gebhart/patrepeval huggingface dataset:
Molecular characterization of a major autoantibody-associated cross-reactive idiotype in Sjogren's syndrome. (1989)

Primary Sjogren's syndrome is an autoimmune disorder characterized by lymphocytic infiltration of the salivary and lacrimal glands, producing associated dry eyes (keratoconjunctivitis sicca), dry mouth, and intermittently swollen salivary glands. A high proportion of the infiltrating B lymphocytes express surface and cytoplasmic Ig bearing a kappa-L chain-associated CRI defined by reactivity with the murine mAb, 17.109. To determine the structural basis for CRI expression in this disease, we generated CRI+ lymphoblastoid cell lines and a cDNA library from lymphocytes extracted from Sjogren's syndrome patients' salivary gland biopsy specimens. Nucleic acid sequence analyses of the mRNA of one such 17.109-CRI+ lymphoblastoid cell line (NOV) reveals the expressed kappa light chain variable region gene (V kappa gene) to be homologous to Humkv325, a conserved V kappa gene used at relatively high frequency in certain B cell malignancies. In addition, synthetic oligonucleotides, corresponding to the first and third frameworks and the second complementarity determining region of the Humkv325 gene, were used to identify and isolate clones from a cDNA library generated from SS salivary gland lymphocytes. Clones annealing specifically with one or more of these oligonucleotide probes contained kappa light chain cDNA. The sequences corresponding to the variable region of two clones (Taykv320 and Taykv306) were homologous to Humkv325. The V kappa genes of four other cDNA clones (Taykv322, Taykv310, Taykv308, and Taykv312) most likely were generated somatically from the rearranged Humkv325 gene through a limited number of nucleic acid base substitutions. Our results suggest that the high frequency of 17.109-CRI expression in Sjogren's syndrome patients results from a multiclonal expansion of B cells using Humkv325, and that the expressed Humkv325 may undergo somatic diversification in an apparent Ag-driven response.
The Role of Bcl-x(L) Protein in Nucleotide Excision Repair–Facilitated Cell Protection Against Cisplatin-Induced Apoptosis (2009)

Many anticancer drugs target the genomic DNA of cancer cells by generating DNA damage and inducing apoptosis. DNA repair protects cells against DNA damage-induced apoptosis. Although the mechanisms of DNA repair and apoptosis have been extensively studied, the mechanism by which DNA repair prevents DNA damage-induced apoptosis is not fully understood. We studied the role of the antiapoptotic Bcl-x(L) protein in nucleotide excision repair (NER)-facilitated cell protection against cisplatin-induced apoptosis. Using both normal human fibroblasts (NF) and NER-defective xeroderma pigmentosum group A (XPA) and group G (XPG) fibroblasts, we demonstrated that a functional NER is required for cisplatin-induced transcription of the bcl-x(l) gene. The results obtained from our Western blots revealed that the cisplatin treatment led to an increase in the level of Bcl-x(L) protein in NF cells, but a decrease in the level of Bcl-x(L) protein in both XPA and XPG cells. The results of our immunofluorescence staining indicated that a functional NER pathway was required for cisplatin-induced translocation of NF-kappaB p65 from cytoplasm into nucleus, indicative of NF-kappaB activation. Given the important function of NF-kappaB in regulating transcription of the bcl-x(l) gene and the Bcl-x(L) protein in preventing apoptosis, these results suggest that NER may protect cells against cisplatin-induced apoptosis by activating NF-kappaB, which further induces transcription of the bcl-x(l) gene, resulting in an accumulation of Bcl-x(L) protein and activation of the cell survival pathway that leads to increased cell survival under cisplatin treatment.
Class II genes of the human major histocompatibility complex. The DO beta gene is a divergent member of the class II beta gene family. (1987)

A novel class II beta chain gene is described. This gene, tentatively called DO beta, displays considerably less polymorphism than beta genes of the DP, DQ, and DR loci. The nucleotide sequence of the DO beta gene is strikingly similar to that of the previously identified murine A beta 2 gene. The DO beta gene displays the same exon/intron organization as other beta genes although the fifth exon and the translated portion of the sixth exon are longer than in other genes. A striking feature of the amino acid sequence deduced from the DO beta gene sequence is the pronounced hydrophobicity of the NH2-terminal region. This feature distinguishes the putative DO beta chain from other class II beta chains and raises the possibility that DO beta chains may interact with an alpha chain that is structurally different from those of the DP, DQ, and DR loci. It further suggests that the putative DO molecule may have a function different from those of other class II antigens.
The Effects of Cardiopulmonary Bypass on Fibrin Formation and Lysis: Is a Normal Fibrinolytic Response Essential? (1996)

Fibrinolytic activity in blood is regulated by a dynamic process that includes control of production, secretion, inhibition, and clearance of fibrinolytic proteins. The concentration of active tissue plasminogen activator (tPA) in the region of the thrombus controls the rate of fibrinolytic activation. We have developed a first-generation kinetic model that can be used to simulate the effects of secretion, inhibition, and clearance reactions on the concentrations of active tPA, active plasminogen activator inhibitor type 1 (PAI-1), and tPA/PAI-1 complex in the circulation. This model was used to estimate the rate and pattern of secretion of tPA and PAI-1 in individual subjects. We also undertook a laboratory evaluation of fibrinolysis in patients with a history of myocardial infarction. Elevated PAI-1 activity in the absence of elevations in other acute-phase proteins suggested an intrinsic increase in PAI-1 secretion in patients post-myocardial infarction. Cardiopulmonary bypass (CPB) results in a major increase in fibrinolytic activity that has been associated with an increased risk for hemorrhage. Fibrinolytic proteins were sampled from patients both during surgery and for 2 days postoperatively. Total tPA antigen rose throughout CPB and returned to baseline in the post-operative period. PAI-1 activity fell during the initial bypass and by the end of bypass had returned to baseline. On the first to second postoperative day there was a large increase in PAI-1 activity and a significant decrease in tPA activity. These data suggest that during this period there is a window of risk for a thromboembolic event. There was, however, a large individual variability in patient response to CPB.
A portable lightweight associate for urban helicopter pilotage (2002)

The Urban Helicopter Associate System (UHAS) is an advanced demonstration prototype of an associate system for aiding pilots of rotorcraft engaged in complex missions in urban environments. It is the first of a evolving class of lightweight associate systems that provide full associate decision aiding in a lightweight computing environment. The UHAS is hosted on a laptop computer, and is intended for limited flight demonstrations in law enforcement and emergency medical services (EMS) scenarios.
Comparison between Free‐Choice and No‐Choice Seedling Bulk Tests for Evaluating Resistance of Rice Cultivars to the Whitebacked Planthopper1 (1984)

During a screening of rice, Oryza sativa L., cultivars for resistance to the whitebacked planthopper Sogatella furcifera (Horváth) by the routinely used free‐choice seedling bulk test, a significantly higher insect population was observed to move over to the susceptible check cultivar soon after infestation. This uneven distribution of insects caused unbalanced infestation among the test cultivars. To avoid this shortcoming, a no‐choice seedling bulk test was conducted in which each row of test cultivar seedlings was excluded from the other by an intervening, vertical, mylar plastic partition, and was exposed to equal insect infestation. The resistance scores of 10 genetically diverse cultivars—‘Muskhan 41’ ( Wbph 1), ‘N22’ ( Wbph 1), ‘N32’ ( Wbph 1), ‘ARC 10239’ ( Wbph 2), ‘ADR 52’ ( Wbph 3), ‘Podiwi A8’ ( wbph 4), ‘Colombo’ ( Wbph 2 + 1 recessive ?), ‘WC 1240’ ( Wbph I + 1 recessive ?), ‘1R 2035‐117‐3’ ( Wbph 1 + Wbph 2), and ‘Taichung Native 1’ (no resistance gene)—from free‐choice and no‐choice seedling bulk tests were compared. Podiwi A8 and N22, rated as moderately resistant and resistant in the free‐choice test, proved to be susceptible and moderately resistant, respectively, in the no‐choice test. The no‐choice test ensures an even distribution of test insects on cultivars and excludes any possibility of their escape from infestation. The technique has important implications in screening for resistance against a number of mobile insect pest species on a wide variety of plants.
The design philosophy of the DARPA Internet Protocols (1995)

The Internet protocol suite, TCP/IP, was first proposed fifteen years ago. It was developed by the Defense Advanced Research Projects Agency (DARPA), and has been used widely in military and commercial systems. While there have been papers and specifications that describe how the protocols work, it is sometimes difficult to deduce from these why the protocol is as it is. For example, the Internet protocol is based on a connectionless or datagram mode of service. The motivation for this has been greatly misunderstood. This paper attempts to capture some of the early reasoning which shaped the Internet protocols.
Step-Growth Polymers for High-Performance Materials (1996)

Recent developments in the application of Ni(0) and Pd(0) catalyzed carbon-carbon bond forming reactions to the preparation of well defined polymer structures by step polymerization reactions are discussed. Three types of coupling reactions using these catalysts are especially applicable to step polymerizations: (a) homocoupling reactions of organic electrophiles, (b) cross-coupling reactions of organic electrophiles with alkenes or alkynes, and (c) cross-coupling reactions of organic electrophiles with organometallic compounds. The organometallic compounds which have been most useful to polymer chemists include: organomagnesium, organozinc, organostannane, and organoboronic acids (and their esters). This survey of the scope of these reactions includes, for each type of reaction, a discussion of: the types of electrophiles and leaving groups, and their reactivity; reaction mechanism; catalysts; selectivities; and limitations.
Sensitivity of Protein Adsorption to Architectural Variations in a Protein-Resistant Polymer Brush Containing Engineered Nanoscale Adhesive Sites (2011)

Patchy polymer brushes contain nanoscale (5-15 nm) adhesive elements, such as polymer coils or nanoparticles, embedded at their base at random positions on the surface. The competition between the brush's steric (protein resistant) repulsions and the attractions from the discrete adhesive elements provides a precise means to control bioadhesion. This differs from the classical approach, where functionality is placed on the brush's periphery. The current study demonstrates the impact of poly(etheylene glycol) (PEG) brush architecture and ionic strength on fibrinogen adsorption on brushes containing embedded poly-l-lysine (PLL, 20K MW) coils or "patches". The consistent appearance of a fibrinogen adsorption threshold, a minimum loading of patches on the surface, below which protein adsorption does not occur, suggests multivalent protein capture: Adsorbing proteins simultaneously engage several patches. The surface composition (patch loading) at the threshold is extremely sensitive to the brush height and ionic strength, varying up to a factor of 5 in the surface loading of the PLL patches (~50% of the range of possible surfaces). Variations in ionic strength have a similar effect, with the smallest thresholds seen for the largest Debye lengths. While trends with brush height were the clearest and most dominant, consideration of the PEG loading within the brush or its persistence length did not reveal a critical brush parameter for the onset of adsorption. The lack of straightforward correlation on brush physics was likely a result of multivalent binding, (producing an additional dependence on patch loading), and might be resolved for univalent adsorption onto more strongly binding patches. While studies with similar brushes placed uniformly on a surface revealed that the PEG loading within the brush is the best indicator of protein resistance, the current results suggest that brush height is more important for patchy brushes. Likely the interactions producing brush extension normal to the interface act similarly to drive lateral tether extension to obstruct patches.
UniCam—2D gestural camera controls for 3D environments (1999)

We present a novel approach to controlling a virtual 3D camera with a 2D mouse or stylus input device that is based on gestural interaction. Our approach to 3D camera manipulation, UniCam, requires only a single-button stylus or mouse to directly invoke specific camera operations within a single 3D view. No 2D widgets or keyboard modifiers are necessary. By gesturally invoking all camera functionality, UniCam reduces the modal nature of typical desktop 3D graphics applications, since remaining mouse or stylus buttons can be used for other application functionality. In addition, the particular choice and refinement of UniCam controls efficiently enables a wide range of camera manipulation tasks, including translation in three-dimensions, orbiting about a point, animated focusing on an object surface, animated navigation around an object, zooming in upon a region, and saving and restoring viewpoints. UniCam's efficiency derives primarily from improved transitions between techniques and to a lesser degree from adaptations of existing techniques. Although we have conducted no formal user evaluations, UniCam is the result of years of iterative development with approximately one hundred users. During this time more conventional modifier key and menu-based implementations were implemented and either refined or rejected. Informally, users appear to require a few hours of training to become proficient with UniCam controls, but then typically choose them almost exclusively even when widget-based controls, such as those provided by an Inventor viewer, are simultaneously available.
Amino acid residues of 5-lipoxygenase-activating protein critical for the binding of leukotriene biosynthesis inhibitors. (1993)

5-Lipoxygenase-activating protein (FLAP) plays an essential role in cellular leukotriene (LT) synthesis and represents the target of three classes of LT biosynthesis inhibitors. We have taken three approaches to localize regions of FLAP involved in the binding of these inhibitors. A comparison of the amino acid sequences of FLAP from eight mammalian species identifies regions of the protein which are highly conserved and consequently may be involved in functional and inhibitor binding properties of the protein. Conversely, amino acids not conserved amongst these species are unlikely to play an essential role in inhibitor binding. Immunoprecipitation of peptide fragments of FLAP cross-linked to photoaffinity analogues of LT biosynthesis inhibitors following site-specific peptide cleavage indicates that the inhibitor attachment site is amino-terminal to 72Trp. Taken together, the cross-species analysis and photoaffinity labelling studies suggest a region within the first hydrophilic loop of FLAP which may be important for inhibitor binding. Site-directed mutagenesis of human FLAP followed by the analysis of FLAP mutants in a radioligand binding assay was used to more accurately define critical amino acid residues within this region. Mutagenesis studies reveal that mutants containing deletions of amino acids in regions of FLAP not conserved between species retain the ability to specifically bind inhibitors. Furthermore, mutants containing deletions in a highly conserved region of the protein (residues 42-61) do not bind inhibitors. These studies have therefore localized specific amino acids of FLAP which are essential for inhibitor binding. The roles that these amino acids play in inhibitor binding and may play in 5-LO activation is under investigation.
Anti-graft-versus-host disease effect of DT390-anti-CD3sFv, a single- chain Fv fusion immunotoxin specifically targeting the CD3 epsilon moiety of the T-cell receptor (1996)

In a recent study, we showed that an immunotoxin (IT) made with a conventional monoclonal antibody targeting the CD3 epsilon moiety of the T-cell receptor (TCR) had a potent, but partial, graft-versus-host disease (GVHD) effect (Vallera et al, Blood 86:4367, 1995). Therefore, in this current study, we determined whether a fusion immunotoxin made with anti-CD3 single-chain Fv (sFv), the smallest unit of antibody recognizing antigen, would have anti-GVHD activity. A fusion protein was synthesized from a construct made by splicing sFv cDNA from the hybridoma 145-2C11 to a truncated form of the diphtheria toxin (DT390) gene. DT390 encodes a molecule that retains full enzymatic activity, but excludes the native DT binding domain. The DT390-anti-CD3sFv hybrid gene was cloned into a vector under the control of an inducible promoter. The protein was expressed in Escherichia coli and then purified from inclusion bodies. The DT390 moiety of the protein had full enzymatic activity compared with native DT and DT390-anti-CD3sFv, with an IC50 of 1 to 2 nmol/L against phytohemagglutinin-stimulated and alloantigen-stimulated T cells. Specificity was shown (1) by blocking the IT with parental anti-CD3 antibody, but not with a control antibody; (2) by failure of DT390-anti-CD3sFv to inhibit lipopolysaccharide-stimulated murine B cells; (3) by failure of an Ig control fusion protein, DT390-Fc, to inhibit T-cell responses; and (4) with in vivo immunohistochemisty studies. GVHD was studied in a model in which C57BL/6 (H-2b)-purified lymph node T cells were administered to major histocompatibility complex (MHC) antigen disparate unirradiated C.B.-17 scid (H-2d) mice to assess GVHD effects in the absence of irradiation toxicity. Flow cytometry studies showed that donor T cells were expanded 57-fold and histopathologic analysis showed the hallmarks of a lethal model of GVHD. Control mice receiving phosphate-buffered saline showed 17% survival on day 80 after bone marrow transplantation, and mice receiving 2 micrograms DT390-Fc fusion toxin control administered in 2 daily doses for 6 days (days 0 through 5) had a 43% survival rate. In contrast, 86% of mice receiving the same dose of DT390-anti-CD3sFv were survivors on day 80, a significant improvement, although survivors still showed histopathologic signs of GVHD. These findings suggest that new anti-GVHD agents can be genetically engineered and warrant further investigation of fusion proteins for GVHD treatment.
Storage protein profile and amino acid content in wild rice Oryza glumaepatula (2013)

- The objective of this work was to determine the total protein profile and the contents of the four major protein fractions (albumin, globulin, prolamin and glutelin) and of the amino acids in the endosperm of the rice wild species Oryza glumaepatula. The experiment was performed with 29 accessions of this species, collected from 13 Brazilian locations, and two commercial cultivars. Protein samples were prepared using dried, polished, and ground grains to obtain homogeneous, dry flour used in the preparation of extracts. Oryza glumaepatula accessions were identified with the highest levels of total protein, albumin and glutelin protein fractions, and amino acids (with the exception of tryptophan) in comparison to the two analized rice cultivars. The albumin and glutelin profiles in SDS-Page were distinct between rice cultivars and O. glumaepatula. This wild species has the potential to increase the nutritional quality of rice storage protein through interspecific crosses.
CCR6 is required for IL-23–induced psoriasis-like inflammation in mice (2009)

Psoriasis is a common immune-mediated chronic inflammatory skin disorder, but the mechanisms of pathogenesis are still poorly understood. IL-23 is expressed in psoriatic skin, and IL-23 injection produces IL-22-dependent psoriasiform changes in mouse skin. Th17 cells produce IL-22 and display CCR6, the CCL20 receptor; CCR6+ T cells and CCL20 are abundant in psoriatic skin. We investigated a possible role for CCR6 in recruiting Th17 cells and producing psoriasiform pathology by injecting IL-23 into the skin of WT and Ccr6-/- mice. Unlike for WT mice, IL-23-injected ears of Ccr6-/- mice showed neither substantial epidermal/dermal changes nor increased Il22 mRNA expression. However, injection of IL-22 yielded equivalent psoriasiform changes in WT and Ccr6-/- mice. Surprisingly, IL-23-injected ears of WT and Ccr6-/- mice contained similar numbers of Th cells able to make IL-17A and/or IL-22. Furthermore, in ears of Rag1-/- mice, IL-23 initially induced skin changes and levels of Il22 mRNA that were indistinguishable from WT mice, revealing at least one non-T cell source for IL-22. We conclude that CCR6 is essential in a model of IL-23-induced, IL-22-mediated dermatitis, which develops in sequential T cell-independent and T cell-dependent phases. These findings reveal an expanded role for CCR6 in IL-23-related responses and identify CCR6 as a potential therapeutic target in psoriasis.
Hydrogen/Deuterium Exchange Reactions of Olefins with Deuterium Oxide Mediated by the Carbonylchlorohydrido‐ tris(triphenylphosphine)ruthenium(II) Complex (2010)

Abstract The catalytic properties of several ruthenium, osmium and rhodium hydride complexes for hydrogen/deuterium (H/D) exchange between olefins and deuterium oxide (D 2 O) were investigated. The most effective catalytic precursor was found to be the carbonylchlorohydridotris(triphenylphosphine)ruthenium(II) complex. Through H/D exchange between metal hydride and D 2 O, and reversible olefin insertion into an RuH(D) bond, protons attached to olefinic carbons and alkyl chains of olefins can all undergo H/D exchange with D 2 O. The catalytic reactions can be used to deuterate both terminal and internal olefins, for example, styrene, stilbene and cyclooctene.
Isolation, Culture, and Characterization of Human Pancreatic Duct Cells (1993)

To establish a suitable control for pancreatic tumor cell lines, we have isolated and cultured primary human pancreatic duct cells from transplant donors. Duct cells were isolated by dissecting the main pancreatic duct and first-degree branches and enzymatic digestion. Aggregates of cells were cultured for 1 up to 5 weeks and monitored for changes in morphology and growth by phase contrast microscopy. Contaminating fibroblasts were mechanically removed from day 4 on and by cloning of epithelial cells. Cultured cells were characterized by phase contrast microscopy, electron microscopy, and immunofluorescence with antibodies against intermediate filaments (cytokeratins, vimentin, desmin), mucins (Du-Pan-2, CA 19-9), carbonic anhydrase II, acinar cell enzymes (amylase, lipase, trypsin), and islet cells. About 90% of the cultured cells could be identified as ductal epithelial cells by their expression of cytokeratins, mucins, and carbonic anhydrase II. These cells showed the ultrastructural features of duct cells. After 3-5 weeks of culture, most of the cultured cells showed co-expression of cytokeratins and vimentin in addition to duct cell markers. About 10% of cells were contaminating fibroblasts (vimentin positive, cytokeratin negative). The cultured normal human duct cells as the postulated cells of origin of the pancreatic adenocarcinoma may serve as a useful control for cultured pancreatic tumor cell lines.