gebhart/patrepeval huggingface dataset:
Cell fusion induced by herpes simplex virus is promoted and suppressed by different viral glycoproteins. (1977)

Some of the factors that regulate membrane fusion resulting in polykaryocyte formationhave been investigated, using the model system of human cells infected with mutants of herpes simplex virus (HSV). One of the mutant viruses used in this study (MP) failed to produce the viral glycoprotein designated C2--a nonlethal defect that has previously been correlated with the polykaryocyte-inducing phenotype of this and other mutant strains (wild-type strains of HSV usually induce the aggregation of infected cells rather than their fusion). The other mutant virus (tsB5), a temperature-sensitive conditional-lethal mutant, failed to produce glycoprotein B2 at non-permissive temperature, whereas the synthesis of all other viral products appeared to be normal. We produced and isolated seven recombinants of MP and tsB5 that expressed both of the parental alterations in glycoprotein synthesis. All of the re-combinant viruses induced the fusion of infected cells at 34 degrees (correlated with the absence of C2 expression) but were unable to cause cell fusion at 39 degrees (correlated with the absence of C2 and of B2 expression), even after infection at multiplicities high enough to ensure that all cells in the cultures synthesized viral macromolecules. These results and studies on the dominance or recessiveness of the fusion-inducing phenotype in mixed infections provide evidence that glycoprotein B2 plays a critical role in the promotion of cell fusion and that glycoprotein C2 can act to suppress fusion.
Sensitization of colorectal and pancreatic cancer cell lines to the prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954) by retroviral transduction and expression of the E. coli nitroreductase gene. (1997)

Expression of genes encoding prodrug-activating enzymes can increase the susceptibility of tumor cells to prodrugs, and may ultimately achieve a better therapeutic index than conventional chemotherapy. CB1954 is a weak, monofunctional alkylating agent which can be activated by Escherichia coli nitroreductase to a potent dysfunctional alkylating agent which crosslinks DNA. We have inserted the nitroreductase gene into an LNCX-based retroviral vector, to allow efficient gene transfer and expression in colorectal (LS174T) and pancreatic (SUIT2, BxPC3, and AsPC1) cancer cell lines. A clone of LS174T cells expressing nitroreductase showed > 50-fold increased sensitivity to CB1954, and nitroreductase-expressing clones of pancreatic tumor lines were up to approximately 500-fold (SUIT2) more sensitive than parental cells. Concentrations of CB1954 minimally toxic to nontransduced cells achieved 100% cell death in a 50:50 mix of parental cells with SUIT2 cells expressing nitroreductase; and marked "bystander" cell killing was seen with just 10% of cells expressing nitroreductase. Significant bystander cell killing was dependent on a high cell density. In conjunction with regional delivery of vectors and tumor selectivity of cell entry and/or gene expression, nitroreductase and CB1954 may be an attractive combination for prodrug-activating enzyme gene therapy of colorectal and pancreatic cancer.
Survival Motor Neuron (SMN) Protein Interacts with Transcription Corepressor mSin3A (2004)

Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality. SMA results from loss of survival motor neuron (SMN) expression and subsequent death of motor neuron cells. To study SMN-associated proteins that may be involved in transcriptional regulation, we carried out immunoprecipitation experiments and found that the transcription corepressor mSin3A associates with SMN protein. Deletional analysis localized the mSin3A-interacting domain to the exon 6 region of SMN. When targeted to a promoter, wild-type SMN was able to repress transcription of a downstream luciferase reporter gene. This repression was relieved by treatment with the histone deacetylase inhibitor trichostatin A in a dose-dependent manner, and deletion of exon 6 abolished the ability of SMN to repress the reporter gene. Analysis of SMN missense mutations within the exon 6 region implicated the SMA-associated mutation Y272C with impairment of the mSin3A-interaction. Gel filtration experiments revealed that wild-type SMN, via the exon 6 region, forms protein supra-complexes exceeding 40,000 kDa in size, whereas the Y272C mutation may affect higher order protein assembly, as the mutant SMN was more abundant in smaller complexes. Together, these findings provide a potential mechanism by which lack of fully functional SMN protein is detrimental to motor neuron survival.
Skil: an imperative language with algorithmic skeletons for efficient distributed programming (1996)

We present Skil, an imperative language enhanced with higher order functions and currying, as well as with a polymorphic type system. The high level of Skil allows the integration of algorithmic skeletons, i.e. of higher order functions representing parallel computation patterns. At the same time, the language can be efficiently implemented. After describing a series of skeletons which work with distributed arrays, we give two examples of parallel programs implemented on the basis of skeletons, namely shortest paths in graphs and Gaussian elimination. Run time measurements show that we approach the efficiency of message passing C up to a factor between 1 and 2.5.
RNA structure: crystal clear? (1997)

Structured RNAs play an essential role in chromosome maintenance, RNA processing, protein biosynthesis, and protein transport. To understand RNA function in these diverse biological systems, the rules for RNA folding and recognition must be learned. Recent crystal structures of hammerhead ribozymes, a group I intron domain, and RNA duplexes provide new insights into the principles of RNA folding and function.
DNA Display of Biologically Active Proteins for In Vitro Protein Selection (2004)

In vitro display technologies are powerful tools for screening peptides with desired functions. We previously proposed a DNA display system in which streptavidin-fused peptides are linked with their encoding DNAs via biotin labels in emulsion compartments and successfully applied it to the screening of random peptide libraries. Here we describe its application to functional and folded proteins. By introducing peptide linkers between streptavidin and fused proteins, we achieved highly efficient (>95%) formation of DNA-protein conjugates. Furthermore, we successfully enriched a glutathione-S-transferase gene by a factor of 20-30-fold per round on glutathione-coupled beads. Thus, DNA display should be useful for rapidly screening or evolving proteins based on affinity selection.
Isolation and characterization of human placental trophoblast subpopulations from first-trimester chorionic villi (1996)

A method for the simultaneous preparation of highly enriched human placental trophoblast populations (villous and extravillous) from first-trimester placental villi (5 to 12 weeks) by using sequential trypsinization, percoll gradient centrifugation, and negative selection with anti-CD9 immunomagnetic separation is described. The purification method resulted in the isolation of four distinct trophoblast populations identified on the basis of morphology and phenotyping: (i) mononuclear villous cytotrophoblast cells which, through differentiation, become committed to syncytium formation; (ii) an extravillous trophoblast population which appeared as a "crazy pavement" and, with subsequent subculturing, differentiated morphologically to mononuclear cells; (iii) an extravillous trophoblast fraction which fused to form multinucleated trophoblast giant cells; and (iv) floating intermediate extravillous trophoblast cells which fused together to form cell clumps and which further differentiated to a mononuclear anchoring intermediate extravillous trophoblast. Short-term cultures of the freshly isolated cell fractions consisted of heterogeneous trophoblasts at different differentiation stages as determined by their varied biochemical and morphological properties. All the isolated trophoblast populations expressed the cytokeratin intermediate filament and the epithelium-specific cell-cell adhesion molecule E-cadherin. The isolated villous trophoblasts in culture expressed integrins alpha 6 and beta 4 and reduced levels of beta 1 subunits, whereas the proliferating extravillous trophoblast cultures expressed alpha 1, alpha 3, and alpha 5 and high levels of beta 1 integrin subunits, vitronectin receptor (alpha V beta 3/beta 5), and major histocompatibility complex class 1 molecules. Furthermore, the isolated trophoblast populations secreted metalloproteases (such as type IV collagenases [mainly 72- and 92-kDa enzymes, i.e., gelatinases A and B]) and urokinase plasminogen activator, as evaluated by substrate gel zymography. This method of isolation should facilitate in vitro studies of trophoblast proliferation, differentiation, invasion, virus interactions, cytokenesis, and immunology.
Molecular weight determination of megadalton DNA electrospray ions using charge detection time‐of‐flight mass spectrometry (1995)

We present results obtained with a novel mass spectrometer capable of determining the mass of multiply charged electrospray ions generated from samples of macromolecules in the megadalton (MDa) size range. The instrument utilizes a sensitive amplifier which can detect the charge on a single ion as it passes through a tube detector. A velocity measurement of an ion with known electrostatic energy provides the ion's mass-to-charge ratio. Simultaneous detection of the ion charge permits a mass assignment to be made for each ion. Electrospray ions of DNA and polymer molecules with masses greater than 1 x 10(6) Da and charge numbers (z) in excess of 425 e(-) are readily detected in this mass spectrometer. The weights of small particles were also measured. The on-axis single-ion detection configuration provides a duty cycle of nearly 100% and extends the practical application of electrospray mass spectrometry to the analysis of very large molecules with relatively inexpensive instrumentation.
Protein Kinases as Targets for Cancer Treatment (2007)

In various types of malignancies, conventional forms of therapy (surgery, radiation and chemotherapy) are often ineffective, as well as harmful. In the last few years, a convergence of scientific advances has enabled the identification of molecular targets and signaling pathways specific to cancer cells, resulting in therapies with enhanced selectivity and efficacy and reduced toxicity. Compound validation has relied on target validation first, although some of the most successful drugs often have effects outside of their postulated mechanism. Protein kinases represent such molecular targets; considerable research effort has been devoted to the development of targeted drugs that inhibit the action of pathogenic kinases, and clinical studies performed so far have validated the positive effects of kinase inhibitors for cancer treatment. In this review, the specificity, mechanism of action and antitumor activity of several new small-molecule inhibitors of tyrosine and serine/threonine kinases are discussed.
Comparison of Immunoblotting and Indirect Enzyme-Linked Immunosorbent Assay Using Different Antigen Preparations for Diagnosing Early Lyme Disease (1988)

We compared immunoblotting and indirect enzyme-linked immunosorbent assay (ELISA) using different antigen preparations to test for antibody to Borrelia burgdorferi in patients with early Lyme disease. With immunoblotting, 16 (53%) of 30 patients had positive tests in acute-phase sera and 25 (83%) had them in convalescent-phase sera. Among 64 controls, false-positive results were obtained in only three individuals with syphilis and in one hospitalized patient with renal allograft rejection. Among the patients with Lyme disease, both IgM and IgG antibodies most commonly bound to the 41-kilodalton (kDa) flagellar antigen, but many patients had binding to other components, particularly those of 25, 55, 58, or 66 kDa, and the order of their appearance was variable. Compared with indirect ELISA (using sonicated whole spirochetes or a flagellin-enriched fraction as the antigen preparation), more patients with Lyme disease had positive tests by immunoblotting, and fewer control subjects had false-positive results. Our results indicate that immunoblotting is superior to indirect ELISA for diagnosing early Lyme disease.
Host-seeking behaviour of mosquitoes: responses to olfactory stimuli in the laboratory (2010)

This chapter reviews the current understanding of odour-mediated host-seeking behaviour in mosquitoes based on laboratory (indoor) studies. Most recent studies have focused on Aedes aegypti L., Anopheles gambiae sensu stricto Giles and Culex quinquefasciatus Say, as these species are all strongly associated with human biting and disease transmission. Where relevant, reference to other mosquito species is provided. Host seeking in mosquitoes is mediated primarily by chemical cues, and therefore most studies focus on the response to host odours and identification of specific compounds or odour blends. Laboratory tools for the study of odour-mediated behaviour include Y-tube and dual-choice (or dual-port) olfactometers, wind tunnels and room-size arenas in which mosquitoes can fly freely. Mosquitoes are observed individually or in groups, usually at a specified age or range of ages, at a pre-determined time of the day when they are considered to be naturally responsive to host cues. Aedes aegypti and An. gambiae respond strongly to natural human skin emanations, whereas Cx. quinquefasciatus shows variation in this behaviour dependent on its geographic origin. Carbon dioxide acts as a principal stimulus for each of these mosquito species although with a variable species-specific effect. Several host-derived compounds have been identified that cause behavioural responses in these mosquito species, including ammonia, L(+)-lactic acid and aliphatic carboxylic acids. In addition, acetone and dimethyl disulfide enhance the attraction of blends of these compounds to Ae. aegypti. Some other ketones, such as 6-methyl-5-hepten-2-one and geranyl acetone disrupt the host-seeking process of Ae. aegypti and An. gambiae. Several aldehydes, such as octanal and nonanal, are attractive to Cx. quinquefasciatus, and reduce upwind flight and the total number of landings in Ae. aegypti. Based on these data odour blends have been identified that are attractive to these mosquito species, albeit less so than natural human odour, indicating that additional, hitherto unidentified, semiochemicals are involved in host-seeking behaviour that are likely to improve the efficacy of blends. Behavioural research combined with studies on molecular olfaction is ongoing to discover compounds that affect the host-seeking process, and further research under semi-field and field conditions is required to explore the effectiveness of putative attractants and repellents in natural circumstances.
Crystalline-Amorphous Core−Shell Silicon Nanowires for High Capacity and High Current Battery Electrodes (2008)

Silicon is an attractive alloy-type anode material for lithium ion batteries because of its highest known capacity (4200 mAh/g). However silicon's large volume change upon lithium insertion and extraction, which causes pulverization and capacity fading, has limited its applications. Designing nanoscale hierarchical structures is a novel approach to address the issues associated with the large volume changes. In this letter, we introduce a core-shell design of silicon nanowires for highpower and long-life lithium battery electrodes. Silicon crystalline-amorphous core-shell nanowires were grown directly on stainless steel current collectors by a simple one-step synthesis. Amorphous Si shells instead of crystalline Si cores can be selected to be electrochemically active due to the difference of their lithiation potentials. Therefore, crystalline Si cores function as a stable mechanical support and an efficient electrical conducting pathway while amorphous shells store Li(+) ions. We demonstrate here that these core-shell nanowires have high charge storage capacity ( approximately 1000 mAh/g, 3 times of carbon) with approximately 90% capacity retention over 100 cycles. They also show excellent electrochemical performance at high rate charging and discharging (6.8 A/g, approximately 20 times of carbon at 1 h rate).
Overcoming tumor necrosis factor and drug resistance of human tumor cell lines by combination treatment with anti-Fas antibody and drugs or toxins. (1993)

Monoclonal mouse anti-Fas antibody is directed against Fas antigen, a M(r) 36,000 encoded polypeptide that belongs to the family of cell surface proteins which includes nerve growth factor receptor, tumor necrosis factor (TNF) receptors, B-cell antigen CD40, and T-cell antigens OX40. Anti-Fas antibody mimics TNF-alpha in its cytolytic activity but not in other TNF-alpha-mediated activities. Thus, we examined if anti-Fas antibody synergizes in cytotoxicity with toxins and drugs. The present studies demonstrate that anti-Fas antibody in combination with diphtheria toxin (DTX), Adriamycin, or cis-platinum results in enhanced cytotoxicity and synergy and also overrides resistance to TNF, drugs, or toxins when tested against a battery of human tumor cell lines. Synergy with anti-Fas and DTX requires that DTX is enzymatically active, since inhibitors of DTX-mediated protein synthesis inhibition resulted in loss of synergy. When the plant toxin ricin was used, there was no synergy with anti-Fas antibody but rather an additive effect. The synergy was not obtained in a TNF receptor-negative line but was achieved with other anti-Fas-resistant lines. Cell lines resistant to either Adriamycin or cis-platinum were rendered sensitive by the combination of drug and anti-Fas antibody. Further, combination treatment of anti-Fas and Adriamycin overcame resistance of the gp 170-expressing, multidrug-resistant MDR ovarian line. In all cases, cytotoxicity was augmented by pretreatment of target cells with gamma-interferon which upregulates Fas antigen expression. These results show that anti-Fas antibody can synergize in cytotoxicity with toxins and chemotherapeutic drugs, and combination treatment can reverse resistance to TNF, toxins, and/or drugs.
An FPGA-based flexible demo-board for endoscopic capsule design optimization (2010)

This work presents a flexible demo system, based on Field Programmable Gate Array (FPGA), that was specifically designed for testing all elements which have to be integrated in an endoscopic capsule, such as an image compression engine, a high-speed telemetric system, illumination system and inertial sensors. Several elements were tested and evaluated, obtaining a maximum frame rate of 19 fps over a transmission channel of 1.5 Mbit/s. The final configuration was chosen for the development of a miniaturized endoscopic capsule prototype.
Commentary Paradoxical roles of IFN-γ in models of Th1-mediated (2002)

T-cell responses to antigens are classified on the basis of the cytokines they produce as either Th1 (IFN-γ, IL-2) or Th2 (IL-4, IL-10), with these Th types being indicative of either cell-mediated or antibody-mediated responses, respectively. Using this classification, T-cell responses in MHC-class-IIrestricted autoimmune diseases appear to be predominantly of the Th1 type, based on the presence of high levels of IFN-γ. This simplistic classification has recently been challenged, however, as disease incidence and severity are frequently elevated in animals that have a deficient IFN-γ response. The recent data discussed here indicate that the cytokine circuits involved in the regulation of cell-mediated and humoral immune responses during the development of autoimmune arthritis are more complex than originally proposed; perhaps our characterization of autoimmune responses as strictly Th1 or Th2 is overly simplistic, especially as it pertains to the role of IFN-γ.
Heregulin targets gamma-catenin to the nucleolus by a mechanism dependent on the DF3/MUC1 oncoprotein. (2003)

The DF3/MUC1 transmembrane oncoprotein is aberrantly overexpressed in most human breast carcinomas and interacts with the Wnt effector gamma-catenin. Here, we demonstrate that MUC1 associates constitutively with ErbB2 in human breast cancer cells and that treatment with heregulin/neuregulin-1 (HRG) increases the formation of MUC1-ErbB2 complexes. The importance of the MUC1-ErbB2 interaction is supported by the demonstration that HRG induces binding of MUC1 and gamma-catenin and targeting of the MUC1-gamma-catenin complex to the nucleolus. Significantly, nucleolar localization of gamma-catenin in response to HRG is dependent on MUC1 expression. Moreover, mutation of a RRK motif in the MUC1 cytoplasmic domain abrogates HRG-induced nucleolar localization of MUC1 and gamma-catenin. In concert with these results, we show nucleolar localization of MUC1 and gamma-catenin in human breast carcinomas but not in normal mammary ductal epithelium. These findings demonstrate that MUC1 functions in cross talk between ErbB2 and Wnt pathways by acting as a shuttle for HRG-induced nucleolar targeting of gamma-catenin.
Pathogen elimination and prevention within a regulated, Designated Pathogen Free, closed pig herd for long‐term breeding and production of xenotransplantation materials (2018)

Ten years after PCV clearance following the second outbreak, due to strict adherence to biosecurity protocols and based on ongoing sentinel diagnostic monitoring (currently monthly), the herd remains DPF including PCV negative.
Detection of ERK activation by a novel monoclonal antibody (1997)

The mitogen-activated protein kinase, ERK is activated by a dual phosphorylation on threonine and tyrosine residues. Using a synthetic diphospho peptide, we have generated a monoclonal antibody directed to the active ERK. The antibody specifically identified the active doubly phosphorylated, but not the inactive mono- or non- phosphorylated forms of ERKs. A direct correlation was observed between ERK activity and the intensity in Western blot of mitogen-activated protein kinases from several species. The antibody was proven suitable for immunofluorescence staining, revealing a transient reactivity with ERKs that were translocated to the nucleus upon stimulation. In conclusion, the antibody can serve as a useful tool in the study of ERK signaling in a wide variety of organisms.
Slant-Hole Completion Test in the Piceance Basin, Colorado (1991)

ABSTRACT The Piceance Basin of western Colorado contains a major gas resource in the tight naturally fractured sandstones, siltstones and coals in the Mesaverde. The objective of the Slant Hole Completion Test, funded by the U.S. Department of Energy, is to evaluate directional and horizontal drilling as an alternate development strategy for these reservoirs. The well is located 700 ft south of the DOE Multiwell Experiment site in Section 34, T6S, R94W, Garfield County, Colorado. The hole was designed to intersect the paludal Mesaverde at 60° beneath the Multiwell pad and continue north to intersect the Cozzette close to 90°. The well is positioned to drill normal to the regional fracture system. Coring operations included a coal pressure core, 276 ft of conventional core across two paludal sandstones, and 118 ft of conventional core perpendicular to the natural fracture system in the Cozzette. Drilling operations proceeded as planned through the first build interval, pressure coring, and conventional coring in the 60° hole. Subsequent caving in the coal and in the adjacent naturally fractured siltstone, in conjunction with lost circulation in the Rollins, necessitated prematurely running 7-in. casing below the Rollins. The remaining 800 ft of hole drilled was 6-in. diameter, cased with 4-1/2-in. liner. The high hole angle, in conjunction with the long tangent (60°) section (1,824 ft), made sliding the 4-3/4-in. motors in the second build extremely difficult. Drillpipe conveyed logging operations were successfully conducted in the Cozzette.