Miracle-dz/UniFAR-FTUs huggingface dataset:
Isoform-Specific Activation of Latent Transforming Growth Factor β (LTGF-β) by Reactive Oxygen Species

Abstract Jobling, M. F. , Mott, J. D. , Finnegan, M. T. , Jurukovski, V. , Erickson, A. C. , Walian, P. J., Taylor, S. E. , Ledbetter, S. , Lawrence, C. M. , Rifkin, D. B. and Barcellos-Hoff, M. H. Isoform-Specific Activation of Latent Transforming Growth Factor β (LTGF-β) by Reactive Oxygen Species. Radiat. Res. 166, 839–848 (2006). The three mammalian transforming growth factor β (TGF-β) isoforms are each secreted in a latent complex in which TGF-β homodimers are non-covalently associated with homodimers of their respective pro-peptide called the latency-associated peptide (LAP). Release of TGF-β from its LAP, called activation, is required for binding of TGF-β to cellular receptors, making extracellular activation a critical regulatory point for TGF-β bioavailability. Our previous work demonstrated that latent TGF-β1 (LTGF-β1) is efficiently activated by ionizing radiation in vivo and by reactive oxygen species (ROS) generated by Fenton chemistry in vitro. In the current study, we determined the specific ROS and protein target that render LTGF-β1 redox sensitive. First, we compared LTGF-β1, LTGF-β2 and LTGF-β3 to determine the generality of this mechanism of activation and found that redox-mediated activation is restricted to the LTGF-β1 isoform. Next, we used scavengers to determine that ROS activation was a function of OH· availability, confirming oxidation as the primary mechanism. To identify which partner of the LTGF-β1 complex was functionally modified, each was exposed to ROS and tested for the ability to form a latent complex. Exposure of TGF-β1 did not alter its ability to associate with LAP, but exposing LAP-β1 to ROS prohibited this phenomenon, while treatment of ROS-exposed LAP-β1 with a mild reducing agent restored its ability to neutralize TGF-β1 activity. Taken together, these results suggest that ROS-induced oxidation in LAP-β1 triggers a conformational change that releases TGF-β1. Using site-specific mutation, we identified a methionine residue at amino acid position 253 unique to LAP-β1 as critical to ROS-mediated activation. We propose that LTGF-β1 contains a redox switch centered at methionine 253, which allows LTGF-β1 to act uniquely as an extracellular sensor of oxidative stress in tissues.
Financial supply cycles in post-transition Europe – introducing a composite index for financial supply

Abstract This paper introduces a new composite index – the financial supply index (FSI) – measuring the level of supply of foreign capital to small open economies. FSI is estimated on a sample of 11 EU new member states (NMS) applying Kalman filtering, principal components and variance-equal weights. Results indicated that the main drivers of financial supply to NMS are externally determined, with economic sentiment and business climate in the Eurozone carrying the highest weight. FSI proved to have a good predictive power for debt inflow dynamics. In addition, we create a new indicator – the Refinancing Risk Ratio, which relates the supply and demand for foreign capital – to quantify the external refinancing conditions and risk faced by the government. We distinguish between two recent episodes of high refinancing risk – one during the global crisis, and the other during the European sovereign debt crisis – but the episodes significantly differ in nature.
Hospital variation in mortality after emergent bowel resections: The role of failure-to-rescue

BACKGROUND Hospital variation in failure-to-rescue (FTR) rates has partially explained nationwide differences in mortality after elective surgeries. To examine the role of FTR among emergency general surgery, we compared nationwide risk-adjusted mortality, complications, and FTR rates after emergent bowel resections. METHODS We identified patients who underwent emergent small or large bowel resections in the 2010 to 2011 Nationwide Inpatient Sample using the American Association for the Surgery of Trauma criteria. We then calculated risk-adjusted mortality rates for each hospital using multivariable logistic regressions and postestimation, which adjusted for patient age, sex, race and ethnicity, payer status, comorbidities, and hospital clustering. After excluding hospitals with fewer than 10 resections per year, we ranked the remaining hospitals by their risk-adjusted mortality rates and divided them into five quintiles. We compared both risk-adjusted complication rates and FTR rates between the top (lowest mortality) and bottom (highest mortality) quintiles. RESULTS We identified 21,564 emergent bowel resections, weighted to 105,925 procedures nationwide. The bottom quintile of hospitals had an overall risk-adjusted mortality rate that was 10.9 times higher than that of the top quintile of hospitals (15.3% vs. 1.4%). While risk-adjusted complication rates were similarly high for both the bottom and the top quintiles of hospitals (22.5% vs. 15.7%), the risk-adjusted FTR rates were 10.8 times higher in the bottom quintile of hospitals relative to the top quintile of hospitals (33.4% vs. 3.1%). Using larger hospital volume thresholds yielded similar findings. Furthermore, large variations existed in complication-specific FTR rates (surgical site infection [6.6%] to myocardial infarction [29.4%]). CONCLUSION Nationwide hospital variation in risk-adjusted mortality rates exist after emergent bowel resections. As complication rates were similar across hospitals, the significantly higher FTR rates at higher-mortality hospitals may drive this variation in mortality. System-level initiatives addressing the management of postoperative complications may improve patient care and reduce variation in outcomes. LEVEL OF EVIDENCE Prognostic and epidemiological study, level IV.
Two types of immunoglobulin-negative Abelson murine leukemia virus-transformed cells: implications for B-lymphocyte differentiation.

Both alleles of immunoglobulin (Ig) heavy-chain joining region (JH) genes in three Ig-negative Abelson murine leukemia virus (Ab-MuLV)-transformed cell lines were characterized by DNA cloning and nucleotide sequence determination. These studies unambiguously identified two distinct types of Ig-negative B-lineage cells. The first type of cell (e.g., R8) is an "immature pre-B cell," and it contains at least one intermediate recombinant structure containing heavy-chain diversity (DH) and JH sequences but no variable region (VH) sequence. This type of cell, which has also been characterized by other investigators, generates mu-positive sublines during subsequent culturing of cells and represents a precursor stage to pre-B cells. The second type of cell (e.g., RAW253) is an "abortive pre-B cell," in that both JH alleles contain nonfunctional VH-DH-JH structures. The nucleotide sequence determinations in this study demonstrated that these nonfunctional V-D-J structures were generated by nonproductive somatic recombinations, involving either out-of-phase joining events, or the formation of termination codons in the DH coding sequences. The identification of abortive pre-B cells suggests that the recombinational joining of Ig VH, DH, and JH segments is not actively regulated by a putative recombinase to preserve the translational reading frame. This in turn implies that a large portion of precursor cells at the early stage of B-cell differentiation are abortive and possibly blocked to further differentiation.
Creativity and science parks: more than just a physical platform?

This study explores how managerial practices can develop and enhance a creative climate in science parks. Based on a case study of one of the most important Italian science parks, Area Science Park, our results suggest that science park management can further enhance the park’s park potential and strengthen ties to its different actors by focusing on creative climate development. In particular, we identify and discuss key aspects that are relevant to this challenge, i.e. promotion of a shared identity, design of structured work processes, use of communal spaces and internal communication technology. Overall, the study contributes to show that creative climate development implies more than merely being located in the physical platform of a science park.
[Demography and employment in Portugal].

The population of Portugal showed a period of slow growth between 1950-60; however, in the 1970s, the return of large numbers of former residents in African territories along with a reduction in emigration changed the trend so that the 1981 census showed a significant increase. The Portuguese economy, on the other hand, is in a state of crisis which has resulted in large numbers of unemployed. The growth of the population along with these hard times has made it more difficult to reduce the rate of unemployment. It is also more difficult for those leaving school to find jobs. The better educated generations are seeking jobs in industry and in other services that Portugal will find difficult to offer in sufficient numbers in the immediate future. At present, the Portuguese economy has a large component of agricultural labor. In any case, the means of economic and social intervention to fight unemployment have limited potential. Therefore, many of those unable to find jobs in Portugal will attempt to emigrate. Many Portuguese are already working in Germany, France, and in other Western European countries but migration today is much more difficult. In addition, these countries cannot be expected to recive many more migrant workers in the future. In fact, those better educated workers from Portugal will not be very interested in the low paying jobs which can be found more easily by foreign workers in Western Euorpe. Many will therefore attempt to find jobs in non-European countries. There has been a recent increase of migration to Canada and the US. A renewal of interest in jobs in Brazil and other South Amerian countries is also to be expected. There may also be a future increase in the number of experts, technicians, and other qualified personnel emigrating to Portuguese speaking African countries if there is adequate security and if these countries find the way to expand economic growth. (author's modified)
Local Government Size and Political Efficacy: Do Citizen Panels Make a Difference?

ABSTRACT Democratic theorists typically suggest that citizens served by small local governments have high levels of political efficacy. However, it is conceivable that large governments can overcome the burden of bigness by introducing structures that involve citizens more closely in decision-making. This paper analyses whether jurisdiction size influences political efficacy in Welsh local government, and whether the presence of a citizen panel makes a difference to the size-efficacy relationship. Multi-level analyses suggest that size is negatively associated with internal and external political efficacy, but that the use of citizen panels bolsters the external efficacy of citizens served by larger local government.
A multi-mode energy-efficient double-precision floating-point multiplier

Energy-efficiency is among the most important goals of the current IC industry. To achieve this goal each subcomponent of a chip must be optimized for energy). Even though a tremendous amount of research has been dedicated to optimizing floating-point multipliers (FPM) for better performance, efforts are continuously being made to further enhance them, indicating their importance in the computing world. Hence a multi-mode operating energy-efficient FPM is introduced in this work. This double-precision multiplier dynamically adapts to three modes of operations based on the effective precision of the inputs: low-precision, asymmetric, and full modes, where a 24×24, 24×53, or 53×53 fraction multiplication is required, respectively. Due to the highly frequent occurrence of low-precision operands (i.e., the least significant bits of the fraction are zeros), switching between these modes saves energy by avoiding unnecessary bitlevel computations. Results show up to 25% and 21% savings in dynamic energy and total energy, respectively. A two-tier 3DIC FPM design is also proposed to further enhance the performance of the multi-mode FPM.
Entry and Ramifications of Neo-Liberalism for Education in Tanzania: What is the Possible Alternative?

What takes place in an education system is influenced by, among other things, ideologies that exist in society. In recent years, the ideological influence on education in Tanzania has changed from Ujamaa thinking to neo-liberalism. This paper traces the entry of the latter into Tanzania’s education and its ramifications. The paper is based on a study whose objectives were to establish how neo-liberalist ideas entered Tanzania’s education system; identify the ramifications and impact of neo-liberalism on the provision of education in Tanzania; and trace the possible ideological alternative for Tanzania’s education. It is argued in the paper that neo-liberalism has been responsible for the introduction of problematic cost-sharing policies in education, the under-financing of education, and attenuation of education quality. On a wider scope, ideology has also caused the failure of locally produced goods, the market for agricultural products to diminish, agricultural crop prices to plummet, the number of youth petty traders to increase in urban centres, and many to lose their jobs. Since Tanzania needs to address the negative impact of neo-liberalism, the paper proposes what could be a suitable alternative ideology for education in the country. Key words : Neo-liberalism, Education, Tanzania
The splicing factor ASF/SF2 is associated with TIA‐1‐related/TIA‐1‐containing ribonucleoproteic complexes and contributes to post‐transcriptional repression of gene expression

TIA‐1‐related (TIAR) protein is a shuttling RNA‐binding protein implicated in several steps of RNA metabolism. In the nucleus, TIAR contributes to alternative splicing events, whereas, in the cytoplasm, it acts as a translational repressor on specific transcripts such as adenine and uridine‐rich element‐containing mRNAs. In addition, TIAR is involved in the general translational arrest observed in cells exposed to environmental stress. This activity is encountered by the ability of TIAR to assemble abortive pre‐initiation complexes coalescing into cytoplasmic granules called stress granules. To elucidate these mechanisms of translational repression, we characterized TIAR‐containing complexes by tandem affinity purification followed by MS. Amongst the identified proteins, we found the splicing factor ASF/SF2, which is also present in TIA‐1 protein complexes. We show that, although mostly confined in the nuclei of normal cells, ASF/SF2 migrates into stress granules upon environmental stress. The migration of ASF/SF2 into stress granules is strictly determined both by its shuttling properties and its RNA‐binding capacity. Our data also indicate that ASF/SF2 down‐regulates the expression of a reporter mRNA carrying adenine and uridine‐rich elements within its 3′ UTR. Moreover, tethering of ASF/SF2 to a reporter transcript strongly reduces mRNA translation and stability. These results indicate that ASF/SF2 and TIA proteins cooperate in the regulation of mRNA metabolism in normal cells and in cells having to overcome environmental stress conditions. In addition, the present study provides new insights into the cytoplasmic function of ASF/SF2 and highlights mechanisms by which RNA‐binding proteins regulate the diverse steps of RNA metabolism by subcellular relocalization upon extracellular stimuli.
Infliximab attenuates inflammatory osteolysis in a model of periodontitis in Wistar rats

Periodontitis is a chronic inflammatory disease related to tooth loss in adults. Infliximab is a chimeric monoclonal antibody against TNF-α and is prescribed for the treatment of systemic inflammatory diseases. This study aimed to investigate the role of infliximab on experimental periodontal disease (EPD). EPD was induced by passing a 3.0 nylon thread around the upper left second molar in Wistar rats. Animals were either treated with intravenous infliximab (1, 5, 7, and 10 mg/kg) or saline solution 30 min before the periodontitis induction and were followed until they were sacrificed on the 11th day. A subset of rats was euthanized on the third day for analysis of gingival myeloperoxidase (MPO) and the blood MPO granulocyte index. In addition, we analyzed the bone loss index (BLI), the periodontal histopathological score, and the periodontal collagen network using confocal microscopy. We also analyzed metalloproteinase-1/-8, RANK, RANK-L, and osteoprotegerin in maxillary tissue by immunohistochemistry Gingival MPO, IL-1β, TNF-α were measured by ELISA. EPD caused leukocytosis, significant increases in BLI and gingival pro-inflammatory cytokines and cell infiltrates, with worse histopathological scores and periodontal collagen derangement. Infliximab (5 mg/kg) reduced granulocyte blood counts, gingival IL-1β, TNF-α, and MPO levels, diminished MMP-1/-8, RANK, and RANK-L bone immunolabeling with better periodontal histopathological scores and collagen network in comparison with the challenged saline group. We concluded that infliximab had significant anti-inflammatory and bone-protective effects in Wistar rats challenged by periodontitis.
Cool sperm: why some placental mammals have a scrotum

Throughout the Cenozoic, the fitness benefits of the scrotum in placental mammals presumably outweighed the fitness costs through damage, yet a definitive hypothesis for its evolution remains elusive. Here, I present an hypothesis (Endothermic Pulses Hypothesis) which argues that the evolution of the scrotum was driven by Cenozoic pulses in endothermy, that is, increases in normothermic body temperature, which occurred in Boreotheria (rodents, primates, lagomorphs, carnivores, bats, lipotyphylans and ungulates) in response to factors such as cursoriality and climate adaptation. The model argues that stabilizing selection maintained an optimum temperature for spermatogenesis and sperm storage throughout the Cenozoic at the lower plesiomorphic levels of body temperature that prevailed in ancestral mammals for at least 163 million years. Evolutionary stasis may have been driven by reduced rates of germ‐cell mutations at lower body temperatures. Following the extinction of the dinosaurs at the Cretaceous–Palaeogene boundary 65.5 mya, immediate pulses in endothermy occurred associated with the dramatic radiation of the modern placental mammal orders. The fitness advantages of an optimum temperature of spermatogenesis outweighed the potential costs of testes externalization and paved the way for the evolution of the scrotum. The scrotum evolved within several hundred thousand years of the K‐Pg extinction, probably associated initially with the evolution of cursoriality, and arguably facilitated mid‐ and late Cenozoic metabolic adaptations to factors such as climate, flight in bats and sociality in primates.
Representational Difference Analysis between Afa/Dr Diffusely Adhering Escherichia coli and Nonpathogenic E. coli K-12

ABSTRACT Diffusely adhering Escherichia coli strains harboring Afa/Dr adhesins (Afa/Dr DAEC) have been associated with diarrhea and urinary tract infections (UTIs). The present work is the first extensive molecular study of a Afa/Dr DAEC strain using the representational difference analysis technique. We have searched for DNA sequences present in strain C1845, recovered from a diarrheagenic child, but absent from a nonpathogenic K-12 strain. Strain C1845 harbors part of a pathogenicity island (PAICFT073) and several iron transport systems found in other E. coli pathovars. We did not find genes encoding factors known to subvert host cell proteins, such as type III secretion system or effector proteins. Several C1845-specific sequences are homologous to putative virulence genes or show no homology with known sequences, and we have analyzed their distribution among Afa/Dr and non-Afa/Dr clinical isolates and among strains from the E. coli Reference Collection. Three C1845-specific sequences (MO30, S109, and S111) have a high prevalence (77 to 80%) among Afa/Dr strains and a low prevalence (12 to 23%) among non-Afa/Dr strains. In addition, our results indicate that strain IH11128, an Afa/Dr DAEC strain recovered from a patient with a UTI, is genetically closely related to strain C1845.
Homocysteine-lowering effect of 500 microg folic acid every other day versus 250 microg/day.

BACKGROUND/AIMS Elevated plasma total homocysteine (tHcy) concentrations are a risk factor for neural tube defects and vascular diseases. Supplementation with folic acid decreases tHcy. We investigated whether supplementation with 500 microg folic acid every other day is as effective in lowering tHcy as 250 microg folic acid each day. METHODS In a 4-week intervention study, 22 healthy young women (18-40 years old) took either 500 microg folic acid every other day (500-microg/2d group) or 250 microg folic acid each day (250-microg/d group). Fasting blood was collected on days 0 and 28. RESULTS Plasma folate concentrations increased by 11.4 nmol/l (6.8-15.9) in the 250-microg/d group and by 9.1 nmol/l (95% CI 1.9-16.3) in the 500-microg/2d group. These increases were not significantly different from each other. THcy concentrations decreased by 1.52 micromol/l (95% CI -2.09 to -0.95; p < 0.001) in the 250-microg/d group and by 0.88 micromol/l (-1.53 to -0.23; p < 0.05) in the 500-microg/2d group. The difference in decrease between the 250-microg/d group and the 500-microg/2d group was 0.64 micromol/l (p = 0.11). CONCLUSION Although not conclusive, this study suggests that supplying subjects with folic acid each day decreases tHcy more effectively than a double dose every other day.
Time-Resolved Perfusion Imaging at the Angiography Suite: Preclinical Comparison of a New Flat-Detector Application to Computed Tomography Perfusion

ObjectivesThe objective of this study was to compare the parameter maps of a new flat-panel detector application for time-resolved perfusion imaging in the angiography room (FD-CTP) with computed tomography perfusion (CTP) in an experimental tumor model. Materials and MethodsTwenty-four VX2 tumors were implanted into the hind legs of 12 rabbits. Three weeks later, FD-CTP (Artis zeego; Siemens) and CTP (SOMATOM Definition AS +; Siemens) were performed. The parameter maps for the FD-CTP were calculated using a prototype software, and those for the CTP were calculated with VPCT-body software on a dedicated syngo MultiModality Workplace. The parameters were compared using Pearson product-moment correlation coefficient and linear regression analysis. ResultsThe Pearson product-moment correlation coefficient showed good correlation values for both the intratumoral blood volume of 0.848 (P < 0.01) and the blood flow of 0.698 (P < 0.01). The linear regression analysis of the perfusion between FD-CTP and CTP showed for the blood volume a regression equation y = 4.44x + 36.72 (P < 0.01) and for the blood flow y = 0.75x + 14.61 (P < 0.01). ConclusionsThis preclinical study provides evidence that FD-CTP allows a time-resolved (dynamic) perfusion imaging of tumors similar to CTP, which provides the basis for clinical applications such as the assessment of tumor response to locoregional therapies directly in the angiography suite.
Leistungsprofile von Inkubatoren technologiebasierter Unternehmen: Eine empirische bestandsaufnahme

Inkubatoren unterstutzen Neugrundungen und junge Unternehmen beim Aufbau ihrer Geschaftstatigkeit. In diesem Beitrag wird auf Basis einer Stichprobe von 72 deutschen Inkubatoren eine Klassifizierung der Inkubatorlandschaft auf Basis ihrer Leistungsangebote vorgenommen. Anhand einer Clusteranalyse konnen drei Inkubatortypen identifiziert werden, deren Leistungsangebote sich deutlich voneinander unterscheiden. Fur den Vergleich und die Konzeption differenzierter Leistungsprofile von Inkubatoren bietet die empirische Analyse gezielt Anhaltspunkte. Auffallend selten stehen Inkubatoren ihren Unternehmen bei der Erstellung von Marktanalysen zur Seite.