Miracle-dz/UniFAR-FTUs huggingface dataset:
Patterns of Genome-Wide Nucleotide Diversity in the Gynodioecious Plant Thymus vulgaris Are Compatible with Recent Sweeps of Cytoplasmic Genes

Abstract Gynodioecy is a sexual dimorphism where females coexist with hermaphrodite individuals. In most cases, this dimorphism involves the interaction of cytoplasmic male sterility (CMS) genes and nuclear restorer genes. Two scenarios can account for how these interactions maintain gynodioecy. Either CMS genes recurrently enter populations at low frequency via mutation or migration and go to fixation unimpeded (successive sweeps), or CMS genes maintain polymorphism over evolutionary time through interactions with a nuclear restorer allele (balanced polymorphism). To distinguish between these scenarios, we used transcriptome sequencing in gynodioecious Thymus vulgaris and surveyed genome-wide diversity in 18 naturally occurring individuals sampled from populations at a local geographic scale. We contrast the amount and patterns of nucleotide diversity in the nuclear and cytoplasmic genome, and find ample diversity at the nuclear level (π = 0.019 at synonymous sites) but reduced genetic diversity and an excess of rare polymorphisms in the cytoplasmic genome relative to the nuclear genome. Our finding is incompatible with the maintenance of gynodioecy via scenarios invoking long-term balancing selection, and instead suggests the recent fixation of CMS lineages in the populations studied.
Integrated in vivo multiomics analysis identifies p21-activated kinase signaling as a driver of colitis

A combination of transcriptomics, proteomics, and phosphoproteomics reveals therapeutic targets in colitis. Tracking inflammation in disease Crohn’s disease and ulcerative colitis are forms of inflammatory bowel disease (IBD), which have limited therapeutic options. Thus, a better understanding of the molecular mechanisms underlying IBD is needed to develop new treatment strategies. Lyons et al. combined RNA microarray, total protein mass spectrometry, and phosphoprotein mass spectrometry analyses of tissues isolated from a mouse model of colitis. Integration of these data sets enabled tracking from gene expression to protein phosphorylation in individual animals over time. Computational analysis of the data identified discrepancies between transcriptomic and proteomic measurements and predicted that the kinase Pak1 mediated colonic inflammation. Treatment of mice with a pharmacological inhibitor of Pak1 ameliorated disease, highlighting the importance of proteomic measurement to the understanding of disease pathogenesis. Inflammatory bowel disease (IBD) is a chronic disorder of the gastrointestinal tract that has limited treatment options. To gain insight into the pathogenesis of chronic colonic inflammation (colitis), we performed a multiomics analysis that integrated RNA microarray, total protein mass spectrometry (MS), and phosphoprotein MS measurements from a mouse model of the disease. Because we collected all three types of data from individual samples, we tracked information flow from RNA to protein to phosphoprotein and identified signaling molecules that were coordinately or discordantly regulated and pathways that had complex regulation in vivo. For example, the genes encoding acute-phase proteins were expressed in the liver, but the proteins were detected by MS in the colon during inflammation. We also ascertained the types of data that best described particular facets of chronic inflammation. Using gene set enrichment analysis and trans-omics coexpression network analysis, we found that each data set provided a distinct viewpoint on the molecular pathogenesis of colitis. Combining human transcriptomic data with the mouse multiomics data implicated increased p21-activated kinase (Pak) signaling as a driver of colitis. Chemical inhibition of Pak1 and Pak2 with FRAX597 suppressed active colitis in mice. These studies provide translational insights into the mechanisms contributing to colitis and identify Pak as a potential therapeutic target in IBD.
Wide-Field Lensing Mass Maps from Dark Energy Survey Science Verification Data.

We present a mass map reconstructed from weak gravitational lensing shear measurements over 139 deg2 from the Dark Energy Survey science verification data. The mass map probes both luminous and dark matter, thus providing a tool for studying cosmology. We find good agreement between the mass map and the distribution of massive galaxy clusters identified using a red-sequence cluster finder. Potential candidates for superclusters and voids are identified using these maps. We measure the cross-correlation between the mass map and a magnitude-limited foreground galaxy sample and find a detection at the 6. 8σ level with 20 arc min smoothing. These measurements are consistent with simulated galaxy catalogs based on N-body simulations from a cold dark matter model with a cosmological constant. This suggests low systematics uncertainties in the map. We summarize our key findings in this Letter; the detailed methodology and tests for systematics are presented in a companion paper.
Ag Transport Through Non-Irradiated and Irradiated SiC

An integrated experimental and modeling study will be carried out to discover the effects of radiation on fission product transport in SiC. SiC is currently used for coatings of fuel particles in Very High Temperature Reactor (VHTR) applications. One of the major problems with SiC in this application is undesired transport of Ag from fuel core into the coolant. Understanding microstructureand environment-dependent mechanisms that control Ag diffusion through SiC is needed in order to design a coating with superior retention capabilities. Specific objectives of this project are: (i) to determine whether observed variation in integral release measurements of Ag through SiC can be explained by differences in grain size and grain boundaries (GB) types among the samples; (2) to identify the effects of irradiation on diffusion of Ag through SiC; and (3) to discover phenomena responsible for significant solubility of Ag in polycrystalline SiC. Diffusion couple experiments and proton irradiation will be combined with state-of-the-art characterization (SIMS, S/TEM-EDS) to identify trends in Ag concentration profiles as a function of radiation dose and temperature. Modeling will bring together ab initio studies of Ag solubility and diffusion coefficients, rate theory models of radiation damage, and kinetic Monte Carlo studies of diffusion through experimentally determined microstructures. Both experiments and modeling will determine diffusion coefficients and Ag concentration profiles so that jointly these two approaches can lead to a discovery of the fundamental mechanisms that control Ag release.
Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study

Objective To assess the non-inferiority of vonoprazan to lansoprazole for secondary prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer (PU) and the safety of vonoprazan during extended use. Design A phase 3, 24-week, multicenter, randomised, double-blind (DB), active-controlled study, followed by a phase 3, ≥28 week, multicenter, single-blind, parallel-group extension study (EXT) in outpatients (n=642) receiving long-term NSAID therapy who are at risk of PU recurrence. The patients received vonoprazan (10 mg or 20 mg) or lansoprazole 15 mg once daily. For DB, non-inferiority of the proportion of patients with recurrent PU within 24 weeks was analysed by Farrington and Manning test (significance level 2.5%, non-inferiority margin 8.3%; primary endpoint), recurrent PU within 12 weeks, bleeding and time-to-event of PU (secondary endpoint) and treatment-emergent adverse events (TEAEs). For EXT, TEAEs (primary endpoint), recurrent PU and safety (secondary) were assessed up to 104 weeks for patients in the extension study. Results The non-inferiority of vonoprazan 10 mg and 20 mg to lansoprazole 15 mg was verified (percentage difference –2.2%,95% CI –6.2% to 1.8%, p<0.001; –2.1%,95% CI –6.1% to 2.0%, p<0.001, respectively). The proportion of patients with endoscopically confirmed recurrent PU within 24 weeks was 3.3%, 3.4% and 5.5%, for vonoprazan 10 mg, 20 mg and lansoprazole 15 mg, respectively. No significant safety concerns were identified. Conclusion The non-inferiority of vonoprazan (10 and 20 mg) was verified in patients receiving long-term NSAIDs in DB; it was effective and well tolerated in EXT for longer than 1 year, with a safety profile similar to lansoprazole (15 mg). Trial registration numbers NCT01452750, NCT01456260; Results.
Therapist Report of Adaptations to Delivery of Evidence-Based Practices Within a System-Driven Reform of Publicly Funded Children’s Mental Health Services

Objective: This study examined clinical adaptations reported by community therapists to multiple evidence-based practices (EBPs) currently implemented in children’s mental health services. Based on an item set informed by Stirman and colleagues’ model (2015), 2 factors emerged describing Augmenting adaptations and Reducing/Reordering adaptations. We used multilevel modeling to examine therapist- and practice-level predictors of therapist reports of each type of adaptation. Method: Data were drawn from an online survey, including a novel therapist report measure of EBP adaptations, completed by 572 therapists (89.2% female, Mage = 37.08 years, 33.4% non-Hispanic White) delivering EBPs in the context of a system-driven, fiscally mandated implementation effort. Results: Analyses revealed that the 2 types of therapist adaptations (Augmenting and Reducing/Reordering) could be readily discriminated, with therapists reporting significantly more Augmenting than Reducing/Reordering adaptations. Therapists of Hispanic/Latino ethnicity and with fewer years of experience reported more extensive Augmenting adaptations, but no therapist background characteristics were associated with Reducing/Reordering adaptations. Therapists’ general attitudes that EBPs diverged from their personal approach to therapy were associated with reporting more Augmenting and Reducing/Reordering adaptations. In contrast, negative perceptions toward the specific EBP predicted Reducing/Reordering adaptations, but not Augmenting adaptations. Conclusions: Community therapist reports suggest that most adaptations undertaken involve engaging with the practice to augment the fit of the EBPs for local contexts; however, when practices were perceived negatively, therapists were more likely to make adaptations reducing or rearranging components.
Novel Protein Glycan–Derived Markers of Systemic Inflammation and C-Reactive Protein in Relation to Glycemia, Insulin Resistance, and Insulin Secretion

OBJECTIVE N-acetylglucosamine/galactosamine (GlycA) and sialic acid (GlycB) moieties of glycosylated serum proteins are nonspecific measures of inflammation, but conclusive data on their relationship with insulin resistance or insulin secretion are missing. Therefore, we aimed to examine the relation of GlycA, GlycB, and C-reactive protein (CRP) to direct measures of insulin sensitivity (insulin sensitivity index [SI]) and insulin secretion (acute insulin response [AIR]). RESEARCH DESIGN AND METHODS This study used cross-sectional analyses and included 1,225 participants with and without type 2 diabetes in the Insulin Resistance Atherosclerosis Study (IRAS). SI and AIR were measured using the frequently sampled intravenous glucose tolerance test, and GlycA and GlycB were measured using nuclear magnetic resonance spectroscopy. RESULTS GlycA and GlycB had a strong correlation with CRP (r = 0.60 [P < 0.001] and r = 0.46 [P < 0.001], respectively). In a linear regression model with both GlycA and CRP as independent variables, GlycA (β × 1 SD, −0.04 ± 0.02; P < 0.01) and CRP (−0.06 ± 0.02; P < 0.001) were independently associated with SI even after adjusting for demographics, smoking, physical activity, plasma glucose, and BMI. However, neither CRP nor GlycA had an independent relationship with AIR. CONCLUSIONS GlycA may complement CRP in evaluating the relationship between inflammation, glucose tolerance, and insulin resistance.
Results of a randomized controlled pilot trial of intravascular renal denervation for management of treatment-resistant hypertension

Abstract Objective: Previous trials of catheter-based renal-artery denervation (RDN) as treatment modality in resistant hypertension (rHT) generated unconvincing results. In the Investigator-Steered Project on Intravascular Denervation for Management of Treatment-Resistant Hypertension (INSPiRED; NCT01505010), we optimized selection and management of rHT patients. Methods: With ethical clearance to randomize 18 patients, three Belgian hypertension centers screened 29 rHT patients on treatment with ≥3 drugs, of whom 17 after optimization of treatment (age <70 years; systolic/diastolic office blood pressure (BP) ≥ 140/90 mm Hg; 24-h BP ≥130/80 mm Hg; glomerular filtration rate [eGFR] ≥ 45 mL/min/1.73 m2; body mass index <40kg/m2) were randomized and 15 were analyzed 6 months later, while medical treatment was continued (n = 9) or combined with RDN by the EnligHTN™ multi-electrode system (n = 6). Results: The baseline-adjusted between-group differences amounted to 19.5/10.4 mm Hg (change in control vs. intervention group, +7.6/+2.2 vs. −11.9/−8.2 mm Hg; P = .088) for office BP, 22.4/13.1 mm Hg (+0.7/+0.3 vs. −21.7/−12.8; mm Hg; P ≤ .049) for 24-h BP, the primary efficacy endpoint, and 2.5 mL/min/1.73 m2 (+1.5 vs. −1.1 mL/min/1.73 m2; P = .86) for eGFR, the primary safety endpoint. At 6 month, ECG voltages and the number of prescribed drugs (P ≤ .036) were lower in RDN patients, but quality of life and adherence, captured by questionnaire and urine analysis were similar in both groups. Changes in BP and adherence were unrelated. No major complications occurred. Conclusions: The INSPiRED pilot suggests that RDN with the EnligHTN™ system is effective and safe and generated insights useful for the design of future RDN trials.
Prognostic role and correlation of CA9, CD31, CD68 and CD20 with the desmoplastic stroma in pancreatic ductal adenocarcinoma

We assessed the prognostic value of hypoxia (carbonic anhydrase 9; CA9), vessel density (CD31), with macrophages (CD68) and B cells (CD20) that can interact and lead to immune suppression and disease progression using scanning and histological mapping of whole-mount FFPE pancreatectomy tissue sections from 141 primarily resectable pancreatic ductal adenocarcinoma (PDAC) samples treated with surgery and adjuvant chemotherapy. Their expression was correlated with clinicopathological characteristics, and overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), also in the context of stroma density (haematoxylin-eosin) and activity (alpha-smooth muscle actin). The median OS was 21 months after a mean follow-up of 20 months (range, 2–69 months). The median tumor surface area positive for CA9 and CD31 was 7.8% and 8.1%, respectively. Although total expression of these markers lacked prognostic value in the entire cohort, nevertheless, high tumor compartment CD68 expression correlated with worse PFS (p = 0.033) and DMFS (p = 0.047). Also, high CD31 expression predicted for worse OS (p = 0.004), PFS (p = 0.008), LPFS (p = 0.014) and DMFS (p = 0.004) in patients with moderate density stroma. High stromal and peripheral compartment CD68 expression predicted for significantly worse outcome in patients with loose and moderate stroma density, respectively. Altogether, in contrast to the current notion, hypoxia levels in PDAC appear to be comparable to other malignancies. CD31 and CD68 constitute prognostic markers in patient subgroups that vary according to tumor compartment and stromal density. Our study provides important insight on the pathophysiology of PDAC and should be exploited for future treatments.
Biased and unbiased estimation in longitudinal studies with informative visit processes

The availability of data in longitudinal studies is often driven by features of the characteristics being studied. For example, clinical databases are increasingly being used for research to address longitudinal questions. Because visit times in such data are often driven by patient characteristics that may be related to the outcome being studied, the danger is that this will result in biased estimation compared to designed, prospective studies. We study longitudinal data that follow a generalized linear mixed model and use a log link to relate an informative visit process to random effects in the mixed model. This device allows us to elucidate which parameters are biased under the informative visit process and to what degree. We show that the informative visit process can badly bias estimators of parameters of covariates associated with the random effects, while allowing consistent estimation of other parameters.
Synthesis of an oxidation-resistant SiC coating on graphite and modeling analysis with thermodynamics calculations

Abstract A graded SiC coating was prepared on a graphite substrate by a pack cementation technique at 1 873 K to improve the oxidation resistance. The HSC Chemistry software was used for thermodynamics calculations. The coating was characterized by means of X-ray diffraction and scanning electron microscopy. Isothermal oxidation testing of the samples was performed at 1 773 K in air. The modeling analysis indicated that aluminum oxide can be reduced and an SiC coating can be formed due to the reaction of silicon with CO and carbon with SiO. The growth of the SiC nanofibers was attributed to the gaseous reaction of SiO with CO. A 600 μm thick SiC layer can be observed at the graphite–coating interface. The simulation and experimental results were consistent with each other. The mass loss of the SiC coated sample was 1.1 % after oxidation for 10 h, whereas the graphite was fully oxidized after 1 h.
High-resolution magneto-optic measurements with a Sagnac interferometer (invited)

A technique for measuring the Faraday effect and the magneto‐optic Kerr effect has been developed. In a Sagnac interferometer, two optical beams follow identical paths in opposite directions. Effects which break time‐reversal symmetry, such as magneto‐optic effects, will cause destructive interference between the two beams. By measuring the phase shift between circular polarization states reflected from a magnetized sample, the polar magneto‐optic Kerr effect is measured to an accuracy of 3 μrad, with a spatial resolution of 2 μm. The interferometric technique provides a number of advantages over conventional polarizer methods, including insensitivity to linear birefringence, the ability to completely determine the magnetization vector in a region, and the ability to sensitively measure magneto‐optic effects without an external field. It is also shown that this device has great potential if incorporated into a near‐field optical device. Some of the considerations for the design of a near‐field Sagnac magn.
Scalable Design of Structured Controllers Using Chordal Decomposition

We consider the problem of designing static feedback gains subject to a priori structural constraints, which is a nonconvex problem in general. Previous work has focused on either characterizing special structures that result into convex formulations, or employing certain techniques to allow convex relaxations of the original problem. In this paper, by exploiting the underlying sparsity properties of the problem, and using chordal decomposition, we propose a scalable algorithm to obtain structured feedback gains to stabilize a large-scale system. We first extend the chordal decomposition theorem for positive semidefinite matrices to the case of matrices with block-chordal sparsity. Then, a block-diagonal Lyapunov matrix assumption is used to convert the design of structured feedback gains into a convex problem, which inherits the sparsity pattern of the original problem. Combining these two results, we propose a sequential design method to obtain structured feedback gains clique-by-clique over a clique tree of the block-chordal matrix, which only needs local information and helps ensure privacy of model data. Several illustrative examples demonstrate the efficiency and scalability of the proposed sequential design method.
Percutaneous cryoablation of breast tumours in patients with stable metastatic breast cancer: safety, feasibility and efficacy.

PURPOSE To evaluate safety, feasibility and efficacy of percutaneous cryoablation of breast tumours in patients with clinically stable metastatic breast cancer, and to compare the findings with reports on alternative procedures, namely surgery and local radiotherapy. METHODS 17 female patients (average age of 54.8 years ± 10.8; range 37-72) with primary breast tumour not surgically treated because of metastatic disease were included. Patients were treated for their primary lesion by percutaneous cryotherapy in period of stable disease. This minimally intervention was performed using ultrasound or CT scan guidance. All patients had clinical and breast-MRI evaluation before and at 1, 3, 6 and 12 months after the procedure. RESULTS All procedures were performed under local anaesthesia and technically successful. The mean largest diameter of the primary lesions was 16 ± 12 mm (size range 5-45 mm). In 15 patients, we obtained a complete regression of the primary breast lesion without recurrence during the follow-up period. Two patients with lesions measured at 40 and 45 mm had recurrence in follow up period. A second session of cryotherapy was performed for these 2 patients, not included in this study. Five patients had painful masses before cryotherapy. All were immediately relieved after the intervention and durably during all follow-up. CONCLUSION These results show that the cryoablation of primary breast lesions seems to be well suited to the palliative care of metastatic patients, particularly because of its good tolerance, low complication rate and ability to provide local or analgesic control. Advances in knowledge: Therapies are limited for these symptomatic patients at metastatic state of primary breast tumour. This study shows that cryoablation in palliative care is achievable in common practice, is effective in local control of the tumour and can provide immediate and long-term analgesic control.
A Novel Pre-Computation Scheme of Window τNAF for Koblitz Curves

Let Ea : y 2 + xy = x + ax + 1/F2m be a Koblitz curve. The window τ -adic nonadjacent-form (window τNAF) is currently the standard representation system to perform scalar multiplications on Ea by utilizing the Frobenius map τ . Pre-computation is an important part for the window τNAF. In this paper, we first introduce μτ̄ -operations in lambda coordinates (μ = (−1)1−a and τ̄ is the complex conjugate of the complex representation of τ). Efficient formulas of μτ̄ -operations are then derived and used in a novel pre-computation scheme to improve the efficiency of scalar multiplications using window τNAF. Our pre-computation scheme costs 7M+5S, 26M+16S, and 66M+36S for window τNAF with width 4, 5, and 6 respectively whereas the precomputation with the state-of-the-art technique costs 11M+8S, 43M+18S, and 107M+36S. Experimental results show that our pre-computation is about 60% faster, compared to the best pre-computation in the literature. It also shows that we can save from 2.5% to 4.9% on the scalar multiplications using window τNAF with our pre-computation.