Miracle-dz/UniFAR-FTUs huggingface dataset:
Surfactant Protein A2 Mutations Associated with Pulmonary Fibrosis Lead to Protein Instability and Endoplasmic Reticulum Stress*

Rare heterozygous mutations in the gene encoding surfactant protein A2 (SP-A2, SFTPA2) are associated with adult-onset pulmonary fibrosis and adenocarcinoma of the lung. We have previously shown that two recombinant SP-A2 mutant proteins (G231V and F198S) remain within the endoplasmic reticulum (ER) of A549 cells and are not secreted into the culture medium. The pathogenic mechanism of the mutant proteins is unknown. Here we analyze all common and rare variants of the surfactant protein A2, SP-A2, in both A549 cells and in primary type II alveolar epithelial cells. We show that, in contrast with all other SP-A2 variants, the mutant proteins are not secreted into the medium with wild-type SP-A isoforms, form fewer intracellular dimer and trimer oligomers, are partially insoluble in 0.5% Nonidet P-40 lysates of transfected A549 cells, and demonstrate greater protein instability in chymotrypsin proteolytic digestions. Both the G231V and F198S mutant SP-A2 proteins are destroyed via the ER-association degradation pathway. Expression of the mutant proteins increases the transcription of a BiP-reporter construct, expression of BiP protein, and production of an ER stress-induced XBP-1 spliced product. Human bronchoalveolar wash samples from individuals who are heterozygous for the G231V mutation have similar levels of total SP-A as normal family members, which suggests that the mechanism of disease does not involve an overt lack of secreted SP-A but instead involves an increase in ER stress of resident type II alveolar epithelial cells.
Modern instruments for increasing the efficiency of the energy transfer in electric vehicles

This paper describes the high efficiency drive unit for an EV, which is designed with accessible solutions for the efficiency increasing. Synchronous utilization of ultracapacitors and three-level inverter brings considerable power savings and enhancement longevity for a lithium battery pack. The total loss and EMI comparison between the two-level and three-level inverter and power measurements on the EV drive unit are presented at the conclusion part of this paper.
Long-term cardiovascular consequences of obesity: 20-year follow-up of more than 15 000 middle-aged men and women (the Renfrew-Paisley study).

AIMS To examine the long-term cardiovascular consequences of obesity and project the cardiovascular consequences of the recent increase in prevalence of obesity. METHODS AND RESULTS Between 1972 and 1976, 15 402 individuals aged 45-64, living in two towns in the west of Scotland underwent comprehensive cardiovascular screening. We analysed all deaths and hospitalizations for cardiovascular reasons occurring over the subsequent 20 years according to baseline body mass index (BMI) category. Compared with normal weight individuals (BMI 18.5-24.9), obesity (BMI > or =30) was associated with an increased adjusted risk of coronary heart disease (hazard ratio for death or hospital admission: 1.60, 95% CI 1.45-1.78), heart failure (2.09, 1.68-2.59), stroke (1.41, 1.21-1.65), venous thrombo-embolism (2.29, 1.60-3.30), and atrial fibrillation (1.75, 1.17-2.65). Obesity was associated with nine additional cardiovascular deaths and 36 additional cardiovascular hospital admissions for every 100 affected middle-aged men over the subsequent 20 years (seven deaths and 28 admissions in women). Assuming no change in cardiovascular risk profile and outcomes related to obesity, the increase in prevalence in 1998, when compared with 1972, is projected to lead to an additional four cardiovascular deaths and 14 admissions per 100 middle-aged men and women over the next 20 years. CONCLUSION Obesity is associated with an increase in a broad range of fatal and non-fatal cardiovascular events. Consideration of only coronary, only fatal, and only first events greatly underestimates the cardiovascular consequences of obesity.
Overview

In the discussion and debate concerning the role of alcohol in cardiovascular disease in this issue there are on the one hand several areas of broad agreement and, on the other, important areas of contention and uncertainty. The title of the topic oversimplifies the problem as there are clearly many different types of cardiovascular disease, ranging from disturbances of blood pressure regulation to all the different manifestations of fatal and nonfatal coronary artery disease, arrhythmias and cardiac failure, as well as diverse forms of ischaemic and haemorrhagic cerebrovascular disease. Adding to the complexity are the varied types of alcoholic beverage for which beneficial or harmful effects are claimed, and the varied manner by which they are imbibed in a social and cultural context by populations with widely differing patterns of cardiovascular risk. It is this complexity which probably accounts for four major paradoxes which will be alluded to below.
Prediction of maximal heart rate in individuals with mental retardation.

PURPOSE It is well known that individuals with mental retardation (MR), especially those with Down syndrome (DS), have low maximal heart rates (MHR). We evaluated the ability to predict MHR in individuals with MR and DS in comparison with persons without MR. METHODS Subjects completed a maximal exercise test on the treadmill with metabolic and HR measurements. Stepwise multiple regression was used to develop prediction equations for subjects with MR (N = 276; 97 with DS) and without (N = 296) MR, ranging in age from 9-46 yr. RESULTS Subjects with MR exhibited significantly lower MHR (177 vs 185 beats.min(-1)) and VO2peak (33.8 vs 35.6 mL.kg-1.min(-1)). In subjects with MR, age was a poor predictor of MHR, Y = 189 - 0.59 (age) (R = 0.30, SEE = 13.8 beats.min-1; P < 0.01), but age was a better predictor for subjects without MR, Y = 205 - 0.64 (age) (R = 0.52, SEE = 9.9 beats.min(-1); P < 0.01). A large sample Z test indicated that these regression coefficients were significantly different (P < 0.01). However, adding DS to the regression improved the prediction for subjects with MR, Y = 210 - (0.56 age) - (15.5 DS) (R = 0.57; SEE = 11.8 beats.min(-1), P < 0.01). CONCLUSION MHR can be predicted with similar accuracy in subjects with and without MR, provided DS is accounted for in the equation for the subjects with MR.
Sphingosine-1-phosphate metabolism: A structural perspective

Abstract Sphingolipids represent an important class of bioactive signaling lipids which have key roles in numerous cellular processes. Over the last few decades, the levels of bioactive sphingolipids and/or their metabolizing enzymes have been realized to be important factors involved in disease development and progression, most notably in cancer. Targeting sphingolipid-metabolizing enzymes in disease states has been the focus of many studies and has resulted in a number of pharmacological inhibitors, with some making it into the clinic as therapeutics. In order to better understand the regulation of sphingolipid-metabolizing enzymes as well as to develop much more potent and specific inhibitors, the field of sphingolipids has recently taken a turn toward structural biology. The last decade has seen the structural determination of a number of sphingolipid enzymes and effector proteins. In these terms, one of the most complete arms of the sphingolipid pathway is the sphingosine-1-phosphate (S1P) arm. The structures of proteins involved in the function and regulation of S1P are being used to investigate further the regulation of said proteins as well as in the design and development of inhibitors as potential therapeutics.
Fluorodeoxyglucose–Positron-Emission Tomography Imaging of Head and Neck Squamous Cell Cancer

SUMMARY: The hybrid technique of PET/CT has significantly impacted the imaging and management of HNSCC since its introduction in 2001 and has become the technique of choice for imaging of this cancer. Diagnostic FDG-PET/CT is useful for identification of an unknown primary tumor, delineation of extent of primary tumor, detection of regional lymph node involvement even in a normal-sized node, detection of distant metastases and occasional synchronous primary tumor, assessment of therapy response, and long-term surveillance for recurrence and metastases. The role of PET/CT is evolving in radiation therapy planning. Combined diagnostic PET/CT provides the best anatomic and metabolic in vivo information for the comprehensive management of HNSCC.
Vasoactive intestinal polypeptide modulates GABAA receptor function through activation of cyclic AMP

Abstract Vasoactive intestinal polypeptide (VIP) has been shown to potentiate current responses elicited by activation of the GABAA receptor (IGABA) in freshly dissociated ganglion cells of the rat retina. Here we tested the hypothesis that this heteroreceptor cross talk is mediated by an intracellular cascade of events that includes the sequential activation of a stimulatory guanine nucleotide binding (Gs) protein and adenylate cyclase, the subsequent increase in levels of cyclic AMP and, finally, the action of the cyclic AMP-dependent protein kinase (PKA). Intracellular dialysis of freshly dissociated ganglion cells with GTPγs irreversibly potentiated IGABA, while GDPßs either decreased or had no effect on IGABA. Additionally, GDPßs blocked the potentiation of IGABA by VIP. Cholera toxin rendered VIP ineffective in potentiating IGABA, while pertussis toxin had no effect on the VIP-induced potentiation of IGABA. Extracellular application of either forskolin or 8-bromo-cyclic AMP potentiated IGABA, as did the introduction of cyclic AMP directly into the intracellular compartment through the recording pipet. Intracellular application of cyclic AMP-dependent protein kinase (PKA) potentiated IGABA, while a PKA inhibitor blocked the potentiating effect of VIP. These results lead us to conclude that activation of a cyclic AMP-dependent second-messenger system mediates the modulation of GABAA receptor function by VIP in retinal ganglion cells.
The effects of institutional legitimacy, social capital, and government relationship on clustered firms’ performance in emerging economies

Purpose – The purpose of this paper is to examine how a clustered foreign firm’s network ties of social capital and government relationship may affect its institutional legitimacy and performance for clustered firms in emerging economies. To accomplish this task, the authors identify network ties (e.g. bridging ties and strong ties) and show, for each, the direct effects on institutional legitimacy and organizational performance. The findings show that bridging ties, strong ties, and government relationship directly and significantly impact organizational performance. Design/methodology/approach – This study used the two-step approach suggested by Anderson and Gerbing (1988). The first step uses confirmatory factor analysis to validate the psychometric properties of the measurement scales. The second step then uses structural equation modeling to examine the proposed hypotheses. The statistical software LISREL 8.80 was used for the data analysis. Findings – This paper finds that industrial clusters serve .
Dilution-Based Emissions Sampling from Stationary Sources: Part 2—Gas-Fired Combustors Compared with Other Fuel-Fired Systems

Abstract This paper presents the design and performance of a compact dilution sampler (CDS) for characterizing fine particle emissions from stationary sources. The sampler is described, along with the methodology adopted for its use. Dilution sampling has a number of advantages, including source emissions that are measured under conditions simulating stack gas entry and mixing in the ambient atmosphere. This is particularly important for characterizing the semivolatile species in effluents as a part of particulate emissions. The CDS characteristics and performance are given, along with sampling methodology. The CDS was compared with a reference dilution sampler. The results indicate that the two designs are comparable for tests on gas-fired units and a diesel electrical generator. The performance data indicate that lower detection limits can be achieved relative to current regulatory methods for particulate emissions. Test data for the fine particulate matter (PM2.5) emissions are provided for comparison with U.S. Environment Protection Agency (EPA) Conditional Test Method 040 for filterable particulate matter (FPM) and the EPA Method 202 for condensable particulate matter. This comparison showed important differences between methods, depending on whether a comparison is done between in situ FPM determinations or the sum of such values with condensable PM from liquid filled impingers chilled in an ice bath. These differences are interpretable in the light of semivolatile material present in the stack effluent and, in some cases, differences in detection and quantification limits. Determination of emissions from combustors using liquid fuels can be readily achieved using 1-hr sampling with the CDS. Emissions from gasfired combustors are very low, requiring careful attention to sample volumes. Sampling volumes corresponding with 6-hr operation were used for the combined mass and broad chemical speciation. Particular attention to dilution sampler operation with clean dilution air also is essential for gas-fired sources.
Transplantation of Embryonic Neural Stem/Precursor Cells Overexpressing BM88/Cend1 Enhances the Generation of Neuronal Cells in the Injured Mouse Cortex

The intrinsic inability of the central nervous system to efficiently repair traumatic injuries renders transplantation of neural stem/precursor cells (NPCs) a promising approach towards repair of brain lesions. In this study, NPCs derived from embryonic day 14.5 mouse cortex were genetically modified via transduction with a lentiviral vector to overexpress the neuronal lineage‐specific regulator BM88/Cend1 that coordinates cell cycle exit and differentiation of neuronal precursors. BM88/Cend1‐overexpressing NPCs exhibiting enhanced differentiation into neurons in vitro were transplanted in a mouse model of acute cortical injury and analyzed in comparison with control NPCs. Immunohistochemical analysis revealed that a smaller proportion of BM88/Cend1‐overexpressing NPCs, as compared with control NPCs, expressed the neural stem cell marker nestin 1 day after transplantation, while the percentage of nestin‐positive cells was significantly reduced thereafter in both types of cells, being almost extinct 1 week post‐grafting. Both types of cells did not proliferate up to 4 weeks in vivo, thus minimizing the risk of tumorigenesis. In comparison with control NPCs, Cend1‐overexpressing NPCs generated more neurons and less glial cells 1 month after transplantation in the lesioned cortex whereas the majority of graft‐derived neurons were identified as GABAergic interneurons. Furthermore, transplantation of Cend1‐overexpressing NPCs resulted in a marked reduction of astrogliosis around the lesioned area as compared to grafts of control NPCs. Our results suggest that transplantation of Cend1‐overexpressing NPCs exerts beneficial effects on tissue regeneration by enhancing the number of generated neurons and restricting the formation of astroglial scar, in a mouse model of cortical brain injury. STEM CELLS 2010;28:127–139
[Prevalence of ESBL-positive strains of Klebsiella pneumoniae in the Czech Republic and their molecular biology analysis].

BACKGROUND One of the problems of contemporary medicine is an increasing number of bacterial strains with hazardous phenotypes of resistance. The feared bacterial pathogens include Klebsiella pneumoniae strains producing AmpA extended-spectrum beta-lactamases. The study focused on the molecular biological characteristics of ESBL-positive strains of Klebsiella pneumoniae collected in the Czech Republic. MATERIALS AND METHODS Clinical material from patients hospitalized in 16 Czech hospitals in September and October 2004 was used to isolate and determine Klebsiella pneumoniae strains by standard identification procedures. Their susceptibility to antibiotics was tested using a dilution micromethod. A Double-Disk Synergy Test was used for phenotype determination of ESBL production. The blaTEM, blaSHV and blaOXA genes coding ESBL production were demonstrated by PCR. Molecular biological characteristics of ESBL-positive strains utilized the genomic DNA isolation, XbaI restrictase digestion and PFGE differentiation. The acquired restriction maps of individual isolates were compared using GelCompar II software and their relationship was determined. RESULTS During the monitored period, 913 Klebsiella pneumoniae strains causing clinically detectable diseases were isolated. Of these, 234 (25.6 %) were determined as ESBL-positive strains. The prevalence of ESBL-positive strains was 38.5 % in ICUs and 15.8 % in standard wards. More than 50 % of ESBL-positive isolates were effectively treated only with meropenem (98 %), cefoperazone/sulbactam (61 %) and amikacin (54 %). Conversely, ESBL-negative strains showed high susceptibility to all tested antibiotics (76-99 %). The molecular biological analysis identified 18 clonal types containing 2-6 identical strains. 17 clones usually contained isolates from one hospital and only in one clone strains from two hospitals were identified. CONCLUSION Based on the above mentioned results, the prevalence of ESBL-positive strains of Klebsiella pneumoniae in the Czech Republic can be perceived as relatively high, especially in the ICUs. An extensive spread of epidemic clones within Czech hospitals and, to a limited extent, between them can be demonstrated.
Age is a major pathobiological determinant of aortic dilatation: a large autopsy study of community deaths.

AIM Aortic dilatation is a well-known phenomenon in the elderly. We therefore aimed to study the pathobiological determinants of aortic dilatation. METHODS Retrospective chart review. The subjects were 833 consecutive autopsy cases (616 men and 217 women) of community deaths. The age at death ranged from 20 to 94 years, with an average of 59.2 years. We measured the internal circumference of the aortic root, arch, descending portion, abdominal portion, and bifurcation in unfixed opened aorta at the time of autopsy. RESULTS The simple correlation between age and aortic circumference was strongest for the descending portion, followed by the arch, abdominal portion, root, and bifurcation. The simple correlation coefficient reached 0.836 for the descending portion (p < 0.001). The circumference of the descending portion increased significantly as the severity of aortic atherosclerosis increased (p for trend < 0.001). Multiple regression analysis showed that age, sex, and body height were significantly correlated with the aortic circumference at all five measurement sites, while severe atherosclerosis was correlated with the aortic circumference at the root, and descending and abdominal portions. Six contributing factors (age, sex, body height, smoking history, hypertension, and severe atherosclerosis) explained 68.5% of the variance in circumference in the descending portion; age explained 57.5%; sex 8.4%; body height 1%; and severe atherosclerosis 0.8%. CONCLUSION The contribution of atherosclerosis to aortic dilation was very weak, representing less than one seventieth of the contribution of age. The aortic circumference, especially in the descending portion, serves as an excellent age-related marker.
Seven-year outcome of the Vermont Intervention Program for Low-Birthweight Infants.

We compared 24 low-birthweight subjects of an experimental intervention (LBWE), 32 no-treatment controls (LBWC), and 37 normal birthweight (NBW) subjects. The intervention involved 7 hospital sessions and 4 home sessions in which a nurse helped mothers adapt to their LBW babies. At age 7, LBWE scored significantly higher than LBWC on the Kaufman Mental Processing Composite (p less than .001), Sequential (p = .02), and Simultaneous (p = .001) Scales, after statistical adjustments for socioeconomic status. LBWE did not differ from NBW (F less than 1). These results bear out a divergence between the LBWE and LBWC that first became statistically significant at age 3. The findings suggest that the intervention prevented cognitive lags among LBW children, and that long-term follow-ups are needed to evaluate the developmental effects of efforts to overcome major biological and environmental risks.
Structure of the Lrp‐regulated serA promoter of Escherichia coli K‐12

Expression of the Escherichia coli serA gene is activated in vivo by the product of the lrp gene, leucine‐responsive regulatory protein (Lrp), an effect partially reversed by L‐leucine. We show here that serA is transcribed from two promoters, P1 45 bp upstream of the translation start site, and P2 92 bp further upstream. Lrp binds to a long AT‐rich sequence from –158 to –82 from the start of the coding region, i.e. upstream of P1 and overlapping P2. It activates transcription from P1 and represses expression from P2. A second regulator, cAMP/CRP, activates P2, an effect that is largely inhibited by Lrp, such that catabolite repressor protein (Crp) and Lrp are rival activators of serA transcription.
The Determinants of Student Migration to Poland Based on the Opolskie Voivodeship Study

Until recently Poland has been considered a country to emigrate from. However, the situation is now beginning to change, and Poland is becoming an immigration country. This also refers to student migration. Polish universities are becoming increasingly attractive to foreign students, who are mainly of Ukrainian origin. They only began to promote their services abroad in 2005 and their foreign student population growth dynamic is one of the highest in the world. The study was conducted in the Opolskie Voivodeship, the first region in Poland where systematic action was taken to address depopulation, and the steps to counteract population decline were included in its strategic policies. One of the objectives of such policies was to stimulate immigration. For this reason, it was decided that the Opolskie Voivodeship might serve as a lab to study migration processes, including the inflow of foreign students.
Structure and biology of complement protein C3, a connecting link between innate and acquired immunity

Complement protein C3 is a central molecule in the complement system whose activation is essential for all the important functions performed by this system. After four decades of research it is now well established that C3 functions like a double‐edged sword: on the one hand it promotes phagocytosis, supports local inflammatory responses against pathogens, and instructs the adaptive immune response to select the appropriate antigens for a humoral response; on the other hand its unregulated activation leads to host cell damage. In addition, its interactions with the proteins of foreign pathogens may provide a mechanism by which these microorganisms evade complement attack. Therefore, a clear knowledge of the molecule and its interactions at the molecular level not only may allow the rational design of molecular adjuvants but may also lead to the development of complement inhibitors and new therapeutic agents against infectious diseases.
Pricing VIX Options with Multifactor Stochastic Volatility

By exploiting the flexibility of the Wishart process, we propose an application of this framework to the pricing of Chicago Board Options Exchange (CBOE) volatility index (VIX) options. Our methodology is analytically tractable and yet flexible enough to efficiently price CBOE VIX options. In particular, the dynamics for the CBOE VIX is carried out in a linear affine way and the discounted Laplace transform exhibits an exponentially affine property. The tractable model structure lightens the computational burden and facilitates a fast identification of the parameter estimates. We empirically show that modeling the stochastic co-volatility factor can significantly improve the in-sample fitting results due to the improved modeling of higher conditional moments in the underlying transition probability density.