gebhart/patrepeval huggingface dataset:
Urticaria and angioedema: a practical approach. (2004)

Urticaria (i.e., pruritic, raised wheals) and angioedema (i.e., deep mucocutaneous swelling) occur in up to 25 percent of the U.S. population. Vasoactive mediators released from mast cells and basophils produce the classic wheal and flare reaction. Diagnosis can be challenging, especially if symptoms are chronic or minimally responsive to therapy. A thorough medical history, physical examination, and methodical investigation are necessary to uncover diagnostic clues. Although serious medical illness can occur concurrently with chronic urticaria, acute urticaria generally is benign and self-limited. The mainstay of therapy for urticaria is avoidance of known triggering agents, judicious use of oral corticosteroids, and treatment with long-acting second-generation antihistamines, H2-receptor antagonists, tricyclic antidepressants, and anti-inflammatory leukotriene antagonists. Consultation for investigative therapy may be necessary if symptoms continue despite a stepwise approach to diagnosis and therapy.
Molecular basis of fast inactivation in voltage and Ca 2+ -activated K + channels: A transmembrane β-subunit homolog (1999)

Voltage-dependent and calcium-sensitive K+ (MaxiK) channels are key regulators of neuronal excitability, secretion, and vascular tone because of their ability to sense transmembrane voltage and intracellular Ca2+. In most tissues, their stimulation results in a noninactivating hyperpolarizing K+ current that reduces excitability. In addition to noninactivating MaxiK currents, an inactivating MaxiK channel phenotype is found in cells like chromaffin cells and hippocampal neurons. The molecular determinants underlying inactivating MaxiK channels remain unknown. Herein, we report a transmembrane beta subunit (beta2) that yields inactivating MaxiK currents on coexpression with the pore-forming alpha subunit of MaxiK channels. Intracellular application of trypsin as well as deletion of 19 N-terminal amino acids of the beta2 subunit abolished inactivation of the alpha subunit. Conversely, fusion of these N-terminal amino acids to the noninactivating smooth muscle beta1 subunit leads to an inactivating phenotype of MaxiK channels. Furthermore, addition of a synthetic N-terminal peptide of the beta2 subunit causes inactivation of the MaxiK channel alpha subunit by occluding its K+-conducting pore resembling the inactivation caused by the "ball" peptide in voltage-dependent K+ channels. Thus, the inactivating phenotype of MaxiK channels in native tissues can result from the association with different beta subunits.
Photocurrent-Determining Processes in Quasi-Solid-State Dye-Sensitized Solar Cells Using Ionic Gel Electrolytes (2003)

Dye-sensitized solar cells (DSCs) using ionic liquids, 1-alkyl-3-methylimidazolium iodide (alkyl: C3−C9), were fabricated with and without a low molecular weight gelator. The highest energy conversion efficiency of 5.0% was obtained from a quasi-solid-state DSC using 1-hexyl-3-methylimidazolium iodide (HMImI). Gelation of these ionic liquids demonstrated better high-temperature durability without decreasing the solar cell efficiency. However, the short-circuit currents (JSC) obtained from these DSCs were about 70% of that obtained from DSCs using organic liquid electrolyte (OLE). To explain the difference of the JSC values between the DSCs using ionic liquid electrolyte (ILE) and OLE, four primitive processes in DSCs, that is, charge transport in the electrolytes, light absorption by I3-, electron diffusion in a TiO2 electrode, and charge recombination, were examined. Viscosities of the ILE decreased with increasing I3- concentration and alkyl chain length. In ILE, measured JSC values increased with increasing I3- concentration up to 0.7−1.4 M, depending on the alkyl chain length. Measured JSC values showed the same tendency as that estimated using a calculation with a model in which the redox couple is transported by diffusion in electrolytes. These results suggest that the slower diffusion of I3- to the counter electrode (CE) limits the JSC values and requires a larger amount of I3- in ILE. However, increasing [I3-] to more than 0.7−1.4 M resulted in the decrease of JSC. At the optimized concentration of I3- in ILE, the influence of the absorption was estimated to be 13% of the decrease on photocurrent. To the estimate electron diffusion length in the TiO2 electrode, the electron diffusion coefficient (De) and electron recombination lifetime (τ) were measured, showing faster De and shorter τ in ILE than in OLE. The faster De was caused by the higher concentration of cation in ILE. However, the shorter τ was caused by the higher concentration of I3- and depended on the concentration. Thus, the electron diffusion lengths (L) in the DSC using ILE were shorter than that using OLE. Their shorter L also reduced the JSC in the ILE and with the increase of I3- concentration. Among the ILE, the increase of alkyl chain length increased τ. This result should explain the highest efficiency observed in HMImI. During the durability test of the DSC at high temperature, a decrease of the efficiency of the cell using ILE was observed in 1000 h. Time course change of I3- concentration measurements revealed that the gelation of the electrolyte depresses a decrease of I3- concentration caused by sublimation of I2. Depression of sublimation of I2 is important to improve the high-temperature durability in nonvolatile ionic liquid electrolyte.
An analysis of a mesa instruction set using dynamic instruction frequencies (1982)

The Mesa architecture is implemented on a variety of processors, and dynamic instruction frequency data for two programs is used to analyze the architecture in an implementation independent fashion.
In vivo and in vitro phosphorylation of annexin II in T cells: potential regulation by annexin V (1995)

In order to understand how signal transduction occurs during T cell activation, it is necessary to identify the key regulatory molecules whose function is influenced by phosphorylation. Annexins II (A-II) and V (A-V) belong to a large family of Ca(2+)-dependent phospholipid-binding proteins. Among many putative functions, annexins may be involved in signal transduction during cellular proliferation and differentiation. In the present study we show that A-II is phosphorylated in vivo in the Jurkat human T cell line. Indeed, A-II is phosphorylated after stimulation by phorbol myristate acetate and on serine residues after T cell antigen receptor (TcR) stimulation. In cytosol from Jurkat cells, A-II is phosphorylated only by Ca2+/phospholipid-stimulated kinases such as Ca(2+)-dependent protein kinases C (cPKCs). A-V inhibits the phosphorylation of A-II and other substrates of cPKCs and has no effect on kinases activated only by phospholipids. In conclusion, A-II is phosphorylated both in vitro and in vivo in Jurkat cells, and may play a role as a substrate during signal transduction in lymphocytes via the TcR through the PKC pathway. On the other hand, A-V could act as a potent modulator of cPKCs in Jurkat cells.
Pathogenic Leptospira species express surface‐exposed proteins belonging to the bacterial immunoglobulin superfamily (2003)

Proteins with bacterial immunoglobulin-like (Big) domains, such as the Yersinia pseudotuberculosis invasin and Escherichia coli intimin, are surface-expressed proteins that mediate host mammalian cell invasion or attachment. Here, we report the identification and characterization of a new family of Big domain proteins, referred to as Lig (leptospiral Ig-like) proteins, in pathogenic Leptospira. Screening of L. interrogans and L. kirschneri expression libraries with sera from leptospirosis patients identified 13 lambda phage clones that encode tandem repeats of the 90 amino acid Big domain. Two lig genes, designated ligA and ligB, and one pseudogene, ligC, were identified. The ligA and ligB genes encode amino-terminal lipoprotein signal peptides followed by 10 or 11 Big domain repeats and, in the case of ligB, a unique carboxy-terminal non-repeat domain. The organization of ligC is similar to that of ligB but contains mutations that disrupt the reading frame. The lig sequences are present in pathogenic but not saprophytic Leptospira species. LigA and LigB are expressed by a variety of virulent leptospiral strains. Loss of Lig protein and RNA transcript expression is correlated with the observed loss of virulence during culture attenuation of pathogenic strains. High-pressure freeze substitution followed by immunocytochemical electron microscopy confirmed that the Lig proteins were localized to the bacterial surface. Immunoblot studies with patient sera found that the Lig proteins are a major antigen recognized during the acute host infection. These observations demonstrate that the Lig proteins are a newly identified surface protein of pathogenic Leptospira, which by analogy to other bacterial immunoglobulin superfamily virulence factors, may play a role in host cell attachment and invasion during leptospiral pathogenesis.
A nucleated assembly mechanism of Alzheimer paired helical filaments (1998)

Alzheimer's disease is characterized by two types of fibrous aggregates in the affected brains, the amyloid fibers (consisting of the Abeta-peptide, generating the amyloid plaques), and paired helical filaments (PHFs; made up of tau protein, forming the neurofibrillary tangles). Hence, tau protein, a highly soluble protein that normally stabilizes microtubules, becomes aggregated into insoluble fibers that obstruct the cytoplasm of neurons and cause a loss of microtubule stability. We have developed recently a rapid assay for monitoring PHF assembly and show here that PHFs arise from a nucleated assembly mechanism. The PHF nucleus comprises about 8-14 tau monomers. A prerequisite for nucleation is the dimerization of tau because tau dimers act as effective building blocks. PHF assembly can be seeded by preformed filaments (made either in vitro or isolated from Alzheimer brain tissue). These results suggest that dimerization and nucleation are the rate-limiting steps for PHF formation in vivo.
Circulating (cell‐free) nucleic acids – A promising, non‐invasive tool for early detection of several human diseases (2007)

Circulating nucleic acids (CNA) are present in small amounts in the plasma of healthy individuals. However, increased levels of plasma CNA have been reported in a number of clinical disorders like cancer, stroke, trauma, myocardial infarction, autoimmune disorders, and pregnancy-associated complications. CNA has received special attention because of its potential application as a non-invasive, rapid and sensitive tool for molecular diagnosis and monitoring of acute pathologies and the prenatal diagnosis of fetal genetic diseases. This review throws light on the current status of blood CNA as a diagnostic marker and its potential as a powerful tool in the future.
A Chemically Modified Green-Fluorescent Protein that Responds to Cleavage of an Engineered Disulphide Bond by Fluorescence Resonance Energy Transfer (FRET)-Based Changes (2005)

Abstract The mixed disulfide of a Green-Fluorescent Protein with an Alexa 532 fluorescent label showed FRET, with quenching of the GFP emission. Reductive cleavage of this disulfide bond destroyed the FRET, giving a change in the ratios of fluorescence intensity at the wavelengths corresponding to the GFP and the Alexa dye. Cleavage by glutathione (second order rate constant at pH 7.4 was 1.18 ± 0.02 × 102 M−1 min−1) was faster than for sodium cyanoborohydride.
Carbohydrate building blocks (1995)

The Raw Materials. Carbohydrate Acetal Derivatives. Other Selectively Protected Sugars. Oxidation Products: Aldonic Acids and Lactones. Reduction Products: Carbohydrate Polyols. 1,6--Anhydro sugars. Unsaturated Sugars. Products of Base Treatment. Products of Acid Treatment. Disaccharides. Miscellaneous Carbohydrate Products. Compendium of Building Blocks. Indexes.
The platelet-derived growth factor beta-receptor kinase insert confers specific signaling properties to a chimeric fibroblast growth factor receptor. (1992)

Signal transduction by tyrosine kinase growth factor receptors involves ligand-induced phosphorylation of substrates for the kinase, resulting in mediation of common or receptor-specific biological signals. We have compared signal transduction pathways for the fibroblast growth factor receptor-1 (FGFR-1), the platelet-derived growth factor beta-receptor (PDGFR-beta), and a chimeric FGFR-1 molecule, FGFRchim, in which the FGFR-1 kinase insert was replaced with that of the PDGFR-beta. The different receptors were characterized and found to be functional as ligand-stimulatable kinases, after expression of the respective human cDNAs in porcine aortic endothelial cells. Substrates for the receptors were analyzed by ligand stimulation of [32P]orthophosphate-labeled cells and immunoprecipitation with phosphotyrosine antiserum. A number of phosphoproteins were induced in all the different types of cells, but components specifically induced after stimulation of FGFR-1 and PDGFR-beta expressing cells could also be detected. Examination of receptor-associated substrates by in vitro kinase assays revealed phosphoproteins of 65 and 85 kDa, which were associated with PDGFR-beta and FGFRchim, but not with FGFR-1. The 85-kDa phosphoprotein could correspond to the regulatory subunit of phosphatidylinositol 3' kinase (PI3-K), since phosphatidylinositol 3' kinase activity was detected after ligand stimulation of FGFRchim- and PDGFR-beta- but not FGFR-1-expressing cells. In addition, ligand stimulation of FGFRchim- and PDGFR-beta-expressing cells, but not FGFR-1-expressing cells, led to induction of actin reorganization in the form of circular membrane ruffling. Thus, replacement of a discrete segment of the intracellular domain of the FGFR-1 with the corresponding stretch from the PDGFR-beta resulted in transfer of PDGFR-beta-specific signaling properties to the chimeric molecule.
Duodenal ulcer prevalence: research into the nature of possible protective dietary lipids (2003)

The varying geographical prevalence of duodenal ulceration has suggested a relationship to staple diet. Previous experiments on animal peptic ulcer models showed that certain foods, particularly the lipid fraction, are ulceroprotective. This paper reports experiments on animal models further to investigate the nature of the protective substances in the most active lipid, that of horse gram. The free fatty acids and triglycerides, sterols, sterol esters and phospholipids from horse gram were extracted and tested for protective activity on rat peptic ulcer models: the pyloric ligation model which is chronic, involving 14 days pre-feeding, and two acute models using ethanol or cysteamine to induce ulceration. The results showed that sterol esters, but not sterols, were protective in the pyloric ligation model. Sterols were protective in the acute models using ethanol-induced and cysteamine-induced ulceration. Phospholipids were protective in both types of model. The free fatty acids and triglycerides gave no protection using the pyloric ligation model. The presence of sterols, sterol esters and phospholipids in the lipid fraction of foods in staple diets may account for the low prevalence of duodenal ulcer in certain geographical areas, despite a uniformly high prevalence of Helicobacter pylori infection.
Crohn's disease-isolated mycobacteria are identical to Mycobacterium paratuberculosis, as determined by DNA probes that distinguish between mycobacterial species (1987)

DNA extracted from an unclassified Crohn's disease-isolated Mycobacterium strain was cloned. The recombinant clones were radiolabeled and hybridized to restriction digests of mycobacterial DNA transferred to nylon membranes. Restriction fragment length polymorphisms (RFLPs) were identified that distinguished between mycobacterial DNA samples. Quantitative estimates of frequencies of DNA base substitution were also obtained. No RFLPs were detected between the DNA of three unclassified Crohn's disease-isolated mycobacteria and Mycobacterium paratuberculosis, although several RFLPs were detected that distinguished between M. paratuberculosis and both M. avium complex serovars 2 and 5. The frequency of DNA base substitution between M. paratuberculosis and M. avium complex serovar 2 was measured as 0.87 (+/- 1.2)%.
A New Era in Prenatal Diagnosis: The Use of Cell-Free Fetal DNA in Maternal Circulation for Detection of Chromosomal Aneuploidies (2013)

Prenatal screening for chromosomal aneuploidies is a fundamental part of routine obstetric care in most countries. Typically, maternal age, weight, ethnicity, serum biomarkers (including pregnancy-associated plasma protein A, human chorionic gonadotropin, α-fetoprotein, inhibin A, and estriol), and sonographic features (i.e., nuchal translucency) are included in a risk algorithm to determine the probability of the fetus being affected. Pregnant women identified as at high risk according to the prenatal screen can then undergo invasive procedures, such as amniocentesis and chorionic villus sampling, to confirm the diagnosis. Current prenatal-screening methods are able to identify approximately 90% of pregnancies affected by trisomy 21 (Down syndrome) at a false-positive rate of approximately 5%. Given that the prevalence of chromosomal aneuploidies is generally quite low, a false-positive rate of 5% means that a large number of women with unaffected pregnancies undergo invasive procedures, putting the fetus at an unnecessary risk for miscarriage. The discovery of fetal cell-free DNA in the plasma of pregnant women 14 years ago opened up the possibility of identifying chromosomal abnormalities noninvasively, through a single blood sample. Approximately 10% of cell-free DNA in the maternal circulation is of fetal origin, and this property was initially exploited to determine rhesus D status and the sex of the unborn fetus. The advent of next-generation DNA sequencing, however, has allowed prenatal detection of chromosomal aneuploidies, including trisomy 21, from maternal blood. In brief, the proportion of chromosome 21 DNA molecules in maternal plasma is measured directly; an increase above a predetermined threshold is indicative of trisomy 21. The clinical performance of this noninvasive prenatal test has been promising, with recent clinical studies having shown a diagnostic sensitivity of 100% and a diagnostic specificity of 98%–99%, compared with full karyotyping by invasive means. When used as a second-tier screening procedure, this technology also has the …
Human Orthologs of Yeast Vacuolar Protein Sorting Proteins Vps26, 29, and 35: Assembly into Multimeric Complexes (2000)

Sorting nexin (SNX) 1 and SNX2 are mammalian orthologs of Vps5p, a yeast protein that is a subunit of a large multimeric complex, termed the retromer complex, involved in retrograde transport of proteins from endosomes to the trans-Golgi network. We report the cloning and characterization of human orthologs of three additional components of the complex: Vps26p, Vps29p, and Vps35p. The close structural similarity between the yeast and human proteins suggests a similarity in function. We used both yeast two-hybrid assays and expression in mammalian cells to define the binding interactions among these proteins. The data suggest a model in which hVps35 serves as the core of a multimeric complex by binding directly to hVps26, hVps29, and SNX1. Deletional analyses of hVps35 demonstrate that amino acid residues 1-53 and 307-796 of hVps35 bind to the coiled coil-containing domain of SNX1. In contrast, hVps26 binds to amino acid residues 1-172 of hVps35, whereas hVps29 binds to amino acid residues 307-796 of hVps35. Furthermore, hVps35, hVps29, and hVps26 have been found in membrane-associated and cytosolic compartments. Gel filtration chromatography of COS7 cell cytosol showed that both recombinant and endogenous hVps35, hVps29, and hVps26 coelute as a large complex ( approximately 220-440 kDa). In the absence of hVps35, neither hVps26 nor hVps29 is found in the large complex. These data provide the first insights into the binding interactions among subunits of a putative mammalian retromer complex.
Technique of electroorganic synthesis (1974)

Electrochemical Engineering Principles as Related to Electroorganic Processes (D. T. Chin & C. Y. Cheng). Performance of Two-Phase Electrolyte Electrolysis (H. Feess & H. Wendt). Design of a Multipurpose, Modularized Electrochemical Cell (L. Carlson et al.). Electrode Materials (B. V. Tilak et al.). Scale-Up of Electroorganic Processes: Some Examples for a Comparison of Electrochemical Syntheses with Conventional Syntheses (D. Degner). Experience in the Scale-Up of the Monsanto Adiponitrile Process (D. E. Danly & C. R. Campbell). The Phillips Electrochemical Flourination Process (W. V. Childs). Use of Rotating Electrodes for Small-Scale Electroorganic Processes (H. V. K. Udupa & K. S. Udupa). Electrochemical Engineering of Electroorganic Processes: Illustrated by an Energy Assessment of Some Large-Tonnage Process Chemicals (T. Beck et al.). Economics of Electroorganic Synthesis (K. B. Keating & V. D. Sutlic). Errata for Part I and Part II. Index.
Isolation of neutralizing anti-C5a monoclonal antibodies from a filamentous phage monovalent Fab display library. (1994)

A panel of mAbs against the activated complement component C5a was obtained from a filamentous phage M13-Fab display library generated from mice immunized with human rC5a. Fabs isolated from the library after iterative selection vs rC5a bound to both rC5a and purified C5. To isolate Fabs specific for neoepitopes expressed on C5a but not on the native complement component C5 the library was rescreened in a competitive manner. The phage Fab library was first incubated with immobilized C5 to deplete C5 reactive Fabs. The C5 nonadherent phage were then incubated with immobilized rC5a in the presence of soluble C5. Bound phage were eluted and subjected to two additional cycles of subtraction with immobilized C5 and selection with immobilized rC5a in the presence of soluble C5. After three cycles of this competitive biopanning four Fabs reactive with rC5a were isolated. Two bound preferentially with and neutralized C5a. Competitive biopanning of phage display libraries may increase the probability of identification of Abs of the desired specificity.
Regulation of the Acute Production of Steroids in Steroidogenic Cells* (1996)

The mechanism regulating the production of steroids in response to trophic hormone stimulation has been the subject of investigation for over three decades. When considering the effects of trophic hormones on the steroidogenic process it is necessary to first distinguish between acute effects and chronic effects. Acute effects are those which result in the very rapid (within minutes) synthesis and secretion of steroids in response to hormone stimulation and involve the rapid translocation of intracellular cholesterol to the site of its cleavage, as will be discussed later. Chronic effects are those which occur on the order of hours to tens of hours and involve increased gene transcription and translation of the proteins involved in the biosynthesis of steroids. This chapter will focus on studies designed to elucidate the mechanisms involved in the acute regulation of steroid production in response to hormone stimulation. Overviews of the effects of chronic stimulation on steroidogenic enzymes have appeared in several excellent review articles (Simpson and Waterman 1983; Miller 1988; Hanukoglu 1992).