_n - \theta^*\| = \tilde{O}( n^{-\alpha/2})$ and $\|w_n - w^*\| = \tilde{O}(n^{-\beta/2});$ here, $\tilde{O}$ hides logarithmic terms. Via comparable lower bounds, we show that these bounds are, in fact, tight. To the best of our knowledge, ours is the first finite-time analysis which achieves these rates. While it was known that the two timescale components decouple asymptotically, our results depict this phenomenon more explicitly by showing that it in fact happens from some finite time onwards. Lastly, compared to existing works, our result applies to a broader family of stepsizes, including non-square summable ones.

  • Open Access English
    Authors: 
    Elisabeth Stelling; Melanie Ricke-Hoch; Sergej Erschow; Steve Hoffman; Anke K. Bergmann; Maren Heimerl; Stefan Pietzsch; Karin Battmer; Alexandra Haase; Britta Stapel; +4 more
    Publisher: Cold Spring Harbor Laboratory

    AbstractCardiac levels of the signal transducer and activator of transcription factor-3 (STAT3) decline with age, and male but not female mice with a cardiomyocyte-specific STAT3 deficiency (CKO) display premature age-related heart failure associated with reduced cardiac capillary density. In the present study isolated male and female CKO-cardiomyocytes exhibit increased prostaglandin (PG)-generating cyclooxygenase-2 (COX-2) expression. The PG-degrading hydroxyprostaglandin-dehydrogenase-15 (HPGD) expression is only reduced in male cardiomyocytes, which is associated with increased PGD2 secretion from isolated male but not female CKO-cardiomyocytes. Reduced HPGD expression in male cardiomyocytes derive from impaired androgen-receptor-(AR)-signaling due to loss of its co-factor STAT3. Elevated PGD2 secretion in males is associated with increased white adipocyte accumulation in aged male but not female hearts. Adipocyte differentiation is enhanced in isolated SCA-1+-cardiac-progenitor-cells (CPC) from young male CKO-mice compared to the adipocyte differentiation of male wildtype (WT)-CPC and CPC isolated from female mice. Epigenetic analysis in freshly isolated male CKO-CPC display hypermethylation in pro-angiogenic genes (Fgfr2, Epas1) and hypomethylation in the white adipocyte differentiation gene Zfp423 associated with upregulated ZFP423 expression and a shift from endothelial to white adipocyte differentiation compared to WT-CPC. The expression of the histone-methyltransferase EZH2 is reduced in male CKO-CPC compared to male WT-CPC whereas no differences in the EZH2 expression in female CPC were observed. Clonally expanded CPC can differentiate into endothelial cells or into adipocytes depending on the differentiation conditions. ZFP423 overexpression is sufficient to induce white adipocyte differentiation of clonal CPC. In isolated WT-CPC, PGD2 stimulation reduces the expression of EZH2 thereby upregulating ZFP423 expression and promoting white adipocyte differentiation.Thus, cardiomyocyte STAT3-deficiency leads to age-related and sex-specific cardiac remodeling and failure in part due to sex-specific alterations in PGD2 secretion and subsequent epigenetic impairment of the differentiation potential of CPC. Causally involved is the impaired AR signaling in absence of STAT3, which reduces the expression of the PG degrading enzyme HPGD.

  • Open Access English
    Authors: 
    Vunnam Srinivasulu; Paul Schilf; Saleh M. Ibrahim; Monther A. Khanfar; Scott McN. Sieburth; Hany A. Omar; Anusha Sebastian; Raed A. Al-Qawasmeh; Matthew J. O'Connor; Taleb H. Al-Tel;
    Publisher: Nature Publishing Group UK

    Octahydroindolo[2,3-a]quinolizine ring system forms the basic framework comprised of more than 2000 distinct family members of natural products. Despite the potential applications of this privileged substructure in drug discovery, efficient, atom-economic and modular strategies for its assembly, is underdeveloped. Here we show a one-step build/couple/pair strategy that uniquely allows access to diverse octahydroindolo[2,3-a]quinolizine scaffolds with more than three contiguous chiral centers and broad distribution of molecular shapes via desymmetrization of the oxidative-dearomatization products of phenols. The cascade demonstrates excellent diastereoselectivity, and the enantioselectivity exceeded 99% when amino acids are used as chiral reagents. Furthermore, two diastereoselective reactions for the synthesis of oxocanes and piperazinones, is reported. Phenotypic screening of the octahydroindolo[2,3-a]quinolizine library identifies small molecule probes that selectively suppress mitochondrial membrane potential, ATP contents and elevate the ROS contents in hepatoma cells (Hepa1–6) without altering the immunological activation or reprogramming of T- and B-cells, a promising approach to cancer therapy. Methods enabling the synthesis of diverse collections of nature-inspired compounds with potential medicinal use are sought after in drug design. Here, the authors report a build/couple/pair strategy to efficiently construct chiral polycyclic scaffolds and show their diversification for drug discovery screening.

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