gebhart/patrepeval huggingface dataset:
Analysis and Detection of Malicious Insiders (2005)

Abstract insiders (an analyst, application administrator, and system administrator), measuring timeliness This paper summarizes a collaborative, six and accuracy of detection. month ARDA NRRC1 challenge workshop to characterize and create analysis methods to counter sophisticated malicious insiders in the 1. The Threat: Malicious Insiders United States Intelligence Community. Based An insider as anyone in an organization with approved upon a careful study of past and projected cases, access, privilege, or knowledge of information systems, we report a generic model of malicious insider information services, and missions. A malicious insider behaviors, distinguishing motives, (cyber and (MI) is one motivated to adversely impact an organiza-physical) actions, and associated observables. tion’s mission through a range of actions that compro-The paper outlines several prototype techniques mise information confidentiality, integrity, and/or avail-developed to provide early warning of insider ability. This research explores three fundamental hy-
The next generation of epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of lung cancer (2014)

The discovery of "driver" genomic alterations in patients with non-small cell lung cancer (NSCLC) has dramatically changed the field of thoracic oncology in recent years. The best understood of these molecular drivers are those involving the epidermal growth factor receptor (EGFR), which when aberrantly activated are integral to the development of a subset of NSCLC tumors. First-generation and second-generation tyrosine kinase inhibitors (TKIs) specific to the activated EGFR have shown significant efficacy and have brought about the era of targeted therapy for NSCLC. The most common resistance mechanism is a threonine-to-methionine substitution (T790M) in exon 20 of the EGFR gene. Although the previous standard of care in patients with EGFR-mutated NSCLC that progressed on initial TKI therapy was chemotherapy, third-generation EGFR TKIs have now been developed and have yielded promising results for this population of patients with NSCLC. This article reviews the emerging data regarding third-generation agents in the treatment of patients with advanced NSCLC.
High density microwave packaging program phase 1-Texas Instruments/Martin Marietta team (2002)

On the ARPA sponsored High Density Microwave Packaging (HDMP) program, a team composed of Texas Instruments (TI), Martin Marietta, and General Electric (GE) is developing a packaging system to support tile conformal phased arrays. Significant volume and weight reductions are projected relative to today's microwave module technology. The team's approach utilizes a stacked module configuration, with a surface contact vertical interconnect between module layers. The module layers are built on a metal matrix composite AlSiC substrate with silicon and MMIC devices mounted face-up in substrate wells. Chip-to-chip interconnect is provided by an enhanced version of Martin Marietta's Microwave High Density Interconnect (MHDI) process. Stacked module assemblies are surface mounted on an RF/DC manifold on the back of the conformal array surface. Incremental technology demonstrations are planned as part of the program, culminating in a 96-element brassboard array demonstration.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Laboratory Experiment Investigating Different Aspects of Catalase Activity in an Inquiry - Based Approach (1997)

The action of the enzyme catalase on aqueous hydrogen peroxide to generate oxygen gas is a well-established demonstration. Catalase is typically obtained by aqueous extraction of a potato, and the potato extract is mixed together with 3% hydrogen peroxide. The oxygen that is produced can be collected over water. Variations on the procedure can demonstrate the dependence of catalytic activity on temperature or the presence of inhibitors.
Native and β-cyclodextrin-enclosed curcumin: entrapment within liposomes and theirin vitrocytotoxicity in lung and colon cancer (2012)

With a view to improving the solubility and delivery characteristics of poorly water-soluble drugs, we prepared β-cyclodextrin-curcumin (βCD-C) inclusion complexes (hydrophilic curcumin) and entrapped both native curcumin (hydrophobic) and the complexes separately into liposomes; these were then assessed for in vitro cytotoxicity in lung and colon cancer cell lines. Optimization of curcumin entrapment within βCD was achieved, with the resultant βCD-C complexes prepared by methanol reflux. Inclusion complexes were confirmed using UV spectroscopy, Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction. The water solubility of βCD-C complexes improved markedly (c.f. native curcumin) and successful entrapment of complexes into liposomes, prepared using a thin-film hydration approach, was also achieved. All the liposomal formulations were characterized for curcumin and βCD-C complex entrapment efficiency, particle size, polydispersity and stability at 2-8°C. Curcumin, βCD-C complex and their optimized liposomal formulations were evaluated for anticancer activity in lung (A-459) and colon (SW-620) cancer cell lines. All curcumin-containing formulations tested were effective in inhibiting cell proliferation, as determined via an MTT assay. The median effective dose (EC(50)) for all curcumin formulations was found to be in the low µM range for both lung and colon cancer cell lines tested. Our results confirm that βCD inclusion complexes of poorly water soluble drugs, such as curcumin can be entrapped within biocompatible vesicles such as liposomes, and this does not preclude their anticancer activity.
Trichomonas vaginalis Is Associated with Pelvic Inflammatory Disease in Women Infected with Human Immunodeficiency Virus (2002)

We assessed the association between the causative agents of vaginal discharge and pelvic inflammatory disease (PID) among women attending a rural sexually transmitted disease clinic in South Africa; the role played by coinfection with human immunodeficiency virus type 1 (HIV-1) was studied. Vaginal and cervical specimens were obtained to detect Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, and bacterial vaginosis. HIV-1 infection was established by use of serum antibody tests. A total of 696 women with vaginal discharge were recruited, 119 of whom had clinical PID. Patients with trichomoniasis had a significantly higher risk of PID than did women without trichomoniasis (P = .03). PID was not associated with any of the other pathogens. When the patients were stratified according to HIV-1 status, the risk of PID in HIV-1-infected patients with T. vaginalis increased significantly (P = .002); no association was found in patients without HIV-1. T. vaginalis infection of the lower genital tract is associated with a clinical diagnosis of PID in HIV-1-infected women.
Mass Screening for Untreated Atrial Fibrillation (2015)

URL: http://www.clinicaltrials.gov. Unique identifier: NCT01593553.
Lessons Learned from the Irinotecan Metabolic Pathway (2003)

Irinotecan, a camptothecin analogue, is a prodrug which requires bioactivation to form the active metabolite SN-38. SN-38 acts as a DNA topoisomerase I poison. Irinotecan has been widely used in the treatment of metastatic colorectal cancer, small cell lung cancer and several other solid tumors. However, large inter-patient variability in irinotecan and SN-38 disposition, as well as severe but unpredictable diarrhea limits the clinical potential of irinotecan. Intense clinical pharmacology studies have been conducted to elucidate its complicated metabolic pathways and to provide scientific rationale in defining strategies to optimize drug therapy. Irinotecan is subjected to be shunted between CYP3A4 mediated oxidative metabolism to form two inactive metabolites APC or NPC and tissue carboxylesterase mediated hydrolysis to form SN-38 which is eventually detoxified via glucuronidation by UGT1A1 to form SN-38G. The pharmacology of this compound is further complicated by the existence of genetic inter-individual differences in activation and deactivation enzymes of irinotecan (e.g., CYP3A4, CYP3A5, UGT1A1) and sharing competitive elimination pathways with many concomitant medications, such as anticonvulsants, St. John's Wort, and ketoconazole. Efflux of the parent compound and metabolites out of cells by several drug transporters (e.g., Pgp, BCRP, MRP1, MRP2) also occurs. This review highlights the latest findings in drug activation, transport mechanisms, glucuronidation, and CYP3A-mediated drug-drug interactions of irinotecan in order to unlock some of its complicated pharmacology and to provide ideas for relevant future studies into optimization of this promising agent.
Adeno-associated viral serotypes produce differing titers and differentially transduce neurons within the rat basal and lateral amygdala (2014)

For laboratories producing their own recombinant adeno-associated viruses, the use of AAV2/2 is likely less desirable since AAV2/2 produces significantly lower titers than many other serotypes of AAV. Numerous AAV serotypes appear to efficiently transduce BLA neurons, with the exception of AAV2/5. Taking into consideration the ability of certain serotypes to achieve high titers and transduce BLA neurons well, in our hands AAV2/DJ8 and AAV2/9 appear to be ideal serotypes to use when targeting neurons within the BLA.
Influenza-Specific Antibody-Dependent Cellular Cytotoxicity: Toward a Universal Influenza Vaccine (2014)

There is an urgent need for universal influenza vaccines that can control emerging pandemic influenza virus threats without the need to generate new vaccines for each strain. Neutralizing Abs to the influenza virus hemagglutinin glycoprotein are effective at controlling influenza infection but generally target highly variable regions. Abs that can mediate other functions, such as killing influenza-infected cells and activating innate immune responses (termed "Ab-dependent cellular cytotoxicity [ADCC]-mediating Abs"), may assist in protective immunity to influenza. ADCC-mediating Abs can target more conserved regions of influenza virus proteins and recognize a broader array of influenza strains. We review recent research on influenza-specific ADCC Abs and their potential role in improved influenza-vaccination strategies.
Hydrogen storage in aligned carbon nanotubes (2001)

Aligned carbon nanotubes (CNTs) with diameters of 50–100 nm, synthesized by plasma-assisted hot filament chemical vapor deposition, were employed for hydrogen adsorption experiments in their as-prepared and pretreated states. Quadruple mass spectroscopy and thermogravimetric analysis show a hydrogen storage capacity of 5–7 wt% was achieved reproducibly at room temperature under modest pressure (10 atm) for the as-prepared samples. Pretreatments, which include heating the samples to 300 °C and removing of the catalyst tips, can increase the hydrogen storage capacity up to 13 wt% and decrease the pressure required for storage. The weight gains were measured after the samples moved out of the hydrogen environment. The release of the adsorbed hydrogen can be achieved by heating the samples up to 300 °C.
The Markov Process in Medical Prognosis (1983)

The physician's estimate of prognosis under alternative treatment plans is a principal factor in therapeutic decision making. Current methods of reporting prognosis, which include five-year survivals, survival curves, and quality-adjusted life expectancy, are crude estimates of natural history. In this paper we describe a general-purpose model of medical prognosis based on the Markov process and show how this simple mathematical tool may be used to generate detailed and accurate assessments of life expectancy and health status.
Withaferin A inhibits breast cancer invasion and metastasis at sub‐cytotoxic doses by inducing vimentin disassembly and serine 56 phosphorylation (2011)

Withaferin A (WFA) is purified from the plant Withania somnifera and inhibits the vimentin cytoskeleton. Vimentin overexpression in cancer correlates with metastatic disease, induction of epithelial to mesenchymal transition and reduced patient survival. As vimentin functions in cell motility, we wanted to test the hypothesis that WFA inhibits cancer metastasis by disrupting vimentin function. These data showed that WFA had weak cytotoxic and apoptotic activity at concentrations less than or equal to 500 nM, but retained potent anti-invasive activity at these low doses. Imaging of breast cancer cell lines revealed that WFA induces perinuclear vimentin accumulation followed by rapid vimentin depolymerization. A concomitant induction of vimentin ser56 phosphorylation was observed, which is consistent with vimentin disassembly. Structure activity relationships were established using a set of chemically modified WFA analogs and showed that the predicted vimentin-binding region of WFA is necessary to induce vimentin ser56 phosphorylation and for its anti-invasive activity. Pharmacokinetic studies in mice revealed that WFA reaches peak concentrations up to 2 μM in plasma with a half-life of 1.36 hr following a single 4 mg/kg dose. In a breast cancer metastasis mouse model, WFA showed dose-dependent inhibition of metastatic lung nodules and induced vimentin ser56 phosphorylation, with minimal toxicity to lung tissue. Based upon these studies, we conclude that WFA is a potent breast cancer anti-metastatic agent and the anti-metastatic activity of WFA is, at least in part, mediated through its effects on vimentin and vimentin ser56 phosphorylation.
Digital filters (3rd ed.) (1989)

Tachykinins are excitatory neuropeptides synthesised in neuronal and glial cells of the human central and peripheral nervous system. They participate in both physiological and certain pathological conditions, i.e. synaptic transmission, nociception and neuroimmunomodulation. Tachykinins act as excitatory neurotransmitters and/or neuromodulators and induce DNA synthesis leading to stimulation of cell division and proliferation. Their biological responses are triggered via the well-established tachykinin receptors NK1, NK2 and NK3 that belong to the G protein-coupled receptor family (GPCRs). Substance P is the most important member of the tachykinin family that constitutes the major endogenous ligand for the NK1 receptor type. The presence of functional NK1 receptors has been documented in malignant brain tumours of glial origin. It has been evidenced that SP-NK1 receptor communication is involved in glioma development and progression. It is possible because the tumour cells display SP-mediated autocrine activity, the ability of cytokines stimulation and MAP kinases activation. It has been suggested that SP receptor antagonists application might be useful in attempts directed at anti-cancer therapy.
Synthesis and Dielectric Investigations of New Swallow-Tailed Monomers and Polymers (1993)

Abstract A new class of liquid crystalline side chain polymers using swallow-tailed mesogens was synthesized. Comparative dielectric investigations on these polymers and on the corresponding low molecular weight substances in the frequency range from 10 Hz to 100 kHz should give information about the dynamic behaviour. The results obtained from the monomers agree well with those of other swallow-tailed liquid crystals and can be explained by an antiparallel orientation of the molecules in the S A phase. There are hints to a tendency to an antiparallel orientation of the side chains in the polymers, too. Key Words: synthesisswallow-tailed monomerspolymersdielectric investigationsantiparallel order
Characterization of the putative fusogenic domain in vesicular stomatitis virus glycoprotein G (1994)

The envelope glycoprotein G of vesicular stomatitis virus induces membrane fusion at low pH. Site-directed mutagenesis of specific amino acids within a segment spanning amino acids 123 to 137 of G protein, which is highly conserved in vesiculoviruses and was previously shown by us to be involved in fusogenic activity (Y. Li, C. Drone, E. Sat, and H. P. Ghosh, J. Virol. 67:4070-4077, 1993), was used to determine the role of this region in low-pH-induced membrane fusion. The mutant glycoproteins expressed in COS cells were assayed for acid-pH-induced cell-cell fusion. Substitution of the variant Pro-123 with Leu had no effect on the fusogenic activity, while substitution of conserved Phe-125 and Asp-137 with Tyr and Asn, respectively, shifted the pH optimum of membrane fusion to a more acidic pH value and decreased the fusion efficiency. The deletion of amino acid residues 124 to 127, 131 to 137, or 124 to 137 produced mutants defective in transport. Mutation of the conserved residues Gly-124 and Pro-127 to Ala and to Gly or Leu, respectively, inhibited cell-cell fusion activity by about 90% without affecting transport of the mutant proteins to the cell surface, suggesting that these two residues may be present within the fusion peptide and thus may be directly involved in fusion. This highly conserved domain containing neutral amino acids of G protein may therefore represent the putative fusion domain of vesicular stomatitis virus G protein.
Ferroelectric nematic suspension (2003)

We report on the development of a dilute suspension of ferroelectric particles in a nematic liquid-crystal (LC) host. We found that the submicron particles do not disturb the LC alignment and the suspension macroscopically appears similar to a pure LC with no readily apparent evidence of dissolved particles. The suspension possesses enhanced dielectric anisotropy, and is sensitive to the sign of an applied electric field.
Session Based Admission Control: A Mechanism for Improving the Performance of an Overloaded Web Server (1998)

This article discusses the decisions involved with hiring a consultant for the medical practice: when to hire one, how to locate the best one for a particular practice, finding a consultant and analyzing their skills in terms of the needs of the practice, and other essential advice to provide the medical practitioner with a basis for making a decision on consultants. The Achilles heel of doctors is the tendency to think they should be able to fix all problems on their own, thus often delay in seeking help for their practice that can alleviate existing problems or keep a practice on track with success. This often leads to excessively long work hours or compounding of problems, when a simple fix could be the solution when analyzed by an outside consultant. Approaches to determining the appropriateness of a particular consultant are presented, along with questions to ask when determining the expertise and the "fit" of a consultant.
Neuromedin B receptor in esophagus: evidence for subtypes of bombesin receptors (1989)

To identify receptors for bombesin-related peptides in the rat esophagus, we measured binding of 125I-Bolton-Hunter neuromedin B (125I-BH-neuromedin B) and 125I-[Tyr4]bombesin to tissue sections from the rat esophagus and compared the results with those for rat pancreas. Esophagus bound both tracers, whereas pancreas bound only 125I-[Tyr4]bombesin. In each tissue binding was saturable, dependent on pH, on time, and on temperature, reversible, and specific. Autoradiography demonstrated binding of both tracers only to the muscularis mucosae of the esophagus and binding of 125I-[Tyr4]bombesin diffusely over pancreatic acini. In the esophagus, the relative potencies for inhibition of binding of both tracers were as follows: neuromedin B greater than bombesin greater than GRP = neuromedin C; similar relative potencies were found for causing contraction of muscle strips from whole esophagus and from the isolated muscularis mucosae. In pancreas tissue sections and dispersed acini, the relative potencies for inhibition of binding of 125I-[Tyr4]bombesin were as follows: bombesin greater than GRP = neuromedin C much greater than neuromedin B. Similar relative potencies were found for stimulation of enzyme secretion from dispersed pancreatic acini. Computer analysis in both tissues demonstrated only a single binding site. The present study demonstrates that rat esophagus muscle possesses specific receptors for bombesin-related peptides. Furthermore, this study shows that the esophageal bombesin receptors represent a previously unidentified class of bombesin receptors in that they have a higher affinity for neuromedin B than for bombesin. In contrast, the pancreatic bombesin receptors have, like all other bombesin receptors described to date, a high affinity for bombesin, but low affinity for neuromedin B.
Identification of Novel Benzoylformate Decarboxylases by Growth Selection (2006)

ABSTRACT A growth selection system was established using Pseudomonas putida , which can grow on benzaldehyde as the sole carbon source. These bacteria presumably metabolize benzaldehyde via the β-ketoadipate pathway and were unable to grow in benzoylformate-containing selective medium, but the growth deficiency could be restored by expression in trans of genes encoding benzoylformate decarboxylases. The selection system was used to identify three novel benzoylformate decarboxylases, two of them originating from a chromosomal library of P. putida ATCC 12633 and the third from an environmental-DNA library. The novel P. putida enzymes BfdB and BfdC exhibited 83% homology to the benzoylformate decarboxylase from P. aeruginosa and 63% to the enzyme MdlC from P. putida ATCC 12633, whereas the metagenomic BfdM exhibited 72% homology to a putative benzoylformate decarboxylase from Polaromonas naphthalenivorans . BfdC was overexpressed in Escherichia coli , and the enzymatic activity was determined to be 22 U/ml using benzoylformate as the substrate. Our results clearly demonstrate that P. putida KT2440 is an appropriate selection host strain suitable to identify novel benzoylformate decarboxylase-encoding genes. In principle, this system is also applicable to identify a broad range of different industrially important enzymes, such as benzaldehyde lyases, benzoylformate decarboxylases, and hydroxynitrile lyases, which all catalyze the formation of benzaldehyde.
Characterization of recombinant plasminogen activator production by primate endothelial cells transduced with retroviral vectors (1994)

Retroviral vector-mediated expression of plasminogen activators (PAs) from endothelial cells (ECs) has been proposed as a potential therapeutic approach for intravascular thrombosis. To define the potential for gene transfer to increase fibrinolytic activity in a primate system, baboon ECs were transduced with retroviral vectors expressing wild-type and glycosylphosphatidylinositol-anchored urokinase, as well as wild-type and serpin-resistant tissue PA (t-PA). Expression of either t-PA or urokinase was increased by one log over baseline levels. There was no specific effect of either t-PA or urokinase overexpression on endogenous t-PA, urokinase, or PA inhibitor 1 (PAI-1) expression. Recombinant urokinase could be anchored to the cell surface at a level eight-fold above that of receptor-bound urokinase. The majority of secreted urokinase accumulated in conditioned medium as a free proenzyme, whereas both wild-type and serpin-resistant t-PA accumulated almost exclusively in complexes with PAI-1. In most but not all of the assays, the urokinase vectors conferred PA activity above that of the t-PA vectors. These data show that PA synthesis and activity are specifically increased subsequent to retroviral vector-mediated gene transfer in primate ECs. However, definition of an optimal PA vector will require in vivo experimentation.