gebhart/patrepeval huggingface dataset:
Measurement of MHC/Peptide Interactions by Gel Filtration (1999)

This unit describes a technique for the direct and quantitative measurement of the capacity of peptide ligands to bind Class I and Class II MHC molecules. The binding of a peptide of interest to MHC is assessed based on its ability to inhibit the binding of a radiolabeled probe peptide to MHC molecules. The establishment of an MHC/peptide binding assay, and its subsequent use in determining the MHC binding capacities of peptide ligands, requires sufficient stocks of purified MHC and both labeled and unlabeled peptides. Accordingly, this unit includes protocols for the purification of Class I and Class II MHC molecules by affinity chromatography, and for the radiolabeling of peptides using the chloramine T method. A support protocol describes alterations in the basic protocol that are necessary when performing direct binding assays, which are required for (1) selecting appropriate high-affinity, assay-specific, radiolabeled ligands and (2) determining the amount of MHC necessary to yield assays with the highest sensitivity. After a 2-day incubation, the bound and unbound radiolabeled species are separated, and their relative amounts are determined. Two methods for separation by size-exclusion gel-filtration chromatography are described, as is data analysis.
Somatic Cell-Like Features of Cloned Mouse Embryos Prepared with Cultured Myoblast Nuclei1 (2003)

Cloning by somatic cell nuclear transfer requires silencing of the donor cell gene expression program and the initiation of the embryonic gene expression program (nuclear reprogramming). Failure to silence the donor cell program could lead to altered embryonic phenotypes. Cloned mouse embryos produced using myoblast nuclei fail to thrive in standard embryo culture media but flourish in somatic cell culture media favored by the donor myoblasts themselves, forming blastocysts at a significant rate, with robust morphologies, high total cell number, and a normal allocation of cells to the inner cell mass in most embryos. Myoblast cloned embryos continue expressing the GLUT4 glucose transporter, which is typically expressed in muscle but not in preimplantation stage embryos. Myoblast clones also exhibit precocious enrichment of GLUT1 at the cell surface. Both myoblast and cumulus cell cloned embryos exhibit enhanced rates of glucose uptake. These observations indicate that silencing of the donor cell genome during cloning either is incomplete or occurs progressively over the course of preimplantation development. As a result, cloned embryos initially exhibit many somatic cell-like characteristics. Tetraploid constructs, which possess a transplanted somatic cell genome plus the oocyte-derived chromosomes, exhibit a more embryonic-like pattern of gene expression and culture preference. We conclude that preimplantation stage cloned embryos have profoundly altered characteristics that are donor cell type specific and that exposure of cloned embryos to standard embryo culture conditions may lead to disruptions in basic homeostasis and inhibition of a range of essential processes including further nuclear reprogramming, contributing to cloned embryo demise.
Europium nanoparticles and time-resolved fluorescence for ultrasensitive detection of prostate-specific antigen. (2001)

The universal streptavidin-coated europium(III) nanoparticle label is suitable for detection of any biotinylated molecule either in solution or on a solid phase. The europium(III) nanoparticle labeling technology is applicable to many areas of modern biochemical analysis, such as immunochemical and multianalyte DNA-chip assays as well as histo- and cytochemistry to improve detection sensitivities.
The Revised NASPE/BPEG Generic Code for Antibradycardia, Adaptive‐Rate, and Multisite Pacing (2002)

In light of evolving pacemaker technology and increasing interest in multisite pacing, the Committee on the Development of Position Statements (CDPS) of the North American Society of Pacing and Electrophysiology (NASPE) created an ad hoc Pacemaker Mode Code Task Force in April 2001 under the chairmanship of David L. Hayes, MD, for the purpose of bringing the NASPE/British Pacing and Electrophysiology Group (BPEG) Generic Pacemaker Code (NBG Code) up to date. The task force, whose members are the authors of this article, designed a revised NBG Code in which three major issues were taken into account. First, it was recognized that all modern pacemakerpulse generators are capable of extensive bidirectional communication with an external programming device, making them "communicating" pulse generators as defined by the current (1987) NBG Code. Second, it was decided that a means of providing basic information regarding the location of multisite pacing would be a useful ingredient of the NBG Code. Third, in view of the extensive antibradycardia pacing capabilities common in modern implantable cardioverter defibrillators and the availability of the NASPE/BPEG Defibrillator Code (NBD Code), it was considered unnecessary for the NBG Code to address the presence or absence of antitachycardia features. The resulting updated version of the NBG Code as described herein was endorsed by the BPEG on September 20, 2001 and adopted by the NASPE Board of Trustees on October 18, 2001. The structure of the revised NBG Code differs from that of the previous version in two respects alone: Position IV specifies only the presence or absence of rate modulation, and Position V specifies only the location or absence of multisite pacing (i.e., biatrial or biventricular pacing with at least two stimulation sites in each case) more than one stimulation site in any single cardiac chamber, or any combination of these. The revised NBG Code is deliberately configured to avoid confusion with earlier mode codes, and it is the authors' hope that it will serve as an enhanced resource for communication among those engaged in every phase of the multidisciplinary practice of cardiac rhythm management.
Detergent-assisted refolding of guanidinium chloride-denatured rhodanese. The effect of lauryl maltoside. (1986)

For the first time, the enzyme rhodanese (thiosulfate:cyanide sulfurtransferase; EC 2.8.1.1) has been renatured from 6 M guanidinium chloride (GdmCl) by direct dilution of the denaturant at relatively high protein concentrations. This has been made possible by using the nonionic detergent dodecyl-beta-D-maltoside (lauryl maltoside). Lauryl maltoside concentration dependence of the renaturation and reactivation time courses were studied using 50 micrograms/ml rhodanese. There was no renaturation at lauryl maltoside (less than 0.1 mg/ml), and the renaturability increased, apparently cooperatively, up to 5 mg/ml detergent. This may reflect weak binding of lauryl maltoside to intermediate rhodanese conformers. The renaturability began to decrease above 5 mg/ml lauryl maltoside and was significantly reduced at 20 mg/ml. Individual progress curves of product formation, for rhodanese diluted into lauryl maltoside 90 min before assay, showed induction phases as long as 7 min before an apparently linear steady state. The induction phase increased with lauryl maltoside concentration and could even be observed in native controls above 1 mg/ml detergent. These results are consistent with suggestions that refolding of GdmCl-denatured rhodanese involves an intermediate with exposed hydrophobic surfaces that can partition into active and inactive species. Further, lauryl maltoside can stabilize those surfaces and prevent aggregation and other hydrophobic interaction-dependent events that reduce the yield of active protein. The rhodanese-lauryl maltoside complex could also form with native enzyme, thus explaining the induction phase with this species. Finally, it is suggested that renaturation of many proteins might be assisted by lauryl maltoside or other "nondenaturing" detergents.
A looking glass perspective: thalidomide and cyclopamine. (1999)

Numerous naturally-occurring and synthetic compounds that were discovered initially because of their toxic properties, were later shown to possess biological activities beneficial to humans that enabled them to serve as templates for the development of useful medicinal agents. A prominent example is thalidomide, a synthetic drug that gained notoriety originally due to its catastrophic teratogenicity in humans. The discovery of thalidomide's efficacy in treating several diseases has resulted in the recrudescence of the drug to society's usage. A current example of this phenomenon is the plant teratogen cyclopamine (11-deoxojervine), whose deleterious terata-inducing effects were restricted to grazing animals, but whose recently discovered inhibition of Sonic hedgehog signal transduction has provided both the potential to increase our understanding of organogenesis and to serve as a lead compound in drug development.
Endothelin-1 Induces Production of the Neutrophil Chemotactic Factor Interleukin-8 by Human Brain-Derived Endothelial Cells (1998)

Increased levels of endothelin-1 (Et-1), a potent vasoconstrictor, have been correlated with hypertension and neuronal damage in ischemic/reperfusion injury. The presence of polymorphonuclear cells (PMNs) in the brain has been shown to be directly responsible for this observed pathology. To address the question of whether Et-1 plays a role in this process, human brain-derived endothelial cells (CNS-ECs) were cultured with Et-1. The results demonstrate that Et-1 induces production of the neutrophil chemoattractant interleukin-8 (IL-8) twofold to threefold after 72 hours; mRNA was maximal after 1 hour of stimulation. Conditioned culture medium derived from Et-1-stimulated CNS-ECs induced a chemotactic response in the PMN migration assay. The inflammatory cytokines tumor necrosis factor-alpha (TNF) and IL-1beta functioned additively with Et-1 in increasing IL-8 production. In contrast, transforming growth factor-beta (TGF-beta), but not IL-10, completely abolished the effect of Et-1 on IL-8 production. However, Et-1 did not modulate intercellular adhesion molecule-1 (ICAM-1) expression. These data demonstrate that Et-1 may be a risk factor in ischemic/reperfusion injury by inducing increased levels of the neutrophil chemoattractant IL-8.
Statistical and Scientific Database Issues (1985)

The purpose of this paper is to summarize the research issues of statistical and scientific databases (SSDB's). It organizes the issues into four major groups: physical organization and access methods, operators, logical organization and user interfaces, and miscellaneous issues. It emphasizes the differences between SSDB's and traditional database applications, and motivates the need for new and innovative techniques for the support of SSDB's. In addition to describing current work in this field, it discusses open research areas and proposes possible approaches to their solution.
Dynamic Simulation for Analysis of Hybrid Electric Vehicle System and Subsystem Interactions, Including Power Electronics (2005)

Simulation tools for hybrid electric vehicles (HEVs) can be classified into steady-state and dynamic models, according to their purpose. Tools with steady-state models are useful for system-level analysis. The information gained is helpful for assessing long-term behavior of the vehicle. Tools that utilize dynamic models give in-depth information about the short-term behavior of sublevel components. In this paper, a dynamic model of a hybrid electric vehicle that includes fuel cells, batteries, ultracapacitors, and induction machine drives is presented. Simulation results of vehicle configurations with a battery, a fuel cell-battery combination and a fuel cell-ultracapacitor combination are discussed. The focus of the model is a detailed assessment of different subsystem components, particularly component losses.
Genetic variations in the heparanase gene (HPSE) associate with increased risk of GVHD following allogeneic stem cell transplantation: effect of discrepancy between recipients and donors (2010)

Graft-versus-host disease (GVHD) is the most common cause of nonrelapse mortality and morbidity after hematopoietic stem cell transplantation (HSCT). The well-documented involvement of heparanase in the process of inflammation and autoimmunity led us to investigate an association between HPSE gene single-nucleotide polymorphisms (SNPs) and the risk of GVHD. The present study indicates a highly significant correlation of HPSE gene SNPs rs4693608 and rs4364254 and their combination with the risk of developing acute GVHD. Moreover, the study revealed that discrepancy between recipient and donor in these SNPs may elevate significantly the risk of acute GVHD. This association was statistically significant when the recipients possessed genotype combinations dictating higher levels of heparanase compared with their human leukocyte antigen (HLA)-matched donors. In addition, HPSE gene SNPs disclosed a correlation with extensive chronic GVHD, nonrelapse mortality, and overall survival. Our study indicates involvement of heparanase in the development of acute and extensive chronic GVHD. Moreover, it suggests a possible mechanism for the aggressive behavior of T lymphocytes leading to GVHD when the recipients possess genotype combinations that dictate high levels of heparanase mRNA compared with their HLA-matched donors expressing low levels of heparanase.
Recent Developments in the Decorporation of Plutonium, Americium and Thorium (1998)

Progress is reported on some of the research priorities identified in the Guidebook for the Treatment of Accidental Contamination of Workers published in 1992. It concludes that the administration of DTPA in drinking water could be an effective treatment for plutonium and americium inhaled as nitrates; that 3,43-LI(1,2-HOPO) is the most effective siderophore analogue yet tested for the decorporation of these actinides, and thorium; and that for thorium the efficacy of treatment will be strongly dependent on the mass likely to be incorporated under different exposure conditions.
Ultra High-speed Novel Bulk Thyristor-SRAM (BT-RAM) Cell with Selective Epitaxy Anode (SEA) (2006)

We developed novel SRAM cells using bulk thyristor-RAM (BT-RAM). BT-RAM, formed on bulk Si wafers, is low cost and has good compatibility with logic process flows. BT-RAM has excellent performance, with a 100-ps read/write, high Ion/Ioff current ratio (>108), and low stand-by current (< 0.5 nA/cell). We can expect the ideal cell size to be as low as 30 F2, one-fourth that of a conventional 6T-SRAM cell, by using selective epitaxy technique for anode regions (SEA). BT-RAM provides us with solutions to many inherent problems in 6T-SRAM in the 65-nm generation and beyond.
Differential Gene Expression in Human Peripheral Blood Mononuclear Cells Induced by Cigarette Smoke and Its Constituents (2005)

In current molecular epidemiology studies, a wide range of methods are used to monitor early biological effects after exposure to xenobiotic agents. Gene expression profiling is considered a promising tool that may provide more sensitive, mechanism-based biomarkers. As a first step toward obtaining information on the applicability of gene expression profiles as a biomarker for early biological effects of carcinogen exposure, we conducted in vitro studies on human peripheral blood mononuclear cells (PBMC). We used cigarette smoke condensate (CSC) and a selection of its genotoxic constituents as model agents, applying cDNA microarray technology to investigate modulated gene expression. In independent experiments using cells from several donors, quiescent PBMC were exposed for 18 h, followed by gene expression analyses on a microarray containing 600 toxicologically relevant genes. The search for candidate biomarker genes was binomial: first we looked for genes responding similarly to all agents; second, for agent-specific genes. Many genes were significantly deregulated by all compounds, but as the direction of deregulation frequently differed per agent, they are not useful as generic biomarkers. Cigarette smoke condensate modulated the expression of many more genes than any of its constituents, with the largest effect in SERPINB2. The affected genes are involved in immune or stress responses, but surprisingly no genes involved in DNA damage response were modulated, and only a few in DNA repair. In conclusion, several genes have been identified as potential biomarkers for population studies on early biological effects caused by cigarette smoke exposure, but no genes were identified that represent a generic biomarker.
Introduction of Nucleophiles and Spectroscopic Probes into Antibody Combining Sites (1988)

A general chemical strategy has been developed whereby antibody combining sites can be selectively derivatized with natural or synthetic molecules, such as catalytic groups, drugs, metals, or reporter molecules. Cleavable affinity labels were used to selectively introduce a thiol into the combining site of the immunoglobulin A MOPC 315. This thiol acted both as a nucleophile to accelerate ester thiolysis 60,000-fold and as a handle for selectively derivatizing the antibody with additional functional groups. For example, derivatization of the antibody with a fluorophore made possible a direct spectroscopic assay of antibody-ligand complexation. This chemistry should not only extend our ability to exploit antibody specificity in chemical catalysis, diagnostics, and therapeutics, but may also prove generally applicable to the functional modification of other proteins for which detailed structural information is unavailable.
Pyrazolate-Based Porphyrinic Metal–Organic Framework with Extraordinary Base-Resistance (2015)

Guided by a top-down topological analysis, a metal-organic framework (MOF) constructed by pyrazolate-based porphyrinic ligand, namely, PCN-601, has been rationally designed and synthesized, and it exhibits excellent stability in alkali solutions. It is, to the best of our knowledge, the first identified MOF that can retain its crystallinity and porosity in saturated sodium hydroxide solution (∼ 20 mol/L) at room temperature and 100 °C. This almost pushes base-resistance of porphyrinic MOFs (even if MOFs) to the limit in aqueous media and greatly extends the range of their potential applications. In this work, we also tried to interpret the stability of PCN-601 from both thermodynamic and kinetic perspectives.
Receptor-induced death in human natural killer cells: involvement of CD16. (1995)

Propriocidal regulation of T cells refers to apoptosis induced by interleukin 2 (IL-2) activation with subsequent antigen receptor stimulation. We examined whether natural killer (NK) cells exhibited cytokine- and ligand-induced death similar to activated T cells. Peripheral NK cells were examined for ligand-induced death using antibodies to surface moieties (CD2, CD3, CD8, CD16, CD56), with and without prior activation of IL-2. Only those NK cells stimulated first with IL-2 and then with CD16 exhibited ligand-induced death; none of the other antibody stimuli induced this phenomenon. Next we examined various cytokines (IL-2, IL-4, IL-6, IL-7, IL-12, IL-13, interferon alpha and gamma) that can activate NK cells and determined if CD16-induced killing occurred. Only IL-2 and IL-12 induced NK cell death after occupancy of this receptor by aggregated immunoglobulin or by cross-linking with antireceptor antibody. The CD16-induced death was inhibited by herbimycin A, indicating that cell death was dependent upon protein tyrosine kinases. Identical to T cells, the form of cell death for NK cells was demonstrated to be receptor-induced apoptosis. Overall these data indicate that highly activated NK cells mediate ligand-induced apoptosis via signaling molecules like CD16. Whereas the propriocidal regulation of T cells is antigen specific, this is not the case for NK cells due to the nature of the receptor. The clinical implications of this finding are considered.
Novel therapeutics for head and neck cancer (2002)

Head and neck squamous cell carcinoma is a clinically challenging disease that resulted in more than 500,000 cases worldwide in 2001. In the United States, head and neck squamous cell carcinoma has accounted for approximately 40,000 cases with 12,000 deaths reported in 2001, which makes it the fifth leading cause of cancer incidence and the sixth leading cause of cancer-related deaths. Patients with recurrent or metastatic disease have a median survival rate of approximately 6 months; and there is little evidence from randomized trials that survival advantages have been achieved over the community standard of cisplatin and infusional 5-fluorouracil combination. Despite significant improvements in diagnosis, local management, and chemotherapy of head and neck cancer, there has been no significant increase in long-term survival rates over the past 30 years. As little progress has been made, new management approaches are required. Novel biologic agents have been developed to target multiple specific regions of the cancer cell. Epidermal growth factor receptor blockers have been investigated, such as anti epidermal growth factor receptor monoclonal antibodies, tyrosine kinase inhibitors, ligand conjugates, immunoconjugates, and antisense oligonucleotides. Farnesyl transferase inhibitors are a class of compounds that inhibit a critical enzymatic step in the constitutive expression of mutated ras genes, which are present in more than 27% of oral cancers. Strategies targeting the p53 gene and protein may halt or reverse the process of tumorigenesis and metastasis as p53 mutations occur in 45 to 70% of head and neck squamous cell carcinoma patients. Continued development of these novel agents may help improve the overall response and survival rate of patients with head and neck cancer.
Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1α/CXC chemokine receptor 4 pathway (2004)

Migration toward pathology is the first critical step in stem cell engagement during regeneration. Neural stem cells (NSCs) migrate through the parenchyma along nonstereotypical routes in a precise directed manner across great distances to injury sites in the CNS, where they might engage niches harboring local transiently expressed reparative signals. The molecular mechanisms for NSC mobilization have not been identified. Because NSCs seem to home similarly to pathologic sites derived from disparate etiologies, we hypothesized that the inflammatory response itself, a characteristic common to all, guides the behavior of potentially reparative cells. As proof of concept, we show that human NSCs migrate in vivo (including from the contralateral hemisphere) toward an infarcted area (a representative CNS injury), where local astrocytes and endothelium up-regulate the inflammatory chemoattractant stromal cell-derived factor 1α (SDF-1α). NSCs express CXC chemokine receptor 4 (CXCR4), the cognate receptor for SDF-1α. Exposure of SDF-1α to quiescent NSCs enhances proliferation, promotes chain migration and transmigration, and activates intracellular molecular pathways mediating engagement. CXCR4 blockade abrogates their pathology-directed chain migration, a developmentally relevant mode of tangential migration that, if recapitulated, could explain homing along nonstereotypical paths. Our data implicate SDF-1α/CXCR4, representative of the inflammatory milieu characterizing many pathologies, as a pathway that activates NSC molecular programs during injury and suggest that inflammation may be viewed not simply as playing an adverse role but also as providing stimuli that recruit cells with a regenerative homeostasis-promoting capacity. CXCR4 expression within germinal zones suggests that NSC homing after injury and migration during development may invoke similar mechanisms.