gebhart/patrepeval huggingface dataset:
Differential Knockdown of δ-Opioid Receptor Subtypes in the Rat Brain by Antisense Oligodeoxynucleotides Targeting mRNA (1999)

Two antisense oligodeoxynucleotides (A-ODN), targeting delta-opioid receptor mRNA (DOR) and two mismatch ODN sequences (mODN) were continuously infused for 24 days into the lateral brain ventricles of Wistar rats. The density of delta-opioid receptors in rat brain homogenates was measured by saturation binding experiments using four selective ligands, two agonists ([D-Ala2, Glu4]-deltorphin and DPDPE) and two antagonists (Dmt-Tic-OH and naltrindole), and by immunoblotting SDS solubilized receptor protein. In brain membranes of mODN or saline-infused rats, the rank order of delta-opioid receptor density, calculated by Bmax values of the four delta-opioid receptor ligands, was: [D-Ala2, Glu4]deltorphin approximately Dmt-Tic-OH approximately naltrindole (86-118 fmo/mg protein) > DPDPE (73.6+/-6.3 fmol/mg protein). At the end of the 24 day infusion of A-ODN targeting DOR nucleotide sequence 280299 (A-ODN280-299), the Bmax of DPDPE (62.4+/-3.2 fmol/mg protein) was significantly higher than that of Dmt-Tic-OH (31.5+/-3.9 fmol/mg protein). Moreover, both the Kd value for DPDPE saturation binding and the Ki value for Dmt-Tic-OH displacement by DPDPE were halved. In contrast, an A-ODN treatment targeting exon 3 (A-ODN741-760) decreased the specific binding of [D-Ala2, Glu4]deltorphin and Dmt-Tic-OH significantly less (67%-81%) than the binding of DPDPE (53%), without changes in DPDPE Ki and KD values. No A-ODN treatment modified the specific binding of the micro-opioid agonist DAMGO and of the k-selective opioid receptor ligand U69593. On the Western blot of solubilized striatum proteins, A-ODN(280-299) and A-ODN(741-760) downregulated the levels of the DOR protein, whereas the corresponding mODN were inactive. The 24-day infusion of A-ODN(280-299) inhibited the rat locomotor response to [D-Ala2, Glu4]deltorphin but not to DPDPE. Intracerebroventricular (i.c.v.) infusion of A-ODN(741-760) reduced the locomotor responses to both delta-opioid receptor agonists, whereas mODN infusion never affected agonist potencies. In conclusion, these results demonstrate that 24-day continuous i.c.v. infusion of A-ODN targeting the nucleotide sequence 280-299 of DOR can differentially knockdown delta1 and delta2 binding sites in the rat brain.
Glial cells express multiple ATP binding cassette proteins which are involved in ATP release (2002)

Rat brain astrocyte and microglia cultures express different members of ATP-binding-cassette (ABC) proteins. RT-PCR analysis showed that astrocytes are equipped with P-glycoprotein (mdr1a, mdr1b), multidrug resistance-associated-protein (mrp1, mrp4, mrp5) and cystic fibrosis transmembrane conductance regulator (CFTR). No transcripts for mrp5 and CFTR were detected in microglia. The ABC protein functional activities are shown by the following results: (i) cyclosporin A (50 microM), verapamil (50 microM), probenecid (1 mM) or sulfinpyrazone (2 mM) enhanced [3H]vincristine accumulation; (ii) cyclosporin A or verapamil but not probenecid or sulfinpyrazone enhanced [3H]digoxin accumulation; (iii) glibenclamide (100 microM) inhibited 36Cl efflux from astrocytes. ATP release from glial cells was inhibited by the pretreatment with ABC protein inhibitors indicating that ABC proteins are involved in nucleotide efflux from glial cells which represent the main source of cerebral extracellular purines.
Waveguide grating filters for dispersion compensation and pulse compression (1993)

Dispersion compensation and pulse compression are theoretically demonstrated using aperiodic waveguide gratings. The gratings are designed to have both a flat amplitude and a quadratic phase response over the pulse bandwidth. This results in nearly transform-limited compressed pulses. The appropriate waveguide grating parameters are obtained by applying the Gel'fand-Levitan-Marchenko inverse scattering method to the coupled mode equations which describe propagation. The technique is illustrated by designing an aperiodic grating which compresses a 60-ps pulse by a factor of three. Limitations and possible extensions of the general method are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Synthesis, characterization, and clinical evaluation of conjugate vaccines composed of the O-specific polysaccharides of Shigella dysenteriae type 1, Shigella flexneri type 2a, and Shigella sonnei (Plesiomonas shigelloides) bound to bacterial toxoids (1993)

The theoretic basis for developing conjugate vaccines, to induce immunoglobulin G (IgG) lipopolysaccharide (LPS) antibodies for the prevention of shigellosis, has been described (J. B. Robbins, C.-Y. Chu, and R. Schneerson, Clin. Infect. Dis. 15:346-361, 1992). The O-specific polysaccharides (O-SPs) of Shigella dysenteriae type 1, S. flexneri type 2a, and S. sonnei were covalently bound to carrier proteins. Alone, the O-SPs were not immunogenic in mice. Conjugates of these O-SPs, injected into young outbred mice subcutaneously as saline solutions containing 2.5 micrograms of saccharide, elicited serum IgG and IgM antibodies with booster responses; adsorption onto alum enhanced their immunogenicity. Injection of 25 micrograms of these conjugates into adult volunteers elicited mild local reactions only. Each conjugate induced a significant rise of the geometric mean serum IgG, IgM, and IgA LPS antibody levels. A second injection 6 weeks later did not elicit booster responses, and adsorption of the conjugates onto alum did not enhance their immunogenicity. Conjugate-induced levels of IgA, but not IgG or IgM, declined to preimmunization levels at day 56. The levels of postimmunization antibodies of the three immunoglobulin classes were similar to or higher than those of recruits in the Israel Defense Force following shigellosis caused by S. flexneri type 2a or S. sonnei. These data provide the basis for evaluating these conjugates to prevent shigellosis.
Analysis of the Assembly Function of the Human Immunodeficiency Virus Type 1 Gag Protein Nucleocapsid Domain (1998)

Previous studies have shown that in addition to its function in specific RNA encapsidation, the human immunodeficiency virus type 1 (HIV-1) nucleocapsid (NC) is required for efficient virus particle assembly. However, the mechanism by which NC facilitates the assembly process is not clearly established. Formally, NC could act by constraining the Pr559gag polyprotein into an assembly-competent conformation or by masking residues which block the assembly process. Alternatively, the capacity of NC to bind RNA or make interprotein contacts might affect particle assembly. To examine its role in the assembly process, we replaced the NC domain in Pr55gag with polypeptide domains of known function, and the chimeric proteins were analyzed for their abilities to direct the release of virus-like particles. Our results indicate that NC does not mask inhibitory domains and does not act passively, by simply providing a stable folded monomeric structure. However, replacement of NC by polypeptides which form interprotein contacts permitted efficient virus particle assembly and release, even when RNA was not detected in the particles. These results suggest that formation of interprotein contacts by NC is essential to the normal HIV-1 assembly process.
A general strategy for the evolution of bond-forming enzymes using yeast display (2011)

The ability to routinely generate efficient protein catalysts of bond-forming reactions chosen by researchers, rather than nature, is a long-standing goal of the molecular life sciences. Here, we describe a directed evolution strategy for enzymes that catalyze, in principle, any bond-forming reaction. The system integrates yeast display, enzyme-mediated bioconjugation, and fluorescence-activated cell sorting to isolate cells expressing proteins that catalyze the coupling of two substrates chosen by the researcher. We validated the system using model screens for Staphylococcus aureus sortase A-catalyzed transpeptidation activity, resulting in enrichment factors of 6,000-fold after a single round of screening. We applied the system to evolve sortase A for improved catalytic activity. After eight rounds of screening, we isolated variants of sortase A with up to a 140-fold increase in LPETG-coupling activity compared with the starting wild-type enzyme. An evolved sortase variant enabled much more efficient labeling of LPETG-tagged human CD154 expressed on the surface of HeLa cells compared with wild-type sortase. Because the method developed here does not rely on any particular screenable or selectable property of the substrates or product, it represents a powerful alternative to existing enzyme evolution methods.
Diffusion curves (2008)

We describe a new vector-based primitive for creating smooth-shaded images, called the diffusion curve . A diffusion curve partitions the space through which it is drawn, defining different colors on either side. These colors may vary smoothly along the curve. In addition, the sharpness of the color transition from one side of the curve to the other can be controlled. Given a set of diffusion curves, the final image is constructed by solving a Poisson equation whose constraints are specified by the set of gradients across all diffusion curves. Like all vector-based primitives, diffusion curves conveniently support a variety of operations, including geometry-based editing, keyframe animation, and ready stylization. Moreover, their representation is compact and inherently resolution-independent. We describe a GPU-based implementation for rendering images defined by a set of diffusion curves in realtime. We then demonstrate an interactive drawing system for allowing artists to create artworks using diffusion curves, either by drawing the curves in a freehand style, or by tracing existing imagery. The system is simple and intuitive: we show results created by artists after just a few minutes of instruction. Furthermore, we describe a completely automatic conversion process for taking an image and turning it into a set of diffusion curves that closely approximate the original image content.
Modifications in a flexible surface loop modulate the isozyme-specific properties of mammalian alkaline phosphatases. (1993)

We have analyzed to what extent the surface loop domain of alkaline phosphatases (APs) is responsible for isozyme-specific functional properties. Unique AatII and RsrII restriction sites were introduced by site-directed mutagenesis at identical positions in murine tissue-nonspecific AP (TNAP) and human placental AP (PLAP) cDNAs to allow the homologous exchange of the loop domain of the TNAP (T domain) and PLAP (P domain) isozymes and the generation of the reciprocally chimeric molecules PLAP-T and TNAP-P. The introduction of the T loop into PLAP reduced the heat stability of PLAP-T to almost that of TNAP. The domain substitution was accompanied by a conformational change that resulted in the loss of immune reactivity with four of 17 epitope-mapped anti-PLAP monoclonal antibodies. The T and P loops provided stabilization to the side chain of specific uncompetitive AP inhibitors. The introduction of the T domain also conferred collagen-binding properties to PLAP-T accounting for half of the binding affinity of TNAP for collagen, while not affecting PLAP binding to IgG. Our data indicate that the surface loop determines overall enzyme stability, differs conformationally in the various isozymes, and modulates catalytic parameters in the presence of protein ligands, thus, accounting in part for isozyme-specific protein interactions.
Bitcoin: A Primer (2013)

Bitcoin is a digital currency that was launched in 2009, and it has attracted much attention recently. This article reviews the mechanics of the currency and offers some thoughts on its characteristics.
Modulation of cell proliferation and cytokine production in acute myeloblastic leukemia by interleukin-1 receptor antagonist and lack of its expression by leukemic cells (1991)

Interleukin-1 (IL-1) is spontaneously produced by acute myeloblastic leukemia (AML) cells. IL-1 also induces synthesis of colony-stimulating factors (CSFs) and sustains leukemic growth. An IL-1-specific inhibitor has been recently purified and cloned; this molecule binds to IL-1 receptors but has no IL-1 activity, fulfilling the characteristics of an IL-1 receptor antagonist (IL-1ra). Because high-affinity binding sites for IL-1ra were shown on AML cells by radioligand binding studies, we studied the effect of IL-1ra on the proliferative activity of blast cells isolated from 16 cases of AML. In each case, spontaneous proliferation was inhibited by addition of the IL-1ra in a dose- dependent manner (1 to 100 ng/mL). Culture supernatants of unstimulated leukemic cells contained IL-1 beta and granulocyte-macrophage CSF (GM- CSF), but when incubated with the IL-1ra, a reduction or disappearance of GM-CSF was observed in 8 of 10 cases, whereas spontaneous IL-1 production was reduced in four of seven cases. By Northern hybridization, IL-1 beta gene transcripts were shown in 20 of 23 AML cases, whereas IL-1ra-specific messenger RNA was present in only two of the patients studied. These data show a role for IL-1 in the spontaneous proliferation and cytokine production of AML cells and suggest that an imbalanced synthesis of IL-1 and of its natural receptor antagonist may contribute to the unrestricted growth of AML cells.
A probabilistic disease-gene finder for personal genomes (2011)

VAAST (the Variant Annotation, Analysis & Search Tool) is a probabilistic search tool for identifying damaged genes and their disease-causing variants in personal genome sequences. VAAST builds on existing amino acid substitution (AAS) and aggregative approaches to variant prioritization, combining elements of both into a single unified likelihood framework that allows users to identify damaged genes and deleterious variants with greater accuracy, and in an easy-to-use fashion. VAAST can score both coding and noncoding variants, evaluating the cumulative impact of both types of variants simultaneously. VAAST can identify rare variants causing rare genetic diseases, and it can also use both rare and common variants to identify genes responsible for common diseases. VAAST thus has a much greater scope of use than any existing methodology. Here we demonstrate its ability to identify damaged genes using small cohorts (n = 3) of unrelated individuals, wherein no two share the same deleterious variants, and for common, multigenic diseases using as few as 150 cases.
Resistance to ACCase-inhibiting herbicides in the weed Lolium multiflorum. (2008)

Resistance to five ACCase-inhibiting herbicides (dictofop, fluazifop, tralkoxydim, cycloxydim and pinoxaden) was investigated in 55 Lolium multiflorum populations from 50 farms in England. Resistance screening experiments at whole plant level showed differences in the response to each herbicide suggesting different resistance mechanisms for different herbicides, despite all of them having the same mode of action. Plants from populations resistant to at least one herbicide were analysed at the molecular level using the derived Cleaved Amplified Polymorphic Sequence method (dCAPS). Three single-site point mutations (ile-1781-leu, asp-2078-gly and cys-2088-arg) known to confer resistance to ACCase inhibitors were found in 13 populations. In the remaining resistant populations a more specific mutation or an enhanced metabolism mechanism might be involved.
Autonomic Computing (2004)

Systems that install, heal, protect themselves and adapt to your needs -automatically Using autonomic computing to reduce costs, improve services, and enhance agility Autonomic components, architectures, standards, and development tools Planning for and implementing autonomic technology Current autonomic solutions from IBM and other leading companiesReducing IT costs, improving service, and enabling the on-demand businessIT operations costs are accelerating, and today's increasingly complex architectures and distributed computing infrastructures only make matters worse. The solution: autonomic computing. Autonomic systems are self-configuring, self-healing, self-optimizing, and self-protecting. They operate intelligently and dynamically, acting your policies and service requirements. This book presents everything IT leaders and managers need to know to prepare for autonomic computing-and to begin leveraging its benefits. Coverage includes: How autonomic computing can reduce costs, improve service levels, enhance agility, simplify management, and help deliver the on demand business The key elements and attributes of autonomic computing systems Current autonomic technologies from IBM and many other leading suppliers Autonomic computing architectures, open standards, development tools, and enablers Implementation considerations, including a new assessment methodology The future of autonomic computing: business opportunities and research challenges
From the Bench to the Field in Low‐Cost Diagnostics: Two Case Studies (2015)

Despite the growth of research in universities on point-of-care (POC) diagnostics for global health, most devices never leave the laboratory. The processes that move diagnostic technology from the laboratory to the field--the processes intended to evaluate operation and performance under realistic conditions--are more complicated than they might seem. Two case studies illustrate this process: the development of a paper-based device to measure liver function, and the development of a device to identify sickle cell disease based on aqueous multiphase systems (AMPS) and differences in the densities of normal and sickled cells. Details of developing these devices provide strategies for forming partnerships, prototyping devices, designing studies, and evaluating POC diagnostics. Technical and procedural lessons drawn from these experiences may be useful to those designing diagnostic tests for developing countries, and more generally, technologies for use in resource-limited environments.
Conformational changes induced in the envelope glycoproteins of the human and simian immunodeficiency viruses by soluble receptor binding (1993)

We have investigated the molecular basis of biological differences observed among cell line-adapted isolates of the human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and the simian immunodeficiency virus (SIV) in response to receptor binding by using a soluble form of CD4 (sCD4) as a receptor mimic. We find that sCD4 binds to the envelope glycoproteins of all of the HIV-1 isolates tested with affinities within a threefold range, whereas those of the HIV-2 and SIV isolates have relative affinities for sCD4 two- to eightfold lower than those of HIV-1. Treatment of infected cells with sCD4 induced the dissociation of gp120 from gp41 and increased the exposure of a cryptic gp41 epitope on all of the HIV-1 isolates. By contrast, neither dissociation of the outer envelope glycoprotein nor increased exposure of the transmembrane glycoprotein was observed when sCD4 bound to HIV-2- or SIV-infected cells. Moreover, immunoprecipitation with sCD4 resulted in the coprecipitation of the surface and transmembrane glycoproteins from virions of the HIV-2 and SIV isolates, whereas the surface envelope glycoprotein alone was precipitated from HIV-1. However, treatment of HIV-1-, HIV-2-, and SIV-infected cells with sCD4 did result in an increase in exposure of their V2 and V3 loops, as detected by enhanced antibody reactivity. This demonstrates that receptor binding to the outer envelope glycoprotein induces certain conformational changes which are common to all of these viruses and others which are restricted to cell line-passaged isolates of HIV-1.
Hypoxic tumor cell radiosensitization: role of the iNOS/NO pathway. (2008)

Hypoxia is a common feature of the tumor microenvironment and a major cause of clinical radioresistance. During the last decades, several strategies to improve tumor oxygenation were developed such as breathing high oxygen content gas under hyperbaric conditions (3 atmosphere) and improving tumor perfusion by nicotinamide, in combination with carbogen breathing and accelerated radiotherapy to counteract tumor repopulation (ARCON). Other strategies to overcome hypoxia induced radioresistance are the use of hypoxic cell radiosensitizers, which mimic oxygen and enhance thereby radiation damage (e.g. the nitroimidazoles) and bioreductive drugs, which undergo intracellular reduction to form active cytotoxic species under low oxygen tension (e.g. mitomycin C and tirapazamine). A meta-analysis of all randomized trials in which some form of hypoxic modification was performed, showed an improved local control and survival, especially in cervix and head-and-neck cancer. Nevertheless, none of the discussed strategies are used in clinical routine because of feasibility and toxicity issues. We developed an alternative strategy that takes advantage of the microenvironment of solid tumors for tumor specific radiosensitization. The inducible isoform of nitric oxide synthase (iNOS) may be induced by bacterial LPS or its derivate lipid A, is expressed by a variety of solid tumors and generates NO at high rates inside tumor cells. This local production of NO results in efficient hypoxic tumor cell radiosensitization, at non-toxic extracellular concentrations of NO. In addition, iNOS is transcriptionally upregulated by hypoxia and proinflammatory cytokines such as interferon-gamma. Hence, we proposed the pro-inflammatory tumor infiltrate as a new target for radiosensitizing strategies and identified two mechanisms: First, tumor associated immune cells (macrophages, T/NK-cells) are a source of mediators that may induce the iNOS/NO pathway inside tumor cells. Second, tumor associated macrophages can produce high levels of NO that may radiosensitize bystander tumor cells. Our ongoing research is focused on combining immunostimulatory and radiosensitizing strategies.
Assembling millions of short DNA sequences using SSAKE (2006)

http://www.bcgsc.ca/bioinfo/software/ssake.
Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (2018)

Among patients with septic shock undergoing mechanical ventilation, a continuous infusion of hydrocortisone did not result in lower 90-day mortality than placebo. (Funded by the National Health and Medical Research Council of Australia and others; ADRENAL ClinicalTrials.gov number, NCT01448109 .).