gebhart/patrepeval huggingface dataset:
5-Nitro-2-(3-Phenylpropylamino)benzoic Acid Is a GPR35 Agonist (2008)

GPR35 is a Gi/o- and G16-coupled receptor abundantly expressed in gastrointestinal tissues and immune cells. Kynurenic acid (a tryptophan metabolite and ionotropic glutamate receptor antagonist) and zaprinast (a phosphodiesterase inhibitor) are GPR35 agonists. Here, we show that the chloride channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) is also a GPR35 agonist. NPPB activates the GPR35-Gi/o and GPR35-G16 pathways in human embryonic kidney 293 (HEK293) cells and induces intracellular calcium mobilization in a concentration-dependent manner in HEK293 cells coexpressing human, rat or mouse GPR35 and the chimeric G protein G(qi5). These results suggest a novel pharmacological activity of NPPB and will provide useful information to search for more potent and selective GPR35 agonists.
Estrogen Receptor (ER)α and ERβ Exhibit Unique Pharmacologic Properties When Coupled to Activation of the Mitogen-Activated Protein Kinase Pathway* (2001)

The rapid, nongenomic effects of estrogen are increasingly recognized as playing an important role in several aspects of estrogen action. Rapid activation of the mitogen-activated protein kinase (MAPK) signaling pathway by estrogen is among the more recently identified of these effects. To explore the role of estrogen receptors (ERs) in mediating these effects, we have transfected ER-negative Rat-2 fibroblasts with complementary DNA clones encoding either human ERalpha or rat ERbeta and examined their ability to couple to activation of MAPK in response to 17beta-estradiol (17beta-E(2)) and other ligands. For both receptors, addition of E(2) resulted in a rapid phosphorylation of MAPK. Activation of MAPK in ERalpha-transfected cells was partially and completely blocked by the antiestrogens tamoxifen and ICI 182,780, respectively. In ERbeta-transfected cells, MAPK activation was less sensitive to inhibition by tamoxifen and ICI 182,780. We have also observed that, in this model system, a membrane-impermeable estrogen (BSA-E(2)) and 17alpha-E(2) were both able to activate MAPK in a manner similar to E(2) alone. Here also, ICI 182,780 blocked the ability of BSA-E(2) to activate MAPK through ERalpha, but failed to block ERbeta-mediated effects. BSA-E(2) treatment, however, failed to activate nuclear estrogen-response-element-mediated gene transcription. These data show that these nuclear ERs are necessary for estrogen's effects at the membrane. This model system will be useful in identifying molecular interactions involved in the rapid effects mediated by the ERs.
Fluorescence “In Situ” Hybridization for the Detection of Biofilm in the Middle Ear and Upper Respiratory Tract Mucosa (2008)

Most chronic bacterial infections are associated with biofilm formation wherein the bacteria attach to mucosal surfaces, wound tissue, or medical device surfaces in the human body via the formation of an extracellular matrix. Biofilms assume complex three-dimensional structures dependent on the species, the strain, and the prevailing environmental conditions and are composed of both the bacteria and the extracellular slime-like matrices, which surround the bacteria. Bacteria deep in the biofilm live under anaerobic conditions and must use alternatives to O(2) as a terminal electron acceptor. Thus, the metabolic rates of these deep bacteria are greatly reduced, which renders them extremely resistant to antibiotic treatment, and for reasons not clearly understood, it is often very difficult to culture biofilm bacteria using traditional microbiologic techniques. To directly identify and visualize biofilm bacteria in a species-specific manner, we developed a confocal laser scanning microscopy (CLSM)-based 16S rRNA fluorescence in situ hybridization (FISH) protocol, to find biofilm bacteria in middle ear and upper respiratory tract mucosa, which preserves the three-dimensional structure of the biofilm and avoids the use of traditional culture techniques.
<b>A NEW TYPE OF GASTRIN DERIVATIVE AND ITS USE FOR PRODUCTION OF CENTRAL REGION-SPECIFIC ANTIGASTRIN </b><b>SERA </b> (1980)

Synthetic H-Gly-Lys-|:Gln1]-human gastrin I was used as haptenic immunogen for production of anti-human gastrin sera. The conjugate of the gastrin derivative with human serum albumin prepared by the action of glutaraldehyde was found to be an efiicient reagent for production in high probability of anti-human gastrin I sera specific to the central region of the hormone molecule (positions 6-12) where the characteristic structure of gastrin exists. Radioimmunoassay using the antisera discriminated human gastrin I from II as well as from CCK, although the systems detected the big form of human gastrin I to almost the same extent as human gastrin I on molar basis. Immunoreactivities in tissue extracts measured by the present system showed the characteristic distribution of gastrin in Japanese monkey and quail intestines and canine brain.
Apical and basolateral endosomes of MDCK cells are interconnected and contain a polarized sorting mechanism. (1996)

We have evaluated transcytotic routes in MDCK cells for their ability to generate a polarized surface distribution of trafficking proteins by following the intracellular sorting of transferrin receptors (TRs). We find that the selective basolateral expression of TRs is maintained in the face of extensive trafficking between the apical and basolateral surfaces. Biochemical studies of receptors loaded with tracer under conditions approaching steady state indicate that TRs internalized from the two surfaces are extensively colocalized within MDCK cells and that both populations of receptors are selectively delivered to the basolateral surface. Tailless TRs in which the cytoplasmic domain has been deleted display an unpolarized cell surface distribution and recycle in an unpolarized fashion. We show by EM that wild-type receptors internalized from each surface are colocalized within endosomal elements distributed throughout the cytoplasm. By preloading endosomal elements directly accessible from the basolateral surface with transferrin (Tf)-HRP, we show that apically internalized TRs rapidly enter the same compartment. We also show that both transcytosing (apically internalized) and recycling (basolaterally internalized) TRs are delivered to the basolateral border by a distinctive subset of exocytotic, 60-nm-diam vesicles. Together, the biochemical and morphological data show that apical and basolateral endosomes of MDCK cells are interconnected and contain a signal-dependent polarized sorting mechanism. We propose a dynamic model of polarized sorting in MDCK cells in which a single endosome-based, signal-dependent sorting step is sufficient to maintain the polarized phenotype.
Identification of 1,5-Naphthyridine Derivatives as a Novel Series of Potent and Selective TGF-β Type I Receptor Inhibitors (2004)

Optimization of the screening hit 1 led to the identification of novel 1,5-naphthyridine aminothiazole and pyrazole derivatives, which are potent and selective inhibitors of the transforming growth factor-beta type I receptor, ALK5. Compounds 15 and 19, which inhibited ALK5 autophosphorylation with IC50 = 6 and 4 nM, respectively, showed potent activities in both binding and cellular assays and exhibited selectivity over p38 mitogen-activated protein kinase. The X-ray crystal structure of 19 in complex with human ALK5 is described, confirming the binding mode proposed from docking studies.
Integrated receiver deghosting and closed-loop surface-multiple elimination (2017)

Accurate surface-related multiple removal is an important step in conventional seismic processing, and more recently, primaries and surface multiples are separated such that each of them is available for imaging algorithms. Current developments in the field of surface-multiple removal aim at estimating primaries in a large-scale inversion process. Using such a so-called closed-loop process, in each iteration primaries and surface multiples will be updated until they fit the measured data. The advantage of redefining surface-multiple removal as a closed-loop process is that certain preprocessing steps can be included, which can lead to an improved multiple removal. In principle, the surface-related multiple elimination process requires deghosted data as input; thus, the source and receiver ghost must be removed. We have focused on the receiver ghost effect and assume that the source is towed close to the sea surface, such that the source ghost effect is well-represented by a dipole source. The receiver ghost effect is integrated within the closed-loop primary estimation process. Thus, primaries are directly estimated without the receiver ghost effect. After receiver deghosting, the upgoing wavefield is defined at zero depth, which is the surface. We have successfully validated our method on a 2D simulated data and on a 2D subset from 3D broadband field data with a slanted cable.
Subject and citation indexing. Part II: The optimal, cluster-based retrieval performance of composite representations (1991)

Measures of cluster-based retrieval effectiveness are computed for five composite representations in the cystic fibrosis (CF) Document Collection. The composite representations are constructed from combinations of two subject representations, based on Medical Subject Headings and subheadings, and two citation representations, consisting of the complete list of cited references and a comprehensive list of citations for each document. Experimental retrieval results are presented as a function of the exhaustivity and similarity of the composite representations and reveal consistent patterns from which optimal performance levels can be identified. The optimal performance values provide an assessment of the absolute capacity of each composite representation to associate documents relevant to the same query and discriminate between documents relevant to different queries in single-link hierarchies. The optimal performance values for all composite representations are completely comparable and are superior to the optimal performance of constituent representations. Optimal performance consistently occurs at low levels of exhaustivity. Exhaustive composite representations that include subject descriptions produce the lowest levels of performance; retrieval results derived from random structures are comparable to the observed results. The effectiveness of the exhaustive representation composed of references and citations is materially superior to the effectiveness of exhaustive composite representations that include subject descriptions. © 1991 John Wiley & Sons, Inc.
Inhibition of Streptococcus suis Adhesion by Dendritic Galabiose Compounds at Low Nanomolar Concentration (2004)

A series of mono-, di-, and tetravalent galabiose (Galalpha1-4Gal) compounds were synthesized in good yields by coupling of a general carboxylic acid-bearing sugar building block to dendritic scaffolds based on the 3,5-di-(2-aminoethoxy)benzoic acid branching unit. Furthermore, a poly(amidoamine)- (PAMAM-) based dendritic galabioside was synthesized containing eight galabiose units. All galabiosides were tested in a hemagglutination assay and a surface plasmon resonance (SPR) competition assay in order to establish their potency in the binding to the bacterial Gram-positive pathogen Streptococcus suis. A monovalent galabioside containing a short spacer was used as a reference compound in all the assays. Variations in the scaffold as well as in the spacer arms were introduced to determine their influence on the inhibition. The best inhibitor of hemagglutination was an octavalent galabioside with a minimal inhibitory concentration (MIC) of 0.3 nM, to the best of our knowledge the first example of inhibition of bacterial binding by a soluble carbohydrate at a subnanomolar concentration.
Chondrocyte death in experimental osteoarthritis is mediated by MEK 1/2 and p38 pathways: role of cyclooxygenase-2 and inducible nitric oxide synthase. (2001)

This study shows that in the early lesions of experimental OA cartilage in situ, activation of the caspase cascade is responsible for induction of chondrocyte death. Marked inhibition of cell death by caspase inhibitors indicates a significant participation of apoptosis in the phenomenon. This phenomenon is linked to the activation of at least 2 major kinase pathways, MEK 1/2 and p38. These pathways are responsible for upregulating the expression of iNOS and COX-2, each of which seems essential for the induction of apoptosis. Data are provided about possible regulation and interregulation of the COX-2 and iNOS systems by prostaglandin E2 and NO.
Extended RTP Profile for Real-time Transport Control Protocol (RTCP)-Based Feedback (RTP/AVPF) (2006)

Real-time media streams that use RTP are, to some degree, resilient
against packet losses. Receivers may use the base mechanisms of the
Real-time Transport Control Protocol (RTCP) to report packet reception
statistics and thus allow a sender to adapt its transmission behavior
in the mid-term. This is the sole means for feedback and feedback-
based error repair (besides a few codec-specific mechanisms). This
document defines an extension to the Audio-visual Profile (AVP) that
enables receivers to provide, statistically, more immediate feedback
to the senders and thus allows for short-term adaptation and efficient
feedback-based repair mechanisms to be implemented. This early
feedback profile (AVPF) maintains the AVP bandwidth constraints for
RTCP and preserves scalability to large groups. [STANDARDS-TRACK]
Synergy between immune cells and adult neural stem/progenitor cells promotes functional recovery from spinal cord injury (2006)

The well regulated activities of microglia and T cells specific to central nervous system (CNS) antigens can contribute to the protection of CNS neural cells and their renewal from adult neural stem/progenitor cells (aNPCs). Here we report that T cell-based vaccination of mice with a myelin-derived peptide, when combined with transplantation of aNPCs into the cerebrospinal fluid (CSF), synergistically promoted functional recovery after spinal cord injury. The synergistic effect was correlated with modulation of the nature and intensity of the local T cell and microglial response, expression of brain-derived neurotrophic factor and noggin protein, and appearance of newly formed neurons from endogenous precursor-cell pools. These results substantiate the contention that the local immune response plays a crucial role in recruitment of aNPCs to the lesion site, and suggest that similar immunological manipulations might also serve as a therapeutic means for controlled migration of stem/progenitor cells to other acutely injured CNS sites.
Direct, Real-Time Measurement of Rapid Inorganic Phosphate Release Using a Novel Fluorescent Probe and Its Application to Actomyosin Subfragment 1 ATPase (1994)

A probe has been developed that can rapidly measure micromolar concentrations of inorganic phosphate (Pi), in particular to follow the release of Pi in real time from enzymes such as phosphatases. Its application is described to investigate the mechanism of actomyosin subfragment 1 ATPase. The probe uses the A197C mutant of Escherichia coli phosphate binding protein (PBP), generated by oligonucleotide-directed mutagenesis. A new fluorophore, N-[2-(1-maleimidyl)ethyl]-7-(diethylamino)coumarin-3-carboxamide (MDCC), was attached to the single cysteine to produce the reporter molecule that was purified free of unlabeled protein and unattached MDCC. The labeled protein has an excitation maximum at 425 nm and emission maximum at 474 nm in the absence of Pi, shifting to 464 nm with a 5.2-fold increase in fluorescence (lambda max/lambda max) when complexed with Pi at pH 7.0, low ionic strength, 22 degrees C. The fluorescence increase is not much altered by change to pH 8 or by increase in ionic strength to 1 M. Pi binds tightly (Kd approximately 0.1 microM) and rapidly (1.36 x 10(8) M-1 s-1) and the dissociation rate constant is 21 s-1, at pH 7.0, low ionic strength, 22 degrees C. A variety of phosphate esters were tested to investigate the specificity of the MDCC-PBP and none gave a significant fluorescence increase at 100 microM or higher concentration. ATP weakly inhibited the Pi-induced fluorescence change, indicating that it binds at least 3000-fold weaker than Pi. Because Pi is a widespread contaminant, the probe is used in conjunction with a "Pi mop", consisting of 7-methylguanosine and purine nucleoside phosphorylase, to remove free Pi from solutions by its conversion to ribose 1-phosphate. Because the equilibrium constant of this reaction is > 100, free Pi can be reduced below 0.1 microM. The probe was used to measure the rate of Pi release during a single turnover of ATP hydrolysis with actomyosin subfragment 1 from rabbit skeletal muscle, to determine to what extent Pi release contributes to the rate limitation of this ATPase. Using a stopped-flow apparatus, a small lag prior to rapid Pi release was detected at pH 7.0, low ionic strength, between 5 and 22 degrees C at both high and low [ATP]. For measurements of a single turnover at low [ATP], the observed rate increased with [actin], showing saturation with a Km with respect to actin of 26 microM.(ABSTRACT TRUNCATED AT 400 WORDS)
The contribution of excitatory amino acids to central sensitization and persistent nociception after formalin-induced tissue injury (1992)

The contribution of excitatory amino acids (EAAs) to the development of central sensitization and persistent nociception in response to tissue injury in rats was examined following the subcutaneous injection of formalin into the hindpaw. Formalin-induced nociceptive behaviors were enhanced by intrathecal pretreatment with the EAAs L-glutamate and L-aspartate. An enhancement of the formalin nociceptive response was also produced by intrathecal pretreatment with the receptor-selective EAA agonists NMDA and trans-(+/- )-1-amino-1,3-cyclopentane dicarboxylic acid (ACPD), but not (R,S)-alpha-amino-3-hydroxy-5-methylisozazole-4-propionic acid hydrobromide (AMPA). The effect of NMDA was enhanced by a combined administration with AMPA or APCD. Formalin nociceptive responses were dose-dependently reduced by intrathecal pretreatment with the NMDA receptor antagonists 2-amino-5-phosphonovaleric acid (APV) and (+)-MK-801 hydrogen maleate, but not the selective AMPA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione or the selective metabotropic EAA receptor antagonist 2-amino-3-phosphonopropionic acid. The results suggest that EAAs acting at the NMDA receptor contribute to central sensitization and persistent nociception following subcutaneous formalin injection.
Physical compatibility of neonatal total parenteral nutrient admixtures containing organic calcium and inorganic phosphate salts (2005)

Commonly used organic calcium and inorganic phosphate salts in cysteine-added, lipid-free TPN formulations at the highest recommended amounts for neonates were compatible when the amino acid concentration was between 1% and 4% and the dextrose concentration was 5% or 10%. The salts remained compatible for up to 30 hours at a room temperature of up to 27 degrees C. Precipitation of dibasic calcium phosphate occurred with lower amino acid concentrations and higher pH values.
Chemospecific Chromium[VI] Catalyzed Oxidation of C−H Bonds at −40 °C (2002)

H5IO6 in the presence of catalytic chromoyl diacetate is a powerful method for oxidation of C-H bonds. Tertiary and oxygen activated C-H bonds are oxidized to tertiary alcohols or ketones at temperatures as low as -40 degrees C. The putative reagent is neutral dioxoperoxy chromium[VI] which undergoes C-H oxidation with retention of stereochemistry. This reagent appears to be the first reagent capable of oxidation of a C-H bond in the presence of an olefin without concomitant epoxidation.
Amine-Assisted Facetted Etching of CdSe Nanocrystals (2005)

The treatment of CdSe nanocrystals (NCs) in a 3-amino-1-propanol (APOL)/water (v/v = 10:1) mixture at 80 degrees C in the presence of O(2) causes them to undergo a slow chemical etching process, as evidenced by spectroscopic and structural investigations. Instead of the continuous blue shift expected from a gradual decrease in NC dimensions, a bottleneck behavior was observed with distinct plateaus in the peak position of photoluminescence (PL) and corresponding maxima in PL quantum yield (i.e., 34 +/-7%). It is presently argued that such etching behavior is a result of two competitive processes taking place on the surface of these CdSe NCs: (i) oxidation of the exposed Se-sites to acidic SeO(x)() entities, which are readily solubilized in the basic APOL/H(2)O mixture, and (ii) coordination of the underlying Cd-sites with both amines and hydroxyl moieties to temporally impede NC dissolution. This is consistent with the HRTEM results, which suggest that the etched NCs adopt pyramidal morphologies with Cd-terminated facets (i.e., (0001) bases and either {011} or {21} sides) and account for the apparent resistance to etching at the plateau regions.
Interferon-alpha as an immunotherapeutic protein. (2002)

Interferon-alpha (IFN-alpha) has proven to be a clinically effective antiviral and antineoplastic therapeutic drug for more than 16 years. During this time, evidence from in vitro laboratory studies and the clinical arena has supported the concept that IFN-alpha is an immunotherapeutic drug. By regulating a diverse set of cytokines and their receptors, IFN-alpha is uniquely positioned to prime the host immune response and provide an effective antineoplastic- and antiviral-immune response. IFN-alpha stimulates the innate cell-mediated response and then participates in the transition of the initial host innate response into an effective adaptive-immune response. IFN-alpha also drives the adaptive cell-mediated CD8+ T-cell response and helps to maintain a CD4+ Th1-cell population balance for an effective antineoplastic and antiviral host defense. This review will describe the current state of knowledge of IFN-alpha as an immunoregulatory protein and address specific issues of IFN-alpha as an immunotherapeutic for antineoplastic and antiviral diseases.
Intramolecular amide bonds stabilize pili on the surface of bacilli (2009)

Gram-positive bacteria elaborate pili and do so without the participation of folding chaperones or disulfide bond catalysts. Sortases, enzymes that cut pilin precursors, form covalent bonds that link pilin subunits and assemble pili on the bacterial surface. We determined the x-ray structure of BcpA, the major pilin subunit of Bacillus cereus. The BcpA precursor encompasses 2 Ig folds (CNA(2) and CNA(3)) and one jelly-roll domain (XNA) each of which synthesizes a single intramolecular amide bond. A fourth amide bond, derived from the Ig fold of CNA(1), is formed only after pilin subunits have been incorporated into pili. We report that the domains of pilin precursors have evolved to synthesize a discrete sequence of intramolecular amide bonds, thereby conferring structural stability and protease resistance to pili.
Two-Dimensional Order in β-Sheet Peptide Monolayers (2000)

Amphiphilic peptides comprising alternating hydrophilic and hydrophobic amino acid residues were designed to form super-secondary structures composed of self-assembled β-strands as monolayers at the air−water interface. Insights provided by in situ grazing-incidence X-ray diffraction (GIXD), surface pressure vs area isotherms, and Fourier transform infrared spectroscopy allow structural characterization of the assembled nanostructures and rational correlation with the peptide sequence. Peptides seven to seventeen amino acids in length were found to form crystalline arrays with coherence lengths in the range of 100 to 1000 Å. Two-dimensional registry of the self-assembled peptides was induced by placement of proline residues at the peptide termini. The films were found to intercalate ordered arrays of ions between juxtaposed β-sheet ribbons to generate peptide−ion composite phases.