Miracle-dz/UniFAR-FTUs huggingface dataset:
Hyperoxic Exposure Leads to Nitrative Stress and Ensuing Microvascular Degeneration and Diminished Brain Mass and Function in the Immature Subject

Background and Purpose— Neonates that survive very preterm birth have a high prevalence of cognitive impairment in later life. A common factor detected in premature infants is their postnatal exposure to high oxygen tension relative to that in utero. Hyperoxia is known to elicit injury to premature lung and retina. Because data on the exposure of the brain to hyperoxia are limited, we studied the effects of high oxygen on this tissue. Methods— Rat pups were exposed from birth until day 6 to 21% or 80% O2. Cerebral vascular density was quantified by lectin immunohistochemistry. Immunoblots for several proteins were performed on brain extracts. We assessed cerebral functional deficits by visual evoked potentials. Results— Exposure of pups to hyperoxia leads to cerebral microvascular degeneration, diminished brain mass, and cerebral functional deficits. These effects are preceded by an upregulation of endothelial nitric oxide synthase (eNOS) in cerebral capillaries and a downregulation of Cu/Zn superoxide dismutase (SOD). The imbalance in nitric oxide (NO) production and antioxidant defenses favors the formation of nitrating agents in the microvessels revealed by increased nitrotyrosine (3-nt) immunoreactivity and decreased expression of NF-&kgr;B and the dependent vascular endothelial growth factor receptor 2. NOS inhibitors and eNOS deletion as well as an SOD mimetic (CuDIPS) restore vascular endothelial growth factor receptor-2 levels and nearly abolish the vasoobliteration. NOS inhibitors and SOD mimetic also prevent O2-induced diminished brain mass and functional deficit. Conclusions— Data identify NO and nitrating agents as major mediators of cerebral microvascular damage, ensuing impaired brain development and function in immature subjects exposed to hyperoxia.
Protective Mechanisms of Green Tea Polyphenols in Skin

Skin is frequently exposed to a variety of environmental, chemical, and genotoxic agents that contribute to disease and carcinogenesis. Ultraviolet light (UVR) is the main external stress that leads to immunosuppresion, oxidative stress, premature aging, and tumor formation. Scientists and health professionals emphasize the importance of prevention strategies to circumvent such unfavorable outcomes. Plant polyphenols are a promising approach to disease prevention and treatment. Green tea is an abundant source of plant polyphenols that exhibit significant antioxidant, chemopreventive, and immunomodulatory effects in protecting the skin.
Patient Characterization Protocols for Psychophysiological Studies of Traumatic Brain Injury and Post-TBI Psychiatric Disorders

Psychophysiological investigations of traumatic brain injury (TBI) are being conducted for several reasons, including the objective of learning more about the underlying physiological mechanisms of the pathological processes that can be initiated by a head injury. Additional goals include the development of objective physiologically based measures that can be used to monitor the response to treatment and to identify minimally symptomatic individuals who are at risk of delayed-onset neuropsychiatric disorders following injury. Research programs studying TBI search for relationships between psychophysiological measures, particularly ERP (event-related potential) component properties (e.g., timing, amplitude, scalp distribution), and a participant’s clinical condition. Moreover, the complex relationships between brain injury and psychiatric disorders are receiving increased research attention, and ERP technologies are making contributions to this effort. This review has two objectives supporting such research efforts. The first is to review evidence indicating that TBI is a significant risk factor for post-injury neuropsychiatric disorders. The second objective is to introduce ERP researchers who are not familiar with neuropsychiatric assessment to the instruments that are available for characterizing TBI, post-concussion syndrome, and psychiatric disorders. Specific recommendations within this very large literature are made. We have proceeded on the assumption that, as is typically the case in an ERP laboratory, the investigators are not clinically qualified and that they will not have access to participant medical records.
An allosteric Sec61 inhibitor traps nascent transmembrane helices at the lateral gate

Membrane protein biogenesis requires the coordinated movement of hydrophobic transmembrane domains (TMD) from the cytosolic vestibule of the Sec61 channel into the lipid bilayer. Molecular insight into TMD integration has been hampered by the difficulty of characterizing intermediates during this intrinsically dynamic process. In this study, we show that cotransin, a substrate-selective Sec61 inhibitor, traps nascent TMDs in the cytosolic vestibule, permitting detailed interrogation of an early pre-integration intermediate. Site-specific crosslinking revealed the pre-integrated TMD docked to Sec61 near the cytosolic tip of the lateral gate. Escape from cotransin-arrest depends not only on cotransin concentration, but also on the biophysical properties of the TMD. Genetic selection of cotransin-resistant cancer cells uncovered multiple mutations clustered near the lumenal plug of Sec61α, thus revealing cotransin’s likely site of action. Our results suggest that TMD/lateral gate interactions facilitate TMD transfer into the membrane, a process that is allosterically modulated by cotransin binding to the plug. DOI: http://dx.doi. org/10.7554/eLife.01483. 001
Tracing Sub-Structure in the European American Population with PCA-Informative Markers

Genetic structure in the European American population reflects waves of migration and recent gene flow among different populations. This complex structure can introduce bias in genetic association studies. Using Principal Components Analysis (PCA), we analyze the structure of two independent European American datasets (1,521 individuals–307,315 autosomal SNPs). Individual variation lies across a continuum with some individuals showing high degrees of admixture with non-European populations, as demonstrated through joint analysis with HapMap data. The CEPH Europeans only represent a small fraction of the variation encountered in the larger European American datasets we studied. We interpret the first eigenvector of this data as correlated with ancestry, and we apply an algorithm that we have previously described to select PCA-informative markers (PCAIMs) that can reproduce this structure. Importantly, we develop a novel method that can remove redundancy from the selected SNP panels and show that we can effectively remove correlated markers, thus increasing genotyping savings. Only 150–200 PCAIMs suffice to accurately predict fine structure in European American datasets, as identified by PCA. Simulating association studies, we couple our method with a PCA-based stratification correction tool and demonstrate that a small number of PCAIMs can efficiently remove false correlations with almost no loss in power. The structure informative SNPs that we propose are an important resource for genetic association studies of European Americans. Furthermore, our redundancy removal algorithm can be applied on sets of ancestry informative markers selected with any method in order to select the most uncorrelated SNPs, and significantly decreases genotyping costs.
Mortality, Morbidity and Health-Seeking Behaviour during the Ebola Epidemic 2014–2015 in Monrovia Results from a Mobile Phone Survey

Between March 2014 and July 2015 at least 10,500 Ebola cases including more than 4,800 deaths occurred in Liberia, the majority in Monrovia. However, official numbers may have underestimated the size of the outbreak. Closure of health facilities and mistrust in existing structures may have additionally impacted on all-cause morbidity and mortality. To quantify mortality and morbidity and describe health-seeking behaviour in Monrovia, Médecins sans Frontières (MSF) conducted a mobile phone survey from December 2014 to March 2015. We drew a random sample of households in Monrovia and conducted structured mobile phone interviews, covering morbidity, mortality and health-seeking behaviour from 14 May 2014 until the day of the survey. We defined an Ebola-related death as any death meeting the Liberian Ebola case definition. We calculated all-cause and Ebola-specific mortality rates. The sample consisted of 6,813 household members in 905 households. We estimated a crude mortality rate (CMR) of 0.33/10,000 persons/day (95%CI:0.25–0.43) and an Ebola-specific mortality rate of 0.06/10,000 persons/day (95%-CI:0.03–0.11). During the recall period, 17 Ebola cases were reported including those who died. In the 30 days prior to the survey 277 household members were reported sick; malaria accounted for 54% (150/277). Of the sick household members, 43% (122/276) did not visit any health care facility. The mobile phone-based survey was found to be a feasible and acceptable alternative method when data collection in the community is impossible. CMR was estimated well below the emergency threshold of 1/10,000 persons/day. Non-Ebola-related mortality in Monrovia was not higher than previous national estimates of mortality for Liberia. However, excess mortality directly resulting from Ebola did occur in the population. Importantly, the small proportion of sick household members presenting to official health facilities when sick might pose a challenge for future outbreak detection and mitigation. Substantial reported health-seeking behaviour outside of health facilities may also suggest the need for adapted health messaging and improved access to health care.
Differential Response to Trichloroethylene-Induced Hepatosteatosis in Wild-Type and PPARα-Humanized Mice

Background Trichloroacetic acid, an oxidative metabolite of trichloroethylene (TRI), is a ligand of the peroxisome proliferator-activated receptor α (PPAR) α, which is involved in lipid homeostasis and anti-inflammation. Objective We examined the role of mouse and human PPARα in TRI-induced hepatic steatosis and toxicity. Methods Male wild-type (mPPARα), Pparα-null, and humanized PPARα (hPPARα) mice on an Sv/129 background were exposed via inhalation to 0, 1,000, and 2,000 ppm TRI for 8 hr/day for 7 days. We assessed TRI-induced steatosis or hepatic damage through biochemical and histopathological measurements. Results Plasma alanine aminotransferase and aspartate aminotransferase activities increased in all mouse lines after exposure to 1,000 and 2,000 ppm TRI. Exposure induced hepatocyte necrosis and inflammatory cells in all mouse lines, but hepatic lipid accumulation was observed only in Pparα-null and hPPARα mice. No differences were observed in TRI-mediated induction of hepatic PPARα target genes except for a few genes that differed between mPPARα and hPPARα mice. However, TRI significantly increased expression of triglyceride (TG)-synthesizing enzymes, diacylglicerol acyltransferases, and PPARγ in Pparα-null and hPPARα mice, which may account for the increased TG in their livers. TRI exposure elevated nuclear factor-kappa B (NFκB) p52 mRNA and protein in all mice regardless of PPARα genotype. Conclusions NFκB-p52 is a candidate molecular marker for inflammation caused by TRI, and PPARα may be involved in TRI-induced hepatosteatosis. However, human PPARα may afford only weak protection against TRI-mediated effects compared with mouse PPARα.
Characterization of Excipient and Tableting Factors That Influence Folic Acid Dissolution, Friability, and Breaking Strength of Oil- and Water-Soluble Multivitamin with Minerals Tablets

Abstract The goal of this study is to characterize the formulation and processing factors that influence folic acid dissolution from oil- and water-soluble multivitamin with minerals tablet formulations for direct compression. The following parameters were studied: bulk filler solubility, soluble to insoluble bulk filler ratio, triturating agent (preblending carrier) solubility, disintegrant usage, compression pressure, and folic acid particle size. Folic acid particle size was determined by using light microscopy, and surface area was measured by using BET adsorption. The tablets were compressed on an instrumented Stokes B2 tablet press, and the friability, weight variation, and dissolution were measured according to USP methods, along with tablet breaking strength. In summary, we found the following factors to be critical to folic acid dissolution: bulk filler solubility (soluble fillers, such as maltose, increase folic acid dissolution); disintegrant amount (levels less than 0.4% (w/w) are ineffectual, whereas levels greater than 1.2% (w/w) did not further increase dissolution); and compression force (generally, maltose produce harder tablets). In addition, folic acid dissolution was less affected by changes in compaction pressure when a “super” disintegrant and maltose, as a bulk filler, were used. It was determined that the trituration agent did not play a significant role in folic acid dissolution. In the range of parameters studied, statistical analysis found no significant interactions between the parameters studied, which means they act independently in an additive manner. The results also show that no one factor is completely responsible for dissolution failure. Thus, it is the combination of formulation factors and processing conditions that collectively add up to produce dissolution failure; however, the use of a disintegrant and a soluble filler such as maltose can make a formulation more robust to the inevitable changes that can occur during commercial production.
Evaluate with Confidence Estimation: Machine ranking of translation outputs using grammatical features

We present a pilot study on an evaluation method which is able to rank translation outputs with no reference translation, given only their source sentence. The system employs a statistical classifier trained upon existing human rankings, using several features derived from analysis of both the source and the target sentences. Development experiments on one language pair showed that the method has considerably good correlation with human ranking when using features obtained from a PCFG parser.
Critical role of CXC chemokines in endotoxemic liver injury in mice

Dear Editor: We read with great interest the recent paper by Li et al. [1], who reported evidence for a critical role of the CXC che-mokines keratinocyte (KC) and macrophage-inflammatory protein-2 (MIP-2) in the pathophysiology of endotoxin (ET)-induced liver injury. The authors showed increased KC and MIP-2 formation during endotoxemia and found that neutralizing antibodies against these chemokines strongly attenuated parenchymal cell apoptosis, prevented neutrophil extravasation, and reduced liver injury after treatment of mice with galactosamine (Gal)/ET [1]. As neutrophil extrav-asation is a prerequisite of injury in this [2] and other inflammatory liver disease models [3], the data of Li et al. [1] appear to identify the missing link and signal, which trigger neutrophil extravasation and the attack on parenchy-mal cells [4]. Moreover, the authors showed a 68% reduction of hepatocellular apoptosis in animals treated with antibod-ies against KC and MIP-2, suggesting an involvement of CXC chemokines in apoptosis signaling, which would be a novel, unrecognized function of CXC chemokines. However, a closer look at the data raises substantial doubts about the interpretations of these results and the validity of the conclusions drawn from these studies. The first concern relates to the inhibition of apoptosis in this model. The assessment of apoptosis with Hoechst stain is clearly not accurate; e.g., 6% apoptosis in control livers [1] is ten-to 100-fold above baseline values [5]. Conversely, the reduced caspase-3 activity, a critical mediator of Gal/ET-induced apoptosis [6], supports the authors' conclusion that anti-CXC antibodies attenuated apoptosis. However, before postulating a novel discovery, the authors should have checked tumor necrosis factor ␣ (TNF-␣) formation. As apoptosis in this model is entirely TNF-dependent [7], the most likely explanation for reduced apoptosis is reduced TNF formation. In fact, injection of high doses of immunoglobulin G (IgG) has been shown to bind ET, which can reduce TNF formation by Kupffer cells [8]. The observation that all IgG treatment attenuated apoptosis and that the combination of two antibodies (twice the IgG dose) had an additive effect [1] is consistent with this explanation. The second concern is related to the conclusion that CXC chemokines are responsible for neutrophil transmigration. The authors showed no effect of the anti-CXC chemokine antibod-ies on leukocyte adherence in postsinusoidal venules, but they did not investigate sinusoidal adherence. As has been shown in this model, neutrophil transmigration occurs from sinusoids and not from venules [2]. Therefore, assessment of sinusoidal neutrophil sequestration would have been …
Stimulation of endothelin mRNA and secretion in rat vascular smooth muscle cells: a novel autocrine function.

Endothelin (ET), a peptide originally isolated from the supernatants of cultured endothelial cells, exerts a wide variety of biological effects in different tissues. Endothelial-cell-synthesized ET-1 has been proposed to act in a paracrine manner on adjacent smooth muscle cells (SMC) in vivo, with effects that include both vascular reactivity (vasodilation/vasoconstriction) and mitogenesis. This study, by the use of immunocytochemically characterized SMC (rVSMC) isolated from the aortas of spontaneously hypertensive rats, has investigated a possible autocrine role for ET in regulation of the vasculature. Although quiescent cultures of rVSMC apparently did not constitutively express prepro ET-1mRNA, ET-specific transcripts could be induced by a variety of growth factors (transforming growth factor beta [TGF-beta]; platelet-derived growth factor-AA homodimer [PDGF-A chain]) and vasoactive hormones (angiotensin II [Ang II], arginine-vasopressin, and ET-1 itself). The kinetics for prepro ET-1mRNA induction in rVSMC were characteristically rapid in onset and transient. Down-regulation of protein kinase C by 48 h pretreatment of rVSMC with phorbol ester markedly reduced the subsequent ability of rVSMC to express ET-1 transcripts and secrete ET-1 peptide in response to Ang II. Inducible prepro ET-1mRNA expression was accompanied by a cycloheximide-inhibitable release of ET-1 peptide into the medium of rVSMC. ET-1 peptide was determined by both radioreceptor- and radioimmunoassay. Stimulated rVSMC accumulated ET-1 (approximately 200 pg.10(6) cells-1 x 4 h-1) at levels that attained biological relevance (approximately 10(-10) M). Sep-pak C18 extracts of medium from stimulated rVSMC elicited contraction of isolated endothelium-denuded rat mesenteric resistance vessels, and this response was characteristically protracted and difficult to "wash out. " Synthetic (porcine) ET-1 promoted the expression of transcripts for PDGF-A chain, TGF-beta, and thrombospondin in quiescent rVSMC. Such effects of ET-1 on gene expression may be relevant to the mitogenic potential of ET-1 on VSMC. Our findings imply a role for ET-1 in the control of vascular function via both paracrine and autocrine regulatory mechanisms. The expression of prepro ET-1mRNA and peptide biosynthesis by rVSMC may have both short-term (e.g., vasoconstriction) and long-term (e.g., structural remodeling) consequences. A sustained loop of autocrine stimulation by ET-1 in SMC could contribute toward the pathogenesis of vasospasm and/or atherosclerosis.
A new parallel-series configuration for hybridization of a line-haul truck

The hybridization of the articulated line-haul heavy duty truck with self-propelled trailer is investigated. In this innovative configuration, the tractor electric hybrid powertrain is arranged in series with the trailer electric motor that provides a share of total traction efforts of the vehicle. This configuration could provide a regenerative braking capability in the trailer and improves the vehicle longitudinal handling and enhances the vehicle lateral stability. Detailed mathematical modeling of the drivetrain components is developed and the energy consumption analyses for typical driving cycles are performed. Simulation results showed the worthwhile capability of the proposed hybrid drivetrain to improve the regenerative braking and enhance the fuel efficiency of the line-haul trucks.
Malinowski modalization, modalization through fibring and the Leibniz hierarchy

We show how various modal systems considered by Malinowski as extensions of classical propositional calculus may be obtained as ﬁbrings of classical propositional calculus and corresponding implica-tive modal logics, using the ﬁbring framework for combining logics of Fern´andez and Coniglio. Taking advantage of this construction and known results of Malinowski, we draw some useful conclusions concerning some limitations of the ﬁbring process. Finally, Malinowski’s constructions are extended to obtain some modal extensions of arbitrary equivalential logics in the context of abstract algebraic logic. These are studied with respect to their algebraic character
Calcium intake is not associated with increased coronary artery calcification: the Framingham Study.

BACKGROUND Adequate calcium intake is known to protect the skeleton. However, studies that have reported adverse effects of calcium supplementation on vascular events have raised widespread concern. OBJECTIVE We assessed the association between calcium intake (from diet and supplements) and coronary artery calcification, which is a measure of atherosclerosis that predicts risk of ischemic heart disease independent of other risk factors. DESIGN This was an observational, prospective cohort study. Participants included 690 women and 588 men in the Framingham Offspring Study (mean age: 60 y; range: 36-83 y) who attended clinic visits and completed food-frequency questionnaires in 1998-2001 and underwent computed tomography scans 4 y later in 2002-2005. RESULTS The mean age-adjusted coronary artery-calcification Agatston score decreased with increasing total calcium intake, and the trend was not significant after adjustment for age, BMI, smoking, alcohol consumption, vitamin D-supplement use, energy intake, and, for women, menopause status and estrogen use. Multivariable-adjusted mean Agatston scores were 2.36, 2.52, 2.16, and 2.39 (P-trend = 0.74) with an increasing quartile of total calcium intake in women and 4.32, 4.39, 4.19, and 4.37 (P-trend = 0.94) in men, respectively. Results were similar for dietary calcium and calcium supplement use. CONCLUSIONS Our study does not support the hypothesis that high calcium intake increases coronary artery calcification, which is an important measure of atherosclerosis burden. The evidence is not sufficient to modify current recommendations for calcium intake to protect skeletal health with respect to vascular calcification risk.