gebhart/patrepeval huggingface dataset:
(±)-Gelliusines A and B, Two Diastereomeric Brominated Tris-indole Alkaloids from a Deep Water New Caledonian Marine Sponge (Gellius or Orina sp.) (1994)

Two new diastereomeric brominated tris-indole alkaloids occurring as enantiomeric pairs, (+/-)-gelliusines A [1] and B [2], have been isolated from a deep water New Caledonian sponge (Gellius or Orina sp.), whose crude extract exhibited cytotoxicity against KB cells. Their structures were elucidated by spectroscopic methods including one- and two-dimensional nmr spectroscopy. The major compound, (+/-) gelliusine A [1], which showed very weak cytotoxicity, proved to be active at the serotonin receptor.
Capsaicin Desensitization of the Nasal Mucosa Reduces Symptoms upon Allergen Challenge in Patients with Allergic Rhinitis (1998)

Patients with birch pollen allergic rhinitis were treated locally, out of season, in the nasal cavity with capsaicin (30 microM) or saline. The capsaicin treatment resulted in a statistically significant reduction of symptoms upon allergen challenge, which lasted for 2 months. Saline had no effect on the symptom score upon allergen challenge. Neither capsaicin nor saline treatment had any effect on allergen challenge-induced nasal mucosal swelling monitored by acoustic rhinometry. Allergen challenge-induced eosinophil migration to the nasal mucosa was affected by neither capsaicin nor the saline treatment. The finding that capsaicin treatment reduces allergic symptoms indicates that selective, non-peptide neurokinin receptor antagonists may be an alternative in the future in the treatment of nasal allergy. However, owing to the pain involved in local capsaicin treatment this treatment is unlikely to be of clinical use.
Molecular Mechanisms of Glucocorticoid Action (2001)

Airway inflammation plays a central role in the pathogenesis of asthma, and glucocorticoids (also referred to as corticosteroids or glucocorticosteroids) are the most effective agents in the management of this chronic disease (1). The antiinflammatory effectiveness of inhaled glucocorticoids in asthma is the result of actions on multiple inflammatory and structural cells in the lung. Glucocorticoids inhibit expression of many inflammatory proteins, and the antiinflammatory effects of glucocorticoids are mediated through receptors that function by modulation of gene expression. Glucocorticoid receptors (GR) are members of the large steroid/nuclear receptor family that includes more than 25 subfamilies of receptors that act primarily as ligand-activated transcription factors (2). The nuclear receptor family includes receptors for estrogen, progesterone, mineralocorticoids, androgens, vitamin D, thyroid hormone, and retinoic acid as well as a large group of ``orphan'' receptors for which endogenous and synthetic ligands have recently been identified (3).
The Sialomucin CD164 (MGC-24v) Is an Adhesive Glycoprotein Expressed by Human Hematopoietic Progenitors and Bone Marrow Stromal Cells That Serves as a Potent Negative Regulator of Hematopoiesis (1998)

Mucin-like molecules represent an emerging family of cell surface glycoproteins expressed by cells of the hematopoietic system. We report the isolation of a cDNA clone that encodes a novel transmembrane isoform of the mucin-like glycoprotein MGC-24, expressed by both hematopoietic progenitor cells and elements of the bone marrow (BM) stroma. This molecule was clustered as CD164 at the recent workshop on human leukocyte differentiation antigens. CD164 was identified using a retroviral expression cloning strategy and two novel monoclonal antibody (MoAb) reagents, 103B2/9E10 and 105.A5. Both antibodies detected CD164/MGC-24v protein expression by BM stroma and subpopulations of the CD34(+) cells, which include the majority of clonogenic myeloid (colony-forming unit-granulocyte-macrophage [CFU-GM]) and erythroid (blast-forming unit-erythroid [BFU-E]) progenitors and the hierarchically more primitive precursors (pre-CFU). Biochemical and functional characterization of CD164 showed that this protein represents a homodimeric molecule of approximately 160 kD. Functional studies demonstrate a role for CD164 in the adhesion of hematopoietic progenitor cells to BM stromal cells in vitro. Moreover, antibody ligation of CD164 on primitive hematopoietic progenitor cells characterized by the cell surface phenotype CD34(BRIGHT)CD38(-) results in the decreased recruitment of these cells into cell cycle, suggesting that CD164 represents a potent signaling molecule with the capacity to suppress hematopoietic cell proliferation.
Leaky Integrate-and-Fire Neuron Circuit Based on Floating-Gate Integrator (2016)

The artificial spiking neural network (SNN) is promising and has been brought to the notice of the theoretical neuroscience and neuromorphic engineering research communities. In this light, we propose a new type of artificial spiking neuron based on leaky integrate-and-fire (LIF) behavior. A distinctive feature of the proposed FG-LIF neuron is the use of a floating-gate (FG) integrator rather than a capacitor-based one. The relaxation time of the charge on the FG relies mainly on the tunnel barrier profile, e.g., barrier height and thickness (rather than the area). This opens up the possibility of large-scale integration of neurons. The circuit simulation results offered biologically plausible spiking activity (<100 Hz) with a capacitor of merely 6 fF, which is hosted in an FG metal-oxide-semiconductor field-effect transistor. The FG-LIF neuron also has the advantage of low operation power (<30 pW/spike). Finally, the proposed circuit was subject to possible types of noise, e.g., thermal noise and burst noise. The simulation results indicated remarkable distributional features of interspike intervals that are fitted to Gamma distribution functions, similar to biological neurons in the neocortex.
Inverse PCR: An Efficient Approach to Cloning cDNA Ends (2003)

Since the first report on cDNA cloning in 1972 (1), this technology has developed into a powerful and universal tool in isolation, characterization, and analysis of both eukaryotic and prokaryotic genes. However, the conventional methods of cDNA cloning require much effort to generate a library that is packaged in phage or plasmid, and then surveyed in a large number of recombinant phages or plasmids. There are three major limitations in these methods. First, a substantial amount (at least 1 mg) of purified mRNA is needed as starting material to generate libraries of sufficient diversity (2). Second, the intrinsic difficulty of multiple sequential enzymatic reactions required for cDNA cloning often leads to low yields and truncated clones (3). Finally, screening of a library with hybridization technique is time-consuming. PCR technology can simplify and improve cDNA cloning. Using PCR with two gene-specific primers, a piece of known sequence cDNA can be specifically and efficiently amplified and isolated from very small numbers (<104) of cells (4). However, it is often difficult to isolate full-length cDNA copies of mRNA on the basis of very limited sequence information. The unknown sequence flanking a small stretch of the known sequence of DNA cannot be amplified by the conventional PCR. Recently, anchored PCR (5–7) and inverse PCR (8–10) have been developed to resolve this problem. Anchored PCR techniques have the common point that DNA cloning goes from a small stretch of known DNA sequence to the flanking unknown sequence region with the aid of a gene-specific primer at one end and a universal primer at other end. Because of only one gene-specific primer in the anchored PCR it is easier to get a high level of nonspecific amplification by PCR than with two gene-specific primers (10,11). The major advantage of inverse PCR (IPCR) is to amplify the flanking unknown sequence by using two gene-specific primers.
High-level and high-throughput recombinant protein production by transient transfection of suspension-growing human 293-EBNA1 cells (2002)

A scalable transfection procedure using polyethylenimine (PEI) is described for the human embryonic kidney 293 cell line grown in suspension. Green fluorescent protein (GFP) and human placental secreted alkaline phosphatase (SEAP) were used as reporter genes to monitor transfection efficiency and productivity. Up to 75% of GFP-positive cells were obtained using linear or branched 25 kDa PEI. The 293 cell line and two genetic variants, either expressing the SV40 large T-antigen (293T) or the Epstein-Barr virus (EBV) EBNA1 protein (293E), were tested for protein expression. The highest expression level was obtained with 293E cells using the EBV oriP-containing plasmid pCEP4. We designed the pTT vector, an oriP-based vector having an improved cytomegalovirus expression cassette. Using this vector, 10- and 3-fold increases in SEAP expression was obtained in 293E cells compared with pcDNA3.1 and pCEP4 vectors, respectively. The presence of serum had a positive effect on gene transfer and expression. Transfection of suspension-growing cells was more efficient with linear PEI and was not affected by the presence of medium conditioned for 24 h. Using the pTT vector, >20 mg/l of purified His-tagged SEAP was recovered from a 3.5 l bioreactor. Intracellular proteins were also produced at levels as high as 50 mg/l, representing up to 20% of total cell proteins.
Use of In Vivo-Generated Biofilms from Hemodialysis Catheters To Test the Efficacy of a Novel Antimicrobial Catheter Lock for Biofilm Eradication In Vitro (2004)

This biofilm study was conducted to assess the in vitro activity of tetrasodium EDTA on catheters that had been routinely removed from hemodialysis patients at Leeds Teaching Hospitals Trust due to maturation of fistula. Catheters were screened by culture of through-catheter flush, and isolates were identified by standard methodologies; 20 isolates were found to be biofilm positive. Initial biofilm cell count levels averaged above 10(5) CFU/1-cm catheter section. Bacteria identified in the biofilms were gram-negative (1 isolate), gram-positive (11 isolates), or mixed species (8 isolates). After a 24-h lock, 40 mg of tetrasodium EDTA per ml was effective at eradicating the total biofilm viable count in almost all cases. The efficacy of tetrasodium EDTA as a catheter lock potentially shows that this agent could substantially reduce catheter-related infections and be used to treat patients with limited access.
Overview of new immunosuppressive therapies (2000)

This review covers the new immunosuppressive drugs that have appeared in the past 5 years. It begins with the newest formulation (Neoral, Sandoz Pharmaceuticals, East Hanover, NJ, USA) of the clinically "mature" drug cyclosporin A and then reviews the literature on tacrolimus, sirolimus, and mycophenolate mofetil. In each case, the emphasis is on the evolution of experience with the drug and on the questions that the drug poses for pediatricians considering the risk-benefit ratio of the drug in children.
Nasal Lymphoid Tissue (NALT) as a Mucosal Immune Inductive Site (1997)

Intranasal (i.n.) immunization is a very effective route for inducing mucosal immunity, but the cellular mechanism responsible for regulating and disseminating these responses is not fully understood. The authors studied the role of nasal lymphoid tissue (NALT) as a mucosal inductive site by using highly purified NALT cells obtained by a new method of mechanical isolation. The NALT cells, like Peyer's patch (PP) cells, were smaller in size and less granular than lymphocytes from salivary glands (SG) and small intestinal lamina propria (LP). The NALT cells isolated from i.n. immunized mice contained antigen-specific antibody-secreting cells (ASC) predominantly of immunoglobulin (Ig)A isotype, similar to those also recovered from salivary glands in a time course study. However, the higher proportion of smaller sized sports formed by NALT cells in ELISPOT assays suggested that these cells were less differentiated precursors of those found in salivary glands. This was supported by the fact that after i.n. immunization, IgA ASC appeared in NALT, as well as in mucosal effector sites SG and LP, but none or very few in another mucosal inductive site, PP. In contrast, after intragastric (i.g.) immunization, IgA ASC were detected in PP, along with the SG and LP, but none or very few in NALT. Furthermore, after i.n. immunization, lymphocytes from NALT but not PP proliferated in response to the specific antigen in culture. These findings imply that NALT served as an inductive site for IgA antibody responses at mucosal effector sites.
Molecular action of methotrexate in inflammatory diseases. (2002)

Despite the recent introduction of biological response modifiers and potent new small-molecule antirheumatic drugs, the efficacy of methotrexate is nearly unsurpassed in the treatment of inflammatory arthritis. Although methotrexate was first introduced as an antiproliferative agent that inhibits the synthesis of purines and pyrimidines for the therapy of malignancies, it is now clear that many of the anti-inflammatory effects of methotrexate are mediated by adenosine. This nucleoside, acting at one or more of its receptors, is a potent endogenous anti-inflammatory mediator. In confirmation of this mechanism of action, recent studies in both animals and patients suggest that adenosine-receptor antagonists, among which is caffeine, reverse or prevent the anti-inflammatory effects of methotrexate.
Asymmetric Synthesis of (S)-β2-Homoarylglycines (2000)

The synthesis of racemic N-phthalyl β2-homoarylglycines 5 and their asymmetric transformation have been investigated. The key step is the stereoselective addition of the (R)-pantolactone to the corresponding prochiral ketene 7.
Granulocyte-macrophage colony-stimulating factor enhances phagocytosis of bacteria by human neutrophils (1986)

In order to determine whether human granulocyte-macrophage colony-stimulating factor (GM-CSF) can enhance phagocytosis, neutrophils were combined with Staphylococcus aureus (S aureus), and both the number of bacteria per neutrophil and the percent of neutrophils phagocytizing were assessed in the absence and presence of GM-CSF. Exposure to GM-CSF did not enable neutrophils to ingest unopsonized bacteria. When bacteria were opsonized with serum, both the number of bacteria per neutrophil and the percent of cells phagocytizing were increased by treatment with GM-CSF. Digestion of extracellular organisms by lysostaphin was used to substantiate phagocytosis. These results indicate that another effect of GM-CSF on the mature neutrophil is the enhancement of phagocytosis.
A fast hierarchical motion vector estimation algorithm using mean pyramid (1995)

In transmitting moving pictures, interframe coding is shown to be effective for compressing video data. A hierarchical motion vector estimation algorithm using mean pyramid is proposed. Using the same measurement window at each level of a pyramid, the proposed algorithm, based on the tree pruning, reduces the computational complexity greatly with its performance comparable to that of the full search (FS). By varying the number of candidate motion vectors which are to be used as the initial search points for motion vector estimation at the next level, the mean squared error of the proposed algorithm varies, ranging between those of the FS and three step search (TSS) methods. Also, depending on the number of candidate motion vectors, the computational complexity of the proposed hierarchical algorithm ranges from 1/8-1/2 of that of the FS. The computer simulation results of the proposed technique compared with the conventional methods are given for various test sequences.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Regulation of adhesion of CD4+ T lymphocytes to intact or heparinase-treated subendothelial extracellular matrix by diffusible or anchored RANTES and MIP-1 beta . (1994)

Chemokines, a superfamily of 8- to 11-kDa mediators of inflammation, affect the attachment of immune cells to vascular endothelia by binding to cell surface glycosaminoglycans. We analyzed whether chemokines are also involved in interactions between CD4+ T lymphocytes and the subendothelial extracellular matrix (ECM). Soluble mediators, such as MIP-1 beta and RANTES, induced the binding of resting human CD4+ T cells to ECM in an integrin-dependent manner. Both MIP-1 beta and RANTES bound to intact ECM and retained their adhesive properties, and moreover, ECM-bound RANTES and MIP-1 beta prolonged the time course of interactions between the CD4+ T cells and the ECM. Because the adhesive effect of these chemokines was restricted by an inhibitor of GTP-binding proteins, the adhesive effect of ECM-bound RANTES and MIP-1 beta, which requires an intact cytoskeleton, seems to involve activation of a G protein-linked receptor. MIP-1 beta and RANTES exert their pro-adhesive effects through interactions with glycosaminoglycans, because heparinase-treated ECM did not bound chemokines and because the chemokines ability to induce T cell adhesion was abrogated if: 1) either of the chemokines is pretreaed with heparin or heparan-sulfate (HS), 2) HS is removed from intact ECM by heparinase, an HS-specific endoglycosidase, or 3) the ECM-bound chemokines are released by pretreatment with heparinase. Hence, the adhesive effects of immobilized chemokines is not restricted to T cells interacting with endothelial cells, but also affects the migration of immune cells which reside and function in the context of ECM.
A superagonist variant of peptide MART1/Melan A27-35 elicits anti-melanoma CD8+ T cells with enhanced functional characteristics: implication for more effective immunotherapy. (1999)

In the present study, we show that a singly substituted peptide derived from the epitope MART1(27-35) and containing a Leu in position 1 (LAGIGILTV; 1L) behaves as a superagonist by in vitro inducing specific T cells with enhanced immunological functions. 1L-specific CTLs can be raised from peripheral blood of HLA-A2+ melanoma patients more efficiently than T cells specific for the cognate peptide. These T cells show a greater sensitivity to native MART1(27-35) when compared with CTL variable raised to parental peptide from the same patients. More importantly, anti-1L but not anti-native T cells display high levels of interferon gamma production at early time points, and readily secreted interleukin-2 in response to native epitope endogenously presented by melanoma cells. Additionally, anti-1L T cells are insensitive to the inhibitory effects of MART1(27-35) natural analogues that antagonize the lytic response of CTLs raised to the cognate peptide. Analysis of T-cell receptor variable beta usage suggests that the native and 1L peptides stimulate different components of the MART1(27-35)-reactive T cell population. These data provide rationale to the use of superagonist analogues of tumor antigens for inducing in vivo immunization potentially able to overcome tumor immune escape and mediate a more significant control of tumor growth.
Role of protein phosphatase‐2A and ‐1 in the regulation of GSK‐3, cdk5 and cdc2 and the phosphorylation of tau in rat forebrain (2000)

In Alzheimer disease brain the activities of protein phosphatase (PP)-2A and PP-1 are decreased and the microtubule-associated protein tau is abnormally hyperphosphorylated at several sites at serine/threonine. Employing rat forebrain slices kept metabolically active in oxygenated artificial CSF as a model system, we investigated the role of PP-2A/PP-1 in the regulation of some of the major abnormally hyperphosphorylated sites of tau and the protein kinases involved. Treatment of the brain slices with 1.0 microM okadaic acid inhibited approximately 65% of PP-2A and produced hyperphosphorylation of tau at Ser 198/199/202, Ser 396/404 and Ser 422. No significant changes in the activities of glycogen synthase kinase-3 (GSK-3) and cyclin dependent protein kinases cdk5 and cdc2 were observed. Calyculin A (0.1 microM) inhibited approximately 50% PP-1, approximately 20% PP-2A, 50% GSK-3 and approximately 30% cdk5 but neither inhibited the activity of cyclin AMP dependent protein kinase A (PKA) nor resulted in the hyperphosphorylation of tau at any of the above sites. Treatment of brain slices with 1 microM okadaic acid plus 0.1 microM calyculin A inhibited approximately 100% of both PP-2A and PP-1, approximately 80% of GSK-3, approximately 50% of cdk5 and approximately 30% of cdc2 but neither inhibited PKA nor resulted in the hyperphosphorylation of tau at any of the above sites. These studies suggest (i) that PP-1 upregulates the phosphorylation of tau at Ser 198/199/202 and Ser 396/404 indirectly by regulating the activities of GSK-3, cdk5 and cdc2 whereas PP-2A regulates the phosphorylation of tau directly by dephosphorylation at the above sites, and (ii) that a decrease in the PP-2A activity leads to abnormal hyperphosphorylation of tau at Ser 198/199/202, Ser 396/404 and Ser 422.
Direct Determination of the Total Concentrations of Magnesium, Calcium, Manganese, and Iron in Addition to their Chemical and Physical Fractions in Dark Honeys (2011)

The present work demonstrates a very simple and rapid method for the reliable determination of total concentrations of Mg, Ca, Mn, and Fe in dark honeys by means of flame atomic absorption spectrometry without any special sample pretreatment except for dissolution in water. An analytical scheme for the partitioning of Mg, Ca, Mn, and Fe in analyzed honeys was proposed as well. For a complementary evaluation of fractionation patterns for studied metals, a two linked column solid phase extraction procedure with a nonionic adsorbing resin Amberlite XAD-16 and a strong cation exchange resin Dowex 50 W × 8–200 in addition to an ultrafiltration procedure with five membranes having molecular weight cut-offs of 5, 10, 30, 50, and 100 kDa were used. In the course of the fractionation analysis, it was found that the most dominant group of species is the one containing cationic forms of metals bound to low molecular weight (<5 kDa, 5–10 kDa) natural honey bioligands and is mostly the case of simple ions and labile species of Mg, Ca, Mn, and Fe. Correspondingly, the contribution of the cationic fraction for these metals in analyzed dark honeys was up to 96% (Mg), 95% (Ca), 90% (Mn), and 86% (Fe). A significant contribution of the hydrophobic fraction was also established; it was maximally 10, 18, 20, and 25% for Mg, Ca, Mn, and Fe, respectively.
Nitric oxide synthase lies downstream from vascular endothelial growth factor-induced but not basic fibroblast growth factor-induced angiogenesis. (1997)

Systemic administration of the nitric oxide (NO) synthase inhibitor Nomega-nitro--arginine methyl ester (L-NAME) to rabbits bearing a corneal implant blocked vascular endothelial growth factor (VEGF), but not basic fibroblast growth factor (bFGF)-induced angiogenesis. L-NAME completely blocked angiogenesis induced by VEGF-transfected MCF-7 breast carcinoma cells and the cells remained dormant in the cornea. Postcapillary endothelial cell migration and growth induced by VEGF were blocked by both the NO synthase inhibitor Nomega-mono-methyl--arginine and by the guanylate cyclase inhibitor LY 83583. We conclude that NO is a downstream imperative of VEGF-, but not bFGF-induced angiogenesis, and propose that the NO synthase/guanylate cyclase pathway is a potential target for controlling tumor angiogenesis in response to VEGF. Our studies support recent evidence that VEGF and bFGF induce angiogenesis by different mechanistic pathways using the alphavbeta5 and alphavbeta3 integrins, respectively.