Miracle-dz/UniFAR-FTUs huggingface dataset:
Constitutive mRNA expression of DNA repair-related genes as a biomarker for clinical radio-resistance: A pilot study in prostate cancer patients receiving radiotherapy

Purpose: Repair of radiation-induced DNA damage is believed to play a critical role in the development of adverse reactions in radiotherapy patients. Constitutive mRNA expression of repair genes was investigated in such patients to analyze whether expression patterns are predictive for therapy-related acute side effects. Materials and methods: Prostate cancer patients (n = 406) receiving intensity-modulated radiotherapy were recruited in a prospective epidemiological study. Adverse effects were monitored during therapy using common toxicity criteria. For expression analyses, samples from 58 patients were selected according to their observed grade of clinical side effects to radiotherapy. Expression profiles were generated from peripheral blood lymphocytes using customized cDNA-arrays which carried probes for 143 DNA repair or repair-related genes. In addition, expression of selected genes was confirmed by quantitative real-time reverse transcription PCR (RT-PCR). Constitutive mRNA expression profiles were analyzed for predicting acute clinical radiosensitivity or radio-resistance. Results: Cluster analysis identified 19 differentially expressed genes. Many of these genes are involved in DNA double strand break repair. Expression levels of these genes differed up to 7-fold from the mean of all patients whereas expression levels of housekeeping genes varied only up to 2-fold. High expression of the identified genes was associated with a lack of clinical radiation sensitivity thus indicating radio-resistance. Conclusions: Constitutive expression of DNA repair-related genes may affect the development of acute side effects in radiotherapy patients, and high expression levels of these genes seem to support protection from adverse reactions.
Kinetics of force recovery following length changes in active skinned single fibres from rabbit psoas muscle

Redevelopment of isometric force following shortening of skeletal muscle is thought to result from a redistribution of cross‐bridge states. We varied the initial force and cross‐bridge distribution by applying various length‐change protocols to active skinned single fibres from rabbit psoas muscle, and observed the effect on the slowest phase of recovery (‘late recovery’) that follows transient changes. In response to step releases that reduced force to near zero (∼8 nm (half sarcomere)−1) or prolonged shortening at high velocity, late recovery was well described by two exponentials of approximately equal amplitude and rate constants of ∼2 s−1 and ∼9 s−1 at 5°C. When a large restretch was applied at the end of rapid shortening, recovery was accelerated by (1) the introduction of a slow falling component that truncated the rise in force, and (2) a relative increase in the contribution of the fast exponential component. The rate of the slow fall was similar to that observed after a small isometric step stretch, with a rate of 0.4–0.8 s−1, and its effects could be reversed by reducing force to near zero immediately after the stretch. Force at the start of late recovery was varied in a series of shortening steps or ramps in order to probe the effect of cross‐bridge strain on force redevelopment. The rate constants of the two components fell by 40–50% as initial force was raised to 75–80% of steady isometric force. As initial force increased, the relative contribution of the fast component decreased, and this was associated with a length constant of about 2 nm. The results are consistent with a two‐state strain‐dependent cross‐bridge model. In the model there is a continuous distribution of recovery rate constants, but two‐exponential fits show that the fast component results from cross‐bridges initially at moderate positive strain and the slow component from cross‐bridges at high positive strain.
Modelling and trading the realised volatility of the FTSE100 futures with higher order neural networks

The motivation for this article is the investigation of the use of a promising class of neural network (NN) models, higher order neural networks (HONNs), when applied to the task of forecasting and trading the 21-day-ahead realised volatility of the FTSE 100 futures index. This is done by benchmarking their results with those of two different NN designs, the multi-layer perceptron (MLP) and the recurrent neural network (RNN), along with a traditional technique, RiskMetrics. More specifically, the forecasting and trading performance of all models is examined over the eight FTSE 100 futures maturities of the period 2007–2008 using the realised volatility of the last 21 trading days of each maturity as the out-of-sample target. The statistical evaluation of our models is done by using a series of measures such as the mean absolute error, the mean absolute percentage error, the root-mean-squared error and the Theil U-statistic. Then we apply a simple trading strategy to exploit our forecasts based on trading at-the-money call options on FTSE 100 futures. As it turns out, HONNs demonstrate a remarkable performance and outperform all other models not only in terms of statistical accuracy but also in terms of trading efficiency. We also note that both the RNNs and MLPs provide sufficient results in the trading application in terms of cumulative profit and average profit per trade.
Hospital cost structure in the USA: what's behind the costs? A business case.

PURPOSE Hospital costs in the USA are a large part of the national GDP. Medical billing and supplies processes are significant and growing contributors to hospital operations costs in the USA. This article aims to identify cost drivers associated with these processes and to suggest improvements to reduce hospital costs. DESIGN/METHODOLOGY/APPROACH A Monte Carlo simulation model that uses @Risk software facilitates cost analysis and captures variability associated with the medical billing process (administrative) and medical supplies process (variable). The model produces estimated savings for implementing new processes. FINDINGS Significant waste exists across the entire medical supply process that needs to be eliminated. Annual savings, by implementing the improved process, have the potential to save several billion dollars annually in US hospitals. The other analysis in this study is related to hospital billing processes. Increased spending on hospital billing processes is not entirely due to hospital inefficiency. RESEARCH LIMITATIONS/IMPLICATIONS The study lacks concrete data for accurately measuring cost savings, but there is obviously room for improvement in the two US healthcare processes. This article only looks at two specific costs associated with medical supply and medical billing processes, respectively. PRACTICAL IMPLICATIONS This study facilitates awareness of escalating US hospital expenditures. Cost categories, namely, fixed, variable and administrative, are presented to identify the greatest areas for improvement. ORIGINALITY/VALUE The study will be valuable to US Congress policy makers and US healthcare industry decision makers. Medical billing process, part of a hospital's administrative costs, and hospital supplies management processes are part of variable costs. These are the two major cost drivers of US hospitals' expenditures that were examined and analyzed.
Does Left/Right Structure Party Positions on European Integration?

How is contestation on European integration structured among national political parties? Are issues arising from European integration assimilated into existing dimensions of domestic contestation? We show that there is a strong relationship between the conventional left/right dimension and party positioning on European integration. However, the most powerful source of variation in party support is the new politics dimension, ranging from Green/alternative/libertarian to Traditional/authoritarian/nationalist.
Well-being of intensive care nurses (WEBIC): a job analytic approach.

AIMS OF THE STUDY This paper presents the results of a validation study of the so-called well-being of intensive care nurses (WEBIC)-questionnaire that is designed to perform a detailed job analysis of intensive care unit (ICU) nurses' jobs. BACKGROUND The WEBIC-questionnaire is based on modern sociotechnical systems theory, and distinguishes four integrated task categories: (1) operational, (2) organizing, (3) preparatory, and (4) supportive tasks. For each task, the WEBIC assesses (1) how demanding this task is, and (2) how satisfying the performance of this task is. Using the WEBIC, information is gathered about ICU nurses' qualitative workload, and typical job-related risks for ICU nurses' well-being at work can be mapped. METHODS A cross-sectional survey on work and well-being of almost 2000 ICU-nurses in 13 different European areas was conducted. Exploratory factor analyses were performed to study the validity of the factorial structure of the WEBIC-questionnaire. The construct validity of the WEBIC-questionnaire was studied by performing hierarchical multiple regression analyses of the WEBIC-factors on two types of job-related well-being, i.e. burnout and general job satisfaction. RESULTS Results of the exploratory factor analyses showed that the hypothesized four-factor structure of the WEBIC is confirmed by our data. Internal consistencies of the different factors varied from 0.77 to 0.91. Intensive care unit nurses' most central (operational) tasks turned out to pose the greatest demands, but also seemed to drive their satisfaction. With respect to the relationships between the four WEBIC-factors, and burnout and general job satisfaction, it was found that, especially for the satisfying tasks, significant relationships with these outcomes were found. CONCLUSION The reliability and construct validity of the WEBIC-questionnaire can be considered satisfactory. Furthermore, the questionnaire provides a systematical and detailed coverage of ICU nurses' tasks. In relation to this, the questionnaire is not only useful for scientific purposes but also for practical use.
Logistic Regression: Why We Cannot Do What We Think We Can Do, and What We Can Do About It

Logistic regression estimates do not behave like linear regression estimates in one important respect: They are affected by omitted variables, even when these variables are unrelated to the independent variables in the model. This fact has important implications that have gone largely unnoticed by sociologists. Importantly, we cannot straightforwardly interpret log-odds ratios or odds ratios as effect measures, because they also reflect the degree of unobserved heterogeneity in the model. In addition, we cannot compare log-odds ratios or odds ratios for similar models across groups, samples, or time points, or across models with different independent variables in a sample. This article discusses these problems and possible ways of overcoming them.
Plasma Cell Membrane Localization of c-MET Predicts Longer Survival in Patients with Malignant Mesothelioma: A Series of 157 Cases from the MESOPATH Group

Introduction: By regulating cell functions such as growth, survival, motility/migration, and invasion, the c-mesenchymal-epithelial transition (c-MET) receptor tyrosine kinase/hepatocyte growth factor (HGF) axis accounts for a critical pathway in malignant pleural mesothelioma. Methods: Overall survival correlations of c-MET and phospho-c-MET immunostainings were investigated in 157 malignant pleural mesothelioma patients for whom paraffin-embedded specimens were referred to our center for pathological diagnosis certification (MESOPATH French National group). Subcellular localization of the activated c-MET receptor after HGF stimulation was assessed in nontumorogenic cell lines. Results: Positive c-MET expression was found in 119 samples (75.8%), more frequently in the epithelioid subtype (p < 0.0001). Among those 119 positive c-MET specimens, 77 (64.7%) were also positive for phospho-c-MET. Both c-MET and phospho-c-MET scoring were independent of patient gender or age. Phospho-c-MET scoring or localization did not associate with survival. Conversely, patients with a c-MET immunohistochemical staining intensity higher than 1, but exclusively confined to plasma membrane, had a median overall survival of 25 months versus 13 months for all other patients. Only exclusive plasma membrane staining remained significantly associated with a worse prognosis in multivariate analysis (hazard ratio = 2.9, 95% confidence interval 1.0–8.2, p = 0.043). Using the HBEC3 immortalized epithelial cell lines treated with HGF, we showed the physiological relevance of phospho-c-MET nuclear translocation. Conclusions: Our results lighten that, disregarding the intracellular c-MET receptor traffic, only c-MET plasma membrane localization could be a relevant prognosis biomarker in malignant pleural mesothelioma. Whether patients with c-MET plasma membrane immunostaining could beneficiate from c-MET-targeted therapies remains to be established in prospective trials.
Have Renewable Portfolio Standards Raised Electricity Rates? Evidence from U.S. Electric Utilities

Renewable Portfolio Standards (RPS) have been a contentious issue amongst policymakers in recent years. Neoclassical theory would suggest that, in the short-run, RPS mandates will raise electricity rates if the cost of electricity generation via renewable energy technologies exceeds that of convention fossil fuel technologies. This study uses a quasi-experimental approach to investigate the effect of RPS policies on retail residential electricity rates. The study provides one of the first econometric investigations of the economic effect of RPS mandates. The empirical approach uses a panel dataset of 2,602 U.S. electric utilities from 1990 to 2006. The empirical findings provide several policy insights on the effect of RPS mandates. First, a state RPS mandate, on average, positively affects the average residential electricity rate. Second, no spillover effect exists for the RPS effect on electricity rates. In other words, utilities that operate in a RPS state, but are not subject to an RPS requirement, do not experience a significant increase in electric rates. Third, the RPS effect on residential electricity rates is significantly lower in states with a higher wind and solar energy potential. Finally, the magnitude of the RPS effect on residential electricity rates increases for utilities subject to higher requirements. The estimated elasticity of residential electricity rates with respect to an RPS requirement equals roughly 0.3.
Visualization of early events in tumor formation of eGFP‐transfected rat colon cancer cells in liver

Colon cancer preferentially metastasizes to the liver. To determine cellular backgrounds of this preference, we generated an enhanced green fluorescent protein (eGFP)‐expressing rat adenocarcinoma cell line (CC531s) that forms metastases in rat liver after administration to the portal vein. Intravital videomicroscopy (IVVM) was used to visualize early events in the development of tumors in livers of live animals from the time of injection of the cancer cells up to 4 days afterward. Based on information obtained with IVVM, tissue areas were selected for further analysis using confocal laser scanning microscopy (CLSM), electron microscopy (EM), and electron tomography. It was shown that initial arrest of colon cancer cells in sinusoids of the liver was due to size restriction. Adhesion of cancer cells to endothelial cells was never found. Instead, endothelial cells retracted rapidly and interactions were observed only between cancer cells and hepatocytes. Tumors developed exclusively intravascularly during the first 4 days. In conclusion, initial steps in the classic metastatic cascade such as adhesion to endothelium and extravasation are not essential for colon cancer metastasis in liver.
On the road again: concurrency and condom use among Uganda truck drivers

Long-distance truck drivers have been shown to be a critical population in the spread of HIV in Africa. In 2009, surveys with 385 Ugandan long-distance truck drivers measured concurrency point prevalence with two methods; it ranged from 37.4% (calendar-method) to 50.1% (direct question). The majority (84%) of relationships reported were long-term resulting in a long duration of overlap (average of 58 months) across concurrent partnerships. Only 7% of these men reported using any condoms with their spouses during the past month. Among all non-spousal relationships, duration of relationship was the factor most strongly associated with engaging in unprotected sex in the past month in a multivariable analyses controlling for partner and relationship characteristics. Innovative intervention programs for these men and their partners are needed that address the realities of truck drivers’ lifestyles.
Durability of Percutaneous Angioplasty and Stent Implantation for the Treatment of Abdominal Aortic Coarctation

Abdominal aortic coarctation (AAC) is an uncommon vascular lesion with serious sequelae related to uncontrolled hypertension. Balloon-expandable stents have recently been utilized in the treatment of AAC as an alternative to surgical intervention. A 17-year-old female presented with hypertension uncontrolled by beta blockade. She underwent angiography, which revealed an isolated supraceliac aortic coarctation without visceral or renal artery involvement. Balloon angioplasty with stent placement was performed. At 2-year follow-up, a restenosis was identified and was treated with repeat balloon-expandable stent placement. Implantation of balloon-expandable stents is a safe and technically feasible treatment modality for abdominal aortic coarctation not involving the renal and mesenteric arteries. However, it is currently unknown whether the long-term durability of this approach may limit its effectiveness when compared to traditional surgical interventions.
Participation of 3′-to-5′ Exoribonucleases in the Turnover of Bacillus subtilis mRNA

ABSTRACT Four 3′-to-5′ exoribonucleases have been identified in Bacillus subtilis: polynucleotide phosphorylase (PNPase), RNase R, RNase PH, and YhaM. Mutant strains were constructed that were lacking PNPase and one or more of the other three ribonucleases or that had PNPase alone. Analysis of the decay of mRNA encoded by seven small, monocistronic genes showed that PNPase was the major enzyme involved in mRNA turnover. Significant levels of decay intermediates, whose 5′ ends were at the transcriptional start site and whose 3′ ends were at various positions in the coding sequence, were detected only when PNPase was absent. A detailed analysis of rpsO mRNA decay showed that decay intermediates accumulated as the result of a block to 3′-to-5′ processivity at the base of stem-loop structures. When RNase R alone was present, it was also capable of degrading mRNA, showing the involvement of this exonuclease in mRNA turnover. The degradative activity of RNase R was impaired when RNase PH or YhaM was also present. Extrapolation from the seven genes examined suggested that a large number of mRNA fragments was present in the PNPase-deficient mutant. Maintenance of the free ribosome pool in this strain would require a high level of activity on the part of the tmRNA trans translation system. A threefold increase in the level of peptide tagging was observed in the PNPase-deficient strain, and selective pressure for increased tmRNA activity was indicated by the emergence of mutant strains with elevated tmRNA transcription.
Glutamate Binding to the GluN2B Subunit Controls Surface Trafficking of N-Methyl-d-aspartate (NMDA) Receptors*♦

Background: Ligand binding is essential for surface delivery of non-NMDA-type glutamate receptors. Results: GluN2B ligand binding site mutants showed reduced surface and synaptic expression correlating with glutamate efficacy. Conclusion: Glutamate binding controls surface delivery of NMDA receptors. Significance: This work extends the receptor classes subject to glutamate regulation of surface delivery and reports parameters controlling synaptic delivery of NMDA receptors critical for neuron function. Trafficking of NMDA receptors to the surface of neurons and to synapses is critical for proper brain function and activity-dependent plasticity. Recent evidence suggests that surface trafficking of other ionotropic glutamate receptors requires ligand binding for exit from the endoplasmic reticulum. Here, we show that glutamate binding to GluN2 is required for trafficking of NMDA receptors to the cell surface. We expressed a panel of GluN2B ligand binding mutants in heterologous cells with GluN1 or in rat cultured neurons and found that surface expression correlates with glutamate efficacy. Such a correlation was found even in the presence of dominant negative dynamin to inhibit endocytosis and surface expression correlated with Golgi localization, indicating differences in forward trafficking. Co-expression of wild type GluN2B did not enhance surface expression of the mutants, suggesting that glutamate must bind to both GluN2 subunits in a tetramer and that surface expression is limited by the least avid of the two glutamate binding sites. Surface trafficking of a constitutively closed cleft GluN2B was indistinguishable from that of wild type, suggesting that glutamate concentrations are typically not limiting for forward trafficking. YFP-GluN2B expressed in hippocampal neurons from GluN2B−/− mice rescued synaptic accumulation at similar levels to wild type. Under these conditions, surface synaptic accumulation of YFP-GluN2B mutants also correlated with apparent glutamate affinity. Altogether, these results indicate that glutamate controls forward trafficking of NMDA receptors to the cell surface and to synapses and raise the intriguing idea that NMDA receptors may be functional at intracellular sites.
Options Market Makers' Hedging and Informed Trading: Theory and Evidence

We develop a model to analyze the effects of hedging activities by options market makers (OMMs) facing informed trading. The model suggests that OMMs׳ hedging activities motivated by adverse-selection risk lead to wider spreads in both stock and options markets. The hedging effect on spreads is more pronounced in the options market than in the stock market. The effect is larger when the OMMs hedge with the underlying asset than with other options. In addition, hedging activities by the OMMs significantly alter the trading strategies of informed traders. Our empirical tests provide evidence consistent with the key implication of our model.
An Empirical Investigation of the Returns to Job Search

The assumption of diminishing returns to job search plays a crucial role in the search model presented recently in this Review by John Seater. This assumption is justified by noting that "spatial aspects of the search process cause diminishing returns" since travel time required to search firms in a circular area increases faster than the area to be searched. Besides being an important property of a class of theoretical models, returns to search may partly explain the paradox of an approximately forty-hour workweek contrasted with a seven-hour "search-week" (see John Barron and Wesley Mellow, p. 396). The interaction of diminishing returns to and positive costs of search may result in an optimal allocation of search time of only a few hours per week. In this paper, I examine whether the assumption of diminishing returns to job search can be supported by the data. Following Seater, the returns to search are measured by the number of firms contacted, and the focus is on the ability of unemployed individuals to translate search time into employee contracts. Returns to search are evaluated by noting whether the "production process" exhibits diminishing returns with respect to the input variable.