Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential Roles of Akt, Rac, and Ral in R-Ras-Mediated Cellular Transformation, Adhesion, and Survival

ABSTRACT Multiple biological functions have been ascribed to the Ras-related G protein R-Ras. These include the ability to transform NIH 3T3 fibroblasts, the promotion of cell adhesion, and the regulation of apoptotic responses in hematopoietic cells. To investigate the signaling mechanisms responsible for these biological phenotypes, we compared three R-Ras effector loop mutants (S61, G63, and C66) for their relative biological and biochemical properties. While the S61 mutant retained the ability to cause transformation, both the G63 and the C66 mutants were defective in this biological activity. On the other hand, while both the S61 and the C66 mutants failed to promote cell adhesion and survival in 32D cells, the G63 mutant retained the ability to induce these biological activities. Thus, the ability of R-Ras to transform cells could be dissociated from its propensity to promote cell adhesion and survival. Although the transformation-competent S61 mutant bound preferentially to c-Raf, it only weakly stimulated the mitogen-activated protein kinase (MAPK) activity, and a dominant negative mutant of MEK did not significantly perturb R-Ras oncogenicity. Instead, a dominant negative mutant of phosphatidylinositol 3-kinase (PI3-K) drastically inhibited the oncogenic potential of R-Ras. Interestingly, the ability of the G63 mutant to induce cell adhesion and survival was closely associated with the PI3-K-dependent signaling cascades. To further delineate R-Ras downstream signaling events, we observed that while a dominant negative mutant of Akt/protein kinase inhibited the ability of R-Ras to promote cell survival, both dominant negative mutants of Rac and Ral suppressed cell adhesion stimulated by R-Ras. Thus, the biological actions of R-Ras are mediated by multiple effectors, with PI3-K-dependent signaling cascades being critical to its functions.
Crystal structure of ethyl 2-[(4-bromophenyl)amino]-3,4-dimethylpent-3-enoate

In the title compound, C15H20BrNO2, there are two independent molecules (A and B) comprising the asymmetric unit and these adopt very similar conformations. In A, the dihedral angle between the CO2 and MeC=CMe2 groups is 80.7 (3)°, and these make dihedral angles of 3.5 (3) and 84.09 (16)°, respectively, with the bromobenzene ring. The equivalent dihedral angles for molecule B are 78.4 (3), 2.1 (3) and 78.37 (12)°, respectively. The most prominent interactions in the crystal packing are amine-N—H⋯O(carbonyl) hydrogen bonds between the two independent molecules, resulting in non-centrosymmetric ten-membered {⋯OC2NH}2 synthons. Statistical disorder is noted for each of the terminal methyl groups of the ethyl residues.
Role of Pancreatic Cholesterol Esterase in the Uptake and Esterification of Cholesterol by Isolated Intestinal Cells 1

Summary Isolated intestinal mucosal cells from normal and common duct-cannu-lated rats have been prepared by collagen-ase dissociation. These cells displayed ultra-structural integrity and retained several metabolic characteristics typical of intact intestinal mucosa. These included galactose accumulation and its inhibition by dinitro-phenol, glucose oxidation, incorporation of labeled leucine into cellular protein, and the uptake and esterification of fatty acid. The uptake of cholesterol by cells from common duct-cannulated rats was comparable to that in cells from control animals; however, esterification was only about 25% of that in control cells. Preincubation of the “defective” cells for 30 min with the purified subunit or active form of pancreatic sterol ester hydrolase had no effect on cholesterol uptake but resulted in a fourfold to sixfold increase in the ability of the cells to esterify cholesterol. These studies provide additional evidence for the essential role of pancreatic sterol ester hydrolase in the mucosal esterification of absorbed cholesterol prior to lymphatic transport.
[Fructose and fructose intolerance].

Although fructose was discovered in 1794, it was realised in recent decades only that its malabsorption can lead to intestinal symptoms while its excessive consumption induces metabolic disturbances. Fructose is a monosaccharide found naturally in most fruits and vegetables. Dietary intake of fructose has gradually increased in the past decades, especially because of the consumption of high fructose corn syrup. With its 16.4 kg/year consumption, Hungary ranks secondly after the United States. Fructose is absorbed in the small intestine by facilitated transport mediated by glucose transporter proteins-2 and -5, and arrives in the liver cells. Here it is transformed enzymatically into fructose-1-phosphate and then, fructose-1,5-diphosphate, which splits further into glyceraldehyde and dihydroxyacetone-phosphate, entering the process of glycolysis, triglyceride and uric acid production. The prevalence of fructose intolerance varies strongly, depending on the method used. The leading symptoms of fructose intolerance are similar, but less severe than those of lactose intolerance. Multiple secondary symptoms can also occur. A symptom-based diagnosis of fructose intolerance is possible, but the gold standard is the H2 breath test, though this is less accurate than in lactose testing. Measuring fructosaemia is costly, cumbersome and not widely used. Fructose intolerance increases intestinal motility and sensitivity, promotes biofilm formation and contributes to the development of gastrooesophageal reflux. Long-term use of fructose fosters the development of dental caries and non-alcoholic steatohepatitis. Its role in carcinogenesis is presently investigated. The cornerstone of dietary management for fructose intolerance is the individual reduction of fructose intake and the FODMAP diet, led by a trained dietetician. The newly introduced xylose-isomerase is efficient in reducing the symptoms of fructose intolerance. Orv. Hetil. , 2016, 157(43), 1708-1716.
Is chronic pain a disease?

The article by Cohen and colleagues ⇓ challenges the concept of persistent pain as a disease and raises some interesting points for discussion. As one of the authors of the article to which they refer ⇓, I appreciate the opportunity to make a reply. There are many points raised in their article and it is not possible to address them all in an article of this length. I will largely confine myself to the central issue of persistent pain as a disease. As Cohen and colleagues correctly assert, the central question is one of definition. In fact, there are two questions that are fundamental to this debate: What is a disease? And, does pain meet the criteria for that definition? In our original article, we gave a definition from the Oxford dictionary, but the definition put forward by Cohen and colleagues is equally valid. Although space is limited, it is worth restating because it is central to the whole issue. Their definition of a disease is as follows; “a disease is any deviation from or interruption …
Mapeamento de competências tecnológicas como ferramenta para avaliação da transferência de tecnologia em Instituições de Pesquisa

Considerando a restrita capacidade de grandes empresas realizarem Pesquisa e Desenvolvimento no Brasil, destaca-se o papel das instituicoes publicas de pesquisa para o desenvolvimento tecnologico. Nos ultimos anos, foram criados Nucleos de Inovacao Tecnologica (NIT) nestas instituicoes, com o objetivo de gerenciar a interacao com as empresas. Usualmente, o registro de patentes e utilizado para acompanhar o desenvolvimento tecnologico. Entretanto, mais do que resultados, deve-se monitorar o processo de forma a poder articular acoes para a promocao da melhoria. Este artigo apresenta resultados parciais de um projeto que, ao avaliar a necessidade de se conhecer as capacidades e competencias tecnologicas geradas pela universidade, conduziu um mapeamento das mesmas, com a delimitacao para a cadeia produtiva de petroleo, gas e polimeros. Este mapeamento baseou-se na logica da criacao de mapas do conhecimento. A instituicao analisada compreende uma Universidade Publica localizada na regiao sul do Brasil. Elaborou-se um mapa da cadeia produtiva. Paralelamente, conduziu-se o levantamento de dados secundarios, a partir de planilhas de registros disponiveis no NIT: (i) patentes; (ii) pesquisadores e historico de contratos; e (iii) empresas incubadas. Os dados foram entao analisados quanto a contribuicao dos respectivos objetos nas diferentes atividades da cadeia produtiva. Os extratos das bases de dados foram unificados para fins de analise de contagem de atividades quanto a ocorrencia ou nao de contribuicao da Universidade. Esta contagem tambem foi desdobrada por classe de atividade e etapa da cadeia produtiva. A analise permitiu a identificacao de algumas potencialidades de aplicacao de competencias tecnologicas existentes na Universidade.
Parasympathetic nervous system activity in hypothyroidism determined by R‐R interval variations on electrocardiogram

Abstract. Little is known about the relationship between hypothyroidism and the parasympathetic nervous system. R‐R interval variations revealed by electrocardiogram (ECG) are known to be a useful clinical indicator of abnormalities of parasympathetic nervous system activity. Studies were conducted in hypothyroid patients, and significant reductions in R‐R interval variations were observed in patients with primary severe hypothyroidism due to Hashimoto's thyroiditis, and in patients with Graves'disease who became severely hypothyroid during antithyroid drug therapy. R‐R interval variations were restored to normal levels in both groups of patients after treatment. The present investigation suggests that in marked hypothyroidism there are hypofunctional abnormalities in the parasympathetic nervous system in association with a reduction in the levels of serum T4 and T3.
Représentation comparative. Application au discours électoral en Suisse, France et États-Unis

RESUME. Dans cet article, nous decrivons et analysons plusieurs methodes afin d'extraire les mots ou expressions les plus representatifs d'un corpus en comparaison avec un corpus de reference. L'emploi de la frequence d'occurrence ou le rang des termes les plus frequents peut fournir une premiere synthese. Une meilleure approche consiste a s'appuyer sur l'hypothese d'une distribution binomiale des mots et le calcul d'un score normalise (score Z) mettant en lumiere les termes ou expressions comparativement les plus usites dans le corpus. Afin d'illustrer la qualite de la representation ainsi obtenue, nous avons applique notre strategie sur des discours electoraux suisses, francais ou americains.
Gel to Liquid‐Crystalline Phase Transitions of Lipids and Membranes Isolated from Escherichia coli Cells

Differential scanning calorimetry (DSC) was used to examine the relationship of the gel to liquid‐crystalline phase transition of lipids to fatty acid composition with membrane lipids and spheroplast membranes isolated from cells of a wild strain and an unsaturated fatty acid auxotroph of Escherichia coli grown under various conditions. These lipids and membranes underwent thermotropic phase transitions at different temperatures depending on the thermal properties of their constituent fatty acids. The lipid phase transition occurred at higher temperatures in biomembranes than in extracted lipids. DSC thermograms of lipids synthesized by bacterial cells which were observed at a temperature scanning rate as slow as 0.3 K min‐1 were characterized by a distinctly plain peak summit. Endothermic peaks given by samples derived from elaidic acid‐enriched cells were relatively narrow and asymmetric. The discrepancy between the transition temperatures measured with extracted lipids and with membraneous fractions, and the shape of the endothermic peaks, are discussed.
Chromatin-Bound p53 Anchors Activated Smads and the mSin3A Corepressor To Confer Transforming Growth Factor β-Mediated Transcription Repression

ABSTRACT In hepatic cells, Smad and SnoN proteins converge with p53 to repress transcription of AFP, an oncodevelopmental tumor marker aberrantly reactivated in hepatoma cells. Using p53- and SnoN-depleted hepatoma cell clones, we define a mechanism for repression mediated by this novel transcriptional partnership. We find that p53 anchors activated Smads and the corepressor mSin3A to the AFP distal promoter. Sequential chromatin immunoprecipitation analyses and molecular modeling indicate that p53 and Smad proteins simultaneously occupy overlapping p53 and Smad regulatory elements to establish repression of AFP transcription. In addition to its well-known function in antagonizing transforming growth factor β (TGF-β) responses, we find that SnoN actively participates in AFP repression by positively regulating mSin3A protein levels. We propose that activation of TGF-β signaling restores a dynamic interplay between p53 and TGF-β effectors that cooperate to effectively target mSin3A to tumor marker AFP and reestablish transcription repression.
Initial home health outcomes under prospective payment.

OBJECTIVE To assess initial changes in home health patient outcomes under Medicare's home health Prospective Payment System (PPS), implemented by the Centers for Medicare and Medicaid Services (CMS) in October 2000. DATA SOURCES/STUDY SETTING Pre-PPS and early PPS data were obtained from CMS Outcome and Assessment Information Set (OASIS) and Medicare claims files. STUDY DESIGN Regression analysis was applied to national random samples (n=164,810) to estimate pre-PPS/PPS outcome and visit-per-episode changes. DATA COLLECTION/EXTRACTION METHODS Outcome episodes were constructed from OASIS data and linked with Medicare claims data on visits. PRINCIPAL FINDINGS Outcome changes (risk adjusted) were mixed and generally modest. Favorable changes included higher improvement rates under PPS for functioning and dyspnea, higher community discharge rates, and lower hospitalization and emergent care rates. Most stabilization (nonworsening) outcome rates also increased. However, improvement rates were lower under PPS for wounds, incontinence, and cognitive and emotional/behavioral outcomes. Total visits per episode (case-mix adjusted) declined 16.6 percent although therapy visits increased by 8.4 percent. CONCLUSIONS The outcome and visit results suggest improved system efficiency under PPS (fewer visits, similar outcomes). However, declines in several improvement rates merit ongoing monitoring, as do subsequent (posthome health) hospitalization and emergent care use. Since only the early PPS period was examined, longer-term analyses are needed.
The peripheral lymphoid compartment is disrupted in flaky skin mice

Flaky skin (fsn) is an autosomal recessive mutation on mouse chromosome 17 that causes severe anaemia, forestomach papillomatosis and a papulosquamous skin disease that resembles psoriasis in humans. In the present paper, it is reported that fsn causes peripheral lymphadenopathy, CD4/CD8 imbalance and hyperresponsiveness to T cell growth factors. Peripheral lymph nodes (PLN) of adult mutant (fsn/fsn) mice were found to contain almost 10‐fold more leucocytes than PLN from phenotypically normal littermates (+/fsn or +/+, hereafter referred to as +/? ). Analysis of PLN cells using mAbs and flow cytometry revealed that this predominantly lymphoid hyperplasia was characterized by approximately equivalent increases in the numbers of CD3+ T cells and CD19+ B cells. However, expansion within the T cell compartment was non‐random, because fsn/fsn PLN had a considerably reduced ratio of CD4+ to CD8+ T cells (1.08 ± 0.37) compared to +/? PLN (2.47 ± 0.44, P < 0.0001). In vitro assays of cellular proliferation in response to T and B cell growth factors showed that fsn/fsn PLN cells were hyperresponsive to IL‐2, IL‐4 and IL‐7 when compared with PLN cells from +/? mice. Studies using mesenteric lymph node and peripheral blood cells showed that hyperresponsive cells are widely distributed in fsn/fsn mice. Experiments in newborn mice showed that the lymphoid disturbances caused by fsn are established at least as early as 2 weeks of age, a time that precedes the onset of the earliest clinical skin lesions. These data implicate a role for the fsn gene product in regulating the size and content of the peripheral lymphoid compartment.
Life Values as an Intrinsic Guide for Cardiopulmonary Rehabilitation Program Engagement: A QUALITATIVE ANALYSIS

Purpose: Participation in cardiovascular and pulmonary rehabilitation (CVPR) programs can lead to improved functional abilities and improved quality of life, but attendance and adherence to these programs remain suboptimal. Behavioral therapies have emphasized the importance of life value identification as a guide for goal setting and behavior change for both psychological and physical health conditions. Individuals who choose to engage in behaviors that align with their life values are thought to be intrinsically reinforced. The purpose of the following qualitative study was to interview patients enrolled in CVPR about their own life values and motivating factors related to healthy behavior changes. Methods: Thirty cardiac or pulmonary patients were recruited from a CVPR program and participated in a semistructured interview about their life values and motivating factors related to program engagement. The data were transcribed and analyzed thematically. Results: Participants identified a wide range of values related to program engagement, and only half of the participants endorsed health as a value. The most frequently endorsed life values included being active, family, and independence. The interviews indicated that, although patients make lifestyle changes in the program to improve their physical health, there are often other values that primarily guide their choice to engage in and maintain lifestyle behaviors. Conclusions: Life values can serve as a powerful guide for individual behavior change. The present study suggests that the piloting of brief values interventions early in CVPR treatment is warranted and has the potential to improve patient outcomes.
An Improved Virtual Space Vector Modulation Scheme for Three-Level Active Neutral-Point-Clamped Inverter

This paper presents an improved virtual space vector modulation (IVSVM) scheme for a three-level active neutral-point-clamped (3L-ANPC) inverter to balance neutral-point potential (NP), reduce switching loss, and suppress common mode voltage (CMV). In the IVSVM scheme, an improved virtual medium vector (VMV) is synthesized by the original medium vector and the adjacent two pairs of the small vectors since there are always two pairs of the small vectors in any regions of the new space vector diagram. The improved VMV provides the flexibility to control the NP balancing under any modulation indexes and power factors in one switching cycle while achieving SL reduction and CMV suppression. This is achieved by the proper selection of two pairs of small vectors in terms of NP charge and the pulse sequence. The experimental platform based on a 3L-ANPC inverter is established and results obtained to verify the effectiveness of the IVSVM control strategy.
Anti-inflammatory action of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and the prevention of diabetes mellitus in obese patients with hypertension.

To the Editor—In their commentary, Chan et al 1 propose that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) should be considered first-choice antihypertensive therapies for obese patients, given the favourable effects of these agents on glucose metabolism. We agree with this assertion and suggest that the antiinflammatory action of renin-angiotensin blockade could be a further underlying mechanism of the beneficial metabolic effects of ACE inhibitors and ARBs in obese patients. Increasing levels of inflammatory biomarkers have been shown to correlate with the development of diabetes mellitus, 2,3 supporting a possible role of inflammation in diabetogenesis. On the other hand, levels of C-reactive protein, the classic marker of systemic inflammation, have been shown to be substantially higher in obese and overweight people than in leaner subjects. 4
Denoising of 4D cardiac micro-CT data using median-centric bilateral filtration

Bilateral filtration has proven an effective tool for denoising CT data. The classic filter uses Gaussian domain and range weighting functions in 2D. More recently, other distributions have yielded more accurate results in specific applications, and the bilateral filtration framework has been extended to higher dimensions. In this study, brute-force optimization is employed to evaluate the use of several alternative distributions for both domain and range weighting: Andrew's Sine Wave, El Fallah Ford, Gaussian, Flat, Lorentzian, Huber's Minimax, Tukey's Bi-weight, and Cosine. Two variations on the classic bilateral filter, which use median filtration to reduce bias in range weights, are also investigated: median-centric and hybrid bilateral filtration. Using the 4D MOBY mouse phantom reconstructed with noise (stdev. ~ 65 HU), hybrid bilateral filtration, a combination of the classic and median-centric filters, with Flat domain and range weighting is shown to provide optimal denoising results (PSNRs: 31.69, classic; 31.58 median-centric; 32.25, hybrid). To validate these phantom studies, the optimal filters are also applied to in vivo, 4D cardiac micro-CT data acquired in the mouse. In a constant region of the left ventricle, hybrid bilateral filtration with Flat domain and range weighting is shown to provide optimal smoothing (stdev: original, 72.2 HU; classic, 20.3 HU; median-centric, 24.1 HU; hybrid, 15.9 HU). While the optimal results were obtained using 4D filtration, the 3D hybrid filter is ultimately recommended for denoising 4D cardiac micro-CT data, because it is more computationally tractable and less prone to artifacts (MOBY PSNR: 32.05; left ventricle stdev: 20.5 HU).
Predicting athletic success motivation using mental skin and emotional intelligence and its components in male athletes.

AIM The aim of this study was to predict athletic success motivation by mental skills, emotional intelligence and its components. METHODS The research sample consisted of 153 male athletes who were selected through random multistage sampling. The subjects completed the Mental Skills Questionnaire, Bar-On Emotional Intelligence questionnaire and the perception of sport success questionnaire. Data were analyzed using Pearson correlation coefficient and multiple regressions. RESULT Regression analysis shows that between the two variables of mental skill and emotional intelligence, mental skill is the best predictor for athletic success motivation and has a better ability to predict the success rate of the participants. Regression analysis results showed that among all the components of emotional intelligence, self-respect had a significantly higher ability to predict athletic success motivation. CONCLUSION The use of psychological skills and emotional intelligence as an mediating and regulating factor and organizer cause leads to improved performance and can not only can to help athletes in making suitable and effective decisions for reaching a desired goal.
Axial Rotation of the Lower Human Spine by Rhythmic Torques Automatically Generated at the Resonant Frequency

Subjects sat on a ‘Balans’ chair supported by the shaft of a large torque generator. The lower but not the upper part of the body was free to make to/fro movements maintained by feeding back a modified velocity signal to the generator. The stiffness could be increased by the use of a position signal. Using the equations for a torsion pendulum the good linearity observed in relationship to the applied forces allowed stiffness, inertia, damping, critical damping and the damping factor to be determined in absolute terms. The method enables parameters relevant to back function and problems to be evaluated. Eleven adults acted as subjects.