Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vivo Responses of Human A375M Melanoma to a σ Ligand: 18F-FDG PET Imaging

σ-ligands can kill tumor cells. Previously we have shown that a short in vitro incubation of C6 tumor cells with σ-ligands (24 h) results in a dose-dependent increase of cellular 18F-FDG uptake and that the magnitude of this increase is predictive of subsequent cell death. Here, we aimed to assess whether the σ-ligand rimcazole inhibits growth of A375M melanoma xenografts in nude mice and whether rimcazole treatment changes 18F-FDG uptake in vivo. Methods: Athymic mice were inoculated with A375M melanoma cells. After 2 wk, tumors had reached a size of 41 ± 6 mm3. We then started a 14-d treatment schedule with daily drug dosing. Control animals were injected with water and treated animals with rimcazole (26 mg/kg) in water. Three small-animal PET scans with 18F-FDG were obtained: on days 0, 7, and 14 of treatment. After the last scan, animals were terminated, and a biodistribution study was performed. Results: Rimcazole treatment resulted in a greater than 4-fold reduction of tumor weight in comparison to controls at day 14 (100 ± 26 vs. 436 ± 117 mg, respectively, P < 0.03). Treatment did not affect the levels of (nonradioactive) glucose in blood, σ-1 and σ-2 receptor expression in the tumor, animal weight, behavior, or appearance. Antitumor activity of rimcazole was accompanied by a transient increase of the tumor uptake of 18F-FDG (measured at day 7). Significant increases of 18F-FDG uptake at day 14 were observed in the liver and pancreas. Conclusion: Rimcazole strongly inhibited the growth of A375M melanoma xenografts. This growth inhibition is accompanied by an early increase of 18F-FDG uptake in the tumor.
Effective Homocysteine-Lowering Vitamin B Treatment in Peritoneal Dialysis Patients

Background Hyperhomocysteinemia, a risk factor for atherosclerosis, is frequently detected in patients with renal failure. Vitamin B supplementation reduces but rarely normalizes homocysteine (Hcy) levels in hemodialysis patients. There are no data about the effects of vitamin B therapy on Hcy levels in patients on peritoneal dialysis (PD). Aims We performed this trial both to observe baseline plasma Hcy levels in PD patients and to assess the effects of vitamin B therapy on Hcy levels in continuous ambulatory PD patients. Methods We conducted a 6-month prospective study of the effects of vitamin B therapy on plasma Hcy levels. Biochemical analyses were obtained at baseline and after every phase of treatment with folic acid, folic acid plus vitamin B12, and folic acid plus vitamin B12 plus vitamin B6. Eighteen of the 25 enrolled patients finished the study. Results Hyperhomocysteinemia was present in 83% of PD patients. We detected a trend toward a significant inverse relationship between baseline Hcy and folate levels. There were no significant correlations between baseline Hcy and vitamin B12, peritoneal membrane permeability, dialytic efficiency, or computed peritoneal Hcy clearance. We obtained an effective decrease in mean Hcy concentration from 20 to 14.8 μmol/L after folic acid and vitamin B12 treatment. We observed a further reduction in mean Hcy level to 12.8 μmol/L using the triple therapy; 72% of patients normalized their Hcy value. Conclusions High doses of folic acid, vitamin B6, and vitamin B12 normalize Hcy values in the majority of PD patients. This treatment may be important in reducing cardiovascular morbidity and mortality.
Noninvasive diagnosis of blunt cerebrovascular injuries: a preliminary report.

BACKGROUND In light of their potential for devastating consequences, a liberalized screening approach for blunt cerebrovascular injuries (BCVI) is becoming increasingly accepted. The "gold standard" for diagnosis of BCVI is arteriography; however, noninvasive diagnostic alternatives offer clear advantages. Recent series have demonstrated the ability of computed tomographic angiography (CTA) and magnetic resonance angiography (MRA) to identify BCVI, but have not compared their accuracy with arteriography. We hypothesized that CTA or MRA could reliably identify BCVI, obviating the need for arteriography. The purpose of this study was to determine the accuracy of CTA and MRA in identifying BCVI in asymptomatic patients. METHODS Asymptomatic patients meeting criteria for BCVI screening underwent arteriography, according to our institutional standard. A subset of patients requiring computed tomographic scanning underwent CTA; a subset of patients requiring magnetic resonance imaging underwent MRA. All of the studies were interpreted by radiologists in a blinded manner. Data were analyzed for sensitivity and specificity. RESULTS Forty-six patients underwent both CTA and arteriography. Of 23 with a normal CTA examination, 7 (30%) had BCVI on arteriography. Of 23 with an abnormal CTA examination, 8 (35%) had a normal arteriogram. The sensitivity, specificity, positive predictive value, and negative predictive value of CTA were 68%, 67%, 65%, and 70%, respectively. CTA missed 55% of grade I injuries, 14% of grade II injuries, and 13% of grade III injuries. Sixteen patients underwent both MRA and arteriography. One (11%) had a false-negative MRA result, and four (57%) had false-positive MRA results (75% sensitivity, 67% specificity, 43% positive predictive value, 89% negative predictive value). CONCLUSION CTA and MRA can identify BCVI, but they miss grade I, II, and III injuries. Future technical modifications may improve their accuracy. A prospective multicenter trial is warranted to define the capabilities and limitations of these noninvasive modalities. In the interim, arteriography remains the gold standard for diagnosis, but if arteriography is not available, CTA or MRA should be used to screen for BCVI in patients at risk.
Reduction of Tissue Plasminogen Activator-Induced Hemorrhage and Brain Injury by Free Radical Spin Trapping after Embolic Focal Cerebral Ischemia in Rats

Thrombolytic stroke therapy with tissue plasminogen activator (tPA) remains complicated by serious risks of cerebral hemorrhage and brain injury. In this study, a novel model of tPA-induced hemorrhage was used in spontaneously hypertensive rats to examine the correlates of hemorrhage, and test methods of reducing hemorrhage and brain injury. Homologous blood clot emboli were used to occlude the middle cerebral artery in spontaneously hypertensive rats, and delayed administration of tPA (6 hours postischemia) resulted in high rates of cerebral hemorrhage 24 hours later. Compared with untreated rats, tPA significantly increased hemorrhage volumes by almost 85%. Concomitantly, infarction and neurological deficits were worsened by tPA. A parallel experiment in normotensive Wistar-Kyoto rats showed markedly reduced rates of hemorrhage, and tPA did not significantly increase hemorrhage volumes. To examine whether tPA-induced hemorrhage was caused by the delayed onset of reperfusion per se, another group of spontaneously hypertensive rats was subjected to focal ischemia using a mechanical method of arterial occlusion. Delayed (6 hours) reperfusion via mechanical means did not induce hemorrhage. However, administration of tPA plus delayed mechanical reperfusion significantly increased hemorrhage volumes. Since reperfusion injury was implicated, a final experiment compared outcomes in spontaneously hypertensive rats treated with tPA plus the free radical spin trap α-phenyl tert butyl nitrone (α-PBN) versus tPA alone. tPA-induced hemorrhage volumes were reduced by 40% with α-PBN, and infarction and neurological deficits were also decreased. These results indicate that (1) blood pressure isanimportant correlate of tPA-induced hemorrhage, (2) tPA interacts negatively with reperfusion injury to promote hemorrhage, and (3) combination therapies with anti-free radical treatments may reduce the severity of tPA-induced hemorrhage and brain injury after cerebral ischemia.
Effect of a Multifaceted Intervention on Adherence to Hand Hygiene among Healthcare Workers: A Cluster-Randomized Trial

Objectives. Adherence to hand hygiene among healthcare workers (HCWs) is widely believed to be a key factor in reducing the spread of healthcare-associated infection. The objective of this study was to evaluate the impact of a multifaceted intervention to increase rates of adherence to hand hygiene among HCWs and to assess the effect on the incidence of hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) colonization. Design. Cluster-randomized controlled trial. Setting. Thirty hospital units in 3 tertiary care hospitals in Hamilton, Ontario, Canada. Intervention. After a 3-month baseline period of data collection, 15 units were randomly assigned to the intervention arm (with performance feedback, small-group teaching seminars, and posters) and 15 units to usual practice. Hand hygiene was observed during randomly selected 15-minute periods on each unit, and the incidence of MRSA colonization was measured using weekly surveillance specimens from June 2007 through May 2008. Results. We found that 3,812 (48.2%) of 7,901 opportunities for hand hygiene in the intervention group resulted in adherence, compared with 3,205 (42.6%) of 7,526 opportunities in the control group (P < .001; independent t test). There was no reduction in the incidence of hospital-acquired MRSA colonization in the intervention group. Conclusion. Among HCWs in Ontario tertiary care hospitals, the rate of adherence to hand hygiene had a statistically significant increase of 6% with a multifaceted intervention, but the incidence of MRSA colonization was not reduced.
Drug Abuse and Eating Disorders: Prevention Implications

This article explores the relationship between drug and alcohol abuse and eating disorders in a sample of adolescent females using a self-report methodology. An Eating Disorders Risk (EDR) Scale is adopted and correlated with drug and alcohol use, other forms of deviance, family and peer relationships, and depression. The findings support the concept of a generalized theory of addictions based on psychosocial, family, and peer factors. Family and peer prevention applications and a need for further research on the correlates of depression are discussed.
Unhappy Husbands: Masculinity and Migration in Transnational Pakistani Marriages

Le present article s'appuie sur un travail de terrain au Pendjab pakistanais et parmi des familles a predominance pendjabi de la ville de Bristol. Il s'interesse a la pratique, courante parmi les Pakistanais residant en Grande-Bretagne, d'aller chercher mari ou femme au Pakistan. Alors que les informateurs de l'auteur soulignent les risques que ces mariages creent pour les femmes, le travail de recherche met en evidence les difficultes sociales, culturelles et economiques rencontrees par les maris migrants, dont la position est assimilable a celle du ghar damad (« gendre au foyer »). Alors que les femmes, des leur plus jeune âge, apprennent les ajustements necessaires pour s'integrer dans la famille de leur mari, les migrants masculins sont rarement prepares a cette situation. L'absence de soutien local par leur famille se combine a une proximite de la belle-famille inhabituelle dans leur culture, d'ou une restructuration des relations de pouvoir sexuees au sein de la maisonnee. La frustration ressentie par ces hommes peut aider a comprendre comment ces mariages peuvent aboutir a des violences conjugales, a l'abandon du domicile ou a un mariage avec une deuxieme epouse. Cependant, le modele du ghar damad presente egalement un interet pour la comprehension ce que vivent de nombreux hommes migrants d'autres nationalites et leurs epouses britanniques.
Prevalence of airflow obstruction and reduced forced vital capacity in an Aboriginal Australian population: The cross‐sectional BOLD study

Mortality and hospital separation data suggest a higher burden of chronic obstructive pulmonary disease (COPD) in indigenous than non‐indigenous subpopulations of high‐income countries. This study sought to accurately measure the true prevalence of post‐bronchodilator airflow obstruction and forced vital capacity reduction in representative samples of Indigenous and non‐Indigenous Australians.
Structural and Functional Characterization of the R-modules in Alginate C-5 Epimerases AlgE4 and AlgE6 from Azotobacter vinelandii

Background: Alginate epimerases consist of catalytic and noncatalytic domains of yet unknown function. Results: The noncatalytic domains of AlgE4 and AlgE6 possess different alginate binding behavior despite highly similar structures. Conclusion: Noncatalytic subunits of AlgE6 and AlgE4 influence the product specificity of the catalytic domain. Significance: This work opens a new route to designing alginate epimerases producing tailored alginates. The bacterium Azotobacter vinelandii produces a family of seven secreted and calcium-dependent mannuronan C-5 epimerases (AlgE1–7). These epimerases are responsible for the epimerization of β-d-mannuronic acid (M) to α-l-guluronic acid (G) in alginate polymers. The epimerases display a modular structure composed of one or two catalytic A-modules and from one to seven R-modules having an activating effect on the A-module. In this study, we have determined the NMR structure of the three individual R-modules from AlgE6 (AR1R2R3) and the overall structure of both AlgE4 (AR) and AlgE6 using small angle x-ray scattering. Furthermore, the alginate binding ability of the R-modules of AlgE4 and AlgE6 has been studied with NMR and isothermal titration calorimetry. The AlgE6 R-modules fold into an elongated parallel β-roll with a shallow, positively charged groove across the module. Small angle x-ray scattering analyses of AlgE4 and AlgE6 show an overall elongated shape with some degree of flexibility between the modules for both enzymes. Titration of the R-modules with defined alginate oligomers shows strong interaction between AlgE4R and both oligo-M and MG, whereas no interaction was detected between these oligomers and the individual R-modules from AlgE6. A combination of all three R-modules from AlgE6 shows weak interaction with long M-oligomers. Exchanging the R-modules between AlgE4 and AlgE6 resulted in a novel epimerase called AlgE64 with increased G-block forming ability compared with AlgE6.
Sequence discriminative distributed training of long short-term memory recurrent neural networks

We recently showed that Long Short-Term Memory (LSTM) recurrent neural networks (RNNs) outperform state-of-the-art deep neural networks (DNNs) for large scale acoustic modeling where the models were trained with the cross-entropy (CE) criterion. It has also been shown that sequence discriminative training of DNNs initially trained with the CE criterion gives signiﬁcant improvements. In this paper, we investigate sequence discriminative training of LSTM RNNs in a large scale acoustic modeling task. We train the models in a distributed manner using asynchronous stochastic gradient descent optimization technique. We compare two sequence discriminative criteria – maximum mutual information and state-level minimum Bayes risk, and we investigate a number of variations of the basic training strategy to better understand issues raised by both the sequential model, and the objective function. We ob-tain signiﬁcant gains over the CE trained LSTM RNN model using sequence discriminative training techniques.
PIN Proteins Perform a Rate-Limiting Function in Cellular Auxin Efflux

Intercellular flow of the phytohormone auxin underpins multiple developmental processes in plants. Plant-specific pin-formed (PIN) proteins and several phosphoglycoprotein (PGP) transporters are crucial factors in auxin transport–related development, yet the molecular function of PINs remains unknown. Here, we show that PINs mediate auxin efflux from mammalian and yeast cells without needing additional plant-specific factors. Conditional gain-of-function alleles and quantitative measurements of auxin accumulation in Arabidopsis and tobacco cultured cells revealed that the action of PINs in auxin efflux is distinct from PGP, rate-limiting, specific to auxins, and sensitive to auxin transport inhibitors. This suggests a direct involvement of PINs in catalyzing cellular auxin efflux.
Factors associated to lifestyle and risk of adult onset asthma.

BACKGROUND Asthma prevalence has been increasing especially in developed countries. The change seems to be associated with changes in lifestyle. We have made a prospective study to assess the effect of lifestyle factors, including smoking, educational level, physical activity and obesity on adult onset asthma. METHODS A population of 10,597 adult twins, initially free of asthma was followed for 9 years. The main outcome measure was questionnaire-based report of physician diagnosed asthma. Logistic regression was used to estimate the risk of asthma predicted by lifestyle factors, with adjustment for atopy and respiratory symptoms. RESULTS Obesity at baseline increased asthma risk (multivariable adjusted OR = 3.00, 95% CI: 1.64-5.50 for those with BMI > or = 30 compared to those with normal weight BMI: 20-24.99). Taller height was associated to lower asthma incidence. Leisure time physical activity had a slightly protective effect on asthma risk among men (P for trend = 0.037) while smoking and education did not have significant effects on the risk of adult onset asthma. CONCLUSIONS Obesity was associated to the risk of adult onset asthma, while short height and low leisure time physical activity can be considered as other potential risk factors.
Racial and ethnic disparities in mortality from acute lung injury*

Objective:Little is known about the influence of race and ethnicity on mortality from acute lung injury (ALI). We sought to determine whether black race or Hispanic ethnicity is independently associated with mortality among patients with ALI. Design:Retrospective cohort study of patients enrolled in the Acute Respiratory Distress Syndrome Network randomized controlled trials. Setting:Adult intensive care units participating in the Acute Respiratory Distress Syndrome Network trials. Patients:A total of 2362 mechanically ventilated patients (1715 white, 449 black, and 198 Hispanic) with ALI. Measurements and Main Results:The primary outcome was 60-day mortality. A secondary outcome was number of ventilator-free days. Crude mortality was 33% for both blacks and Hispanics compared with 27% for whites (p = 0.02). After adjusting for demographic and clinical covariates, the association between race/ethnicity and mortality persisted (odds ratio [OR] = 1.42; 95% confidence interval [CI] 1.10–1.84 for blacks; OR = 1.94; 95% CI, 1.36–2.77 for Hispanics; OR = 1.00 for whites). After adjustment for severity of illness (Acute Physiology Score), black race was no longer significantly associated with mortality (OR = 1.25; 95% CI, 0.95–1.66), whereas the association with Hispanic ethnicity persisted (OR = 2.00; 95% CI, 1.37–2.90). Hispanics had significantly fewer ventilator-free days compared with whites after adjustment for demographic and clinical covariates (mean difference in days = −2.3; 95% CI −3.90 to −0.70). Conclusions:Black and Hispanic patients with ALI have a significantly higher risk of death compared with white patients. This increased risk seemed to be mediated by increased severity of illness at presentation for blacks, but was unexplained among Hispanics.
O6‐methylguanine DNA methyltransferase and p53 status predict temozolomide sensitivity in human malignant glioma cells

Temozolomide (TMZ) is a methylating agent which prolongs survival when administered during and after radiotherapy in the first‐line treatment of glioblastoma and which also has significant activity in recurrent disease. O6‐methylguanine DNA methyltransferase (MGMT) is a DNA repair enzyme attributed a role in cancer cell resistance to O6‐alkylating agent‐based chemotherapy. Using a panel of 12 human glioma cell lines, we here defined the sensitivity to TMZ in acute cytotoxicity and clonogenic survival assays in relation to MGMT, mismatch repair and p53 status and its modulation by dexamethasone, irradiation and BCL‐XL. We found that the levels of MGMT expression were a major predictor of TMZ sensitivity in human glioma cells. MGMT activity and clonogenic survival after TMZ exposure are highly correlated (p < 0.0001, r2 = 0.92). In contrast, clonogenic survival after TMZ exposure does not correlate with the expression levels of the mismatch repair proteins mutS homologue 2, mutS homologue 6 or post‐meiotic segregation increased 2. The MGMT inhibitor O6‐benzylguanine sensitizes MGMT‐positive glioma cells to TMZ whereas MGMT gene transfer into MGMT‐negative cells confers protection. The antiapoptotic BCL‐XL protein attenuates TMZ cytotoxicity in MGMT‐negative LNT‐229 but not in MGMT‐positive LN‐18 cells. Neither ionizing radiation (4 Gy) nor clinically relevant concentrations of dexamethasone modulate MGMT activity or TMZ sensitivity. Abrogation of p53 wild‐type function strongly attenuates TMZ cytotoxicity. Conversely, p53 mimetic agents designed to stabilize the wild‐type conformation of p53 sensitize glioma cells for TMZ cytotoxicity. Collectively, these results suggest that the determination of MGMT expression and p53 status will help to identify glioma patients who will or will not respond to TMZ.
Wind Turbine Condition Assessment Through Power Curve Copula Modeling

Power curves constructed from wind speed and active power output measurements provide an established method of analyzing wind turbine performance. In this paper, it is proposed that operational data from wind turbines are used to estimate bivariate probability distribution functions representing the power curve of existing turbines so that deviations from expected behavior can be detected. Owing to the complex form of dependency between active power and wind speed, which no classical parameterized distribution can approximate, the application of empirical copulas is proposed; the statistical theory of copulas allows the distribution form of marginal distributions of wind speed and power to be expressed separately from information about the dependency between them. Copula analysis is discussed in terms of its likely usefulness in wind turbine condition monitoring, particularly in early recognition of incipient faults such as blade degradation, yaw, and pitch errors.
Barriers to Entry and Competitive Behavior: Evidence from Reforms of Cable Franchising Regulations

Between 2005 and 2008, 19 of the 50 states of the U.S. reformed the franchising process for cable television, significantly easing entry into local markets. Using a difference-in-differences approach that exploits the staggered introduction of reforms, we find that prices for “Basic” service declined systematically by about 5.5 to 6.8 percent following the reforms, but we find no statistically significant effect on average price for the more popular “Expanded Basic” service. We also find that the reforms led to increased actual entry in reformed states, by about 11.6% relative to non reformed states. Our analysis shows that the decline in price for “Basic” service holds for markets that did not experience actual entry, consistent with limit pricing by incumbents. To control for potential state-level shocks correlated with the reforms, we undertake a sample-split test examining changes in local markets which faced a greater threat of entry (because they were close to a prominent second entrant); we find larger declines in prices, for both “Basic” and “Expanded Basic” services in these markets. Our results are consistent with limit pricing models that predict incumbents respond to increased threat of entry, and suggest that the reforms facilitated entry and modestly benefitted consumers in reformed states.