gebhart/patrepeval huggingface dataset:
PARticipation in inflammation (2003)

In this issue of the JCI, Ferrell and colleagues report that mice lacking the proteinase-activated receptor-2 (PAR-2) were protected against a form of adjuvant-induced arthritis (1). Herein we discuss protease-activated receptors, their mechanism of activation, and the contexts in which they are thought to function. A useful unifying hypothesis emerges: protease-activated receptors link tissue injury to appropriate cellular responses, and such responses, while normally homeostatic, may contribute to disease.

Protease-activated receptor-1 (PAR-1), the prototypical PAR, was identified in a search for the receptors that mediate the activation of platelets and other cells by the coagulation protease thrombin. Known to be a seven transmembrane domain G-protein–coupled receptor, PAR-1 is activated by proteolysis (Figure ​(Figure1).1). Thrombin binds to PAR-1’s N-terminal exodomain and cleaves it after Arg41 to generate a new receptor N-terminus. The first six amino acids of this new N-terminus, SFLLRN, then serve as a tethered ligand that binds intramolecularly to the receptor’s heptahelical bundle to effect transmembrane signaling and G protein activation. Thus PARs are, in essence, peptide receptors that carry their own ligands, which lie hidden until revealed by receptor cleavage. The synthetic peptide SFLLRN, which mimics the PAR-1 tethered ligand, is a PAR-1 agonist and activates PAR-1 independent of thrombin and receptor cleavage. Such peptide agonists have provided a ready tool for probing the effects of PAR activation in vitro and in vivo.



Figure 1

Mechanism of PAR-1 activation. The N-terminus of PAR-1, a seven transmembrane domain G protein–coupled receptor, contains a protease cleavage site that, once cleaved by thrombin, results in a new N-terminus. The new N-terminal sequence, SFLLRN, ...



Four PARs are currently known (recent reviews include refs. 2–4). PAR-1, PAR-3, and PAR-4 can be activated by thrombin, and thrombin is almost certainly a physiological activator of these receptors in vivo. Several other proteases can cleave these receptors productively and may also contribute to their function in vivo. PAR-2 can be activated by multiple trypsin-like serine proteases including: trypsin itself, mast cell tryptase, neutrophil proteinase 3, tissue factor/factor VIIa/factor Xa, and membrane-tethered serine protease-1. However PAR-2 is not cleaved by thrombin.
Specific interaction of IgE antibodies with a carbohydrate epitope of honey bee venom phospholipase A2 (1987)

Phospholipase A2 (E.C. 3.1.1.4.) is a major allergen of honey bee venom. It exists in a glycosylated and an unglycosylated variant. Both forms and the glycopeptide isolated after exhaustive proteolytic digestion were tested in RAST and RAST inhibition studies. IgE from 11 of 14 bee venom allergy sera exhibited significantly higher, and in two cases exclusive, affinity towards glycosylated phospholipase. In RAST inhibition experiments using phospholipase coupled to discs five of the sera were completely inhibited by glycopeptide at 0.1 mg/ml; four sera were partially inhibited and two sera could not be inhibited. Glycoasparagine, lacking all amino acids except the carbohydrate-linking asparagine, inhibits IgE-binding to glycopeptide discs up to 100%. These data clearly demonstrate that an oligosaccharide of a structural type frequently found in glycoproteins can represent an epitope which is recognized by IgE antibodies from allergic patients, which are specifically directed against the parent glycoprotein.
Olfactory Receptors in Non-Chemosensory Organs: The Nervous System in Health and Disease (2016)

Olfactory receptors (ORs) and down-stream functional signaling molecules adenylyl cyclase 3 (AC3), olfactory G protein α subunit (Gαolf), OR transporters receptor transporter proteins 1 and 2 (RTP1 and RTP2), receptor expression enhancing protein 1 (REEP1), and UDP-glucuronosyltransferases (UGTs) are expressed in neurons of the human and murine central nervous system (CNS). In vitro studies have shown that these receptors react to external stimuli and therefore are equipped to be functional. However, ORs are not directly related to the detection of odors. Several molecules delivered from the blood, cerebrospinal fluid, neighboring local neurons and glial cells, distant cells through the extracellular space, and the cells' own self-regulating internal homeostasis can be postulated as possible ligands. Moreover, a single neuron outside the olfactory epithelium expresses more than one receptor, and the mechanism of transcriptional regulation may be different in olfactory epithelia and brain neurons. OR gene expression is altered in several neurodegenerative diseases including Parkinson's disease (PD), Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and sporadic Creutzfeldt-Jakob disease (sCJD) subtypes MM1 and VV2 with disease-, region- and subtype-specific patterns. Altered gene expression is also observed in the prefrontal cortex in schizophrenia with a major but not total influence of chlorpromazine treatment. Preliminary parallel observations have also shown the presence of taste receptors (TASRs), mainly of the bitter taste family, in the mammalian brain, whose function is not related to taste. TASRs in brain are also abnormally regulated in neurodegenerative diseases. These seminal observations point to the need for further studies on ORs and TASRs chemoreceptors in the mammalian brain.
Recovered Heart Failure with Reduced Ejection Fraction and Outcomes: A Prospective Study (2017)

One in four treated patients with HFrEF showed recovery of systolic function. HF-recovered patients had significantly improved mortality and morbidity relative to HFpEF and HFrEF subjects. Further research is needed to identify optimal medications and device indications for HF-recovered patients.
Iron Stores, Blood Donation, and Insulin Sensitivity and Secretion (2005)

Blood donation is simultaneously associated with increased insulin sensitivity and decreased iron stores. Stored iron seems to impact negatively on insulin action even in healthy people, and not just in classic pathologic conditions associated with iron overload (hemochromatosis and hemosiderosis). According to these observations, it is imperative that a definition of excessive iron stores in healthy people be formulated.
Aromatic alkaloids from the marine sponge Chelonaplysilla sp (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAromatic alkaloids from the marine sponge Chelonaplysilla spSteven C. Bobzin and D. John FaulknerCite this: J. Org. Chem. 1991, 56, 14, 4403–4407Publication Date (Print):July 1, 1991Publication History Published online1 May 2002Published inissue 1 July 1991https://pubs.acs.org/doi/10.1021/jo00014a015https://doi.org/10.1021/jo00014a015research-articleACS PublicationsRequest reuse permissionsArticle Views467Altmetric-Citations46LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Protein synthesis-dependent formation of protein kinase Mzeta in long- term potentiation (1996)

The maintenance of long-term potentiation (LTP) in the CA1 region of the hippocampus has been reported to require both a persistent increase in phosphorylation and the synthesis of new proteins. The increased activity of protein kinase C (PKC) during the maintenance phase of LTP may result from the formation of PKMzeta, the constitutively active fragment of a specific PKC isozyme. To define the relationship among PKMzeta, long-term EPSP responses, and the requirement for new protein synthesis, we examined the regulation of PKMzeta after sub-threshold stimulation that produced short-term potentiation (STP) and after suprathreshold stimulation by single and multiple tetanic trains that produced LTP. We found that, although no persistent increase in PKMzeta followed STP, the degree of long-term EPSP potentiation was linearly correlated with the increase of PKMzeta. The increase was first observed 10 min after a tetanus that induced LTP and lasted for at least 2 hr, in parallel with the persistence of EPSP enhancement. Both the maintenance of LTP and the long-term increase in PKMzeta++ were blocked by the protein synthesis inhibitors anisomycin and cycloheximide. These results suggest that PKMzeta is a component of a protein synthesis-dependent mechanism for persistent phosphorylation in LTP.
Dielectric Loaded Substrate Integrated Waveguide (SIW) ${H}$-Plane Horn Antennas (2010)

A dielectric loaded substrate integrated waveguide (SIW) H-plane sectoral horn antenna has been proposed in this paper. The horn and the loaded dielectric are integrated by using the same single substrate resulting in easy fabrication and low cost. Two antennas with rectangular and elliptical shaped loaded dielectrics were designed and fabricated. These antennas have high gain and narrow beamwidths both in the E-plane and in the H-plane. The results from the simulation and those from the measurement are in good agreement. To demonstrate applications of the array, the small aperture elliptical dielectric loaded antenna has been used to form an array to obtain higher gain and to form a one-dimensional monopulse antenna array.
Activation of ventrolateral preoptic neurons by the somnogen prostaglandin D 2 (1998)

Prostaglandin D2 (PGD2) is an extensively studied sleep-promoting substance, but the neuroanatomical basis of PGD2-induced sleep is only partially understood. To determine potential regions involved in this response, we used Fos immunohistochemistry to identify neurons activated by infusion of PGD2 into the subarachnoid space below the rostral basal forebrain. PGD2 increased nonrapid eye movement sleep and induced striking expression of Fos in the ventrolateral preoptic area (VLPO), a cluster of neurons that may promote sleep by inhibiting the tuberomammillary nucleus, the source of the ascending histaminergic arousal system. Fos expression in the VLPO was positively correlated with the preceding amount of sleep and negatively correlated with Fos expression in the tuberomammillary nucleus. PGD2 also increased Fos immunoreactivity in the basal leptomeninges and several regions implicated in autonomic regulation. These observations suggest that PGD2 may induce sleep via leptomeningeal PGD2 receptors with subsequent activation of the VLPO.
Cuticular Photophores of Two Decapod Crustaceans, Oplophorus spinosus and Systellaspis debilis (1998)

The organization, ultrastructure, growth, and development of two types of cuticular photophore in oplophorid shrimps (Oplophorus spinosus and Systellaspis debilis) are described. Photophores located in the third maxilliped consist of a unit structure comprising a single photocyte and associated pigment cells. Reflecting pigment cells contain white pigment and form an apical cap above the photocyte; sheath cells contain red carotenoid pigment and form a light-absorbing layer around the photophore. Photophores located on the pleopods are compound structures comprising many photocytes. They also contain the same types of pigment cell that are found in the unit photophores of the maxilliped. Paracrystalline bodies at the apical ends of the photocytes in both types of photophore are thought to be associated with light generation. Both types of photophore have mechanisms for tilting in the pitch plane. In the maxilliped, the apices of the photophores are connected to a ligament that has its origin in the propodus. Flexion or extension of the dactylus displaces the ligament, which tilts the photophores synchronously. The cuticular window beneath each photophore remains stationary. The tilt mechanism of the pleopod photophores is quite different, and depends upon muscular contraction. A main and an accessory longitudinal muscle cause backwards rotation of the photophore by deforming the cuticle surface. A loop muscle that passes around the anterior face of the photophore causes forward rotation. The two mechanisms optimize the use of the photophores in ventral camouflage. They allow photophore rotation to compensate for changes in the shrimp's orientation in the plane of pitch and thus maintain the ventral direction of the luminescence.
PROLONGATION OF RENAL ALLOGRAFT SURVIVAL BY A CHIMERIC ANTI-HUMAN CD40 MONOCLONAL ANTIBODY IN NONHUMAN PRIMATES. (2000)

Larsen, Christian P.1; Odom, Kris1; Hollenbaugh, Diane3; Bray, Robert2; Hennigar, Randy2; Pearson, Thomas C.1 Author Information
Tissue Redox Activity as a Hallmark of Carcinogenesis: From Early to Terminal Stages of Cancer (2013)

The study shows that tissue redox balance is very sensitive to the progression of cancer and can be used as a diagnostic marker of carcinogenesis. The study also suggests that the noncancerous tissues of a cancer-bearing organism are susceptible to oxidative damage and should be considered a therapeutic target.
Pyrophosphate Detection in Water by Fluorescence Competition Assays: Inducing Selectivity through the Choice of the Indicator (2002)

Displacement of the previously bound, and quenched, fluorescent indicator (I) by coordination of the pyrophosphate ion to the two CuII centers of the receptor R results in the generation of the natural fluorescence of the indicator, and thus signals pyrophosphate recognition (see scheme). Discrimination from interfering anions (HPO42−, SO42−, NO3−, Cl−, NCO−, N3−, acetate, benzoate) can be achieved by tuning the indicator affinity towards the receptor.
New Metallodendrimers Containing an Octakis(diphenylphosphino)-Functionalized Silsesquioxane Core and Ruthenium(II)-Based Chromophores (2000)

A new class of surface-modified dendrimers has been prepared by reactions of 8 equiv of the terpyridine-functionalized polyether monodendrons with a polyhedral oligomeric silsesquioxane (POSS) core. Subsequent reactions of these spherically shaped organic dendrimers with Ru(II)-based precursors afford photo- and redox-active metallodendrimers. These new dendrimers have been characterized using a combination of mass spectral analysis (MALDI-TOF/MS, ESI/MS, and FAB/MS), nuclear magnetic resonance (1H, 13C, 29Si, and 31P(1H) NMR), photophysical analyses (electronic absorption, emission, excited-state lifetime, and quantum yield) and electrochemical measurement (cyclic voltammetry). Specifically, 31P(1H) NMR is used to monitor the completion of reactions and the purity of dendrimers and metallodendrimers. These new metallodendrimers exhibit large extinction coefficients that coincide with the number of peripheral Ru(II)-based chromophores. With the use of (-CH2-Ph-tpy)RuII(bpy)2 type of chromophores, all metallodendrimers are found emissive at room temperature, with lifetimes in the range of 605-890 ns. Photophysical data also indicate similar steady-state emission maxima and single-exponential decay kinetics for all metallodendrimers, and the observed overall quantum yields of the G1, G2, and G3 metallodendrimers are found to be 14, 20, and 7 times higher than that of the monomeric model complex (CH3-Ph-tpy)Ru(bpy)2(PF6)2. Electrochemical studies reveal the presence of surface-confined species, in addition to the ligand-centered and metal-centered redox processes.
Binding of plasminogen to cultured human endothelial cells. (1986)

Endothelial cells are known to release the two major forms of plasminogen activator, tissue plasminogen activator (TPA) and urokinase. We have previously demonstrated that plasminogen (PLG) immobilized on various surfaces forms a substrate for efficient conversion to plasmin by TPA (Silverstein, R. L., Nachman, R. L., Leung, L. L. K., and Harpel, P. C. (1985) J. Biol. Chem. 260, 10346-10352). We now report the binding of human PLG to cultured human umbilical vein endothelial cell (HUVEC) monolayers, utilizing a newly devised cell monolayer enzyme-linked immunosorbent assay system. PLG binding to HUVEC was concentration dependent and saturable at physiologic PLG concentration (2 microM). Binding of PLG was 70-80% inhibited by 10 mM epsilon-aminocaproic acid, suggesting that it is largely mediated by the lysine-binding sites of PLG. PLG bound at an intermediate level to human fibroblasts, poorly to human smooth muscle cells, and not at all to bovine smooth muscle or bovine endothelial cells; unrelated proteins such as human albumin and IgG failed to bind HUVEC. PLG binding to HUVEC was rapid, reaching a steady state within 20 min, and quickly reversible. 125I-PLG bound to HUVEC with an estimated Kd of 310 +/- 235 nM (S.E.); each cell contained 1,400,000 +/- 1,000,000 (S.E.) binding sites. Functional studies demonstrated that HUVEC-bound PLG is activatable by TPA according to Michaelis-Menten kinetics (Km, 5.9 nM). Importantly, surface-bound PLG was activated with a 12.7-fold greater catalytic efficiency than fluid phase PLG. These results indicate that PLG binds to HUVEC in a specific and functional manner. Binding of PLG to endothelial cells may play a pivotal role in modulating thrombotic events at the vessel surface.
Risk factors for developing multiple sclerosis after childhood optic neuritis (1997)

We reviewed the records of all children (younger than 16 years of age) who presented with a diagnosis of optic neuritis (ON) identified through the comprehensive records-linkage system at the Mayo Clinic and identified 94 cases between 1950 and 1988 with a documented history of idiopathic ON. Detailed follow-up information was available on 79 patients, with a median length of follow-up of 19.4 years. Life-table analysis showed that 13% of the 79 patients with isolated ON had progressed to clinically or laboratory-supported definite multiple sclerosis (MS) by 10 years of follow-up, 19% by 20 years, 22% by 30 years, and 26% by 40 years. Gender, age, funduscopic findings, visual acuity, or family history of either ON or MS did not predict the development of MS. The presence of bilateral sequential or recurrent ON increased the risk of developing MS (p = 0.002; hazard ratio = 5.09), whereas the presence of infection within 2 weeks before the onset of ON decreased the risk of developing MS (p = 0.060; hazard ratio = 0.24). This study of childhood ON supports the lower risk of recurrence and progression to MS compared with adults.
Minor histocompatibility antigens: targets for tumour therapy and transplant tolerance (2008)

Minor histocompatibility (H) antigens are allogeneic targets of T-cell mediated immune reactivity following allogeneic haematopoietic stem cell transplantation. Depending on the tissue expression profile of the minor H antigens this immune reactivity clinically results in graft-vs-host disease or in graft-vs-leukaemia effects. Targeting haematopoietic-specific minor H antigens by adoptive immunotherapy will evoke leukaemia-specific allo-immune responses, thereby enhancing graft-vs-leukaemia effects. Recently, a novel alternative role for minor H antigens in transplantation has been described; minor H antigen-specific T cells appear to be able to regulate allo-immune responses after solid organ transplantation. This diversity in immune reactivity suggests a broad clinical potential of minor H antigens, both in haematopoietic stem cell transplantation and in solid organ transplantation.
Mitigating the Metabolic Liability of Carbonyl Reduction: Novel Calpain Inhibitors with P1′ Extension (2018)

Dysregulation of calpains 1 and 2 has been implicated in a variety of pathological disorders including ischemia/reperfusion injuries, kidney diseases, cataract formation, and neurodegenerative diseases such as Alzheimer's disease (AD). 2-(3-Phenyl-1<i>H</i>)-pyrazol-1-yl)nicotinamides represent a series of novel and potent calpain inhibitors with high selectivity and <i>in vivo</i> efficacy. However, carbonyl reduction leading to the formation of the inactive hydroxyamide was identified as major metabolic liability in monkey and human, a pathway not reflected by routine absorption, distribution, metabolism, and excretion (ADME) assays. Using cytosolic clearance as a tailored <i>in vitro</i> ADME assay coupled with <i>in vitro</i> hepatocyte metabolism enabled the identification of analogues with enhanced stability against carbonyl reduction. These efforts led to the identification of P1' modified calpain inhibitors with significantly improved pharmacokinetic profile including P1' <i>N</i>-methoxyamide <b>23</b> as potential candidate compound for non-central nervous system indications.
Cutting Edge: A Small Molecule Antagonist of LFA-1-Mediated Cell Adhesion (1999)

LFA-1 (CD18,CD11a) is a cell-adhesion molecule that mediates critical immunological processes. In this paper we report the discovery and characterization of (R)-5-(4-bromobenzyl)-3-(3, 5-dichlorophenyl)-1,5-dimethylimidazolidine-2,4-dione (BIRT 377), an orally bioavailable small molecule that interacts specifically with LFA-1 via noncovalent binding to the CD11a chain and prevents LFA-1 from binding to its ligand, ICAM-1. BIRT 377 inhibits lymphocyte activity both in vitro and in vivo, in functional assays that require LFA-1-mediated cell adhesion. These results demonstrate that LFA-1-mediated leukocyte adhesion can be antagonized with noncharged, low m.w. molecules and suggest that the potential therapeutic value of adhesion inhibitors can be attained with a small, orally bioavailable compound.
Refractive index measurement for biomaterial samples by total internal reflection (2006)

The refractive index of biological tissue is a fundamental parameter in applications of optical diagnosis and laser treatments. In the present work, the refractive indices and thermo-optic coefficients of some basic biomaterials, such as blood plasma, haemoglobin solution and lipid membrane, were studied by the method of total internal reflection at the wavelengths of 532 and 632.8 nm that are the most frequently used laser wavelengths in the biomedical field. The effects of the sample concentration and the temperature on refractive index were measured, and empirical relationships were summarized, accompanied by a theoretical explanation based on molecular polarization theory. The results provide some fundamental data for the refractive indices of these biomaterials under variant conditions, and also demonstrate that the total internal reflection method is a feasible and reliable way to measure the refractive indices of biological samples.
Open issues and challenges in providing quality of service guarantees in high-speed networks (1993)

In this paper we identify the challenges and open issues involved in providing quality-of-service (QOS) guarantees to sessions in a high-speed wide area network and briefly survey research in this area. Four approaches towards providing QOS guarantees are described and discussed: the tightly controlled approach, the approximate approach, the bounding approach, and the observation-based approach.