gebhart/patrepeval huggingface dataset:
Specificity of expression and effects of eicosanoid mediators in normal physiology and human diseases 1 (1995)

The eicosanoids are a family of oxygenated arachidonic acid derivatives that potently mediate diverse physiological and pathophysiological processes. Recent research on eicosanoids has revealed novel pathways of synthesis, a family of related cell membrane receptors, and distinctive roles in cellular functions. There are two cyclooxygenases that convert arachidonic acid to thromboxane and prostaglandins, one of which is localized in the endoplasmic reticulum and the other in the nuclear envelope. The cyclooxygenases differ in their susceptibility to inhibition by nonsteroidal antiinflammatory drugs. The leukotriene-generating pathway consists of a cytosolic perinuclear 5-lipoxygenase, two integral nuclear envelope proteins, termed 5-lipoxygenase-activating protein and LTC4 synthase, and a cytosolic LTA4 hydrolase. Each protein of the leukotriene synthetic pathway is a target for specific pharmacological intervention. Cellular recognition and effects of eicosanoids are mediated by at least 12 different G protein-associated primary receptors, which differ in tissue distribution, signaling mechanisms, and cellular behavior, as well as binding specificity. Transient localized increases in tissue concentrations of eicosanoids and the concurrent upregulation of complementary receptors influence differentiation, migration, and specific activities of cells in immunity and other integrated physiological responses.
Historical Perspective on Medical Errors (2003)

* Department of Surgery, The University of Texas Medical Branch, Galveston, TX, USA **Correspondence address: Dennis C Gore, MD, FACS, Department of Surgery, The University of Texas Medical Branch, 301 University Blvd, Galveston TX 77555-1172, USA. Received November 4, 2002; revised January 28, 2003; accepted April 8, 2003.
Electronic beam steering in wire and patch antenna systems using switched parasitic elements (2002)

We explore the application of two alternative methods of electronically controlling the radiation pattern from an antenna array which has a single feed line. Type (a) involves switching one of the parasitic elements to become active. Type (b) requires switching the parasitic elements located in the vicinity of the active element between short circuit (i.e. continuous conduction in the element) and open circuit at a point where the induced current is minimised. Both techniques offer a reduced radiation loss in the feed network and relatively simple control circuitry and tracking software.
Influence of Sulphate Ions on the Structure of AA Amyloid Fibrils (1990)

To explore the possible interaction of sulphated GAG with AA amyloid peptides, human AA amyloid fibrils were exposed to buffers containing various salts, and the accessibility of free amino groups on the peptides to reductive methylation was examined. Sodium chloride had little effect except at concentrations of 1 M, where it reduced the accessibility of AA peptides to labelling. In contrast 70 mM Na2SO4 led to a significant increase in peptide accessibility to labelling. The results suggest that, at least in part, GAG interact with AA peptides through their sulphate moieties.
Altering the Specificity of the Antibody Response to HIV gp120 with a Glycoconjugate Antigen (2016)

Some conserved glycans on the HIV envelope protein are targets of broadly neutralizing antibodies (bnAbs) of HIV. BnAbs provide a precise definition of broadly neutralizing epitopes on the envelope protein of HIV. These epitopes are promising for vaccine design. Many glycan-related antigens with high affinity to bnAbs have been tested as immunogens in vivo. However, it was found that no bnAb-like antibodies were induced. Vaccination with different immunogens containing the same neutralizing epitope may enhance the affinity maturation of antibodies which focus on the shared epitope. This combined immunization strategy showed great potential in peptide epitope-based vaccine design. However, it has not yet been explored on glycan-related epitopes to date. Herein, we take 2G12 as a model to validate this strategy on glycan-related epitopes. A high-affinity antigen of 2G12 was constructed by conjugating the D1 arm tetramannoside to bovine serum albumin. Then, the glycoconjugate was coimmunized with a recombinant gp120, which was expected to selectively benefit the induction of antibodies recognizing the neutralizing epitope of 2G12 on gp120. Mice were inoculated with the two antigens simultaneously or alternately to determine the suitable regimen for this strategy. The serological assays demonstrated that the antibody titers and subtypes responded to the whole gp120 were not improved, and the proportion of antibodies competitively bound to the 2G12 epitope was not enhanced significantly either. However, the coimmunized glycoconjugate selectively raised the proportion of antibodies recognizing D1 arm tetramannoside-related structures on gp120. These results provide important experience for the design of glycan-dependent bnAb-based vaccines.
Predictive Value of Aurora-A/STK15 Expression for Late Stage Epithelial Ovarian Cancer Patients Treated by Adjuvant Chemotherapy (2007)

AURKA overexpression is seen in the majority of late stage epithelial ovarian cancers, most likely due to increased AURKA DNA copy numbers and/or chromosome 20 aneusomy. Importantly, AURKA overexpression may differentially affect taxane and non-taxane-based adjuvant therapy responses. The study sheds new light on AURKA expression and regulation in epithelial cancers in vivo and specifically shows its value as a clinically relevant marker and as a potential therapeutic target per se.
The cloning, DNA sequence, and overexpression of the gene araE coding for arabinose-proton symport in Escherichia coli K12. (1988)

A lambda placMu1 insertion was made into araE, the gene for arabinose-proton symport in Escherichia coli. A phage containing an araE'-'lacZ fusion was recovered from the lysogen and its restriction map compared with that of the 61-min region of the E. coli genome to establish the gene order thyA araE orf lysR lysA galR; araE was transcribed toward orf. A 4.8-kilobase SalI-EcoRI DNA fragment containing araE was subcloned from the phage lambda d(lysA+ galR+ araE+) into the plasmid vector pBR322. From this plasmid a 2.8-kilobase HincII-PvuII DNA fragment including araE was sequenced and also subcloned into the expression vector pAD284. The araE gene was 1416-base pairs long, encoding a hydrophobic protein of 472 amino acids with a calculated Mr of 51,683. The amino acid sequence was homologous with the xylose-proton symporter of E. coli and the glucose transporters from a human hepatoma HepG2 cell line, human erythrocytes, and rat brain. The overexpressed araE gene product was identified in Coomassie-stained sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels of cell membranes as a protein of apparent Mr 35,000 +/- 1,150. Arabinose protected this protein against reaction with N-ethylmaleimide.
Managing strategic outsourcing. (2004)

One of the greatest challenges for companies is to know what to outsource and when. This article describes how to outsource effectively and thereby be more flexible and responsive to market demands.
Structural invariants of antigen binding: comparison of immunoglobulin VL-VH and VL-VL domain dimers. (1985)

Antigen-combining site arises by noncovalent association of the variable domain of the immunoglobulin heavy chain (VH) with that of the light chain (VL). To analyze the invariant features of the binding region (VL-VH domain interface), we compared the known immunoglobulin three-dimensional structures by a variety of methods. The interface forms a close-packed, twisted, prism-shaped "beta-barrel" characterized by cross-sectional dimensions 1.04 X 0.66 nm and a top-to-bottom twist angle of 212 degrees. The geometry of the interface is preserved via invariance of some 15 side chains, both inside the domains and on their surface. Buried polar residues form a conserved hydrogen-bonding network that has a similar topological connectivity in the two domain types; two hydrogen bonds contributed by invariant side chains extend across the interface and anchor the beta-sheets in their relative orientation. Invariant aromatic residues close-pack at the bottom of the binding-site beta-barrel with their ring planes oriented perpendicularly in the characteristic "herringbone" packing mode. Electrostatic computations that implicitly include solvent effects show the domains to be stabilized by large electrostatic forces. However, structures that were crystallized at lower pH have their electrostatic energies appropriately lowered, implying that full ionization of carboxyl side chains is essential for efficient electrostatic stabilization. The unusual mode of domain-domain association in the VL-VL dimer RHE correlates with its overall repulsive electrostatic energy (+54 kJ/mol), as opposed to negative (i.e., stabilizing) energy values (-263 to -543 kJ/mol) found in the domains of the other structures. The VL-VL dimer REI mimics closely the interface geometry of VL-VH dimers although its domain-domain contact area is lower by 18%.
A Phase II Trial of Bexarotene, a Retinoid X Receptor Agonist, in Non-M3 Acute Myeloid Leukemia (2008)

Abstract In vitro, bexarotene inhibits the proliferation of non-M3 AML cell lines and induces differentiation of leukemic blasts. Our previous phase I study in non-M3 AML showed evidence of leukemic response as manifested by reduction in bone marrow blast counts (15% response rate), improved platelet counts (41%) and improved neutrophil counts (26%). Based on these results, a phase II trial in non-M3 AML was initiated at the phase I MTD. In the current phase II trial, bexarotene (300mg/m2) was administered daily as monotherapy until disease progression or unacceptable side effects occurred. Fourteen patients have been enrolled: 8M/6F, median age 74 (range 20–83), 9 secondary AML (MDS or prior chemotherapy), 9 primary refractory or relapsed &amp;lt; 1 year after induction, 5 no prior induction chemotherapy, 5 requiring hydroxyurea at the time of enrollment for leukemic blast control, 4 prior allogeneic stem cell transplant, 12 blood transfusion dependent, 11 platelet transfusion dependent, and 8 neutropenic. Overall, no significant adverse events were noted. All patients received prophylactic antihyperlipidemic agents and achieved good lipid control. Two patients developed mild hypothyroidism related to bexarotene. Five patients were evaluable with bone marrow biopsy at 2 months: 1 50% reduction in absolute blasts, 1 SD and 3 PD. Similar to data from our prior phase I study, evidence of clinical activity was manifested as platelet count response in 1 patient and neutrophil increases attributable to bexarotene in 2 patients. When combining the results of our phase I experience (27 patients) with our phase II data (14 patients), there is a suggestion of increased activity in patients with 5q minus abnormalities with 4/7 (57%) benefiting (2 BM response, 4 neutrophil improvements and 1 platelet response). Conversely rates of clinical benefit were lower in patients with multiple (&amp;gt;3) cytogenetic abnormalities (2/13), relapse after stem cell transplant (1/9) or requiring hydroxyurea for peripheral blast control at the time of study enrollment (0/10). Bexarotene is very well tolerated at the dose level studied. Early evidence for clinical activity has been seen as exemplified by improvement in platelet count, increased neutrophil counts and decreased bone marrow blasts. In summary, we conclude that bexarotene is an active agent in a subgroup of patients with AML. Study enrollment continues with amended inclusion criteria to focus on patients more likely to benefit from treatment.
The biogenesis of platelets from megakaryocyte proplatelets (2005)

Platelets are formed and released into the bloodstream by precursor cells called megakaryocytes that reside within the bone marrow. The production of platelets by megakaryocytes requires an intricate series of remodeling events that result in the release of thousands of platelets from a single megakaryocyte. Abnormalities in this process can result in clinically significant disorders. Thrombocytopenia (platelet counts less than 150,000/microl) can lead to inadequate clot formation and increased risk of bleeding, while thrombocythemia (platelet counts greater than 600,000/microl) can heighten the risk for thrombotic events, including stroke, peripheral ischemia, and myocardial infarction. This Review will describe the process of platelet assembly in detail and discuss several disorders that affect platelet production.
Splice Variants of the Dual Specificity Tyrosine Phosphorylation-regulated Kinase 4 (DYRK4) Differ in Their Subcellular Localization and Catalytic Activity (2010)

Dual specificity tyrosine phosphorylation-regulated kinases, DYRKs, are a family of conserved protein kinases that play key roles in the regulation of cell differentiation, proliferation, and survival. Of the five mammalian DYRKs, DYRK4 is the least studied family member. Here, we show that several splice variants of DYRK4 are expressed in tissue-specific patterns and that these variants have distinct functional capacities. One of these variants contains a nuclear localization signal in its extended N terminus that mediates its interaction with importin α3 and α5 and that is capable of targeting a heterologous protein to the nucleus. Consequently, the nucleocytoplasmic mobility of this variant differs from that of a shorter isoform in live cell imaging experiments. Other splicing events affect the catalytic domain, including a three-amino acid deletion within subdomain XI that markedly reduces the enzymatic activity of DYRK4. We also show that autophosphorylation of a tyrosine residue within the activation loop is necessary for full DYRK4 kinase activity, a defining feature of the DYRK family. Finally, by comparing the phosphorylation of an array of 720 peptides, we show that DYRK1A, DYRK2, and DYRK4 differ in their target recognition sequence and that preference for an arginine residue at position P -3 is a feature of DYRK1A but not of DYRK2 and DYRK4. Therefore, we highlight the use of subcellular localization as an important regulatory mechanism for DYRK proteins, and we propose that substrate specificity could be a source of functional diversity among DYRKs.
Distributed Alternating Direction Method of Multipliers (2012)

We consider a network of agents that are cooperatively solving a global unconstrained optimization problem, where the objective function is the sum of privately known local objective functions of the agents. Recent literature on distributed optimization methods for solving this problem focused on subgradient based methods, which typically converge at the rate O (1/√k), where k is the number of iterations. In this paper, k we introduce a new distributed optimization algorithm based on Alternating Direction Method of Multipliers (ADMM), which is a classical method for sequentially decomposing optimization problems with coupled constraints. We show that this algorithm converges at the rate O (1/k).
Functional evidence that intercellular adhesion molecule‐1 (icam‐1) is a ligand for lfa‐1d‐ependent adhesion in t cell‐mediated cytotoxicity (1988)

Although intercellular adhesion molecule-1 (ICAM-1) has been implicated as a ligand in some LFA-1-dependent adhesion, its importance to T cell function has not been established. The present studies investigate the importance of ICAM-1 for human cytotoxic T lymphocytes (CTL), both in their formation of antigen-independent conjugates (AIC) and in their lysis of targets. Analysis of monoclonal antibody (mAb) inhibition of AIC formation indicate that ICAM-1 mAb 1 blocks (a) AIC formation with some but not all targets; (b) the LFA-1 pathway but not the CD2/LFA-3 pathway of adhesion; (c) by binding to the target cell, not the T cell. In studies of cell-mediated lysis (CML) ICAM-1 mAb inhibited lysis of some targets, such as U-937, that use ICAM-1 predominantly in AIC formation; CML on some other targets is not inhibited by ICAM-1 mAb. These data indicate that ICAM-1 is a ligand for AIC formation, antigen-specific CTL recognition and cytolysis of particular target cells. The data also indicate that ICAM-1 is not used in LFA-1-dependent CTL interactions with all kinds of target cells, suggesting the existence of alternative ligands for LFA-1.
Solución numérica de ecuaciones diferenciales (2003)

Circular RNA (circRNA) plays an important role in diverse stress-related neuropsychiatric disorders like depression, anxiety and cognitive disorders. Here, using a circRNA microarray, we found that circSYNDIG1, an unreported circRNA, was significantly downregulated in the hippocampus of chronic unpredictable mild stress (CUMS) mice and further validated this finding in corticosterone (CORT) and lipopolysaccharide (LPS) mice by qRT-PCR, and it was negatively correlated with depressive- and anxiety-like behaviors of these three stressed mice. Furthermore, the interaction of miR-344-5p and circSYNDIG1 was confirmed by in situ hybridization (FISH) assay in hippocampus and dual luciferase reporter assay in 293 T cells. And miR-344-5p mimics could simulate the dendritic spine density reduction, depressive- and anxiety-like behaviors and memory impairment induced by CUMS. Overexpression of circSYNDIG1 in hippocampus significantly ameliorated these abnormal changes induced by CUMS or miR-344-5p. It indicated that circSYNDIG1 functions as an miR-344-5p sponge to inhibit miR-344-5p impact, resulting in the increase of dendritic spine density and the subsequent amelioration of the abnormal behaviors. Therefore, the downregulation of circSYNDIG1 in hippocampus participates in CUMS-induced depressive and anxiety-like behavior of mice though miR-344-5p. These findings represent the first evidence for the involvement of circSYNDIG1 and its coupling mechanism in depression and anxiety, suggesting that circSYNDIG1 and miR-344-5p might be new targets for the treatment of stress-related disorder.
HLA-DR4-IE chimeric class II transgenic, murine class II-deficient mice are susceptible to experimental allergic encephalomyelitis. (1996)

To investigate the development of HLA-DR-associated autoimmune diseases, we generated transgenic (Tg) mice with HLA-DRA-IE alpha and HLA-DRB1*0401-IE beta chimeric genes. The transgene-encoded proteins consisted of antigen-binding domains from HLA-DRA and HLA-DRB1*0401 molecules and the remaining domains from the IE(d)-alpha and IE(d)-beta chains. The chimeric molecules showed the same antigen-binding specificity as HLA-DRB1*0401 molecules, and were functional in presenting antigens to T cells. The Tg mice were backcrossed to MHC class II-deficient (IA beta-, IE alpha-) mice to eliminate any effect of endogenous MHC class II genes on the development of autoimmune diseases. As expected, IA alpha beta or IE alpha beta molecules were not expressed in Tg mice. Moreover, cell-surface expression of endogenous IE beta associated with HLA-DRA-IE alpha was not detectable in several Tg mouse lines by flow cytometric analysis. The HLA-DRA-IE alpha/HLA-DRB1*0401-IE beta molecules rescued the development of CD4+ T cells in MHC class II-deficient mice, but T cells expressing V beta 5, V beta 11, and V beta 12 were specifically deleted. Tg mice were immunized with peptides, myelin basic protein (MBP) 87-106 and proteolipid protein (PLP) 175-192, that are considered to be immunodominant epitopes in HLA-DR4 individuals. PLP175-192 provoked a strong proliferative response of lymph node T cells from Tg mice, and caused inflammatory lesions in white matter of the CNS and symptoms of experimental allergic encephalomyelitis (EAE). Immunization with MBP87-106 elicited a very weak proliferative T cell response and caused mild EAE. Non-Tg mice immunized with either PLP175-192 or MBP87-106 did not develop EAE. These results demonstrated that a human MHC class II binding site alone can confer susceptibility to an experimentally induced murine autoimmune disease.
Proteomic Analysis of Pharmacologically Preconditioned Cardiomyocytes Reveals Novel Phosphorylation of Myosin Light Chain 1 (2001)

Proteomic analysis of rabbit ventricular myocytes revealed a novel posttranslational modification to myosin light chain 1 (MLC1), consisting of phosphorylation at two sites. Subproteomic extraction to isolate myofilament-enriched fractions enabled determination of the extent of phosphorylation, which increased from 25.7+/-1.6% to 34.0+/-2.7% (mean+/-SE, n=4; P<0.05) after adenosine treatment at levels sufficient to pharmacologically precondition the myocytes (100 micromol/L). Mass spectrometry of MLC1 tryptic digests identified two peptide fragments modified by phosphorylation. These two phosphopeptides were characterized by peptide mass fingerprinting to determine the phosphorylation sites within rabbit ventricular MLC1, which correspond to Thr69 and Ser200 of rat MLC1, and to Thr64 and Ser194 or 195 of human MLC1. This proteomic analysis of preconditioned myocardium has revealed a previously unsuspected in vivo posttranslational modification to MLC1.
Phenotypic and Genotypic Characterization of Group B Streptococcal Isolates in Southern Brazil (2010)

One-hundred sixty-eight group B streptococcal (GBS) isolates from a Brazilian hospital were phenotypically and genotypically characterized. Isolates were recovered from human sources from April 2006 to May 2008 and classified as either invasive, noninvasive, or colonizing isolates. Classical methods for serotyping and antibiotic resistance profiling were employed. Clonal groups were also defined by pulsed-field gel electrophoresis (PFGE). Results showed that susceptibility to beta-lactam antimicrobials was predominant among the isolates. Only 4.7% were resistant to erythromycin and clindamycin. The erm(B) gene was widely detected in our GBS isolates, according to our phenotypic results (constitutive macrolide-lincosamide-streptogramin B [cMLSB] resistance phenotype), and the erm(A) gene was also detected in some isolates. MLSB resistance was restricted to strains isolated from patients with noninvasive infections and carriers. Serotype Ia was predominant (38.1%), serotype IV isolates were found at a high frequency (13.1%), and few isolates of serotype III were identified (3%). Pulsed-field gel electrophoresis results revealed a variety of types, reflecting the substantial genetic diversity among GBS strains, although a great number of isolates could be clustered into two major groups with a high degree of genetic relatedness. Three main PFGE clonal groups were found, and isolates sharing the same PFGE type were grouped into different serotypes. Furthermore, in a few cases, isolates from the same patients and possessing the same PFGE type were of different serotypes. These findings could be related to the occurrence of capsular switching by horizontal transfer of capsular genes.