gebhart/patrepeval huggingface dataset:
TPL2-mediated activation of ERK1 and ERK2 regulates the processing of pre-TNFα in LPS-stimulated macrophages (2008)

Activation of the TPL2-MKK1/2-ERK1/2 signalling pathway is essential for lipopolysaccharide (LPS)-stimulated production of TNF alpha in macrophages. Here, we demonstrate that, unexpectedly, TPL2-deficient or MKK1-inhibited macrophages produce near normal levels of pre-TNF alpha when TLR2, TLR4 and TLR6 are activated by their respective agonists, but fail to secrete TNFalpha. We show that LPS stimulates the appearance of pre-TNFalpha at the cell surface and that this is prevented by inhibition of MAPK kinases 1 and 2 (MKK1/2) or in TPL2-deficient macrophages. However, the transport of pre-TNF alpha from the Golgi to the plasma membrane is unaffected by inhibition of the TPL2-MKK1/2-ERK1/2 pathway. Finally, we show that TACE, the protease that cleaves pre-TNF alpha to secreted TNFalpha, is phosphorylated by ERK1 and ERK2 (ERK1/2) at Thr735 in LPS-stimulated macrophages. Therefore, although TACE activity per se is not required for the LPS-stimulated cell surface expression of pre-TNF alpha, the phosphorylation of this protease might contribute to, or be required for, the cell surface expression of the pre-TNF alpha-TACE complex.
RELATIONSHIP BETWEEN ISOKINETIC LEG STRENGTH AND KNEE FRONTAL PLANE PROJECTION ANGLE DURING SINGLE LEG SQUAT AMONG MALE JUNIOR ATHLETES (2019)

Background: Those with increased dynamic knee valgus are vulnerable to increased risk of non-contact kneeinjuries. However, studies on the top down kinetic chain of lower limb mechanics during dynamic motionssuch as single leg squat (SLS) among trained males were scarce.Objective: The objective of the study was to evaluate the relationship between isokinetic hip and knee strengthand frontal plane projection angle (FPPA) of the knee joint during SLS.Methods: Thirty-two male junior athletes (twelve cyclists, ten runners and ten squash players) were screenedfor excessive dynamic knee valgus (DKV) prior to participation. Only those within the normal value of DKV wereincluded. Their hip and knee isokinetic strength in sagittal plane were evaluated at 60Âº/s of angular velocityfor both legs using dynamometer. Two dimensional knee FPPA was evaluated during SLS at 60Âº of knee flexion.Pearson correlation was evaluated between knee FPPA during SLS and isokinetic leg strength.Results: Correlations between knee FPPA and hip and knee isokinetic strength were not statistically significantexcept between knee flexion peak torque/body weight (r = -0.35, p = 0.05) and hamstring to quadriceps ratio(r = -0.39, p = 0.03) of non-dominant leg.Conclusions: Isokinetic hip and knee strength and knee FPPA during SLS was correlated only for non-dominantleg during SLS among male junior athletes. DKV during SLS may be reduced through strengthening the musclesaround hip and knee joints.
Low Number of Owner-Reported Suspected Transmission of Foodborne Pathogens From Raw Meat-Based Diets Fed to Dogs and/or Cats (2021)

The aim of this worldwide survey was to determine owner-reported frequency of pathogen transmission to humans living in or in contact with households feeding their pets raw, minimally processed (MP) diets. A total of 5,611 responses were gathered from 62 countries with 77.1% of households feeding only MP diets to dog and/or cat(s) with no confirmed cases of pathogen transmission or infection by laboratory testing. Eleven households (0.20%; 95% CI, 0.10-0.36) were classified as having experienced "probable" transmission, and 20 households (0.36%; 95% CI, 0.22-0.56) were classified as having experienced "possible" transmission to result in a total of 31 households (0.55%; 95% CI, 0.38-0.79) being identified as potential cases of transmission. The remainder of households (<i>n</i> = 5,580 = 99.45%; 95% CI, 99.21-99.62) were not considered to have experienced potential transmission of foodborne pathogens based on their responses to the survey. The most frequently reported pathogens were <i>Salmonella</i> (<i>n</i> = 11, 0.2%), <i>Campylobacter</i> (<i>n</i> = 6, 0.1%), and <i>Escherichia coli</i> (<i>n</i> = 4, 0.1%), with the most common age group being adults age 18-65 (<i>n</i> = 29, 78.4% of cases). Beef and chicken were the most common proteins reported as being fed in case households, although this was not associated with pathogen transmission. Households feeding a greater number of different protein sources, including pork, turkey, duck, rabbit, and salmon, were associated with decreased risk of pathogen transmission. Additional risk factors associated with pathogen transmission included preparing either MP diets in a separate location, with different utensils than human food, mixing MP diets with dry (kibble) diets and feeding a limited variety of protein sources. Based on the results of this survey, confirmed pathogen transmission from MP diets to humans appears to be rare. We conclude that potential or probable cases of pathogen transmission is likely dependent upon hygiene and food safety measures, and more education surrounding food safety should reduce risk.
TIN-X: target importance and novelty explorer (2017)

cbologa@salud.unm.edu.
Abstract 5688: Chemopreventive potential of ‘jamun’ (Indian blackberry) against estrogen-mediated mammary carcinogenesis (2010)

Abstract Colored fruits, particularly berries, are emerging as highly chemoprotective because of their antioxidant, anti-proliferative and anti-inflammatory activities. In this study, we investigated chemoprotective potential of Eugenia jambolana Lam., commonly known as ‘jamun’ or Indian blackberry. Jamun is widely used as a fruit in India and several other Asian countries, besides its use in the treatment of various ailments, including diabetes mellitus. Anthocyanin pigments in the jamun were extracted with acidic ethanol, and the crude anthocyanin extract was purified by ethyl acetate partitioning, amberlite XAD7/HP20 column chromatography, followed by Sephadex LH-20 column Chromatography. Anthocyanin content in jamun pulp powder was found to be 0.08% by HPLC-PDA (at 520nm). Upon hydrolysis, the jamun extract yielded five anthocyanidins, namely delphinidin (20.3%), cyanidin (6.6%), petunidin (24.6%), peonidin (2.8%) and malvidin (44.2%) as detected by HPLC and confirmed by mass spectral analysis. The jamun extract had high antioxidant potential as reflected by ABTS scavenging (IC50, 12 µg/ml), DPPH scavenging (IC50, 110 µg/ml), and ferrous ions-chelating activities (IC50, 50 µg/ml). In vivo chemopreventive effect of jamun was investigated using the estrogen-mediated ACI rat mammary tumorigenesis model. Groups of female rats were given control (AIN 93M) diet or diet supplemented with jamun pulp powder (5%, w/w). Two weeks later, one half of the animals from each group were treated with subcutaneous silastic implants of 17β-estradiol (1.2 cm; 9 mg). Diet and water were provided ad libitum. Twelve weeks later immediately before the appearance of mammary tumors, all groups were euthanized and blood and mammary tissue were collected. No significant difference was observed in body weight gain and diet intake when compared with control, suggesting that jamun diet was well tolerated. Estrogen treatment resulted in substantial (30-fold) elevation of the plasma prolactin, a key factor in mammary tumorigenesis. The plasma prolactin levels were significantly offset by jamun-supplemented diet. To determine molecular mechanisms of its chemopreventive effects, mammary tissues were analyzed for the expression of cyclin D1 and estrogen receptor alpha (ERα). Western blot analysis showed that jamun diet significantly down-regulated the levels of both cyclin D1 and ERα. Together, these data suggest that jamun contains compounds with high antioxidant and antiproliferative activities, suggesting that consumption of jamun fruit may be useful in the prevention/treatment of breast cancer (Supported from CA-125152 and Agnes Brown Duggan Endowment). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5688.
Uncoupling of Calcium Channel α1 and β Subunits in Developing Neurons (2004)

Calcium channel beta subunits are key modulators of calcium channel function and membrane targeting of the pore-forming alpha1 subunit. Here we show that an invertebrate (Lymnaea stagnalis) homolog of P/Q- and N-type calcium channels (LCav2), although colocalized with beta subunits in synapses of mature neurons, is physically uncoupled from the beta subunits in the leading edge of growth cones of outgrowing neurons. Moreover, LCav2 channels that mediate transmitter release in mature synapses also participate in neuronal outgrowth in growth cones. The differential association of beta subunits with synaptic calcium channels and those expressed in emergent neuronal growth suggests that beta subunits may play a role in the transformation of Cav2 calcium channel function in immature neurons and mature synapses.
Comparison of morphology of isolated cells obtained from aortas of normal and cholesterol fed rabbits. (1975)

Cells from aortas of healthy newborn and adult rabbits were liberated by digestion with trypsin and collagenase. In the same way were obtained free cells from the aortas of rabbits with far advanced experimental atherosclerosis. More than 90 p. 100 of the cells from all groups were viable. Isolated cells were used for electron microscopic examination. In material obtained from aortas of newborn rabbits, endothelial cells, fibroblasts and smooths muscle cells were present. In adult rabbits two kinds of endothelial cells, fibroblasts, several varieties of myocytes and foam cells were found. The bulk of aortic cells isolated from rabbits with experimental atherosclerosis consisted of endothelial cells and smooth myocytes. The cytoplasm of all myocytes contained lipid vacuoles. The lipid-loaded myocytes corresponded to the typical foam cells. Lipid content was relatively scanty in the endothelial cells. The presence of myocytes foam cells like in the aortas of healthy adult rabbits, identical as in material from experimental atherosclerosis, may support the view that these cellular changes so far considered as typical for atherosclerosis are common, and may be treated as an exponent of the natural process of aging of the vascular wall.
Supplementary Table 2 from Personalized <i>In Vitro</i> and <i>In Vivo</i> Cancer Models to Guide Precision Medicine (2023)

&lt;p&gt;Supplementary Table 2. Drug Library Concentrations.&lt;/p&gt;
Characterization and modeling of drift noise in Fourier transform spectroscopy: implications for signal processing and detection limits (1997)

A theoretical analysis of long-term drift noise in Fourier transform spectroscopy is presented. Theoretical predictions are confirmed by experiment. Fractional Brownian motion is employed as a stochastic process model for drift noise. A formulation of minimum detectable signal is given that properly accounts for drift noise. The spectral exponent of the low-frequency drift noise is calculated from experimental data. A frequency-dependent optimal spectrum averaging time is found to exist beyond which the minimum detectable signal increases indefinitely. It is also shown that the minimum detectable signal in an absorbance or transmission measurement degrades indefinitely with the time elapsed since background spectrum acquisition.
Multipass optical amplifier using a double confocal resonator geometry (1987)

We examine multipass optical amplifier configurations designed for amplification of short optical pulses. The multipass configurations are based on a double confocal resonator which is formed by introducing small angular rotations of the four mirrors forming two adjacent confocal resonators. Further small rotations and displacements of these mirrors convert the double confocal resonator into a multipass configuration which causes an incident beam to pass through two beam waists on each round trip. These beam waists occur at one spatial location, or at two different spatial locations, depending on the orientation and location of the mirrors and the imaging of the incident beam. Configurations based on symmetric confocal mirror pairs maintain a constant diameter at the beam waists. Configurations based on asymmetric confocal resonators cause a progressive increase, or decrease, in the beam waist diameter on successive passes.
Mechano-reception in osteoblast-like cells (1995)

Response to mechanical stimulation is a basic biological phenomenon. Nearly all cells process mechanical input and respond to it by inducing and modulating biochemical pathways. In organisms with tissues, if the average mechanical load is increased, some tissues can increase their performance and often increase their bulk by cell division. A reduction in mechanical loading decreases performance, catabolic activity gains, and the tissue degenerates. The process of anabolism and catabolism regulated by mechanical loading is a second-to-second, minute-to-minute, and hour-to-hour process that works together with local and systemic hormones to ensure that the tissue can meet the demands of the mechanical environment. On the other hand, a mechanical load that is too high can cause tissue and matrix failure and damage to the cells, which can result in inflammation. In this paper, we review the possible biophysical and cell biological mechanisms that might be responsible for transducing physiological and hyperphysiological mechanical loading into the biological response of skeletal cells. We speculate on what the mechanism of mechano-transduction in bone might be compared with that of other cells and on how information produced by mechanical loading might be passed on to other cells to achieve a coordinated tissue response.
A Combined Antitumor Strategy Mediated by a New Targeted Nanosystem to Hepatocellular Carcinoma (2021)

The developed formulation resulted in a high and synergistic antitumor effect, revealing a translational potential to improve therapeutic approaches against HCC.
Expansion of a recurrent V beta 5.3+ T-cell population in newly diagnosed and untreated HLA-DR2 multiple sclerosis patients. (1996)

We have used a PCR-based technology to study the V beta 5 and V beta 17 repertoire of T-cell populations in HLA-DR2 multiple sclerosis (MS) patients. We have found that the five MS DR2 patients studied present, at the moment of diagnosis and prior to any treatment, a marked expansion of a CD4+ T-cell population bearing V beta 5-J beta 1.4 beta chains. The sequences of the complementarity-determining region 3 of the expanded T cells are highly homologous. One shares structural features with that of the T cells infiltrating the central nervous system and of myelin basic protein-reactive T cells found in HLA-DR2 MS patients. An homologous sequence was not detectable in MS patients expressing DR alleles other than DR2. However, it is detectable but not expanded in healthy DR2 individuals. The possible mechanisms leading to its in vivo proliferation at the onset of MS are discussed.
Method for time–temperature–transformation diagrams using DSC data: Linseed aliphatic epoxy resin (2014)

ABSTRACT A novel method to generate time–temperature–transformation (TTT) diagrams from Differential Scanning Calorimetry (DSC) data is presented. The methodology starts with dynamical DSC information to obtain the total transformation heat, followed by an isothermal‐dynamic temperature ramp that allows the inclusion of diffusion‐controlled reaction kinetic. The cure kinetics is modeled using an auto‐catalytic Kamal–Sourour model, complemented with a Kissinger model that allows the direct prediction of one energy of activation, DiBenedetto's equation for the glass transition temperature as a function of the cure degree and adjusted reaction constants to include diffusion mechanisms. The methodology uses a nonlinear least‐squares regression method following J.P. Hernández‐Ortiz and T.A. Osswald's methodology (J. Polym. Eng. 2004, 25, 23). A typical linseed epoxy resin (EP) presents two different kinetics control mechanisms, thereby providing a good model to validate the proposed experimental and theoretical method. TTT diagrams for EPs at two different accelerator concentrations are calculated from direct integration of the kinetic model. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131 , 40566.
Dusting Powder (2016)

This Glossary of Terms Related to Pharmaceutics is needed by practitioners in the field of pharmaceutics as this field fulfills an important and crucial role, different from the roles of other scientific disciplines involved in the drugmaking process. The glossary contains 168 definitions used in pharmaceutics. These are related to various aspects of this discipline, such as: (1) physicochemical characterization of pharmaceutical preparations and the active ingredients they contain; (2) unit operations used in the practice of pharmaceutics; (3) terms related to the various dosage forms; (4) terms related to the various modes and routes of drug delivery; (5) terms used in pharmacokinetics and biopharmaceutics in general; and additional miscellaneous terms. The field of pharmaceutics itself is of a multidisciplinary nature as its practitioners come from a variety of disciplines, such as chemistry or various biological sciences, thus a glossary containing authoritative definitions would be useful for them. The terms used in pharmaceutics are rarely covered by existing glossaries, and in the cases they are, their definitions are often inappropriate for the field of pharmaceutics and require new or modified definitions to better fit the new context.
Hit-to-Probe-to-Lead Optimization Strategies: A Biology Perspective to Conquer the Valley of Death (2016)

INTRODUCTION Central to the drug discovery process is gene identification followed by determination of the expression of genes in a given disease and understanding of the function of the gene products (1). This is the critical target identification and validation phase and is the first step in the drug discovery and development process. Linking a particular disease with cellular biology, deciphering the pathways involved, associating the genes participating in these pathways, pin pointing the critical genes involved, and identifying the therapeutic target require a multipronged approach. It takes a highly integrated and concerted effort by teams of scientists from biology and chemistry and quite often takes many years. Pharmaceutical industry relies primarily, but not exclusively, on academia for this invaluable information, and the potential for druggability then becomes the starting point for pharmaceutical research with an ultimate goal of developing a marketable product. From examining case histories for 35 important pharmaceutical innovations, a recent report co-authored by researchers from the Manhattan Institute and the Tufts Center for the Study of Drug Development strengthens the above assertion that National Institutes of Health (NIH)-sponsored research in academia tends to be concentrated on the basic science of physiology, biochemistry, molecular biology of disease pathways and may lead to the identification of biological targets that might prove vulnerable to drugs yet to be developed (2). Contributions by the pharmaceutical industry are more applied-in-nature, leading to the discovery and development of treatment and cure (drugs) for adverse medical conditions. The authors conclude that the NIH-sponsored and privatesector drug research are complementary to one another and are equally necessary in order to provide patients with better care and treatment (2).
Synthesis and Use of Chiral Sulfinamides (2008)

This chapter contains sections titled: Introduction Synthesis of Chiral Sulfinamides and Chiral Sulfinylimines Use of Chiral Sulfinamides Summary References
Living carbocationic copolymerizations. I. Synthesis and characterization of isobutylene/p‐methylstyrene copolymers (1995)

Abstract The isobutylene (IB)– p ‐methylstyrene (pMeSt) monomer pair readily produces by living copolymerization nearly random copolymers with up to M̄ n ≈ 50,000 g mol −1 and M̄ w /M̄ n ≈ 1·4. The livingness of the copolymerization process and the compositional homogeneity of the copolymers have been demonstrated by the following four diagnostic plots: (A) M̄ n (number‐average molecular weight) and corresponding N (number of moles of copolymer formed) vs W p (weight of copolymer formed) for the diagnosis of chaintransfer; (B) −ln (1 – C ) ( C = conversion of monomers) vs time for the diagnosis of termination; (C) copolymer composition vs molecular weight; and (D) cumulative copolymer composition vs conversion for the diagnosis of true homogeneous copolymers. The theory for the use of the −ln(1 – C ) vs time plot for the quantitation of irreversible termination in copolymerization has been developed. The exact conditions (i.e. nature of reagents, reagent concentrations, temperature, etc.) which lead to desirable products in terms of conversion, molecular weight, molecular weight distribution (MWD) and copolymer composition, were developed systematically by analyzing the results of a large number of experiments. The following combination of chemicals was found to lead to living copolymerization, and uniform high molecular weight, narrow MWD copolymers: IB–pMeSt 97 : 3 mol/mol with 5‐ tert ‐butyl‐1,3‐dicumyl methyl ether (5‐tBu‐1,3‐DiCumOMe) initiator, TiCl 4 coinitiator, ethyl chloride (EtCl) solvent, triethylamine (TEA) electron pair donor (ED) and 2,6‐di‐ tert ‐butylpyridine (DtBP) proton trap at −52, −65 and −85°C.
Creep and Wear in Vitamin E-Infused Highly Cross-Linked Polyethylene Cups for Total Hip Arthroplasty (2018)

Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Common risk variants identified in autism spectrum disorder (2017)

Abstract Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 ASD cases and 27,969 controls that identifies five genome-wide significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), seven additional loci shared with other traits are identified at equally strict significance levels. Dissecting the polygenic architecture we find both quantitative and qualitative polygenic heterogeneity across ASD subtypes, in contrast to what is typically seen in other complex disorders. These results highlight biological insights, particularly relating to neuronal function and corticogenesis and establish that GWAS performed at scale will be much more productive in the near term in ASD, just as it has been in a broad range of important psychiatric and diverse medical phenotypes.