gebhart/patrepeval huggingface dataset:
Inhibition of Sphingosine 1-Phosphate Lyase for the Treatment of Rheumatoid Arthritis: Discovery of (<i>E</i>)-1-(4-((1<i>R</i>,2<i>S</i>,3<i>R</i>)-1,2,3,4-Tetrahydroxybutyl)-1<i>H</i>-imidazol-2-yl)ethanone Oxime (LX2931) and (1<i>R</i>,2<i>S</i>,3<i>R</i>)-1-(2-(Isoxazol-3-yl)-1<i>H</i>-imidazol-4-yl)butane-1,2,3,4-tetraol (LX2932) (2010)

Sphingosine 1-phosphate lyase (S1PL) has been characterized as a novel target for the treatment of autoimmune disorders using genetic and pharmacological methods. Medicinal chemistry efforts targeting S1PL by direct in vivo evaluation of synthetic analogues of 2-acetyl-4(5)-(1(R),2(S),3(R),4-tetrahydroxybutyl)-imidazole (THI, 1) led to the discovery of 2 (LX2931) and 4 (LX2932). The immunological phenotypes observed in S1PL deficient mice were recapitulated by oral administration of 2 or 4. Oral dosing of 2 or 4 yielded a dose-dependent decrease in circulating lymphocyte numbers in multiple species and showed a therapeutic effect in rodent models of rheumatoid arthritis (RA). Phase I clinical trials indicated that 2, the first clinically studied inhibitor of S1PL, produced a dose-dependent and reversible reduction of circulating lymphocytes and was well tolerated at dose levels of up to 180 mg daily. Phase II evaluation of 2 in patients with active rheumatoid arthritis is currently underway.
Efficacy of the hepatocyte-specific contrast medium FP 736-04 for computed tomography in two experimental models of diffuse liver disease. (1998)

Efficacy of the hepatocyte-specific contrast medium FP 736-04 for computed tomography in two experimental models of diffuse liver disease.
Double-Layer Capacitance of Carbide Derived Carbons in Sulfuric Acid (2005)

Nanoporous carbons obtained by selective leaching of Ti and Al from , as well as B from , were investigated as electrode materials in electric double-layer capacitors. Cyclic voltammetry tests were conducted in from on carbons synthesized at 600, 800, 1000, and . Results show that the structure and pore sizes can be tailored and that the optimal synthesis temperature is . Specific capacitances for CDCs and CDCs were 175 and , respectively, compared to multiwall carbon nanotubes and two types of activated carbon, measured herein to be 15, 52, and , respectively.
The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro (2017)

Banisteriopsis caapi is the basic ingredient of ayahuasca, a psychotropic plant tea used in the Amazon for ritual and medicinal purposes, and by interested individuals worldwide. Animal studies and recent clinical research suggests that B. caapi preparations show antidepressant activity, a therapeutic effect that has been linked to hippocampal neurogenesis. Here we report that harmine, tetrahydroharmine and harmaline, the three main alkaloids present in B. caapi, and the harmine metabolite harmol, stimulate adult neurogenesis in vitro. In neurospheres prepared from progenitor cells obtained from the subventricular and the subgranular zones of adult mice brains, all compounds stimulated neural stem cell proliferation, migration, and differentiation into adult neurons. These findings suggest that modulation of brain plasticity could be a major contribution to the antidepressant effects of ayahuasca. They also expand the potential application of B. caapi alkaloids to other brain disorders that may benefit from stimulation of endogenous neural precursor niches.
[Control of the placement of a central venous catheter using Doppler ultrasound]. (1990)

Precise placement of central venous catheters is necessary to prevent complications and assure proper functioning. Chest X-ray is the current standard method of locating the catheter tip. This is usually not feasible in the operating room setting, particularly after the induction of anesthesia. Intravascular ECG registration using the catheter as a lead and identification of intra-atrial P-waves has been suggested as an alternative. In the present study we evaluated the use of Doppler sonography as a noninvasive method of locating the catheter tip and detecting faulty placement. Two hundred patients scheduled for insertion of a central venous catheter took part in this study. The catheters were inserted via standard routes (internal or external jugular vein, basilar or cephalic vein). A Doppler sonographic device with a 2 mHz probe was used (Parke Electronics 915L). The probe was applied to the right sternal border and affixed at the position where the characteristic venous flow sound was most distinct. The signals were displayed visually, subjected to spectral analysis, and also recorded for later evaluation. A rapid injection of 2-5 ml isotonic saline causes turbulences which can readily be heard and recognized without special training. The position of every catheter was later confirmed by radiography, and in 159 patients the intraatrial ECG method was subjected to direct comparison with the sonographic method. The turbulences due to the injected fluid were found to cause an increased amplitude at frequencies above 350 Hz. If the catheter tip was positioned correctly there was no discernable time lag between the start of the injection and perception of turbulences.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased Lysine and Seed Storage Protein in Rice Plants Recovered from Calli Selected with Inhibitory Levels of Lysine plus Threonine and <i>S</i>-(2-Aminoethyl)cysteine (1987)

Experiments were designed to test whether variation in percent lysine in seed proteins could be recovered in plants regenerated from callus subjected to inhibitory levels of lysine plus threonine. Anther-derived callus was subjected to 1 millimolar lysine plus threonine for three successive passages and then once to the same concentration of S-(2-aminoethyl)cysteine. Plants were regenerated from the resistant callus. Plants recovered directly from tissue culture were normal in color, size and were 50% or less fertile. Second and third generation plants produced a wide range of variants including albinos, deep green plants both short and tall, and totally fertile as well as partially fertile plants. All regenerated plants produced chalky or opaque seed. One unique second generation line had 14% more lysine in seed storage proteins than the controls. This characteristic was transmitted to the next generation. The high lysine plants had reduced seed size with significantly higher levels of seed storage protein than the controls. The phenotypes recovered provide experimental materials for basic studies in protein synthesis and lysine metabolism and may become a source of material for rice breeding.
Features of the spermidine-binding site of deoxyhypusine synthase as derived from inhibition studies. Effective inhibition by bis- and mono-guanylated diamines and polyamines (1993)

Several types of basic compounds structurally related to spermidine, one of the substrates for deoxyhypusine synthase, were tested as inhibitors of this enzyme. The results indicate that inhibitory compounds associate with the enzyme at the site of spermidine binding and must possess two charged primary amino or guanidino groups, or one of each. The efficiency of inhibition is related to the maximum possible distance between the primary amino groups and is adversely affected by substitutions on the secondary amino group or in the carbon chains of polyamines. The mono-guanyl derivatives are much more effective inhibitors than the parent amines or their bis-guanylated counterparts, N1-guanyl-1,7-diaminoheptane being the most effective compound with a Ki value of about 10 nM. Based on these observations we have proposed a model for the spermidine-binding site of deoxyhypusine synthase. Studies with Chinese hamster ovary cells reveal a direct correlation between prevention of hypusine formation by several guanyldiamines and their in vitro inhibition of deoxyhypusine synthase. This evidence for disruption of the initial step in the post-translational maturation of eukaryotic initiation factor 5A provides a basis for the potential control of protein biosynthesis and cell proliferation.
Enzyme-Linked Immunosorbent Assay for Detection of Filovirus Species-Specific Antibodies (2010)

Several enzyme-linked immunosorbent assays (ELISAs) for the detection of filovirus-specific antibodies have been developed. However, diagnostic methods to distinguish antibodies specific to the respective species of filoviruses, which provide the basis for serological classification, are not readily available. We established an ELISA using His-tagged secreted forms of the transmembrane glycoproteins (GPs) of five different Ebola virus (EBOV) species and one Marburg virus (MARV) strain as antigens for the detection of filovirus species-specific antibodies. The GP-based ELISA was evaluated by testing antisera collected from mice immunized with virus-like particles as well as from humans and nonhuman primates infected with EBOV or MARV. In our ELISA, little cross-reactivity of IgG antibodies was observed in most of the mouse antisera. Although sera and plasma from some patients and monkeys showed notable cross-reactivity with the GPs from multiple filovirus species, the highest reactions of IgG were uniformly detected against the GP antigen homologous to the virus species that infected individuals. We further confirmed that MARV-specific IgM antibodies were specifically detected in specimens collected from patients during the acute phase of infection. These results demonstrate the usefulness of our ELISA for diagnostics as well as ecological and serosurvey studies.
Chromium In Human Nutrition (1988)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More
An Efficient Thiol‐Ene Chemistry for the Preparation of Amphiphilic PHA‐Based Graft Copolymers (2012)

We present a straightforward method to prepare amphiphilic graft copolymers consisting of hydrophobic poly(3-hydroxyalkanoates) (PHAs) backbone and hydrophilic α-amino-ω-methoxy poly(oxyethylene-co-oxypropylene) (Jeffamine®) units. Poly(3-hydroxyoctanoate)-co-(3-hydroxyundecenoate) (PHOU) was first methanolyzed to obtain the desired molar mass. The amino end groups of Jeffamine were converted into thiol by a reaction with N-acetylhomocysteine thiolactone and subsequently photografted. This "one-pot" functionalization prevents from arduous and time-consuming functionalization of the hydrophilic precursor or tedious modifications of PHAs, thus simplifying the process. The amphiphilic nature of modified PHAs leads to water-soluble copolymers exhibiting thermoresponsive behavior.
The pharmacology of psilocybin (2002)

Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is the major psychoactive alkaloid of some species of mushrooms distributed worldwide. These mushrooms represent a growing problem regarding hallucinogenic drug abuse. Despite its experimental medical use in the 1960s, only very few pharmacological data about psilocybin were known until recently. Because of its still growing capacity for abuse and the widely dispersed data this review presents all the available pharmacological data about psilocybin.
Nuclear endpoint of Wnt signaling: Neoplastic transformation induced by transactivating lymphoid-enhancing factor 1 (1999)

The interaction between beta-catenin and LEF-1/TCF transcription factors plays a pivotal role in the Wnt-1 signaling pathway. The level of beta-catenin is regulated by partner proteins, including glycogen synthase kinase-3beta (GSK-3beta) and the adenomatous polyposis coli (APC) tumor suppressor protein. Genetic defects in APC are responsible for a heritable predisposition to colon cancer. APC protein and GSK-3beta bind beta-catenin, retain it in the cytoplasm, and facilitate the proteolytic degradation of beta-catenin. Abrogation of this negative regulation allows beta-catenin to translocate to the nucleus and to form a transcriptional activator complex with the DNA-binding protein lymphoid-enhancing factor 1 (LEF-1). This complex is thought to be involved in tumorigenesis. Here we show that covalent linkage of LEF-1 to beta-catenin and to transcriptional activation domains derived from the estrogen receptor or the herpes simplex virus protein VP16 generates transcriptional regulators that induce oncogenic transformation of chicken embryo fibroblasts. The chimeras between LEF-1 and beta-catenin or VP16 are constitutively active, whereas fusions of LEF-1 to the estrogen receptor are regulatable by estrogen. These experiments document the oncogenicity of transactivating LEF-1 and show that the transactivation domain normally provided by beta-catenin can be replaced by heterologous activation domains. These results suggest that the transactivating function of the LEF-1/beta-catenin complex is critical for tumorigenesis and that this complex transforms cells by activating specific LEF-1 target genes.
Suppression of Signal Transducer and Activator of Transcription 3–Dependent B Lymphocyte Terminal Differentiation by Bcl-6 (2000)

Lymphocytes usually differentiate into effector cells within days after antigen exposure, except in germinal centers where terminal differentiation is delayed while somatic hypermutation creates high-affinity antibody mutants. Here we investigate whether arrest of terminal differentiation can be mediated by BCL-6, a transcriptional repressor that is expressed by germinal center B cells and is required for this phase of B cell development. We find that BCL-6 suppresses the differentiation of transformed and primary B cells to plasma cells by inhibiting the signal transducer and activator of transcription 3-dependent expression of the major regulator of plasma cell development, the B lymphocyte-induced maturation protein (Blimp-1). This function of BCL-6 as a repressor of B lymphocyte differentiation may also underlie the association between chromosomal translocations of its gene and B cell lymphomas.
A 24‐week, double‐blind, placebo‐controlled study of three dosages of Cerebrolysin in patients with mild to moderate Alzheimer's disease (2006)

Cerebrolysin (Cere) is a compound with neurotrophic activity shown to be effective in Alzheimer's disease in earlier trials. The efficacy and safety of three dosages of Cere were investigated in this randomized, double-blind, placebo-controlled, study. Two hundred and seventy-nine patients were enrolled (69 Cere 10 ml; 70 Cere 30 ml; 71 Cere 60 ml and 69 placebo). Patients received iv infusions of 10, 30, 60 ml Cere or placebo 5 days/week for the first 4 weeks and thereafter, two iv infusions per week for 8 weeks. Effects on cognition and clinical global impressions were evaluated 4, 12 and 24 weeks after the beginning of the infusions using the CIBIC+ and the modified Alzheimer's Disease Assessment Scale (ADAS)-cog. At week 24, significant improvement of cognitive performance on the ADAS-cog (P=0.038) and global function (CIBIC+; P>0.001) was observed for the 10 ml dose. The 30 and 60 ml doses showed significant improvement of the global outcome but failed to show significant improvement of cognition. The results are consistent with a reversed U-shaped dose-response relationship for Cere. The percentage of patients reporting adverse events was similar across all study groups. Cere treatment was well tolerated and led to significant, dose-dependent improvement of cognition and global clinical impression.
Effect of Growth Hormone on Intestinal Na+/Glucose Cotransporter Activity (2001)

Growth hormone increases intestinal sugar transport, but only in tissue that has not been exposed to endogenous GH for over 3 hours.
Effect of light irradiation on anthocyanin production by suspended culture of <i>Perilla frutescens</i> (1991)

After a series of experiments on photoperiodicity and light intensity under daylight supplied by an ordinary fluorescent lamp in cultivations using a flask and a roux bottle, it was found that irradiation at 27.2 W/m(2) for the whole period was effective for anthocyanin production by a suspended culture of Perilla frutescens (shiso). A high amount of anthocyanin pigments, 3.0 g/L, was obtained in a bubble column bioreactor after 10 days of cultivation at an aeration rate of 0.1 vvm with light irradiation at 27.2 W/m(2), while 2 g/L was obtained at 13.6 W/m(2) and very little at 54.4 W/m(2). A high amount of anthocyanin pigments, 2.9 g/L, was also produced using an aerated and agitated bioreactor at an agitation speed of 130 rpm, an aeration rate of 0.1 vvm and light irradiation intensity of 27.2 W/m(2). The amount of anthocyanin produced was more than twice that without light irradiation, Keeping the other cultivation conditions the same. The results obtained also showed that the amount of anthocyanin pigment accumulated in a shake flask could be rather well reproduced in bioreactors for both aerated culture, and aerated and agitated culture, by improving the conditions of light irradiation, which conspicuously affects metabolite formation.
CC Chemokine Ligand 5/RANTES Chemokine Antagonists Aggravate Glomerulonephritis Despite Reduction of Glomerular Leukocyte Infiltration (2003)

The chemokine CC chemokine ligand (CCL)5/RANTES as well as its respective receptor CCR5 mediate leukocyte infiltration during inflammation and are up-regulated early during the course of glomerulonephritis (GN). We tested the effects of the two CCL5/RANTES blocking analogs, Met-RANTES and amino-oxypentane-RANTES, on the course of horse apoferritin (HAF)-induced GN. HAF-injected control mice had proliferative GN with mesangial immune complex deposits of IgG and HAF. Daily i.p. injections of Met-RANTES or amino-oxypentane-RANTES markedly reduced glomerular cell proliferation and glomerular macrophage infiltration, which is usually associated with less glomerular injury and proteinuria in HAF-GN. Surprisingly, however, HAF-GN mice treated with both analogs showed worse disease with mesangiolysis, capillary obstruction, and nephrotic range albuminuria. These findings were associated with an enhancing effect of the CCL5/RANTES analogs on the macrophage activation state, characterized by a distinct morphology and increased inducible NO synthetase expression in vitro and in vivo, but a reduced uptake of apoptotic cells in vivo. The humoral response and the Th1/Th2 balance in HAF-GN and mesangial cell proliferation in vitro were not affected by the CCL5/RANTES analogs. We conclude that, despite blocking local leukocyte recruitment, chemokine analogs can aggravate some specific disease models, most likely due to interactions with systemic immune reactions, including the removal of apoptotic cells and inducible NO synthetase expression.
Navigating in Unfamiliar Geometric Terrain (1997)

Consider a robot that has to travel from a start location s to a target t in an environment with opaque obstacles that lie in its way. The robot always knows its current absolute position and that of the target. It does not, however, know the positions and extents of the obstacles in advance; rather, it finds out about obstacles as it encounters them. We compare the distance walked by the robot in going from s to t to the length of the shortest (obstacle-free) path between s and t in the scene. We describe and analyze robot strategies that minimize this ratio for different kinds of scenes. In particular, we consider the cases of rectangular obstacles aligned with the axes, rectangular obstacles in more general orientations, and wider classes of convex bodies both in two and three dimensions. For many of these situations, our algorithms are optimal up to constant factors. We study scenes with nonconvex obstacles, which are related to the study of maze traversal. We also show scenes where randomized algorithms are provably better than deterministic algorithms.
Induction of erythroid-specific gene expression in lymphoid cells. (1993)

Erythropoietin (Epo) is a cytokine which specifically regulates differentiation and proliferation of erythroid progenitor cells. We report here that Epo receptor expressed in interleukin 3-dependent lymphoid Ba/F3 cells transmits both differentiation and growth signals. Epo stimulation of these cells leads to activation of transcription and/or translation of the erythroid-specific transcription factors GATA-1 and SCL, followed by the accumulation of both alpha- and beta-globin chains. These results suggest that expression and activation of the Epo receptor regulates erythroid-specific gene expression and might play a role in determining a cell lineage in vivo and that GATA-1 and SCL may exert their effects after Epo binds to its receptor. It was further found that chimeric receptors composed of extracellular domains of Epo receptor and cytoplasmic domains of interleukin 2 or interleukin 3 receptors could also induce erythroid-specific gene expression in Ba/F3 cells. Taking these data together with previous observations, we conclude that interaction of the extracellular domains of the Epo receptor with other membrane components is essential for transmission of both the erythroid differentiation and the growth signals.
A Primer for Applying Propensity-Score Matching (2010)

This document provides a guide to the key aspects of implementing Propensity-Score Matching (PSM) methodology. It summarizes the basic conditions under which PSM can be used to estimate the impact of a program and the data required, presenting examples of PSM applications. It explains how the Conditional Independence Assumption, combined with the Overlap Condition, reduces selection bias when participation in a program is determined by observable characteristics. It also describes different matching algorithms and some tests to assess the quality of the matching.