Miracle-dz/UniFAR-FTUs huggingface dataset:
Title: Evaluation of the Transmammary Delivery of Firocoxib in Sows to Alleviate Pain Associated with Piglet Castration, Teeth Clipping, & Tail Docking-NPB #16-118 Investigator:

Painful processing procedures in piglets such as tail docking, castration and teeth clipping are an emerging animal welfare concern. We hypothesized that transmammary delivery of a non-steroidal anti-inflammatory drug, firocoxib, would reduce pain associated with processing in piglets. The first study compared the pharmacokinetics, efficacy, safety and tissue residue concentrations of four doses of firocoxib (0.5, 1.0, 1.5, or 2.0 mg/kg) administered to sows and delivered to nursing piglets prior to processing. Sixteen sows, 5±2 d postpartum, were randomly assigned to one of four treatment groups. On d 0 sows received a single intramuscular dose of firocoxib at 7±1 h before piglet surgical castration, tail docking, and teeth clipping (males) or sham handling (females). Firocoxib, cortisol and prostaglandin E2 (PGE2) concentrations were determined from selected samples collected from sows and three piglets/litter (two barrows and one gilt) at 0, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h after drug administration. On d 21, piglets were weighed and all animals were euthanized and necropsied. Tissues were collected from 3 piglets/litter for histological examination and drug residue analysis. Mean (±SEM) peak plasma firocoxib concentrations (Cmax) were 107.90±15.18, 157.50±24.91, 343.68±78.89, and 452.83±90.27 ng/mL in sows receiving 0.5, 1.0, 1.5, and 2.0 mg/kg firocoxib, respectively, and 9.53±1.21, 31.04±6.79, 53.30±11.1, and 44.03±7.47 ng/mL in their respective piglets. Mean plasma terminal half-life values ranged from 26 to 31 h in sows and 30 to 48 h in piglets. Barrows nursing sows that received 2.0 mg/kg firocoxib had a lower mean plasma cortisol concentration at 1±1 h after processing compared to barrows nursing sows that received 1.0 mg/kg (P=0.0416) and 0.5 mg/kg of firocoxib (P=0.0397). Piglets nursing sows that received 1.5 mg/kg firocoxib had consistently the lowest concentrations of circulating PGE2 suggesting inhibition of the cyclooxygenase enzyme by firocoxib. From processing to weaning, litters of sows receiving 2.0 mg/kg firocoxib gained more weight than litters of sows that received 0.5 mg/kg (P=0.008) or 1.0 mg/kg (P=0.005). No signs of NSAID toxicity were observed on examination of the kidney, liver, stomach and small intestine and concentrations of firocoxib and the descyclopropylmethyl metabolite were below the limit of detection (0.01 μg/g) in all tissues examined from sows and piglets. These findings indicate that maternal delivery of firocoxib to suckling piglets before tail docking and castration may safely reduce processing-induced stress and enhance production by increasing weaning weights. The second study evaluated changes in cranial skin and ocular temperature, assessed using infrared thermography (IRT), and gait, assessed using a pressure mat, as biomarkers of pain in piglets after transmammary
Can the universe be in a mixed state? or did God have a choice in creating the universe?

Quantum mechanics with a fundamental density matrix (W-QM) has been proposed and discussed recently. Moreover, it has been con-jectured that the universe is not in a pure state but in a mixed state in W-QM. In this paper, I argue that this conjecture has several potential problems that quantum mechanics does not have.
Extensively Drug-Resistant Tuberculosis and Tetralogy of Fallot: Two Demons Together

The pulmonary tuberculosis is endemic in India, and the incidence of extensively drug-resistant tuberculosis (XDR-TB) is also rising. Though the incidence of pulmonary tuberculosis is high in acyanotic congenital heart disease, in Tetralogy of Fallot, which is a low flow condition, this association is infrequent. We report a rare association of extensively drugresistant tuberculosis and Tetralogy of Fallot in a young adult patient who presented with breathlessness on exertion, hemoptysis and frequent respiratory infections. The patient was successfully managed by bronchial artery embolization, venesections, pulmonary outflow valvuloplasty and regime for Extensively drug-resistant tuberculosis.
Percolation models of pathogen spillover

Predicting pathogen spillover requires counting spillover events and aligning such counts with process-related covariates for each spillover event. How can we connect our analysis of spillover counts to simple, mechanistic models of pathogens jumping from reservoir hosts to recipient hosts? We illustrate how the pathways to pathogen spillover can be represented as a directed graph connecting reservoir hosts and recipient hosts and the number of spillover events modelled as a percolation of infectious units along that graph. Percolation models of pathogen spillover formalize popular intuition and management concepts for pathogen spillover, such as the inextricably multilevel nature of cross-species transmission, the impact of covariance between processes such as pathogen shedding and human susceptibility on spillover risk, and the assumptions under which the effect of a management intervention targeting one process, such as persistence of vectors, will translate to an equal effect on the overall spillover risk. Percolation models also link statistical analysis of spillover event datasets with a mechanistic model of spillover. Linear models, one might construct for process-specific parameters, such as the log-rate of shedding from one of several alternative reservoirs, yield a nonlinear model of the log-rate of spillover. The resulting nonlinearity is approximately piecewise linear with major impacts on statistical inferences of the importance of process-specific covariates such as vector density. We recommend that statistical analysis of spillover datasets use piecewise linear models, such as generalized additive models, regression clustering or ensembles of linear models, to capture the piecewise linearity expected from percolation models. We discuss the implications of our findings for predictions of spillover risk beyond the range of observed covariates, a major challenge of forecasting spillover risk in the Anthropocene. This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’.
Known Evolutionary Paths Are Accessible to Engineered ß-Lactamases Having Altered Protein Motions at the Timescale of Catalytic Turnover

The evolution of new protein functions is dependent upon inherent biophysical features of proteins. Whereas, it has been shown that changes in protein dynamics can occur in the course of directed molecular evolution trajectories and contribute to new function, it is not known whether varying protein dynamics modify the course of evolution. We investigate this question using three related ß-lactamases displaying dynamics that differ broadly at the slow timescale that corresponds to catalytic turnover yet have similar fast dynamics, thermal stability, catalytic, and substrate recognition profiles. Introduction of substitutions E104K and G238S, that are known to have a synergistic effect on function in the parent ß-lactamase, showed similar increases in catalytic efficiency toward cefotaxime in the related ß-lactamases. Molecular simulations using Protein Energy Landscape Exploration reveal that this results from stabilizing the catalytically-productive conformations, demonstrating the dominance of the synergistic effect of the E014K and G238S substitutions in vitro in contexts that vary in terms of sequence and dynamics. Furthermore, three rounds of directed molecular evolution demonstrated that known cefotaximase-enhancing mutations were accessible regardless of the differences in dynamics. Interestingly, specific sequence differences between the related ß-lactamases were shown to have a higher effect in evolutionary outcomes than did differences in dynamics. Overall, these ß-lactamase models show tolerance to protein dynamics at the timescale of catalytic turnover in the evolution of a new function.
Integrated single-cell potency and expression landscape in mammary epithelium reveals novel bipotent-like cells associated with breast cancer risk

The identification of progenitor and stem like cells in epithelial tissues, as well as those that may serve as the cell of origin for epithelial cancers, is an outstanding challenge. Here we present a novel algorithm, called LandSCENT, which constructs a 3-dimensional integrated landscape of cell-states, encompassing cell-potency and expression subtypes, to facilitate the identification of progenitor and stem-like cells. Application to thousands of single-cell RNA-Seq profiles from the normal mammary epithelium reveals a rare 5% subpopulation of highly potent single-cells. The integrated landscape naturally predicts that these cells define a bi-potent-like state, a result not obtainable via standard methods or without invoking prior assumptions. The bi-potent-like cells are overrepresented within the basal compartment but also overlap with an immature luminal phenotype. We characterize the transcriptome of these cells and show that is enriched for a mammary stem-cell module. We further identify YBX1, a regulator of breast cancer risk identified from GWAS, as the key transcription factor defining this candidate bi-potent cellular phenotype. We validate the putative bi-potency of YBX1-marked cells using independent FACS-sorted bulk expression data. In addition, YBX1 is overexpressed in basal breast cancer and correlates with clinical outcome. In summary, we here provide a novel computational framework which may serve to identify and prioritize candidate normal or cancer progenitor/stem-like single-cell phenotypes, for subsequent functional studies.
Does the leaf economic spectrum hold within plant functional types? A Bayesian multivariate trait meta-analysis

We investigated whether global leaf economic relationships are also present within plant functional types (PFTs), and the extent to which this hierarchical structure can be used to constrain trait estimates. We developed a hierarchical multivariate Bayesian model that assumes separate means and covariance structures within and across PFTs and fit this model to seven leaf traits from the TRY database related to leaf morphology, biochemistry, and photosynthetic metabolism. Trait correlations were generally consistent in direction within and across PFTs, and consistent with predictions of the leaf economic spectrum. However, correlation strength varied substantially across PFTs indicating that leaf economic relationships within PFTs are often confounded by the unique physiology of certain plant types or environmental conditions in certain biomes. Leveraging covariance in multivariate models reduced uncertainties in mean trait estimates, particularly for undersampled trait-PFT combinations. However, additional constraint from the across-PFT hierarchy was limited. Data accessibility The R code and ancillary data for running these analyses is publicly available online via the Open Science Framework at https://osf.io/w8y73/. The TRY data request used for this analysis has been archived at http://try-db.org, and can be retrieved by providing the TRY data request ID (#1584). Alternatively, the exact preformatted data used in this analysis are available on request to Alexey Shiklomanov (alexey.shiklomanov@pnnl.gov).
Future of NAEP Long-Term Trend Assessments A white paper prepared for the National Assessment Governing Board

The National Assessment of Educational Progress (NAEP) encompasses several distinct assessments. In addition to its main series of periodic assessments at grades 4, 8, and 12 in various subject areas (main NAEP), these include the NAEP Long-Term Trend (LTT). The National Assessment Governing Board (Governing Board), created by Congress to formulate policy for NAEP, strives to minimize administrative and testing burdens entailed by NAEP data collections and to realize efficiencies in NAEP operations. Accordingly, the Governing Board's Strategic Vision calls for an examination of policy and technical implications related to the future of NAEP LTT assessments in reading and mathematics. A stakeholder outreach event, to be held early next year, will inform the Governing Board's deliberations as to whether LTT assessments should be continued independently from main NAEP assessments, whether it is feasible to blend LTT assessments with main NAEP assessments, and related questions. This white paper has been commissioned by the Governing Board in preparation for that event. It is intended as both a summary of the history of the LTT and an analysis of some options that the Governing Board and the National Center for Education Statistics (NCES) may wish to consider.
Gender-specific 11-dehydro-thromboxane B2 levels in acute coronary syndrome and its association with clinical outcomes

Despite knowing that females are at a higher risk of major adverse cardiac events (MACE) and poor prognosis after percutaneous transluminal coronary angioplasty (PTCA), there are very few studies focusing on urinary 11-dehyrdo-thromboxane B2 (dh-TxB2) concentration (for aspirin non-responsiveness) differences among males and females. The present prospective observational study aimed to evaluate the dh-TxB2 levels and associate them with clinical outcomes in males and females with acute coronary syndrome (ACS) after PTCA. The dh-TxB2 ELISA assay was carried out twice, at baseline and 6 months follow-up, and outcomes were assessed for 1 year. The average cut-off value of dh-TxB2 was ≥1,496 pg/mg creatinine by the receiver operating characteristic curve estimation. A total of 192 patients (140 men and 52 women) were enrolled. At baseline, 17 (12.1%) males and 7 (13.5%) females had high dh-TxB2 levels, whereas at 6 months, 22 (15.9%) males and 4 (7.8%) females showed high dh-TxB2 levels. The concentration of dh-TxB2 was higher in females than males at baseline. Composite MACE was not different between genders significantly even when the dh-TxB2 levels were high. Women experienced higher MACE incidences than men (13.5% vs. 9.3%).
Preventing Use-After-Free Attacks with Fast Forward Allocation

Memory-unsafe languages are widely used to implement critical systems like kernels and browsers, leading to thousands of memory safety issues every year. A use-after-free bug is a temporal memory error where the program accidentally visits a freed memory location. Recent studies show that useafter-free is one of the most exploited memory vulnerabilities. Unfortunately, previous efforts to mitigate use-after-free bugs are not widely deployed in real-world programs due to either inadequate accuracy or high performance overhead. In this paper, we propose to resurrect the idea of one-time allocation (OTA) and provide a practical implementation with efficient execution and moderate memory overhead. With onetime allocation, the memory manager always returns a distinct memory address for each request. Since memory locations are not reused, attackers cannot reclaim freed objects, and thus cannot exploit use-after-free bugs. We utilize two techniques to render OTA practical: batch page management and the fusion of bump-pointer and fixed-size bins memory allocation styles. Batch page management helps reduce the number of system calls which negatively impact performance, while blending the two allocation methods mitigates the memory overhead and fragmentation issues. We implemented a prototype, called FFmalloc, to demonstrate our techniques. We evaluated FFmalloc on widely used benchmarks and real-world large programs. FFmalloc successfully blocked all tested useafter-free attacks while introducing moderate overhead. The results show that OTA can be a strong and practical solution to thwart use-after-free threats.
The role of genetic factors in HBV-related HCC: perspectives from local genetic backgrounds and clinical epidemiology

Familial clustering of hepatitis B surface antigen carriers (HBsAg) and hepatocellular carcinoma (HCC) has led to the evaluation of the role of genetics in hepatitis B-related diseases. Consistent reports indicate that the HLA-DP and -DQ loci are associated with persistent hepatitis B virus (HBV) infection. However, for hepatocarcinogenesis, existing studies have low power and conflicting data. Global single nucleotide polymorphism (SNP) data was collected from the 1000 Genomes Project and correlated with local epidemiological information. Southeastern Asia has a higher prevalence of HBsAg than Northeastern Asia; this was used in the evaluation of persistent HBV infection. The higher incidence of HCC in West Africa compared with East Africa was used in the evaluation of hepatocarcinogenesis. The allele frequencies for SNPs were significantly different between East Asians and Africans. Therefore, SNPs that have been identified in persistent HBV infections in East Asia may not be completely applicable in Africa. SNPs in NTCP, CTF19, and the HLA-DQ and -DP loci showed North-to-South allele frequency changes in East Asia. These findings confirm the role of genetics in persistent HBV infection. Some of the SNPs in the HLA loci show a trend of West-to-East allele frequency changes in Africa, indicating they may participate in hepatocarcinogenesis. Among the non-HLA related SNPs, rs2596542 in MICA shows a strong trend of allele frequency changes and is correlated with HCC incidence in Africa. SNPs in KIF1, IL-1A, and STAT4 also show, albeit with low statistical power, allele frequency trends compatible with HCC incidence. Taken together, there are strong correlations between background genetics in HLA-DP and -DQ loci with persistent HBV infection and hepatocarcinogenesis. The correlations were weak-positive in non-HLA loci. Received: First Decision: Revised: Accepted: Published: Science Editor: Copy Editor: Production Editor: Jing Yu Page 2 of 12 Tai et al. Hepatoma Res 2020;6:74 I http://dx.doi. org/10.20517/2394-5079.2020. 54
Arfaptine-1 et biogenèse des granules de sécrétion

247 2. Goldberg JL. Intrinsic neuronal regulati on of axon and dendrite growth. Curr Opin Neurobiol 2004 ; 14 : 551–5. 3. Moore D, Blackmore M, Hu Y, et al. KLF family members regulate intrinsic axon regeneration ability. Science 2009 ; 326 : 298. 4. Beattie MS, Bresnahan JC, Lopate G. Metamorphosis alters the response to spinal cord transection in Xenopus laevis frogs. J Neurobiol 1990 ; 21 : 1108-22. 5. Avci HX, Lebrun C, Wehrle R, et al. Thyroid hormone triggers the developmental loss of axonal regenerative capacity via thyroid hormone receptor 1 and kruppel-like factor 9 in Purkinje cells. Proc Natl Acad Sci USA 2012 ; 109 : 14206-11. 6. Oppenheimer JH, Schwartz HL. Molecular basis of thyroid hormone-dependent brain development. Endocr Rev 1997 ; 18 : 462-75. 7. Dusart I, Flamant F. Profound morphological and functional changes of rodent Purkinje cells between the first and the second postnatal weeks: a metamorphosis? Front Neuroanat 2012 ; 6 : 11. 8. Kress E, Samarut J, Plateroti M. Thyroid hormones and the control of cell proliferation or cell differentiation: paradox or duality? Mol Cell Endocrinol 2009 ; 313 : 36-49. 9. McNabb FMA. Avian thyroid development and adaptive plasticity. Gen Comp Endocrinol 2006 ; 147 : 93-101. 10 Fisher DA, Polk DH, Wu SY. Fetal thyroid metabolism: a pluralistic system. Thyroid 1994 ; 4 : 367-71. 11 Hasan SJ, Keirstead HS, Muir GD, Steeves JD. Axonal regeneration contributes to repair of injured brainstem-spinal neurons in embryonic chick. J Neurosci 1993 ; 13 : 492-507. 12 Meuli-Simmen C, Meuli M, Hutchins GM, et al. The fetal spinal cord does not regenerate after in utero transection in a large mammalian model. Neurosurgery 1996 ; 39 : 555-61. 13 St Germain DL, Galton VA, Hernandez A. Defining the roles of the iodothyronine deiodinases: current concepts and challenges. Endocrinology 2008 ; 150 : 1097-107. 14 Gould SJ. Le véritable père de l’homme est l’enfant. In : Darwin et les grandes énigmes de la vie. Paris : Seuil, 1984 : 64-71. des capacités de régénération axonale dans le SNC des mammifères supérieurs fait partie d’un programme plus vaste, permettant de synchroniser les adaptations qui sont nécessaires à un organisme juvénile pour se mouvoir indépendamment, et évoluer dans son milieu naturel. En ce sens, ce vaste programme pourrait être considéré comme une réminiscence de la métamorphose observée chez les amphibiens. Il reste cependant à découvrir les composants de cette métamorphose effectivement déclenchés par la T3, et à comprendre l’avantage sélectif que procure cette réduction considérable des capacités de réparation et de plasticité neuronales au cours de l’évolution des vertébrés. Cette analyse apportera peut-être des idées nouvelles pour traiter les lésions aujourd’hui irréversibles du système nerveux central. ‡ Thyroid hormone T3 triggers the developmental loss of axonal regenerative capacity
The Impact of Graphical Displays of Pro Forma Earnings Information on Professional and Nonprofessional Investors' Earnings Judgments

ABSTRACT: Regulation G (SEC 2003b) requires managers to reconcile textual non-GAAP performance measures (i.e., pro forma disclosures) to GAAP. Graphical disclosures also require reconciliation; however, neither the format nor the placement of the reconciliation is specified. We apply cognitive fit theory to argue that the influence of graphical information presentation formats is contingent on investor type and judgment complexity. Participants in our study viewed a simulated Investor Relations website for a large drug retailer and made judgments regarding current fiscal year earnings performance, earnings potential, and investment amount. We manipulated graphical (GAAP-only versus GAAP and pro forma) and textual (GAAP-only versus pro forma reconciled to GAAP) earnings disclosure content in a 2 × 2 between-participants design. We find that nonprofessional investors' current fiscal year earnings performance, earnings potential, and investment amount judgments are all influenced by graphical displays, which.
Investigations into the molecular mechanisms of trichloroethylene cardiotoxicity in vivo and in vitro

Trichloroethylene (TCE) is among the most common water contaminant in the United States and around the world. It is estimated that between 9% and 34% of all drinking water sources contain some TCE. The EPA set a drinking water standard for TCE at 5 parts per billion (ppb) in 1989, however since this date, many studies have shown TCE is dangerous to the health of adults and unborn children, even at low-level exposures. These studies reveal exposure to TCE can cause multi-organ damage, especially for the kidney, liver, reproductive and development systems. We investigated how TCE can effect embryonic heart development by identifing possible target mechanisms changing after exposure. Acute and chronic exposure to rat cardiomyocytes produced altered calcium flow and significant changes with TCE doses as low as 10ppb. Embryonic carcinoma cells, rat cardiomyocytes and fetal heart tissue all showed global changes in gene expression after low-dose TCE exposure, including critical ion channels that drive calcium flux. High levels of folic acid supplementation in combination with 10ppb TCE exposure in maternal diets caused significant genetic modifications in mRNA expression levels of Day 10 embryonic mouse cardiac tissue. We also found both high and low folate maternal diets leads to similar phenotypic outcomes in embryo