Miracle-dz/UniFAR-FTUs huggingface dataset:
In vivo and in vitro functional characterization of Andersen's syndrome mutations

The inward rectifier K+ channel Kir2.1 carries all Andersen's syndrome mutations identified to date. Patients exhibit symptoms of periodic paralysis, cardiac dysrhythmia and multiple dysmorphic features. Here, we report the clinical manifestations found in three families with Andersen's syndrome. Molecular genetics analysis identified two novel missense mutations in the KCNJ2 gene leading to amino acid changes C154F and T309I of the Kir2.1 open reading frame. Patch clamp experiments showed that the two mutations produced a loss of channel function. When co‐expressed with Kir2.1 wild‐type (WT) channels, both mutations exerted a dominant‐negative effect leading to a loss of the inward rectifying K+ current. Confocal microscopy imaging in HEK293 cells is consistent with a co‐assembly of the EGFP‐fused mutant proteins with WT channels and proper traffick to the plasma membrane to produce silent channels alone or as hetero‐tetramers with WT. Functional expression in C2C12 muscle cell line of newly as well as previously reported Andersen's syndrome mutations confirmed that these mutations act through a dominant‐negative effect by altering channel gating or trafficking. Finally, in vivo electromyographic evaluation showed a decrease in muscle excitability in Andersen's syndrome patients. We hypothesize that Andersen's syndrome‐associated mutations and hypokalaemic periodic paralysis‐associated calcium channel mutations may lead to muscle membrane hypoexcitability via a common mechanism.
Sexuality: Experience of Women with Physical Disabilities

It was aimed to describe the experiences at the practice of sexuality of women with physical disabilities. This study is part of a doctoral thesis entitled sexuality in women with acquired deficiency: nursing in health promotion and empowerment. It was conducted an exploratory descriptive study with qualitative approach, which was carried out from June to October, in the year of 2010. The survey participants were six women members of an association of people with physical disabilities. Data collection was based on focal group. Analysis and discussion by means of the classification of the speeches were performed according to the analysis of content and pertinent literature. In the results, the following categories and sub-categories were identified: concepts, covering self-image and sexuality; social actors, responsible for the promotion of sexuality, with highlight for men, family and health professionals; challenges experienced in the practice of sexuality, with highlight on prejudice and fear of sexual abuse due to the disability. We could state that the focus groups favored the discussion and the self-knowledge of the women with respect to sexuality.
Chatbots and conversational agents: A bibliometric analysis

Chatbots are replacing some of the jobs that are traditionally performed by human workers, such as online customer service agents and educators. From the initial stage of rule-based chatbots to the era of rapid development in artificial intelligence (AI), the performance of chatbots keeps improving. Chatbots can nowadays “chat” like a human being and they can learn from experience. The purpose of this research is to examine the past research on chatbots (also known as conversational agents) using the quantitative bibliometric analysis. The contribution of this research is to help researchers to identify research gaps for the future research agenda in chatbots. The results of the analysis found a potential research opportunity in chatbots due to the emergence of the deep learning technology. This new technology may change the direction of future research in chatbots. Several recommendations for future research are provided based on the results obtained from our analysis.
Stromal cell–derived factor 2 is critical for Hsp90-dependent eNOS activation

SDF2 promotes the activation of the enzymes that produce the gasotransmitter nitric oxide. Maximizing nitric oxide production The gas nitric oxide causes blood vessels to relax and blood pressure to drop. In endothelial cells, the enzyme eNOS produces nitric oxide. The chaperone protein Hsp90 promotes the activation of eNOS by enhancing its phosphorylation. Siragusa et al. found that SDF2 bound eNOS, enhancing the phosphorylation of eNOS and NO production by promoting the binding of eNOS to Hsp90. Endothelial nitric oxide synthase (eNOS) catalyzes the conversion of l-arginine and molecular oxygen into l-citrulline and nitric oxide (NO), a gaseous second messenger that influences cardiovascular physiology and disease. Several mechanisms regulate eNOS activity and function, including phosphorylation at Ser and Thr residues and protein-protein interactions. Combining a tandem affinity purification approach and mass spectrometry, we identified stromal cell–derived factor 2 (SDF2) as a component of the eNOS macromolecular complex in endothelial cells. SDF2 knockdown impaired agonist-stimulated NO synthesis and decreased the phosphorylation of eNOS at Ser1177, a key event required for maximal activation of eNOS. Conversely, SDF2 overexpression dose-dependently increased NO synthesis through a mechanism involving Akt and calcium (induced with ionomycin), which increased the phosphorylation of Ser1177 in eNOS. NO synthesis by iNOS (inducible NOS) and nNOS (neuronal NOS) was also enhanced upon SDF2 overexpression. We found that SDF2 was a client protein of the chaperone protein Hsp90, interacting preferentially with the M domain of Hsp90, which is the same domain that binds to eNOS. In endothelial cells exposed to vascular endothelial growth factor (VEGF), SDF2 was required for the binding of Hsp90 and calmodulin to eNOS, resulting in eNOS phosphorylation and activation. Thus, our data describe a function for SDF2 as a component of the Hsp90-eNOS complex that is critical for signal transduction in endothelial cells.
The Mitochondrial Complex(I)ty of Cancer

Recent evidence highlights that the cancer cell energy requirements vary greatly from normal cells and that cancer cells exhibit different metabolic phenotypes with variable participation of both glycolysis and oxidative phosphorylation. NADH–ubiquinone oxidoreductase (Complex I) is the largest complex of the mitochondrial electron transport chain and contributes about 40% of the proton motive force required for mitochondrial ATP synthesis. In addition, Complex I plays an essential role in biosynthesis and redox control during proliferation, resistance to cell death, and metastasis of cancer cells. Although knowledge about the structure and assembly of Complex I is increasing, information about the role of Complex I subunits in tumorigenesis is scarce and contradictory. Several small molecule inhibitors of Complex I have been described as selective anticancer agents; however, pharmacologic and genetic interventions on Complex I have also shown pro-tumorigenic actions, involving different cellular signaling. Here, we discuss the role of Complex I in tumorigenesis, focusing on the specific participation of Complex I subunits in proliferation and metastasis of cancer cells.
Application of Partially Conducting Polymeric Materials for High Voltage Outdoor Insulator in Polluted Environments

Partially conducting polymers are investigated for high voltage outdoor insulation as a possible solution to the pollution flashover p-roblems. The polymers studied include polyurethane, Silicone rubber and epoxies. Silicon carbide was added to achieve electrical conduction. Composite materials have been developed which show promise for the proposed application. Results of the investigation are discussed.
Health and income: a meta-analysis to explore cross-country, gender and age differences.

BACKGROUND Evidence of an effect of income on self-reported poor health (SRPH) is widely available in the literature. We compare this effect across age, different countries and between men and women using meta-analysis. Studies that report on an effect of income lack a homogenous effect size. To overcome this problem we propose a method to derive a homogenous effect size to enable us to compare the effect of income across groups. METHODS We take a meta-analytical approach to examine the effect of income on SRPH. The data consists of reported and calculated odds ratios as a measure of effect for SRPH outcomes across different income categories. Self-reported health outcomes are dichotomised into 'good' and 'poor'. With least-squares techniques, we estimate the functional parameters that describe the log-linear association between income and SRPH. Subsequently, F-tests are performed to show variations between the groups. RESULTS The relationship between income and SRPH is log-linear for most countries but not significantly for Sweden and the Netherlands. Our results show significant differences in the effect of income between countries. We find that men require a higher income than women to achieve comparable SRPH outcomes, and that the effect of income depends on age. CONCLUSIONS There is significant income related variation in SRPH between different countries even if the levels of income or the standards of living are comparable. For women income affects SRPH differently than for men. The effect of income on SRPH depends on the age of the individual respondent.
Dynamic Mode Decomposition for perturbation estimation in human robot interaction

In many settings, e.g. physical human-robot interaction, robotic behavior must be made robust against more or less spontaneous application of external forces. Typically, this problem is tackled by means of special purpose force sensors which are, however, not available on many robotic platforms. In contrast, we propose a machine learning approach suitable for more common, although often noisy sensors. This machine learning approach makes use of Dynamic Mode Decomposition (DMD) which is able to extract the dynamics of a nonlinear system. It is therefore well suited to separate noise from regular oscillations in sensor readings during cyclic robot movements under different behavior configurations. We demonstrate the feasibility of our approach with an example where physical forces are exerted on a humanoid robot during walking. In a training phase, a snapshot based DMD model for behavior specific parameter configurations is learned. During task execution the robot must detect and estimate the external forces exerted by a human interaction partner. We compare the DMD-based approach to other interpolation schemes and show that the former outperforms the latter particularly in the presence of sensor noise. We conclude that DMD which has so far been mostly used in other fields of science, particularly fluid mechanics, is also a highly promising method for robotics.
Exercise-Induced Intrapulmonary Arteriovenous Shunting and Pulmonary Gas Exchange

Recent research suggests the recruitment of intrapulmonary shunt vessels during exercise, which may contribute to the exercise-induced impairment in pulmonary gas exchange. These findings are consistent with substantial anatomical data demonstrating large-diameter (>25 &mgr;m) anatomical shunts in the lung, but are contrary to the considerable functional gas exchange-dependent research that has not detected right-to-left physiological shunt during exercise.
Complete Resolution of a Recurrent Canine Anal Sac Squamous Cell Carcinoma with Palliative Radiotherapy and Carboplatin Chemotherapy

Anal sac squamous cell carcinoma (SCC) is a rare tumor in dogs. Only eight cases have been described in the literature, and previous reports of treatment only describe surgery or palliative treatment with non-steroidal anti-inflammatory drugs. We report a case of a 12-year-old female neutered Labrador with locally advanced anal sac SCC. The dog was treated with four cycles of carboplatin 300 mg/m2 and four weekly fractions of 8.5 Gy radiation. The dog achieved a complete response, and one year later the dog is still alive and well with no evidence of tumor recurrence. Radiotherapy in combination with carboplatin chemotherapy was effective in the long-term control of this rare disease.
A supply and Demand approach to the Institutional Performance of Haiti

The recent political crisis in Haiti, the poorest country in the western hemisphere, has again called the attention of the international community This paper tries to describe the development path of Haiti, and advances some hypotheses explaining its reasons, Since the traditional explanations proposed by Marxists and neoclassical economists seem to be insufficient, this paper offers an Institutional approach to improve our understanding of the causes of poverty in Haiti and to visualize policy solutions. The claim is that the supply and demand of enforceable institutions had been low, due to suboptimal strategies played by the dictators and the public/army. The suboptimal equilibrium has been predate/disobey the law, and predate/organize a cue. This hypothesis reinforces Douglass North's idea of ‘path dependence, and suggests that more education and/or the reduction of the scope of government could be long- term solutions for the repeated political economy problems that Haiti has experienced during the past 200 years.
Identification of new sensitive biomarkers for the in vivo response to interferon‐β treatment in multiple sclerosis using DNA‐array evaluation

Objective: Neutralizing antibodies (NAbs) occur in a proportion of multiple sclerosis (MS) patients treated with interferon (IFN)‐β. NAbs impair the effect of treatment. The biological effect of IFN‐β can be measured as the induction of the myxovirus resistance protein A (MxA) molecule. However, other markers could be more sensitive for evaluating the response to IFN‐β. We used DNA array analysis to identify genes that are strongly induced in blood cells by IFN‐β, and measured their expression in MS patients with different NAb levels.
Cytomegalovirus DNA can be detected in peripheral blood mononuclear cells from all seropositive and most seronegative healthy blood donors over time

BACKGROUND: A poor correlation between cytomegalovirus (CMV) seroreactivity and the risk of CMV transmission prompted an investigation of the presence of CMV DNA in peripheral blood mononuclear cells (PBMNCs) from seropositive and seronegative blood donors. Because latent CMV exists in monocytes, monocyte‐enriched cells were analyzed separately. STUDY DESIGN AND METHODS: Samples from 270 blood donors were tested with a sensitive polymerase chain reaction (PCR) test that detects two CMV genes, and the results were correlated to CMV serology. Cross‐reactivity with other herpesvirus genes was not recorded. RESULTS: PCR testing demonstrated that 71 percent of seropositive donors harbor CMV in PBMNCs. Thus, not all seropositive donors were CMV DNA positive when individual samples were tested. Tests repeated over a period of time showed that all seropositive individuals were positive. Increased sensitivity was obtained with enriched monocytes. Among seronegative donors, 55 percent harbored CMV DNA in monocyte‐enriched PBMNCs, while 14 percent had CMV DNA in PBMNCs. CONCLUSION: All seropositive donors harbored latently infected PBMNCs, as demonstrated by the testing of samples collected over time. In addition, a substantial proportion of seronegative individuals are CMV carriers and might transfer infection. The findings concur with clinical evidence of CMV transmission by blood components from seronegative individuals and with in vitro reactivation of CMV in PBMNCs from seronegative donors.
Notch3 Activation Is Sufficient but Not Required for Inducing Human T-Lineage Specification

Although the role for the individual Notch receptors in early hematopoiesis have been thoroughly investigated in mouse, studies in human have been mostly limited to the use of pan-Notch inhibitors. However, such studies in human are important to predict potential side effects of specific Notch receptor blocking reagents because these are currently being considered as therapeutic tools to treat various Notch-dependent diseases. In this study, we studied the individual roles of Notch1 and Notch3 in early human hematopoietic lineage decisions, particularly during T-lineage specification. Although this process in mice is solely dependent on Notch1 activation, we recently reported Notch3 expression in human uncommitted thymocytes, raising the possibility that Notch3 mediates human T-lineage specification. Although expression of a constitutive activated form of Notch3 (ICN3) results in the induction of T-lineage specification in human CD34+ hematopoietic progenitor cells, similar to ICN1 overexpression, loss-of-function studies using blocking Abs reveal that only Notch1, but not Notch3, is critical in this process. Blocking of Notch1 activation in OP9-DLL4 cocultures resulted in a complete block in T-lineage specification and induced monocytic and plasmacytoid dendritic cell differentiation instead. In fetal thymus organ cultures, impeded Notch1 activation resulted in B and dendritic cell development. In contrast, Notch3 blocking Abs only marginally affected T-lineage specification and hematopoietic differentiation with a slight increase in monocyte development. No induction of B or dendritic cell development was observed. Thus, our results unambiguously reveal a nonredundant role for Notch1 in human T-lineage specification, despite the expression of other Notch receptors.
Levetiracetam, Phenytoin, and Valproate Act Differently on Rat Bone Mass, Structure, and Metabolism

Summary: Purpose: Long‐term treatment with antiepileptic drugs (AEDs) is associated with increased risk of fractures. Phenytoin (PHT) and valproate (VPA) have both been suggested to influence bone health, whereas levetiracetam (LEV) is scarcely studied. The present study compares the effect of these AEDs on bone mass, biomechanical strength, and bone turnover in rats.
Detection of serum hepatitis C virus RNA in HCV antibody‐seropositive volunteer blood donors

Approximately 90% of subjects with chronic hepatitis resulting from hepatitis C virus infection have hepatitis C virus RNA in serum. However, the prevalence of hepatitis C virus RNA in serum from subjects with hepatitis C virus antibody associated with persistent normal liver biochemical values is unclear. Do these subjects have resolved or continuing infection with hepatitis C virus? The aim of this study was to examine whether subjects with hepatitis C virus antibody but normal ALT levels had evidence of ongoing infection. Our study population was divided into four groups. Groups 1, 2 and 3 comprised hepatitis C virus antibody‐positive volunteer blood donors. Group 1 was made up of subjects found to be hepatitis C virus antibody‐positive on enzyme‐linked immunosorbent assay with persistent abnormal ALT levels (59 donors: 53 positive on recombinant immunoblot assay and 6 indeterminate). Group 2 members were hepatitis C virus antibody positive, with persistent normal ALT levels (50 donors: 39 positive on recombinant immunoblot assay and 11 indeterminate). Group 3 members were hepatitis C virus seropositive but negative on second‐generation recombinant immunoblot assay (n = 48). Twenty patients (not blood donors) with chronic liver disease who were anti‐hepatitis C virus seronegative were used as controls (group 4). Serum samples from all four groups were assayed for hepatitis C virus RNA on reverse transcription and a 40‐cycle polymerase chain reaction with a combination of primers from the highly conserved 5′‐noncoding and less‐conserved third and fourth nonstructural regions. All assays were confirmed on hybridization with an internal probe. In group 1,55 of 59 subjects (93.2%) had hepatitis C virus RNA in serum. In group 2, 21 of 50 subjects (42%) had hepatitis C virus RNA in serum. Twenty‐one of the 39 recombinant immunoblot assay‐positive subjects (53.9%) had hepatitis C virus RNA, compared with none of the 11 recombinant immunoblot assay‐indeterminant subjects (p = 0.001 on x2 assay). In recombinant immunoblot assay‐positive subjects with normal ALT readings less than 1 mo apart, 7 of 8 (87.5%) had RNA in serum, compared with 14 of 31 patients (45%) who were followed for at least 1 mo (mean, 6.1 ± 6.7) (p = 0.03 on X2 assay). No subject in group 3 or in group 4 had hepatitis C virus RNA in serum. In conclusion, approximately 40% to 50% of subjects with hepatitis C virus antibody positivity and persistent normal liver biochemical values have continuing hepatitis C virus infection. (HEPATOLOGY 1993;18:485–490.)
Acute formaldehyde exposure induced early Alzheimer-like changes in mouse brain

Abstract Alzheimer’s disease (AD) is a serious, common, global disease, yet its etiology and pathogenesis are incompletely understood. Although an association between AD and exposure to air pollutants has been discussed, the effects of pollutants on the functioning of the brain remain unclear. The indoor environment is where exposure to formaldehyde (FA) can occur. Whether exposure to FA contributes to the development of AD needs to be investigated. To determine the objective, C57BL/6 mice were exposed daily to FA (0, 0.155, 1.55 and 15.5 mg/kg/day) for 1 week. After acute FA exposure, some early AD-like changes [cognitive deficits, pathological alterations in the mouse brain, accumulation of total β-amyloid plaques 1-42 (Aβ1-42) and hyper-phosphorylated tau (Tau-P) in the cerebral cortex] were detected after exposure to high concentrations of FA (1.55 or 15.5 mg/kg/day). The permeability of the blood–brain barrier (BBB), activation of astrocyte and microglia, oxidative stress (OS) and inflammation were analyzed to explore the toxicity mechanisms behind the development of early AD-like changes. While exposed to a low concentration of FA (0.155 mg/kg/day) had little or no adverse effects on the mouse brain. The results indicated that acute FA exposure induced early AD-like changes in mouse brain, increased the susceptibility of AD in mouse.
Persistence Characteristics of Latin American Financial Markets

The financial rates of return from Latin American stock and currency markets are found to be non-normal, non-stationary, non-ergodic and long-term dependent, i.e., they have long memory. The degree of long- term dependence is measured by monofractal (global) Hurst exponents from wavelet multiresolution analysis (MRA). Scalograms and scalegrams provide the respective visualizations of these wavelet coefficients and the power spectrum of the rates of return. The slope of the power spectrum identifies the Hurst exponent and thereby the degree of scaling dependence that cannot be determined by Box-Jenkins type time series analysis. Our dependency and time and frequency scaling results are consistent with similar empirical findings from American, European, and Asian financial markets, extending the domain of the empirical investigation of the dynamics and risk characteristics of financial markets and refuting the hypothesis of perfectly efficient markets.