Miracle-dz/UniFAR-FTUs huggingface dataset:
Chemical enrichment of galaxy clusters from hydrodynamical simulations

We present cosmological hydrodynamical simulations of galaxy clusters aimed at studying the process of metal enrichment of the intra-cluster medium (ICM). These simulations have been performed by implementing a detailed model of chemical evolution in the TREE-PM+SPM GADGET-2 code. This model allows us to follow the metal release from Type II supernovae (SNII), Type Ia supernovae (SNIa) and asymptotic giant branch (AGB) stars by properly accounting for the lifetimes of stars of different mass, as well as to change the stellar initial mass function (IMF), the lifetime function and the stellar yields. As such, our implementation of chemical evolution represents a powerful instrument to follow the cosmic history of metal production. The simulations presented here have been performed with the twofold aim of checking numerical effects, as well as the impact of changing the model of chemical evolution and the efficiency of stellar feedback. In general, we find that the distribution of metals produced by SNII is more clumpy than for the product of low-mass stars, as a consequence of the different time-scales over which they are released. Using a standard Salpeter IMF produces a radial profile of iron abundance which is in fairly good agreement with observations available out to ≃0.6R 500 . This result holds almost independent of the numerical scheme adopted to distribute metals around star-forming regions. The mean age of enrichment of the ICM corresponds to redshift z ∼ 0.5, which progressively increases outside the virial region. Increasing resolution, we improve the description of a diffuse high-redshift enrichment of the inter-galactic medium (IGM). This turns into a progressively more efficient enrichment of the cluster outskirts, while having a smaller impact at R ≤ 0.5R 500 . As for the effect of the model of chemical evolution, we find that changing the IMF has the strongest impact. Using an IMF, which is top-heavier than the Salpeter one, provides a larger iron abundance, possibly in excess of the observed level, also significantly increasing the [O/Fe] relative abundance. Our simulations always show an excess of low-redshift star formation and, therefore, of the abundance of oxygen in central cluster regions, at variance with observations. This problem is not significantly ameliorated by increasing the efficiency of the stellar feedback.
Cdc50p Plays a Vital Role in the ATPase Reaction Cycle of the Putative Aminophospholipid Transporter Drs2p*♦

Members of the P4 subfamily of P-type ATPases are believed to catalyze transport of phospholipids across cellular bilayers. However, most P-type ATPases pump small cations or metal ions, and atomic structures revealed a transport mechanism that is conserved throughout the family. Hence, a challenging problem is to understand how this mechanism is adapted in P4-ATPases to flip phospholipids. P4-ATPases form heteromeric complexes with Cdc50 proteins. The primary role of these additional polypeptides is unknown. Here, we show that the affinity of yeast P4-ATPase Drs2p for its Cdc50-binding partner fluctuates during the transport cycle, with the strongest interaction occurring at a point where the enzyme is loaded with phospholipid ligand. We also find that specific interactions with Cdc50p are required to render the ATPase competent for phosphorylation at the catalytically important aspartate residue. Our data indicate that Cdc50 proteins are integral components of the P4-ATPase transport machinery. Thus, acquisition of these subunits may have been a crucial step in the evolution of flippases from a family of cation pumps.
Uncovering Expected Returns: Information in Analyst Coverage Proxies

We show that analyst coverage proxies contain information about expected returns. We decompose analyst coverage into abnormal and expected components using a simple characteristic-based model and show that firms with abnormally high analyst coverage subsequently outperform firms with abnormally low coverage by approximately 80 basis points per month. We also show abnormal coverage rises following exogenous shocks to underpricing and predicts improvements in firms’ fundamental performance, suggesting that return predictability stems from analysts more heavily covering underpriced stocks. Our findings highlight the usefulness of analysts’ actions in expected return estimations, and a potential inference problem when coverage proxies are used to study information asymmetry and dissemination.
Can Machine Think

Recent advances in permutable methodologies and homogeneous configurations do not necessarily obviate the need for superblocks. Given the current status of constanttime archetypes, computational biologists particularly d esire the improvement of superblocks, which embodies the robust principles of electrical engineering. We explore a novel application for the extensive unification of SCSI disks and lambda calculus, which we call Norice.
Hematogenous Vertical Transmission of Herpes Simplex Virus Type 1 in Mice

ABSTRACT Herpes simplex virus type 1 (HSV-1) is a neurotropic virus that causes severe disease and death in newborn humans but, to date, it remains unclear how neonatal infection occurs. We show here that the vertical transmission of HSV-1 in mice is mainly hematogenous and involves the colonization of the neonate central nervous system (CNS). HSV-1 DNA was mainly detected in the blood and CNS of the offspring born to latently infected mothers; no significant differences were seen between the viral DNA concentrations in the blood of these mothers and their female progeny (either neonate or adult). The administration of acyclovir during gestation reduced or eliminated both the maternal and the neonatal viral DNA in the blood. Embryo transfer was performed to ensure (as far as possible) that only vertical hematogenous infection took place. Immunohistochemical analysis detected viral proteins in the encephalon of the offspring. Immunofluorescence studies provided immunoreactive evidence of HSV-1 proteins in the neurons of the hippocampus and showed that these viruses can molecularly reactivate after hyperthermia. Neonatal HSV-1 infection therefore appears to be mainly caused by hematogenous vertical transmission, and the viruses that colonize the offspring CNS are capable of molecular reactivation after a period of latency.
Panel growth regressions with general predetermined variables: Likelihood-based estimation and bayesian averaging

In this paper I estimate empirical growth models simultaneously considering endogenous regressors and model uncertainty. In order to apply Bayesian methods such as Bayesian Model Averaging (BMA) to dynamic panel data models with predetermined or endogenous variables and fixed effects, I propose a likelihood function for such models. The resulting maximum likelihood estimator can be interpreted as the LIML counterpart of GMM estimators. Via Monte Carlo simulations, I conclude that the finite-sample performance of the proposed estimator is better than that of the commonly-used standard GMM. In contrast to the previous consensus in the empirical growth literature, empirical results indicate that once endogeneity and model uncertainty are accounted for, the estimated convergence rate is not significantly different from zero. Moreover, there seems to be only one variable, the investment ration, that causes long-run economic growth.
Diabetes Prediction: A Deep Learning Approach

Nowadays, Diabetes is one of the most common and severe diseases in Bangladesh as well as all over the world. It is not only harmful to the blood but also causes different kinds of diseases like blindness, renal disease, kidney problem, heart diseases etc. that causes a lot of death per year. So, it badly needs to develop a system that can effectively diagnose the diabetes patients using medical details. We propose a strategy for the diagnosis of diabetes using deep neural network by training its attributes in five-fold and ten-fold crossvalidation fashion. The Pima Indian Diabetes (PID) data set is retrieved from the UCI machine learning repository database. The results on PID dataset demonstrate that deep learning approach design an auspicious system for the prediction of diabetes with prediction accuracy of 98.35%, F1 score of 98, and MCC of 97 for five-fold cross-validation. Additionally, accuracy of 97.11%, sensitivity of 96.25%, and specificity of 98.80% are obtained for ten-fold cross-validation. The experimental results exhibit that the proposed system provides promising results in case of five-fold cross-validation.
In Vivo Two-Photon Ca2+ Imaging Reveals Selective Reward Effects on Stimulus-Specific Assemblies in Mouse Visual Cortex

Experiences can alter functional properties of neurons in primary sensory neocortex but it is poorly understood how stimulus–reward associations contribute to these changes. Using in vivo two-photon calcium imaging in mouse primary visual cortex (V1), we show that association of a directional visual stimulus with reward results in broadened orientation tuning and sharpened direction tuning in a stimulus-selective subpopulation of V1 neurons. Neurons with preferred orientations similar, but not identical to, the CS+ selectively increased their tuning curve bandwidth and thereby exhibited an increased response amplitude at the CS+ orientation. The increase in response amplitude was observed for a small range of orientations around the CS+ orientation. A nonuniform spatial distribution of reward effects across the cortical surface was observed, as the spatial distance between pairs of CS+ tuned neurons was reduced compared with pairs of CS− tuned neurons and pairs of control directions or orientations. These data show that, in primary visual cortex, formation of a stimulus–reward association results in selective alterations in stimulus-specific assemblies rather than population-wide effects.
Plasma carotenoid levels are not directly related to heavy metal exposure or reproductive success in three insectivorous passerines

The authors measured plasma carotenoid levels in three insectivorous bird species, the pied flycatcher (Ficedula hypoleuca), the blue tit (Cyanistes caeruleus), and the great tit (Parus major) in metal‐polluted and unpolluted sites around a copper smelter. Their aim was to determine whether there was interspecific, age‐related, or yearly variation in carotenoid levels and their responses to the ambient pollution level. The three bird species showed qualitatively and quantitatively similar carotenoid profiles, with lutein being always the predominant plasma carotenoid. Ficedula hypoleuca nestlings showed higher plasma carotenoid levels in the unpolluted than in the polluted area, whereas no significant differences were found in F. hypoleuca females or in nestlings or females of the Parids. Yearly comparison of plasma concentrations (only for P. major nestlings) showed, however, that levels varied nonsynchronously between polluted and unpolluted sites among the breeding seasons, with the yearly variation being higher in the polluted area. The survival of nestlings did not depend on their plasma carotenoid concentrations. The two Parid species showed lower nestling survival at sites with high metal exposure levels. The authors conclude that plasma carotenoid levels showed a marked spatial, temporal, and age‐related variation, but were not directly related to heavy metal exposure or the reproductive success of birds. Environ. Toxicol. Chem. 2012;31:1363–1369. © 2012 SETAC
In silico and in vitro evaluation of exonic and intronic off-target effects form a critical element of therapeutic ASO gapmer optimization

With many safety and technical limitations partly mitigated through chemical modifications, antisense oligonucleotides (ASOs) are gaining recognition as therapeutic entities. The increase in potency realized by ‘third generation chemistries’ may, however, simultaneously increase affinity to unintended targets with partial sequence complementarity. However, putative hybridization-dependent off-target effects (OTEs), a risk historically regarded as low, are not being adequately investigated. Here we show an unexpectedly high OTEs confirmation rate during screening of fully phosphorothioated (PS)-LNA gapmer ASOs designed against the BACH1 transcript. We demonstrate in vitro mRNA and protein knockdown of off-targets with a wide range of mismatch (MM) and gap patterns. Furthermore, with RNase H1 activity residing within the nucleus, hybridization predicted against intronic regions of pre-mRNAs was tested and confirmed. This dramatically increased ASO-binding landscape together with relatively high potency of such interactions translates into a considerable safety concern. We show here that with base pairing-driven target recognition it is possible to predict the putative off-targets and address the liability during lead design and optimization phases. Moreover, in silico analysis performed against both primary as well as spliced transcripts will be invaluable in elucidating the mechanism behind the hepatoxicity observed with some LNA-modified gapmers.
Progression of Cardio-Metabolic Risk Factors in Subjects Born Small and Large for Gestational Age

Background Subjects born small (SGA) and large (LGA) for gestational age have an increased risk of cardio-metabolic alterations already during prepuberty. Nevertheless, the progression of their cardio-metabolic profile from childhood to adolescence has not been fully explored. Our aim was to assess potential changes in the cardio-metabolic profile from childhood to adolescence in subjects born SGA and LGA compared to those born appropriate (AGA) for gestational age. Methods This longitudinal study included 35 AGA, 24 SGA and 31 LGA subjects evaluated during childhood (mean age (±SD) 8.4±1.4 yr) and then re-assessed during adolescence (mean age 13.3±1.8 yr). BMI, blood pressure, insulin resistance (fasting insulin, HOMA-IR) and lipids were assessed. A cardio-metabolic risk z-score was applied and this consisted in calculating the sum of sex-specific z-scores for BMI, blood pressure, HOMA-IR, triglycerides and triglycerides:high-density lipoprotein cholesterol ratio. Results Fasting insulin and HOMA-IR were higher in SGA and LGA than AGA subjects both during childhood (all P<0.01) and adolescence (all P<0.01). Similarly, the clustered cardio-metabolic risk score was higher in SGA and LGA than AGA children (both P<0.05), and these differences among groups increased during adolescence (both P<0.05). Of note, a progression of the clustered cardio-metabolic risk score was observed from childhood to adolescence within SGA and within LGA subjects (both P<0.05). Conclusions SGA and LGA subjects showed an adverse cardio-metabolic profile during childhood when compared to AGA peers, with a worsening of this profile during adolescence. These findings indicate an overtime progression of insulin resistance and overall estimated cardiovascular risk from childhood to adolescence in SGA and LGA populations.
Pilot study of a ketogenic diet in relapsing-remitting MS

Objective To assess the safety and tolerability of a modified Atkins diet (KDMAD), a type of ketogenic diet (KD), in subjects with relapsing MS while exploring potential benefits of KDs in MS. Methods Twenty subjects with relapsing MS enrolled into a 6-month, single-arm, open-label study of the KDMAD. Adherence to KDMAD was objectively monitored by daily urine ketone testing. Fatigue and depression scores and fasting adipokines were obtained at baseline and on diet. Brain MRI was obtained at baseline and 6 months. Intention to treat was used for primary data analysis, and a per-protocol approach was used for secondary analysis. Results No subject experienced worsening disease on diet. Nineteen subjects (95%) adhered to KDMAD for 3 months and 15 (75%) adhered for 6 months. Anthropometric improvements were noted on KDMAD, with reductions in body mass index and total fat mass (p < 0.0001). Fatigue (p = 0.002) and depression scores (p = 0.003) were improved. Serologic leptin was significantly lower at 3 months (p < 0.0001) on diet. Conclusions KDMAD is safe, feasible to study, and well tolerated in subjects with relapsing MS. KDMAD improves fatigue and depression while also promoting weight loss and reducing serologic proinflammatory adipokines. Classification of evidence The study is rated Class IV because of the absence of a non-KD control group.
Effect of oral glucocorticoid treatment on serum inflammatory markers in acute asthma

BACKGROUND Acute asthma is associated with elevated serum concentrations of products of activated T cells and eosinophils. AIMS To compare the changes in concentrations of these products with disease severity and changes in lung function following oral prednisolone treatment. METHODS Twenty patients (mean age 8.7 years) were recruited on admission with acute asthma to a district general hospital. Disease severity was recorded before and after treatment with oral prednisolone using a validated pulmonary index score. Serum concentrations of interleukin (IL)-4, IL-5, soluble (s)CD25 (soluble IL-2 receptor), using a specific enzyme linked immunosorbent assay, and eosinophil cationic protein (ECP), using radioimmunoassay, were measured concomitantly. Non-asthmatic children (n = 6, mean age 9.2 years) undergoing elective surgery were recruited as controls, and serum samples were obtained on one occasion without treatment. Main outcome measures were changes in serum concentrations of cytokines and ECP, clinical asthma severity score, and peak expiratory flow rate. RESULTS As expected, oral glucocorticoid treatment in the children with asthma was associated with clinical improvement and also with significant reductions in serum concentrations of IL-5 (mean 5.59 to 2.19 pg/ml, p = 0.0001), sCD25 (mean 2236 to 1772 pg/ml, p = 0.002), and ECP (mean 54.3 to 33.1 pg/ml, p = 0.0001). Serum IL-4 concentrations, in most patients and all the controls, remained below the sensitivity of the assay. However, serum concentrations of IL-5, sCD25, and ECP remained significantly higher than in controls, even after treatment with oral glucocorticoids (p = 0.03). CONCLUSIONS These data suggest that T cell mediated inflammation may persist in childhood asthma despite apparent clinical remission associated with conventional doses of prednisolone. The long term consequences of persistent inflammation after an apparently treated acute attack of asthma require clarification. Clinical assessment and pulmonary function are inadequate surrogates for airway inflammation.
The role of inorganic pyrophosphate in aortic valve calcification.

BACKGROUND AND AIM OF THE STUDY Aortic valve (AV) calcification is a major cause of morbidity and mortality, yet the molecular mechanisms involved are poorly understood. Hence, an ex vivo model of calcification in intact AVs was developed in order to test the role of orthophosphate and pyrophosphate (PPi), both of which factors are known to influence vascular calcification. METHODS Porcine AV leaflets were cultured in serum-free medium under static conditions for eight days, over which time leaflet architecture and viability were preserved. Calcification was measured as the incorporation of 45Ca, with confirmation by Alizarin Red staining. RESULTS Calcification required both a high phosphate concentration (3.8 mM) and removal of PPi with alkaline phosphatase or inorganic pyrophosphatase. Calcification occurred predominantly on the fibrosa and was arrested by the bisphosphonate etidronate, a non-hydrolyzable analog of PPi. Leaflets released PPi into the medium, and this was enhanced by MLS38949, a specific inhibitor of tissue non-specific alkaline phosphatase (TNAP). Furthermore, leaflets synthesized PPi from extracellular ATP, which was reduced by β,γ-methylene-ATP, an inhibitor of ectonucleotide pyrophosphorylase phosphodiesterase (NPP1). CONCLUSION The ex vivo AV calcification model developed in the present study showed that extracellular PPi, produced by valvular tissue, is a potent inhibitor of valvular calcification. In addition to synthesis, hydrolysis by TNAP also controls PPi levels and calcification. The results suggest that a decreased synthesis or increased hydrolysis of pyrophosphate may contribute to valvular calcification, and that bisphosphonates or inhibitors of TNAP are potential preventive strategies of the process. TNAP are potential preventive strategies.
Serious complications after infective endocarditis.

INTRODUCTION The objective of the present study was to review all cases of infective endocarditis at our hospital between 2002 and 2006 concerning the bacteriological aetiology and outcomes. MATERIAL AND METHODS This is a retrospective study based on medical records from patients in whom the discharge diagnosis infective endocarditis was established according to Duke's criteria. The study included 151 patients. RESULTS The most prominent risk factors were valvular prostheses (22%) and known valvular disease (21%). The median diagnostic delay was four days (0-103 days). The most prominent causative microorganism was Staphylococcus aureus (41%), followed by non-haemolytic streptococci (21%), haemolytic streptococci (10%) and enterococci (14%). The most frequently occurring complications were embolic events (29%) and valvular insufficiency (26%). Renal insufficiency, multi-organic failure and disseminated intravascular coagulation occurred in 36 patients (24%). Half of the patients (51%) received surgical treatment. The overall in-hospital mortality was 29%, and 16% had severe sequelae at discharge. High mortality was found, particularly in the elderly patients, in patients who had staphylococcal endocarditis and in patients with valvular prosthesis. CONCLUSION Despite considerable progress in diagnostics and treatment facilities, infective endocarditis remains a serious disease with long diagnostic delay times, high complication rates and a high mortality.
Molecular characterization and immunolocalization of the olfactory co‐receptor Orco from two blood‐feeding muscid flies, the stable fly (Stomoxys calcitrans, L.) and the horn fly (Haematobia irritans irritans, L.)

Biting flies are economically important blood‐feeding pests of medical and veterinary significance. Chemosensory‐based biting fly behaviours, such as host/nutrient source localization and ovipositional site selection, are intriguing targets for the development of supplemental control strategies. In an effort to expand our understanding of biting fly chemosensory pathways, transcripts encoding the highly conserved insect odorant co‐receptor (Orco) were isolated from two representative biting fly species, the stable fly (Scal\Orco) and the horn fly (Hirr\Orco). Orco forms a complex with an odour‐specific odorant receptor to form an odour‐gated ion channel. The biting fly transcripts were predicted to encode proteins with 87–94% amino acid similarity to published insect Orco sequences and were detected in various immature stages as well as in adult structures associated with olfaction, i.e. the antennae and maxillary palps, and gustation, i.e. the proboscis. Further, the relevant proteins were immunolocalized to specific antennal sensilla using anti‐serum raised against a peptide sequence conserved between the two fly species. Results from the present study provide a basis for functional evaluation of repellent/attractant effects on as yet uncharacterized stable fly and horn fly conventional odorant receptors.