gebhart/patrepeval huggingface dataset:
Anti-Interleukin-6 Therapy for Crohns Disease (2003)

Proinflammatory cytokines have been demonstrated to play a crucial role in the pathogenesis and physiopathology of various chronic inflammatory conditions including Crohn's disease (CD). Among these cytokines, interleukin-6 (IL-6) must be especially important because increased serum concentrations of acute phase proteins, reduced level of serum albumin, and remarkable thrombocytosis are all well-explained by the increased level of IL-6. Moreover, IL-6 is capable of stimulating even IL-6 receptor (IL-6R) negative cells such as vascular endothelial cells when complexed to soluble form of IL-6R (sIL-6R), and serum level of IL-6 as well as sIL-6R has been demonstrated to increase during inflammation. To investigate the therapeutic potential of IL-6 signaling blockade for CD, anti-IL-6R monoclonal antibody (mAb) was introduced to various murine models of colitis. Anti-IL-6R mAb successfully prevented wasting disease and the development of macroscopic and histological lesions. It suppressed the accumulation of ICAM-1 positive and Mac-1 positive cells in the lamina propria (LP) and the expression of ICAM-1 and VCAM-1 by vascular endothelial cells. Expansion of colonic and splenic CD4(+) T cells was reduced as well as the colonic expression of tumor necrosis factor alpha (TNF-alpha), IL-1beta, and interferon gamma (IFN-gamma) mRNA without affecting the production of transforming growth factor beta (TGF-beta), IL-10, and IL-4 mRNA. The treatment also suppressed established colitis by inducing LP T cell apoptosis. These results strongly suggest that specific targeting of IL-6/sIL-6R pathway will be a promising new approach for the treatment of CD, and the clinical trial of humanized anti-IL-6R mAb is now under way.
Sequence diversity of small, round-structured viruses in the Norwalk virus group (1994)

We have determined the nucleotide sequences of a highly conserved region of the RNA-dependent RNA polymerase of the prototype Snow Mountain agent (SMA) and of four other small, round-structured viruses (antigenically Norwalk virus [NV]-like or SMA-like) following reverse transcription-PCR amplification of viral RNA obtained from human stools. The stool samples were either from volunteers administered SMA or from sporadic cases and outbreaks of gastroenteritis that occurred in Japan and the United Kingdom between 1984 and 1992. The GLPSG and YGDD RNA polymerase motifs were in the proper locations in the sequences of the five SRSVs, but each sequence was distinct from the 8FIIa prototype NV sequence and from each other. Analysis of the sequences and reactivities in a new NV antigen enzyme-linked immunosorbent assay showed that the five viruses could be divided into two groups (serogroups) with NV and SMA, respectively, being the prototypes. The sequences of the capsid region and a nonstructural region (2C) were determined from one strain from each group. One virus (SRSV-KY-89/89/J), isolated in Japan and antigenically similar to the prototype NV (isolated 21 years earlier in Ohio), showed a remarkable level of sequence similarity to NV. KY-89 and the 8FIIa NV showed 87.2% nucleotide similarity over 2,516 continuous nucleotides amounting to 96 to 98.9% amino acid similarity in three distinct domains in two open reading frames. Between the prototype SMA and NV, the polymerase region showed 63% nucleotide and 59% amino acid similarity, respectively. Two other antigenically SMA-like isolates (SRSV-925/92/UK and SRSV-OTH-25/89/J), from the United Kingdom and Japan, showed 80% nucleotide and 88 to 92% amino acid similarity in the polymerase region to the prototype SMA isolated 16 and 13 years earlier in the United States. The capsid region of the antigenically SMA-like OTH-25 virus showed 53% nucleotide and 65% amino acid similarity to the prototype NV capsid region. Domains of sequence diversity and conversation were identified within the capsid protein of these two distinct prototype serotypes of virus. These results indicate that NV-like and SMA-like agents are still circulating, and sequence comparisons will be useful to identify and classify distinct viruses in the NV group.
Isolation of lymphocytes and their innate immune characterizations from liver, intestine, lung and uterus. (2005)

In steady-state conditions, the number and distribution of lymphocyte populations are under homeostatic control. New lymphocytes are continuously produced in primary and secondary lymphoid organs and then achieve immune-competence within different tissues, and they must challenge with resident cells for survival. The first step in the study of tissue lymphoid cells is their isolation in intact and viable form appropriate for establishment of in vitro culture systems. For reasons of simplicity, cell purity, cell yields and various purposes, lymphocytes obtained from different tissues in different labs were subjected to diverse protocols. To fully elucidate the nature of the local immune system as well as to adequately study the innate role of lymphocytes in liver, intestine, lung and uterus, we briefly reviewed the characterization of resident lymphocytes, and additional information on those cells from non-lymphoid tissues by using the recommended operation procedure was also presented.
Alcohol synthesis by catalytic hydrogenation of CO2 over Rh-Co/SiO2 (2000)

The effect of the cobalt additive on Rh/SiO2 catalysts prepared by co-impregnation was examined to improve the reactivity in CO2 hydrogenation. The CO2 conversion increased significantly with the amount of cobalt added. Although the methanol selectivity was very low over nonpromoted Rh/SiO2 catalyst, more than 10% selectivity to methanol was obtained over the catalysts with cobalt added in the range of Co/Rh = 0.1–1 (atomic ratio). The methanol yield over Rh–Co/SiO2 catalyst was higher than the sum of the yields of Rh/SiO2 and Co/SiO2 catalysts. Physically mixed Rh/SiO2 and Co/SiO2 catalysts did not promote methanol formation. Based on the results of X-ray diffraction and X-ray photoelectron spectroscopy, it was suggested that Rh–Co alloy was formed on the catalyst surface to change the electronic states of rhodium, resulting in promotion of methanol formation. Copyright © 2000 John Wiley & Sons, Ltd.
Enhanced half-life of genetically engineered human IgG1 antibodies in a humanized FcRn mouse model: potential application in humorally mediated autoimmune disease (2006)

Journal Article Enhanced half-life of genetically engineered human IgG1 antibodies in a humanized FcRn mouse model: potential application in humorally mediated autoimmune disease Get access Stefka B. Petkova, Stefka B. Petkova 1Jackson Laboratory, Bar Harbor, ME 04609, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Shreeram Akilesh, Shreeram Akilesh 1Jackson Laboratory, Bar Harbor, ME 04609, USA4Present address: Department of Pathology, Washington University, St Louis, MO, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas J. Sproule, Thomas J. Sproule 1Jackson Laboratory, Bar Harbor, ME 04609, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Gregory J. Christianson, Gregory J. Christianson 1Jackson Laboratory, Bar Harbor, ME 04609, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Hana Al Khabbaz, Hana Al Khabbaz 1Jackson Laboratory, Bar Harbor, ME 04609, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Aaron C. Brown, Aaron C. Brown 1Jackson Laboratory, Bar Harbor, ME 04609, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Leonard G. Presta, Leonard G. Presta 2Department of Antibody Engineering, Genentech Inc., South San Francisco, CA, USA5Present address: Schering-Plough Biopharma, Palo Alto, CA, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Y. Gloria Meng, Y. Gloria Meng 3Department of Assay and Automation Technology, Genentech Inc., South San Francisco, CA, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Derry C. Roopenian Derry C. Roopenian 1Jackson Laboratory, Bar Harbor, ME 04609, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar International Immunology, Volume 18, Issue 12, December 2006, Pages 1759–1769, https://doi.org/10.1093/intimm/dxl110 Published: 31 October 2006 Article history Received: 25 April 2006 Accepted: 20 September 2006 Published: 31 October 2006
Chemical recognition and binding kinetics in a functionalized tunnel junction (2012)

4(5)-(2-mercaptoethyl)-1H-imidazole-2-carboxamide is a molecule that has multiple hydrogen bonding sites and a short flexible linker. When tethered to a pair of electrodes, it traps target molecules in a tunnel junction. Surprisingly large recognition-tunneling signals are generated for all naturally occurring DNA bases A, C, G, T and 5-methyl-cytosine. Tunnel current spikes are stochastic and broadly distributed, but characteristic enough so that individual bases can be identified as a tunneling probe is scanned over DNA oligomers. Each base yields a recognizable burst of signal, the duration of which is controlled entirely by the probe speed, down to speeds of 1 nm s -1, implying a maximum off-rate of 3 s -1 for the recognition complex. The same measurements yield a lower bound on the on-rate of 1 M -1 s -1. Despite the stochastic nature of the signals, an optimized multiparameter fit allows base calling from a single signal peak with an accuracy that can exceed 80% when a single type of nucleotide is present in the junction, meaning that recognition-tunneling is capable of true single-molecule analysis. The accuracy increases to 95% when multiple spikes in a signal cluster are analyzed.
Upregulation of Phosphodiesterase 1A1 Expression Is Associated With the Development of Nitrate Tolerance (2001)

Induction of PDE1A1 in nitrate-tolerant vessels may be one mechanism by which NO/cGMP-mediated vasodilation is desensitized and Ca(2+)-mediated vasoconstriction is supersensitized. Inhibiting PDE1A1 expression and/or activity could be a novel therapeutic approach to limit nitrate tolerance.
Discovery of Bicyclic Thymidine Analogues as Selective and High-Affinity Inhibitors of Mycobacterium tuberculosis Thymidine Monophosphate Kinase (2004)

Thymidine monophosphate kinase of Mycobacterium tuberculosis (TMPKmt) represents an attractive target for selectively blocking bacterial DNA synthesis. Hereby, we report on the discovery of a novel class of bicyclic nucleosides (10 and 11) and one dinucleoside (12), belonging to the most selective inhibitors of TMPKmt discovered so far.
Atom Transfer Polymerization of Methyl Methacrylate Mediated by Alkylpyridylmethanimine Type Ligands, Copper(I) Bromide, and Alkyl Halides in Hydrocarbon Solution (1999)

Schiff bases of types 1, 2, and 3, easily prepared by the condensation of primary amines with pyridine-2-carboxaldehyde, glyoxal, or 2-acetylpyridine, respectively, are described as ligands for a copper(I) catalyst in the atom transfer polymerization of a range of methacrylates in toluene and xylene solution. Increasing the length of the alkyl group on ligands of type 1 increases the solubility of the catalyst in nonpolar solvents. The rate of polymerization increases on going from R = ethyl to propyl; however, on increasing the length of R further, we see no effect on the rate. The molecular weight distribution is narrow for all ligands where R = n-alkyl, and the number-average molecular weight (Mn) increases linearly with conversion. A decrease in rate and a loss of control are observed when branching is introduced in the α-position of the side chain. The polymerization is approximately first order in initiator, 0.90 ± 0.22, CuBr, 0.90 ± 0.13, and methyl methacrylate, 0.93 ± 0.01. Polymerization with CuBr in conjunction with diazabutadiene ligands does not proceed very effectively, due to the high stability of the copper(I) complexes with regard to oxidation. The mechanism of the reaction is complex and may differ on subtle changes in ligand, metal, solvent, etc. The ligand systems presented in this paper offer a wide range of versatility when choosing the most effective system for a particular application. The Schiff base ligands, when used as described, provide an excellent method for achieving the controlled polymerization of a wide range of methacrylates at relatively mild temperatures in hydrocarbon, noncoordinating, solvents.
A model independent source code repository (1999)

Software repositories, used to support program development and maintenance, invariably require an abstract model of the source code. This requirement restricts the repository user to the analyses and queries supported by the data model of the repository. In this work, we present a software repository system based on an existing information retrieval system for structured text. Source code is treated as text, augmented with supplementary syntactic and semantic information. Both the source text and supplementary information can then be queried to retrieve elements of the code. No transformations are necessary to satisfy the requirements of a database storage model. As a result, the system is free of many of the limitations imposed by existing systems. 1 Introduction In order to store computer source code in a database, the source code must be abstracted in some manner so that it satisfies the requirements of the data model supported by the chosen database system. Databases applied to t...
Triplex and quadruplex DNA structures studied by electrospray mass spectrometry (2002)

DNA triplex and quadruplex structures have been successfully detected by electrospray ionization mass spectrometry (ESI-MS). Circular dichroism and UV-melting experiments show that these structures are stable in 150 mM ammonium acetate at pH 7 for the quadruplexes and pH 5.5 for the triplexes. The studied quadruplexes were the tetramer [d(TGGGGT)](4), the dimer [d(GGGGTTTTGGGG)](2), and the intramolecular folded strand dGGG(TTAGGG)(3), which is an analog of the human telomeric sequence. The absence of sodium contamination allowed demonstration of the specific inclusion of n - 1 ammonium cations in the quadruplex structures, where n is the number of consecutive G-tetrads. We also detected the complexes between the quadruplexes and the quadruplex-specific drug mesoporphyrin IX. MS/MS spectra of [d(TGGGGT)](4) and the complex with the drug are also reported. As the drug does not displace the ammonium cations, one can conclude that the drug binds at the exterior of the tetrads, and not between them. For the triplex structure the ESI-MS spectra show the detection of the specific triplex, at m/z values typically higher than those typically observed for duplex species. Upon MS/MS the antigene strand, which is bound into the major groove of the duplex, separates from the triplex. This is the same dissociation pathway as in solution. To our knowledge this is the first report of a triplex DNA structure by electrospray mass spectrometry.
Molecular Inversion Probe Analysis of Gene Copy Alterations Reveals Distinct Categories of Colorectal Carcinoma (2006)

Genomic instability is a major feature of neoplastic development in colorectal carcinoma and other cancers. Specific genomic instability events, such as deletions in chromosomes and other alterations in gene copy number, have potential utility as biologically relevant prognostic biomarkers. For example, genomic deletions on chromosome arm 18q are an indicator of colorectal carcinoma behavior and potentially useful as a prognostic indicator. Adapting a novel genomic technology called molecular inversion probes which can determine gene copy alterations, such as genomic deletions, we designed a set of probes to interrogate several hundred individual exons of >200 cancer genes with an overall distribution covering all chromosome arms. In addition, >100 probes were designed in close proximity of microsatellite markers on chromosome arm 18q. We analyzed a set of colorectal carcinoma cell lines and primary colorectal tumor samples for gene copy alterations and deletion mutations in exons. Based on clustering analysis, we distinguished the different categories of genomic instability among the colorectal cancer cell lines. Our analysis of primary tumors uncovered several distinct categories of colorectal carcinoma, each with specific patterns of 18q deletions and deletion mutations in specific genes. This finding has potential clinical ramifications given the application of 18q loss of heterozygosity events as a potential indicator for adjuvant treatment in stage II colorectal carcinoma.
Formation and Identification of Graphene (2009)

The graphene flakes were prepared by a micromechanical cleavage of a highly oriented pyrolytic graphite (HOPG) and were deposited on silicon substrates covered with thin films of SiO 2 , ZnS or ZrO 2 of different thickness. A good adhesion and good contrast have been achieved. The films have been studied with the Raman scattering technique. In this work we present a modeling of the light beam passage through a three layer system graphene-thin film-silicon and a calculation of the graphene vision contrast dependence on the incident light wavelength. A refractive index and a thickness of the covering thin film were also varied in this work. As a conclusion a material being transparent in a visible spectral range with the refractive index ranging from 2 to 2.2 should be chosen for the best graphene layer contrast.
Persistent Signaling by Dysregulated Thrombin Receptor Trafficking Promotes Breast Carcinoma Cell Invasion (2004)

Increased expression of protease-activated receptor 1 (PAR1), a G protein-coupled receptor for thrombin, has previously been correlated with breast carcinoma cell invasion. PAR1 is irreversibly proteolytically activated, internalized, and sorted directly to lysosomes, a critical process for the termination of signaling. We determined that activated PAR1 trafficking is severely altered in metastatic breast carcinoma cells but not in nonmetastatic or normal breast epithelial cells. Consequently, the proteolytically activated receptor is not sorted to lysosomes and degraded. Altered trafficking of proteolytically activated PAR1 caused sustained activation of phosphoinositide hydrolysis and extracellular signal-regulated kinase signaling, even after thrombin withdrawal, and enhanced cellular invasion. Thus, our results reveal that a novel alteration in trafficking of activated PAR1 causes persistent signaling and, in addition to other processes and proteins, contributes to breast carcinoma cell invasion.
Immunohistochemical localization in normal tissues of different epitopes in the multidrug transport protein P170: evidence for localization in brain capillaries and crossreactivity of one antibody with a muscle protein. (1989)

Using peroxidase immunohistochemistry, we examined the distribution of P170, a multidrug transport protein, in normal tissues by use of two different monoclonal antibodies (MAb). MAb MRK16 is a MAb that has been shown to react with an epitope in P170 located on the external face of the plasma membrane of multidrug-resistant human cells. MAb C219 has been shown to react with P170 in many mammalian species, and detects an epitope located on the cytoplasmic face of the plasma membrane. Using MRK16, we have previously described the localization of P170 on the bile canalicular face of hepatocytes, the apical surface of proximal tubular cells in kidney, and the surface epithelium in the lower GI tract in normal human tissues. In this work, we report that MRK16 also detects P170 in the capillaries of some human brain samples. A similar pattern was found using MAb C219 in rat tissues. in addition, MAb C219 showed intense localization in selected skeletal muscle fibers and all cardiac muscle fibers in rat and human tissues. ATPase cytochemistry showed that these reactive skeletal muscle fibers were of the type I (slow-twitch) class. Other additional sites of C219 reactivity in rat tissues were found in pancreatic acini, seminal vesicle, and testis. Electrophoretic gel immunoblotting showed two protein bands reactive with MAb C219. In liver, MAb C219 reacted with a approximately 170 KD band. In skeletal and cardiac muscle, MAb C219 reacted with a approximately 200 KD band which migrated in the same position as myosin. This band also reacted with an antibody to skeletal muscle myosin. This result suggests that C219 may crossreact with the heavy chain of muscle myosin in cardiac and skeletal muscle. Because MAb C219 reacts with proteins other than P170, it should be used with caution in studies of multidrug resistance.
Insight into the mechanisms of enhanced retinal transduction by the engineered AAV2 capsid variant ‐7m8 (2016)

Recently, we described a modified AAV2 vector-AAV2-7m8-having a capsid-displayed peptide insertion of 10 amino acids with enhanced retinal transduction properties. The insertion of the peptide referred to as 7m8 is responsible for high-level gene delivery into deep layers of the retina when virus is delivered into the eye's vitreous. Here, we further characterize AAV2-7m8 mediated gene delivery to neural tissue and investigate the mechanisms by which the inserted peptide provides better transduction away from the injection site. First, in order to understand if the peptide exerts its effect on its own or in conjunction with the neighboring amino acids, we inserted the 7m8 peptide at equivalent positions on three other AAV capsids, AAV5, AAV8, and AAV9, and evaluated its effect on their infectivity. Intravitreal delivery of these peptide insertion vectors revealed that only AAV9 benefited from 7m8 insertion in the context of the retina. We then investigated AAV2-7m8 and AAV9-7m8 properties in the brain, to better evaluate the spread and efficacy of viral transduction in view of the peptide insertion. While 7m8 insertion led to higher intensity gene expression, the spread of gene expression remained unchanged compared to the parental serotypes. Our results indicate that the 7m8 peptide insertion acts by increasing efficacy of cellular entry, with little effect on the spread of viral particles in neural tissue. The effects of peptide insertion are capsid and tissue dependent, highlighting the importance of the microenvironment in gene delivery using AAV. Biotechnol. Bioeng. 2016;113: 2712-2724. © 2016 Wiley Periodicals, Inc.