gebhart/patrepeval huggingface dataset:
Agent Tcl: a flexible and secure mobile-agent system (1998)

A mobile agent is an autonomous program that can migrate under its own control from machine to machine in a heterogeneous network. In other words, the program can suspend its execution at an arbitrary point, transport itself to another machine, and then resume execution from the point of suspension. Mobile agents have the potential to provide a single, general framework in which a wide range of distributed applications can be implemented efficiently and easily. Several challenges must be faced, however, most notably reducing migration overhead, protecting a machine from malicious agents (and an agent from malicious machines), and insulating the agent against network and machine failures. Agent Tcl is a mobile-agent system under development at Dartmouth College that has evolved from a Tcl-only system into a multiple-language system that currently supports Tcl, Java, and Scheme. In this thesis, we examine the motivation behind mobile agents, describe the base Agent Tcl system and its sec...
In Vitro Proteolytic Processing of the MD145 Norovirus ORF1 Nonstructural Polyprotein Yields Stable Precursors and Products Similar to Those Detected in Calicivirus-Infected Cells (2003)

The MD145-12 strain (GII/4) is a member of the genus Norovirus in the Caliciviridae and was detected in a patient with acute gastroenteritis in a Maryland nursing home. The open reading frame 1 (ORF1) (encoding the nonstructural polyprotein) was cloned as a consensus sequence into various expression vectors, and a proteolytic cleavage map was determined. The virus-encoded cysteine proteinase mediated at least five cleavages (Q(330)/G(331), Q(696)/G(697), E(875)/G(876), E(1008)/A(1009), and E(1189)/G(1190)) in the ORF1 polyprotein in the following order: N-terminal protein; nucleoside triphosphatase; 20-kDa protein (p20); virus protein, genome linked (VPg); proteinase (Pro); polymerase (Pol). A time course analysis of proteolytic processing of the MD145-12 ORF1 polyprotein in an in vitro coupled transcription and translation assay allowed the identification of stable precursors and final mapped cleavage products. Stable precursors included p20VPg (analogous to the 3AB of the picornaviruses) and ProPol (analogous to the 3CD of the picornaviruses). Less stable processing intermediates were identified as p20VPgProPol, p20VPgPro, and VPgPro. The MD145-12 Pro and ProPol proteins were expressed in bacteria as active forms of the proteinase and used to further characterize their substrate specificities in trans cleavage assays. The MD145-12 Pro was able to cleave its five mapped cleavage sites in trans and, in addition, could mediate trans cleavage of the Norwalk virus (GI/I) ORF1 polyprotein into a similar proteolytic processing profile. Taken together, our data establish a model for proteolytic processing in the noroviruses that is consistent with nonstructural precursors and products identified in studies of caliciviruses that replicate in cell culture systems.
Discovery and identification of serum potential biomarkers for pulmonary tuberculosis using iTRAQ‐coupled two‐dimensional LC‐MS/MS (2013)

Pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis is a chronic disease. Currently, there are no sufficiently validated biomarkers for early diagnosis of TB infection. In this study, a panel of potential serum biomarkers was identified between patients with pulmonary TB and healthy controls by using iTRAQ-coupled 2D LC-MS/MS technique. Among 100 differentially expressed proteins screened, 45 proteins were upregulated (>1.25-fold at p < 0.05) and 55 proteins were downregulated (<0.8-fold at p < 0.05) in the TB serum. Bioinformatics analysis revealed that the differentially expressed proteins were related to the response to stimulus, the metabolic and immune system processes. The significantly differential expression of apolipoprotein CII (APOCII), CD5 antigen-like (CD5L), hyaluronan-binding protein 2 (HABP2), and retinol-binding protein 4 (RBP4) was further confirmed using immunoblotting and ELISA analysis. By forward stepwise multivariate regression analysis, a panel of serum biomarkers including APOCII, CD5L, and RBP4 was obtained to form the disease diagnostic model. The receiver operation characteristic curve of the diagnostic model was 0.98 (sensitivity = 93.42%, specificity = 92.86%). In conclusion, APOCII, CD5L, HABP2, and RBP4 may be potential protein biomarkers of pulmonary TB. Our research provides useful data for early diagnosis of TB.
Inflammasome Activation by Adenylate Cyclase Toxin Directs Th17 Responses and Protection against Bordetella pertussis (2010)

Inflammasome-mediated IL-1beta production is central to the innate immune defects that give rise to certain autoinflammatory diseases and may also be associated with the generation of IL-17-producing CD4(+) T (Th17) cells that mediate autoimmunity. However, the role of the inflammasome in driving adaptive immunity to infection has not been addressed. In this article, we demonstrate that inflammasome-mediated IL-1beta plays a critical role in promoting Ag-specific Th17 cells and in generating protective immunity against Bordetella pertussis infection. Using a murine respiratory challenge model, we demonstrated that the course of B. pertussis infection was significantly exacerbated in IL-1R type I-defective (IL-1RI(-/-)) mice. We found that adenylate cyclase toxin (CyaA), a key virulence factor secreted by B. pertussis, induced robust IL-1beta production by dendritic cells through activation of caspase-1 and the NALP3-containing inflammasome complex. Using mutant toxins, we demonstrate that CyaA-mediated activation of caspase-1 was not dependent on adenylate cyclase enzyme activity but was dependent on the pore-forming capacity of CyaA. In addition, CyaA promoted the induction of Ag-specific Th17 cells in wild-type but not IL-1RI(-/-) mice. Furthermore, the bacterial load was enhanced in IL-17-defective mice. Our findings demonstrate that CyaA, a virulence factor from B. pertussis, promotes innate IL-1beta production via activation of the NALP3 inflammasome and, thereby, polarizes T cell responses toward the Th17 subtype. In addition to its known role in subverting host immunity, our findings suggest that CyaA can promote IL-1beta-mediated Th17 cells, which promote clearance of the bacteria from the respiratory tract.
MOSES: Supporting and Enforcing Security Profiles on Smartphones (2014)

Smartphones are very effective tools for increasing the productivity of business users. With their increasing computational power and storage capacity, smartphones allow end users to perform several tasks and be always updated while on the move. Companies are willing to support employee-owned smartphones because of the increase in productivity of their employees. However, security concerns about data sharing, leakage and loss have hindered the adoption of smartphones for corporate use. In this paper we present MOSES, a policy-based framework for enforcing software isolation of applications and data on the Android platform. In MOSES, it is possible to define distinct Security Profiles within a single smartphone. Each security profile is associated with a set of policies that control the access to applications and data. Profiles are not predefined or hardcoded, they can be specified and applied at any time. One of the main characteristics of MOSES is the dynamic switching from one security profile to another. We run a thorough set of experiments using our full implementation of MOSES. The results of the experiments confirm the feasibility of our proposal.
Third-generation architecture boosts speed and density of field-programmable gate arrays (2002)

Using a combination of architectural and process improvements, a third-generation family of field-programmable gate arrays (FPGAs) features up to twice the density and speed of currently-available FPGA devices. The architecture was devised to allow complete and efficient automated design implementation of FPGA-based designs, as well as maximum density and performance. This architecture is described. User-configurable on-chip static memory resources further contribute to the high integration levels available to users of the third-generation devices.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The Cyclin K/Cdk12 complex maintains genomic stability via regulation of expression of DNA damage response genes (2011)

Various cyclin-dependent kinase (Cdk) complexes have been implicated in the regulation of transcription. In this study, we identified a 70-kDa Cyclin K (CycK) that binds Cdk12 and Cdk13 to form two different complexes (CycK/Cdk12 or CycK/Cdk13) in human cells. The CycK/Cdk12 complex regulates phosphorylation of Ser2 in the C-terminal domain of RNA polymerase II and expression of a small subset of human genes, as revealed in expression microarrays. Depletion of CycK/Cdk12 results in decreased expression of predominantly long genes with high numbers of exons. The most prominent group of down-regulated genes are the DNA damage response genes, including the critical regulators of genomic stability: BRCA1 (breast and ovarian cancer type 1 susceptibility protein 1), ATR (ataxia telangiectasia and Rad3-related), FANCI, and FANCD2. We show that CycK/Cdk12, rather than CycK/Cdk13, is necessary for their expression. Nuclear run-on assays and chromatin immunoprecipitations with RNA polymerase II on the BRCA1 and FANCI genes suggest a transcriptional defect in the absence of CycK/Cdk12. Consistent with these findings, cells without CycK/Cdk12 induce spontaneous DNA damage and are sensitive to a variety of DNA damage agents. We conclude that through regulation of expression of DNA damage response genes, CycK/Cdk12 protects cells from genomic instability. The essential role of CycK for organisms in vivo is further supported by the result that genetic inactivation of CycK in mice causes early embryonic lethality.
Improved procedure for preparation of optically active 3-hydroxyglutarate monoesters and 3-hydroxy-5-oxoalkanoic acids (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTImproved procedure for preparation of optically active 3-hydroxyglutarate monoesters and 3-hydroxy-5-oxoalkanoic acidsPeter D. Theisen and Clayton H. HeathcockCite this: J. Org. Chem. 1988, 53, 10, 2374–2378Publication Date (Print):May 1, 1988Publication History Published online1 May 2002Published inissue 1 May 1988https://pubs.acs.org/doi/10.1021/jo00245a051https://doi.org/10.1021/jo00245a051research-articleACS PublicationsRequest reuse permissionsArticle Views1126Altmetric-Citations104LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Addition of animal and microbial lipases to curd. Effects on free fatty acid composition during ripening (1991)

Cheese-making tests were conducted in the laboratory, using animal (kid, lamb, calf) and microbial lipases, present in various commercial formulations, to aid in the development of f1avour.The hydrolytic action of these lipases toward glycerides led to the Iiberation of substantial amounts of fatty acids whose composition showed distinct differences depending on the origin of the lipases that were utilized. Those of animal origin tended to liberate short chain fatty acids, mainly C 4 : 0 and C 6 : 0 , while those of microbial origin did not show any preference for low or high molecular weight fatty acids so that the composition of free fatty acids was almost the same as that of untreated samples. The different behaviour of these adjuvants in the development of the aroma allows various lipase selections to be made according to the intensity of the "sharp" flavour desired in the marketable product. lipase 1 curd 1 fatty acid compostlon Rsum -Addition de lipases d'origine animale et microbienne au caill. Effets sur la composition en acides gras libres au cours de la maturation. On a men des essais de fabrication de fromage au laboratoire, en utilisant comme additifs pour la formation du got "piquant, des lipases d'origine animale (chevreau, agneau, veau) et d'origine microbienne (Mucor miehei, Aspergillus niger) sous forme de prparations commerciales diverses. L'action hydrolytique considrable sur les glycrides a men la libration de grandes quantits d'acides gras libres dont la composition prsente des diffrences nettes suivant l'origine des enzymes utilises. Les lipases d'origine animale librent prfrentiellement des acides gras volatils, surtout C 4 : 0 et C 6 : 0 , tandis que celles d'origine microbienne ne manifestent aucune prfrence, ni pour les acides faible poids molculaire ni pour ceux haut poids molculaire, tant il est vrai que la composition des acides gras libres est presque gale celle observe dans l'chantillon non trait. La diffrence de comportement de ces additifs sur la formation de l'arme, permet de faire des choix selon /'intensit du got "piquant que l'on veut raliser dans le produit commercialiser. lipase / caill / composition des acides gras
Relationship of Lipoprotein-Associated Phospholipase A2 Mass and Activity with Incident Vascular Events among Primary Prevention Patients Allocated to Placebo or to Statin Therapy: An Analysis from the JUPITER Trial (2012)

Among JUPITER trial participants allocated to placebo, levels of Lp-PLA(2) activity, but not mass, were associated with cardiovascular risk. However, Lp-PLA(2) no longer predicted risk or modified clinical outcomes when participants were treated with rosuvastatin.
Reversibility of Adverse, Calcineurin-Dependent Cardiac Remodeling (2011)

Together, these data establish and define the deleterious effects of calcineurin signaling in the adult heart and reveal that calcineurin-dependent hypertrophy with concentric geometry precedes systolic dysfunction and heart failure. Furthermore, these findings demonstrate that during much of the disease process, calcineurin-dependent remodeling remains reversible.
A Simple Classification of Crohnʼs Disease: Report of the Working Party for the World Congresses of Gastroenterology, Vienna 1998 (2000)

Crohn's disease is a heterogeneous entity. Previous attempts of classification have been based primarily on anatomic location and behavior of disease. However, no uniform definition of patient subgroups has yet achieved broad acceptance. The aim of this international Working Party was to develop a simple classification of Crohn's disease based on objective variables. Eight outcome-related variables relevant to Crohn's disease were identified and stepwise evaluated in 413 consecutive cases, a database survey, and by clinical considerations. Allocation of variables was conducted with well-defined Crohn's disease populations from Europe and North America. Cross-table analyses were performed by chi-square testing. Three variables were finally elected: Age at Diagnosis [below 40 years (A1), equal to or above 40 years (A2)], Location [terminal ileum (L1), colon (L2), ileocolon (L3), upper gastrointestinal (L4)], and Behavior [nonstricturing nonpenetrating (B1), stricturing (B2), penetrating (B3)]. The allocation of patients to these 24 subgroups proved feasible and resulted in specific disease clusters. Cross-table analyses revealed associations between Age at Diagnosis and Location, and between Behavior and Location (all p < 0.001). The Vienna classification of Crohn's disease provides distinct definitions to categorize Crohn's patients into 24 subgroups. Operational guidelines should be used for the characterization of patients in clinical trials as well as for correlation of particular phenotypes with putative biologic markers or environmental factors.
An analysis of using high-frequency sinusoidal illumination to measure the 3D shape of translucent objects (2011)

Using optical triangulation methods to measure the shape of translucent objects is difficult because subsurface scattering contaminates measurements of the “direct” reflection at the surface. A number of recent papers have shown that high-frequency sinusoidal illumination patterns allow isolating this direct component, which in turn enables accurate estimation of the shape of translucent objects. Despite these encouraging results, there is currently no rigorous mathematical analysis of the expected error in the measured surface as it relates to the parameters of these systems: the frequency of the projected sinusoid, the geometric configuration of the source and camera, and the optical properties of the target object. We present such an analysis, which confirms earlier empirical results and provides a much needed tool for designing 3D scanners for translucent objects.
Tumor targeting with biotinylated tumor necrosis factor alpha: structure-activity relationships and mechanism of action on avidin pretargeted tumor cells. (1998)

We have recently described a new strategy for targeting biotinylated tumor necrosis factor-alpha (TNF-alpha) to tumors, based on pretargeting with biotinylated antibodies and avidin. Here, we have analyzed the structure-activity relationships of several biotin-TNF-alpha conjugates and studied the mechanism of their interaction with avidin and TNF-alpha receptors on tumor cells. The study has been carried out using an in vitro model based on human melanoma Colo 38 cells and monoclonal antibody 225, an antibody against the high molecular weight melanoma-associated antigen. Immunochemical and cytotoxicity studies showed that biotin-TNF-alpha but not TNF-alpha persists for several hours on the surface of cells pretargeted with biotin-monoclonal antibody 225 and avidin and triggers cytolytic effects. Studies on the mechanism of action showed that biotin-TNF-alpha trimers can slowly dissociate from targeted cells in a bioactive form, through trimer-monomer-trimer transitions. Structure-activity relationship studies showed that nonbiotinylated subunits must be present in the biotin-TNF-alpha trimers for efficient release of bioactive TNF-alpha. Colo 38 cells targeted with biotin-TNF-alpha were able to kill mouse L-M cells in coculture experiments, indicating that the released TNF-alpha can interact also with TNF-alpha receptors expressed by bystander cells. In conclusion, the targeting complex works as a system that slowly releases bioactive TNF-alpha in the microenvironment of the targeted cell. This opens up the possibility that cells other than those reached by the targeting antibody (e.g., endothelial cells and local cells of the immune system) can be affected in vivo.
Alvocidib Potentiates the Activity of Cytarabine and Mitoxantrone through the Targeting of MCL-1 When Administered in a Time Sequential Regimen in AML (2015)

Abstract Alvocidib has demonstrated a significant improvement in the complete response rates of newly diagnosed acute myeloid leukemia (AML) patients when administered before cytarabine and mitoxantrone (FLAM regimen) in a randomized Phase 2 study compared to 7+3, the current standard of care. Although the mechanism of action of alvocidib as a single agent is documented, the mechanism underlying synergy found in the FLAM regimen is still not fully understood. The FLAM regimen was originally developed based on the perceived benefit of time-sequential cell cycle arrest (alvocidib) followed by release of the cells from cell cycle arrest and inhibition of DNA replication (cytarabine) during S-phase. However, recent reports suggest that the transcriptional repression of key anti-apoptotic proteins (eg., MCL-1) mediated by alvocidib's CDK9 inhibition, drive the activity in the FLAM regimen. We, therefore, hypothesized that MCL-1 transcriptional repression constitutes the primary mechanism for the synergism observed with the treatment of the FLAM regimen. Here, we demonstrate that treatment with alvocidib, followed by treatment with cytarabine and mitoxantrone, is synergistic in vitro and correlates with the downregulation of MCL-1 expression. The FLAM regimen results in significant increases in caspase activity in comparison to any single agent within the combination. As has been previously reported, we also observe that increased activity of cytarabine in alvocidib-treated cells corresponds with progression into the S-phase of the cell cycle, following the washout of alvocidib. However, this observation accounts for only a small portion of the inhibition of cell proliferation. This is further confirmed by the observation that CDK4/6 (cell cycle) specific inhibitors, such as palbociclib, do not show synergistic increases in caspase activity following treatment in the same setting. In various AML cell lines treated with MCL-1 siRNA, followed by cytarabine and mitoxantrone treatment, we also observe a synergistic increase in the inhibition of cell proliferation. Therefore, considering our earlier work showing that MCL-1 dependence predicts AML patient response to the FLAM regimen, we propose that MCL-1 repression is the primary mechanism of alvocidib's biological activity and also a primary mechanism conferring resistance to cytarabine. We also conclude that the FLAM regimen is an effective regimen, clinically, in treating patients with high-risk AML, as a consequence of its inhibition of transcription via CDK9. Disclosures Kim: Tolero Pharmaceuticals: Employment. Bahr:Tolero Pharmaceuticals: Employment. Soh:Tolero Pharmaceuticals: Employment. Bearss:Tolero Pharmaceuticals: Employment. Lee:Tolero Pharmaceuticals: Employment. Peterson:Tolero Pharmaceuticals: Employment. Whatcott:Tolero Pharmaceuticals: Employment. Siddiqui-Jain:Tolero Pharmaceuticals: Employment. Weitman:Tolero Pharmaceuticals: Employment. Bearss:Tolero Pharmaceuticals: Employment. Warner:Tolero Pharmaceuticals: Employment.
Studies on the Dissolution of Glucose in Ionic Liquids and Extraction Using the Antisolvent Method (2013)

Biomass, the fibrous material derived from plant cell walls, is a potentially clean and renewable nonfood feedstock for liquid fuel and chemical production in future biorefineries. The capability of ionic liquids to act as selective solvents and catalysts for biomass processing has already been proven. Thus, they are considered as an alternative to conventional solvents. Nevertheless, phase equilibria with biomass derived compounds is still lacking in the literature. To overcome the lack of experimental data on phase equilibria of biomass carbohydrates in ionic liquids, the solubility of d-glucose in four ionic liquids was measured within a temperature range from 283 to 373 K. Solubility data were successfully correlated with local composition thermodynamic models such as NRTL and UNIQUAC. In this work, the possibility of extracting glucose from these ionic liquids using the antisolvent method has been also evaluated. The parameters affecting the extraction process are the ionic liquid type, ethanol/ionic liquid ratio, temperature, water content, and time. Results indicate that ethanol can be successfully used as an antisolvent to separate glucose from ionic liquids.