Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypertensive Kidney Injury and the Progression of Chronic Kidney Disease.

The kidney is a major site for hypertensive target organ damage which is second only to diabetic nephropathy as a primary cause for end-stage renal disease (ESRD). Moreover, the presence of chronic kidney disease (CKD), including that caused by hypertension, has been shown to be a strong independent risk factor for adverse cardiovascular outcomes.1 Nevertheless, major aspects of clinical hypertensive renal disease remain poorly understood such as the marked differences in individual susceptibility to hypertensive renal damage and the apparent variable renoprotective effectiveness of antihypertensive classes. Using experimental models to achieve clearer insights into such phenomenon through an integrated team approach has been a major focus of our laboratory. This review provides an overview of the collective contributions of this investigative team to address these unresolved issues of clinical hypertensive renal damage (Acknowledgments). One of the most striking of such clinical observations is the fact that although hypertension is a major population risk for ESRD, this is primarily because of the huge prevalence of hypertension in the general population. The individual risk is surprisingly small (<0.5%). 2,3 This is because the renal pathology typically observed in the vast majority of individuals with essential hypertension is that of benign nephrosclerosis described as an accelerated aging of the renal vasculature.3–5 It is characterized by a very slowly progressive thickening and sclerosis of the renal resistance vessels, whereas the glomerular capillaries are largely spared. Some ischemic glomerular loss does occur but is limited and happens slowly over decades. Given that significant reductions in renal function and ESRD only develop after large losses of glomerular filtration surface area have occurred, it is perhaps not too surprising that ESRD occurs infrequently in essential hypertension. In fact, except for some genetically susceptible groups, such as blacks, the only individuals with …
Inhibition of sugar uptake by methotrexate in cultured Ehrlich ascites carcinoma cells.

Methotrexate (MTX) decreases adenosine 5′-triphosphate pools and inhibits glycolysis in cultured Ehrlich ascites carcinoma cells. The purpose of this study was to examine the effects of MTX on sugar transport and phosphorylation. Cells that were grown in continuous spinner cultures were incubated in media with and without 2 × 10-6 m MTX for 24 hr and assayed at intervals for rates of uptake of 3- O -methyl-d-glucose (to measure the rates of sugar transport), of 2-deoxy-d-glucose (to measure the rates of sugar transport and phosphorylation), and of glucose into total cellular material (to compare with the data obtained with the non-metabolizable sugars). MTX progressively and profoundly inhibited 2-deoxy-d-glucose uptake; the effect was on the Vmax and the apparent Km for 2-deoxy-d-glucose was normal. Adenosine 5′-triphosphate depletion by glucose deprivation inhibited 2-deoxy-d-glucose uptake to a similar degree. MTX progressively inhibited the rates of protein synthesis. Hexokinase activity in cell extracts was normal during first 6 hr and decreased after 24 hr. Cycloheximide progressively decreased 2-deoxy-d-glucose uptake rates, which corresponded to the decreases of hexokinase activity in cell extracts. Rates of 3- O -methyl-d-glucose transport were decreased by up to 50% in MTX-treated and in adenosine 5′-triphosphate-depleted cells. This decrease was not due to a change in the saturability characteristics of the transport system, to inhibition of protein synthesis, or to effects on a ouabain-sensitive adenosine-5′-triphosphatase. Hypoxanthine prevented the inhibitions of 3- O -methyl-d-glucose and of 2-deoxy-d-glucose uptakes by MTX. Glucose uptakes into total cellular material were reduced by 50% in cells incubated with MTX for 24 hr, by 30% in cells incubated with cycloheximide for 24 hr, and by 30% in glucose-deprived cells.
Chapter 5 C-reactive protein and procalcitonin concentrations in bronchoalveolar lavage fluid as a predictor of ventilator-associated pneumonia

Objective Diagnosis of ventilator-associated pneumonia (VAP) is difficult. The usefulness of high-sensitivity PCT (ProCa-S) and – CRP (CRPH) in bronchoalveolar lavage fluid (BALF) and serum in the prediction of VAP was determined. Study design The study was conducted over a 28-month period (November 1999 – June 2002) at the University Hospital Maastricht. BALF samples were collected from patients admitted to the intensive care unit. Differential cell-count and quantitative culture of BALF were performed. CRP and PCT on BALF were determined by means of two high sensitivity kits (CRPH and ProCa-S respectively). Since both kits were designed for use on serum, validation for use on BALF was performed. Results 117 patients were included. 43.6% (51/117) had microbiologically confirmed VAP. Both CRPH as ProCa-S showed good matrix effect, linearity and intraand interassay variation. No significant differences in PCT and CRP levels in serum and BALF were found between the VAP and the nonVAP group. Conclusions Both the ProCa-S as the CRPH kit can be used for assessing the concentration of respectively PCT and CRP in BALF. PCT and CRP levels in BALF appeared to be of no additional value in the diagnosis of VAP. Chapter 4 CRP and PCT in the prediction of VAP⏐77
Best Split-Half and Maximum Reliability

The paper addresses an iterative method by which a test can be dichotomized in parallel halves and ensures maximum split-half reliability. The method assumes availability of data on scores of binary items. Since, it was aiming at splitting a test in parallel halves, no assumption was made regarding form or availability of reference test. Empirical verification is also provided. Other properties of the iterative methods discussed. New measures of degree of parallelism given. Simultaneous testing of single multidimensional hypothesis of equality of mean, variance and correlation of parallel tests can also be carried out by testing equality of regression lines of test scores on scores of each of the parallel halves, ANOVA or by Mahalanobis�� 2 . The iterative method can be extended to find split-half reliability of a battery of tests. The method thus provides answer to much needed question of splitting a test uniquely in parallel halves ensuring maximum value of the split-half reliability. The method may be adopted while reporting a test.
Topology Optimization of a High-Temperature Superconducting Field Winding of a Synchronous Machine

This paper presents topology optimization (TO) of the high-temperature superconductor (HTS) field winding of an HTS synchronous machine. The TO problem is defined in order to find the minimum HTS material usage for a given HTS synchronous machine design. Optimization is performed using a modified genetic algorithm with local optimization search based on on/off sensitivity analysis. The results show an optimal HTS coil distribution, achieving compact designs with a maximum of approximately 22% of the available space for the field winding occupied with HTS tape. In addition, this paper describes potential HTS savings, which could be achieved using multiple power supplies for the excitation of the machine. Using the TO approach combined with two excitation currents, an additional HTS saving of 9.1% can be achieved.
Initiation Timing of Low-Intensity Pulsed Ultrasound Stimulation for Tendon-Bone Healing in a Rabbit Model

Background: Low-intensity pulsed ultrasound stimulation (LIPUS) has been proven to be a beneficial biophysical therapy for tendon-bone (T-B) healing. However, the optimal time to initiate LIPUS treatment has not been determined yet. LIPUS initiated at different stages of the inflammatory phase may profoundly affect T-B healing. Purpose: An established rabbit model was used to preliminarily investigate the effect of LIPUS initiation timing on T-B healing. Study Design: Controlled laboratory study. Methods: A total of 112 mature rabbits that underwent partial patellectomy were randomly assigned to 4 groups: daily mock sonication (control group) and daily ultrasonication started immediately postoperatively (immediate group), on postoperative day 7 (7-day delayed group), or on postoperative day 14 (14-day delayed group). Peripheral leukocyte counts at the inflammatory phase were used to assess postoperative inflammation. The rabbits were sacrificed at 8 or 16 weeks postoperatively for microarchitectural, histological, and mechanical evaluations of the patella–patellar tendon (PPT) junction. Results: The biomechanical properties of the PPT junction were significantly improved in the LIPUS-treated groups. Significantly higher ultimate strength and stiffness were seen in the 7-day delayed group compared with the other groups at 8 weeks postoperatively (P < .05 for all). Newly formed bone expansion from the remaining patella in the ultrasonic treatment groups was significantly increased and remodeled compared with the control group. Micro–computed tomography analysis showed that the 7-day delayed group had significantly more bone volume and bone mineral content at the interface as compared with the other groups at 8 weeks postoperatively (P < .05 for all). Histologically, the ultrasonic treatment groups exhibited a significantly better PPT junction, as shown by more formation and remodeling of the fibrocartilage layer and newly formed bone. Additionally, peripheral leukocyte counts displayed a significant increase from postoperative day 1 to day 3 in the immediate group as compared with the other groups. Furthermore, postoperative hydrarthrosis was more likely in the immediate group. Conclusion: LIPUS started at postoperative day 7 had a more prominent effect on T-B healing compared with the other treatment regimens in this study. Clinical Relevance: The findings of the study may help optimize the initiation timing of LIPUS for T-B healing.
Reticulated platelets and uninhibited COX‐1 and COX‐2 decrease the antiplatelet effects of aspirin

Background: The mechanisms for the variability in antiplatelet effects of aspirin are unclear. Immature (reticulated) platelets may modulate the antiplatelet effects of aspirin through uninhibited cyclooxygenase (COX)‐1 and COX‐2. Objectives: To evaluate the role of reticulated platelets in the antiplatelet effects of aspirin. Methods: Sixty healthy volunteers had platelet studies performed before and 24 h after a single 325‐mg dose of aspirin. Platelet studies included light transmission aggregometry; P‐selectin and integrin αIIbβ3 expression, and serum thromboxane B2 (TxB2) levels. Reticulated platelets and platelet COX‐2 expression were measured using flow cytometry. Results: Subjects were divided into tertiles based on the percentage of reticulated platelets in whole blood. Baseline platelet aggregation to 1 μg mL−1 collagen, and postaspirin aggregations to 5 μm and 20 μm ADP and collagen, were greater in the upper than in the lower tertile of reticulated platelets. Stimulated P‐selectin and integrin αIIbβ3 expression were also higher in the upper tertile both before and after aspirin. Platelet COX‐2 expression was detected in 12 ± 7% (n = 10) of platelets in the upper tertile, and in 7 ± 3% (n = 12) of platelets in the lower two tertiles (P = 0.03). Postaspirin serum TxB2 levels were higher in the upper (5.5 ± 4 ng mL−1) than in the lower tertile (3.2 ± 2.5 ng mL−1, P = 0.03), and decreased even further with ex vivo additional COX‐1 and COX‐2 inhibition. The incidence of aspirin resistance (≥ 70% platelet aggregation to 5 μm ADP) was significantly higher in the upper tertile (45%) than in the lower tertile (5%, P < 0.0001). Conclusions: Reticulated platelets are associated with diminished antiplatelet effects of aspirin and increased aspirin resistance, possibly because of increased reactivity, and uninhibited COX‐1 and COX‐2 activity.
Feasibility Analysis and Dynamic Voltage Scaling in Fault-Tolerant Real-Time Embedded Systems

We investigate dynamic voltage scaling (DVS) in realtime embedded systems that use checkpointing for fault tolerance. We present feasibility-of-scheduling tests for checkpointing schemes for a constant processor speed as well as for variable processor speeds. DVS is then carried out on the basis of the feasibility analysis. We incorporate practical issues such as faults during checkpointing and state restoration, rollback recovery time, memory access time and energy, and DVS overhead. Simulation results are presented for real-life checkpointing data and embedded processors.
The Interaction of Supertyphoon Maemi ( 2003 ) with a Warm Ocean

Understanding the interaction of ocean eddies with tropical cyclones is critical for improving the understanding and prediction of the tropical cyclone intensity change. Here an investigation is presented of the interaction between Supertyphoon Maemi, the most intense tropical cyclone in 2003, and a warm ocean eddy in the western North Pacific. In September 2003, Maemi passed directly over a prominent (700 km 500 km) warm ocean eddy when passing over the 22°N eddy-rich zone in the northwest Pacific Ocean. Analyses of satellite altimetry and the best-track data from the Joint Typhoon Warning Center show that during the 36 h of the Maemi–eddy encounter, Maemi’s intensity (in 1-min sustained wind) shot up from 41 m s 1 to its peak of 77 m s . Maemi subsequently devastated the southern Korean peninsula. Based on results from the Coupled Hurricane Intensity Prediction System and satellite microwave sea surface temperature observations, it is suggested that the warm eddies act as an effective insulator between typhoons and the deeper ocean cold water. The typhoon’s self-induced sea surface temperature cooling is suppressed owing to the presence of the thicker upper-ocean mixed layer in the warm eddy, which prevents the deeper cold water from being entrained into the upper-ocean mixed layer. As simulated using the Coupled Hurricane Intensity Prediction System, the incorporation of the eddy information yields an evident improvement on Maemi’s intensity evolution, with its peak intensity increased by one category and maintained at category-5 strength for a longer period (36 h) of time. Without the presence of the warm ocean eddy, the intensification is less rapid. This study can serve as a starting point in the largely speculative and unexplored field of typhoon–warm ocean eddy interaction in the western North Pacific. Given the abundance of ocean eddies and intense typhoons in the western North Pacific, these results highlight the importance of a systematic and in-depth investigation of the interaction between typhoons and western North Pacific eddies.
The IPOS New International Standard of Quality Cancer Care: integrating the psychosocial domain into routine care

Jimmie Holland, Maggie Watson and Jeff Dunn Department of Psychiatry and Behavioral Sciences, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Psychology Research Group, Sycamore House, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK Griffith Health Institute, Griffith University, Australia School of Social Science, University of Queensland, Australia Viertel Centre for Research in Cancer Control, Cancer Council Queensland, Australia
Era of Multi-Core Processors

Since the very beginning of integrated circuits development, processors were invented with ever-increasing clock frequencies and sophisticated in-build optimisation strategies. Due to physical limitations, this 'free lunch' of speedup has come to an end. Physical constraints put up multiple barriers in achieving high performance computing within power budgets. Computer architects are trying to cross these performance restricting walls using number of innovative processor architectures employing area concurrency. These processors are commonly known as multi-core processors. The following article gives a summary of recent trends and challenges in multi-core processor architectures. It discusses how 40 years of parallel computing research need to be considered in the upcoming multi-core era. I feel that the future research must be driven from two sides-a better expression of hardware structures, and a domain-specific understanding of software parallelism.
Hepatorenal Syndrome: A Review of Pathophysiology and Current Treatment Options

Cirrhosis is a result of advanced liver disease and is characterized by ﬁ brosis of liver tissue and conversion of normal architecture into regenerative nodules, 1,2 leading to a loss of liver function. According to the Centers for Disease Control, cirrhotic liver disease is responsible for 15,000 deaths per year in the United States. 3,4 Portal hypertension (de ﬁ ned as elevation of hepatic venous pressure gradient (cid:1) 5 mm Hg) is a hallmark of cirrhosis, which is the result of a complicated process of in ﬂ ammation, necrosis, collagen deposition, and regenerating nodules in the liver parenchyma. 5,6 Increased portal pressure ultimately reduces portal blood ﬂ ow, leading to the release of vasodilators and blood pooling in the splanchnic circulation. This results in renal hypoperfusion, with consequent activation of the renal – angiotensin – aldosterone system and ﬂ uid retention. 7 Combined with decreased oncotic forces from hypoalbuminemia, ﬂ uid leakage from the splanchnic circulation begins to exceed the capacity of the lymphatic drainage system, and ascites, a characteristic complication of decompensated cirrhosis, develops. 5 –
Discovery and Functional Assessment of Gene Variants in the Vascular Endothelial Growth Factor Pathway

Angiogenesis is a host‐mediated mechanism in disease pathophysiology. The vascular endothelial growth factor (VEGF) pathway is a major determinant of angiogenesis, and a comprehensive annotation of the functional variation in this pathway is essential to understand the genetic basis of angiogenesis‐related diseases. We assessed the allelic heterogeneity of gene expression, population specificity of cis expression quantitative trait loci (eQTLs), and eQTL function in luciferase assays in CEU and Yoruba people of Ibadan, Nigeria (YRI) HapMap lymphoblastoid cell lines in 23 resequenced genes. Among 356 cis‐eQTLs, 155 and 174 were unique to CEU and YRI, respectively, and 27 were shared between CEU and YRI. Two cis‐eQTLs provided mechanistic evidence for two genome‐wide association study findings. Five eQTLs were tested for function in luciferase assays and the effect of two KRAS variants was concordant with the eQTL effect. Two eQTLs found in each of PRKCE, PIK3C2A, and MAP2K6 could predict 44%, 37%, and 45% of the variance in gene expression, respectively. This is the first analysis focusing on the pattern of functional genetic variation of the VEGF pathway genes in CEU and YRI populations and providing mechanistic evidence for genetic association studies of diseases for which angiogenesis plays a pathophysiologic role.
Inhibiting eukaryotic transcription. Which compound to choose? How to evaluate its activity?

This review deals first with general questions: how to evaluate transcription inhibition, describe changes in nuclear structure due to transcription inhibition, report on genes that are paradoxically stimulated by transcription inhibition. Next, it reviews the characteristics and mechanisms of commonly used inhibitors. α-amanitin is highly selective for RNAP II and RNAP III but its action is slow, actinomycin D is fast but its selectivity is poor, CDK9 inhibitors such as DRB, flavopiridol, are fast and reversible but many genes escape transcription inhibition. New compounds such as triptolide are fast, selective and completely arrest transcription as they trigger rapid degradation of RNAP II.
Using Population Count Data to Assess the Effects of Changing River Flow on an Endangered Riparian Plant

Abstract: Methods for using simple population count data to project extinction risk have been the focus of much recent theoretical work, but few researchers have used these approaches to address management questions. We analyzed 15 years of census data on the federally endangered endemic riparian plant Pityopsis ruthii (Small) with the diffusion approximation (DA). Our goals were to evaluate relative extinction risk among populations in two different watersheds (in Tennessee, U.S.A.) and potential effects of variation in managed river flow on population dynamics. Populations in both watersheds had high projected risks of extinction within 50 years, but the causes of this risk differed. Populations of P. ruthii on the Hiwassee River had higher initial population sizes but significantly lower average growth rates than those on the Ocoee River. The only populations with low predicted short‐term extinction risk were on the Ocoee. Growth rates for populations on both rivers were significantly reduced during periods of lower river flow. We found only marginal evidence of a quadratic relationship between population performance and flow. These patterns are consistent with the idea that low flows affect P. ruthii due to growth of competing vegetation, but the degree to which very high flows may reduce population growth is still unclear. Simulations indicated that populations were most sensitive to growth rates in low‐flow years, but small changes in the frequency of these periods did not strongly increase risk for most populations. Consistent with results of other studies, DA estimates of extinction risk had wide confidence limits. Still, our results yielded several valuable insights, including the need for greater monitoring of populations on the Hiwassee and the importance of low‐flow years to population growth. Our work illustrates the potential value of simple methods for analyzing count data despite the challenges posed by uncertainty in estimates of extinction risk.
Altered effector functions of NK cells in chronic hepatitis C are associated with IFNL3 polymorphism

Interferon α‐mediated effector functions of NK cells may contribute to the control of HCV replication and the pathogenesis of liver disease. The single‐nucleotide polymorphism rs12979860 near IFNL3 (previously known as IL28B) is important in response to IFN‐α treatment and in spontaneous resolution of acute hepatitis C. The role of the IFNL3 polymorphism in NK cell function is unclear. Thus, we investigated the role of IFNL3 polymorphism in type I IFN‐dependent regulation of NK cell functions in patients with cHC and healthy control subjects. We demonstrated a marked polarization of NK cells toward cytotoxicity in response to IFN‐α stimulation in patients with hepatitis C. That TRAIL up‐regulation was present, particularly in patients with the IFNL3‐TT allele, was supported by a shift in the pSTAT‐1:pSTAT‐4 ratios toward pSTAT‐1. In patients bearing the IFNL3‐TT allele, NK cell effector function correlated with liver disease activity. In contrast, higher cytokine production of NK cells was observed in healthy individuals with the IFNL3‐CC genotype, which may support spontaneous HCV clearance in acute infection. Overall, these findings show that the role of NK cells may differ in chronic infection vs. early antiviral defense and that the IFNL3 genotype differentially influences NK cell function.