Miracle-dz/UniFAR-FTUs huggingface dataset:
Five families with arginine519‐cysteine mutation in COL2A1: Evidence for three distinct founders

Arginine519‐cysteine mutation in the type II procollagen gene (COL2A1) is known to be associated with mild spondyloepiphyseal dysplasia (SED) and precocious generalized osteoarthritis (OA). Five families have now been identified with this mutation. To determine whether a common founder was responsible for the mutation in these five families, we defined the haplotype of the mutation‐bearing chromosome using four restriction fragment length polymorphisms (RFLPs) and the 3′‐untranslated region VNTR. Haplotype frequencies were estimated for 69 control samples. Three distinct mutation‐bearing haplotypes were identified, with three families sharing a common haplotype. For three distinct haplotypes to have derived from a single founder, three independent recombination events would have had to occur. Thus the arg519 codon appears to represent a possible site of recurrent mutations in COL2A1, an uncommon phenomenon in collagen genes. Hum Mutat 12:172–176, 1998. © 1998 Wiley‐Liss, Inc.
Variants of intrafamilial sexual abuse experience: Implications for short- and long-term development

This study examines short- and long-term maladaptive outcomes in a sample of sexually abused females and a comparison group. The sample consists of intrafamilial sexual abuse victims ages 6–16 years at entry into the study and a demographically similar comparison group. The outcomes examined included measures of behavior and psychological problems such as aggressive behavior, depression, dissociation, and low self-esteem; and measures at two time points, first at entry into the study (median age 11 years) and approximately 7 years later (median age 18 years). The specific questions being addressed were (a) whether subgroups or profiles, based on the specific characteristics of the sexual abuse experienced, can be identified in this sample of abused females; and (b) whether these profile groups predict different patterns of adverse short- or long-term outcomes.
Obesity and restless legs syndrome in men and women

Background: Obesity and restless legs syndrome (RLS) are both associated with hypofunction of dopamine in the CNS. We therefore examined whether individuals who are obese have an increased risk of RLS in two ongoing US cohorts, the Nurses’ Health Study II and the Health Professional Follow-up Study. Methods: We included 65,554 women and 23,119 men free of diabetes, arthritis, and pregnancy in the current analyses. Information on RLS was assessed using a set of standardized questions. Participants were considered to have RLS if they met four RLS diagnostic criteria recommended by the International RLS Study Group and had restless legs ≥5 times/month. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using logistic regression models adjusting for age, smoking, use of antidepressant, phobic anxiety score, and other covariates. Log ORs from the two cohorts were pooled by a fixed-effects model. Results: There were 6.4% of women and 4.1% of men who were considered to have RLS. Multivariate adjusted ORs for RLS were 1.42 (95% CI: 1.3, 1.6; p trend <0.0001) for participants with body mass index (BMI) >30 vs <23 kg/m2 and 1.60 (95% CI: 1.5, 1.8; p trend <0.0001) for highest vs lowest waist circumference quintiles. Greater BMI in early adulthood (age 18–21 years) and weight gain were also associated with a higher prevalence of RLS (p trend <0.01 for both). Conclusions: Both overall and abdominal adiposity are associated with increased likelihoods of having restless legs syndrome (RLS). Further prospective studies are warranted to clarify causative association between obesity and risk of developing RLS. BMI = body mass index; CI = confidence interval; HPFS = Health Professionals Follow-up Study; NHS II = Nurses’ Health Study II; OR = odds ratios; RLS = restless legs syndrome.
Glutamate AMPA receptors change in motor neurons of SOD1G93A transgenic mice and their inhibition by a noncompetitive antagonist ameliorates the progression of amytrophic lateral sclerosis‐like disease

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder involving the selective degeneration of motor neurons. In a small proportion of patients, ALS is caused by mutations in copper/zinc superoxide dismutase (SOD1), and mice overexpressing SOD1G93A mutant develop a syndrome that closely resembles the human disease. Excitotoxicity mediated by glutamate AMPA receptors has been suggested to be implicated in the selective susceptibility of motor neurons occurring in ALS. In SOD1G93A mice, we found that levels of GluR2 AMPA subunit, which plays a pivotal role in the maintenance of calcium impermeability of AMPA receptors, are decreased in spinal motor neurons before symptom onset in concomitance with a modest increase of GluR3 expression, a calcium‐permeable AMPA subunit. This effect can result in a higher number of calcium‐permeable AMPA receptors on motor neurons of SOD1G93A mice, predisposing these cells to be injured by AMPA‐mediated glutamate firing. In support of this, we showed that treatment with a new noncompetitive AMPA antagonist, ZK 187638, partially protected motor neurons, improved motor function, and prolonged the survival of SOD1G93A mice. © 2005 Wiley‐Liss, Inc.
A Distinct Role of Neutrophil Lactoferrin in RelA/p65 Phosphorylation on Ser536 by Recruiting TNF Receptor-Associated Factors to IκB Kinase Signaling Complex1

The activation of NF-κB by neutrophil lactoferrin (Lf) is regulated via the IκB kinase (IKK) signaling cascade, resulting in the sequential phosphorylation and degradation of IκB. In this study, we observed that Lf protein augmented p65 phosphorylation at the Ser536, but not the Ser276 residue, and stimulated the translocation of p65 into the nucleus. Lf was also shown to enhance the association between p65 and CREB-binding protein/p300 in vivo. To elucidate the mechanism by which Lf triggers these signaling pathways, we attempted to delineate the roles of the upstream components of the IKK complex, using their dominant-negative mutants and IKKα−/− and IKKβ−/− mouse embryonic cells. We demonstrated that both IKKα and IKKβ as well as NF-κB-inducing kinase are indispensable for Lf-induced p65 phosphorylation. However, MAPK kinase kinase 1 is not essentially required for this activation. We also observed that Lf-induced p65 phosphorylation was either partially or completely abrogated as the result of treatment with the mutant forms of TNFR-associated factor (TRAF) 2, TRAF5, or TRAF6. Moreover, we demonstrated that Lf directly interacted with TRAF5. Expression of the dominant-negative mutant of TRAF5 or its small interfering RNA almost completely abrogated the Lf-induced p65 phosphorylation. These results suggest that signaling pathways, including TRAFs/NF-κB-inducing kinase/IKKs, may be involved in the regulation of Lf-induced p65 activation, thereby resulting in the activation of members of the NF-κB family.
Exogenous, but not endogenous nociceptin modulates mesolimbic dopamine release in mice

The effect of nociceptin (an endogenous ligand of the ORL1 receptor) on mesolimbic dopamine release and simultaneous horizontal locomotion was studied in freely moving mice undergoing microdialysis of the nucleus accumbens. Intracerebroventricular (i.c.v.) administration of nociceptin (7 nmol) induced a long‐lasting suppression of mesolimbic dopamine release and horizontal locomotion in wild‐type but not ORL1 knockout mice. I.c. v. administration of the recently reported peptide nociceptin antagonist [Nphe1, Arg14, Lys15] nociceptin‐NH2 (known also as UFP‐101, 5 nmol) completely abolished the suppressive effect of nociceptin on mesolimbic dopamine release. However, UFP‐101 administration alone induced a mild and lasting suppression of mesolimbic dopamine release in both wild‐type and ORL1 knockout mice that was magnified in ORL1 knockout mice by coadministration of nociceptin. UFP‐101 administration alone suppressed locomotion in both genotypes. These results confirm that the suppressive action of nociceptin on mesolimbic dopamine release is mediated entirely by the ORL1 receptor, and that UFP‐101 effectively antagonizes this action. However, the lack of a stimulatory effect of UFP‐101 in wild‐type mice indicates that despite being sensitive to exogenous nociceptin action, basal mesolimbic dopaminergic activity is not determined by endogenous nociceptin in mice.
Return to Capital in a Real Business Cycle Model

Can the neoclassical growth model generate fluctuations in the return to capital similar to those observed in the United States? Equating stock market returns with the return to capital, the bulk of the literature concludes that it cannot. This article makes two contributions. First is an equivalence for the neoclassical growth model between a stock market return and a return based on income and capital stock data. While the stock market return is extremely volatile, the income-based return is not. Second is the finding that the neoclassical growth model with shocks to labor productivity alone can account for the bulk of the observed volatility of the income-based return to capital (expressed relative to the volatility of income) but little of the volatility of the stock market return. Simultaneously explaining the volatility of the two measures of the return to capital within the neoclassical model will require a theory of the stock market that breaks our return-equivalence results.
Classifying Daily Tour Service Attributes by Three-Factor Theory of Customer Satisfaction

ABSTRACT Understanding the effect of daily tour service quality on tourist satisfaction is critical because tourist satisfaction is an important determinant of a company’s financial performance. Therefore, this study aims to identify the daily tour service quality attributes and to measure the asymmetric impact of each service attribute on overall tourist satisfaction. A survey was conducted in Myra–Demre–Kekova Tour, Antalya-Turkey with the participation of 424 Russian tourists. Exploratory factor analysis results offered six service attributes for the daily tour, namely: transportation, tour guide, food and beverage facility, shopping facility, stopover facility, and museums and sites. The results of penalty reward contrast analysis showed that all of the attributes were basic factors, the only exception was food and beverage facility, which had an insignificant effect on overall satisfaction. The findings of this study highlight the importance of generating new services that may excite the participants of daily tours and create memorable experiences.
A rapid method for detecting and distinguishing clinically important yeasts by heteroduplex mobility assays (HMAs).

Heteroduplex Mobility Assays (HMAs) of 700 bp amplified products of a 17S rDNA region were used to identify and differentiate seven yeast species of clinical importance Candida albicans, Torulopsis (Candida) glabrata, Candida tropicalis, Candida parapsilosis, Candida (Pichia) guilliermondii and Hansenula (Pichia) anomala. Distance of heteroduplex migration (dHE) was found to be negatively correlated to the number of nucleotide differences between amplified DNA sequences.
MultiAmdahl: Optimal Resource Allocation in Heterogeneous Architectures

Future multiprocessor chips will integrate many different units, each tailored to a specific computation. When designing such a system, the chip architect must decide how to distribute limited system resources such as area, power, and energy among the computational units. We extend MultiAmdahl, an analytical optimization technique for resource allocation in heterogeneous architectures, for energy optimality under a variety of constant system power scenarios. We conclude that reduction in constant system power should be met by reallocating resources from general-purpose computing to heterogeneous accelerator-dominated computing, to keep the overall energy consumption at a minimum. We extend this conclusion to offer an intuition regarding energy-optimal resource allocation in data center computing.
Amnioreduction in a singleton pregnancy: A systematic review

The aim of this study was to investigate the risk of adverse events following amnioreduction in a singleton pregnancy. A systematic review was conducted. Literature was identified by searching two bibliographical databases between 1991 and 2011, without language restrictions. The data extracted and overall rates and confidence intervals for each adverse event were calculated. Four studies met the selection criteria for systematic review. The rate of symptom relief in one study was 100%. Because of the small numbers and wide confidence intervals, an exact quantification of risk of adverse events cannot be determined.
Information asymmetry and energy efficiency: evidence from the housing market

Current policies addressing the carbon externality from energy consumption in the building stock often hinge on the assumption that markets efficiently capitalize the energy performance of assets. This paper uses different identification strategies to examine the capitalization of energy efficiency in the housing market, addressing methodological shortcomings in the existing literature. The results indicate that energy efficiency is capitalized into home prices, but OLS estimates are biased downwards: using the IV approach, we find that as the level of energy efficiency increases by ten percent, the market value of the dwelling increases by around 2.2 percent. These results are confirmed in a repeat-sales analysis. Importantly, examining the role of energy performance certificates (EPCs), we document that the extent of capitalization of energy efficiency is not affected by the presence of an EPC, questioning the need for such government-imposed certification programs. JEL Codes: D12, Q51, R21
Concomitant Efavirenz Reduces Pharmacokinetic Exposure to the Antimalarial Drug Artemether–Lumefantrine in Healthy Volunteers

Background:The antiretroviral drug efavirenz (EFV) and the antimalarial artemisinin-based combination therapy artemether–lumefantrine (AL) are commonly co-administered to treat HIV and malaria. EFV is a known inducer of cytochrome P450 3A4, which converts artemether to dihydroartemisinin (DHA) that is also active and metabolizes longer acting lumefantrine (LR). A study in healthy volunteers was completed to address the concern that EFV impacts AL pharmacokinetics (PKs). Methods:Adults received AL (80/480 mg twice daily) for 3-days before and during EFV co-administration (600 mg daily for 26 days) with intensive PK for artemether, DHA, and LR conducted after the last AL dose for each period. EFV PK was evaluated with and without AL. PK parameters were estimated using noncompartmental methods. Results:Twelve subjects completed the 2-period study. PK exposure for artemether, DHA, and LR [as estimated by the area under the concentration time curve (AUClast)] decreased or trended toward decrease with EFV, compared with when administered alone [−51% (P = 0.084), −46% (P = 0.005), and −21% (P = 0.102), respectively]. Day-7 LR levels, previously deemed predictive of treatment success, were 46% lower (P = 0.002) with EFV, but the LR half-life was unchanged. EFV PK exposure was minimally altered after AL co-administration [AUC0–24 hrs decreased by 17% (P = 0.034)]. Conclusions:Exposure to DHA, but not LR, was significantly lower during EFV-AL co-administration compared with that during administration of AL alone. These findings may have implications for the treatment efficacy of AL, particularly in children. However, the observed modest changes probably do not warrant dosage adjustment during co-administration of AL with EFV.
Interobserver agreement of the German translation of the Motivational Interviewing Sequential Code for Observing Process Exchanges (MI-SCOPE;D).

The aim of this study is to assess the interobserver agreement of the German translation of the MI-SCOPE. We applied it to transcribed counseling sessions on smoking cessation and relapse prevention with women postpartum. The MI-SCOPE is an instrument to assess and quantify MI-specific processes. Twenty percent random samples for parsing and coding each were drawn from 162 transcripts of MI sessions from the treatment arm of an RCT to assess interobserver agreement. Whole transcripts were coded. Each transcript was randomly assigned to two of three raters who parsed and coded the transcripts separately. Cohen's κ was computed to assess interobserver agreement. Concordance about parses ranged between κ = . 702 and κ = . 955 (25th percentile-median-75th percentile: .896-.918-.936). The kappas did not differ significantly between the three combinations of raters (H = 2.648; df = 2, p = .266). Concordance about codes for all 46 categories ranged between κ = . 590 and κ = . 822 (25th percentile-median-75th percentile: .680-.718-.748). The kappas did not differ significantly between the three combinations of raters (H = 4.095; df = 2, p = .129). The German translation of the MI-SCOPE yielded good to excellent κ for parsing as well as for coding. This indicates that MI as an intervention can be taught, learned, and adherence to MI as an intervention may be objectively observed and assessed.
Deformation patterns in genotyped patients with hypertrophic cardiomyopathy.

AIMS Echocardiographic strain imaging with two-dimensional speckle tracking is an emerging tool for defining cardiac function and identifying preclinical hypertrophic cardiomyopathy (HCM). In HCM, a reverse septal contour is a strong predictor of mutation positive sarcomeric HCM. The objective of this study was to determine whether left ventricular (LV) deformation patterns can differentiate between genotype positive and negative patients within a large HCM cohort. METHODS AND RESULTS One hundred and thirty one patients (89 males, age 55 ± 15 years) with clinically diagnosed HCM underwent comprehensive transthoracic echocardiography inclusive of LV strain imaging, LV dimensions and ejection fraction, septal contour and thickness, and identification of obstructive physiology. Longitudinal peak systolic strain was assessed from 17 LV myocardial segments blinded to the patient's genetic test results derived from comprehensive genotyping of nine myofilament HCM-associated genes. Genotyping revealed that 51 of 131 patients (39%) were mutation positive for sarcomeric/myofilament-HCM (genotype positive). Regional strain was lower in genotype-positive patients in mid inferoseptal (P = 0.004), basal anteroseptal (P = 0.04), and basal inferoseptal segments (P = 0.002) compared with HCM patients lacking a mutation (genotype negative). Strain patterns in reverse-curve, genotype-positive HCM differed significantly from genotype negative, sigmoidal HCM in multiple segments. However, when comparing genotype-negative and genotype-positive patients with the same septal morphology, there were no significant regional strain differences. Septal thickness positively correlated with global and basal anteroseptal longitudinal strain (r = 0.34 and r = 0.54, respectively, P < 0.0001). CONCLUSION Significant regional strain differences in genotyped HCM patients are dependent upon septal morphology or thickness, not genotype. Phenotypic expression of deformation patterns appears heterogeneous.
Interleukin-4 mediates down regulation of antiviral cytokine expression and cytotoxic T-lymphocyte responses and exacerbates vaccinia virus infection in vivo

Interleukin-4 (IL-4) promotes the growth of Th2-type cells while down regulating the development of Th1-type cells. It has been suggested that the actions of this factor inhibit Th1-type effector activity in vivo and may underlie the development of diseases normally controlled by cell-mediated immune responses. Here, we show that clearance of recombinant vaccinia viruses (VV) engineered to express the gene for murine IL-4 is markedly delayed in mice compared with control recombinant VV. While antiviral antibody levels and NK activity in mice given control virus or IL-4-expressing virus were similar, antiviral cytotoxic T-lymphocyte responses were profoundly suppressed throughout the course of infection with the latter. Limiting dilution analysis of IL-4-virus-infected spleens revealed a marked reduction in numbers of cytotoxic T-lymphocyte precursors. Furthermore, reverse transcriptase PCR analysis of splenic mRNA prepared from mice infected with the IL-4-expressing VV showed a marked down regulation of IL-12, gamma interferon, and IL-2 gene expression compared with that from mice given control virus. IL-4 also inhibited the production of nitric oxide (NO), a potent mediator of antimicrobial activity. Together, these data show that IL-4 markedly suppresses the development of antiviral cell-mediated immune responses in vivo with deleterious effects on virus clearance.
Trauma training in simulation: translating skills from SIM time to real time.

BACKGROUND : Training surgical residents to manage critically injured patients in a timely fashion presents a significant challenge. Simulation may have a role in this educational process, but only if it can be demonstrated that skills learned in a simulated environment translate into enhanced performance in real-life trauma situations. METHODS : A five-part, scenario-based trauma curriculum was developed specifically for this study. Midlevel surgical residents were randomized to receiving this curriculum in didactic lecture (LEC) fashion or with the use of a human performance simulator (HPS). A written learning objectives test was administered at the completion of the training. The first four major trauma resuscitations performed by each participating resident were captured on videotape in the emergency department and graded by two experienced judges blinded to the method of training. The assessment tool used by the judges included an evaluation of both initial trauma evaluation or treatment skills (part I) and crisis management skills (part II) as well as an overall score (poor/fail, adequate, or excellent). RESULTS : The two groups of residents received almost identical scores on the posttraining written test. Average SIM and LEC scores for part I were also similar between the two groups. However, SIM-trained residents received higher overall scores and higher scores for part II crisis management skills compared with the LEC group, which was most evident in the scores received for the teamwork category (p = 0.04). CONCLUSIONS : A trauma curriculum incorporating simulation shows promise in developing crisis management skills that are essential for evaluation of critically injured patients.