gebhart/patrepeval huggingface dataset:
Human neutrophils employ the myeloperoxidase/hydrogen peroxide/chloride system to oxidatively damage apolipoprotein A‐I (2001)

The structural integrity of apolipoprotein A-I (apo A-I) is critical to the physiological function of high-density lipoprotein (HDL). Oxidized lipoproteins are thought to be of central importance in atherogenesis, and oxidation products characteristic of myeloperoxidase, a heme protein secreted by activated phagocytes, have been detected in human atherosclerotic tissue. At plasma concentrations of halide ion, hypochlorous acid is a major product of the myeloperoxidase-hydrogen peroxide-chloride system. We therefore investigated the effects of activated human neutrophils, a potent source of myeloperoxidase and hydrogen peroxide, on the protein and lipid components of HDL. Both free and HDL-associated apo A-I exposed to activated human neutrophils underwent extensive degradation as monitored by RP-HPLC and Western blotting with a polyclonal antibody to apo A-I. Replacement of the neutrophils with reagent HOCl resulted in comparable damage (at molar oxidant : HDL subclass 3 ratio = 100) as observed in the presence of activated phagocytes. Apo A-I degradation by activated neutrophils was partially inhibited by the HOCl scavenger methionine, by the heme inhibitor azide, by chloride-free conditions, by the peroxide scavenger catalase, and by a combination of superoxide dismutase (SOD)/catalase, implicating HOCl in the cell-mediated reaction. The addition of a protease inhibitor (3,4-dichloroisocoumarin) further reduced the extent of apo A-I damage. In contrast to the protein moiety, there was little evidence for oxidation of unsaturated fatty acids or cholesterol in HDL3 exposed to activated neutrophils, suggesting that HOCl was selectively damaging apo A-I. Our observations indicate that HOCl generated by myeloperoxidase represents one pathway for protein degradation in HDL3 exposed to activated phagocytes.
Magnetic barcode imaging for contrast agents (2016)

MBI has the potential to overcome significant limitations in the interpretation, quantitation, and multiplexing of contrast enhancement by MR imaging probes. Magn Reson Med 77:970-978, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
Perforin-mediated lysis of tumor cells by Mycobacterium bovis Bacillus Calmette-Guérin-activated killer cells. (2000)

Immunotherapy with Bacillus Calmette-Guérin (BCG) is clinically established in the treatment of superficial bladder cancer. In our attempt to clarify the underlying immunological mechanism, we could previously show that stimulation of PBMC with BCG leads to the generation of cytotoxic BCG-activated killer (BAK) cells. Among others, these BAK cells as well as lymphokine-activated killer (LAK) cells have been suggested as possible effector cells during BCG therapy. To understand BCG-induced activation of effector lymphocytes more precisely, we investigated the lytic pathways of human BAK cells and compared BAK cell cytotoxicity with LAK cell cytotoxicity. Perforin and Fas ligand (FasL) are the major cytolytic molecules of cytotoxic lymphocytes. Our results demonstrate that BAK and LAK cells showed an increased expression of perforin and FasL as compared with unstimulated controls. Killing of T-24 bladder tumor as well as Jurkat cells by BAK and LAK cells was predominantly mediated via perforin as demonstrated by a drastically reduced lysis in the presence of concanamycin A and EGTA/MgCl2, respectively. In contrast, lysis (radioactive release assay) and membrane disintegration (Annexin V binding) of both targets by BAK and LAK cells could not be blocked with an inhibitory anti-FasL monoclonal antibody (NOK-1). Nevertheless, T-24 and Jurkat were susceptible to killing by recombinant soluble FasL and by Chinese hamster ovary cells expressing membrane-bound FasL. We conclude that cellular mediators of BCG effector mechanisms, such as BAK and LAK cells, kill their targets via perforin and independent of the FasL pathway. Because we also found increased numbers of perforin-expressing lymphocytes in patients after BCG therapy, our findings have potential clinical relevance because BCG therapy would not be impaired by FasL resistance of target cells, which recently has been described for some tumors.
The X-ray Structure of Epoxide Hydrolase from Agrobacterium radiobacter AD1 (1999)

Epoxide hydrolases catalyze the cofactor-independent hydrolysis of reactive and toxic epoxides, They play an essential role in the detoxification of various xenobiotics in higher organisms and in the bacterial degradation of several environmental pollutants. The first x-ray structure of one of these, from Agrobacterium radiobacter AD1, has been determined by isomorphous replacement at 2.1-Angstrom resolution. The enzyme shows a two domain structure with the core having the alpha/beta hydrolase-fold topology. The catalytic residues, Asp(107) and His(275), are located in a predominantly hydrophobic environment between the two domains. A tunnel connects the back of the active-site cavity with the surface of the enzyme and provides access to the active site for the catalytic water molecule, which in the crystal structure, has been found at hydrogen bond distance to His275. Because of a crystallographic contact, the active site has become accessible for the Gln(134) side chain, which occupies a position mimicking a bound substrate. The structure suggests Tyr(152)/Tyr(215) as the residues involved in substrate binding, stabilization of the transition state, and possibly protonation of the epoxide oxygen.
GES DAAC tools for accessing and visualizing MODIS data (2003)

The NASA Goddard Earth Sciences Distributed Active Archive Center (GES DAAC) has the unique position of an intermediary between users and MODIS data. To help users accessing and manipulating MODIS data, various tools were developed by the MODIS Data Support Team (MDST). Some of these tools are described below: WHOM - the Web based Hierarchical Ordering Mechanism (WHOM) for Terra data is a customized version of the larger DAAC Web-based data gateway. WHOM offers enhanced graphic interfaces to identify temporal and spatial data coverage while searching and ordering MODIS data archived at the GES DAAC. An alternative "No Frills" page provides quick access (by passing navigation) directly to WHOM pages for products which users want to order. Browse images allow science data users to evaluate the data before ordering. MODIS Level 1B browse images are produced from the 1 km Calibrated Radiances product using channels 1, 4, 3 as true color during the day, and channel 32 as false color during the night. Subsampled at 5-km resolution products are generated at the GES DAAC so users can download smaller files. Subsetting Tools - calibrated radiance (Level 1B) channel subsetting is being developed as an extension to the EOS Core System (ECS). The front end, a graphic user interface, is part of WHOM. The new Simple Scalable Script-Based Science Processor (S4P) that interacts with ECS drives the back end for data retrieval, archiving and distribution of the subsetted data. Visualization Tools - the MDST has developed two very simple IDL-based tools to map MODIS swath products. The first, geoview, has a simple, graphic interface, while the second, simap, is a command line utility. Modis-atmos was designed to work with atmospheric products. HDFLook for MODIS is a result of joint collaboration between the GES DAAC and the University of Lille, France. An HDF-EOS version of a popular MSPHINX program was developed to work with all MODIS and many other HDF-EOS data. Its main features include: geo-mapping, geo-projection conversion, interactive and batch mode processing, subsetting and subsampling, stitching of several granules, multi-granule processing, and conversion into GIS-compatible formats.
Cyclic AMP stimulates efflux of intracellular sterol from cholesterol-loaded cells. (1993)

The interaction of high density lipoprotein with its putative receptor stimulates translocation and efflux of intracellular sterols by a process involving activation of protein kinase C. This study shows that activation of cAMP-dependent protein kinase also stimulates efflux of intracellular sterols. When intracellular sterol pools of cholesterol-loaded cultured human skin fibroblasts and bovine aortic endothelial cells were radiolabeled with the biosynthetic precursor [3H]mevalonolactone, high density lipoprotein3 (HDL3)-mediated 3H-sterol efflux was enhanced by addition of the adenylylcyclase activator forskolin, the phosphodiesterase inhibitors theophylline and 3-isobutyl-1-methylxanthine, and the cAMP analogues N6-benzoyl-cAMP (N6-cAMP) and 8-thiomethyl-cAMP. The effect of N6-cAMP was abolished by an inhibitor of cAMP-dependent protein kinase (H8). The enhanced sterol efflux was independent of receptor binding of HDL3, as similar effects were observed in the presence of tetranitromethane-modified HDL3, which lacks receptor binding activity. N6-cAMP stimulated efflux of several subspecies of newly synthesized sterols, including cholesterol. Elevation of cAMP levels increased the proportion of radiosterols that were accessible to treatment of cells with the enzyme cholesterol oxidase, suggesting that activation of cAMP-dependent protein kinase stimulates translocation of sterols from intracellular compartments to the plasma membrane where they desorb from the cell surface. Thus, at least two distinct protein kinase signalling pathways modulate transport of intracellular sterols in cholesterol-loaded cells.
Similarity of the transfer factors in Novikoff ascites tumor and other amino acid-incorporating systems. (1970)

A highly active in vitro amino acid-polymerizing system has been isolated from Novikoff ascites tumor cells. Considerable difficulty was encountered in the resolution of the transfer enzyme complex. However, purified ribosomes and the transfer components were prepared, and it was possible to demonstrate that 2 factors are involved in the polymerization of amino acids by this tumor cell system. The 2 factors were interchangeable with components of the rabbit reticulocyte system. Other investigators have shown that the 2 transfer factors of the rat liver and reticulocyte systems are interchangeable. These findings suggest that the polysomal mechanism of protein synthesis is quite similar in all mammalian cells and possibly in all cells. However, the ribosomes and Factor T2 or G of the mammalian and microbial systems are not interchangeable.
Immunotargeting of antioxidant enzyme to the pulmonary endothelium. (1996)

Oxidative injury to the pulmonary endothelium has pathological significance for a spectrum of diseases. Administration of antioxidant enzymes, superoxide dismutase (SOD) and catalase (Cat), has been proposed as a method to protect endothelium. However, neither these enzymes nor their derivatives possess specific affinity to endothelium and do not accumulate in the lung. Previously we have described a monoclonal antibody to angiotensin-converting enzyme (ACE) that accumulates selectively in the lung after systemic injection in rats, hamsters, cats, monkeys, and humans. In the present work we describe a system for selective intrapulmonary delivery of CuZn-SOD and Cat conjugated with biotinylated anti-ACE antibody mAb 9B9 (b-mAb 9B9) by a streptavidin (SA)-biotin bridge. Both enzymes biotinylated with biotin ester at biotin/enzyme ratio 20 retain enzymatic activity and bind SA without loss of activity. We have constructed tri-molecular heteropolymer complexes consisting of b-mAb 9B9, SA, and biotinylated SOD or biotinylated Cat and have studied biodistribution and pulmonary uptake of these complexes in the rat after i.v. injection. Biodistribution of biotinylated enzymes was similar to that of nonmodified enzymes. Binding of SA markedly prolonged lifetime of biotinylated enzymes in the circulation. In contrast to enzymes conjugated with nonspecific IgG, other enzyme derivatives, and nonmodified enzymes, biotinylated enzymes conjugated with b-mAb 9B9 accumulated specifically in the rat lung (9% of injected SOD/g of lung tissue and 7.5% of injected Cat/g of lung tissue). Pulmonary uptake of nonmodified enzymes or derivatives with nonspecific IgG did not exceed 0.5% of injected dose/g. Both SOD and Cat conjugated with b-mAb 9B9 were retained in the rat lung for at least several hours. Trichloracetic acid-precipitable radiolabeled Cat was associated with microsomal and plasma membrane fractions of the lung tissue homogenate. Thus, modification of antioxidant enzymes with biotin and SA-mediated conjugation with b-mAb 9B9 prolongs the circulation of enzymes resulting in selective accumulation in the lung and intracellular delivery of enzymes to the pulmonary endothelium. These results provide the background for an approach to provide protection of pulmonary endothelium against oxidative insults.
Monitor unit settings for intensity modulated beams delivered using a step‐and‐shoot approach (2000)

Two linear accelerators have been commissioned for delivering IMRT treatments using a step-and-shoot approach. To assess beam startup stability for 6 and 18 MV x-ray beams, dose delivered per monitor unit (MU), beam flatness, and beam symmetry were measured as a function of the total number of MU delivered at a clinical dose rate of 400 MU per minute. Relative to a 100 MU exposure, the dose delivered per MU by both linear accelerators was found to be within +/-2% for exposures larger than 4 MU. Beam flatness and symmetry also met accepted quality assurance standards for a minimum exposure of 4 MU. We have found that the performance of the two machines under study is well suited to the delivery of step-and-shoot IMRT. A system of dose calculation has also been commissioned for applying head scatter corrections to fields as small as 1x1 cm2. The accuracy and precision of the relative output calculations in water was validated for small fields and fields offset from the axis of collimator rotation. For both 6 and 18 MV x-ray beams, the dose per MU calculated in a water phantom agrees with measured data to within 1% on average, with a maximum deviation of 2.5%. The largest output factor discrepancies were seen when the actual radiation field size deviated from the set field size. The measured output in water can vary by as much 16% for 1x1 cm2 fields, when the measured field size deviates from the set field size by 2 mm. For a 1 mm deviation, this discrepancy was reduced to 8%. Steps should be taken to ensure collimator precision is tightly controlled when using such small fields. If this is not possible, very small fields should not contribute to a significant portion of the treatment, or uncertainties in the collimator position may effect the accuracy of the dose delivered.
Plasmid DNA gene therapy: studies with the human interleukin-2 gene in tumor cells in vitro and in the murine B16 melanoma model in vivo. (1996)

The plasmid DNA vector pVCL-1102 containing the coding sequence for the human IL-2 gene was evaluated for expression in tumor cells in vitro and in vivo. In vitro transfection of murine B16 tumor cells with pVCL-1102 resulted in the expression of 36,000 IU (5.7 micrograms) of biologically active IL-2/10(6) cells/48 h. In vitro transfection of human tumor lines and primary cultures from human biopsies with pVCL-1102 resulted in the expression of 1,289 to 9345 IU of IL-2/10(6) cells/48 h and 30 to 794 IU of IL-2/10(6) cells/48 h, respectively. In vivo, direct intratumor injection of pVCL-1102 resulted in retention of intact plasmid DNA in the tumor tissue and IL-2 secretion by cell cultures derived from the injected tumors. Formulation of pVCL-1102 with the cationic lipid DMRIE/DOPE inhibited DNA degradation and enhanced in vivo transfection efficiency over plasmid DNA alone. Antitumor activity of the pVCL-1102/DMRIE/DOPE complex was evaluated in a B16 melanoma model in mice. An IL-2-specific effect could not be demonstrated in a subcutaneous model because the intratumor injection of plasmid DNA lacking the IL-2 coding sequence also resulted in a significant reduction in tumor volume. However, an IL-2-specific effect was observed when B16 cells were transfected in vitro prior to implantation into the mouse. Transient transfection of B16 cells with pVCL-1102 rendered the cells less tumorigenic in vivo and produced a significant reduction in tumor volume. These data demonstrate that a plasmid DNA expression vector can be used to deliver the IL-2 gene to tumor cells in vitro and in vivo, resulting in the expression of significant levels of IL-2 protein. These data also illustrate the need for the use of appropriate controls when evaluating the in vivo biological activity of plasmid DNA in murine tumor models.
Notch signaling and inherited disease syndromes (2003)

The Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in organisms as diverse as insects, nematodes, echinoderms and mammals. Disruptions in conserved developmental pathways frequently result in inherited congenital anomalies in humans. Mutations in genes encoding Notch pathway components underlie three inherited human diseases: Alagille syndrome, spondylocostal dysostosis, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Mouse models for these three diseases have been developed, and are leading to novel insights into the pathology of these diseases in humans.
Identification of Src, Fyn, and Lyn SH3-binding proteins: implications for a function of SH3 domains. (1994)

Src homology 3 (SH3) domains mediate protein-protein interactions necessary for the coupling of cellular proteins involved in intracellular signal transduction. We previously established solution-binding conditions that allow affinity isolation of Src SH3-binding proteins from cellular extracts (Z. Weng, J. A. Taylor, C. E. Turner, J. S. Brugge, and C. Seidel-Dugan, J. Biol. Chem. 268:14956-14963, 1993). In this report, we identified three of these proteins: Shc, a signaling protein that couples membrane tyrosine kinases with Ras; p62, a protein which can bind to p21rasGAP; and heterogeneous nuclear ribonucleoprotein K, a pre-mRNA-binding protein. All of these proteins contain proline-rich peptide motifs that could serve as SH3 domain ligands, and the binding of these proteins to the Src SH3 domain was inhibited with a proline-rich Src SH3 peptide ligand. These three proteins, as well as most of the other Src SH3 ligands, also bound to the SH3 domains of the closely related protein tyrosine kinases Fyn and Lyn. However, Src- and Lyn-specific SH3-binding proteins were also detected, suggesting subtle differences in the binding specificity of the SH3 domains from these related proteins. Several Src SH3-binding proteins were phosphorylated in Src-transformed cells. The phosphorylation of these proteins was not detected in cells transformed by a mutant variant of Src lacking the SH3 domain, while there was little change in tyrosine phosphorylation of other Src-induced phosphoproteins. In addition, the coprecipitation of v-Src with two tyrosyl-phosphorylated proteins with M(r)s of 62,000 and 130,000 was inhibited by incubation with a Src SH3 peptide ligand, suggesting that the binding of these substrate proteins is dependent on interactions with the SH3 domain. These results strongly suggest a role for the Src SH3 domain in the recruitment of substrates to this protein tyrosine kinase, either through direct interaction with the SH3 domain or indirectly through interactions with proteins that bind to the SH3 domain.
Two Transduction Pathways Mediate Rapid Effects of Abscisic Acid in Commelina Guard Cells (1994)

Andrew C. Allan, Mark D. Fricker, Jane L. Ward, Michael H. Beale, Anthony J. Trewavas, Two Transduction Pathways Mediate Rapid Effects of Abscisic Acid in Commelina Guard Cells, The Plant Cell, Vol. 6, No. 9 (Sep., 1994), pp. 1319-1328
TRAM-1, A Novel 160-kDa Thyroid Hormone Receptor Activator Molecule, Exhibits Distinct Properties from Steroid Receptor Coactivator-1 (1997)

Nuclear hormone receptors (NRs) are ligand-dependent transcription factors that regulate target gene transcription. We report the molecular cloning and characterization of a novel human cDNA encoding TRAM-1, a thyroid hormone receptor activator molecule, a approximately 160-kDa protein homologous with SRC-1/TIF2, by far-Western-based expression screening. TRAM-1 binds to thyroid hormone receptor (TR) and other NRs in a ligand-dependent manner and enhances ligand-induced transcriptional activity of TR. The AF-2 region in NRs has been thought to play a critical role in mediating ligand-dependent transactivation by the interaction with coactivators. Surprisingly, TRAM-1 retains strong ligand-dependent interaction with an AF-2 mutant of TR (E457A), while SRC-1 fails to interact with this mutant. Furthermore, we identified a critical TRAM-1 binding site in rat TRbeta1 outside of AF-2, as TRAM-1 shows weak ligand-dependent interaction with a helix 3 ligand binding domain TR mutant (K288A), compared with SRC-1. These results suggest that TRAM-1 is a coactivator that may exhibit its activity by interacting with subdomains of NRs other than the AF-2 region, in contrast to SRC-1/TIF2.
Identification of a colorectal tumor-associated antigen (COA-1) recognized by CD4(+) T lymphocytes. (2003)

Only a limited number of target molecules have been shown to be recognized by colon tumor-reactive T cells, limiting the options for the development of immunotherapies for patients with colon cancer. The current studies were undertaken in an attempt to generate tumor-reactive T cells that could be used to identify and characterize novel colon tumor-associated antigens. Multiple CD4(+) T-cell clones isolated either from tumor-infiltrating lymphocytes or peripheral blood mononuclear cells that were sensitized in vitro with autologous tumor cells from a colon cancer patient, 1869, recognized autologous tumor cells in a class II HLA-DR-restricted manner. One of the peripheral blood mononuclear cell clones, clone C111, was used to screen pools of clones that were generated from an autologous colon tumor cell line cDNA library. A cDNA clone that was isolated encoded a protein that was termed colorectal tumor-associated antigen-1 (COA-1). This product was recognized in the context of the two autologous HLA-DRbeta1 alleles, HLA-DRbeta1*0402 and DRbeta1*1301. The nucleotide sequence of the COA-1 transcript was nearly identical to multiple expressed sequence tag sequences that encode variants of Socius, a protein that was found recently to bind to members of the Rnd family of GTPases. The COA-1 gene was expressed at relatively comparable levels in colorectal and melanoma tumor cells, EBV-infected B cells, normal B cells, and cultured fibroblast cell lines. However, the gene that was isolated from normal cell types contained a single nucleotide substitution, resulting in an amino acid change near the COOH terminus of the protein. Although the minimal epitope recognized by CD4(+) cells was encoded by sequences that were upstream from this substitution, C111 T cells did not appear to recognize the normal gene product. Therefore, this alteration may either affect the localization or the processing of this gene product, which may at least in part be responsible for the differential recognition of tumor and normal cells.
Inactivation of Nisin by Glutathione in Fresh Meat (1999)

ABSTRACT: Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS) was used to determine the fate of nisin in meat products. Nisin in 0.02N HCl was added to fresh and cooked meat and meat juice and samples were stored at 4 °C overnight. Residual nisin solutions and meat juice and meat extract supernatants were analyzed for antimicrobial activity and for nisin. Nisin was recovered from cooked meat extract and cooked meat juice; however, only nisin bound to a food component was detected in fresh meat extract. Mass spectra for raw meat and juice showed a signal 307 Da greater than the mass of nisin. Results indicated that nisin was likely inactivated in raw meat by an enzymatic reaction with glutathione.