gebhart/patrepeval huggingface dataset:
Bcl-2 targeting siRNA expressed by a T7 vector system inhibits human tumor cell growth in vitro (2004)

A T7 promoter driven siRNA expression vector system (Bcl-2/T7) that targets Bcl-2 mRNA in MCF-7 human cancer cells was designed in the present study. In the presence of prebound T7 RNA polymerase, successful expression of Bcl-2 siRNA as well as its function was demonstrated via cell proliferation assays, Bcl-2 Elisa, and TUNEL assay. MCF-7 breast cancer cells transfected with Bcl-2/T7 show decreased levels of Bcl-2 expression at the protein level as well as decreased cell proliferation. Also, the number of apoptotic cells was increased in cells expressing Bcl-2 siRNA. Previous studies have shown that Bcl-2 levels are increased in a large number of different types of cancer. Therefore, the ability of Bcl-2/T7 to produce functional Bcl-2 siRNA in breast cancer cells suggests a potential role for this delivery system in cancer gene therapy.
Cutting Edge: TLR4 Activation Mediates Liver Ischemia/Reperfusion Inflammatory Response via IFN Regulatory Factor 3-Dependent MyD88-Independent Pathway (2004)

The triggering molecular mechanism of ischemia-reperfusion injury (IRI), which in clinical settings results in excessive and detrimental inflammatory responses, remains unclear. This study analyzes the role of the TLR system in an established murine model of liver warm ischemia followed by reperfusion. By contrasting in parallel TLR knockout mice with their wild-type counterparts, we found that TLR4, but not TLR2, was specifically required in initiating the IRI cascade, as manifested by liver function (serum alanine aminotransferase levels), pathology, and local induction of proinflammatory cytokines/chemokines (TNF-alpha, IL-6, IFN-inducible protein 10). We then investigated the downstream signaling pathway of TLR4 activation. Our results show that IFN regulatory factor 3, but not MyD88, mediated IRI-induced TLR4 activation leading to liver inflammation and hepatocellular damage. This study documents the selective usage of TLR in a clinically relevant noninfectious disease model, and identifies a triggering molecular mechanism in the pathophysiology of liver IRI.
Escherichia coli gpt gene provides dominant selection for vaccinia virus open reading frame expression vectors (1988)

Mycophenolic acid, an inhibitor of purine metabolism, was shown to block the replication of vaccinia virus in normal cell lines. This observation led to the development of a dominant one-step plaque selection system, based on expression of the Escherichia coli gpt gene, for the isolation of recombinant vaccinia viruses. Synthesis of xanthine-guanine phosphoribosyltransferase enabled only the recombinant viruses to form large plaques in a selective medium containing mycophenolic acid, xanthine, and hypoxanthine. To utilize the selection system efficiently, we constructed a series of plasmids that contain the E. coli gpt gene and allow insertion of foreign genes into multiple unique restriction endonuclease sites in all three reading frames between the translation initiation codon of a strong late promoter and synthetic translation termination sequences. The selection-expression cassette is flanked by vaccinia virus DNA that directs homologous recombination into the virus genome. The new vectors allow high-level expression of complete or partial open reading frames and rapid construction of recombinant viruses by facilitating the cloning steps and by simplifying their isolation. The system was tested by cloning the E. coli beta-galactosidase gene; in 24 h, this enzyme accounted for approximately 3.5% of the total infected-cell protein.
6-(Alkylamino)-9-alkylpurines. A New Class of Potential Antipsychotic Agents (1997)

A series of 6-(alkylamino)-9-alkylpurines was synthesized and evaluated for the property of antagonizing the behavioral effects in animals of the dopamine agonist apomorphine. This model for identifying potential antipsychotic agents is based on the hypothesis that agents that antagonize apomorphine-induced aggressive behavior in rats and apomorphine-induced climbing in mice, but that do not block stereotyped behavior, could have an antipsychotic effect in humans without producing extrapyramidal side effects. The antiaggressive-behavior activity of lead compound 1 (6-(dimethylamino)-9-(3-phenylalaninamidobenzyl)-9H-purine) was improved 48-fold with 6-(cyclopropylamino)-9-(cyclopropylmethyl)-2-(trifluoromethyl)-9H- purine (80) (po ED50 of 2 mg/kg), which was obtained through an iterative sequence of structure--activity relationship studies that encompassed evaluation of the effects of structure variations at the purine 9-, 6-, and 2-positions. Potency was enhanced with a 9-cyclopropyl group, the duration of action was improved with the 6-(cyclopropylamino) substituent, potency was further enhanced with an N-formyl prodrug, and an agent with reduced cardiovascular effect emerged with the 2-trifluoromethyl purine 80. This potential antipsychotic agent was not developed further due to undesirable effects on the stomach.
Identification and Biological Activity of the Active Metabolite of Clopidogrel (2000)

Like ticlopidine, the ADP receptor antagonist clopidogrel is inactive in vitro and must be administered i.v. or orally to exhibit antiaggregatory and antithrombotic activities. We have previously shown that hepatic metabolism is necessary for activity. This study demonstrates that an active metabolite can be generated from human liver microsomes incubated with clopidogrel. Using several analytical methodologies (LC/MS, NMR, chiral supercritical fluid chromatography), we have identified its structure. In vitro, this highly unstable compound, different from that formed from ticlopidine, exhibited all the biological activities of clopidogrel observed ex vivo: Irreversible inhibition of the binding of 33P-2MeS-ADP to washed human platelets (IC50) = 0.53 microM), selective inhibition of ADP-induced platelet aggregation (IC)50 = 1.8 microM) and ADP-induced adenylyl cyclase down-regulation. The irreversible modification of the ADP-receptor site which is responsible for the biological activity could be explained by the formation of a disulfide bridge between the reactive thiol group of the active metabolite and a cysteine residue of the platelet ADP receptor.
Spatial pattern of cdc2 expression in relation to meristem activity and cell proliferation during plant development. (1992)

The p34 protein kinase encoded by the cdc2 gene is a key component of the eukaryotic cell cycle required for the G1- to S-phase transition and entry into mitosis. To study the regulation of plant meristem activity and cell proliferation, we have examined the tissue-specific accumulation of cdc2 transcripts in Arabidopsis thaliana and the related crucifer radish (Raphanus sativus) by in situ hybridization using A. thaliana cdc2 cDNA sequences as a probe. cdc2 transcripts accumulated in leaf primordia and within the vegetative shoot apical meristem. During flower development, high levels of expression were observed in meristems, in the basal regions of developing organs, in the developing vasculature, and associated with rib meristems elaborated late in the development of some floral organs. In root tips, cdc2 transcripts accumulated in the meristematic region and adjacent daughter cells but were not detected in the quiescent center. There was strong hybridization throughout the pericycle, and a further localized accumulation of cdc2 transcripts was observed in the initial stages of the activation of a new meristem at sites of lateral root development. We conclude that cdc2 expression is a critical factor in the regulation of meristem activity and establishment of proliferative competence.
Overexpression of the insulin‐like growth factor I receptor in human colon carcinomas (2002)

Our results demonstrate that, in addition to IGF-II, a strong overexpression of IGF-IR is found in the majority of colorectal carcinomas, supporting the hypothesis of an important role of the IGF system in the pathogenesis of colorectal carcinoma.
Defective Interfering Passages of Sindbis Virus: Nature of the Intracellular Defective Viral RNA (1974)

BHK cells infected with defective-interfering passages of Sindbis virus accumulate a species of RNA (20S) that is about half the molecular weight of the major viral mRNA (26S). We have performed competitive hybridization experiments with these species of RNA and have established that 20S RNA contains approximately 50% of the nucleotide sequences present in 26S RNA. Our further studies, however, demonstrate that 20S RNA is unable to carry out the messenger function of 26S RNA. We found very little of the defective RNA associated with polysomes in vivo. In addition, it was unable to stimulate protein synthesis in vitro under conditions in which 26S RNA was translated. We have also examined viral RNA synthesis in BHK cells infected with standard or defective-interfering passages of Sindbis virus. This comparison suggests that defective partioles do not synthesize a functional replicase.
Altered presynaptic protein NACP is associated with plaque formation and neurodegeneration in Alzheimer's disease. (1996)

We have recently identified, in the brain tissue of patients afflicted with Alzheimer's disease (AD), the non-A beta component of AD amyloid (NAC) as a new constituent of amyloid. NAC is derived from a larger precursor, NACP, a presynaptic protein. To better understand the role of NACP/NAC in the pathogenesis of AD, we used semiquantitative immunoblotting and combined double-immunocytochemistry/laser scanning confocal microscopy to study the concentration and distribution of NACP/NAC in human brain, and compared them to the concentration and distribution of the presynaptic marker synaptophysin and the amyloid marker A beta. The semiquantitative immunoblotting demonstrated that the NACP concentration is slightly increased in the AD frontal cortex without statistical significance, whereas synaptophysin was reduced in its levels in AD. Consequently the proportion of NACP/synaptophysin was more than double in the AD frontal cortex as compared with controls. In the AD neocortex, NACP was colocalized with approximately 80% of the synaptophysin-immunoreactive structures (presumably the presynaptic terminals) and with the dystrophic neuritic component of the plaques. Computer-aided analysis showed that numbers of NACP-immunoreactive structures along synaptophysin-immunoreactive structures were significantly diminished (30 to 40%) in AD. Although the overall numbers of NACP-positive structures were decreased, there was a significant increase in the intensity of NACP-immunoreactivity per structure in AD. This increased intensity of NACP immunoreactivity per structure in AD was not observed with anti-synaptophysin, consistent with immunoblotting-based quantification. Antibodies against NAC immunoreacted with amyloid in 35% of the diffuse plaques and 55% of the mature plaques. Normal aged control brains containing small groups of diffuse plaques were negative with anti-NAC. Double-immunolabeling studies with A beta antibodies showed that NAC immunoreactivity is more abundant in the center portion of amyloid rather than in the periphery. These studies suggest that there is a connection between metabolism of presynaptic proteins and amyloid formation, and that NAC might follow diffuse A beta accumulation resulting in the formation of compact amyloid and mature plaques.
A new technique for recording compliance of human hand veins. (1981)

1 A new technique for determining venous compliance at a standardized congestion pressure has been developed based on the optical method described by Nachev, Collier & Robinson (1971). It uses a linear variable differential transformer for a direct and continuous recording of venous compliance. 2 This method has been used to establish dose-response curves for the constrictor effects of noradrenaline, adrenaline, 5-hydroxytryptamine and dihydroergotamine after direct local infusion. 3 A parallel shift to the right of the noradrenaline dose-response curves was observed after local infusion of phentolamine, showing that the method can be used also to study interactions between agonists and antagonists on human veins in vivo. The usefulness of this technique for investigating the effects of orally administered drugs has also been established. The venoconstrictor action of dihydroergotamine reached its maximum after 1.5 h and remained almost constant for the period of observation (8 h).
General phase modulation method for stored waveform inverse Fourier transform excitation for Fourier transform ion cyclotron resonance mass spectrometry (1989)

A general phase modulation algorithm has been developed for the stored waveform inverse Fourier transform (SWIFT) excitation method used in Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR or FTMS). The algorithm, based on the time shifting theorem and the uncertainty principle, shows that the quadratic phase modulation is the theoretically optimal method for square magnitude spectral profiles. For more complicated magnitude spectral profiles, the corresponding phase functions can be generated through the algorithm by using a nonlinear grid on the frequency domain. The degree of dynamic range reduction can be estimated from a simple equation.
Recent developments in bacterial protein glycan coupling technology and glycoconjugate vaccine design (2012)

The discovery of the Campylobacter jejuni N-linked glycosylation system combined with its functional expression in Escherichia coli marked the dawn of a new era in glycoengineering. The process, termed protein glycan coupling technology (PGCT), has, in particular, been applied to the development of glycoconjugate vaccines. In this review, we highlight recent technical developments in this area, including the first structural determination of the coupling enzyme PglB, the use of glycotags for optimal glycan attachment and the possible applications of other glycosylation systems and how these may improve and extend PGCT.
Coronary artery disease mortality in patients treated for hodgkin's disease (1992)

The authors conducted a follow-up study of the association between mediastinal irradiation, chemotherapy, and mortality from coronary artery disease in 4665 patients treated for Hodgkin's disease. Study subjects were followed after the diagnosis of Hodgkin's disease until death or the closing date of the study. The average duration of follow-up was 7 years; 2415 patients died, and 124 cases of coronary artery disease were identified from death certificates, including 68 cases of acute myocardial infarction. The age-adjusted relative risks (RR) of death with any coronary artery disease after mediastinal irradiation and after chemotherapy were 1.87 (95% confidence interval [CI], 0.92 to 3.80) and 1.28 (CI, 0.77 to 2.15), respectively. A significantly increased risk of death in the subcategory myocardial infarction was observed after mediastinal irradiation (RR, 2.56; CI, 1.11 to 5.93) but not after chemotherapy (RR, 0.97; CI, 0.53 to 1.77). These results support the hypothesis that radiation therapy to the mediastinum increases the risk of coronary artery disease.
Metabolic and Cardiovascular Parameters in Type 1 Diabetes at Extreme Altitude (2004)

At extreme altitude, highly motivated trekkers with Type 1 diabetes but free from long-term complications present metabolic and cardiovascular parameters comparable with those of control subjects despite a worsening in metabolic control. This type of physical activity must be accompanied by careful glucose monitoring.
Electromagnetic near-field computations for a broadcast monopole using Numerical Electromagnetics Code (NEC) (1983)

Abstract : An often ignored aspect of electromagnetic radiation from antennas is the characterization of their near-fields. A computer program, Numerical Electromagnetics Code, is validated for accurate near-field computations and applied to a model of a broadcast monopole. E- and H-fields are plotted as a function of position along the antenna for various distances from the surface. The fields are also plotted as a function of radical distance outward for various heights. (Author)
A New Thrombus Imaging Agent Human Recombinant Fibrin Binding Domain Labeled With In-111 (1995)

The amino-terminal domain of fibronectin has a fibrin binding site and a site for covalent cross-linking to fibrin. This fibrin binding domain was isolated from human recombinant fibronectin and labeled with In-111; the final molecular weight was 12 kD. It was applied to a pilot study of 62 patients; 30 who were thought to have deep vein thrombosis and 32 controls. All 30 patients had either impedance plethysmography, duplex ultrasound, contrast venography, or various combinations of the three. Eight disagreements in the 30 patients suspected of having deep vein thrombosis were registered between fibrin binding domain imaging and the other examinations. Three of the patients with negative scan results had clots that were 1 week old or older, and this may be a limitation of the technique. In three other patients who had negative scan results, but positive alternative studies, there was a history of previous episodes of deep vein thrombosis and this could be a cause of false-positive results in the other modalities. There was one documented false-negative scan in a fresh clot. Normal scans were obtained in the lower extremities of the control patients, except in two who demonstrated uptake at the sites of insulin injections. The initial results of this feasibility study are encouraging and warrant further investigation.
Production and characterization of two human glioma xenograft-localizing monoclonal antibodies. (1986)

Multiple fusions following immunization of athymic mice with the extensively characterized human glioma cell line D-54 MG resulted in the selection of several antibodies (Mabs) highly reactive with tumors of neuroectodermal origin and unreactive with normal nervous system tissue. Two Mabs, C12 and D12, which localized specifically to tumors in athymic mouse-human glioma xenograft paired label localization assays, are IgG3 antibodies; both bind readily to staphylococcal protein A in column purification and radioimmunoprecipitation procedures. Both iodinate via the chloramine-T method yielding 125I-immunoreactive product by direct cell surface radioimmunoassay and absorption assay. By indirect cell surface radioimmunoassay, a cultured cell line panel consisting of 17 gliomas, 3 medulloblastomas, 2 neuroblastomas, 2 melanomas, and 2 fetal and 2 adult brain-derived cell lines was examined; the two Mabs were highly similar but distinct in their reactivity profiles. Each was positive with greater than 47% of the gliomas tested (C12, 9 of 17; D12, 8 of 17); and with 1 of 3 medulloblastomas, 1 of 2 melanomas, and cell lines derived from 12- and 16-week-gestation human fetal brain. No reactivity was observed with neuroblastoma or adult brain-derived cell lines or with neutral glycolipids and gangliosides extracted from D-54 MG xenografts or human glioma cell lines. Notable extraneuroectodermal reactivity included that of Mab D12 for splenic trabeculae and the spermatids and Sertoli cells in the testes. Following immunoprecipitation of [3H]leucine labeled cell membrane preparations, Mabs C12 and D12 have consistently yielded unique bands in the Mr 180,000 and Mr 88,000 regions respectively. When used in paired label localization experiments in s.c. D-54 MG xenograft-bearing athymic mice, Mabs C12 and D12 demonstrate similar localization patterns, attaining peak localization indices at day 3 (D12) or 4 (C12); the maximum percentage of injected Mab bound to tumor ranged from 5% (D12) to 8% (C12). The peak tumor/normal brain localization ratios (167-181) attained by these Mabs at days 1-2 followed by their rapid clearance suggest that these Mabs are potentially useful imaging and therapeutic agents for further investigation.
A Novel Method for Applying Reduced Graphene Oxide Directly to Electronic Textiles from Yarns to Fabrics (2013)

Conductive, flexible, and durable reduced RGO textiles with a facile preparation method are presented. BSA proteins serve as universal adhesives for improving the adsorption of GO onto any textile, irrespective of the materials and the surface conditions. Using this method, we successfully prepared various RGO textiles based on nylon-6 yarns, cotton yarns, polyester yarns, and nonwoven fabrics.
Two formal analyses of attack graphs (2003)

An attack graph is a succinct representation of all paths through a system that end in a state where an intruder has successfully achieved his goal. Today Red Teams determine the vulnerability of networked systems by drawing gigantic attack graphs by hand. Constructing attack graphs by hand is tedious, error-prone, and impractical for large systems. By viewing an attack as a violation of a safety property, we can use off-the-shelf model checking technology to produce attack graphs automatically: a successful path from the intruder's viewpoint is a counterexample produced by the model checker In this paper we present an algorithm for generating attack graphs using model checking as a subroutine. Security analysts use attack graphs for detection, defense and forensics. In this paper we present a minimization analysis technique that allows analysts to decide which minimal set of security measures would guarantee the safety of the system. We provide a formal characterization of this problem: we prove that it is polynomially equivalent to the minimum hitting set problem and we present a greedy algorithm with provable bounds. We also present a reliability analysis technique that allows analysts to perform a simple cost-benefit trade-off depending on the likelihoods of attacks. By interpreting attack graphs as Markov Decision Processes we can use the value iteration algorithm to compute the probabilities of intruder success for each attack the graph.
Pharmacokinetic/pharmacodynamic models for the depletion of Vβ5.2/5.3 T cells by the monoclonal antibody ATM‐027 in patients with multiple sclerosis, as measured by FACS (2004)

All aspects of effects of the monoclonal antibody ATM-027 on Vbeta5.2/5.3+ T cells were modelled and the phase II trial was simulated from phase I data. The effects of categorizing a continuous scale were also evaluated.
ANTIGENIC STUDIES OF CANDIDA (1961)

Hasenclever, H. F. (U. S. Public Health Service, Bethesda, Md.), and William O. Mitchell. Antigenic studies of Candida. I. Observations of two antigenic groups in Candida albicans. J. Bacteriol. 82:570-573. 1961.-Two distinct antigenic groups, detected by tube agglutination, have been observed among strains of Candida albicans. Adsorption of an antiserum with a heterologous strain did not remove the agglutinating properties for the homologous strain. Homologous adsorption of the antiserum did remove its agglutinating properties. Seventy-one isolates of C. albicans have been screened with this adsorbed antiserum and 38 were agglutinated at a serum dilution of 1:240 to 1:480 (group A), whereas 33 were not agglutinated at a serum dilution of 1:30 (group B). Thirty-five of the strains were studied with rabbit antisera prepared against each of six strains (three from each group). Agglutination reactions of these strains with samples of each antiserum adsorbed individually with each immunizing strain verified the results of the screening agglutination reactions. All the agglutinating properties of antisera prepared against the three group B strains were removed by adsorption with suspensions of either group A or group B strains. The identity of all isolates used in this study was confirmed by chlamydospore formation, fermentation, and carbohydrate assimilation reactions.