Miracle-dz/UniFAR-FTUs huggingface dataset:
Geodynamics and evolution of the Miocene mineralization in the Cycladic - Pelagonian belt, Hellenides

The paper aims to provide a sound account of the type of Miocene mineralisations in the Cycladic - Pelagonian belt and their relationship with the geodynamic evolution of the area. Skarn and manto types, epithermal pre­ cious and base metals mineralisation, and vein magnesite in ultramafics are associated to distinct stages of the geodynamic evolution of the belt. Extensional tectonics favoured their generation. Late stages of extensional tectonics resulted in the formation of vertical to subvertical NW-SE trending fault zones, which were then used as conduits for ascending hydrothermal fluids. The relationship between the geodynamics and the metallogenetic evolution of the belt is discussed on the basis of available data on the geology of four critical areas: Tinos and Mykonos islands, Laurium and Northern Euboea. along brittle fractures, indicating strong hydrofracturing typical of skarns formed at shallow depths. The presence of acidic igneous dyke rocks along extensional faults cross-cutting previously formed hornfelses and skarns in Laurium and in Serifos, points to the existence of residual liquid granodioritic magma at relatively deeper parts. The E-W and NW-SE vein type massive sulfide mineralisation cross-cutting hornfelses and skarns in Laurium (Vein 80) and Thera respectively, indicates that intense hydrothermal activity followed the HT skarn stage.
Ethnic differences in risk factors and total risk of cardiovascular disease based on the Norwegian CONOR study

Background: Risk of cardiovascular disease varies between ethnic groups and the aim of this study was to investigate differences in cardiovascular risk factors, and total cardiovascular risk between ethnic groups in Norway. Design: Cross-sectional study using data from the Cohort of Norway (CONOR). Methods: A sample of 62,145 participants, 40–65 years of age, originating from 11 geographical regions, were included in our study. Self-reported variables, blood samples and physical measurements were used to estimate age- and time-adjusted mean values of cardiovascular risk factors for different ethnic groups. The 10-year risks of cardiovascular mortality and cardiovascular events were calculated using the Framingham and NORRISK risk models. Results: We observed differences between ethnic groups for cardiovascular risk factors and both Framingham and NORRISK risk scores. NORRISK showed significant differences by ethnicity in women only. Immigrants from the Indian subcontinent had the lowest high-density lipoprotein (HDL) levels, the highest levels of blood glucose, triglycerides, total cholesterol/HDL ratio, waist hip ratio and diabetes prevalence. Immigrants from the former Yugoslavia had the highest Framingham scores, high blood pressure, high total cholesterol/HDL ratio, overweight measures and smoking. Low cardiovascular risk was observed among East Asian immigrants. Conclusion: The previously reported excess cardiovascular risk among immigrants from the Indian subcontinent was supported in this study. We also showed that immigrants from the former Yugoslavian countries had a higher total 10-year risk of cardiovascular events than other ethnic groups. This study adds information about ethnic groups in Norway which needs to be addressed in further research and targeted prevention strategies.
Adventitial Fibroblasts Induce a Distinct Proinflammatory/Profibrotic Macrophage Phenotype in Pulmonary Hypertension

Macrophage accumulation is not only a characteristic hallmark but is also a critical component of pulmonary artery remodeling associated with pulmonary hypertension (PH). However, the cellular and molecular mechanisms that drive vascular macrophage activation and their functional phenotype remain poorly defined. Using multiple levels of in vivo (bovine and rat models of hypoxia-induced PH, together with human tissue samples) and in vitro (primary mouse, rat, and bovine macrophages, human monocytes, and primary human and bovine fibroblasts) approaches, we observed that adventitial fibroblasts derived from hypertensive pulmonary arteries (bovine and human) regulate macrophage activation. These fibroblasts activate macrophages through paracrine IL-6 and STAT3, HIF1, and C/EBPβ signaling to drive expression of genes previously implicated in chronic inflammation, tissue remodeling, and PH. This distinct fibroblast-activated macrophage phenotype was independent of IL-4/IL-13–STAT6 and TLR–MyD88 signaling. We found that genetic STAT3 haplodeficiency in macrophages attenuated macrophage activation, complete STAT3 deficiency increased macrophage activation through compensatory upregulation of STAT1 signaling, and deficiency in C/EBPβ or HIF1 attenuated fibroblast-driven macrophage activation. These findings challenge the current paradigm of IL-4/IL-13–STAT6–mediated alternative macrophage activation as the sole driver of vascular remodeling in PH, and uncover a cross-talk between adventitial fibroblasts and macrophages in which paracrine IL-6–activated STAT3, HIF1α, and C/EBPβ signaling are critical for macrophage activation and polarization. Thus, targeting IL-6 signaling in macrophages by completely inhibiting C/EBPβ or HIF1α or by partially inhibiting STAT3 may hold therapeutic value for treatment of PH and other inflammatory conditions characterized by increased IL-6 and absent IL-4/IL-13 signaling.
Interleukin 12 Protects from a T Helper Type 1–mediated Autoimmune Disease, Experimental Autoimmune Uveitis, through a Mechanism Involving Interferon γ, Nitric Oxide, and Apoptosis

Pathogenic effector T cells in experimental autoimmune uveitis (EAU) are T helper type 1–like, and interleukin (IL)-12 is required for their generation and function. Therefore, we expected that IL-12 administration would have disease-enhancing effects. Mice were immunized with a uveitogenic regimen of the retinal antigen interphotoreceptor retinoid-binding protein, treated with IL-12 (100 ng/d for 5 d), and EAU was assessed by histopathology. Unexpectedly, IL-12 treatment failed to enhance EAU in resistant strains and downregulated disease in susceptible strains. Only treatment during the first, but not during the second, week after immunization was consistently protective. High levels of interferon γ (IFN-γ) were present in the serum during IL-12 treatment, but subsequent antigen-specific IFN-γ production in protected mice was diminished, as were IL-5 production, lymph node cell proliferation, and serum antibody levels. Treated mice had fewer cells and evidence of enhanced apoptosis in the draining lymph nodes. Unlike wild-type mice, IFN-γ–deficient, inducible nitric oxide synthase (iNOS)-deficient, and Bcl-2lck transgenic mice were poorly protected by IL-12, whereas IL-10–deficient mice were protected. We conclude that administration of IL-12 aborts disease by curtailing development of uveitogenic effector T cells. The data are compatible with the interpretation that IL-12 induces systemic hyperinduction of IFN-γ, causing activation of iNOS and production of NO, which mediates protection at least in part by triggering Bcl-2 regulated apoptotic deletion of the antigen-specific T cells as they are being primed.
On the maximum number of Hamiltonian paths in tournaments

By using the probabilistic method, we show that the maximum number of directed Hamiltonian paths in a complete directed graph with n vertices is at least (e−o(1)) (n! /2n−1). © 2001 John Wiley & Sons, Inc. Random Struct. Alg. , 18: 291–296, 2001
Foreign Ownership, Returns to Scale and Productivity: Evidence from UK Manufacturing Establishments

This paper calculates returns to scale and productivity growth in UK manufacturing establishments in the electronics and food industries. Our results show that foreign establishments tend to have lower returns to scale than their domestic counterparts. We also examine the effect of the acquisition of a domestic establishment by a foreign owner on returns to scale and productivity growth. We use a matching and difference-in-differences methodology which allows us to construct a reasonable counterfactual and to determine the post-acquisition changes in RTS and productivity that can be attributed to the incidence of acquisition, rather than to changes in other external conditions. In both sectors, acquisition has a negative effect on RTS, although the effect appears stronger in the food sector. The effect of foreign acquisition on productivity differs between sectors; establishments in the electronics sector experience a reduction in productivity post acquisition, while plants in the food sector increase productivity.
Block Bootstrap Estimation of the Distribution of Cumulative Outdoor Degradation

An interesting prediction problem involving degradation of materials exposed to outdoor environments (weathering) is estimating the distribution of future cumulative degradation using small- to moderate-sized degradation datasets. This distribution, which is assumed to arise as a result of the uncertainty/variability in the weather, can be expressed mathematically as the distribution of the sum of a periodic dependent time series and is approximately normal by the central limit theorem. The estimation of this distribution is thus equivalent to estimating the mean and the variance of the distribution. In this article, we propose a block bootstrap-based approach for the estimation and a novel technique to estimate the variance of the distribution. We provide an example involving the degradation of a solar reflector material, as well as the results of a simulation study to show the efficacy of the proposed estimators. We also give a procedure for constructing an approximate confidence interval for the probability of failure.
Autoradiographic localization of adenosine uptake sites in rat brain using [3H]nitrobenzylthioinosine

The adenosine uptake site has been localized in rat brain by an in vitro light microscopic autoradiographic method, using [3H]nitrobenzylthioinosine ( [3H]NBI) as the probe. The binding characteristics of [3H]NBI on slide-mounted sections are comparable to those seen in studies performed on brain homogenates. A very high density of uptake sites occurs in the nucleus tractus solitarius, in the superficial layer of the superior colliculus, in several thalamic nuclei, and also in geniculate body nuclei. A high density of sites are also observed in the nucleus accumbens, the caudate putamen, the dorsal tegmentum area, the substantia nigra, and the central gray. The localization of the adenosine uptake site in brain may provide information on the functional activity of the site and suggests the involvement of the adenosine system in the central regulation of cardiovascular function.
Thermal Via Allocation for 3D ICs Considering Temporally and Spatially Variant Thermal Power

All existing methods for thermal-via allocation are based on a steady-state thermal analysis and may lead to excessive number of thermal vias. This paper develops an accurate and efficient thermal-via allocation considering temporally and spatially variant thermal-power. The transient temperature is calculated using macromodel by a structured and parameterized model reduction, which generates temperature sensitivity with respect to thermal-via density. By defining a thermal-violation integral based on the transient temperature, a nonlinear optimization problem is formulated to allocate thermal-vias and minimize thermal violation integral. This optimization problem is transformed into a sequence of subproblems by Lagrangian relaxation, and each subproblem is solved by quadratic programming using sensitives from the macromodel. Experiments show that compared to the existing method using steady-state thermal analysis, our method is 126times faster to obtain the temperature profile, and reduces the number of thermal vias by 2.04times under the same temperature bound
Potential targets of FOXL2, a transcription factor involved in craniofacial and follicular development, identified by transcriptomics

FOXL2 is a gene encoding a forkhead transcription factor, whose mutations are responsible for the blepharophimosis-ptosis-epicanthus inversus syndrome that often involves premature ovarian failure. FOXL2 is one of the earliest ovarian markers and it offers, along with its targets, an excellent model to study ovarian development and function in normal and pathological conditions. We have recently shown that the aromatase gene is a target of FOXL2, and only three other targets have been reported so far. To detect potential transcriptional targets of FOXL2, we used DNA chips and quantitative PCR to compare the transcriptomes of granulosa-like cells overexpressing, or not, FOXL2. This analysis showed that mediators of inflammation, apoptotic and transcriptional regulators, genes involved in cholesterol metabolism, and genes encoding enzymes and transcription factors involved in reactive oxygen species detoxification were up-regulated. On the other hand, FOXL2 down-regulated the transcription of several genes involved in proteolysis and signal transduction and in transcription regulation. A bioinformatic analysis was conducted to discriminate between potential target promoters activated and repressed by FOXL2. In addition, the promoters of strongly activated genes were enriched in forkhead recognition sites, suggesting that these genes might be direct FOXL2 targets. Altogether, these results provide insight into the activity of FOXL2 and may help in understanding the mechanisms of pathogenesis of FOXL2 mutations if the targets prove to be the same in the ovary.
Regulation of lymphocyte function by ORAI and STIM proteins in infection and autoimmunity

Abstract Store‐operated Ca2+ entry (SOCE) in cells of the immune system is mediated by Ca2+ release‐activated Ca2+ (CRAC) channels that are formed by ORAI1 and its homologues ORAI2 and ORAI3. They are activated by stromal interaction molecules (STIM) 1 and 2 in response to depletion of endoplasmic reticulum Ca2+ stores. Loss‐of‐function mutations in the human ORAI1 and STIM1 genes abolish CRAC channel function and SOCE in a variety of non‐excitable cells including lymphocytes and other immune cells, resulting in a unique clinical syndrome termed CRAC channelopathy. It is dominated by severe immunodeficiency and autoimmunity due to impaired SOCE and defects in the function of several lymphocyte subsets. These include CD8+ T cells, CD4+ effector and regulatory T cells, natural killer (NK) cells and B cells. This review provides a concise discussion of the role of CRAC channels in these lymphocyte populations and the regulation of adaptive immune responses to infection, in autoimmunity and inflammation.
Is Violent Radicalisation Associated with Poverty, Migration, Poor Self-Reported Health and Common Mental Disorders?

Background Doctors, lawyers and criminal justice agencies need methods to assess vulnerability to violent radicalization. In synergy, public health interventions aim to prevent the emergence of risk behaviours as well as prevent and treat new illness events. This paper describes a new method of assessing vulnerability to violent radicalization, and then investigates the role of previously reported causes, including poor self-reported health, anxiety and depression, adverse life events, poverty, and migration and socio-political factors. The aim is to identify foci for preventive intervention. Methods A cross-sectional survey of a representative population sample of men and women aged 18–45, of Muslim heritage and recruited by quota sampling by age, gender, working status, in two English cities. The main outcomes include self-reported health, symptoms of anxiety and depression (common mental disorders), and vulnerability to violent radicalization assessed by sympathies for violent protest and terrorist acts. Results 2.4% of people showed some sympathy for violent protest and terrorist acts. Sympathy was more likely to be articulated by the under 20s, those in full time education rather than employment, those born in the UK, those speaking English at home, and high earners (>£75,000 a year). People with poor self-reported health were less likely to show sympathies for violent protest and terrorism. Anxiety and depressive symptoms, adverse life events and socio-political attitudes showed no associations. Conclusions Sympathies for violent protest and terrorism were uncommon among men and women, aged 18–45, of Muslim heritage living in two English cities. Youth, wealth, and being in education rather than employment were risk factors.
Influence of abutment design on retention of metal copings cemented to implants

Abstract Objective The study evaluated the influence of abutment design on the retention of implant-cemented metal copings. Material and methods Two abutments of the same system with the same indications, height and the total occlusal convergence, but of different designs were evaluated. Ten RN synOcta abutments (Straumann, Waltham, MA) and ten RN titanium solid abutments (Straumann, Waltham, MA) were tightened to 35 Ncm on 20 implant analogs previously placed in resin blocks. Twenty plastic burnout copings were waxed, included, cast and machined by a single operator. Coping was inspected for surface irregularities using a stereomicroscope at 10x magnification, and then, they were cemented (Temp Bond NE, Kerr, Romulus, MI) with 5 kg load for 10 min. The samples were stored for 24 h in room temperature and 100% humidity and then subjected to pull-out test at a crosshead speed of 0.5 mm/min. The load required to dislodge each coping was recorded (kgf) and and mean values for each group statistically calculated. Means and standard deviations of loads at failure were analyzed using Student’s t-test. Results The mean load required to dislodge the copings showed by synOcta abutments (11.19 kgf) was statiscally higher than s solid abutments (10.18 kgf). Conclusions: It was concluded that the abutment design influenced significantly the retention of metal copings.
Folding Properties of Cytosine Monophosphate Kinase from E. coli Indicate Stabilization through an Additional Insert in the NMP Binding Domain

The globular 25 kDa protein cytosine monophosphate kinase (CMPK, EC ID: 2.7.4.14) from E. coli belongs to the family of nucleoside monophosphate (NMP) kinases (NMPK). Many proteins of this family share medium to high sequence and high structure similarity including the frequently found α/β topology. A unique feature of CMPK in the family of NMPKs is the positioning of a single cis-proline residue in the CORE-domain (cis-Pro124) in conjunction with a large insert in the NMP binding domain. This insert is not found in other well studied NMPKs such as AMPK or UMP/CMPK. We have analyzed the folding pathway of CMPK using time resolved tryptophan and FRET fluorescence as well as CD. Our results indicate that unfolding at high urea concentrations is governed by a single process, whereas refolding in low urea concentrations follows at least a three step process which we interpret as follows: Pro124 in the CORE-domain is in cis in the native state (Nc) and equilibrates with its trans-isomer in the unfolded state (Uc - Ut). Under refolding conditions, at least the Ut species and possibly also the Uc species undergo a fast initial collapse to form intermediates with significant amount of secondary structure, from which the trans-Pro124 fraction folds to the native state with a 100-fold lower rate constant than the cis-Pro124 species. CMPK thus differs from homologous NMP kinases like UMP/CMP kinase or AMP kinase, where folding intermediates show much lower content of secondary structure. Importantly also unfolding is up to 100-fold faster compared to CMPK. We therefore propose that the stabilizing effect of the long NMP-domain insert in conjunction with a subtle twist in the positioning of a single cis-Pro residue allows for substantial stabilization compared to other NMP kinases with α/β topology.
Socio-demographic and living conditions of tribes of Mysore District, Karnataka

The present study is an effort to explore the socio-emographic and living conditions among the Hakkipikki, Iruliga, Jenukuruba and Kadukuruba children of 0-6 year’s age group of Mysore District, Karnataka. The study reveals that most of the children fall under low income category, majority of the tribal communities are living in tiled roofs, no separate kitchen, no proper ventilation but electrified houses, poor drainage and lavatory facility.
CDX2 is essential for cell proliferation and polarity in porcine blastocysts

The role of CDX2 in trophectoderm (TE) cells has been extensively studied, yet the results are contradictory and species specific. Here, CDX2 expression and function were explored in early porcine embryos. Notably, siRNA-mediated gene knockdown and lentivirus-mediated TE-specific gene regulation demonstrated that CDX2 is essential for the maintenance of blastocyst integrity by regulating the BMP4-mediated blastocyst niche and classic protein kinase C (PKC)-mediated TE polarity in mammalian embryos. Mechanistically, CDX2-depleted porcine embryos stalled at the blastocyst stage and exhibited apoptosis and inactive cell proliferation, possibly resulting from BMP4 downregulation. Moreover, TE cells in CDX2-depleted blastocysts displayed defective F-actin apical organization associated with downregulation of PKCα (PRKCA). Collectively, these results provide further insight into the functional diversity of CDX2 in early mammalian embryos. Summary: The transcription factor CDX2 functions in the trophectoderm of pig embryos to maintain polarity and integrity of the blastocyst, revealing further diversity in CDX2 activities across mammals.
Deferasirox treatment of iron-overloaded chelation-naïve and prechelated patients with myelodysplastic syndromes in medical practice: results from the observational studies eXtend and eXjange

EXtend and eXjange were prospective, 1‐yr, non‐interventional, observational, multicentre studies that investigated deferasirox, a once‐daily oral iron chelator, in iron‐overloaded chelation‐naïve and prechelated patients with myelodysplastic syndromes (MDS), respectively, treated in the daily‐routine setting of office‐based physicians. No inclusion or exclusion criteria or additional monitoring procedures were applied. Deferasirox was administered as recommended in the European Summary of Product Characteristics. Haematological parameters and adverse events (AEs) were collected at two‐monthly intervals. Data from 123 chelation‐naïve patients with MDS (mean age 70.4 yrs) with median baseline serum ferritin level of 2679 (range 184–16 500) ng/mL, and 44 prechelated patients with MDS (mean age 69.6 yrs) with median baseline serum ferritin level of 2442 (range 521–8565) ng/mL, were assessed. The mean prescribed daily dose of deferasirox at the first visit was 15.7 and 18.7 mg/kg/d, respectively. Treatment with deferasirox produced a significant reduction in median serum ferritin levels in chelation‐naïve patients with MDS from 2679 to 2000 ng/mL (P = 0.0002) and a pronounced decrease in prechelated patients with MDS from 2442 to 2077 ng/mL (P = 0.06). The most common drug‐related AEs were gastrointestinal, increased serum creatinine levels and rash. These studies demonstrate that deferasirox used in physicians’ medical practices is effective in managing iron burden in transfusion‐dependent patients with MDS.