Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Antihypertensive Therapy on Mechanics of Cerebral Arterioles in Rats

The purpose of this study was to examine effects of antihypertensive treatment on structure and mechanics of cerebral arterioles and the incidence of stroke in stroke-prone spontaneously hypertensive rats (SHRSP). Treatment of hypertension was begun at 3 months of age with cilazapril (45 mg/kg/day), an angiotensin converting enzyme (ACE) inhibitor, or with hydralazine (18 mg/kg/day). Cilazapril and hydralazine reduced systolic arterial pressure (from 195±8 to 125±5 and 148±3 mm Hg, respectively [mean±SEM]; p<0.05). To examine structure and mechanics of cerebral arterioles, we measured pressure (servonull), external diameter, and cross-sectional area of the vessel wall (histologically) in pial arterioles of normotensive Wistar-Kyoto (WKY) rats and SHRSP that were untreated or that were treated for 3 months with cilazapril or with hydralazine. Arterioles were maximally dilated with EDTA. In WKY rats, cilazapril and hydralazine did not alter pial arteriolar pressure, external diameter, or cross-sectional area of the vessel wall. In SHRSP, both cilazapril and hydralazine reduced cross-sectional area of the vessel wall to levels not significantly different from WKY rats (from 1,911±155 to l,244±101 and lr388±59 μm2 respectively, compared with l,405±95 /tm2 for untreated WKY rats). Cilazapril was more effective than hydralazine in reducing pial arteriolar pressure (from 110 ±6 to 62 ±2 mm Hg with cilazapril versus 79 ±5 mm Hg for hydralazine compared with 60±4 mm Hg for untreated WKY rats). Cilazapril, but not hydralazine, attenuated reductions in external diameter of pial arterioles (from 91 ±4 to 100 ±4 (μm for cilazapril versus 91 ±3 fim for hydralazine compared with 107 ±3 fim for untreated WKY rats). Stress-strain curves indicate that cilazapril was more effective than hydralazine in attenuating increases in distensibility of pial arterioles in SHRSP. Both treatments prevented the occurrence of stroke in SHRSP, whereas eight of 15 untreated SHRSP developed strokes. Thus, both an ACE inhibitor and hydralazine prevented hypertrophy of cerebral arterioles and stroke in SHRSP, even though the ACE inhibitor was more effective than hydralazine in lowering intra-arteriolar pressure. In contrast, only the ACE inhibitor attenuated increases in distensibility and "remodeling" (reduction in external diameter) of cerebral arterioles, perhaps due to its greater efficacy in reducing pial arteriolar pressure at the doses used in this study. These findings suggest that determinants of distensibility and vascular remodeling may be different from determinants of vascular hypertrophy.
Ultralow impedance analysis and evaluation of power distribution network for decoupling capacitor embedded interposers of 3-D integrated LSI system

We evaluated low-impedance power distribution network (PDN) of decoupling capacitor embedded interposers for 3-D integrated LSI system. Measurements are carried out using the developed impedance analyzer system of a wide frequency range for evaluating ultralow impedance, and calculations are carried out using 2.5-D and 3-D finite element method (FEM) electromagnetic field simulator. We fabricated various types of capacitor mounted or capacitor embedded interposers test element group (TEG), such as surface-mounted and embedded chip capacitors, and thin film capacitors on silicon interposers using the same simple design to compare measurement results with calculation ones. As a result, the ultralow impedance evaluation system that has a high measurement dynamic range at the entire measurable frequency band can be realized. Furthermore, by using 2.5-D and 3-D FEM electromagnetic field simulator, it is expected that the accurate and wideband comparative verification of the PDN impedance analysis and evaluation can be realized.
Confirmation of STAT4, IL2/IL21, and CTLA4 polymorphisms in rheumatoid arthritis.

OBJECTIVE Recent advances have led to novel identification of genetic polymorphisms that are associated with susceptibility to rheumatoid arthritis (RA). Currently, 5 loci (HLA, PTPN22, TRAF1/C5, TNFAIP3, and STAT4) have been consistently reported, whereas others have been observed less systematically. The aim of the present study was to independently replicate 3 recently described RA susceptibility loci, STAT4, IL2/IL21, and CTLA4, in a large Dutch case-control cohort, and to perform a meta-analysis of all published studies to date and investigate the relevance of the findings in clinically well-defined subgroups of RA patients with or without autoantibodies. METHODS The STAT4, IL2/IL21, and CTLA4 gene polymorphisms (rs7574865, rs6822844, and rs3087243, respectively) were genotyped in 877 RA patients and 866 healthy individuals. A meta-analysis of all published studies of disease association with these polymorphisms was performed using the Mantel-Haenszel fixed-effects method. RESULTS An association of STAT4, IL2/IL21, and CTLA4 with RA was detected in Dutch patients (odds ratio [OR] 1.19 [P=0.031], OR 0.84 [P=0.051], and OR 0.87 [P=0.041], respectively). Results from the meta-analysis confirmed an association of all 3 polymorphisms with RA in Caucasians (OR 1.24 [P=1.66x10(-11)], OR 0.78 [P=5.6x10(-5)], and OR 0.91 [P=1.8x10(-3)], respectively). The meta-analysis also revealed that STAT4 predisposed to disease development equally in patients with autoantibodies and those without autoantibodies, and that CTLA4 enhanced the development of anti-citrullinated protein antibody (ACPA)-positive RA as compared with ACPA-negative RA. CONCLUSION Our results replicate and firmly establish the association of STAT4 and CTLA4 with RA and provide highly suggestive evidence for IL2/IL21 loci as a risk factor for RA. Given the strong statistical power of our meta-analysis to confirm a true-positive association, these findings provide considerable support for the involvement of CTLA4 in distinct subsets of RA patients.
Persistent Hepatitis C Virus Infection Impairs Ribavirin Antiviral Activity through Clathrin-Mediated Trafficking of Equilibrative Nucleoside Transporter 1

ABSTRACT Ribavirin (RBV) continues to be an important component of interferon-free hepatitis C treatment regimens, as RBV alone does not inhibit hepatitis C virus (HCV) replication effectively; the reason for this ineffectiveness has not been established. In this study, we investigated the RBV resistance mechanism using a persistently HCV-infected cell culture system. The antiviral activity of RBV against HCV was progressively impaired in the persistently infected culture, whereas interferon lambda 1 (IFN-λ1), a type III IFN, showed a strong antiviral response and induced viral clearance. We found that HCV replication in persistently infected cultures induces an autophagy response that impairs RBV uptake by preventing the expression of equilibrative nucleoside transporter 1 (ENT1). The Huh-7.5 cell line treated with an autophagy inducer, Torin 1, downregulated membrane expression of ENT1 and terminated RBV uptake. In contrast, the autophagy inhibitors hydroxychloroquine (HCQ), 3-methyladenine (3-MA), and bafilomycin A1 (BafA1) prevented ENT1 degradation and enhanced RBV antiviral activity. The HCV-induced autophagy response, as well as treatment with Torin 1, degrades clathrin heavy chain expression in a hepatoma cell line. Reduced expression of the clathrin heavy chain by HCV prevents ENT1 recycling to the plasma membrane and forces ENT1 to the lysosome for degradation. This study provides a potential mechanism for the impairment of RBV antiviral activity in persistently HCV-infected cell cultures and suggests that inhibition of the HCV-induced autophagy response could be used as a strategy for improving RBV antiviral activity against HCV infection. IMPORTANCE The results from this work will allow a review of the competing theories of antiviral therapy development in the field of HCV virology. Ribavirin (RBV) remains an important component of interferon-free hepatitis C treatment regimens. The reason why RBV alone does not inhibit HCV replication effectively has not been established. This study provides a potential mechanism for why RBV antiviral activity is impaired in persistently HCV-infected cell cultures and suggests that inhibition of the HCV-induced autophagy response could be used as a strategy to increase RBV antiviral activity against HCV infection. Therefore, it is anticipated that this work would generate a great deal of interest, not only among virologists but also among the general public.
Device performance of inverted polymer solar cells with AgSiO(2) nanoparticles in active layer.

UNLABELLED Localized surface plasmon mediated polymer solar cells (PSCs) were fabricated using the Ag/SiO(2) nanoparticles (NPs). The inverted PSC structure without poly (3,4-ethylenedioxythiophene) polystyrene sulfonate ( PEDOT PSS) was prepared due to the efficient insertion of Ag/SiO(2) NPs in the vicinity of active layer, which led to an enhancement in photo-conversion efficiency (PCE). This enhancement mainly comes from the light scattering by the SiO(2) shell and the localized surface plasmon effect by the Ag core, but we also considered the structural issues such as the NP distribution, the swelling of the active layer and of the metal electrode.
Predictive utility of circulating methylated DNA in serum of melanoma patients receiving biochemotherapy.

PURPOSE Currently, no validated blood-based assays accurately predict treatment response or outcome in melanoma patients. We hypothesized that methylation of tumor-related genes detected in serum DNA could predict disease outcome and therapeutic response in patients receiving concurrent biochemotherapy (BC) for metastatic melanoma. PATIENTS AND METHODS American Joint Committee on Cancer stage IV melanoma patients (N = 50) had blood drawn before administration of BC. Patients (n = 47) were classified as BC responders or nonresponders. Responders (n = 23) demonstrated a complete or partial response following BC; nonresponders (n = 24) demonstrated progressive disease. Hypermethylation of Ras association domain family 1 (RASSF1A), retinoic acid receptor-beta2 (RAR-beta2), and O6-methylguanine DNA methyltransferase (MGMT) genes were assessed by methylation-specific polymerase chain reaction. RESULTS Circulating methylated RASSF1A was significantly less frequent for responders (three of 23 patients; 13%) than nonresponders (10 of 24 patients; 42%; P = .028). Patients with RASSF1A, RAR-beta2, or at least one serum methylated gene had significantly worse overall survival than patients with no methylated genes (log-rank, P = .013, .021, and .01, respectively). Methylated RASSF1A was the only factor that significantly correlated with overall survival and BC response (risk ratio, 2.38; 95% CI, 1.16 to 4.86; P = .018; odds ratio = 0.21; 95% CI, 0.05 to 0.90; P = .036). CONCLUSION Detection of circulating methylated DNA in serum can predict response to BC and disease outcome.
Embedded control with predictive diagnostics algorithm of the induction machine drive system

Fault diagnostics of AC induction machines (ACIM) have been widely researched however, an integrated algorithm for motor control with automated fault detection, prevention and condition monitoring is still missing. Condition monitoring can reduce the downtime of the processes and increase the maximum interval between failures, thus minimizing the number and cost of unscheduled maintenances, which is highly beneficial. In addition, embedding a systems condition analysis algorithm in to the motor control algorithm results in to an integrated approach; this can reduce the cost of the system and enhance its integrity. Thus, a new algorithm is introduced for the control of ACIM and the power inverter with embedded systems fault prediction and diagnosis. The embedded control and diagnostics algorithm is implemented using the analog devices Blackfintrade ADSP-BF561 dual core digital signal processor (DSP). Core 1 is dedicated to implement the control algorithm while core 2 mainly implements the fault prediction and diagnostics algorithm. The diagnostics algorithm can shutdown the drive system on an imminent catastrophic fault. The algorithm employs various techniques to detect and predict different faults of the AC drive system. In this paper, the inverter fault prediction and diagnosis are covered. The DSP communicates the systems electrical and mechanical parameters to a Windows XPtrade PC through the USB connection, which is mainly used to monitors and displays the electrical parameters of the inverter and the motor it also allows update of the DSP controller for speed/torque adjustments
Natural History of Sudden Sensorineural Hearing Loss

This is a prospective in-depth study of patients with sudden idiopathic sensorineural hearing loss. We found that 65% recover completely to functional hearing levels spontaneously and independent of any type of medical treatment. The majority do so within 14 days and many within the first few days. Prognosis can be predicted according to the slope of the initial audiogram (low-frequency losses do better than high-frequency losses), hearing at 8 kHz, erythrocyte sedimentation rates, in some select instances spatial disorientation symptoms, and speech discrimination scores. There was a very poor correlation between hearing and vestibular test abnormalities, except hypoactive calorics. There were no correlations with age (excepting the very elderly), with antecedent respiratory infections. hypertension, diabetes, or other chronic diseases. We conclude that there is a fundamental difference in the behavior of apical and basal cochlea losses, that hearing recovery is always better at low than at high frequencies, that because of the high spontaneous recovery rates, tympanotomies seeking perilymph fistulas should be delayed ten days unless there is a progressive hearing loss, and that none of the current recommended treatments, especially histamine, have any effect on the outcome.
Single or multiple injections of methamphetamine increased dopamine turnover but did not decrease tyrosine hydroxylase levels or cleave caspase‐3 in caudate‐putamen

Methamphetamine (METH), leading to striatal dopamine (DA) nerve terminal toxicity in mammals, is also thought to induce apoptosis of striatal neurons in rodents. We investigated the acute effects induced by multiple injections of METH (4 × 5 mg/kg, i.p.) at 2‐h intervals or a single injection of METH (20 mg/kg, i.p.) on terminal dopaminergic toxicity markers, including DA levels, DA turnover, and tyrosine hydroxylase (TH) immunoreactivity in rat caudate‐putamen (CPu). We further investigated whether both treatment paradigms would change Bax and activate caspase‐3 expression, thus triggering striatal apoptotic mitochondria‐dependent biochemical cascades. The first injection of METH (5 mg/kg, i.p.) produced a significant release of DA that peaked 30 min and stayed above control levels up to 1.5 h within CPu. In another set of experiments, rats were killed 1 and 24 h following the last injection, for tissue DA and metabolite content measurement and Western blot analysis (24 h). Multiple doses induced DA depletion and increased turnover at both endpoints. Single‐dose METH reproduced these effects at 24 h; however, turnover was significantly higher than that evoked by the multiple doses at 24 h. Although both paradigms evoked similar DA depletion, however, none of the dosing regimens induced changes in TH expression at 24 h. The former paradigm produced an increase in Bax expression in CPu not sufficient to induce cleavage of caspase‐3 proenzyme at 24 h. This study suggests that both paradigm induced changes in striatal dopaminergic markers that are independent of terminal degeneration and striatal apoptotic mitochondria‐dependent caspase‐3 driven cascade within 24 h. Synapse 60:185–193, 2006. Published 2006 Wiley‐Liss, Inc.
Evaluation of tests of central nervous system performance after hypoxemia for a model for cognitive impairment

The sensitivity of several neurophysiological and cognitive tests to different levels of hypoxia was investigated. Cerebral hypoxia in healthy volunteers may be a disease model for dementia or other forms of brain dysfunction. Twelve healthy subjects were included in a randomized, single-blind, placebo-controlled, three-period cross-over trial. They received three air/N2 gas mixtures via mask breathing [aimed at peripheral oxygen saturation (SPO2) values of > 97% (placebo), 90% and 80%, with normal end-tidal CO2]. Central nervous system effects were tested regularly for 130 min by saccadic and smooth pursuit eye movements, electro-encephalogram, visual analogue scales and cognitive tests. Treatments were well tolerated. Compared to SPO2 90%, SPO2 80% reduced saccadic peak velocity by 16.4 °/s [confidence interval (CI) –26.3, –6.4], increased occipital delta power by 14.3% (CI 3.6, 25.1), and significantly increased most cognitive reaction times. SPO2 80% also decreased correct responses for the binary choice task and serial word recognition [–1.3 (–2.2, –0.3) and –3.5 (–6.2, –0.8), respectively] compared to SPO2 90%. Cognitive performance was decreased by SPO2 80% and increased by SPO2 90% compared to placebo. Sensitive effect measurements can be identified for these interventions. The applicability as a model for cognitive impairment should be investigated further.
What makes a species vulnerable to extinction? Comparative life-history traits of two sympatric snakes

Although it is well known that species vary in their vulnerability to extinction, the reasons are poorly understood. Theory predicts that long-lived species with ‘slow’ life histories (small litters, slow growth, late maturation) should be at greater risk than short-lived species with high potential rates of increase. This hypothesis was tested by comparing life-history traits of two species of sympatric, elapid snakes: the endangered broad-headed snake, Hoplocephalus bungaroides, and common small-eyed snake, Cryptophis nigrescens. From 1992 to 2000 a mark–recapture study of both species was undertaken in Morton National Park, south-eastern Australia, and this information was used to construct transition matrices for each species. The endangered H. bungaroides was found to mature late (6 years of age), had a high juvenile (54.7%) and adult (81.6%) survival rate, and a long generation length (10.4 years). In striking contrast, the common C. nigrescens matured early (within 3 years), had a lower juvenile (30.4%) and adult (74.4%) survival rate (but higher recruitment rate), and a substantially shorter generation length (5.9 years). Elasticity analyses revealed that H. bungaroides was considerably more sensitive to survival past the age of 2 years (68.6%) than C. nigrescens (37.4%). These results provide support for the hypothesis that species with slow life histories are more vulnerable to extinction.
Stable Growth of Wild-Type Hepatitis A Virus in Cell Culture

ABSTRACT Human wild-type (wt) hepatitis A virus (HAV), the causative agent of acute hepatitis, barely grows in cell culture and in the process accumulates attenuating and cell culture-adapting mutations. This genetic instability of wt HAV in cell culture is a major roadblock to studying HAV pathogenesis and producing live vaccines that are not overly attenuated for humans. To develop a robust cell culture system capable of supporting the efficient growth of wt HAV, we transfected different cell lines with in vitro RNA transcripts of wt HAV containing the blasticidin resistance gene. Blasticidin-resistant colonies grew only in transfected Huh7 cells and produced infectious virus. HAV was genetically stable in Huh7 cells for at least nine serial passages and did not accumulate attenuating or cell culture-adapting mutations. Treatment with alpha interferon A/D cured the blasticidin-resistant Huh7 cells of the HAV infection. The cured cells, termed Huh7-A-I cells, did not contain virus or HAV antigens and were sensitive to blasticidin. Huh7-A-I cells were more permissive than parental cells for wt HAV infection, including a natural isolate from a human stool sample, and produced 10-fold-more infectious particles. This is the first report of a cell line that allows the genetically stable growth of human wt HAV. The viral vectors and cells described here should allow better insight into the pathogenesis of HAV and the development of attenuated vaccines. The cell lines susceptible to wt HAV growth may also be used to detect and isolate infectious virus from patient and environmental samples.
Branchiobdellidan infestation on endangered white-clawed crayfish (Austropotamobius pallipes) in the UK

SUMMARY Branchiobdellidans or crayfish worms are clitellate annelids and ectosymbionts of freshwater crayfish. An investigation of branchiobdellidan infestation was undertaken in a population of endangered white-clawed crayfish (Austropotamobius pallipes) in the river Aire, UK. Thirty two percent of animals were infested either by the adult parasite or their cocoons (n=107). Parasite burden increased with host size, but did not differ with sex. Observations of crayfish gill tissue revealed a strong positive relationship between melanization of filaments and parasite prevalence and burden. Taxonomic identification revealed that 1 species of branchiobdellidan was present, Branchiobdella astaci. The first sequences were generated for this species and phylogenetically analysed alongside published sequences for 5 other branchiobdellidan species in Europe. The position of B. astaci within the genus Branchiobdella was confirmed, and it was found to cluster as a sister group to B. parasita.
Memory of Ordinal Number Categories in Macaque Monkeys

What mechanism underlies serial order memory? Studying preverbal serial memory shows that macaque monkeys reproducing a sequence of items can acquire knowledge of item ordinal position. In our previous experiment, macaques were repeatedly presented with image lists (first shown sequentially and then simultaneously on a touch screen together with a distractor chosen randomly from other lists). The task was to touch list images in the correct order. The monkeys' natural tendency was to categorize images by their ordinal position or number because their most common error was touching the distractor when it had the same ordinal number (in its own list) as the correct image. Item-to-item associations were used to complete the categorization strategy. Proposing a dynamic image-salience hypothesis for serial recall (based on category-to-image influence and a salience computation for identifying touch targets), we now study the category label characteristics in the context of this hypothesis. We found that these category labels are absolute, ordinal-number-based categories (first, second, etc.), not relative memorized as relative distance from the beginning and the end of the list, and not based on fixed ranking of reward contingency/image familiarity. Even isolated from item–item associations, the categories demonstrate category tuning (as well as the corresponding overlap of adjacent ordinal number codes). Moreover, monkeys choose images by proximity of their category to the current touch number, irrespective of the accuracy of the preceding choice. Category tuning itself is symmetric relative to correct ordinal position, but is skewed by other factors (reward, etc.). Tuning width increases with list length, with a concurrent increased use of item-to-item associations for determining touch order.