Miracle-dz/UniFAR-FTUs huggingface dataset:
Homocysteine Accelerates Senescence of Endothelial Cells via DNA Hypomethylation of Human Telomerase Reverse Transcriptase

Objective—Homocysteine can accelerate the senescence of endothelial progenitor cells or endothelial cells (ECs) via telomerase inactivation and length shortening. However, the underlying mechanism is unclear. Here, we investigated whether homocysteine promotes endothelial senescence by reducing the expression and activity of human telomerase reverse transcriptase (hTERT) by DNA methylation to reduce ECs telomerase activity. Approach and Results—When compared with primary human umbilical vein endothelial cells grown under standard conditions, ECs with chronic homocysteine treatment showed accelerated upregulation of p16, p21, and p53, markers of cellular senescence, during 6 to 10 passages. Interestingly, homocysteine-stimulated but not angiotensin II–stimulated ECs senescence could be reversed by hypermethylation induced by folic acid or s-adenosylmethionine supplementation. Meanwhile, homocysteine promoted the shortening of telomere length specifically related to restoration of hTERT transcriptional expression and CCCTC-binding factor binding sites with hTERT promoter hypomethylation, as detected by quantitative real-time polymerase chain reaction, Western blot, methylation-specific polymerase chain reaction, and bisulfite sequencing assay. Electrophoretic mobility shift assay and chromatin immunoprecipitation results showed that homocysteine-reduced telomere activity and homocysteine-induced EC senescence might contribute to hTERT promoter demethylation by increasing CCCTC-binding factor repression and interfering in the SP1 binding to the demethylated hTERT promoter, which might relate with reduced of DNA methyltransferase 1. Furthermore, the CCCTC-binding factor–dependent mechanism of homocysteine-reduced hTERT expression via DNA demethylation was confirmed in aortic endothelia of mice with hyperhomocysteine levels. Conclusions—CCCTC-binding factor and SP1 cross talk may contribute to homocysteine-reduced hTERT DNA methylation and expression in endothelial senescence.
A Genetic Polymorphism Maintained by Natural Selection in a Temporally Varying Environment

Environments that are crowded with larvae of the fruit fly, Drosophila melanogaster, exhibit a temporal deterioration in quality as waste products accumulate and food is depleted. We show that natural selection in these environments can maintain a genetic polymorphism with one group of genotypes specializing on the early part of the environment and a second group specializing on the late part. These specializations involve trade‐offs in fitness components. The early types emerge first from crowded cultures and have high larval feeding rates, which are positively correlated with competitive ability but exhibit lower absolute viability than the late phenotype, especially in food contaminated with the nitrogenous waste product, ammonia. The late emerging types have reduced feeding rates but higher absolute survival under conditions of severe crowding and high levels of ammonia. Organisms that experience temporal variation within a single generation are not uncommon, and this model system provides some of the first insights into the evolutionary forces at work in these environments.
How Reliable Is Perfusion MR in Acute Stroke?: Validation and Determination of the Penumbra Threshold Against Quantitative PET

Background and Purpose— Perfusion magnetic resonance imaging (pMR) is increasingly used in acute stroke, but its physiologic significance is still debated. A reasonably good correlation between pMR and positron emission tomography (PET) has been reported in normal subjects and chronic cerebrovascular disease, but corresponding validation in acute stroke is still lacking. Methods— We compared the cerebral blood flow (CBF), cerebral blood volume, and mean transit time (MTT) maps generated by pMR (deconvolution method) and PET (15O steady-state method) in 5 patients studied back-to-back with the 2 modalities at a mean of 16 hours (range, 7 to 21 hours) after stroke onset. We also determined the penumbra thresholds for pMR-derived MTT, time to peak (TTP), and Tmax against the previously validated probabilistic PET penumbra thresholds. Results— In all patients, the PET and pMR relative distribution images were remarkably similar, especially for CBF and MTT. Within-patient correlations between pMR and PET were strong for absolute CBF (average r2=0.45) and good for MTT (r2=0.35) but less robust for cerebral blood volume (r2=0.24). However, pMR overestimated absolute CBF and underestimated MTT, with substantial variability in individual slopes. Removing individual differences by normalization to the mean resulted in much stronger between-patient correlations. Penumbra thresholds of ≈6, 4.8, and 5.5 seconds were obtained for MTT delay, TTP delay, and Tmax, respectively. Conclusions— Although derived from a small sample studied relatively late after stroke onset, our data show that pMR tends to overestimate absolute CBF and underestimate MTT, but the relative distribution of the perfusion variables was remarkably similar between pMR and PET. pMR appears sufficiently reliable for clinical purposes and affords reliable detection of the penumbra from normalized time-based thresholds.
Factors impacting self-care for urinary incontinence.

INTRODUCTION Behavioral strategies such as pelvic floor muscle exercises (PFME), bladder retraining, and dietary modifications are generally considered to be the first line of treatment for urinary incontinence (UI). Yet little is understood about the client's abilities/motivation to manage their UI in the home setting. Self-care, the ability of clients to act on their own behalf to achieve and maintain health, is a fundamental component of these strategies. Despite the frequently chronic nature of UI, there is growing evidence that such maintenance of behavioral therapies is sporadic at best. OBJECTIVE The purpose of this study was to enhance understanding of self-care strategies that individuals with UI employ, the perceived benefits of these strategies, the factors that influence their self-care choices, and the factors that impede or facilitate maintenance of behavioral therapies. METHOD In this qualitative descriptive study, individual and focus group interviews with community-dwelling participants were conducted to enhance understanding regarding the participants' management of UI at home and why they maintain certain strategies and not others. Data were collected via loosely constructed individual (n=25) and focus group (n=3) interviews to facilitate open discussion of participants' perceptions. RESULTS Thirty-eight individuals (33 women and 5 men) participated in the study. Analysis of data resulted in a major category of self-care strategies related to UI that was further subcategorized into factors that facilitated PFME and barriers to PFME performance. Factors that facilitated PFME included: (a) realistic goals and expectation, (b) positive affirmation, (c) follow up, and (d) maintaining an exercise routine. Barriers noted were: (a) insufficient information, (b) characteristics of the exercises, (c) competing interests, (d) financial cost, and (e) minor psychosocial impact. CONCLUSIONS This study described the self-care strategies that participants with UI had initiated and maintained and additionally explored the perceived facilitators and barriers to self-care choices. Two major themes emerged: (a) self-care efforts were motivated by desire for a normal daily lifestyle and (b) participants were motivated to maintain strategies by the ability to visualize progress and by knowledge that they were progressing. These findings support the need for client-focused teaching that is grounded in the individual's daily realities and goals.
Compact distributed RLC interconnect models-Part II: Coupled line transient expressions and peak crosstalk in multilevel networks

For pt. I see ibid., vol. 47, no. 11, (Nov. 2000). Novel compact expressions that describe the transient response of high-speed resistance, inductance, and capacitance (RLC) coupled interconnects are rigorously derived. These new distributed rlc models reveal that peak crosstalk voltage is over 60% larger for 3 GHz high-speed interconnects than predicted by current distributed RC models. Simplified forms of the compact models enable physical insight and accurate estimation of peak crosstalk voltage between two and three distributed RLC interconnects.
Maximally entangled states of four nonbinary particles

Systems of four nonbinary particles, each having three or more internal states, exhibit maximally entangled states that are inaccessible to four qubits. This breaks the pattern of two- and three-particle systems, in which the existing graph states are equally accessible to binary and nonbinary systems alike. We compare the entanglement properties of these special states (called P-states) with those of the more familiar GHZ and cluster states accessible to qubits. The comparison includes familiar entanglement measures, the "steering" of states by projective measurements, and the probability that two such measurements, chosen at random, leave the remaining particles in a Bell state. These comparisons demonstrate not only that P-state entanglement is stronger than the other types, but that it is maximal in a well-defined sense. We prove that GHZ, cluster, and P-states represent all possible entanglement classes of four-particle graph states with a prime number (>2) of states per particle.
The G1613A Mutation in the HBV Genome Affects HBeAg Expression and Viral Replication through Altered Core Promoter Activity

Infection of hepatitis B virus (HBV) causes acute and chronic hepatitis and is closely associated with the development of cirrhosis and hepatocellular carcinoma (HCC). Previously, we demonstrated that the G1613A mutation in the HBV negative regulatory element (NRE) is a hotspot mutation in HCC patients. In this study, we further investigated the functional consequences of this mutation in the context of the full length HBV genome and its replication. We showed that the G1613A mutation significantly suppresses the secretion of e antigen (HBeAg) and enhances the synthesis of viral DNA, which is in consistence to our clinical result that the G1613A mutation associates with high viral load in chronic HBV carriers. To further investigate the molecular mechanism of the mutation, we performed the electrophoretic mobility shift assay with the recombinant RFX1 protein, a trans-activator that was shown to interact with the NRE of HBV. Intriguingly, RFX1 binds to the G1613A mutant with higher affinity than the wild-type sequence, indicating that the mutation possesses the trans-activating effect to the core promoter via NRE. The trans-activating effect was further validated by the enhancement of the core promoter activity after overexpression of RFX1 in liver cell line. In summary, our results suggest the functional consequences of the hotspot G1613A mutation found in HBV. We also provide a possible molecular mechanism of this hotspot mutation to the increased viral load of HBV carriers, which increases the risk to HCC.
Upregulation of a Disintegrin and Metalloproteinase With Thrombospondin Motifs-7 by miR-29 Repression Mediates Vascular Smooth Muscle Calcification

Objective—Vascular calcification significantly increases cardiovascular morbidity and mortality. We recently reported that the deficiency of cartilage oligomeric matrix protein (COMP) leads to vascular mineralization. We characterized the COMP-degrading metalloproteinase, a disintegrin and metalloproteinase with thrombospondin motifs-7 (ADAMTS-7). Here, we tested whether ADAMTS-7 facilitates vascular calcification. Methods and Results—ADAMTS-7 expression was markedly upregulated in calcifying rat vascular smooth muscle cells (VSMCs) in vitro, calcified arteries of rats with chronic renal failure in vivo, and radial arteries of uraemic patients. Silencing of ADAMTS-7 markedly reduced COMP degradation and ameliorated VSMC calcification, whereas ectopic expression of ADAMTS-7 greatly enhanced COMP degradation and exacerbated mineralization. The transcriptional activity of ADAMTS-7 promoter was not altered by high phosphate. We used bioinformatics and quantitative polymerase chain reaction analysis to demonstrate that high-phosphate upregulated ADAMTS-7 mRNA and protein via miR-29a/b repression, which directly targeted the 3′ untranslated region of ADAMTS-7 in VSMCs. MicroRNA (MiR)-29a/b mimic markedly inhibited but miR-29a/b inhibitor greatly enhanced high-phosphate–induced ADAMTS-7 expression, COMP degradation, and subsequent VSMC calcification. ADAMTS-7 silencing significantly diminished miR-29a/b repression–exaggerated VSMC calcification. Conclusion—Our data reveal a novel mechanism by which ADAMTS-7 upregulation by miR-29a/b repression mediates vascular calcification, which may shed light on preventing cardiovascular morbidity and mortality.
Ten factors that impede improvement of verification and validation processes in software intensive organizations

In spite of the potential benefits that the correct application of software verification and validation processes, techniques and tools can provide, their institutionalized use in the software industry does not reach the minimum capability levels required to gain these benefits. Moreover, this circumstance is aggravated in the small and medium SIOs because of the lack of available human and economic resources. In this paper, ten of the most important factors that prevent the correct institutionalization of the software verification and validation efficient practices are presented. These factors are obtained from the authors' experience in several software process improvement initiatives in software verification and validation processes. Copyright © 2008 John Wiley & Sons, Ltd.
Verification and Synthesis of Timing Contracts for Embedded Controllers

Timing contracts for embedded controller implementation specify the constraints on the time instants at which certain operations are performed such as sampling, actuation, computation, etc. In this paper, we consider the problem of verifying the stability of embedded control systems under such timing contracts. Reformulating the problem in the framework of impulsive linear systems, we provide theoretical conditions for stability and a verification algorithm based on reachability analysis. In the second part of the paper, given a model of the plant and of the controller we propose an approach to synthesize timing contracts that guarantee stability.
Assessing the effects of titanium dioxide nanoparticles on microbial communities in stream sediment using artificial streams and high throughput screening

Nano-titanium dioxide (nano-TiO2) is an engineered nanomaterial used in a wide array of commercial products. The production and use of large amounts of nano-TiO2 is resulting in the unintended release to the environment. Nano-TiO2 is known to be cytotoxic due primarily to its ability to generate reactive oxygen species, and negative impacts on a variety of organisms have been demonstrated, but the effects of nano-TiO2 on complex microbial communities under ecologically relevant conditions have rarely been tested. We conducted a controlled manipulative experiment using recirculating model streams dosed with a one-time amendment of 1mg L-1 nano-TiO2 (specifically P25). Within one day bacterial cell numbers in the treated streams were 25% lower than in the control streams, but by 30 days post-treatment bacterial numbers in the treated streams had recovered. Treated streams also showed significantly higher per-cell respiration rates than controls on days 8 and 15. Tag pyrosequencing of bacterial 16S rRNA genes indicated that bacterial communities in the nano-TiO2 treated streams were highly similar to each other and distinct from the control streams on days 1 through 23, but by day 30 the community composition in the treated streams had returned to being indistinguishable from the control streams. Our results demonstrate that one-time addition of nano-TiO2, representative of an accidental release, can have a rapid but temporary effect on the size, activity and composition of sediment bacterial communities. The use of high-throughput screening (HTS) enabled us to test the effects of four different types of nanoTiO2 (P25, PW6, pure anatase particles, and pure rutile particles) at various concentrations to bacterial communities collected from sediments from two different streams. To simulate the effects of sunlight, various concentrations of nanoTiO2 and bacteria suspension was exposed under a xenon arc lamp for one hour. In Chicago River communities, incubation of all types of nanoTiO2 of concentrations 1 mg/L and higher significantly decreased bacterial viability compared to 0 mg liter-1 controls. Although Nippersink Creek communities were sensitive to nanoTiO2, incubation of only the highest concentration of P25 (25 mg liter-1) with illumination lowered bacterial viability significantly. Our results confirmed that illumination is an important contributor to short-term nanoTiO2 toxicity and indicate a difference in the bacterial community responses to nanoTiO2 based on anthropogenic pollution in the habitat.
Prevalence of Work-Related Asthma in Michigan, Minnesota, and Oregon

Introduction. Adults who have asthma that is caused or aggravated by triggers at work experience a reduced quality of life. In this study, the authors sought to estimate the proportion of asthma that is associated with work using a state-based survey of adults with asthma. Methods. In 2005, Michigan, Minnesota, and Oregon piloted the Behavioral Risk Factor Surveillance System Adult Asthma Call-Back Survey, with sample sizes of 867, 469, and 1072, respectively. Six questions addressing work-related asthma (WRA) were analyzed to generate estimates of the proportion of adult asthma that is work-related and compare those with and without WRA. Results. Over half of all adults with asthma (53%) reported that their asthma was caused or made worse by any job they ever had, and among these respondents reporting WRA, only 21.5% to 25.1% reported ever telling or being told by a health professional that their asthma was work-related. Additionally, adults with WRA consistently reported poorer asthma control and higher health care utilization than adults with non-WRA. Conclusions. WRA is a common but frequently unrecognized health problem, and this lack of recognition might contribute to poorer asthma control among adults with WRA. Because early recognition, treatment, and management of WRA are crucial for improving long-term prognosis, clinicians need to include assessment of workplace triggers in both their diagnostic and treatment plans for adult patients with asthma.
Influence of marrow erythropoietic activity on serum erythropoietin levels after autologous hematopoietic stem cell transplantation.

BACKGROUND AND OBJECTIVE Serum erythropoietin (sEpo) concentration depends primarily on the rate of renal production in response to hypoxia. However, sEpo levels increase inappropriately after conditioning for autologous stem cell transplantation (ASCT) before progressively returning to adequate levels. We investigated the possible influence of erythropoietic activity on these observations. DESIGN AND METHODS Forty patients undergoing an ASCT, 8 with bone marrow (BMT) and 32 with peripheral blood stem cells (PBSC), were separated into 3 groups. Group 1 was formed of the 8 BMT patients (median time to 1% reticulocytes: 39 days), group 2 of 16 PBSC patients with relatively slow erythroid engraftment (> or = 15 days to 1% reticulocytes, median 19 days) and group 3 of 16 PBSC patients with prompt erythroid recovery (< 15 days to 1% reticulocytes, median 13 days). Marrow erythroid activity was assessed by serum transferrin receptor levels (sTfR). Serum Epo (sEpo) levels were expressed in relation to the degree of anemia as observed/predicted (O/P) ratios of (O/P) log (sEpo). RESULTS Serum sTfR levels decreased by more than 50% in all 3 groups after conditioning, reaching their nadir on day 7. Nadir values doubled by day 28 in group 3, day 60 in group 2, but not within 100 days in group 1. O/P sEpo ratios increased inappropriately in all 3 groups after conditioning but then declined at very differing speeds in the 3 groups. In group 1, ratios remained above 1.10 through to day 28 and above 1.00 through to day 42, before leveling off at around 1.00 thereafter. In group 2, ratios remained above 1.00 through to day 14, than decreased to a minimum of 0.89 by day 42 before returning to 1.00 by day 100. In group 3, ratios decreased to 0.84 by day 21 and remained below 0.90 thereafter. INTERPRETATION AND CONCLUSIONS We conclude that sEpo levels are not only influenced by tissue oxygenation but also depend on the mass of erythroid precursors in the bone marrow. This may be the main explanation for the observed changes in sEpo levels during ASCT.
Job coach factors associated with community-based employment service programme outcome measures for people with disabilities – a Taiwan case study

Purpose. The aim of this study is to explore whether/which job coach factors were significantly associated with the community-based employment service (CBES) programme outcome measures in Taiwan. Method. This study used the 2003–2005 CBES programme for People with Disabilities Database in Taipei City in Taiwan (n = 3924) to do a secondary data analysis using hierarchical multiple linear regression. Results. This study found that ‘occurrences of the services provided by the job coaches’ variable was definitely the dominant predictor and explained additional 19.6% and 27.8% of the variances of annual salary and annual working month outcome measures, respectively. In addition, among six composition variables of ‘occurrences of the services provided by the job coaches’, ‘occurrences of follow-up guidance’, ‘occurrences of intensive guidance’, and ‘occurrences of consultation before interviews with employer/director of human resources’ were more powerful than the other three in predicting outcomes. Conclusions. Job coach factors in this study were significantly correlated with CBES programme outcome measures for people with disabilities in Taiwan after controlling for the socio-demographic variables. It indicates that the more inputs in the people with disabilities made by job coaches equates to better outcomes in this Taiwan case study.
Making peripheral participation legitimate: reader engagement experiments in wikipedia

Open collaboration communities thrive when participation is plentiful. Recent research has shown that the English Wikipedia community has constructed a vast and accurate information resource primarily through the monumental effort of a relatively small number of active, volunteer editors. Beyond Wikipedia's active editor community is a substantially larger pool of potential participants: readers. In this paper we describe a set of field experiments using the Article Feedback Tool, a system designed to elicit lightweight contributions from Wikipedia's readers. Through the lens of social learning theory and comparisons to related work in open bug tracking software, we evaluate the costs and benefits of the expanded participation model and show both qualitatively and quantitatively that peripheral contributors add value to an open collaboration community as long as the cost of identifying low quality contributions remains low.