Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and characterization of novel long-term metabolites of oxymesterone and mesterolone in human urine by application of selected reaction monitoring GC-CI-MS/MS.

The search for metabolites with longer detection times remains an important task in, for example, toxicology and doping control. The impact of these long-term metabolites is highlighted by the high number of positive cases after reanalysis of samples that were stored for several years, e.g. samples of previous Olympic Games. A substantial number of previously alleged negative samples have now been declared positive due to the detection of various long-term steroid metabolites the existence of which was unknown during the Olympic Games of 2008 and 2012. In this work, the metabolism of oxymesterone and mesterolone, two anabolic androgenic steroids (AAS), was investigated by application of a selected reaction monitoring gas chromatography-chemical ionization-triple quadrupole mass spectrometry (GC-CI-MS/MS) protocol for metabolite detection and identification. Correlations between AAS structure and GC-CI-MS/MS fragmentation behaviour enabled the search for previously unknown but expected AAS metabolites by selection of theoretical transitions for expected metabolites. Use of different hydrolysis protocols allowed for evaluation of the detection window of both phase I and phase II metabolites. For oxymesterone, a new metabolite, 18-nor-17β-hydroxymethyl-17α-methyl-4-hydroxy-androst-4,13-diene-3-one, was identified. It was detectable up to 46 days by using GC-CI-MS/MS, whereas with a traditional screening (detection of metabolite 17-epioxymesterone with electron ionization GC-MS/MS) oxymesterone administration was only detectable for 3.5 days. A new metabolite was also found for mesterolone. It was identified as 1α-methyl-5α-androstan-3,6,16-triol-17-one and its sulfate form after hydrolysis with Helix pomatia resulted in a prolonged detection time (up to 15 days) for mesterolone abuse. Copyright © 2017 John Wiley & Sons, Ltd.
Economic dispatch considering valve point effects using modified teaching learning based optimisation

In this paper, Modified Teaching Learning Based Optimisation is used to solve the Economic Dispatch problems of the generating units considering valve point loadings effects. The formulation of the objective function is carried out in such a way that the losses are neglected and a clarified solution is obtained from the generating units. A recently developed optimisation is the Teaching Learning Based Optimisation which operates on two different phases-teacher phase and learner phase. A modification is done in the Teaching Learning Based Optimisation and is used in this paper as Modified Teaching Learning Based Optimisation. Here, in addition to the two phases, an mutation phase is also introduced. In contrast to the other Optimisation methods this proposed method does not require any algorithm specific parameters, it does not depend on any tuning parameters of algorithm and it enables global optimum solution and also avoids premature convergence to local optima of the objective function. The proposed method finds an optimum solution, such that minimum fuel cost solution can be obtained with extraordinary convergence rates and high consistency. The proposed method is tested on standard IEEE bus with 13 generating unit system, 40 generating unit system with valve point effects. The effectiveness of this method is demonstrated by comparing the results with other optimization techniques. Also, the result confirms that this proposed method has a great potential in determining the optimum solution.
Public Professionals’ Engagement in Coproduction: The Impact of the Work Environment on Elderly Care Managers’ Perceptions on Collaboration With Client Councils

In the context of public service delivery, public professionals nowadays intensively collaborate with citizens. The joint, sometimes mandatorily, efforts of citizens and professionals to provide public services have become known as “coproduction. ” Although coproduction directly affects professionals’ work environment, professionals’ attitudes toward coproduction are hardly studied. This article explains variation in professionals’ engagement in coproduction from characteristics of their work environment, specifically their perceived level of autonomy, perceived organizational support for coproduction, and perceived red tape associated with coproduction activities. Survey research was conducted to question managers of Dutch organizations for elderly care about their interaction with client councils, an example of coproduction activities in the domain of health care. The results show that perceived autonomy in coproduction, red tape associated with coproduction, and organizational support affect professionals’ engagement. Organizational support moreover reinforces the effect of work autonomy on professionals’ perception on the importance of coproduction. These findings add to the study of coproduction and can help support public organizations to improve coproduction.
Professional Networks and their Coevolution with Executive Careers: Evidence from North America and Europe

This paper examines how networks of professional contacts contribute to the development of the careers of executives of North American and European companies. We build a dynamic model of career progression in which career moves may both depend upon existing networks and contribute to the development of future networks. We test the theory on an original dataset of nearly 73 000 executives in over 10 000 firms. In principle professional networks could be relevant both because they are rewarded by the employer and because they facilitate job mobility. Our econometric analysis suggests that, although there is a substantial positive correlation between network size and executive compensation, with an elasticity of around 20%, almost all of this is due to unobserved individual characteristics. The true causal impact of networks on compensation is closer to an elasticity of 1 or 2% on average, all of this due to enhanced probability of moving to a higher-paid job. And there appear to be strongly diminishing returns to network size.
Medication discrepancies in integrated electronic health records

Introduction Medication discrepancies are associated with adverse drug events. Electronic health records (EHRs) may reduce discrepancies, especially if integrated with pharmacy dispensing. We determined the prevalence of discrepancies within a national healthcare system with EHR–pharmacy linkage to characterise the medications involved and to identify factors associated with discrepancies. Methods We conducted a retrospective cohort study of ambulatory care patients at Veterans Affairs Boston Healthcare System, April 2010–July 2011. The primary outcome was the presence of any medication discrepancy or specific types of discrepancies: commission—present in the record but not taken by patient; omission—not present in the record; duplication—present more than once; or alteration in dose or frequency—present but taken differently than documented. Results Sixty-two patients (60%) had at least one medication discrepancy. Prevalence of commissions, omissions, duplications and alterations were 36%, 27%, 11% and 19%, respectively. The involved medications differed by type of discrepancy, but non-opioid analgesics and herbal therapies were common among commissions and omissions. In adjusted analyses, an increasing number of medications was associated with more commissions (OR 1.2; 95% CI 1.1 to 1.3) and duplications (OR 1.2; 95% CI 1.1 to 1.4) and fewer omissions (OR 0.9; 95% CI 0.8 to 1.0). Discussion In a system with a well established EHR linked to pharmacy dispensing, medication discrepancies occurred in 60% of ambulatory clinic patients. Patients with a greater number of medications were more likely to have errors of commission and duplication, but less likely to have errors of omission. Our findings highlight that relying on EHRs alone will not ensure an accurate medication list and stress the need to review medication taking thoroughly with patients to capitalise on the full potential of EHRs.
Toleration as recognition

Acknowledgments Introduction 1. Liberal theories of toleration 2. The limits of liberal toleration 3. Toleration reconsidered 4. The Islamic veil in French schools 5. Should we tolerate racism? 6. Same-sex marriage 7. Toleration and identity politics Conclusion Bibliography Index.
Regulation of paxillin-p130-PI3K-AKT signaling axis by Src and PTPRT impacts colon tumorigenesis

Protein tyrosine phosphatase receptor T (PTPRT) is frequently mutated in a variety of human cancers including colorectal cancer. Here we report that PTPRT knockout increases the size of mouse colon tumors in the Apcmin+/− genetic background, suggesting that inactivation of PTPRT promotes tumor progression. We previously demonstrated that PTPRT dephosphorylates paxillin at tyrosine-Y88 residue. Consistently, phosphorylation of Y88 paxillin (pY88) is up-regulated in colon tumors derived from Apcmin+/− Ptprt−/− mice. An important downstream effector of pY88 paxillin is the oncogene Akt. Here, we show that pY88 paxillin impacts the Akt pathway by regulating the interaction between p130cas and the p85 regulatory subunit of PI3-Kinase. Additionally, while pY88 paxillin is a substrate of the tumor suppressor phosphatase PTPRT, the corresponding kinase has not been previously identified. In this study, we demonstrate that the oncogenic kinase Src directly phosphorylates paxillin at Y88. Moreover, colorectal cancer cells that express high levels of pY88 paxillin are sensitive to dasatinib treatment, suggesting that pY88 paxillin may serve as a predictive biomarker for Src family kinase inhibitors.
Line contribution to the critical Casimir force between a homogeneous and a chemically stepped surface

Recent experimental realizations of the critical Casimir effect have been implemented by monitoring colloidal particles immersed in a binary liquid mixture near demixing and exposed to a chemically structured substrate. In particular, critical Casimir forces have been measured for surfaces consisting of stripes with periodically alternating adsorption preferences, forming chemical steps between them. Motivated by these experiments, we analyze the contribution of such chemical steps to the critical Casimir force for the film geometry and within the Ising universality class. By means of Monte Carlo simulations, mean-field theory and finite-size scaling analysis we determine the universal scaling function associated with the contribution to the critical Casimir force due to individual, isolated chemical steps facing a surface with homogeneous adsorption preference or with Dirichlet boundary condition. In line with previous findings, these results allow one to compute the critical Casimir force for the film geometry and in the presence of arbitrarily shaped, but wide stripes. In this latter limit the force decomposes into a sum of the contributions due to the two homogeneous parts of the surface and due to the chemical steps between the stripes. We assess this decomposition by comparing the resulting sum with actual simulation data for the critical Casimir force in the presence of a chemically striped substrate.
Ant foraging on complex trails: route learning and the role of trail pheromones in Lasius niger

SUMMARY Ants are central place foragers and use multiple information sources to navigate between the nest and feeding sites. Individual ants rapidly learn a route, and often prioritize memory over pheromone trails when tested on a simple trail with a single bifurcation. However, in nature, ants often forage at locations that are reached via more complex routes with multiple trail bifurcations. Such routes may be more difficult to learn, and thus ants would benefit from additional information. We hypothesized that trail pheromones play a more significant role in ant foraging on complex routes, either by assisting in navigation or route learning or both. We studied Lasius niger workers foraging on a doubly bifurcating trail with four end points. Route learning was slower and errors greater on alternating (e.g. left–right) versus repeating routes (e.g. left–left), with error rates of 32 and 3%, respectively. However, errors on alternating routes decreased by 30% when trail pheromone was present. Trail pheromones also aid route learning, leading to reduced errors in subsequent journeys without pheromone. If an experienced forager makes an error when returning to a food source, it reacts by increasing pheromone deposition on the return journey. In addition, high levels of trail pheromone suppress further pheromone deposition. This negative feedback mechanism may act to conserve pheromone or to regulate recruitment. Taken together, these results demonstrate further complexity and sophistication in the foraging system of ant colonies, especially in the role of trail pheromones and their relationship with learning and the use of private information (memory) in a complex environment.
Multipoint dixon technique for water and fat proton and susceptibility imaging

Extensions to a previously described three‐point Dixon magnetic resonance imaging technique are presented that use alternative water/fat phase‐encoding strategies. The technique is generalized to phase encoding of (−θ,0,θ) or (0,θ,2θ) radians, and the signal‐to‐noise ratio (S/N) performance is evaluated. It was found that a θ of 2π/3 radians has optimal S/N but that a θ of π radians is a good compromise and that phase encoding of (O,π, 2π) radians offer an advantage over the previous method, which used (−π, O, π) increments, in that a T2′ (intravoxel susceptibility dephasing) image may be obtained in addition to the usual water, fat, and B0 images. A new four‐point method with phase encoding of (O, π, 2π, 3π) radians that can also provide a measure of the spectral width of the fat resonance is suggested. The disadvantages of the method are the extra imaging time and low S/N efficiency.
(ICORG 05-03): prospective randomized non-inferiority phase III trial comparing two radiation schedules in malignant spinal cord compression (not proceeding with surgical decompression); the quality of life analysis

Abstract Background: The optimal primary external beam radiation therapy (EBRT) radiation schedule for malignant epidural spinal cord compression (MSCC) remains to be determined. The ICORG 05-03 trial assessed if a 10 Gy single fraction radiation schedule was not inferior to one with 20 Gray (Gy) in five daily fractions, in terms of functional motor outcome, for the treatment of MSCC in patients not proceeding with surgical decompression. This article reports on two of the secondary endpoints, Quality of life (QoL), assessed according to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) version 3.0 (EORTC Data Center, Brussels, Belgium) and pain control assessed using a visual analog scale. Methods: A randomized, parallel group, multicenter phase III trial was conducted by Cancer Trials Ireland (formerly All-Ireland Cooperative Oncology Research Group, ICORG), across five hospital sites in Ireland and Northern Ireland. Patients were randomized to 10 Gy single fraction of EBRT or 20 Gy in five fractions in a 1:1 ratio. Patients with baseline and 5-week follow up QoL data are included in this analysis. Findings: From 2006 to 2014, 112 eligible patients were enrolled for whom 57 were evaluated for this secondary analysis. After adjusting for pre-intervention scores, there was no statistically significant difference in post-treatment Summary scores (excl. FI and QL), or pain scores between the two RT schedules at 5 weeks and 3 months following EBRT. There was a statistically significant relationship between the pretreatment and post-treatment Summary scores (p = .002) but not between the pre-treatment and post-treatment pain scores. Interpretation: Primary radiotherapy for the treatment of MSCC significantly improves QoL in patients not proceeding with surgical decompression. After adjusting for pre-intervention scores, there was no statistically significant difference between a 10 Gy single fraction radiation schedule and one with 20 Gy in five daily fractions on post-treatment QoL Summary scores. For most patients, an effective treatment with low burden would be desirable. A single fraction schedule should be considered for this group of patients.
Humoral immune response in acute hepatitis C virus infection.

BACKGROUND There is little information on the timing, magnitude, specificity, and clinical relevance of the antibody response to acute hepatitis C virus (HCV) infection. We investigated the specificity, titer, and neutralizing potential of antibody responses to acute infection by examining 12 injection drug users before, during, and after infection. METHODS Seroconversion was defined as incident detection of HCV-specific antibodies by using a commercially available enzyme-linked immuosorbent assay (ELISA). HCV protein-specific antibody responses were measured using recombinant antigens in an ELISA. For neutralization assays, plasma was incubated with human immunodeficiency virus (HIV)-HCV H77 or control HIV-murine leukemia virus (MLV) pseudotype virus and then allowed to infect Hep3B hepatoma cells. RESULTS The mean time to HCV seroconversion was 6 weeks after the onset of viremia. Antibody responses to nonstructural proteins were detected before responses to the structural proteins, and antibodies to both were primarily restricted to the immunoglobulin G1 (IgG1) subclass. The maximum median end point titers for antibody responses to structural and nonstructural proteins were 1 : 600 and 1 : 6400, respectively. Antibodies that neutralized a retroviral pseudotype bearing HCV 1a envelope glycoproteins were detected at seroconversion in only 1 subject and at 6-8 months after seroconversion in 3 subjects. The delayed appearance of neutralizing antibodies was consistent with the late development of antibodies specific for the viral envelope glycoproteins, which are believed to mediate virus neutralization. CONCLUSION The humoral immune response to acute HCV infection is of relatively low titer, is restricted primarily to the IgG1 subclass, and is delayed. A better understanding of why production of neutralizing antibody is delayed may improve efforts to prevent HCV infection.
Effect of time variation in the Higgs vacuum expectation value on the cosmic microwave background

A time variation in the Higgs vacuum expectation value alters the electron mass and thereby changes the ionization history of the universe. This change produces a measurable imprint on the pattern of cosmic microwave background (CMB) fluctuations. The nuclear masses and nuclear binding energies, as well as the Fermi coupling constant, are also altered, with negligible impact on the CMB. We calculate the changes in the spectrum of the CMB fluctuations as a function of the change in the electron mass m{sub e}. We find that future CMB experiments could be sensitive to |{delta}m{sub e}/m{sub e}|{approx}|{delta}G{sub F}/G{sub F}|{approx}10{sup -2}-10{sup -3}. However, we also show that a change in m{sub e} is nearly, but not exactly, degenerate with a change in the fine-structure constant {alpha}. If both m{sub e} and {alpha} are time varying, the corresponding CMB limits are much weaker, particularly for l<1000. (c) 2000 The American Physical Society.
Using metaphors as modifiers: children's production of metaphoric compounds

Although much research has investigated children's use of metaphoric language, methodological concerns raise questions about the conclusions, and it remains unclear whether preschoolers can produce metaphors. These studies employed a new methodology to test children's ability to produce metaphors incorporated into metaphoric compounds. In two studies, 59 children aged 2;8–4;3, 63 children aged 4;4–6;1, and 34 adults participated in elicited production tasks. In Study 1, subjects in the COMPOUND condition corrected a puppet's incorrect compound labels for pictures that had metaphoric resemblances to other objects (e.g. ‘leaf-bug’ for a bug shaped like a stick). Subjects in the NON-METAPHORIC condition heard incorrect compounds describing pictures without obvious metaphoric resemblance (e.g. ‘leaf-bug’ for a round black beetle). Children in the REVERSAL condition heard compounds with nouns reversed (e.g. ‘bug-leaf’ for the stick-bug) to discover whether children distinguished between the literal and metaphoric labels. Study 2 provided an additional test of children's metaphoric–literal distinction. Results showed that children as young as 3;0 produced intentional, appropriate metaphors incorporated into compound nouns when the stimuli and puppet's labels primed recognition of metaphoric similarity and compound production. Moreover, children showed evidence of a distinction between literal and metaphoric labels. The data show that preschool children have an early ability to use metaphoric language but that significant developmental change occurs between the ages of 3;0 and 5;0 as well as beyond 5;0. Additionally, metaphoric language in preschoolers is not limited to single-word renamings.
Nuclear magnetic resonance (NMR) applied to membrane–protein complexes

Abstract Increasing evidence suggests that most proteins occur and function in complexes rather than as isolated entities when embedded in cellular membranes. Nuclear magnetic resonance (NMR) provides increasing possibilities to study structure, dynamics and assembly of such systems. In our review, we discuss recent methodological progress to study membrane–protein complexes (MPCs) by NMR, starting with expression, isotope-labeling and reconstitution protocols. We review approaches to deal with spectral complexity and limited spectral spectroscopic sensitivity that are usually encountered in NMR-based studies of MPCs. We highlight NMR applications in various classes of MPCs, including G-protein-coupled receptors, ion channels and retinal proteins and extend our discussion to protein–protein complexes that span entire cellular compartments or orchestrate processes such as protein transport across or within membranes. These examples demonstrate the growing potential of NMR-based studies of MPCs to provide critical insight into the energetics of protein–ligand and protein–protein interactions that underlie essential biological functions in cellular membranes.