gebhart/patrepeval huggingface dataset:
Gender-Related Differences in Proliferative Responses of Vascular Smooth Muscle Cells to Endothelin-1 (2001)

Endothelin-1 is an endothelium-derived factor which alters tone and proliferation of vascular smooth muscle and has been implicated in the development of atherosclerosis. Estrogen modulates production of and contractile responses to endothelin-1. Since atherosclerosis is less in estrogen-replete women compared to men, experiments were designed to determine whether or not there were gender-associated differences in proliferative responses to endothelin-1 and effect of estrogen status on those responses. Proliferation of smooth muscle cells derived from coronary arteries of sexually mature, gondally intact male and female and oophorectomized female pigs was determined by thymidine incorporation in the absence and presence of endothelin-1 with and without 17beta-estradiol. Endothelin-1 (10(-9) M to 10(-7) M) significantly inhibited proliferation only in coronary smooth muscle cells from intact female pigs. Addition of beta-estradiol inhibited proliferation of cells from intact females but there was not a synergistic effect with endothelin-1. Gender associated inhibition of smooth muscle proliferation by endothelin-1 may contribute, in part, to cardioprotection noted in estrogen-replete states.
Identification of SFRP1 as a Candidate Mediator of Stromal-to-Epithelial Signaling in Prostate Cancer (2005)

Genetic changes in epithelial cells initiate the development of prostatic adenocarcinomas. As nascent tumors grow and undergo progression, epithelial tumor cells are intimately associated with stromal cells. Stromal cells within the tumor microenvironment acquire new properties, including the capacity to promote phenotypic and genetic progression in adjacent epithelial cells. Affymetrix microarrays were used to identify 119 genes differentially expressed between normal-derived and carcinoma-derived prostatic stromal cells. These included 31 genes encoding extracellular proteins that may act as stromal-to-epithelial paracrine signals. Further investigation of one of these genes, secreted frizzled related protein 1 (SFRP1), revealed that its expression parallels prostatic growth with high expression during prostatic development, low expression in the adult prostate, and elevated expression in prostatic tumor stroma. In addition, as prostatic epithelial cells progressed to a tumorigenic state under the influence of tumor stroma, SFRP1 became overexpressed in the progressed epithelial cells. To further understand the roles of SFRP1 in the prostate, we tested the affects of increased SFRP1 levels on prostatic tissues and cells. Treatment of developing prostates with SFRP1 in culture led to increased organ growth. Treatment of a human prostatic epithelial cell line with SFRP1 led to increased proliferation, decreased apoptosis, and decreased signaling through the Wnt/beta-catenin pathway in vitro and increased proliferation in vivo. These data suggest that overexpression of SFRP1 by prostatic tumor stroma may account for the previously reported capacity of prostatic tumor stroma to provide a pro-proliferative paracrine signal to adjacent epithelial cells.
In VitroStudies Indicate that Miquelianin (Quercetin 3-O-ß-D-Glucuronopyranoside) is Able to Reach the CNS from the Small Intestine (2003)

Miquelianin (quercetin 3-O-beta-D-glucuronopyranoside) is one of the flavonoids of St. John's wort (Hypericum perforatum L.) whose antidepressant activity has been shown by the forced swimming test, an in vivo pharmacological model with rats. However, nothing is known about its ability to reach the CNS after oral administration. We examined the pathway of miquelianin from the small intestine to the central nervous system using three in vitro membrane barrier cell systems. In the Caco-2 cell line, miquelianin showed a higher uptake (1.93 +/- 0.9 pmol x min(-1) x cm(-2)) than hyperoside (quercetin 3-O-beta-D-galactopyranoside; 0.55 +/- 0.18 pmol x min(-1) x cm(-2)) and quercitrin (quercetin 3-O-alpha-L-rhamnopyranoside; 0.22 +/- 0.08 pmol x min(-1) x cm(-2)). The permeability coefficient of miquelianin (Pc = 0.4 +/- 0.19 x 10(-6) cm/sec) was in the range of orally available drugs assuming sufficient absorption from the small intestine. Uptake and permeability of the examined compounds was increased by the MRP-2 inhibitor MK-571 indicating a backwards transport by this membrane protein. Porcine cell cultures of brain capillary endothelial cells were used as a model of the blood-brain barrier (bbb) and epithelial cells of the plexus chorioidei as a model of the blood-CSF barrier (bcb). Results indicate no active transport in one direction. Although moderate, the permeability coefficients (bbb: Pc = 1.34 +/- 0.05 x 10(-6) cm/sec; bcb: Pc = 2.0 +/- 0.33 x 10(-6) cm/sec) indicate the ability of miquelianin to cross both barriers to finally reach the CNS.
Electrostatic actuation of liquid droplets for micro-reactor applications (1998)

A device for the electrostatic transport and manipulation of liquid droplets on a solid surface is described. Arrays of microelectrodes are fabricated on a substrate, which is covered by a hydrophobic layer. Water droplets, typically a microliter in volume, take spherical shape on the surface and are caused to move by switching the voltage applied to the electrode array. The transport of droplets, deflection of a droplet in either of the bifurcating paths, and the mixing of two droplets by coalescence are experimentally demonstrated. The device can be used for microchemical reactors where transport, sorting and mixing of reagents constitute basic unit operation.
Analysis of somatic mutation in five B cell subsets of human tonsil. (1994)

Using a series of phenotypic markers that include immunoglobulin (Ig)D, IgM, IgG, CD23, CD44, Bcl-2, CD38, CD10, CD77, and Ki67, human tonsillar B cells were separated into five fractions representing different stages of B cell differentiation that included sIgD+ (Bm1 and Bm2), germinal center (Bm3 and Bm4), and memory (Bm5) B cells. To establish whether the initiation of somatic mutation correlated with this phenotypic characterization, we performed polymerase chain reaction and subsequent sequence analysis of the Ig heavy chain variable region genes from each of the B cell subsets. We studied the genes from the smallest VH families (VH4, VH5, and VH6) in order to facilitate the mutational analysis. In agreement with previous reports, we found that the somatic mutation machinery is activated only after B cells reach the germinal center and become centroblasts (Bm3). Whereas 47 independently rearranged IgM transcripts from the Bm1 and Bm2 subsets were nearly germline encoded, 57 Bm3-, and Bm4-, and Bm5-derived IgM transcripts had accumulated an average of 5.7 point mutations within the VH gene segment. gamma transcripts corresponding to the same VH gene families were isolated from subsets Bm3, Bm4, and Bm5, and had accumulated an average of 9.5 somatic mutations. We conclude that the molecular events underlying the process of somatic mutation takes place during the transition from IgD+, CD23+ B cells (Bm2) to the IgD-, CD23-, germinal center centroblast (Bm3). Furthermore, the analysis of Ig variable region transcripts from the different subpopulations confirms that the pathway of B cell differentiation from virgin B cell throughout the germinal center up to the memory compartment can be traced with phenotypic markers. The availability of these subpopulations should permit the identification of the functional molecules relevant to each stage of B cell differentiation.
Fenneropenaeus indicus is protected from white spot disease by oral administration of inactivated white spot syndrome virus (2005)

Fenneropenaeus indicus could be protected from white spot disease (WSD) caused by white spot syndrome virus (WSSV) using a formalin-inactivated viral preparation (IVP) derived from WSSV-infected shrimp tissue. The lowest test quantity of lyophilized IVP coated onto feed at 0.025 g(-1) (dry weight) and administered at a rate of 0.035 g feed g(-1) body weight d(-1) for 7 consecutive days was sufficient to provide protection from WSD for a short period (10 d after cessation of IVP administration). Shrimp that survived challenges on the 5th and 10th days after cessation of IVP administration survived repeated challenges although they were sometimes positive for the presence of WSSV by a polymerase chain reaction (PCR) assay specific for WSSV. These results suggest that F. indicus can be protected from WSD by simple oral administration of IVP.
Sample Processing with Hydrophobic Microfluidics (1999)

Hydrophobic microfluidics is a method for controlling fluid flow in microfluidic systems using short restrictions in channel diameter that act as passive valves. Systems designed using hydrophobic microfluidics have the advantage of easily interfacing with external hardware and integrating with external analysis equipment. This allows it to take advantage of both the micro and macro realms, whichever is most suited for the application, as well as allowing for an inexpensive integration of microfluidics into a company's sample analysis protocols. This method of fluid control is excellent for highly parallel sample analysis, such as DNA processing.
Clinical, microbiological and immunological features of subjects with refractory periodontal diseases (1988)

Abstract 27 subjects with active destructive periodontal diseases were treated by modified Widman flap surgery and systemic tetracycline and divided into 4 groups based on pre‐ and post‐therapy hazard rates (% of sites losing &gt; 3 mm of attachment in 1 year). Pre‐ and post‐therapy hazard rates were respectively: group T (3 subjects) &lt; 4 and &lt; 4; group II (8 subjects) &gt; 4 and &lt; 4; group III (3 subjects) &lt; 4 and &gt; 4; group IV (refractory group of 13 subjects) &gt; 4 and &gt; 4. Baseline mean pocket depths and attachment loss of groups 1 and II subjects were less than groups III and IV subjects and exhibited less suppuration. 6 group IV subjects lost a total of 38 teeth after therapy, in contrast to no tooth loss in subjects in the other 3 groups. Redness, bleeding on probing, plaque levels and age did not differ among groups. Subjects in the 4 groups differed in the subgingival species to which they showed elevated serum antibody responses. Group IV subjects showed elevated responses to a select range of gram‐negative species, including A. actinomycetemcomitans strains Y4 or ATCC 29523, F. nucleatum and B. intermedius. No subject in any of the other groups exhibited an elevated response to B. intermedius. The mean % of each species in all sampled sites, both before and after therapy, was computed for each subject. Subjects in groups III and IV (high post‐therapy hazard rates) exhibited elevated mean levels of B. forsythus, F. nucleatum, S. intermedius, E. corrodens , and B. gingivalis. Groups I and II subjects showed elevated mean levels of an unnamed Actinomyces species. Refractory subjects (group IV) did not constitute a homogeneous group. While subjects in this group had higher levels of pathogens, it appeared that they differed in the combinations of predominant species. 3 major microbial complexes were observed: (1) B. forsythus, F. nucleatum and W. recta (3 subjects); (2) S. intermedius, B. gingivalis and P. micros (3 subjects); (3) S. intermedius and F nucleatum (7 subjects) with or without B. gingivalis.
Why Is Carbonic Anhydrase Essential to Escherichia coli ? (2003)

The can (previously yadF) gene of Escherichia coli encodes a beta-class carbonic anhydrase (CA), an enzyme which interconverts CO(2) and bicarbonate. Various essential metabolic processes require either CO(2) or bicarbonate and, although carbon dioxide and bicarbonate spontaneously equilibrate in solution, the low concentration of CO(2) in air and its rapid diffusion from the cell mean that insufficient bicarbonate is spontaneously made in vivo to meet metabolic and biosynthetic needs. We calculate that demand for bicarbonate is 10(3)- to 10(4)-fold greater than would be provided by uncatalyzed intracellular hydration and that enzymatic conversion of CO(2) to bicarbonate is therefore necessary for growth. We find that can expression is ordinarily required for growth in air. It is dispensable if the atmospheric partial pressure of CO(2) is high or during anaerobic growth in a closed vessel at low pH, where copious CO(2) is generated endogenously. CynT, the single E. coli Can paralog, can, when induced with azide, replace Can; also, the gamma-CA from Methanosarcina thermophila can at least partially replace it. Expression studies showed that can transcription does not appear to respond to carbon dioxide concentration or to be autoregulated. However, can expression is influenced by growth rate and the growth cycle; it is expressed best in slow-growing cultures and at higher culture densities. Expression can vary over a 10-fold range during the growth cycle and is also elevated during starvation or heat stress.
The relationship between transplacental O2 diffusion and placental expression of PlGF, VEGF and their receptors in a placental insufficiency model of fetal growth restriction (2003)

Placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) are involved in placental angiogenesis through interactions with the VEGFR-1 and VEGFR-2 receptors. The placenta of pregnancies whose outcome is fetal growth restriction (FGR) are characterized by abnormal angiogenic development, classically associated with hypoxia. The present study evaluated the near-term expression of this growth factor family in an ovine model of placental insufficiency-FGR, in relationship to uteroplacental oxygenation. Compared to controls, FGR pregnancies demonstrated a 37% increase in uterine blood flow (FGR vs. control, 610.86+/-48.48 vs. 443.17+/-37.39 ml min(-1) (kg fetus)(-1); P<0.04), which was associated with an increased maternal uterine venous PO2 (58.13+/-1.00 vs. 52.89+/-1.26 mmHg; P<0.02), increased umbilical artery systolic/diastolic ratio (3.90+/-0.33 vs. 2.12+/-0.26, P<0.05), and fetal hypoxia (arterial PO2; 12.79+/-0.97 vs. 18.65+/-1.6 mmHg, P<0.005). Maternal caruncle PlGF mRNA was increased in FGR (P<0.02), while fetal cotyledon VEGF mRNA was reduced (P<0.02). VEGFR-1 mRNA was also reduced in FGR fetal cotyledon (P<0.001) but was not altered in caruncle tissue. Immunoblot analysis of PlGF and VEGF demonstrated single bands at 19,000 and 18,600 Mr, respectively. Caruncle PlGF concentration was increased (P<0.04), while cotyledon VEGF was decreased (P<0.05) in FGR placentae. The data establish that uterine blood flow is not reduced in relationship to metabolic demands in this FGR model and that the transplacental PO2 gradient is increased, maintaining umbilical oxygen uptake per unit of tissue. Furthermore, these data suggest that an increased transplacental gradient of oxygen generates changes in angiogenic growth factors, which may underline the pathophysiology of the post-placental hypoxic FGR.
Drug Delivery Systems. 1. Site‐Specific Drug Delivery Using Liposomes as Carriers (1989)

Drug delivery systems, offering controlled delivery of biologically active agents, are rapidly gaining importance in pharmaceutical research and development. To achieve controlled drug delivery, i.e., the administration of drugs so that optimal amount reaches the target site to cure or control the disease state, increasingly sophisticated systems containing different carriers have been developed. Macromolecules represent one of the carriers involved, and they have taken on a significantly prominent role in various modes of administration of therapeutic agents. Among macromolecules, for example, synthetic copolymers, polysaccharides, liposomes, polyanions and antibodies, as drug carriers, liposomes have proved most effective for diseases affecting the reticuloendothelial system and blood cells in particular. Liposomes, which are vesicles consisting of one or more concentrically ordered assemblies of phospholipids bilayers, range in size from a nanometer to several micrometers. Phospholipids such as egg phosphatidylcholine, phosphatidylserine, synthetic dipalmitoyl-DL-alpha-phosphatidylcholine or phosphatidylinositol, have been used in conjunction with cholesterol and positively or negatively charged amphiphiles such as stearylamine or phosphatidic acid. Alteration of surface charge has been shown to enhance drug incorporation and also influence drug release. Because of the multifold characteristics as drug carriers, liposomes have been investigated extensively as carriers of anticancer agents for the past several years. Liposomal entrapments include a variety of pharmacologically active compounds such as antimalarial, antiviral, anti-inflammatory and anti-fungal agents as well as antibiotics, prostaglandins, steroids and bronchodilators to name a few. The liposomal entrapment has been shown to have considerable effect on the pharmacokinetics and tissue distribution of administered drugs. Despite the potential value of liposomes as unique carriers, the major obstacles are the first order targeting of a systemically given liposomes, physical stability and manufacture of the liposomal products and these problems still remain to be overcome. Drug delivery systems evolving in the 1980s have become increasingly dependent on fundamental cell-biology and receptor-mediated endocytotic mechanisms. Drug delivery systems during the 1990s may take advantage of the specificity of receptor-mediated uptake mechanisms as well as polymer chemistry and cell-biology in order to introduce more precise and efficient target-specific delivery systems that are based especially on the liposome technology.
RISK FACTORS FOR CORONARY HEART DISEASE IN ADULT FEMALE TWINS (1987)

The contributions of shared genes and shared environments to familial aggregation of coronary heart disease risk factors were investigated by genetic and epidemiologic analysis of 434 adult female twin pairs from the Kaiser-Permanente Twin Registry in Oakland, California, during 1978 and 1979. Initial estimates of genetic heritability were statistically significant for serum levels of high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides, and Quetelet index, but were only marginally significant for systolic and diastolic blood pressures. These estimates were biased, however, because sisters in the same identical twin pair were more similar than sisters in the same fraternal twin pair not only with respect to shared genes but also with respect to shared environmental and behavioral influences. Heritability was estimated again after adjusting for shared environmental and behavioral effects by multiple regression analysis. Genetic heritability remained significant for HDL cholesterol (0.66), LDL cholesterol (0.88), triglycerides (0.53), and relative weight (0.55) but not for systolic (0.42) and diastolic (0.25) blood pressures. The strong genetic components of the levels of LDL cholesterol, HDL cholesterol, and relative weight may in part explain why some women have high levels of these coronary disease risk factors despite following recommended health behaviors.
Glyoxalase I fromBrassica juncea: molecular cloning, regulation and its over‐expression confer tolerance in transgenic tobacco under stress (1999)

Despite its ubiquitous presence, the role of glyoxalase I has not been well investigated in plants. In order to find out its physiological functions, we have cloned and characterized a cDNA from Brassica juncea encoding glyoxalase I (Gly I) and made transgenic tobacco plants harbouring Gly I in both sense and antisense orientation. The transgenic nature of the plants was confirmed by Southern blotting, and the estimated number of genes inserted ranged from one to six. The transcript and protein levels of glyoxalase I were also monitored in transgenic plants. The expression of glyoxalase I in B. juncea was upregulated in response to salt, water and heavy metal stresses. In response to a high concentration of salt, the transcript level averaged threefold higher in 72 h, and an increase in the protein was also seen by immunoblotting. The transgenic plants over-expressing glyoxalase I showed significant tolerance to methylglyoxal and high salt, as tested in detached leaf disc senescence assay. A comparison of plants expressing high and low levels of glyoxalase I showed that the tolerance to different salt concentrations was correlated with the degree of glyoxalase I expression. Our results suggest an important role of glyoxalase I in conferring tolerance to plants under stress conditions.
Sequence-to-Sequence ASR Optimization via Reinforcement Learning (2017)

Despite the success of sequence-to-sequence approaches in automatic speech recognition (ASR) systems, the models still suffer from several problems, mainly due to the mismatch between the training and inference conditions. In the sequence-to-sequence architecture, the model is trained to predict the grapheme of the current time-step given the input of speech signal and the ground-truth grapheme history of the previous time-steps. However, it remains unclear how well the model approximates real-world speech during inference. Thus, generating the whole transcription from scratch based on previous predictions is complicated and errors can propagate over time. Furthermore, the model is optimized to maximize the likelihood of training data instead of error rate evaluation metrics that actually quantify recognition quality. This paper presents an alternative strategy for training sequence-to-sequence ASR models by adopting the idea of reinforcement learning (RL). Unlike the standard training scheme with maximum likelihood estimation, our proposed approach utilizes the policy gradient algorithm. We can (1) sample the whole transcription based on the model's prediction in the training process and (2) directly optimize the model with negative Levenshtein distance as the reward. Experimental results demonstrate that we significantly improved the performance compared to a model trained only with maximum likelihood estimation.
p38 maintains E-cadherin expression by modulating TAK1–NF-κB during epithelial-to-mesenchymal transition (2010)

Epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells is a pathological process that occurs during peritoneal dialysis. EMT leads to peritoneal fibrosis, ultrafiltration failure and eventually to the discontinuation of therapy. Signaling pathways involved in mesothelial EMT are thus of great interest, but are mostly unknown. We used primary mesothelial cells from human omentum to analyze the role of the p38 MAPK signaling pathway in the induction of EMT. The use of specific inhibitors, a dominant-negative p38 mutant and lentiviral silencing of p38α demonstrated that p38 promotes E-cadherin expression both in untreated cells and in cells co-stimulated with the EMT-inducing stimuli transforming growth factor (TGF)-β1 and interleukin (IL)-1β. p38 inhibition also led to disorganization and downregulation of cytokeratin filaments and zonula occludens (ZO)-1, whereas expression of vimentin was increased. Analysis of transcription factors that repress E-cadherin expression showed that p38 blockade inhibited expression of Snail1 while increasing expression of Twist. Nuclear translocation and transcriptional activity of p65 NF-κB, an important inducer of EMT, was increased by p38 inhibition. Moreover, p38 inhibition increased the phosphorylation of TGF-β-activated kinase 1 (TAK1), NF-κB and IκBα. The effect of p38 inhibition on E-cadherin expression was rescued by modulating the TAK1-NF-κB pathway. Our results demonstrate that p38 maintains E-cadherin expression by suppressing TAK1-NF-κB signaling, thus impeding the induction of EMT in human primary mesothelial cells. This represents a novel role of p38 as a brake or 'gatekeeper' of EMT induction by maintaining E-cadherin levels.