Modulation of extracellular matrix by nutritional hepatotrophic factors in thioacetamide-induced liver cirrhosis in the rat

Nutritional substances associated to some hormones enhance liver regeneration when injected intraperitoneally, being denominated hepatotrophic factors (HF). Here we verified if a solution of HF (glucose, vitamins, salts, amino acids, glucagon, insulin, and triiodothyronine) can revert liver cirrhosis and how some extracellular matrices are affected. Cirrhosis was induced for 14 weeks in 45 female Wistar rats (200 mg) by intraperitoneal injections of thioacetamide (200 mg/kg). Twenty-five rats received intraperitoneal HF twice a day for 10 days (40 mL·kg-1·day-1) and 20 rats received physiological saline. Fifteen rats were used as control. The HF applied to cirrhotic rats significantly: a) reduced the relative mRNA expression of the genes: Col-α1 (-53%), TIMP-1 (-31.7%), TGF-β1 (-57.7%), and MMP-2 (-41.6%), whereas Plau mRNA remained unchanged; b) reduced GGT (-43.1%), ALT (-17.6%), and AST (-12.2%) serum levels; c) increased liver weight (11.3%), and reduced liver collagen (-37.1%), regenerative nodules size (-22.1%), and fibrous septum thickness. Progranulin protein (immunohistochemistry) and mRNA (in situ hybridization) were found in fibrous septa and areas of bile duct proliferation in cirrhotic livers. Concluding, HF improved the histology and serum biochemistry of liver cirrhosis, with an important reduction of interstitial collagen and increased extracelullar matrix degradation by reducing profibrotic gene expression

D-Brane Propagation in Two-Dimensional Black Hole Geometries

We study propagation of D0-brane in two-dimensional Lorentzian black hole backgrounds by the method of boundary conformal field theory of SL(2,R)/U(1) supercoset at level k. Typically, such backgrounds arise as near-horizon geometries of k coincident non-extremal NS5-branes, where 1/k measures curvature of the backgrounds in string unit and hence size of string worldsheet effects. At classical level, string worldsheet effects are suppressed and D0-brane propagation in the Lorentzian black hole geometry is simply given by the Wick rotation of D1-brane contour in the Euclidean black hole geometry. Taking account of string worldsheet effects, boundary state of the Lorentzian D0-brane is formally constructible via Wick rotation from that of the Euclidean D1-brane. However, the construction is subject to ambiguities in boundary conditions. We propose exact boundary states describing the D0-brane, and clarify physical interpretations of various boundary states constructed from different boundary conditions. As it falls into the black hole, the D0-brane radiates off to the horizon and to the infinity. From the boundary states constructed, we compute physical observables of such radiative process. We find that part of the radiation to infinity is in effective thermal distribution at the Hawking temperature. We also find that part of the radiation to horizon is in the Hagedorn distribution, dominated by massive, highly non-relativistic closed string states, much like the tachyon matter. Remarkably, such distribution emerges only after string worldsheet effects are taken exactly into account. From these results, we observe that nature of the radiation distribution changes dramatically across the conifold geometry k=1 (k=3 for the bosonic case), exposing the `string - black hole transition' therein.Comment: 51 pages, 5 figures, v2: referece added, note added replying the comment made in hep-th/060206

Association of labor induction with offspring risk of autism spectrum disorders

IMPORTANCE: Induction of labor is a frequently performed obstetrical intervention. It would thus be of great concern if reported associations between labor induction and offspring risk of autism spectrum disorders (ASD) reflected causal influence. OBJECTIVE: To assess the associations of labor induction with ASD, comparing differentially exposed relatives (siblings and cousins discordant for induction). DESIGN, SETTING, AND PARTICIPANTS: Follow-up of all live births in Sweden between 1992 and 2005, defined in the Medical Birth Register. The register was linked to population registers of familial relations, inpatient and outpatient visits, and education records. Diagnoses of ASD were from 2001 through 2013, and data were analyzed in the 2015-2016 year. EXPOSURES: Induction of labor. MAIN OUTCOMES AND MEASURES: Autism spectrum disorders identified by diagnoses from inpatient and outpatient records between 2001 and 2013. Hazard ratios (HRs) quantified the association between labor induction and offspring ASD. In addition to considering a wide range of measured confounders, comparison of exposure-discordant births to the same woman allowed additional control for all unmeasured factors shared by siblings. RESULTS: The full cohort included 1362950 births, of which 22077 offspring (1.6%) were diagnosed with ASD by ages 8 years through 21 years. In conventional models of the full cohort, associations between labor induction and offspring ASD were attenuated but remained statistically significant after adjustment for measured potential confounders (HR, 1.19; 95% CI, 1.13-1.24). When comparison was made within siblings whose births were discordant with respect to induction, thus accounting for all environmental and genetic factors shared by siblings, labor induction was no longer associated with offspring ASD (HR, 0.99; 95% CI, 0.88-1.10). CONCLUSIONS AND RELEVANCE: In this nationwide sample of live births we observed no association between induction of labor and offspring ASD within sibling comparison. Our findings suggest that concern for ASD should not factor into the clinical decision about whether to induce labor.NonePublishe

Conformal Transformations in Cosmology of Modified Gravity: the Covariant Approach Perspective

The 1+3 covariant approach and the covariant gauge-invariant approach to perturbations are used to analyze in depth conformal transformations in cosmology. Such techniques allow us to obtain very interesting insights on the physical content of these transformations, when applied to non-standard gravity. The results obtained lead to a number of general conclusions on the change of some key quantities describing any two conformally related cosmological models. In particular, it is shown that the physics in the Einstein frame has characteristics which are completely different from those in the Jordan frame. Even if some of the geometrical properties of the cosmology are preserved (homogeneous and isotropic Universes are mapped into homogeneous and isotropic universes), it can happen that decelerating cosmologies are mapped into accelerated ones. Differences become even more pronounced when first-order perturbations are considered: from the 1+3 equations it is seen that first-order vector and tensor perturbations are left unchanged in their structure by the conformal transformation, but this cannot be said of the scalar perturbations, which include the matter density fluctuations. Behavior in the two frames of the growth rate, as well as other evolutionary features, like the presence or absence of oscillations, etc., appear to be different too. The results obtained are then explicitly interpreted and verified with the help of some clarifying examples based on $f(R)$-gravity cosmologies.Comment: 26 pages, 8 figure

Kinetic modeling of H-mode pedestal with effects from anomalous transport and MHD stability

Scaling of the H-mode pedestal in tokamak plasmas with type I ELMs and dependence of the pedestal properties and the resulting divertor head load width with the plasma elongation and plasma current are investigated using the kinetic neoclassical XGC0 code for DIII-D and Alcator C-Mod tokamaks. The simulations in this study use realistic diverted geometry and are self-consistent with the inclusion of kinetic neoclassical physics, theory-based anomalous transport models with the E×B flow shearing effects, as well as an MHD ELM triggering criterion. Scalings for the pedestal width and height are developed as a function of the scanned plasma parameters. The nonlinear interplay between anomalous and neoclassical effects motivates the development of a self-consistent simulation model that includes neoclassical and anomalous effects simultaneously. It is demonstrated that the divertor heat load width depend on the plasma currents. In the development of this dependence, effects of neutral collisions and anomalous transport are taken into account. Changes in the neoclassical divertor heat load fluxes associated with the introduction of the neutral collision and anomalous transport effects are described.За допомогою кінетичного неокласичного коду XGC0 для розрядів в токамаках DIII-D і Alcator C-Mod досліджено скейлінг п’єдесталу в плазмі, що перебуває в режимі поліпшеного утримання, з прикордонними локалізованими модами (ПЛМ) першого типу, властивості п’єдесталу і потоку тепла на дивертор в залежності від витягнутості плазми та струму плазми. У розрахунках використовуються: реалістична геометрія дивертора, кінетична модель для неокласичних ефектів, модель аномального транспорту, яка враховує ефекти шира (ExB)-потоків, і умови збудження ПЛМ-нестійкостей. У результаті розрахунків отримані скейлінгі для ширини і висоти п’єдесталу як функції параметрів плазми. Нелінійна взаємодія неокласичних ефектів і ефектів, пов'язаних з аномальним транспортом, є мотивацією для розробки самоузгодженої чисельної моделі, яка одночасно включає ефекти аномального і неокласичного транспорту. Показано, що потоки тепла на дивертор залежать від плазмових струмів. Також представлено результати дослідження залежності напівширини профілів тепла на дивертор від ефектів, пов'язаних з аномальним транспортом і зіткненнями з нейтральними частинками.С помощью кинетического неоклассического кода XGC0 для разрядов в токамаках DIII-D и Alcator C-Mod исследованы скэйлинг пьедестала в плазме, находящейся в режиме улучшенного удержания, с приграничными локализованными модами (ПЛМ) первого типа, и зависимость свойств пьедестала и потока тепла на дивертор от вытянутости плазмы и тока плазмы. В расчетах используются: реалистичная геометрия дивертора, кинетическая модель для неоклассических эффектов, модель аномального транспорта, которая учитывает эффекты шира (ExB)-потоков, и условия возбуждения ПЛМ-неустойчивостей. В результате расчетов получены скэйлинги для ширины и высоты пьедестала как функции параметров плазмы. Нелинейное взаимодействие неоклассических эффектов и эффектов, связанных с аномальным транспортом, является мотивацией разработки самосогласованной численной модели, которая одновременно включает эффекты аномального и неоклассического транспорта. Показано, что потоки тепла на дивертор зависят от плазменных токов. Также представлены результаты исследования зависимости полуширины профилей тепла на дивертор от эффектов, связанных с аномальным транспортом и столкновениями с нейтральными частицами

Inferring Deleterious-Mutation Parameters in Natural Daphnia Populations

Deng and Lynch (1, 2) proposed to characterize deleterious genomic mutations from changes in the mean and genetic variance of fitness traits upon selfing in outcrossing populations. Such observations can be readily acquired in cyclical parthenogens. Selfing and life-table experiments were performed for two such Daphnia populations. A significant inbreeding depression and an increase of genetic variance for all traits analyzed were observed. Deng and Lynch's (2) procedures were employed to estimate the genomic mutation rate (U), mean dominance coefficient ( [Image: see text] ), mean selection coefficient ( [Image: see text] ), and scaled genomic mutational variance ( [Image: see text] ). On average, [Image: see text] , [Image: see text] , [Image: see text] and [Image: see text] (^ indicates an estimate) are 0.84, 0.30, 0.14 and 4.6E-4 respectively. For the true values, the [Image: see text] and [Image: see text] are lower bounds, and [Image: see text] and [Image: see text] upper bounds

Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs

Substance abuse and addiction are the most costly of all the neuropsychiatric disorders. In the last decades, much progress has been achieved in understanding the effects of the drugs of abuse in the brain. However, efficient treatments that prevent relapse have not been developed. Drug addiction is now considered a brain disease, because the abuse of drugs affects several brain functions. Neurological impairments observed in drug addicts may reflect drug-induced neuronal dysfunction and neurotoxicity. The drugs of abuse directly or indirectly affect neurotransmitter systems, particularly dopaminergic and glutamatergic neurons. This review explores the literature reporting cellular and molecular alterations reflecting the cytotoxicity induced by amphetamines, cocaine and opiates in neuronal systems. The neurotoxic effects of drugs of abuse are often associated with oxidative stress, mitochondrial dysfunction, apoptosis and inhibition of neurogenesis, among other mechanisms. Understanding the mechanisms that underlie brain dysfunction observed in drug-addicted individuals may contribute to improve the treatment of drug addiction, which may have social and economic consequences.http://www.sciencedirect.com/science/article/B6SYS-4S50K2J-1/1/7d11c902193bfa3f1f57030572f7034

Multiplicity distributions at high energies as a sum of Poissonian-like distributions

It is shown that at collider energies experimental multiplicity distributions are well parameterized by a sum of Gupta-Sarma distributions. This extends earlier description of the lower energy data by the two parameter sum of Poissonians. Implications of the proposed parametrization for LHC are discussed.Comment: 16 pages, Latex, 4 EPS figure