Miracle-dz/UniFAR-FTUs huggingface dataset:
Toward an automated methodology for the valuation of reliability

Abstract There is a significant body of research related to the valuation of reliability in transportation. Such work has tended to rely on the stated preference methodology, where respondents are asked to make trade-offs between the mean and standard deviation of travel time. The literature has suggested that a revealed preference (RP) methodology may provide an alternative means of estimating a value of reliability. In this article we show how emerging data sources reveal travelers' preferences and, in combination with traditional choice modeling methods, can be used to estimate a value of reliability. We illustrate this RP methodology using smart-card data from the multimodal public transport network of London, UK. We are able to estimate a useable “reliability ratio” for three of four public transport modes modeled, and account for an unexpected result based upon the data available.
Long term survival in persons with hemophilia and chronic hepatitis C: 40 year outcomes of a large single center cohort

We studied the course of chronic HCV infections in a cohort of 222 persons with hemophilia (PWH) and von Willebrand disease followed at our center since 1973. Twenty two (10%) developed end stage liver disease (ESLD). Forty years after HCV infection, cumulative incidence of ESLD was 12.3% and overall survival was 45.5%. Those who were infected with HCV only (n = 100) had a survival of 75.2%, while those infected with HIV (n = 122) had a survival of 24% (P < 0.001). Survivals were significantly longer for those infected with HCV at younger age (< 15 years) compared to those infected over age 30 years (P = 0.014). Cause specific deaths for ESLD and bleeding were 8.8% and 8.3% respectively. For HIV negative subjects, the annual hazard of death from ESLD and bleeding was near zero for the first 10 years, and then rose slowly over the next 20 years to 0.4/100py for ESLD and 0.2/100py for bleeding. Sixty subjects completed 79 treatment episodes. Sustained viral response rates increased from 7/21 (33%) between 1990 and 2001, to 17/29 (58%) between 2002 and 2011, and to 27/29 (93%), since 2012 with the advent of the directly acting antiviral agents. These results confirm the very slow ESLD progression rate in HIV negative PWH. However, the risk of death from both ESLD and bleeding increases steadily with longer duration of HCV infection. More aggressive surveillance to detect those with early fibrosis is needed now that curative treatment is possible in >95% of individuals. Am. J. Hematol. 91:E335–E340, 2016. © 2016 Wiley Periodicals, Inc.
Towards understanding mechanisms governing cytotoxicity of metal oxides nanoparticles: Hints from nano-QSAR studies

Abstract The production of nanomaterials increases every year exponentially and therefore the probability these novel materials that they could cause adverse outcomes for human health and the environment also expands rapidly. We proposed two types of mechanisms of toxic action that are collectively applied in a nano-QSAR model, which provides governance over the toxicity of metal oxide nanoparticles to the human keratinocyte cell line (HaCaT). The combined experimental–theoretical studies allowed the development of an interpretative nano-QSAR model describing the toxicity of 18 nano-metal oxides to the HaCaT cell line, which is a common in vitro model for keratinocyte response during toxic dermal exposure. The comparison of the toxicity of metal oxide nanoparticles to bacteria Escherichia coli (prokaryotic system) and a human keratinocyte cell line (eukaryotic system), resulted in the hypothesis that different modes of toxic action occur between prokaryotic and eukaryotic systems.
Targeting Cellular Squalene Synthase, an Enzyme Essential for Cholesterol Biosynthesis, Is a Potential Antiviral Strategy against Hepatitis C Virus

ABSTRACT Hepatitis C virus (HCV) exploits host membrane cholesterol and its metabolism for progeny virus production. Here, we examined the impact of targeting cellular squalene synthase (SQS), the first committed enzyme for cholesterol biosynthesis, on HCV production. By using the HCV JFH-1 strain and human hepatoma Huh-7.5. 1-derived cells, we found that the SQS inhibitors YM-53601 and zaragozic acid A decreased viral RNA, protein, and progeny production in HCV-infected cells without affecting cell viability. Similarly, small interfering RNA (siRNA)-mediated knockdown of SQS led to significantly reduced HCV production, confirming the enzyme as an antiviral target. A metabolic labeling study demonstrated that YM-53601 suppressed the biosynthesis of cholesterol and cholesteryl esters at antiviral concentrations. Unlike YM-53601, the cholesterol esterification inhibitor Sandoz 58-035 did not exhibit an antiviral effect, suggesting that biosynthesis of cholesterol is more important than that of cholesteryl esters for HCV production. YM-53601 inhibited transient replication of a JFH-1 subgenomic replicon and entry of JFH-1 pseudoparticles, suggesting that at least suppression of viral RNA replication and entry contributes to the antiviral effect of the drug. Collectively, our findings highlight the importance of the cholesterol biosynthetic pathway in HCV production and implicate SQS as a potential target for antiviral strategies against HCV. IMPORTANCE Hepatitis C virus (HCV) is known to be closely associated with host cholesterol and its metabolism throughout the viral life cycle. However, the impact of targeting cholesterol biosynthetic enzymes on HCV production is not fully understood. We found that squalene synthase, the first committed enzyme for cholesterol biosynthesis, is important for HCV production, and we propose this enzyme as a potential anti-HCV target. We provide evidence that synthesis of free cholesterol is more important than that of esterified cholesterol for HCV production, highlighting a marked free cholesterol dependency of HCV production. Our findings also offer a new insight into a role of the intracellular cholesterol pool that is coupled to its biosynthesis in the HCV life cycle.
Quantum-interference magnetoconductivity in the variable-range-hopping regime.

Calcul de la contribution a la dependance, vis-a-vis du champ magnetique, de la vitesse de l'effet tunnel assiste par phonons, entre deux sites. Cet effet nai←t d'une interference entre l'amplitude d'une transition directe et celle d'une transition indirecte, impliquant un troisieme site unique. Determination d'une expression concernant la magnetoconductivite sous champ faible dans l'approximation de milieu effectif
Acute Aortic Dissection Type A: Age-related Management and Outcomes Reported in the German Registry for Acute Aortic Dissection Type A (GERAADA) of Over 2000 Patients

Objective:To determine the association between age and clinical presentation, management and surgical outcomes in a large contemporary, prospective cohort of patients with acute aortic dissection type A (AADA). Background:AADA is one of the most life-threatening cardiovascular diseases, and delayed surgery or overly conservative management can result in sudden death. Methods:The perioperative and intraoperative conditions of 2137 patients prospectively reported to the multicenter German Registry for Acute Aortic Dissection Type A were analyzed. Results:Of all patients with AADA, 640 (30%) were 70 years or older and 160 patients (7%) were younger than 40 years. The probability of aortic dissection extension to the supra-aortic vessels and abdominal aorta decreased with age (P < 0.0001 and P = 0.0017, respectively). In 1447 patients (69%), the aortic root was preserved and supracoronary replacement of the ascending aorta was done. The probability of this procedure increased with age (P < 0.0001). The incidence of new postoperative neurological disorders was not influenced by age. The lowest probability of 30-day mortality was noted in the youngest patients (11%–14% for patients aged between 20 and 40 years) and rose progressively with age, peaking at 25% in octogenarians. Conclusions:This study reflects current results after surgical treatment of AADA in relation to patient age. Current survival rates are acceptable, even in very elderly patients. The contemporary surgical mortality rate among young patients is lower than that previously reported in the literature. The postoperative stroke incidence does not increase with age.
Does Head Start Make a Difference?

Although there is a broad hi-partisan support for Head Start, the evidence of positive longterm effects of the program is not overwhelming. Using data from the National Longitudinal Survey's Child-Mother file, we examine the impact of the program on a range of child outcomes. We compare non-parametric estimates of program effects with estimates from parametric models that control for selection by including mother fixed effects. This comparison suggests that studies that ignore selection can be substantially misleading; it also suggests that the impact of selection differs considerably across racial and ethnic groups. After controlling for selection, we find positive and persistent effects of participation in Head Start on the test scores of white and Hispanic children. These children are also less likely to have repeated a grade. We find no effects on the test scores or schooling attainment of African-American children. White children who attend Head Start are more likely to receive a measles shot, while African-American enrollees receive measles shots at an earlier age. African-American children who attend Head Start are also taller than their siblings. In a sample of the children's mothers, we find evidence that whites who attended Head Start as children are taller and have higher AFQT scores than their siblings who did not
Prospects for Mild Therapeutic Hypothermia and Improved CPR in Cardiopulmonary Cerebral Resuscitation

Each year in the United States there are ~450,00 deaths from myocardial infarction (MI) [1] (with 310,000of these deaths occurring before the patient reaches the hospital) as a result of a non-perfusing arrhythmia, principally ventricular fibrillation. [2] This mode of sudden cardiac arrest (SCA) is also responsible for the majority of the 190,000 in-hospital deaths from MI, which typically occur within the first 24 hours following admission. [3] Especially tragic is that 50% of these deaths occur in persons ~60 years of age or less. [4] An estimated additional 20,000 incidents of SCA occur as a result of asphyxiation, drowning, electrocution, and genetic or developmental predisposition to lethal arrhythmias (Wolf-Parkinson‟s White Syndrome, congenital thickening of the interventricular septum, and idiopathic arrhythmic disease) and other non-atherosclerosis causes. This latter category of SCA typically occurs in individuals whose mean age is less than 35. [5],[6]
Effect of the metabolic syndrome on organ damage and mortality in patients with systemic lupus erythematosus: a longitudinal analysis.

OBJECTIVES To study the effect of the metabolic syndrome (MetS) on organ damage and mortality in patients with SLE. METHODS Consecutive patients who fulfilled ≥4 ACR criteria for SLE were assessed for the MetS in October 2010. The MetS was defined by the updated joint consensus criteria, using the Asian criteria for central obesity. Longitudinal data on organ damage and mortality were retrieved. The association between MetS and new damage and mortality was studied by logistic regression. RESULTS A total of 577 SLE patients were followed (93% women; age 41.2±13.4 years; SLE duration 9.3±7.2 years) and 85 (14.7%) patients qualified the MetS. After a follow-up of 66.3±1.8 month, new organ damage and vascular events developed in 128(22%) and 23(4.0%) patients, respectively. Thirty-nine (6.8%) patients succumbed. Patients with the MetS, compared to those without, had significantly more SLICC damage score accrual (0.70±1.0 vs 0.26±0.6; p<0.001), new vascular events (11% vs 2.8%; p=0.001), all-cause (14% vs 5.5%; p=0.003) and vascular (7.1% vs 0.2%; p<0.001) mortality. Logistic regression revealed that the MetS was significantly associated with new damage in the renal (OR 5.48[2.06-14.6]; p=0.001) and endocrine system (OR 38.0[4.50-321]; p=0.001), adjusted for age, sex, SLE duration, ever smoking, antiphospholipid antibodies and the new use of glucocorticoids or hydroxychloroquine since recruitment. Moreover, the presence of the MetS also significantly increased the risk of new vascular events (OR 3.38[1.31-8.74];p=0.01) and vascular mortality (OR 28.3[3.24-247]; p=0.002) after adjustment for the same covariates. CONCLUSION In this longitudinal study, the MetS is significantly associated with new organ damage, vascular events and mortality in patients with SLE.
Treatment of hepatocellular carcinoma: value of percutaneous microwave coagulation.

OBJECTIVE Percutaneous microwave coagulation therapy (PMCT) is a new therapeutic technique for the treatment of solid neoplasms that uses an energy source different from those of other interstitial therapies. We report our initial experience using PMCT to treat hepatocellular carcinomas. MATERIALS AND METHODS NIne hepatocellular carcinomas exceeding 3 cm in diameter in nine patients were treated with PMCT. Within 2 weeks before PMCT, all patients had been treated with transcatheter arterial embolization therapy, which had failed to produce complete necrosis of the tumors. PMCT was done under local anesthesia. A 14-gauge guiding needle was inserted percutaneously toward the lesion under sonographic guidance, and a needle electrode was positioned precisely within the lesion. Microwaves of 2450 MHz in frequency were produced for 60 sec with a 60-W emission. Three to 12 microwave emissions were administered in each case. RESULTS Dynamic CT showed that unenhanced areas indicative of coagulation necrosis developed in all lesions. All lesions appeared smaller without enhancement: on CT, the tumor diameters (mean +/- SD) were 48 +/- 13 mm before treatment and 41 +/- 13 mm 1 month after treatment. Follow-up studies showed that five lesions were controlled without any signs of recurrence. All patients tolerated the treatments well, and no serious complications occurred. CONCLUSION Our preliminary experience suggests that PMCT may be a useful alternative to other forms of interstitial therapy for the treatment of hepatocellular carcinomas.
The efficacy of an experimental dentifrice containing 0.454% w/w stannous fluoride in providing relief from the pain of dentin hypersensitivity: an 8-week clinical study.

PURPOSE To compare the efficacy of a 0.454% w/w stannous fluoride containing anhydrous dentifrice and a negative control dentifrice containing 1,000 ppm fluoride (as sodium monofluorophosphate) at reducing dentin hypersensitivity over an 8-week period, following twice daily brushing. METHODS This was a randomized, examiner blind, two-treatment arm, stratified (by maximum baseline Schiff sensitivity score), parallel design, single-site study in 118 subjects, who had at least two sensitive teeth, and met all the criteria at the screening and baseline visit. The study was conducted in Las Vegas, NV, USA. Tactile threshold (Yeaple Probe) and evaporative (air-blast) sensitivity (with Schiff sensitivity scale) were employed as clinical measures to compare the efficacy of the test dentifrice containing 0.454% w/w stannous fluoride to the negative control (Colgate Cavity Protection) at reducing sensitivity at Weeks 4 and 8. RESULTS 117 subjects completed the clinical study. At the 4- and 8-week time points, between treatment analyses demonstrated the test dentifrice to be significantly better at relieving subjects' sensitivity, for both validated clinical measures, compared to the negative control (at 4 weeks Schiff P < 0.0001 tactile threshold P < 0.0001; at 8 weeks Schiff P < 0.0001; tactile threshold P < 0.0001).
Anatomical Evidence for Rod Input to the Parvocellular Pathway in the Visual System of the Primate

The question whether midget bipolar cells in macaque monkey retina receive input from rods was investigated using double‐label immunocytochemistry. Flat midget bipolar cells (labelled with antibodies against recoverin) were found to be pre‐ and postsynaptic to All amacrine cells (labelled with antibodies against calretinin). These results support physiological evidence that rod photoreceptor signals could reach the parvocellular pathway at an early stage of visual processing.
Suppression of human tumor cell proliferation by Smurf2‐induced senescence

The limitation of proliferative potential in human somatic cells imposed by replicative senescence has been proposed as a mechanism of tumor suppression. The E3 ubiquitin ligase Smurf2 is up‐regulated during replicative senescence in response to telomere shortening, and induces senescence when expressed adventitiously in early passage or telomerase‐immortalized human fibroblasts. To investigate the generality of Smurf2's control of cell proliferation, we have studied the effects of Smurf2 up‐regulation on cell proliferation in early passage human mammary epithelial cells which normally do not show elevated expression of Smurf2 during senescence, and in 16 human cancer cell lines derived from both sarcomas and carcinomas. Here we report that Smurf2 up‐regulation induced senescence in a wide variety of human cell types, including highly neoplastic cell lines. Consistent with our previous findings, the ability of Smurf2 to arrest cell proliferation did not require its ubiquitin ligase activity. Furthermore, expression of the cyclin‐dependent kinase inhibitor p21 was increased in tumor cells undergoing Smurf2‐induced senescence, and such increase occurred independently of the transactivation function of p53. Our results, which reveal a previously unsuspected tumor suppression function for Smurf2‐induced senescence, suggest that modulation of Smurf2 action may be a useful strategy for inhibition of cancer cell growth. J. Cell. Physiol. 215: 613–620, 2008. © 2008 Wiley‐Liss, Inc.
CYP1A in TCDD Toxicity and in Physiology–with Particular Reference to CYP Dependent Arachidonic Acid Metabolism and other Endogenous Substrates

Toxicologic and physiologic roles of CYP1A enzyme induction, the major biochemical effect of aryl hydrocarbon receptor activation by TCDD and other receptor ligands, are unknown. Evidence is presented that CYP1A exerts biologic effects via metabolism of endogenous substrates (i.e., arachidonic acid, other eicosanoids, estrogens, bilirubin, and melatonin), production of reactive oxygen, and effects on K+ and Ca2+ channels. These interrelated pathways may connect CYP1A induction to TCDD toxicities, including cardiotoxicity, vascular dysfunction, and wasting. They may also underlie homeostatic roles for CYP1A, especially when transiently induced by common chemical exposures and environmental conditions (i.e., tryptophan photoproducts, dietary indoles, and changes in oxygen tension).
Pseudomonas aeruginosa Exoenzyme S, a Double ADP-ribosyltransferase, Resembles Vertebrate Mono-ADP-ribosyltransferases*

Previous data indicated that Pseudomonas aeruginosa exoenzyme S (ExoS) ADP-ribosylated Ras at multiple sites. One site appeared to be Arg41, but the second site could not be localized. In this study, the sites of ADP-ribosylation of c-Ha-Ras by ExoS were directly determined. Under saturating conditions, ExoS ADP-ribosylated Ras to a stoichiometry of 2 mol of ADP-ribose incorporated per mol of Ras. Nucleotide occupancy did not influence the stoichiometry or velocity of ADP-ribosylation of Ras by ExoS. Edman degradation and mass spectrometry of V8 protease generated peptides of ADP-ribosylated Ras identified the sites of ADP-ribosylation to be Arg41 and Arg128. ExoS ADP-ribosylated the double mutant, RasR41K,R128K, to a stoichiometry of 1 mol of ADP-ribose incorporated per mol of Ras, which indicated that Ras possessed an alternative site of ADP-ribosylation. The alternative site of ADP-ribosylation on Ras was identified as Arg135, which was on the same α-helix as Arg128. Arg41 and Arg128 are located within two different secondary structure motifs, β-sheet and α-helix, respectively, and are spatially separated within the three-dimensional structure of Ras. The fact that ExoS could ADP-ribosylate a target protein at multiple sites, along with earlier observations that ExoS could ADP-ribosylate numerous target proteins, were properties that have been attributed to several vertebrate ADP-ribosyltransferases. This prompted a detailed alignment study which showed that the catalytic domain of ExoS possessed considerably more primary amino acid homology with the vertebrate mono-ADP-ribosyltransferases than the bacterial ADP-ribosyltransferases. These data are consistent with the hypothesis that ExoS may represent an evolutionary link between bacterial and vertebrate mono-ADP-ribosyltransferases.
English Language Narratives of Filipino Children.

Purpose The current study focuses on describing the English language narrative skills of children who have been exposed to the Filipino language. Method Eight children between the ages of 6;0 (years;months) and 7;7 who spoke primarily English but who were exposed to the Filipino language at home participated. Each child produced three narrative samples based on wordless picture books. Samples were analyzed for narrative complexity as well as measures of productivity and grammaticality. Results The complexity of children's narratives was comparable to that reported in the literature for monolingual English-speaking children. Grammaticality measures show use of an average of 16.55% Filipino-influenced English forms across three stories. The observed patterns of Filipino-influenced English were predictable based on the comparison of English and Filipino structures. Variability in maze use was related to the amount of exposure to Filipino. Clinical Implications Care should be taken to evaluate grammaticality with respect to nonstandard English forms predicted by the rules of the language in contact with English. Further, maze use may be related to level of exposure to another language and should be further explored when using such information in language evaluation.