1,023 research outputs found

    The label of madness: the effects of career choice and gender on perceptions of mental illness

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    People with creative abilities have often been stereotyped as insane, neurotic, and prone to addiction (Kaufman, Bromley, & Cole, 2006; Corrigan, 2005). These labels have perpetuated the stigma for many generations (Ludwig, 1995). In addition, females have often been stereotyped as bad at math, but are assumed to be more verbal and creative (Quinn & Spencer, 2001). The present study hypothesized that creative writers would be stereotyped as more mentally ill, neurotic, and addicted to substances compared to scientists. It was also predicted that gender would exacerbate the phenomenon such that females would be particularly vulnerable to this stereotype. Statistical analyses revealed some interesting gender by major interactions: female creative writers were perceived as the most mentally ill, but were closely followed by male science majors. Male creative writers were actually perceived to have a relatively low level of mental illness. Interestingly, male scientists were rated as having the highest levels of drug and alcohol abuse, whereas male creative writers were perceived to have relatively fewer symptoms of substance abuse. The reverse pattern was true for females. This research confirmed the stereotype of insanity among artists for females but also revealed a tendency towards pathology-based stereotyping of male scientists. Stereotypes negatively affect the targeted populations and perpetuate the stigmas against them. This research attempted to advance understanding as an initial step towards alleviating unwarranted stereotypes

    Yeast-based strategy for identification of 11β-HSD1 inhibitors

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    Glucocorticoids are hormones with a vital role in regulation of metabolic and defence responses. Their metabolism plays an important role in the pathogenesis of obesity, a major risk factor for metabolic syndrome, a collection of disorders such as insulin resistance, dyslipidemia and hypertension. At intracellular level the production of active glucocorticoids is regulated by two hydroxysteroid dehydrogenase enzyme isoforms 11β-HSD1 and 11β-HSD2, respectively. 11β-HSD2 is predominantly expressed in mineralocorticoid target tissues and acts as oxidase catalysing conversion of cortisol into cortisone. The isoform 11β-HSD1, expressed in a wide array of tissues and with highest levels in the liver, acts mainly as a reductase converting the cortisone into the biologically active hormone cortisol, in a NADPH dependent manner. Due to its implication in the metabolism of glucocorticoids, 11β-HSD1 has become a primary target for the treatment of metabolic syndrome. In the last years many strategies have been developed for the screening of molecules with inhibitory effects against this target enzyme. All known approaches present unique features and are suitable for specific screening models. Nevertheless, due to the great therapeutic and economical interest around the treatment of metabolic syndrome, many research groups are constantly focused on the development of new and more successful strategies for identification of hits with improved pharmaceutical properties. In this study an innovative synthetic biology platform for synthesis and screening of 11β-HSD1 inhibitors has been conceived and investigated. This strategy is based on the production of diverse chemical scaffolds in the yeast Saccharomyces cerevisiae, in which the molecules are directly screened through intracellular functional assays. Providing all necessary genetic information, the biosynthetic pathway of plant triterpenoids, a big class of natural compounds with many beneficial effects on human health, was reconstructed in the baker’s yeast. Moreover, by applying DNA family shuffling methods, a library of chimeric triterpenoid synthase cDNAs was constructed. The chimeric sequences, potential carriers of new enzymatic functions, were assembled together with the wild-type molecules in expressible yeast artificial chromosomes (eYACs). Furthermore, the construction of two yeast assays strains functionally co-expressing the murine glucocorticoid receptor (GR) and the human 11β-HSD1 enzyme is presented. In both developed strains, with different mechanisms, the reductase activity of the enzyme 11β-HSD1 on cortisone is connected with an easily detectable fluorescent signal. Cells that produce compounds with inhibitory activity against 11β-HSD1 can be identified through changes in fluorescence and isolated to further investigate the active molecules. The developed yeast-assays were validated using carbenoxolone, a known 11β-HSD1 inhibitor, and may represent useful tools for a first quick and easy screening of large number of membrane permeable putative inhibitory compounds

    A FLUID STRUCTURE INTERACTION STRATEGY WITH APPLICATION TO LOW REYNOLDS NUMBER FLAPPING FLIGHT

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    In this work a structured adaptive mesh refinement (S-AMR) strategy for fluid-structure interaction (FSI) problems in laminar and turbulent incompressible flows is developed. The Eulerian computational grid consists of nested grid blocks at different refinement levels. The grid topology and data-structure is managed by using the Paramesh© toolkit. The filtered Navier-Stokes equations are evolved in time by means of an explicit second-order projection scheme, where spatial derivatives are approximated with second order central differences on a staggered grid. The level of accuracy of the required variable interpolation operators is studied, and a novel divergence-preserving prolongation scheme for velocities is evolved. A novel direct-forcing embedded-boundary method is developed to enforce boundary conditions on a complex moving body not aligned with the grid lines. In this method, the imposition of no-slip conditions on immersed bodies is done on the Lagrangian markers that represent their wet surfaces, and the resulting force is transferred to the surrounding Eulerian grid points by a moving least squares formulation. Extensive testing and validation of the resulting strategy is done on a numerous set of problems. For transitional and turbulent flow regimes the large-eddy simulation (LES) approach is used. The grid discontinuities introduced in AMR methods lead to numerical errors in LES, especially if non-dissipative, centered schemes are used. A simple strategy is developed to vary the filter size for filtered variables around grid discontinuities. A strategy based on explicit filtering of the advective term is chosen to effectively reduce the numerical errors across refinement jumps. For all the FSI problems reported, the complete set of equations governing the dynamics of the flow and the structure are simultaneously advanced in time by using a predictor-corrector strategy. Dynamic fluid grid adaptation is implemented to reduce the number of grid points and computation costs. Applications to flapping flight comprise the study of flexibility effects on the aerodynamic performance of a hovering airfoil, and simulation of the flow around an insect model under prescribed kinematics and free longitudinal flight. In the airfoil simulations, it is found that peak performance is located in structural flexibility-inertia regions where non-linear resonances are present

    Past and Future Trends in Refugee Migration on the Regional Level in Germany – An Analysis and Projection of Labor Market Effects

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    Since 2013, more than two million refugees have arrived in Germany and have been allocated across federal states and districts according to legal policies. A steadily increasing number of refugees is now entering the German labor market, albeit under varying economic and demographic contexts. However, regional differences in refugees’ labor market integration have received little attention both retrospectively and particularly prospectively, given the projected population decline across Germany. Addressing this apparent shortcoming in the literature, we collect data on refugee arrivals by gender, nationality, approval rates, and regional allocation from 1995 to 2019. Applying principal component analysis and time series analysis, we first analyze past patterns of refugee migration to Germany and project both arrivals and regional allocations by gender and nationality until 2030. Then, combining the collected migration figures for German labor market regions and official labor market statistics, we investigate past regional employment effects from 2008 to 2019. Next, we calculate corresponding future employment effects conditional on our projected refugee figures, our estimation results, and official regional demographic forecasts until 2030. Our findings suggest that refugee migration does not affect German labor market regions equally, but instead has and will continue to lead to distinct regional employment effects. Moreover, the labor market integration differs by gender and origin of the refugees. Consequently, the interaction of regional employment effects with projected population change gives rise to different regional mitigation potentials in view of the upcoming population decline. * This article belongs to a special issue on "Refugee Migration to Europe – Challenges and Potentials for Cities and Regions"

    Migration Forecasting—Significance and Approaches

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    International migration is a global phenomenon with a current estimate of 281 million people globally being counted as migrants, defined as living outside one’s country of origin, with an increasing tendency [1]. Reasons for migration are diverse, and classically defined by Lee [2] into the two categories of push and pull factors, with the first being factors repelling individuals from their region of origin, such as violent conflicts, poor nutritional and health standards, lack of work, or restrictions to freedom of speech. Pull factors instead are those attracting individuals to a specific region, such as better opportunities in employment or education, or better climatic circumstances. Issues arising from international migration differ very much between countries witnessing mostly negative net migration (origin countries) in comparison to those with regular positive net migration (target countries (the notions actually address the origin and the target country associated with one specific migration. We, however, borrow them here to characterize groups of countries)). The first case is low- to middle-income regions, i.e., large parts of Latin America, Africa, Asia, and Eastern Europe. The latter case is high-income regions, i.e., Western Europe, North America, Oceania, or Western Asia [1]. Whereas migration outflows from origin countries are often characterized by the loss of young and qualified individuals (brain drain), which then hampers the development of these countries [3], high inflows to the target countries are sometimes seen as problematic if the migrants originate from less developed and less egalitarian countries, in which case the migrants are perceived as a threat to security or the social systems of the target country by critics [4]. On the backhand side, migration can be seen as a chance. Outflows from origin countries might release tensions on the labor markets there if there is an oversupply of the labor force, which may lead to higher burdens on social systems. In the target countries, inflows by young migrants can be interpreted as a potential stabilizer for the age structure of the population and supply a potential labor force [4]. These societies, in most cases, are affected by a demographic transition, marked by low fertility and decreasing mortality rates, which then leads to aging and depopulation if not averted by immigration [5]

    Directed evolution of Rhodotorula gracilisd-amino acid oxidase using single-cell hydrogel encapsulation and ultrahigh-throughput screening

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    Engineering catalytic and biophysical properties of enzymes is an essential step en route to advanced biomedical and industrial applications. Here, we developed a high-throughput screening and directed evolution strategy relying on single-cell hydrogel encapsulation to enhance the performance of D -Amino acid oxidase from Rhodotorula gracilis ( Rg DAAOx), a candidate enzyme for cancer therapy. We used a cascade reaction between Rg DAAOx variants surface displayed on yeast and horseradish peroxidase (HRP) in the bulk media to trigger enzyme-mediated crosslinking of phenol-bearing fluorescent alginate macromonomers, resulting in hydrogel formation around single yeast cells. The fluorescent hydrogel capsules served as an artificial phenotype and basis for pooled library screening by fluorescence activated cell sorting (FACS). We screened a Rg DAAOx variant library containing ∼10 6 clones while lowering the D -Ala substrate concentration over three sorting rounds in order to isolate variants with low K m . After three rounds of FACS sorting and regrowth, we isolated and fully characterized four variants displayed on the yeast surface. We identified variants with a more than 5-fold lower K m than the parent sequence, with an apparent increase in substrate binding affinity. The mutations we identified were scattered across the Rg DAAOx structure, demonstrating the difficulty in rationally predicting allosteric sites and highlighting the advantages of scalable library screening technologies for evolving catalytic enzymes

    Microcephaly and macrocephaly. A study on anthropometric and clinical data from 308 subjects

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    Head circumference is the auxological parameter that most correlates with developmental anomalies in childhood. Head circumference (HC) two standard deviations (SD) below or above the mean defines microcephaly and macrocephaly, respectively. The aim of this retrospective study was to explore anthropometric parameters and clinical characteristics among subjects with abnormalities in HC who had been referred for developmental assessment. One hundred and sixty four subjects with microcephaly and 144 subjects with macrocephaly were enrolled from birth to 18 months of age. Head circumference at birth and the association with variables related to maternal health status, gestational age, growth pattern, brain imaging and clinical characteristics were analyzed. In some cases, an etiological diagnosis was made. In the two considered conditions, we found different anthropometric and clinical associations, some of which were statistically significant, with implications for ongoing neurodevelopmental surveillance

    Fertility Response to the COVID-19 Pandemic in Developed Countries – On Pre-pandemic Fertility Forecasts

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    The COVID-19 pandemic has affected all areas of our lives. Among other outcomes, the academic literature and popular media both discuss the potential effects of the pandemic on fertility. As fertility is an important determinant of population development and population forecasts are important for policy decisions and planning, we need to address to which extent fertility forecasts performed before the pandemic still apply. Using Monte Carlo forecasting based on principal components of fertility rates, we quantify the effects of the pandemic on fertility for 22 countries and discuss whether forecasts made prior to the pandemic need adjustment based on more recent data. Among the studied countries, 14 countries show no significant effect of the pandemic at all, while six countries have significantly lowered numbers of births in comparison to counterfactual trajectories that assume that past trends will hold. These countries are primarily in the Mediterranean and East Asia. For Finland and South Korea, there is statistical evidence for increased fertility in the early phases of the pandemic. In all cases with statistically significant fertility differentials caused by the pandemic, reproductive behavior normalized quickly. Therefore, we find no evidence for long-term effects of the pandemic on fertility, leading to the conclusion that pre-pandemic fertility forecasts still apply

    Perancangan Tekstil Untuk Busana Anak

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