141 research outputs found

    Predictors of Increases in Alcohol Problems and Alcohol Use Disorders in Offspring in the San Diego Prospective Study.

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    BackgroundThe 35-year-long San Diego Prospective Study documented 2-fold increases in alcohol problems and alcohol use disorders (AUDs) in young-adult drinking offspring compared to rates in their fathers, the original probands. The current analyses use the same interviews and questionnaires at about the same age in members of the 2 generations to explore multiple potential contributors to the generational differences in adverse alcohol outcomes.MethodsUsing data from recent offspring interviews, multiple cross-generation differences in characteristics potentially related to alcohol problems were evaluated in 3 steps: first through direct comparisons across probands and offspring at about age 30; second by backward linear regression analyses of predictors of alcohol problems within each generation; and finally third through R-based bootstrapped linear regressions of differences in alcohol problems in randomly matched probands and offspring.ResultsThe analyses across the analytical approaches revealed 3 consistent predictors of higher alcohol problems in the second generation. These included the following: (i) a more robust relationship to alcohol problems for offspring with a low level of response to alcohol; (ii) higher offspring values for alcohol expectancies; and (iii) higher offspring impulsivity.ConclusionsThe availability of data across generations offered a unique perspective for studying characteristics that may have contributed to a general finding in the literature of substantial increases in alcohol problems and AUDs in recent generations. If replicated, these results could suggest approaches to be used by parents, healthcare workers, insurance companies, and industry in their efforts to mitigate the increasing rates of alcohol problems in younger generations

    Disformal transformations on the CMB

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    In this work we study the role of disformal transformation on cosmological backgrounds and its relation to the speed of sound for tensor modes. A speed different from one for tensor modes can arise in several contexts, such as Galileons theories or massive gravity, nevertheless the speed is very constrained to be one by observations of gravitational wave emission. It has been shown that in inflation a disformal trans- formation allows to set the speed for tensor modes to one without making changes to the curvature power spectrum. Here we show that this invariance does not hold when considering the CMB anisotropy power spectrum. It turns out that the after doing the transformation there is an imprint on the acoustic peaks and the diffusion damping. This has interesting consequences; here we explore quartic galileon theories which allow a modified speed for tensor modes. For these theories the transformation can be used to constraint the parameter space in different regime

    The speed of Galileon gravity

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    We analyse the speed of gravitational waves in coupled Galileon models with an equation of state ωphgr=−1 now and a ghost-free Minkowski limit. We find that the gravitational waves propagate much faster than the speed of light unless these models are small perturbations of cubic Galileons and the Galileon energy density is sub-dominant to a dominant cosmological constant. In this case, the binary pulsar bounds on the speed of gravitational waves can be satisfied and the equation of state can be close to -1 when the coupling to matter and the coefficient of the cubic term of the Galileon Lagrangian are related. This severely restricts the allowed cosmological behaviour of Galileon models and we are forced to conclude that Galileons with a stable Minkowski limit cannot account for the observed acceleration of the expansion of the universe on their own. Moreover any sub-dominant Galileon component of our universe must be dominated by the cubic term. For such models with gravitons propagating faster than the speed of light, the gravitons become potentially unstable and could decay into photon pairs. They could also emit photons by Cerenkov radiation. We show that the decay rate of such speedy gravitons into photons and the Cerenkov radiation are in fact negligible. Moreover the time delay between the gravitational signal and light emitted by explosive astrophysical events could serve as a confirmation that a modification of gravity acts on the largest scales of the Universe

    Effects of Using Alternative Extreme Pressure (EP) and Anti-Wear (AW) Additives with Oxy-Nitrided Samples

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    Oxy-nitriding is a widely used industrial process aiming to improve the tribological properties and performance of components. Previous studies have shown the effectiveness of the treatment with friction and wear performance, but very few have focussed on optimising this behaviour. The lubrication properties of several EP and AW additives were examined to investigate their effectiveness in improving the tribological properties of the layers formed after treatment. Previous studies showed the presence of an oxide layer on the sample could improve the effectiveness of the sulphurised olefin (SO) and tricresyl phosphate (TCP) additives. The friction and wear behaviour of oxy-nitrided samples were analysed using a tribometer and surface profiler. Scanning electron microscope, energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy were employed to identify the morphologies and chemical compositions of the treated surface before and after testing. No real effect on friction was observed when using the SO or TCP additives, mostly due to lack of interaction with the less reactive iron nitride layer and their roles as anti-wear additives. However, when the zinc dialkyldithiophosphate-containing lubricant was used, a higher friction coefficient was observed. Greater improvements in anti-wear properties with the presence of additives in comparison with only using base oil were reported, with the TCP additive producing the lowest wear rates. The study effectively demonstrated that the additive package type used could impact the tribological and tribochemical properties of oxy-nitrided surfaces

    Antibiotic Stress, Genetic Response and Altered Permeability of E. coli

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    BACKGROUND: Membrane permeability is the first step involved in resistance of bacteria to an antibiotic. The number and activity of efflux pumps and outer membrane proteins that constitute porins play major roles in the definition of intrinsic resistance in Gram-negative bacteria that is altered under antibiotic exposure. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe the genetic regulation of porins and efflux pumps of Escherichia coli during prolonged exposure to increasing concentrations of tetracycline and demonstrate, with the aid of quantitative real-time reverse transcriptase-polymerase chain reaction methodology and western blot detection, the sequence order of genetic expression of regulatory genes, their relationship to each other, and the ensuing increased activity of genes that code for transporter proteins of efflux pumps and down-regulation of porin expression. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that, in addition to the transcriptional regulation of genes coding for membrane proteins, the post-translational regulation of proteins involved in the permeability of Gram-negative bacteria also plays a major role in the physiological adaptation to antibiotic exposure. A model is presented that summarizes events during the physiological adaptation of E. coli to tetracycline exposure

    BTN3A2 Expression in Epithelial Ovarian Cancer Is Associated with Higher Tumor Infiltrating T Cells and a Better Prognosis

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    BTN3A2/BT3.2 butyrophilin mRNA expression by tumoral cells was previously identified as a prognostic factor in a small cohort of high grade serous epithelial ovarian cancer (HG-EOC). Here, we evaluated the prognostic value of BT3.2 at the protein level in specimen from 199 HG-EOC patients. As the only known role of butyrophilin proteins is in immune regulation, we evaluated the association between BT3.2 expression and intratumoral infiltration of immune cells by immunohistochemistry with specific antibodies against BT3.2, CD3, CD4, CD8, CD20, CD68 and CD206. Epithelial BT3.2 expression was significantly associated with longer overall survival and lower risk of disease progression (HR = 0.651, p = 0.006 and HR = 0.642, p = 0.002, respectively) and significantly associated with a higher density of infiltrating T cells, particularly CD4+ cells (0.272, p<0.001). We also observed a strong association between the relative density of CD206+ cells, as evaluated by the ratio of intratumoral CD206+/CD68+ expression, and risk of disease progression (HR = 1.355 p = 0.044, respectively). In conclusion, BT3.2 protein is a potential prognostic biomarker for the identification of HG-EOC patients with better outcome. In contrast, high CD206+/CD68+ expression is associated with high risk of disease progression. While the role of BT3.2 is still unknown, our result suggest that BT3.2 expression by epithelial cells may modulates the intratumoral infiltration of immune cells

    De Novo and Rare Inherited Copy-Number Variations in the Hemiplegic Form of Cerebral Palsy

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    PurposeHemiplegia is a subtype of cerebral palsy (CP) in which one side of the body is affected. Our earlier study of unselected children with CP demonstrated de novo and clinically relevant rare inherited genomic copy-number variations (CNVs) in 9.6% of participants. Here, we examined the prevalence and types of CNVs specifically in hemiplegic CP.MethodsWe genotyped 97 unrelated probands with hemiplegic CP and their parents. We compared their CNVs to those of 10,851 population controls, in order to identify rare CNVs

    BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

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    Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License
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