Miracle-dz/UniFAR-FTUs huggingface dataset:
Simulating star formation in molecular cores. II. The effects of different levels of turbulence

We explore, by means of a large ensemble of SPH simulations, how the level of turbulence affects the collapse and fragmentation of a star-forming core. All our simulated cores have the same mass (5.4 M ○. ), the same initial density profile (chosen to fit observations of L1544), and the same barotropic equation of state, but we vary (a) the initial level of turbulence (as measured by the ratio of turbulent to gravitational energy, α turb = U turb /|Ω| = 0, 0.01, 0.025, 0.05, 0.10 and 0.25) and (b), for fixed α turb , the details of the initial turbulent velocity field (so as to obtain good statistics). A low level of turbulence (α turb ∼ 0.05) suffices to produce multiple systems, and as α turb is increased, the number of objects formed and the companion frequency both increase. The mass function is bimodal, with a flat low-mass segment representing single objects ejected from the core before they can accrete much, and a Gaussian high-mass segment representing objects which because they remain in the core grow by accretion and tend to pair up in multiple systems. The binary statistics reported for field G-dwarfs by Duquennoy & Mayor (1991, A&A, 248, 485) are only reproduced with α turb ∼ 0.05. For much lower values of α turb (≤0.025), insufficient binaries are formed. For higher values of α turb (≥0,10), there is a significant sub-population of binaries with small semi-major axis and large mass-ratio (i.e. close binaries with components of comparable mass). This sub-population is not present in Duquennoy & Mayor's sample, although there is some evidence for it in the pre-Main Sequence population of Taurus analyzed by White & Ghez (2001, ApJ, 556, 265). It arises because with larger α turb , more low-mass objects are formed, and so there is more scope for the binaries remaining in the core to be hardened by ejecting these low-mass objects. Hard binaries thus formed then tend to grow towards comparable mass by competitive accretion of material with relatively high specific angular momentum.
Tissue inhibitor of metalloproteinase-1 exacerbated renal interstitial fibrosis through enhancing inflammation.

BACKGROUND Tissue inhibitor of metalloproteinase-1 (TIMP-1) is associated with renal fibrosis. Furthermore, it is a multi-functional protein, and whether it has other roles in renal fibrosis is unknown. As several inflammatory mediators are substrates of matrix metalloproteinases (MMPs), TIMP-1 might affect renal fibrosis via inflamatory pathways. METHODS Plasmids containing the sense and antisense human TIMP-1 sequence were stably transfected into the human kidney proximal tubular epithelial cell line (HKC), MMP-2 and MMP-9 siRNA were transiently transfected into HKC and the transfected cells were stimulated with phorbol 12-myristate 13-acetate (PMA). In vivo, we established unilateral ureteral obstruction (UUO) models by using homozygote human TIMP-1 transgenic mice. The expression of intercellular adhesion molecule-1 (ICAM-1) in transfected cells and F4/80-positive cells in the renal interstitium were examined by indirect immunofluorescence. Protein levels in the cells and UUO models were examined by western blot, and the activities of the gelatinases and TIMP-1 were examined by gelatin zymography and reverse zymography, respectively. RESULTS After stimulation with PMA, the activities of the gelatinases were decreased, ICAM-1 was upregulated, and soluble ICAM-1 in the supernatant was decreased, in HKC transfected with sense TIMP-1, and ICAM-1 was increased in HKC transfected with MMP-9 siRNA. At 14 days after UUO, it was found that compared with wild-type mice, in transgenic mice, with upregulation of TIMP-1, activities of gelatinases were downregulated, ICAM-1, transforming growth factor-beta1 (TGF-beta1), collagens I and III were upregulated, and the extent of renal fibrosis and infiltration of macrophages was more severe. CONCLUSION Overexpression of TIMP-1 could promote renal interstitial fibrosis through the inflammatory pathway, which might be partly induced by upregulating ICAM-1.
Radiological progression and lung function decrements among silica-exposed ceramic workers: a longitudinal study

Abstract Objectives: This follow-up study set out to evaluate the natural course and radiographic progression of silicosis among ceramic workers and describe the risk factors related with disease progression. Materials and methods: We retrospectively analyzed the data of ceramic workers with silicosis who were referred to our hospital between February 2010 and March 2018. A total of 165 ceramic workers followed at least 24 months and with at least two chest radiographs were included in the study. Results: The duration of silica exposure ranged from 5.5 to 27 (median 13.6) years. The numbers of patients according to follow-up time were as follows: 38 (2–2.9) years, 77 (3–3.9) years, 26 (4–4.9) years, 17 (5–5.9) years, and 7 (≥6) years. Overall 62 of 165 (37.5%) cases showed radiologic evidences of progression ranging from 2 to 8.9 years (mean 3.7 years). Pulmonary function loss rate among silicosis patients was 36.9% (61/165). Multiple logistic regression analysis showed a significant relation between radiographic progression and age (OR, 1.079: 95% CI, 1.011–1.152), follow-up time (OR, 1.557: 95% CI, 1.144–2.118), and the ILO category (category 2 or 3) at first visit (OR, 3.507: 95% CI, 1.505–8.170). Conclusions: Our findings suggest that one-third of Turkish ceramic workers with silicosis who were followed up to 8.9 years showed progression that was related to increasing age greater ILO category at time of initial visit and follow-up duration.
A dynamic analysis of the shade-induced plasticity in Arabidopsis thaliana rosette leaf development reveals new components of the shade-adaptative response.

BACKGROUND AND AIMS It is well known that plant aerial development is affected by light intensity in terms of the date of flowering, the length of stems and petioles, and the final individual leaf area. The aim of the work presented here was to analyse how shade-induced changes in leaf development occur on a dynamic basis from the whole rosette level to that of the cells. METHODS Care was taken to ensure that light intensity was the only source of micro-meteorological variation in the study. The dynamics of leaf production, rosette expansion, individual leaf area expansion and epidermal cell expansion were analysed in Arabidopsis thaliana plants grown under two light intensities in three independent experiments. KEY RESULTS The total area of rosette leaves was reduced by the shading treatment. Both the number of leaves produced and their individual leaf areas were reduced. The reduction in leaf number was associated with a reduction in leaf initiation rate and the duration of the phase of leaf production. The reduction in individual leaf area was associated with a reduction in leaf expansion rate and an increase in the duration of leaf expansion. The changes in leaf expansion dynamics were accompanied by a decrease in epidermal cell number which was partly compensated for by an increase in epidermal cell area. Overall, the whole rosette leaf expansion rate was reduced by shading, whereas the total duration of rosette leaf expansion was unaffected. This was mainly due to the accumulation of the increases in the durations of expansion of each individual leaf which was associated with an increase in cell expansion. CONCLUSIONS The dynamic analysis presented here reveals a new shade-adaptative response mediated via the control of area expansion at the cell, organ and whole plant levels.
A report on state‐wide implementation of newborn screening for X‐linked Adrenoleukodystrophy

Minnesota became the fourth state to begin newborn screening (NBS) for X‐linked adrenoleukodystrophy (X‐ALD) in 2017. As there is limited retrospective data available on NBS for X‐ALD, we analyzed Minnesota's NBS results from the first year of screening. C26:0 lysophosphatidylcholine (C26:0‐LPC) screening results of 67,836 infants and confirmatory testing (ABCD1 gene and serum VLCFA analysis) for screen positives were obtained. Fourteen infants (nine males, five females) screened positive for X‐ALD and all were subsequently confirmed to have X‐ALD, with zero false positives. The birth prevalence of X‐ALD in screened infants was 1 in 4,845 and 1 in 3,878 males, more than five times previous reported incidences. Pedigrees of affected infants were analyzed, and 17 male (mean age of 17) and 24 female relatives were subsequently diagnosed with X‐ALD. Phenotypes of these family members included self‐reported mild neuropathy symptoms in two males and seven females, and childhood cerebral disease (ccALD) and adrenal insufficiency in one male. We observed fewer cases of ccALD and adrenal insufficiency than expected in male family members (5.9% of males for both) compared to previous observations. Together, these findings suggest that the spectrum of X‐ALD may be broader than previously described and that milder cases may previously have been underrepresented. Other challenges included a high frequency of variants of uncertain significance in ABCD1 and an inability to predict phenotypic severity. We posit that thoughtful planning to address these novel challenges and coordination by dedicated specialists will be imperative for successful implementation of population‐based screening for X‐ALD.
Sonic Hedgehog Ligand: A Role in Formation of a Mesenchymal Niche in Human Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is characterised by desmoplasia, thought to support progression and chemotherapeutic resistance. The Hedgehog pathway is known to play an important role in this cancer. While the upregulation of Sonic hedgehog (Shh) in the epithelium of PDAC is known, we investigated its expression in the tumour microenvironment in order to find new targets for new chemotherapeutical approaches. Immunohistochemistry was used for the investigation of Shh and Vimentin in primary human pancreatic tissues. Gene (qRT-PCR) and protein (immunofluorescence) expression of Shh, αSMA (a marker of the mesenchymal phenotype) and periostin (a marker of mesenchymal cells within a mixed population) were investigated in in vitro cell models. Shh expression was significantly upregulated in the stromal and epithelial compartments of poorly-differentiated PDAC samples, with a strong correlation with the amount of stroma present. Characterisation of stromal cells showed that there was expression of Shh ligand in a mixed population comprising αSMA+ myofibroblasts and αSMA− mesenchymal stem cells. Moreover, we demonstrated the interaction between these cell lines by showing a higher rate of mesenchymal cell proliferation and the upregulation of periostin. Therefore, targeting stromal Shh could affect the equilibrium of the tumour microenvironment and its contribution to tumour growth.
High-dimensional Gaussian model selection on a Gaussian design

We consider the problem of estimating the conditional mean of a real Gaussian variable $\nolinebreak Y=\sum_{i=1}^p\nolinebreak\theta_iX_i+\nolinebreak \epsilon$ where the vector of the covariates $(X_i)_{1\leq i\leq p}$ follows a joint Gaussian distribution. This issue often occurs when one aims at estimating the graph or the distribution of a Gaussian graphical model. We introduce a general model selection procedure which is based on the minimization of a penalized least-squares type criterion. It handles a variety of problems such as ordered and complete variable selection, allows to incorporate some prior knowledge on the model and applies when the number of covariates $p$ is larger than the number of observations $n$. Moreover, it is shown to achieve a non-asymptotic oracle inequality independently of the correlation structure of the covariates. We also exhibit various minimax rates of estimation in the considered framework and hence derive adaptiveness properties of our procedure.
The knob protein KAHRP assembles into a ring-shaped structure that underpins virulence complex assembly

Plasmodium falciparum mediates adhesion of infected red blood cells (RBCs) to blood vessel walls by assembling a multi-protein complex at the RBC surface. This virulence-mediating structure, called the knob, acts as a scaffold for the presentation of the major virulence antigen, P. falciparum Erythrocyte Membrane Protein-1 (PfEMP1). In this work we developed correlative STochastic Optical Reconstruction Microscopy–Scanning Electron Microscopy (STORM-SEM) to spatially and temporally map the delivery of the knob-associated histidine-rich protein (KAHRP) and PfEMP1 to the RBC membrane skeleton. We show that KAHRP is delivered as individual modules that assemble in situ, giving a ring-shaped fluorescence profile around a dimpled disk that can be visualized by SEM. Electron tomography of negatively-stained membranes reveals a previously observed spiral scaffold underpinning the assembled knobs. Truncation of the C-terminal region of KAHRP leads to loss of the ring structures, disruption of the raised disks and aberrant formation of the spiral scaffold, pointing to a critical role for KAHRP in assembling the physical knob structure. We show that host cell actin remodeling plays an important role in assembly of the virulence complex, with cytochalasin D blocking knob assembly. Additionally, PfEMP1 appears to be delivered to the RBC membrane, then inserted laterally into knob structures.
Dacomitinib (PF-00299804), an Irreversible Pan-HER Inhibitor, Inhibits Proliferation of HER2-Amplified Breast Cancer Cell Lines Resistant to Trastuzumab and Lapatinib

The human EGF (HER) family of receptors has been pursued as therapeutic targets in breast cancer and other malignancies. Trastuzumab and lapatinib are standard treatments for HER2-amplified breast cancer, but a significant number of patients do not respond or develop resistance to these drugs. Here we evaluate the in vitro activity of dacomitinib (PF-00299804), an irreversible small molecule pan-HER inhibitor, in a large panel of human breast cancer cell lines with variable expression of the HER family receptors and ligands, and with variable sensitivity to trastuzumab and lapatinib. Forty-seven human breast cancer and immortalized breast epithelial lines representing the known molecular subgroups of breast cancer were treated with dacomitinib to determine IC50 values. HER2-amplified lines were far more likely to respond to dacomitinib than nonamplified lines (RR, 3.39; P < 0.0001). Furthermore, HER2 mRNA and protein expression were quantitatively associated with response. Dacomitinib reduced the phosphorylation of HER2, EGFR, HER4, AKT, and ERK in the majority of sensitive lines. Dacomitinib exerted its antiproliferative effect through a combined G0–G1 arrest and an induction of apoptosis. Dacomitinib inhibited growth in several HER2-amplified lines with de novo and acquired resistance to trastuzumab. Dacomitinib maintained a high activity in lines with acquired resistance to lapatinib. This study identifies HER2-amplified breast cancer lines as most sensitive to the antiproliferative effect of dacomitinib and provides a strong rationale for its clinical testing in HER2-amplified breast cancers resistant to trastuzumab and lapatinib. Mol Cancer Ther; 11(9); 1978–87. ©2012 AACR.
Protein Structure and Function Predicting Protein Stability Changes from Sequences Using Support Vector Machines

Motivation: The prediction of protein stability change upon mutations is key to understanding protein folding and misfolding. At present, methods are available to predict stability changes only when the atomic structure of the protein is available. Methods addressing the same task starting from the protein sequence are, however, necessary in order to complete genome annotation, especially in relation to single nucleotide polymorphisms (SNPs) and related diseases. Results: We develop a method based on support vector machines that, starting from the protein sequence, predicts the sign and the value of free energy stability change upon single point mutation. We show that the accuracy of our predictor is as high as 77% in the specific task of predicting the G sign related to the corresponding protein stability. When predicting the G values, a satisfactory correlation agreement with the experimental data is also found. As a final blind benchmark, the predictor is applied to proteins with a set of disease-related SNPs, for which thermodynamic data are also known. We found that our predictions corroborate the view that disease-related mutations correspond to a decrease in protein stability.
Applying causal models to explore the mechanism of action of simvastatin in progressive multiple sclerosis

Significance Traditional analysis of clinical trials precludes a mechanistic understanding of drug actions. This is further compounded by the use of outcome measures in clinical trials not directly related to the mechanism of action of the medication under study. Here, we applied structural equation models to the double-blind randomized controlled trial of simvastatin in secondary progressive multiple sclerosis to investigate causal associations that underlie treatment effects. Our results suggest that beneficial effects of simvastatin on reducing the rate of brain atrophy and slowing the deterioration of disability are independent of serum cholesterol reduction. Our work demonstrates that structural models can elucidate the statistical pathways underlying treatment effects in clinical trials of poorly understood neurodegenerative disorders, such as progressive multiple sclerosis. Understanding the mode of action of drugs is a challenge with conventional methods in clinical trials. Here, we aimed to explore whether simvastatin effects on brain atrophy and disability in secondary progressive multiple sclerosis (SPMS) are mediated by reducing cholesterol or are independent of cholesterol. We applied structural equation models to the MS-STAT trial in which 140 patients with SPMS were randomized to receive placebo or simvastatin. At baseline, after 1 and 2 years, patients underwent brain magnetic resonance imaging; their cognitive and physical disability were assessed on the block design test and Expanded Disability Status Scale (EDSS), and serum total cholesterol levels were measured. We calculated the percentage brain volume change (brain atrophy). We compared two models to select the most likely one: a cholesterol-dependent model with a cholesterol-independent model. The cholesterol-independent model was the most likely option. When we deconstructed the total treatment effect into indirect effects, which were mediated by brain atrophy, and direct effects, simvastatin had a direct effect (independent of serum cholesterol) on both the EDSS, which explained 69% of the overall treatment effect on EDSS, and brain atrophy, which, in turn, was responsible for 31% of the total treatment effect on EDSS [β = −0.037; 95% credible interval (CI) = −0.075, −0.010]. This suggests that simvastatin’s beneficial effects in MS are independent of its effect on lowering peripheral cholesterol levels, implicating a role for upstream intermediate metabolites of the cholesterol synthesis pathway. Importantly, it demonstrates that computational models can elucidate the causal architecture underlying treatment effects in clinical trials of progressive MS.
Strategic Basins of Attraction, the Path Dominance Core, and Network Formation Games

Given the preferences of players and the rules governing network formation, what networks are likely to emerge and persist? And how do individuals and coalitions evaluate possible consequences of their actions in forming networks? To address these questions we introduce a model of network formation whose primitives consist of a feasible set of networks, player preferences, the rules of network formation, and a dominance relation on feasible networks. The rules of network formation may range from non-cooperative, where players may only act unilaterally, to cooperative, where coalitions of players may act in concert. The dominance relation over feasible networks incorporates not only player preferences and the rules of network formation but also assumptions concerning the degree of farsightedness of players. A specification of the primitives induces an abstract game consisting of (i) a feasible set of networks, and (ii) a path dominance relation defined on the feasible set of networks. Using this induced game we characterize sets of network outcomes that are likely to emerge and persist. Finally, we apply our approach and results to characterize the equilibrium of well known models and their rules of network formation, such as those of Jackson and Wolinsky (1996) and Jackson and van den Nouweland (2005).
The Enhancement of H2 Evolution over Sr1−1.5xTbxWO4 Solid Solution under Ultraviolet Light Irradiation

In this work, Sr1−1.5xTbxWO4 (0 ≤ x ≤ 0.2) solid solutions were synthesized via a traditional high-temperature solid state method. Le Bail fitting on the powder X-ray diffraction (XRD) pattern showed that these solid solutions are pure phase. Scanning electron microscopy showed that the SrWO4 and Sr0.82Tb0. 12WO4 samples are composed of micrometer particles and submicron crystallites, respectively. Ultraviolet–visible diffuse reflectance spectra suggested that the bandgaps of Sr1−1.5xTbxWO4 are narrower than the undoped sample. The Sr0.82Tb0. 12WO4 sample, with the assistance of 1.5 wt % Ru-cocatalyst, exhibits the best performance for H2 evolution in 5 vol % aqueous triethanolamine (TEOA), which results in about 6.1 and 2.8 times efficiency improvement compared with the intrinsic SrWO4 in methanol and aqueous TEOA, respectively. All the photocatalysts recycled after the photocatalytic reactions showed no degradation when checked by powder XRD.
Practice, Knowledge and Needs of Occupational Therapy Practitioners Providing Services to Parents with Physical Impairments: A Pilot Study

Abstract This survey study describes practice patterns, knowledge, skills, resources, and needs of occupational therapy practitioners providing services to parents with physical impairments. Participants (n = 51) primarily worked in outpatient rehabilitation (30%), inpatient rehabilitation (21%), and acute care (15%) settings. Participants reported evaluating and providing interventions for nine role-focused parenting activities. All participants agreed addressing the instrumental activities of daily living (IADL) of parenting should be part of occupational therapy practice. Adaptive equipment and techniques were utilized to increase participation of parents with physical impairments in child rearing. Lack of resources for childcare equipment and need for more training were barriers. Ninety-eight percent of participants agreed advancing the role of occupational therapy for parents with physical impairments is needed.