Miracle-dz/UniFAR-FTUs huggingface dataset:
Associations of a Human G Protein &bgr;3 Subunit Dimorphism With Insulin Resistance and Carotid Atherosclerosis

Background and Purpose— The C825T dimorphism of the gene encoding the human G protein &bgr;3 subunit (GNB3) is associated with hypertension and obesity. Although these findings suggest an association with insulin resistance and atherosclerosis, this hypothesis has yet been tested only partially. Methods— To investigate this hypothesis, the C825T dimorphism was determined in a population of 932 middle-aged white subjects of middle European (Austrian) origin. Insulin sensitivity was measured with the short insulin tolerance test; intima-media thickness of the carotid artery and morphological plaque burden were measured by ultrasound. Results— Insulin sensitivity was found to be significantly lower in carriers of the T allele (3.55±1.27 versus 3.92±1.30%/min, P =0.012) in the group of male subjects with abdominal body fat distribution (waist-to-hip ratio >0.9). No effect was observed in women or men with a waist-to-hip ratio <0.9. Advanced carotid artery plaques were more frequent (odds ratio, 1.606; 95% confidence interval, 1.002 to 2.575;P =0.04) in carriers of the T allele regardless of sex. No effect was observed with regard to carotid artery intima-media thickness. Conclusions— In summary, our results demonstrate that the GNB3 825T allele is associated with reduced insulin sensitivity in men with abdominal fat distribution and with more advanced carotid atherosclerosis in middle-aged white men and women.
Effect of spectacles on changes of spherical hypermetropia in infants who did, and did not, have strabismus

AIM To explore why emmetropisation fails in children who have strabismus. METHODS 289 hypermetropic infants were randomly allocated spectacles and followed. Changes in spherical hypermetropia were compared in those who had strabismus and those who did not. The effect of wearing glasses on these changes was assessed using t tests and regression analysis. RESULTS Mean spherical hypermetropia decreased in both eyes of “normal” children (p<0.001). The consistent wearing of glasses impeded this process in both eyes (p<0.007). In the children with strabismus, there were no significant changes in either eye, irrespective of treatment (p>0.05). CONCLUSIONS In contrast with normal infants, neither eye of those who had strabismus emmetropised, irrespective of whether the incoming vision was clear or blurred. It is suggested that these eyes did not “recognise” the signal of blurred vision, and that they remained long sighted because they were destined to squint. Hence, the children did not squint because they were long sighted, and glasses did not prevent them squinting.
Metastatic competence of BW5147 T‐lymphoma cell lines is correlated with in vitro invasiveness, motility and F‐actin content

The aim of our study was to investigate whether the level of actin polymerization plays a role in the motile and tissue infiltrating behavior of malignant lymphoma cells. For a panel of cell lines derived from the murine BW5147 T‐cell lymphoma, we had previously shown a correlation between experimental metastasis formation and in vitro monolayer invasion. We have analyzed the motility and the F‐actin content of six non‐metastatic, noninvasive (meta‐inv‐) and five metastatic, invasive (meta+inv+) variants of BW5147. Fourier analysis of cell contours was used to quantify shape changes of cells. All meta+inv+ lines rapidly protruded and retracted pseudopodia, whereas only one of the six meta‐inv‐ lines showed this type of motility. Flow cytometry of cells stained with fluorescein‐labeled phalloidin showed that the motile meta+inv+ cell lines have a higher F‐actin content than their nonmotile meta‐inv‐ counterparts. The results indicate that in lymphoma cells a high level of actin polymerization is a prerequisite for the formation of pseudopodia, which in turn are necessary for infiltration of the cells into tissues, and eventually for efficient metastasis formation. A corollary of this conclusion is that regulation of actin polymerization is a possible target for intervention aimed at moderating the spread of malignant lymphoma. J. Leukoc. Biol. 55: 552–556; 1994.
Cell Wall Targeting of Laccase of Cryptococcus neoformans during Infection of Mice

ABSTRACT Laccase is a major virulence factor of the pathogenic fungus Cryptococcus neoformans, which afflicts both immunocompetent and immunocompromised individuals. In the present study, laccase was expressed in C. neoformans lac1Δ cells as a fusion protein with an N-terminal green fluorescent protein (GFP) using C. neoformans codon usage. The fusion protein was robustly localized to the cell wall at physiological pH, but it was mislocalized at low pH. Structural analysis of the laccase identified a C-terminal region unique to C. neoformans, and expression studies showed that the region was required for efficient transport to the cell wall both in vitro and during infection of mouse lungs. During infection of mice, adherence to alveolar macrophages was also associated with a partial mislocalization of GFP-laccase within cytosolic vesicles. In addition, recovery of cryptococcal cells from lungs of two strains of mice (CBA/J and Swiss Albino) later in infection was also associated with cytosolic mislocalization, but cells from the brain showed almost exclusive localization to cell walls, suggesting that there was more efficient cell wall targeting during infection of the brain. These data suggest that host cell antifungal defenses may reduce effective cell wall targeting of laccase during infection of the lung but not during infection of the brain, which may contribute to a more predominant role for the enzyme during infection of the brain.
Expression of plasminogen activator inhibitor‐1 by olfactory ensheathing glia promotes axonal regeneration

Olfactory ensheathing glia (OEG) cells are known to facilitate repair following axotomy of adult neurons, although the molecular mechanisms involved are not fully understood. We previously identified plasminogen activator inhibitor‐1 (PAI‐1), proteinase‐activated receptor‐1 (PAR‐1), and thrombomodulin (TM) as candidates to regulate rat OEG‐dependent axonal regeneration. In this study, we have validated the involvement of these proteins in promoting axonal regeneration by immortalized human OEGs. We studied the effect of silencing these proteins in OEGs on their capacity to promote the regeneration of severed adult retinal ganglion cells (RGCs) axons. Our results support the role of glial PAI‐1 as a downstream effector of PAR‐1 in promoting axon regeneration. In contrast, we found that TM inhibits OEG induced‐axonal regeneration. We also assessed the signaling pathways downstream of PAR‐1 that might modulate PAI‐1 expression, observing that specifically inhibiting Gαi, Rho kinase, or PLC and PKC downregulated the expression of PAI‐1 in OEGs, with a concomitant reduction in OEG‐dependent axon regeneration in adult RGCs. Our findings support an important role for the thrombin system in regulating adult axonal regeneration by OEGs. © 2011 Wiley‐Liss, Inc.
High rate of tuberculosis reinfection during a nosocomial outbreak of multidrug-resistant tuberculosis caused by Mycobacterium bovis strain B.

We present a study of a nosocomial outbreak of multidrug-resistant tuberculosis caused by Mycobacterium bovis in 31 patients, 30 of whom were infected with human immunodeficiency virus; all 31 died of progressive tuberculosis. All M. bovis strains had identical spoligotyping patterns and showed resistance to 12 antituberculosis drugs. Reinfection was suggested in 11 cases and confirmed in 4 by molecular typing methods. The causative strain was named "B strain. "
Polypharmacy in nursing home in Europe: results from the SHELTER study.

BACKGROUND This study assesses prevalence and patients characteristics related to polypharmacy in a sample of nursing home residents. METHODS We conducted a cross-sectional analysis on 4,023 nursing home residents participating to the Services and Health for Elderly in Long TERm care (SHELTER) project, a study collecting information on residents admitted to 57 nursing home in 8 countries. Data were collected using the interRAI instrument for long-term care facilities. Polypharmacy status was categorized in 3 groups: non-polypharmacy (0-4 drugs), polypharmacy (5-9 drugs) and excessive polypharmacy (≥ 10 drugs). RESULTS Polypharmacy was observed in 2,000 (49.7%) residents and excessive polypharmacy in 979 (24.3%) residents. As compared with non-polypharmacy, excessive polypharmacy was directly associated not only with presence of chronic diseases but also with depression (odds ratio [OR] 1.81; 95% confidence interval [CI] 1.38-2.37), pain (OR 2.31; 95% CI 1.80-2.97), dyspnoea (OR 2.29; 95% CI 1.61-3.27), and gastrointestinal symptoms (OR 1.73; 95% CI 1.35-2.21). An inverse association with excessive polypharmacy was shown for age (OR for 10 years increment 0.85; 95% CI 0.74-0.96), activities of daily living disability (OR for assistance required vs independent 0.90; 95% CI 0.64-1.26; OR for dependent vs independent 0.59; 95% CI 0.40-0.86), and cognitive impairment (OR for mild or moderate vs intact 0.64; 95% CI 0.47-0.88; OR for severe vs intact 0.39; 95% CI 0.26-0.57). CONCLUSIONS Polypharmacy and excessive polypharmacy are common among nursing home residents in Europe. Determinants of polypharmacy status include not only comorbidity but also specific symptoms, age, functional, and cognitive status.
An Amplitude and Phase Mismatches Calibration Technique for the LINC Transmitter With Unbalanced Phase Control

The linear amplifier with nonlinear components (LINC) is highly efficient because it uses a highly efficient nonlinear power amplifier (PA). However, the linearity performance of the LINC system is easily degraded by amplitude and phase mismatches between the two paths. In this paper, we propose a novel mismatch calibration technique for the LINC system that calibrates both phase and amplitude mismatches with only phase control. The technique detects mismatches between two paths without any iteration using predefined five test vector signals. In addition, this technique corrects the path mismatches using unbalanced phase control. Therefore, the proposed scheme does not require additional amplitude mismatch control blocks such as dc/dc converters or low drop output regulators (LDO). The linearity performance of the proposed LINC system is measured with 7-MHz bandwidth orthogonal frequency-division multiplexing (OFDM) signals. According to the measurement results, the proposed technique significantly enhances linearity. The measurement results also shows that the proposed LINC system satisfies the error vector magnitude (EVM) requirement for a 16-state quadratic amplitude modulation (QAM) signal (-24 dB) and a 64-QAM signal (-31 dB) up to 3.8- and 2.35-dB amplitude mismatches, respectively, with any phase mismatch.
Copper and iron homeostasis in plants: the challenges of oxidative stress.

SIGNIFICANCE Photosynthesis, the process that drives life on earth, relies on transition metal (e.g., Fe and Cu) containing proteins that participate in electron transfer in the chloroplast. However, the light reactions also generate high levels of reactive oxygen species (ROS), which makes metal use in plants a challenge. RECENT ADVANCES Sophisticated regulatory networks govern Fe and Cu homeostasis in response to metal ion availability according to cellular needs and priorities. Molecular remodeling in response to Fe or Cu limitation leads to its economy to benefit photosynthesis. Fe toxicity is prevented by ferritin, a chloroplastic Fe-storage protein in plants. Recent studies on ferritin function and regulation revealed the interplay between iron homeostasis and the redox balance in the chloroplast. CRITICAL ISSUES Although the connections between metal excess and ROS in the chloroplast are established at the molecular level, the mechanistic details and physiological significance remain to be defined. The causality/effect relationship between transition metals, redox signals, and responses is difficult to establish. FUTURE DIRECTIONS Integrated approaches have led to a comprehensive understanding of Cu homeostasis in plants. However, the biological functions of several major families of Cu proteins remain unclear. The cellular priorities for Fe use under deficiency remain largely to be determined. A number of transcription factors that function to regulate Cu and Fe homeostasis under deficiency have been characterized, but we have not identified regulators that mediate responses to excess. Importantly, details of metal sensing mechanisms and cross talk to ROS-sensing mechanisms are so far poorly documented in plants.
The use of the VerifyNow system to monitor antiplatelet therapy: A review of the current evidence

Multiple studies have demonstrated the effectiveness of dual or triple antiplatelet therapy with aspirin, clopidogrel and glycoprotein (GP) IIb/IIIa therapy in patients with acute coronary syndromes as well as in patients undergoing coronary stent implantation. In the last few years, it is becoming clear that not all patients receive the full benefits with the current standard dosages of antiplatelet therapy. Specifically, numerous studies have revealed a wide interindividual variability in the response to these antiplatelet agents and, more importantly, both nonresponsiveness as well as a heightened residual platelet reactivity have been linked to the occurrence of adverse cardiovascular events. Therefore, assays that identify those patients with an impaired responsiveness or a heightened platelet reactivity despite dual antiplatelet therapy may contribute to better risk stratification and will probably improve clinical outcome when appropriate action is initiated. Likewise, a considerable number of patients do not achieve the minimal inhibition of aggregation threshold with the current recommended weight-adjusted dosages of GP IIb/IIIa therapy. Identifying and optimizing the absolute degree of platelet inhibition in this subgroup of patients will probably improve clinical outcome. The VerifyNow platform is one of the most user friendly point-of-care platelet function test systems because it produces rapid results at the patient bedside. The purpose of the present paper is to give insight into the principal mechanisms of the VerifyNow system, to discuss its clinical utility for the monitoring of antiplatelet therapy and to discuss the proposed cut-off levels to segregate responders from non-responders for the different types of antiplatelet therapy.
Effects of the High-Temperature Plasma Immersion Ion-Implantation Treatment on Corrosion Behavior of Ti-6Al-4V

Nitrogen implantation into Ti alloys at higher temperatures improves their mechanical and corrosion resistance properties by forming a thicker nitride layer. In this paper, two different sets of Ti-6Al-4V samples were plasma immersion ion implantation (PIII)-treated using nitrogen plasma, varying the treatment time from 30 to 150 min (800 degC) and the process temperature from 400 degC to 800 degC (t=60 min). Nanoindentation measurements of the PIII-treated samples at 800 degC during 150 min showed the highest hardness value, 24 GPa, which is about four times bigger than untreated sample hardness. The N penetration at these conditions reached approximately 150 nm as analyzed by Auger spectroscopy. On the other hand, the lowest passive current density (3times10-7 Amiddotcm-2) was obtained for a PIII-treated sample during 30 min at higher temperature (800 degC). The corrosion resistance of this sample is almost the same as for the untreated specimen. Corrosion behavior evidenced that in strong oxidizing media, all PIII-treated samples are more corrosion resistant than the untreated one. PIII processing at higher temperatures promotes smoothing of the sample surface as observed by scanning electron microscopy (SEM). Grazing incidence X-ray diffraction analyses of the untreated samples identified the two typical Ti phases, Ti alpha and Ti beta. After the implantation, Ti2N and TiO2 phases were also detected
Recent developments and future directions for the use of pharmacogenomics in cardiovascular disease treatments

ABSTRACT Introduction: Cardiovascular disease is still the leading cause of death worldwide. There are many environmental and genetic factors that play a role in the development of cardiovascular disease. The treatment of cardiovascular disease is beginning to move in the direction of personalized medicine by using biomarkers from the patient’s genome to design more effective treatment plans. Pharmacogenomics have already uncovered many links between genetic variation and response of many different drugs. Areas covered: This article will focus on the main polymorphisms that impact the risk of adverse effects and response efficacy of statins, clopidogrel, aspirin, β-blockers, warfarin dalcetrapib and vitamin E. The genes discussed include SLCO1B1, ABCB1, CYP3A4, CYP3A5, CYP2C19, PTGS1, PTGS2, ADRB1, ADCY9, CYP2C19, PON1, CES1, PEAR1, GPIIIa, CYP2D6, CKORC1, CYP2C9 and Hp. Expert opinion: Although there are some convincing results that have already been incorporated in the labelling treatment guidelines, most gene-drug relationships have been inconsistent. A better understanding of the relationships between genetic factors and drug response will provide more opportunities for personalized diagnosis and treatment of cardiovascular disease.
A wideband beam-forming antipodal tapered slot antenna, embedded in a dielectric

By embedded in a dielectric, we propose a wideband antipodal tapered slot antenna with equal half-power beamwidth (HPBW) in two principal plane patterns to solve the problem that the antipodal tapered slot antenna has broad HPBW in H-plane and narrow HPBW in E-plane. This antenna is designed to be used as an element of a base station antenna array. To reduce the width of the antenna, circular-ends rectangular slots are etched to the antenna. Moreover, in order to suppress the unknown effect in the machining process, an open stub is added to the feeding microstrip line. This antenna achieves a wide bandwidth of 1.67-6.4GHz, a maximal gain of 14.07dB and optimized radiation patterns with equal HPBW in two principal plane patterns.
Plasminogen Activator Inhibitor Type I Controls Cardiomyocyte Transforming Growth Factor-&bgr; and Cardiac Fibrosis

Background: Fibrosis is the pathological consequence of stress-induced tissue remodeling and matrix accumulation. Increased levels of plasminogen activator inhibitor type I (PAI-1) have been shown to promote fibrosis in multiple organ systems. Paradoxically, homozygous genetic deficiency of PAI-1 is associated with spontaneous age-dependent, cardiac-selective fibrosis in mice. We have identified a novel PAI-1-dependent mechanism that regulates cardiomyocyte-derived fibrogenic signals and cardiac transcriptional pathways during injury. Methods: Cardiac fibrosis in subjects with homozygous mutation in SERPINE-1 was evaluated with late gadolinium-enhanced cardiac magnetic resonance imaging. A murine cardiac injury model was performed by subcutaneous infusion of either saline or Angiotensin II by osmotic minipumps. We evaluated blood pressure, cardiac function (by echocardiography), fibrosis (with Masson Trichrome staining), and apoptosis (with TUNEL staining), and we performed transcriptome analysis (with RNA sequencing). We further evaluated fibrotic signaling in isolated murine primary ventricular myocytes. Results: Cardiac fibrosis was detected in 2 otherwise healthy humans with complete PAI-1 deficiency because of a homozygous frameshift mutation in SERPINE-1. In addition to its suppressive role during spontaneous cardiac fibrosis in multiple species, we hypothesized that PAI-1 also regulates fibrosis during cardiac injury. Treatment of young PAI-1−/− mice with Angiotensin II induced extensive hypertrophy and fibrotic cardiomyopathy, with increased cardiac apoptosis and both reactive and replacement fibrosis. Although Angiotensin II-induced hypertension was blunted in PAI-1−/− mice, cardiac hypertrophy was accelerated. Furthermore, ventricular myocytes were found to be an important source of cardiac transforming growth factor-&bgr; (TGF-&bgr;) and PAI-1 regulated TGF-&bgr; synthesis by cardiomyocytes in vitro as well as in vivo during cardiac injury. Transcriptome analysis of ventricular RNA after Angiotensin II treatment confirmed that PAI-1 deficiency significantly enhanced multiple TGF-&bgr; signaling elements and transcriptional targets, including genes for extracellular matrix components, mediators of extracellular matrix remodeling, matricellular proteins, and cardiac integrins compared with wild-type mice. Conclusions: PAI-1 is an essential repressor of cardiac fibrosis in mammals. We define a novel cardiomyocyte-specific regulatory mechanism for TGF-&bgr; production by PAI-1, which explains the paradoxical effect of PAI-1 deficiency in promoting cardiac-selective fibrosis. Thus, PAI-1 is a molecular switch that controls the cardiac TGF-&bgr; axis and its early transcriptional effects that lead to myocardial fibrosis.
Automatic evaluation of complex design decisions in component-based software architectures

The quality of modern industrial plants depends on the quality of the hardware used, as well as software. While the impact on quality is comparably well understood by making decisions about the choice of hardware components, this is less true for the decisions on software components. The quality of the resulting software system is strongly influenced by its software architecture. Especially in early project phases a software architect has to make many design decisions. Each design decision highly influences the software architecture and thus, the resulting software quality. However, the impact on the resulting quality of architecture design decisions is hard to estimate in advance. For instance, a software architect could decide to deploy software components on a dedicated server in order to improve the system performance. However, such a decision may increase the network overhead as side-effect. Model-driven approaches have been shown as promising techniques enabling design-time quality prediction for different quality attributes such as performance or reliability. However, such approaches are limited in their automated decision support to simple design decisions like the exchange of one single component. In this paper, we present an approach that automatically evaluates complex design decisions in software architecture models. Such design decisions require the reuse of subsystems with many involved components coming with inhomogeneous architectures. We evaluate our approach using a real-world example system demonstrating the benefits of our approach.