Miracle-dz/UniFAR-FTUs huggingface dataset:
Valsartan plus hydrochlorothiazide: a review of its use since its introduction

Introduction: This review focuses on the role of the fixed-dose combination (FDC) drug valsartan/hydrochlorothiazide (HCTZ) in the treatment of hypertension. Effective blood pressure control often is not achieved with monotherapy and, instead, requires combinations of drugs with different mechanisms of action to produce additive or synergistic effects. Areas covered: FDC valsartan/HCTZ enhances not only efficacy for blood pressure control but also provides beneficial effects on target organs beyond that expected from arterial pressure reduction alone. Data describe key clinical trial experiences with the FDC, with particular attention to efficacy and tolerability. Literature searches of these various topics were conducted in January 2011. There is evidence of potential benefits with this combination associated with left ventricular hypertrophy, left ventricular dysfunction and renal disease. The FDC is an effective treatment for patients with hypertension and is superior to monotherapy than either drug alone. Expert opinion: In addition to the benefits of each drug, valsartan/HCTZ's metabolic interactions reduce some of the negative effects of both compounds. With its increased simplicity, minimal side-effect profile and efficacy without a significant cost penalty, valsartan/HCTZ represents an excellent choice for antihypertensive therapy.
Requirements on a community-based intervention for stimulating physical activity in physically disabled people: a focus group study amongst experts

Abstract Purpose: To explore ideas experts, working in the field of physical activity for people with a disability, pose on a stimulating movement intervention for physically disabled people longer than one year post rehabilitation or not familiar with rehabilitation. Methods: Four semi-structured focus groups were conducted with experts (n = 28). Transcripts were analysed following thematic analysis, using the integrated physical activity for people with a disability and intervention mapping model. Results: Experts expressed no need for a new intervention, but, instead, a need for adapting an existing intervention, and increased collaboration between organisations. Such an adapted intervention should aim to change participants and environmental attitude towards physical activity, and to increase visibility of potential activities. Several methods were mentioned, for instance individual coaching. Potential participants should be personally approached via various intermediates. The intervention owner and government are responsible for stimulating physical activity and should finance an intervention together with health insurances and the user. Conclusions: According to experts adapting an existing intervention, together with increased collaboration between organisations, will be effective in stimulating physical activity in the target population. This study provides requirements on an intervention to stimulate physical activity, and suggestions for the approach of the target population, finance, and responsibility. Implications for Rehabilitation There is no need for designing a new intervention, but need for adaptation of an existing intervention for stimulating physical activity in physically disabled people. An intervention to stimulate physical activity in physically disabled people should aim to change participants and environmental attitude towards physical activity, and to increase the visibility of potential activities. Methods for stimulating physical activity in physically disabled people could be the use of individual coaching, feedback, a trial period, and role models. Potential participants should be personally approached via a network of intermediate organisations and via marketing, and the social environment.
Use of Intracardiac Echocardiography for Early Detection of Phrenic Nerve Injury During Cryoballoon Pulmonary Vein Isolation

Use of Intracardiac Echocardiography for Early Detection of Phrenic Nerve Injury. Cryoballoon catheter ablation has recently emerged as an effective tool to achieve pulmonary vein isolation (PVI). Right‐sided PVI with cryoballoon ablation has been associated with a significant incidence of phrenic nerve palsy. Multiple modalities are currently utilized to monitor phrenic nerve function during ablation. We describe a novel approach toward monitoring and diagnosing phrenic nerve palsy using intracardiac echocardiography (ICE) during cryoballoon ablation of the right pulmonary veins. This technique of monitoring has the advantage of continuous direct diaphragmatic visualization without the use of fluoroscopy, hence significantly minimizing radiation to both the patient and the operator. In addition, this technique does not require extra personnel to monitor the diaphragm using manual palpation. Further prospective studies of our and other methods for prevention of phrenic nerve palsy are required. (J Cardiovasc Electrophysiol, Vol. 23, pp. 874‐876, August 2012)
Computer Aided Diagnosis of Intractable Epilepsy with MRI Imaging Based on Textural Information

We designed a machine learning system based on a one-class support vector machine (OC-SVM) classifier in view of the detection of abnormalities in magnetic resonance images (MRIs) of patients with intractable epilepsy. This system performs a voxelwise analysis and outputs clusters of detected voxels ranked by size and suspicion degree. Features correspond to a combination of six maps: three tissue probabilities (grey matter, white matter and cerebrospinal fluid), cortical thickness, grey matter extension, and greywhite matter junction. The OC-SVM is trained using 29 controls, and tested on two patients with histologically proven focal cortical dysplasia (FCD). To assess the performance of the OC-SVM classifier, the classifier was compared with a statistical parametric mapping (SPM) single subject analysis using junction and extension maps only. The identified regions were also visually evaluated by an expert and compared to other data such as FDG-positron Emission tomography (PET) and magneto encephalography (MEG). For the two patients, both analyses agreed with the visually determined localization of the FCD lesions. No match was found for the other detected regions. The OC-SVM classifier was more specific in region localization and generated fewer false positive detections than the mass-univariate SPM approach.
Modeling propagation characteristics of multimode graded-index waveguides with finite elements using edge-based elements

Realizing electrical printed circuit boards with integrated optical interconnects for high bandwidth interconnects requires numerical models and procedures for analyzing and optimizing signal propagation within optical multimode waveguides. This paper presents a method based on the finite element method with edge elements in order to calculate the propagation constants of the guided modes of graded-index waveguides. This type of waveguides can be implemented in thin-glass applying an ion-exchange process.
Optimal Dyck reachability for data-dependence and alias analysis

A fundamental algorithmic problem at the heart of static analysis is Dyck reachability. The input is a graph where the edges are labeled with different types of opening and closing parentheses, and the reachability information is computed via paths whose parentheses are properly matched. We present new results for Dyck reachability problems with applications to alias analysis and data-dependence analysis. Our main contributions, that include improved upper bounds as well as lower bounds that establish optimality guarantees, are as follows: First, we consider Dyck reachability on bidirected graphs, which is the standard way of performing field-sensitive points-to analysis. Given a bidirected graph with n nodes and m edges, we present: (i) an algorithm with worst-case running time O(m + n · α(n)), where α(n) is the inverse Ackermann function, improving the previously known O(n2) time bound; (ii) a matching lower bound that shows that our algorithm is optimal wrt to worst-case complexity; and (iii) an optimal average-case upper bound of O(m) time, improving the previously known O(m · logn) bound. Second, we consider the problem of context-sensitive data-dependence analysis, where the task is to obtain analysis summaries of library code in the presence of callbacks. Our algorithm preprocesses libraries in almost linear time, after which the contribution of the library in the complexity of the client analysis is only linear, and only wrt the number of call sites. Third, we prove that combinatorial algorithms for Dyck reachability on general graphs with truly sub-cubic bounds cannot be obtained without obtaining sub-cubic combinatorial algorithms for Boolean Matrix Multiplication, which is a long-standing open problem. Thus we establish that the existing combinatorial algorithms for Dyck reachability are (conditionally) optimal for general graphs. We also show that the same hardness holds for graphs of constant treewidth. Finally, we provide a prototype implementation of our algorithms for both alias analysis and data-dependence analysis. Our experimental evaluation demonstrates that the new algorithms significantly outperform all existing methods on the two problems, over real-world benchmarks.
Real time monitoring of BMP Smads transcriptional activity during mouse development

Bone morphogenetic protein (BMP) signaling is a key pathway in the patterning and development of organisms as diverse as fruit fly and humans. However, the determination of net BMP signaling, paramount to understanding organogenesis, is limited to the analysis of fixed material. We generated a transgenic mouse that reports the transcriptional response of BMP Smad activation by coupling a well established BMP response element (BRE), isolated from the Id1 promoter, to green fluorescent protein (BRE:gfp). We monitored BMP Smad transcriptional activity in fresh and fixed BRE:gfp embryos. GFP expression was observed where expected on the basis of known signaling sites, but also in specific cell populations in which BMP signaling had been implicated but not directly demonstrated. Deletion of Smad5 reduced GFP in vivo as expected. The BRE:gfp transgenic mice are a novel tool, which will facilitate the identification of specific BMP Smad responsive cell types and allow BMP Smad signaling to be monitored in real time, supporting studies in development and disease. genesis 46:335–346, 2008. © 2008 Wiley‐Liss, Inc.
Chinese hotel guest perception of international chain hotels under the same hotel brand in different travel destinations

A qualitative approach was employed to examine how Chinese hotel guests perceive international chain hotels in different travel destinations (i.e. China and abroad) under the same brand. A total of 13,204 reviews were retrieved from online hotel review Web sites, namely DaoDao.com and Ctrip.com. Content analysis of the reviews showed discrepancies in the perceptions. Chinese favoritism toward the West affected the perception of hotel service quality. Empirical results revealed the belief that hotel services in Western cities and Hong Kong are better compared with those of hotels in China. However, the perception in terms of location, rooms and facilities, cleanliness, and value was mainly affected by the experience during the actual hotel stay. No noticeable influence of Chinese favoritism was found.
The multiple stressor ecological risk assessment for the mercury‐contaminated South River and upper Shenandoah River using the Bayesian network‐relative risk model

We have conducted a regional scale risk assessment using the Bayesian Network Relative Risk Model (BN‐RRM) to calculate the ecological risks to the South River and upper Shenandoah River study area. Four biological endpoints (smallmouth bass, white sucker, Belted Kingfisher, and Carolina Wren) and 4 abiotic endpoints (Fishing River Use, Swimming River Use, Boating River Use, and Water Quality Standards) were included in this risk assessment, based on stakeholder input. Although mercury (Hg) contamination was the original impetus for the site being remediated, other chemical and physical stressors were evaluated. There were 3 primary conclusions from the BN‐RRM results. First, risk varies according to location, type and quality of habitat, and exposure to stressors within the landscape. The patterns of risk can be evaluated with reasonable certitude. Second, overall risk to abiotic endpoints was greater than overall risk to biotic endpoints. By including both biotic and abiotic endpoints, we are able to compare risk to endpoints that represent a wide range of stakeholder values. Third, whereas Hg reduction is the regulatory priority for the South River, Hg is not the only stressor driving risk to the endpoints. Ecological and habitat stressors contribute risk to the endpoints and should be considered when managing this site. This research provides the foundation for evaluating the risks of multiple stressors of the South River to a variety of endpoints. From this foundation, tools for the evaluation of management options and an adaptive management tools have been forged. Integr Environ Assess Manag 2017;13:85–99. © 2016 SETAC
How does access to education influence political candidacy? Lessons from school openings in Sweden

How does availability of education affect who becomes a political representative? Theorists have pointed out access to education as a key to a well-functioning democracy, but few empirical studies have examined how changes in the access to education influence the chances of becoming a politician. In this paper we analyze the effects of a substantial series of school openings during the early 20th century in Sweden which provided adolescents with better access to secondary education. We use unique administrative data pertaining to the entire Swedish population born between 1916 and 1945. According to our empirical results the opening of a new lower secondary school in a municipality increased the baseline probability of running for political office by more than 10 percent and the probability of holding office by more than 20 percent.
Core LXXLL Motif Sequences in CREB-binding Protein, SRC1, and RIP140 Define Affinity and Selectivity for Steroid and Retinoid Receptors*

An α-helical motif containing the sequence LXXLL is required for the ligand-dependent binding of transcriptional co-activators to nuclear receptors. By using a peptide inhibition assay, we have defined the minimal “core” LXXLL motif as an 8-amino acid sequence spanning positions −2 to +6 relative to the primary conserved leucine residue. In yeast two-hybrid assays, core LXXLL motif sequences derived from steroid receptor co-activator (SRC1), the 140-kDa receptor interacting protein (RIP140), and CREB-binding protein (CBP) displayed differences in selectivity and affinity for nuclear receptor ligand binding domains. Although core LXXLL motifs from SRC1 and RIP140 mediated strong interactions with steroid and retinoid receptors, three LXXLL motifs present in the global co-activator CBP were found to have very weak affinity for these proteins. Core motifs with high affinity for steroid and retinoid receptors were generally found to contain a hydrophobic residue at position −1 relative to the first conserved leucine and a nonhydrophobic residue at position +2. Our results indicate that variant residues in LXXLL core motifs influence the affinity and selectivity of co-activators for nuclear receptors.
The Long Reach of One’s Spouse

You marry your spouse “for better, for worse” and “for richer, for poorer,” but does your choice of partner make you richer or poorer? It is unknown whether people’s dispositional characteristics can seep into their spouses’ workplace. Using a representative, longitudinal sample of married individuals (N = 4,544), we examined whether Big Five personality traits of participants’ spouses related to three measures of participants’ occupational success: job satisfaction, income, and likelihood of being promoted. For both male and female participants, partner conscientiousness predicted future job satisfaction, income, and likelihood of promotion, even after accounting for participants’ conscientiousness. These associations occurred because more conscientious partners perform more household tasks, exhibit more pragmatic behaviors that their spouses are likely to emulate, and promote a more satisfying home life, enabling their spouses to focus more on work. These results demonstrate that the dispositional characteristics of the person one marries influence important aspects of one’s professional life.
Properties of a murine retroviral recombinant of avian acute leukemia virus E26: a murine fibroblast assay for v-ets function

A replication-defective murine retroviral construct, termed pME26, was generated by inserting avian gag-myb-ets sequences derived from the cloned avian acute leukemia virus E26 into an Abelson murine leukemia virus-derived retroviral vector. ME26 virus can be rescued efficiently from transfected NIH 3T3 cells by replicating murine leukemia viruses. Either pME26-transfected nonproducers or ME26 virus-infected NIH 3T3 cells expressed a 135-kilodalton fusion protein (p135) which was detectable by immunoprecipitation with antiserum directed against avian leukemia virus p27gag, myb or ets oncogene protein, or murine leukemia virus p15gag and was principally localized in the nucleus. NIH 3T3 cells infected with ME26 exhibited morphological alterations and increased proliferation in reduced serum and formed small colonies in agar suspension. Discrete foci could be readily recognized in cells maintained in a defined medium containing 0.03 to 0.1% calf serum. In newborn NFS/N mice, ME26 induced a significantly higher mortality and incidence of erythroid and myeloid leukemias. Analysis of a series of mutants affecting the expression of various portions of p135 indicated that the v-ets gene acts to mitogenically stimulate the proliferation of NIH 3T3 fibroblasts and reduces or abolishes their serum dependence. These properties provide an assay system to study functions of the ets gene family.
Contrasting effects of copper limitation on the photosynthetic apparatus in two strains of the open ocean diatom Thalassiosira oceanica

There is an intricate interaction between iron (Fe) and copper (Cu) physiology in diatoms. However, strategies to cope with low Cu are largely unknown. This study unveils the comprehensive restructuring of the photosynthetic apparatus in the diatom Thalassiosira oceanica (CCMP1003) in response to low Cu, at the physiological and proteomic level. The restructuring results in a shift from light harvesting for photochemistry—and ultimately for carbon fixation—to photoprotection, reducing carbon fixation and oxygen evolution. The observed decreases in the physiological parameters Fv/Fm, carbon fixation, and oxygen evolution, concomitant with increases in the antennae absorption cross section (σPSII), non-photochemical quenching (NPQ) and the conversion factor (φe:C/ηPSII) are in agreement with well documented cellular responses to low Fe. However, the underlying proteomic changes due to low Cu are very different from those elicited by low Fe. Low Cu induces a significant four-fold reduction in the Cu-containing photosynthetic electron carrier plastocyanin. The decrease in plastocyanin causes a bottleneck within the photosynthetic electron transport chain (ETC), ultimately leading to substantial stoichiometric changes. Namely, 2-fold reduction in both cytochrome b6f complex (cytb6f) and photosystem II (PSII), no change in the Fe-rich PSI and a 40- and 2-fold increase in proteins potentially involved in detoxification of reactive oxygen species (ferredoxin and ferredoxin:NADP+ reductase, respectively). Furthermore, we identify 48 light harvesting complex (LHC) proteins in the publicly available genome of T. oceanica and provide proteomic evidence for 33 of these. The change in the LHC composition within the antennae in response to low Cu underlines the shift from photochemistry to photoprotection in T. oceanica (CCMP1003). Interestingly, we also reveal very significant intra-specific strain differences. Another strain of T. oceanica (CCMP 1005) requires significantly higher Cu concentrations to sustain both its maximal and minimal growth rate compared to CCMP 1003. Under low Cu, CCMP 1005 decreases its growth rate, cell size, Chla and total protein per cell. We argue that the reduction in protein per cell is the main strategy to decrease its cellular Cu requirement, as none of the other parameters tested are affected. Differences between the two strains, as well as differences between the well documented responses to low Fe and those presented here in response to low Cu are discussed.
Writing current reduction for high-density phase-change RAM

By developing a chalcogenide memory element that can be operated at low writing current, we have demonstrated the possibility of high-density phase-change random access memory. We have investigated the phase transition behaviors as a function of various process factors including contact size, cell size and thickness, doping concentration in chalcogenide material and cell structure. As a result, we have observed that the writing current is reduced down to 0.7 mA.
Phase I trial of carboplatin and infusional cyclosporin in advanced malignancy.

PURPOSE To determine the maximal-tolerated dose (MTD) of infusional cyclosporine (CSA) with fixed-dose carboplatin (CBDCA). PATIENTS AND METHODS Clonogenic cytotoxicity assays were performed to assess the effect of CSA on reversal of resistance to CBDCA. The phase I study was performed in three phases. In phases 1 and 2, escalating-dose CSA (5, 7.5, 8.8, or 9.5 mg/kg/d) with fixed-dose CBDCA 300 or 250 mg/m2 were administered. Phase 3 required an initial cycle of CBDCA 250 mg/m2 alone, followed by combination therapy with CBDCA 250 mg/m2 and CSA (8.8, 9.5, or 10.0 mg/kg/d). RESULTS Preincubation of platinum-resistant A2780 human ovarian cancer cells with CSA 2 micrograms/mL significantly enhanced CBDCA cytotoxicity in clonogenic assays. Fifty-one patients received 130 courses of therapy. The phase 1 MTD was thrombocytopenia (CSA 7.5 mg/kg/d and CBDCA 300 mg/m2) attributable to the effects of CBDCA alone. The phase 2 MTD was reversible nephrotoxicity (serum creatinine elevations to 3.6 and 4.4 mg/dL) and neutropenia (CSA 9.5 mg/kg/d and CBDCA 250 mg/m2). In phase 3, headache was observed in five patients and hypertension in one patient at CSA 10 mg/kg/d. The expected change in platelet count predicted for CBDCA alone was compared with the actual change; no excessive thrombocytopenia was observed with addition of CSA. Steady-state CSA levels of 2 micrograms/mL capable of reversing platinum resistance in vitro were observed. Four objective responses were observed. CONCLUSION CSA is effective in reversing CBDCA resistance in A2780 ovarian cancer cells. Short-term infusions of CSA < or = 8.8 mg/kg/d in combination with CBDCA are well-tolerated for heavily pretreated patients and result in CSA levels known to reverse CBDCA resistance in vitro.