1,069 research outputs found

    The Math Gender Gap: The Role of Culture

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    This paper investigates the effect of gender-related culture on the math gender gap by analysing math test scores of second-generation immigrants, who are all exposed to a common set of host country laws and institutions. We find that immigrant girls whose parents come from more gender-equal countries perform better (relative to similar boys) than immigrant girls whose parents come from less gender-equal countries, suggesting an important role of cultural beliefs on the role of women in society on the math gender gap. The transmission of cultural beliefs accounts for at least two thirds of the overall contribution of gender-related factors

    Bilinear softening parameters and equivalent LEFM R-curve in quasibrittle failure

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    For composites and adhesive joints, the determination of the cohesive zone parameters from Double Cantilever Beam specimens loaded with pure moments is now well established and documented. However, for quasibrittle materials used in Civil Engineering such as concrete or wood, the difficulty to apply a pure bending moment lies inappropriated the method used for composites. Nevertheless, the one-to-one correspondence which exists between the R-curve and the softening curve is here revisited and adapted for any kind of specimen geometry and for the bilinear approximation of the softening function, well-known to successfully describe the failure of a wide group of quasibrittle materials. It is shown that even though the connections between the cohesive parameters and the ‘equivalent LEFM’ R-curve are geometry and material dependent, their trends are preserved whatever the specimen geometry and the material are. The outline of a general estimation procedure of the cohesive zone parameters funded on the equivalent LEFM R-curve is proposed

    Mechanism of the Aryl-F Bond-Forming Step from Bi(V) Fluorides.

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    In this article, we describe a combined experimental and theoretical mechanistic investigation of the C(sp2)-F bond formation from neutral and cationic high-valent organobismuth(V) fluorides, featuring a dianionic bis-aryl sulfoximine ligand. An exhaustive assessment of the substitution pattern in the ligand, the sulfoximine, and the reactive aryl on neutral triarylbismuth(V) difluorides revealed that formation of dimeric structures in solution promotes facile Ar-F bond formation. Noteworthy, theoretical modeling of reductive elimination from neutral bismuth(V) difluorides agrees with the experimentally determined kinetic and thermodynamic parameters. Moreover, the addition of external fluoride sources leads to inactive octahedral anionic Bi(V) trifluoride salts, which decelerate reductive elimination. On the other hand, a parallel analysis for cationic bismuthonium fluorides revealed the crucial role of tetrafluoroborate anion as fluoride source. Both experimental and theoretical analyses conclude that C-F bond formation occurs through a low-energy five-membered transition-state pathway, where the F anion is delivered to a C(sp2) center, from a BF4 anion, reminiscent of the Balz-Schiemann reaction. The knowledge gathered throughout the investigation permitted a rational assessment of the key parameters of several ligands, identifying the simple sulfone-based ligand family as an improved system for the stoichiometric and catalytic fluorination of arylboronic acid derivatives

    Variables Sociodemográficas y niveles de salud en población general: Un estudio en la isla de Formentera

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    Se presentan los resultados de la primera fase de un estudio epidemiológico descriptivo transversal realizado en la isla de Formentera. Se ha utilizado el General Health Questionnaire (GHQ), en su versión de 28 items, en una muestra de población general constituida por 697 personas. El GHQ es una escala que evalúa síntomas somáticos de origen psicológico, angustia o ansiedad, disfunción social en las actividades diarias y depresión y suele utilizarse como instrumento de screening. Los resultados indican que un 20% de los entrevistados puede ser considerado como probable caso, dándose un porcentaje mayor de probables casos positivos entre las mujeres, las personas más jóvenes y las mayores y entre quienes carecen de ocupación laboral. Concretamente, las mujeres puntúan significativamente más alto en las escalas que evalúan los síntomas somáticos de origen psicológico y las personas sin trabajo en aquellas que evalúan angustia/ ansiedad, disfunción social en las actividades diarias y depresión. No existen diferencias estadísticamente significativas entre los grupos diferenciados según estado civil, nivel de estudios o nivel económico

    HIV-1 selectively targets gut-homing CCR6+CD4+ T cells via mTOR-dependent mechanisms

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    Gut-associated lymphoid tissues are enriched in CCR6+ Th17-polarized CD4+ T cells that contribute to HIV-1 persistence during antiretroviral therapy (ART). This raises the need for Th17-targeted immunotherapies. In an effort to identify mechanisms governing HIV-1 permissiveness/persistence in gut-homing Th17 cells, we analyzed the transcriptome of CCR6+ versus CCR6- T cells exposed to the gut-homing inducer retinoic acid (RA) and performed functional validations in colon biopsies of HIV-infected individuals receiving ART (HIV+ART). Although both CCR6+ and CCR6- T cells acquired gut-homing markers upon RA exposure, the modulation of unique sets of genes coincided with preferential HIV-1 replication in RA-treated CCR6+ T cells. This molecular signature included the upregulation of HIV-dependency factors acting at entry/postentry levels, such as the CCR5 and PI3K/Akt/mTORC1 signaling pathways. Of note, mTOR expression/phosphorylation was distinctively induced by RA in CCR6+ T cells. Consistently, mTOR inhibitors counteracted the effect of RA on HIV replication in vitro and viral reactivation in CD4+ T cells from HIV+ART individuals via postentry mechanisms independent of CCR5. Finally, CCR6+ versus CCR6- T cells infiltrating the colons of HIV+ART individuals expressed unique molecular signatures, including higher levels of CCR5, integrin β7, and mTOR phosphorylation. Together, our results identify mTOR as a druggable key regulator of HIV permissiveness in gut-homing CCR6+ T cells

    Phosphorylated c-Src in the nucleus is associated with improved patient outcome in ER-positive breast cancer

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    Elevated c-Src protein expression has been shown in breast cancer and <i>in vitro</i> evidence suggests a role in endocrine resistance. To investigate whether c-Src is involved in endocrine resistance, we examined the expression of both total and activated c-Src in human breast cancer specimens from a cohort of oestrogen receptor (ER)-positive tamoxifen-treated breast cancer patients. Tissue microarray technology was employed to analyse 262 tumour specimens taken before tamoxifen treatment. Immunohistochemistry using total c-Src and activated c-Src antibodies was performed. Kaplan–Meier survival curves were constructed and log-rank test were performed. High level of nuclear activated Src was significantly associated with improved overall survival (<i>P</i>=0.047) and lower recurrence rates on tamoxifen (<i>P</i>=0.02). Improved patient outcome was only seen with activated Src in the nucleus. Nuclear activated Src expression was significantly associated with node-negative disease and a lower NPI (<i>P</i><0.05). On subgroup analysis, only ER-positive/progesterone receptor (PgR)-positive tumours were associated with improved survival (<i>P</i>=0.004). This shows that c-Src activity is increased in breast cancer and that activated Src within the nucleus of ER-positive tumours predicts an improved outcome. In ER/PgR-positive disease, activated Src kinase does not appear to be involved in <i>de novo</i> endocrine resistance. Further study is required in ER-negative breast cancer as this may represent a cohort in which it is associated with poor outcome

    Thermal Stabilization of an Endoglucanase by Cyclization

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    An intein-driven protein splicing approach allowed for the covalent linkage between the N- and C-termini of a polypeptide chain to create circular variants of the endo-β-1,3-1,4-glucanase, LicA, from Bacillus licheniformis. Two circular variants, LicA-C1 and LicA-C2, which have connecting loops of 20 and 14 amino acids, respectively, showed catalytic activities that are approximately two and three times higher, respectively, compared to that of the linear LicA (LicA-L1). The thermal stability of the circular variants was significantly increased compared to the linear form. Whereas the linear glucanase lost half of its activity after 3 min at 65 °C, the two circular variants have 6-fold (LicA-C1) and 16-fold (LicA-C2) increased half-life time of inactivation. In agreement with this, fluorescence spectroscopy and differential scanning calorimetry studies revealed that circular enzymes undergo structural changes at higher temperatures compared to that of the linear form. The effect of calcium on the conformational stability and function of the circular LicAs was also investigated, and we observed that the presence of calcium ions results in increased thermal stability. The impact of the length of the designed loops on thermal stability of the circular proteins is discussed, and it is suggested that cyclization may be an efficient strategy for the increased stability of proteins

    Impact of very early antiretroviral therapy during acute HIV infection on long-term immunovirological outcomes

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    Acute HIV infection; Antiretroviral treatment; Immune recoveryInfección aguda por VIH; Tratamiento antirretroviral; Recuperación inmunitariaInfecció aguda per VIH; Tractament antiretroviral; Recuperació immunitàriaObjectives We aimed to determine if starting antiretroviral therapy (ART) in the first 30 days after acquiring HIV infection has an impact on immunovirological response. Methods Observational, ambispective study including 147 patients with confirmed acute HIV infection (January/1995-August/2022). ART was defined as very early (≤30 days after the estimated date of infection), early (31-180 days), and late (>180 days). We compared time to viral suppression (viral load [VL] <50 copies/ml) and immune recovery (IR) (CD4+/CD8+ ratio ≥1) according to the timing and type of ART using survival analysis. Results ART was started in 140 (95.2%) patients. ART was very early in 24 (17.1%), early in 77 (55.0%), and late in 39 (27.9%) cases. Integrase strand transfer inhibitor (INSTI)-based regimens were the most used in both the overall population (65%) and the very early ART group (23/24, 95.8%). Median HIV VL and CD4+/CD8+ ratio pre-ART were higher in the very early ART group (P <0.05). Patients in the very early and early ART groups and treated with INSTI-based regimens achieved IR earlier (P <0.05). Factors associated with faster IR were the CD4+/CD8+ ratio pre-ART (hazard ratio: 9.3, 95% CI: 3.1-27.8, P <0.001) and INSTI-based regimens (hazard ratio: 2.4, 95% CI: 1.3-4.2, P = 0.003). Conclusions The strongest predictors of IR in patients who start ART during AHI are the CD4+/CD8+ ratio pre-ART and INSTI-based ART regimens.This work was founded by Instituto de Salud Carlos III (Acción Estratégica en Salud) and Fondo Europeo de Desarrollo Regional (FEDER) through grant PI20/00823. The study was also supported by the Spanish Network for AIDS Research (RIS) through the Instituto de Salud Carlos III – Red Temática de Investigación Cooperativa en Sida (RD06/006, RD12/0017/0018 and RD16/0002/0006) as part of the Plan Nacional R+D+I and by ISCIII Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER). For this project, PS has received a grant from the Catalan Society of Infectious Diseases and Clinical Microbiology (SCMIMC) funded by ViiV Healthcare. MJB is supported by the Miguel Servet program funded by the Spanish Health Institute Carlos III (CPII22/00005). The funders had no role in the study design, data collection, and interpretation, or the decision to submit the work for publication

    Accurate ab initio spin densities

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    We present an approach for the calculation of spin density distributions for molecules that require very large active spaces for a qualitatively correct description of their electronic structure. Our approach is based on the density-matrix renormalization group (DMRG) algorithm to calculate the spin density matrix elements as basic quantity for the spatially resolved spin density distribution. The spin density matrix elements are directly determined from the second-quantized elementary operators optimized by the DMRG algorithm. As an analytic convergence criterion for the spin density distribution, we employ our recently developed sampling-reconstruction scheme [J. Chem. Phys. 2011, 134, 224101] to build an accurate complete-active-space configuration-interaction (CASCI) wave function from the optimized matrix product states. The spin density matrix elements can then also be determined as an expectation value employing the reconstructed wave function expansion. Furthermore, the explicit reconstruction of a CASCI-type wave function provides insights into chemically interesting features of the molecule under study such as the distribution of α\alpha- and β\beta-electrons in terms of Slater determinants, CI coefficients, and natural orbitals. The methodology is applied to an iron nitrosyl complex which we have identified as a challenging system for standard approaches [J. Chem. Theory Comput. 2011, 7, 2740].Comment: 37 pages, 13 figure
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