gebhart/patrepeval huggingface dataset:
P3–P3′ Residues Flanking Scissile Bonds in Factor VIII Modulate Rates of Substrate Cleavage and Procofactor Activation by Thrombin (2012)

Thrombin-catalyzed activation of factor VIII (FVIII) occurs through proteolysis at three P1 Arg residues: Arg(372) and Arg(740) in the FVIII heavy chain and Arg(1689) in the FVIII light chain. Cleavage at the latter two sites is relatively fast compared with cleavage at Arg(372), which appears to be rate-limiting. Examination of the P3-P3' residues flanking each P1 site revealed that those sequences at Arg(740) and Arg(1689) are more optimal for thrombin cleavage than at Arg(372), suggesting these sequences may impact reaction rates. Recombinant FVIII variants were prepared with mutations swapping scissile bond flanking sequences in the heavy chain individually and in combination with a second swap or with a P1 point mutation. Rates of generation of A1 and A3-C1-C2 subunits were determined by Western blotting and correlated with rates of cleavage at Arg(372) and Arg(1689), respectively. Rates of thrombin cleavage at Arg(372) were increased ~10- and ~3-fold compared with that of wild-type FVIII when it was replaced with P3-P3' residues flanking Arg(740) and Arg(1689), respectively, and these values paralleled increased rates of A2 subunit generation and procofactor activation. Positioning of more optimal residues flanking Arg(372) abrogated the need for initial cleavage at Arg(740) to facilitate this step. These results show marked changes in cleavage rates correlate with the extent of cleavage-optimal residues flanking the scissile bond and modulate the mechanism for procofactor activation.
X-ray Diffraction and X-ray Spectroscopy Studies of Cobalt-Doped Anatase TiO2:Co Nanopowders (2017)

Co-doped TiO2 is one of the most extensively studied oxides for applying as dilute magnetic semiconductors due to its room temperature magnetism. Here we present results of the studies of Ti0.97Co0.03O2 nanopowders synthesized by microwave-assisted hydrothermal method by means of X-ray diffraction, soft X-ray absorption spectroscopy (Ti L2,3 and Co L2,3 spectra), hard X-ray absorption spectroscopy (Co K spectra), and 1s3p resonant inelastic X-ray scattering at the Co K edge. According to X-ray diffraction data and Ti L2,3 X-ray absorption spectra, all the samples before the thermal treatment exhibit anatase structure with substantial amount of amorphous phase. After annealing the Ti0.97Co0.03O2 samples in vacuum or hydrogen at 700 °C, the anatase structure persists while amorphous phase contribution is eliminated. Surface-sensitive soft X-ray absorption Co L2,3 spectroscopy revealed only Co2+ ions tetrahedrally coordinated by oxygen ions and no sign of metallic Co. Co2+ tetrahedral sites (instead of typical octahedral ones) are an additional evidence for Co2+ localization at the distorted TiO2 particle surface. Bulk-sensitive X-ray diffraction, Co K X-ray absorption spectroscopy, and 1s3p resonant inelastic X-ray scattering at the Co K edge revealed clustering of metallic cobalt inside of the large agglomerates formed by TiO2 nanoparticles in annealed TiO2:Co nanopowders.
Aura of Corroles (2009)

Corroles display distinctive structural, spectroscopic, and photophysical properties, as well as some exceptional chemical reactivities that are not shared by other molecules. In addition, low-valent metal complexes are extremely reactive when chelated by corroles and the opposite holds for the high-valent counterparts. One aim of this account is to provide a thorough understanding of the underlying principles that govern these phenomena, while the other goal is to demonstrate how these features may be used advantageously for utilization of corroles and their corresponding metal complexes in applications for which they could display superior performances. The main examples that are emphasized regarding the above respect are catalysis, imaging, and aspects relevant to drug development.
Evaluation of pentamorphone in humans: a new potent opiate. (1989)

We evaluated the analgesic properties of 14-beta-n-pentylaminomorphinone (pentamorphone), a new morphinan derivative, in 23 male volunteers divided into 6 groups who were given either placebo (1 per group) or 0.015, 0.03, 0.06, 0.12, 0.24, 0.48 microgram.kg-1 pentamorphone intravenously. Analgesia was evaluated by the maximal tolerance to a spring-loaded rod on the tibia and manubrium. Analgesic assessments and arterial blood samples were taken prior to and at set time intervals following drug administration. Pentamorphone produced a linear increase in pain tolerance with increasing dose as well as a dose-dependent depression of ventilation. Pentamorphone had no effect on blood pressure or heart rate in the doses used. Plasma histamine levels at 5 minutes were not elevated with any of the dosages. Pentamorphone appears to be an analgesic with clinically tolerable side effects in the range 0.12 to 0.24 microgram.kg-1 that merits further evaluation under clinical conditions.
Phosphatidylinositol 3-Kinase/AKT Pathway Regulates the Endoplasmic Reticulum to Golgi Traffic of Ceramide in Glioma Cells (2008)

Different lines of evidence indicate that both aberrant activation of the phosphatidylinositol 3-OH kinase (PI3K)/Akt survival pathway and down-regulation of the death mediator ceramide play a critical role in the aggressive behavior, apoptosis resistance, and adverse clinical outcome of glioblastoma multiforme. Furthermore, the inhibition of the PI3K/Akt pathway and the up-regulation of ceramide have been found functional to the activity of many cytotoxic treatments against glioma cell lines and glioblastomas as well. A reciprocal control between PI3K/Akt and ceramide signaling in glioma cell survival/death is suggested by data demonstrating a protective role of PI3K/Akt on ceramide-induced cell death in glial cells. In this study we investigated the role of the PI3K/Akt pathway in the regulation of the ceramide metabolism in C6 glioma cells, a cell line in which the PI3K/Akt pathway is constitutively activated. Metabolic experiments performed with different radioactive metabolic precursors of sphingolipids and microscopy studies with fluorescent ceramides demonstrated that the chemical inhibition of PI3K and the transfection with a dominant negative Akt strongly inhibited ceramide utilization for the biosynthesis of complex sphingolipids by controlling the endoplasmic reticulum (ER) to Golgi vesicular transport of ceramide. These findings constitute the first evidence for a PI3K/Akt-dependent regulation of vesicle-mediated movements of ceramide in the ER-Golgi district. Moreover, the findings also suggest the activation of the PI3K/Akt pathway as crucial to coordinate the biosynthesis of membrane complex sphingolipids with cell proliferation and growth and/or to maintain low ceramide levels, especially as concerns those treatments that promote ceramide biosynthesis in the ER.
Unilateral Bronchospasm After Interpleural Analgesia (1992)

Departments of Anesthesiology, Georgia Baptist Medical Center, Atlanta, and Medical College of Georgia. Augusta, Georgia Accepted for publication September 24, 1991. Address correspondence to Dr. Shantha, Department of Anesthesiology, Georgia Baptist Medical Center; 300 Boulevard N.E., Atlanta, GA 30312. I thank Dr. Dav T. Shantha, Victoria Kay T. Shantha, The Medical Center anesthesia associates, and Southeastern Pain Institute at Georgia Baptist Medical Center for their help in the preparation of this manuscript.
Radixin is a novel member of the band 4.1 family. (1991)

Radixin is an actin barbed-end capping protein which is highly concentrated in the undercoat of the cell-to-cell adherens junction and the cleavage furrow in the interphase and mitotic phase, respectively (Tsukita, Sa., Y. Hieda, and Sh. Tsukita. 1989 a.J. Cell Biol. 108:2369-2382; Sato, N., S. Yonemura, T. Obinata, Sa. Tsukita, and Sh. Tsukita. 1991. J. Cell Biol. 113:321-330). To further understand the structure and functions of the radixin molecule, we isolated and sequenced the cDNA clones encoding mouse radixin. Direct peptide sequencing of radixin and immunological analysis with antiserum to a fusion protein were performed to confirm that the protein encoded by these clones is identical to radixin. The composite cDNA is 4,241 nucleotides long and codes for a 583-amino acid polypeptide with a calculated molecular mass of 68.5 kD. Sequence analysis has demonstrated that mouse radixin shares 75.3% identity with human ezrin, which was reported to be a member of the band 4.1 family. We then isolated the cDNA encoding mouse ezrin. Sequence analysis and Northern blot analysis revealed that radixin and ezrin are similar but distinct (74.9% identity), leading us to conclude that radixin is a novel member of the band 4.1 family. In erythrocytes the band 4.1 protein acts as a key protein in the association of short actin filaments with a plasma membrane protein (glycophorin), together with spectrin. Therefore, the sequence similarity between radixin and band 4.1 protein described in this study favors the idea that radixin plays a crucial role in the association of the barbed ends of actin filaments with the plasma membrane in the cell-to-cell adherens junction and the cleavage furrow.
Methods, Challenges and Potentials of Single Cell RNA-seq (2012)

RNA-sequencing (RNA-seq) has become the tool of choice for transcriptomics. Several recent studies demonstrate its successful adaption to single cell analysis. This allows new biological insights into cell differentiation, cell-to-cell variation and gene regulation, and how these aspects depend on each other. Here, I review the current single cell RNA-seq (scRNA-seq) efforts and discuss experimental protocols, challenges and potentials.
Relative corticosteroid insensitivity of alveolar macrophages in severe asthma compared with non-severe asthma (2008)

Alveolar macrophages from patients with severe asthma demonstrate CS insensitivity associated with increased p38 MAPK activation that may result from impaired inducibility of MKP-1.
One-step all-in-one dry reagent immunoassays with fluorescent europium chelate label and time-resolved fluorometry (1996)

The availability of an intrinsically fluorescent, inert, and stable Eu chelate label made it feasible to design one-step all-in-one immunoassays with time-resolved fluorometry for detection. Both competitive and noncompetitive immunoassays are performed in microtitration wells containing all assay-specific components in a stable dry form. Only the sample and one assay buffer common for all analytes need to be added. Model assays for human chorionic gonadotropin (hCG), alpha-fetoprotein (AFP), and progesterone all reached equilibrium in 15 min or less without compromising the performance characteristics of the measurements, all of which perform at least equivalent to state-of-the-art assays. The detection limits for hCG, AFP, and progesterone were 0.3 IU/L, 0.1 microgram/L, and 0.5 nmol/L, respectively. The assay ranges for hCG and AFP were linear to 5000 IU/L and 1200 micrograms/L, respectively. The immunoassay format can be readily implemented in a fully automated random-access immunoassay system with optimal performance characteristics and no handling of analyte-specific assay components.
Human tryptase fibrinogenolysis is optimal at acidic pH and generates anticoagulant fragments in the presence of the anti-tryptase monoclonal antibody B12 (1997)

Human tryptase is uniquely regulated by its association with heparin and resists inhibition by biological protease inhibitors. The effects of pH and B12, an IgG anti-tryptase mAb, on cleavage of the synthetic substrate tosyl-Gly-Pro-Lys-p-nitroanilide and of the biological substrate fibrinogen by tryptase were examined. Tosyl-Gly-Pro-Lys-pnitroanilide cleavage was optimal at neutral pH and was inhibited by the B12 mAb at acidic and neutral pH values. At pH 7.5, inhibition was reversible and noncompetitive. In contrast, the optimal pH for tryptase to cleave fibrinogen was acidic. B12 dramatically enhanced the rate and extent that tryptase cleaved all three fibrinogen subunits at pH 6.0 to 6.5, but inhibited these activities at neutral pH. Major fibrinogen cleavage fragments generated at acidic pH by the B12:tryptase complex were identical with those made by plasmin. Thus, at acid pH, tryptase alone destroyed the ability of fibrinogen to clot, while the B12:tryptase complex increased the rate of fibrinogenolysis and also generated the anticoagulant, fragment D. The acidic pH optimum for tryptase fibrinogenolysis may direct this activity to tissue sites of inflammation. A putative biological equivalent to B12 would limit tryptase fibrinogenolytic activity at sites of neutral pH, such as blood, but would augment activity at acidic sites.
Cloning and expression of cDNA for human vascular anticoagulant, a Ca2+‐dependent phospholipid‐binding protein (1988)

Based on sequence information from tryptic peptides an almost full-size cDNA coding for the human vascular anticoagulant was isolated from a placental cDNA library and sequenced. The coding region was cloned into an Escherichia coli expression vector and the protein expressed at high levels. The recombinant protein was purified and found to be indistinguishable from its natural counterpart in several biological assays.
[Diagnostic value of biochemical tumor markers in serum of patients with cancer of the ovary]. (1983)

A comparison of several serum tumor markers (lactate dehydrogenase (LDH), LDH isozyme, hydroxybutylrate dehydrogenase (HBD), alkaline phosphatase (ALP), cholinesterase (Choline-E), aldolase (ALD), leucine aminopeptidase (LAP), gamma-glutamyl transpeptidase (gamma-GTP), human chorionic gonadotropin (HCG), carcinoembryonic antigen (CEA) and alpha 1-fetoprotein (AFP)) was made in patients with carcinoma or benign tumor of the ovary and healthy control subjects. The greatest positive rates were obtained with the markers HBD (76.5%) and Choline-E (73.3%) for patients with carcinoma of the ovary, respectively. However, based on false positive results, Choline-E was also greatest (50.0%) for patients with benign tumor of the ovary. The lowest false positive rates were obtained with ALD, but the positive rates for patients with stage I and II diseases were 0.0%. The most suitable single marker for patients with stage I and II diseases was HBD (62.5%), followed by LDH (41.7%). Three of 4 patients with early cancer, who had normal serum LDH levels, showed abnormal LDH isozyme patterns (elevated LDH-4 and -5). A combination of LDH activity and LDH isozyme resulted in an increase in the positive results (41.7% to 70.0%), that is, the cancer patients were positive for one of the two markers. For CEA, AFP and HCG, the positive results were 26.9%, 19.0% and 7.1%, respectively. Positive and false positive rates for ALP were 36.7% and 7.1%, but the positive rates in the early stage were lower (14.3%), compared to those for LDH and HBD. HBD and LDH activities in the ovarian malignant tissues and ascitic fluids were significantly higher than those in the benign tumor tissues and ascitic fluids, resulting in a significant elevation of serum LDH and HBD levels in the patients. Moreover, it was suggested that inhibition test of ALP by the inhibitors might be able to identify the tissue origin of ALP in the cancer patients.
A novel multilocus sequence typing scheme for the opportunistic pathogen Propionibacterium acnes and characterization of type I cell surface-associated antigens (2011)

We have developed a novel multilocus sequence typing (MLST) scheme and database (http://pubmlst.org/pacnes/) for Propionibacterium acnes based on the analysis of seven core housekeeping genes. The scheme, which was validated against previously described antibody, single locus and random amplification of polymorphic DNA typing methods, displayed excellent resolution and differentiated 123 isolates into 37 sequence types (STs). An overall clonal population structure was detected with six eBURST groups representing the major clades I, II and III, along with two singletons. Two highly successful and global clonal lineages, ST6 (type IA) and ST10 (type IB(1)), representing 64 % of this current MLST isolate collection were identified. The ST6 clone and closely related single locus variants, which comprise a large clonal complex CC6, dominated isolates from patients with acne, and were also significantly associated with ophthalmic infections. Our data therefore support an association between acne and P. acnes strains from the type IA cluster and highlight the role of a widely disseminated clonal genotype in this condition. Characterization of type I cell surface-associated antigens that are not detected in ST10 or strains of type II and III identified two dermatan-sulphate-binding proteins with putative phase/antigenic variation signatures. We propose that the expression of these proteins by type IA organisms contributes to their role in the pathophysiology of acne and helps explain the recurrent nature of the disease. The MLST scheme and database described in this study should provide a valuable platform for future epidemiological and evolutionary studies of P. acnes.
Liquid crystalline phases in concentrated aqueous solutions of Na+ DNA. (1986)

Concentrated aqueous saline solutions of short (146-base-pair) DNA fragments suddenly become turbid and iridescent when the DNA concentration is slightly increased or the temperature is decreased. Microscopic examination through crossed polarizing filters shows that turbidity and iridescence is due to formation of a liquid crystalline DNA phase similar to cholesteric liquid crystals formed by other semirigid, but nonelectrolyte, chiral polymers. Several distinct textures of the liquid crystalline phase or phases are observed depending on DNA concentration, temperature, and method of sample preparation. Textures observed include spherulites with Maltese crosses, striated and highly colored ribbons, whorls of periodic interference fringes, and colored flakes. The liquid crystalline DNA phase coexists in metastable equilibrium with the isotropic phase over a relatively narrow temperature/concentration range--approximately 175-250 mg/ml and 25-62 degrees C (limit of measurements). At higher concentrations and temperatures above approximately equal to 25 degrees C, the solutions appear fully liquid crystalline. When concentrated solutions are cooled below room temperature, crystals form due to precipitation of supporting electrolyte. A partial phase diagram is reported for the isotropic----liquid crystal----crystal transitions of solutions of DNA in buffered saline (2 M Na+). The general features of this phase diagram and the critical DNA volume fraction for formation of the anisotropic phase are consistent with the observed and theoretically predicted phase behavior of rodlike or semirigid nonelectrolyte polymers.
Ion Suppression in Mass Spectrometry (2003)

Whenever mass spectrometric assays are developed, ion suppression studies should be performed using expected physiologic concentrations of the analyte under investigation.
Overview of multicarrier CDMA (1997)

The authors present an overview of new multiple access schemes based on a combination of code division and multicarrier techniques, such as multicarrier code-division multiple access (MC-CDMA), multicarrier direct sequence CDMA (multicarrier DS-CDMA), and multitone CDMA (MT-CDMA).
Cetyltrimethylammonium Bromochromate: A New and Efficient Oxidant for Organic Substrates (2007)

Abstract Cetyltrimethylammonium bromochromate is a versatile reagent for the effective and selective oxidation of organic substrates, particularly for alcohols, under mild conditions.
Early-onset severe rod-cone dystrophy in young children with RPE65 mutations. (2000)

RPE65 mutations on both alleles may be associated with early-onset severe rod-cone dystrophy. Visual functions of the four patients were better than is usually seen in LCA, in particular in cases associated with retGC1 mutations. RPE65 mutations should be suspected in infants who appear to be blind in dim surroundings but react to objects in bright illumination and have nonrecordable rod ERGs and residual cone ERGs.
An Elastically Stretchable TFT Circuit (2004)

An elastically stretchable, skin-like transistor circuit is demonstrated. The circuit is built on an elastomeric substrate patterned with stretchable gold film interconnects. Inverters were made by surface-mounting flexible amorphous-silicon thin-film transistors on the elastomeric substrate. The electrical performance of the inverters was evaluated prior to, during, and after uni-axial stretching by up to 12%. Performance in the relaxed state before and after stretching was identical. Small changes in circuit performance were seen in the stretched state. This first elastic transistor circuit demonstrates the functionality of stretchable interconnects, and the feasibility of fabricating active circuits on electronic skin.
Synthesis and Biological Activities of Some New 2-(N-Aryl amino )-4-(Fluoroaryl) thiazoles (1979)

Department of Chemistry, University of Rajasthan, Jaipur-302 004 Department of Chemistry, J. V. College, Bataut-250 611 <em>Manuscript received 24 January 1979, revised 16 May 1979, accepted 6 October 1979</em> Twentyone new 2-(N-arylamino)-4-(fiuoroaryl) thiszoles have been synthesized by the condensation of the appropriate aryithiourea with corresponding fluorophenacyl bromide in ethanol. These new compounds have been characterized by elemental analyses and spectral studies. Some representative compounds have been screened for various biological activities viz. insecticidal, virucidal, bactericidal, fungicidal, herbicidal and antiarthritic.
Stealth Proteins: In Silico Identification of a Novel Protein Family Rendering Bacterial Pathogens Invisible to Host Immune Defense (2005)

There are a variety of bacterial defense strategies to survive in a hostile environment. Generation of extracellular polysaccharides has proved to be a simple but effective strategy against the host's innate immune system. A comparative genomics approach led us to identify a new protein family termed Stealth, most likely involved in the synthesis of extracellular polysaccharides. This protein family is characterized by a series of domains conserved across phylogeny from bacteria to eukaryotes. In bacteria, Stealth (previously characterized as SacB, XcbA, or WefC) is encoded by subsets of strains mainly colonizing multicellular organisms, with evidence for a protective effect against the host innate immune defense. More specifically, integrating all the available information about Stealth proteins in bacteria, we propose that Stealth is a D-hexose-1-phosphoryl transferase involved in the synthesis of polysaccharides. In the animal kingdom, Stealth is strongly conserved across evolution from social amoebas to simple and complex multicellular organisms, such as Dictyostelium discoideum, hydra, and human. Based on the occurrence of Stealth in most Eukaryotes and a subset of Prokaryotes together with its potential role in extracellular polysaccharide synthesis, we propose that metazoan Stealth functions to regulate the innate immune system. Moreover, there is good reason to speculate that the acquisition and spread of Stealth could be responsible for future epidemic outbreaks of infectious diseases caused by a large variety of eubacterial pathogens. Our in silico identification of a homologous protein in the human host will help to elucidate the causes of Stealth-dependent virulence. At a more basic level, the characterization of the molecular and cellular function of Stealth proteins may shed light on fundamental mechanisms of innate immune defense against microbial invasion.