Miracle-dz/UniFAR-FTUs huggingface dataset:
Rho GTPases are involved in the regulation of NF-kappaB by genotoxic stress.

A common cellular response to genotoxic agents and inflammatory cytokines is the activation of NF-kappaB. Here, we addressed the question of whether small GTPases of the Rho family are involved in the stimulation of NF-kappaB signaling by genotoxic agents or TNFalpha in HeLa cells. Inhibition of isoprenylation of Rho proteins by use of the HMG-CoA reductase inhibitor lovastatin attenuated UV-, doxorubicin-, and TNFalpha-induced degradation of IkappaBalpha as well as drug-stimulated DNA binding activity of NF-kappaB. Furthermore, NF-kappaB-regulated gene expression stimulated by either UV irradiation or treatment with TNFalpha was abrogated by lovastatin pretreatment. This indicates that isoprenylated regulatory proteins participate in the regulation of NF-kappaB by DNA-damaging agents as well as by TNFalpha. Specific blockage of Rho signaling by Clostridium difficile toxin B attenuated UV- and doxorubicin-induced activation of NF-kappaB, but did not affect stimulation of NF-kappaB by TNFalpha. Obviously, signaling to NF-kappaB by genotoxic and nongenotoxic stimuli occurs via different molecular mechanisms, either involving Rho GTPases or not. Based on the data, we suggest Rho GTPases to be essentially required for genotoxic stress-induced signaling to NF-kappaB.
Virus Spread in Networks

The influence of the network characteristics on the virus spread is analyzed in a new-the <i>N</i> -intertwined Markov chain-model, whose only approximation lies in the application of mean field theory. The mean field approximation is quantified in detail. The <i>N</i> -intertwined model has been compared with the exact 2<sup>N</sup>-state Markov model and with previously proposed ldquohomogeneousrdquo or ldquolocalrdquo models. The sharp epidemic threshold tau<sub>c</sub> , which is a consequence of mean field theory, is rigorously shown to be equal to tau<sub>c</sub> = 1/(lambda<sub>max</sub>(<i>A</i>)) , where lambda<sub>max</sub>(<i>A</i>) is the largest eigenvalue-the spectral radius-of the adjacency matrix <i>A</i> . A continued fraction expansion of the steady-state infection probability at node <i>j</i> is presented as well as several upper bounds.
A Flexible and Efficient Higher Order FE-BI-MLFMA for Scattering by a Large Body With Deep Cavities

The hybrid finite element-boundary integral-multilevel fast multipole algorithm (FE-BI-MLFMA) is applied to solve the challenge problem of scattering by a large body with deep cavities in this paper. The hierarchical higher order curvilinear vector finite element (HCVFE) is employed to reduce the numerical dispersion error in the FEM and to efficiently model the geometry of the cavity. The coupling approaches are investigated at the interface between the FE region and the BI region for handling the problem of the different order basis functions and meshes used in the FE and BI region. The problems encountered with the previous decomposition algorithm of FE-BI-MLFMA are pointed out and analyzed in this paper. A special algorithm of FE-BI-MLFMA is designed based on the distinct geometry characteristics of deep cavity. Numerical results are presented to demonstrate the accuracy, efficiency and flexibility of the higher order FE-BI-MLFMA for scattering by a large body with big and deep cavities.
E-mail Survey Response Rates: A Review

Electronic mail (e-mail) has been used to distribute surveys and collect data from online users for almost fifteen years. However, some have suggested that the use of e-mail is becoming obsolete. This study analyzes response rates to e-mail surveys undertaken since 1986 and examines five influences to response rates: the year the study was undertaken, the number of questions in the survey, the number of pre-notification contacts, the number of follow-up contacts and survey topic salience. Response rates to e-mail surveys have significantly decreased since 1986. Correlation and regression analyses suggest that year that the survey was undertaken and number of follow-up contacts had the most influence on response rates. A discussion of other influences and future research into this area is provided.
A Framework to Assist Health Professionals in Recommending High-Quality Apps for Supporting Chronic Disease Self-Management: Illustrative Assessment of Type 2 Diabetes Apps

Background This paper presents an approach to assist health professionals in recommending high quality apps for supporting chronic disease self-management. Most app reviews focus on popularity, aesthetics, functionality, usability, and information quality. There is no doubt these factors are important in selecting trustworthy apps which are appealing to users, but behavioral theory may be also be useful in matching the apps to user needs. Objective The framework developed aims to be methodologically sound, capable of selecting popular apps which include content covered by evidence-based programs, consistent with behavioral theory, as well as a patient-centered approach for matching apps to patients’ individual needs. Methods A single disease—type 2 diabetes—was selected to illustrate how the framework can be applied as this was deemed to represent the types of strategies used in many chronic diseases. A systematic approach based on behavioral theory and recommendations from best practice guidelines was developed for matching apps to patients’ needs. In March 2014, a series of search strategies was used to identify top-rated iPhone and Android health apps, representing 29 topics from five categories of type 2 diabetes self-management strategies. The topics were chosen from published international guidelines for the management of diabetes. The senior author (KH) assessed the most popular apps found that addressed these topics using the Behavioral Theory Content Survey (BTS), which is based on traditional behavioral theory. A tool to assist decision making when using apps was developed and trialed with health professionals for ease of use and understanding. Results A total of 14 apps were assessed representing all five topic categories of self-management. Total theoretical scores (BTS scores) were less than 50 on a 100-point scale for all apps. Each app scored less than 50% of the total possible BTS score for all four behavioral theories and for most of the 20 behavioral strategies; however, apps scored higher than 50% of the total possible BTS score for specific strategies related to their primary focus. Our findings suggest that the apps studied would be more effective when used in conjunction with therapy than as stand-alone apps. Apps were categorized according to topic and core intervention strategies. A framework for matching apps to identified patient needs was developed based on app categorization and principles of patient-centered care. The approach was well accepted and understood by a convenience sample of health practitioners. Conclusions The framework presented can be used by health practitioners to better match apps with client needs. Some apps incorporate highly interactive strategies of behavioral theory, and when used as an adjunct may increase patient participation and the effectiveness of therapy.
The Association of a SNP Upstream of INSIG2 with Body Mass Index is Reproduced in Several but Not All Cohorts

A SNP upstream of the INSIG2 gene, rs7566605, was recently found to be associated with obesity as measured by body mass index (BMI) by Herbert and colleagues. The association between increased BMI and homozygosity for the minor allele was first observed in data from a genome-wide association scan of 86,604 SNPs in 923 related individuals from the Framingham Heart Study offspring cohort. The association was reproduced in four additional cohorts, but was not seen in a fifth cohort. To further assess the general reproducibility of this association, we genotyped rs7566605 in nine large cohorts from eight populations across multiple ethnicities (total n = 16,969). We tested this variant for association with BMI in each sample under a recessive model using family-based, population-based, and case-control designs. We observed a significant (p < 0.05) association in five cohorts but saw no association in three other cohorts. There was variability in the strength of association evidence across examination cycles in longitudinal data from unrelated individuals in the Framingham Heart Study Offspring cohort. A combined analysis revealed significant independent validation of this association in both unrelated (p = 0.046) and family-based (p = 0.004) samples. The estimated risk conferred by this allele is small, and could easily be masked by small sample size, population stratification, or other confounders. These validation studies suggest that the original association is less likely to be spurious, but the failure to observe an association in every data set suggests that the effect of SNP rs7566605 on BMI may be heterogeneous across population samples.
Clinical Trials of Adult T-Cell Leukaemia/Lymphoma Treatment

Adult T-cell leukaemia/lymphoma (ATLL) is an aggressive malignancy of mature activated T cells caused by human T-cell lymphotropic virus type I (HTLV-1). Prognosis is severe because of intrinsic chemoresistance and severe immuosuppression. Four different subtypes are described with different outcomes, and treatment strategies vary according to the different clinical courses. Japanese trials show that combinations of chemotherapy can increase the response rates especially in the lymphoma subtype. However, patients have a high rate of relapse and the outcome remains extremely poor. Recently, a worldwide meta-analysis demonstrated that the combination of Zidovudine and Interferon-alpha (IFN) is effective in the leukemic subtypes (smoldering, chronic, and acute) and influences favorably the course of the disease. In order to prevent relapse, clinical trials testing new drugs such as monoclonal antibodies or combinations such as arsenic/IFN are needed. Finally, allogeneic stem cell transplantation is a feasible option but bears a very high rate of complications.
Fired up or burned out? Exploring the effects of leadership challenge demands on leadership behaviors through engagement and burnout

Leadership research has traditionally explored the consequences of leadership behaviors while giving far less attention to understanding why leaders behave the way they do toward subordinates. Moreover, the few theoretical frameworks and studies that do address antecedents of leadership behavior have focused almost entirely on personality and other individual differences while largely overlooking situational determinants, particularly proximal situational determinants that would help explain why a variety of leadership behaviors exist at varying levels in the same organization. To fill these gaps in theory and research, this dissertation proposes that leaders’ job demands may serve as a proximal situational determinant of “constructive” and “destructive” forms of leadership. Specifically, by integrating transactional stress theory and the challenging job assignments model, I introduce the construct of leadership challenge demands and propose a theoretical model that depicts the process whereby leadership challenge demands come to influence three types of leadership behavior: transformational leadership, abusive supervision, and passive leadership. In essence, the model depicts two competing reactions that leaders may have to leadership challenge demands. On one hand, leaders high on leadership self-efficacy are proposed to react favorably to leadership challenge demands through feelings of engagement and therefor exhibit transformational leadership. On the other hand, leaders low in leadership self-efficacy are proposed to react negatively to leadership challenge demands through feelings of burnout and therefore exhibit passive leadership or abusive supervision. The hypothesized model was tested in a sample of 153 managers and 631 direct reports at a Fortune 500 company. Results showed that while leadership challenge demands are
A Major Fraction of Endoplasmic Reticulum-located Glutathione Is Present as Mixed Disulfides with Protein*

The tripeptide glutathione is the most abundant thiol/disulfide component of the eukaryotic cell and is known to be present in the endoplasmic reticulum lumen. Accordingly, the thiol/disulfide redox status of the endoplasmic reticulum lumen is defined by the status of glutathione, and it has been assumed that reduced and oxidized glutathione form the principal redox buffer. We have determined the distribution of glutathione between different chemical states in rat liver microsomes by labeling with the thiol-specific label monobromobimane and subsequent separation by reversed phase high performance liquid chromatography. More than half of the microsomal glutathione was found to be present in mixed disulfides with protein, the remainder being distributed between the reduced and oxidized forms of glutathione in the ratio of 3:1. The high proportion of the total population of glutathione that was found to be in mixed disulfides with protein has significant implications for the redox state and buffering capacity of the endoplasmic reticulum and, hence, for the formation of disulfide bonds in vivo.
Analysis and Improvements of Zapping Times in IPTV Systems

IPTV is becoming a serious alternative to traditional broadcast schemes, such as cable, satellite or terrestrial, to deliver TV to the home. However, the expectation of the user is that IPTV provides the same or even better quality of experience (QoE). An important part of QoE for linear TV services is the channel change time (CCT) also known as zapping time. Due to its relevance many ideas and concepts have been published which describe how to optimize or speed up the CCT. First, to be able to judge the challenges and benefits of the available concepts, a common understanding of the contributors to the CCT is necessary. This article provides an overview of all elements in the IPTV end-to-end chain influencing the CCT from the head end down to the set-top box (STB) and finally to the display. Second, various techniques for reducing the CCT are presented and discussed.
Clinical course in Crohn's disease: Results of a five-year population-based follow-up study (the IBSEN study)

Background. There are few population-based, prospective studies on the clinical course in patients with Crohn's disease (CD). Aim. To extend the observation period in a population-based prospective study (the IBSEN study) to find out more about the initial 5-year clinical course in CD patients and to relate the findings to the Vienna classification. Methods. All patients diagnosed with inflammatory bowel disease (IBD) in southeastern Norway in the 4 years 1990–1993 were followed prospectively. The patients were invited to a systematic follow-up visit at their local hospital 1 and 5 years after inclusion in the study. The visits included a structured interview, a clinical examination and colonoscopy. Results. Out of 843 patients initially diagnosed with IBD, 200 patients with definite CD were alive and had sufficient data for analysis 5 years after diagnosis. Changes in disease localization and behaviour in relation to the Vienna classification were observed in 27 (13.5%) and 35 patients (17.5%), respectively. During the observation period, 56 patients (28%) underwent surgery with intestinal resection, and half of these had disease localized in the terminal ileum. At the time of the 5-year visit, oral sulfasalazin and 5-aminosalicylic acid (5-ASA) were the most frequently used medications (by 54% of the patients), while oral glucocorticosteroids and azathioprine were being used by 25% and 13%, respectively. Seventy-two percent of the patients had taken oral glucocorticosteroids at some time in the course of the 5-year period. The majority of the patients had intestinal symptoms at 5 years, but only 16% had symptoms that interfered with everyday activities. Fourteen percent of the patients had had a relapse-free 5-year course; however, relapse was not related to the initial Vienna classification. When the patients described the clinical course, 44% reported an improvement in symptoms during the follow-up period. Conclusions: The 5-year clinical course in an unselected cohort of CD patients was mostly mild. The frequency of surgery was lower than that observed in other studies and only a minority of the patients had symptoms that interfered with everyday activities 5 years after the initial diagnosis. The Vienna classification predicted the risk of surgery, but did not predict symptoms at 5 years, relapses during the observation period or the course of disease as described by the patients.
Rituximab serum concentrations during immuno-chemotherapy of follicular lymphoma correlate with patient gender, bone marrow infiltration and clinical response

Background Treatment of follicular lymphoma with rituximab is currently recommended at a dose of 375 mg/m2. We aimed to provide a rationale for optimal dosing and scheduling of this anti-CD20 antibody based on pharmacokinetics. Design and Methods Clinical efficacy of immunochemotherapy with rituximab, fludarabine and mitoxantrone followed by 2-monthly rituximab maintenance was evaluated in 29 patients with previously untreated follicular lymphoma in a prospective phase II trial (AGMT-NHL9). Pharmacokinetic analysis was assessed in 17 patients. Results Induction treatment resulted in high clinical response rates (complete remission 66%; ORR 100%). Significantly higher complete remission rates were observed in female patients (86 vs. 47%; Odds Ratio 6.8, 95% CI: 1.12; 41.82; P=0.05). Rituximab pharmacokinetic analysis showed a high variability ranging over almost 1 order of magnitude at maintenance cycle 1 (area under the curve 1,540–12,025 g/L*days). Median area under the curve was lower in men (81%) and in patients with initial bone marrow infiltration (76%). Higher rituximab serum concentrations before next therapy (Ctrough) were associated with female sex (P=0.04) as well as with absence of initial bone marrow infiltration (P=0.001). Ctrough correlated with remission quality (complete vs. partial remission; P=0.005) and progression-free survival (P=0.03). A decline in rituximab Ctrough below 25,000 ng/mL was observed 9.5 to 62 months before clinical relapse (P=0.008). Conclusions The results of this pilot trial suggest that more differentiated dosing schedules based on gender and bone marrow infiltration should be explored for rituximab therapy for lymphoma. This study was registered in ClinicalTrials.gov (Identifier: NCT01560117).
Expression of ciliary neurotrophic factor (CNTF) and its tripartite receptor complex by cells of the human optic nerve head

Purpose Ciliary neurotrophic factor (CNTF) promotes gene expression, cell survival and differentiation in various types of peripheral and central neurons, glia and nonneural cells. The level of CNTF rises rapidly upon injury to neural tissue, suggesting that CNTF exerts its cytoprotective effects after release from cells via mechanisms induced by cell injury. The purpose of this study was to determine if cells in the optic nerve head express CNTF and its tripartite receptor complex. Methods Well-established optic nerve head astrocytes (ONHA) and lamina cribrosa (LC) cell cultures were derived from normal human donors. Total RNA was reverse transcribed and polymerase chain reaction (PCR) amplified for mRNA detection. Cytoplasmic protein expression was determined by immunocytochemistry and Western blot analysis of the cellular lysates. Serum free medium was concentrated and used for detecting extracellular proteins. CNTF complexed with CNTFR-α was assayed by immunoprecipitation. Results Cells isolated from the human optic nerve head express CNTF and its tripartite receptor complex members (CNTFR-α, gp130, LIFR-β). Conclusions Taken together, these data suggest a possible neuroprotective role of CNTF in the optic nerve head.
Quality of life in amyotrophic lateral sclerosis/motor neuron disease: A structured review

Amyotrophic lateral sclerosis/motor neuron disease and other related disorders are fatal progressive neurodegenerative conditions that have a substantial impact on quality of life (QoL). This systematic review examines the different methods and instruments used to assess QoL in this condition from which recommendations are made of those that evidence suggests are the most appropriate. Databases were used to survey the available literature to cover as many different approaches and papers as possible. Due to the wide variety of approaches to the measurement of QoL data across the papers, no meta-analysis was possible. The available evidence suggests that at the present time the most appropriate measures are the SF-36, a generic widely used QoL measure, and the disease specific ALSAQ-40. However, as many of the validation studies on the ALSAQ-40 were undertaken by the developers of this instrument, further independent research is desirable to confirm these conclusions.
Crystal structure of UDP‐N‐acetylmuramoyl‐L‐alanine:D‐glutamate ligase from Escherichia coli

UDP‐N‐acetylmuramoyl‐L‐alanine:D‐glutamate ligase (MurD) is a cytoplasmic enzyme involved in the biosynthesis of peptidoglycan which catalyzes the addition of D‐glutamate to the nucleotide precursor UDP‐N‐acetylmuramoyl‐L‐alanine (UMA). The crystal structure of MurD in the presence of its substrate UMA has been solved to 1.9 Å resolution. Phase information was obtained from multiple anomalous dispersion using the K‐shell edge of selenium in combination with multiple isomorphous replacement. The structure comprises three domains of topology each reminiscent of nucleotide‐binding folds: the N‐ and C‐terminal domains are consistent with the dinucleotide‐binding fold called the Rossmann fold, and the central domain with the mononucleotide‐binding fold also observed in the GTPase family. The structure reveals the binding site of the substrate UMA, and comparison with known NTP complexes allows the identification of residues interacting with ATP. The study describes the first structure of the UDP‐N‐acetylmuramoyl‐peptide ligase family.