gebhart/patrepeval huggingface dataset:
Security properties of typed applets (1998)

This paper formalizes the folklore result that strongly-typed applets are more secure than untyped ones. We formulate and prove several security properties that all well-typed applets possess, and identify sufficient conditions for the applet execution environment to be safe, such as procedural encapsulation, type abstraction, and systematic type-based placement of run-time checks. These results are a first step towards formal techniques for developing and validating safe execution environments for applets.
History of Pharmacovigilance (2014)

Beneficial and harmful properties of medical remedies have been known to mankind for thousands of years. In more recent times, serious adverse reactions associated with medical products resulted in the evolution of regulatory changes and an effort to discover drug safety issues as early as possible. Pharmacovigilance is the practice used by sponsors and regulatory bodies to detect harmful effects associated with medical products to identify potential risks and enable warnings to reach physicians in a timely manner. This chapter examines the evolution of pharmacovigilance and the history of regulatory actions following major drug-associated events.
Conserved economics of transcription termination in eubacteria (2002)

A secondary structure in the nascent RNA followed by a trail of U residues is believed to be necessary and sufficient to terminate transcription. Such structures represent an extremely economical mechanism of transcription termination since they function in the absence of any additional protein factors. We have developed a new algorithm, GeSTer, to identify putative terminators and analysed all available complete bacterial genomes. The algorithm classifies the structures into five classes. We find that potential secondary structure sequences are concentrated downstream of coding regions in most bacterial genomes. Interestingly, many of these structures are not followed by a discernible U-trail. However, irrespective of the nature of the trail sequence, the structures show a similar distribution, indicating that they serve the same purpose. In contrast, such a distribution is absent in archaeal genomes, indicating that they employ a distinct mechanism for transcription termination. The present algorithm represents the fastest and most accurate algorithm for identifying terminators in eubacterial genomes without being restricted by the classical Escherichia coli paradigm.
A single amino acid substitution abolishes feedback inhibition of vaccinia virus thymidine kinase. (1992)

Exploitation of differences in the substrate specificity of the type I and type II thymidine kinases (EC 2.7.1.21, TK) expressed by the Herpesviridae and Poxviridae (and human cells), respectively, has lead to the development of effective antiherpetic drugs such as acyclovir and gancyclovir. Analysis of type I TK protein sequences reveals a consensus sequence which corresponds to domain IV of type II TK proteins such as that encoded by vaccinia virus (VV). The type I descriptor (Xpho - + + Xpho) differs at the second position from the type II consensus sequence (Xpho Xphi + + Xpho) by having an aspartic acid residue (D) substituted for a glutamine (Q). To test the hypothesis that this substitution may be responsible for the observed differences in substrate specificity of these enzymes and as a approach to identify the nucleoside binding site of the type II VV TK, site-directed mutagenesis was employed to alter glutamine 114 (Q114) within domain IV of VV TK to a histidine (Q114H) or an aspartic acid (Q114D). All of the mutant enzymes retained full enzymatic activity as compared to wild-type VV TK when thymidine or bromodeoxyuridine were used as substrates. However, unlike the wild-type herpes simplex (type 1) TK enzyme, neither wild-type nor domain IV VV TK mutants were able to phosphorylate acyclovir or cytidine substrates. Surprisingly, the domain IV VVTK mutants displayed a dramatic loss of feedback inhibition by dTTP. Mutations of the Q114 position also lead to a difference in ATP binding as demonstrated by an altered elution pattern of Q114H and Q114D from an ATP-agarose affinity column with dTTP. Taken together, these results suggest that domain IV of VV TK is not involved directly in substrate discrimination but instead participates in feedback inhibition by dTTP.
MFG-E8–mediated uptake of apoptotic cells by APCs links the pro- and antiinflammatory activities of GM-CSF (2007)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances protection against tumors and infections, but GM-CSF-deficient mice develop inflammatory disease. Here we show that GM-CSF is required for the expression of milk fat globule EGF 8 (MFG-E8) in antigen-presenting cells, and that MFG-E8-mediated uptake of apoptotic cells is a key determinant of GM-CSF-triggered tolerance and immunity. Upon exposure to apoptotic cells, GM-CSF-deficient antigen-presenting cells (APCs) produce an altered cytokine profile that results in decreased Tregs and increased Th1 cells, whereas concurrent ablation of IFN-gamma promotes Th17 cells. In wild-type mice, MFG-E8 attenuates the vaccination activity of GM-CSF-secreting tumor cells through Treg induction, whereas a dominant-negative MFG-E8 mutant potentiates GM-CSF-stimulated tumor destruction through Treg inhibition. These findings clarify the immunoregulatory effects of apoptotic cells and suggest new therapeutic strategies to modulate CD4(+) T cell subsets in cancer and autoimmunity.
Role of Nutrient Limitation and Stationary-Phase Existence in Klebsiella pneumoniae Biofilm Resistance to Ampicillin and Ciprofloxacin (2003)

Biofilms formed by Klebsiella pneumoniae resisted killing during prolonged exposure to ampicillin or ciprofloxacin even though these agents have been shown to penetrate bacterial aggregates. Bacteria dispersed from biofilms into medium quickly regained most of their susceptibility. Experiments with free-floating bacteria showed that stationary-phase bacteria were protected from killing by either antibiotic, especially when the test was performed in medium lacking carbon and nitrogen sources. These results suggested that the antibiotic tolerance of biofilm bacteria could be explained by nutrient limitation in the biofilm leading to stationary-phase existence of at least some of the cells in the biofilm. This mechanism was supported by experimental characterization of nutrient availability and growth status in biofilms. The average specific growth rate of bacteria in biofilms was only 0.032 h(-1) compared to the specific growth rate of planktonic bacteria of 0.59 h(-1) measured in the same medium. Glucose did not penetrate all the way through the biofilm, and oxygen was shown to penetrate only into the upper 100 micro m. The specific catalase activity was elevated in biofilm bacteria to a level similar to that of stationary-phase planktonic cells. Transmission electron microscopy revealed that bacteria were affected by ampicillin near the periphery of the biofilm but were not affected in the interior. Taken together, these results indicate that K. pneumoniae in this system experience nutrient limitation locally within the biofilm, leading to zones in which the bacteria enter stationary phase and are growing slowly or not at all. In these inactive regions, bacteria are less susceptible to killing by antibiotics.
Interparticle Coupling Effect on the Surface Plasmon Resonance of Gold Nanoparticles:  From Theory to Applications (2007)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInterparticle Coupling Effect on the Surface Plasmon Resonance of Gold Nanoparticles: From Theory to ApplicationsSujit Kumar Ghosh and Tarasankar PalView Author Information Department of Chemistry, Raidighi College, Raidighi-743383, South 24-Parganas, India, and Department of Chemistry, Indian Institute of Technology, Kharagpur-721302, India Cite this: Chem. Rev. 2007, 107, 11, 4797–4862Publication Date (Web):November 14, 2007Publication History Received3 November 2006Published online14 November 2007Published inissue 1 November 2007https://pubs.acs.org/doi/10.1021/cr0680282https://doi.org/10.1021/cr0680282research-articleACS PublicationsCopyright © 2007 American Chemical SocietyRequest reuse permissionsArticle Views41633Altmetric-Citations2303LEARN 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 SUBJECTS:Aggregation,Gold,Metal nanoparticles,Nanoparticles,Plasmonic nanoparticles Get e-Alerts
Force Field Validation Using Protein Side Chain Prediction (2002)

The prediction of protein side chain conformations is used to evaluate the accuracy of force field parameters. Specifically, new torsional parameters have recently been reported for the OPLS-AA force field, which achieved substantially better accuracy with respect to high level gas-phase quantum chemical calculations [J. Phys. Chem. B 2001, 105, 6474]. Here we demonstrate that these new parameters also lead to qualitatively improved side chain prediction accuracy. The primary emphasis is on the prediction of single side chain conformations, with the rest of the protein held fixed at the native configuration. Errors due to incomplete sampling can thus be essentially eliminated, using a combination of rotamer search and energy minimization. In addition, the protein environment is modeled realistically using implicit solvation and an explicit representation of crystal packing effects. Aided by the development of new algorithms, these calculations have been performed with modest computational requirements (a cluster of PCs) on a database of 36 proteins (∼5000 total residues). The side chain prediction tests that we employ are quite general and can be used to evaluate nonbonded or solvation parameters as well. As such, they provide a useful complement to decoy studies for force field validation.
Syntheses and Biological Activities of Selenium Analogs of .ALPHA.-Rat Atrial Natriuretic Peptide. (1993)

alpha-Rat atrial natriuretic peptide (7--28) (rANP (7--28)) and a series of its analogs in which half cystine residue(s) were substituted with half selenocystine residue(s) were synthesized by using the Fmoc-based solid-phase method followed by cyclization by means of dimethylsulfoxide (DMSO)-trifluoroacetic acid (TFA) oxidation. These analogs possess comparable activities in both receptor binding and cGMP accumulation in rat vascular smooth muscle cells to those of rAMP (7--28).
Fluorine‐containing optical adhesives for optical communications systems (1991)

Abstract Fluroinated epoxy resin adhesives containing diglycidylether of bisphenol AF (DGEBAF) with a fluorine content of 25.7 wt % are developed for fabrication of optical communications devices. These adhesives, formulated with a diluent of butanediol diglycidylether (BDDG) and a curing agent of polyether polyamine (Q694), can be cured at a curing temperature as low as 65°C and exhibit high transparency of more than 80% in the wavelength range of 0.5–1.3 μm. Moreover, they significantly reduce return loss at optical‐glass/adhesive interfaces because of the low refractive indices of ca. 1.52 and also improve heat durability of optical devices. They are successfully applied to submarine optical fiber transmission system.
Bacterial Virus f29 DNA-Packaging Motor and Its Potential Applications in Gene Therapy and Nanotechnology (2005)

A controllable, 30-nm imitating DNA-packaging motor was constructed. The motor is driven by six synthetic adenosine triphosphate (ATP)-binding RNA (packaging RNA [pRNA]) monomers, similar to the driving of a bolt with a hex nut. Conformational change and sequential action of the RNA with fivefold (viral capsid)/sixfold (pRNA hexamer) mismatch could ensure continuous rotation of the motor with ATP as energy. In the presence of ATP and magnesium, a 5-microm synthetic DNA was packaged using this motor. On average, one ATP was used to translocate two bases of DNA. The DNA-filled capsids were subsequently converted into up to 109 PFU/mL of infectious virus. The three-dimensional structures of pRNA monomer, dimer, and hexamer have been probed by photoaffinity crosslinking, chemical modification interference, cryo-atomic force microscopy, and computer modeling. The pRNA's size and shape can be controlled and manipulated at will to form stable dimers and trimers. Cryo-atomic force microscopy revealed that monomers, dimers, and trimers displayed a checkmark outline, elongated shape, and triangular structure, respectively. The motor can be turned off by gamma-S-ATP or EDTA and turned on again with the addition of ATP or magnesium, respectively. The formation of ordered structural arrays of the motor complex and its components, the retention of motor function after the 3'-end extension of the pRNA, and the ease of RNA dimer, trimer, and hexamer manipulation with desired shape and size make this RNA-containing motor a promising tool for drug and gene delivery and for use in nanodevices.
Influence of Peroxide Impurities in Povidone and Crospovidone on the Stability of Raloxifene Hydrochloride in Tablets: Identification and Control of an Oxidative Degradation Product (2000)

The purpose of this study was to identify a degradation product in a tablet formulation of raloxifene hydrochloride (R-HCl), delineate the role of excipients in its formation, and develop a rational strategy for its control. The degradant was identified as an N-oxide derivative of the drug substance based upon spectroscopic characterization and chromatographic comparison to the synthetic N-oxide. To identify the factors contributing to the formation of N-oxide, binary mixtures of each excipient with R-HCl were exposed to 125 degrees C in open containers. Raloxifene hydrochloride underwent an order of magnitude increase in conversion to the N-oxide in the presence of two excipients, povidone and crospovidone, as compared with its conversion in the presence of other excipients. To confirm a hypothesis that peroxide impurities in these two excipients contributed to the oxidation of the drug substance, tablet lots were spiked with quantities of H2O2 equivalent to 200, 400, 600, and 800 ppm peroxide over the intrinsic levels present in povidone and crospovidone. A strong correlation was observed between the total peroxide level and the quantity of the N-oxide formed upon accelerated storage. From these experiments a rational limit test for peroxide content in povidone and crospovidone was adopted as part of a control strategy to limit formation of the degradation product.
Poly(dimethylsiloxane) as a Material for Fabricating Microfluidic Devices (2002)

This Account summarizes techniques for fabrication and applications in biomedicine of microfluidic devices fabricated in poly(dimethylsiloxane) (PDMS). The methods and applications described focus on the exploitation of the physical and chemical properties of PDMS in the fabrication or actuation of the devices. Fabrication of channels in PDMS is simple, and it can be used to incorporate other materials and structures through encapsulation or sealing (both reversible and irreversible).
Pathogenic Forms of Tau Inhibit Kinesin-Dependent Axonal Transport through a Mechanism Involving Activation of Axonal Phosphotransferases (2011)

Aggregated filamentous forms of hyperphosphorylated tau (a microtubule-associated protein) represent pathological hallmarks of Alzheimer's disease (AD) and other tauopathies. While axonal transport dysfunction is thought to represent a primary pathogenic factor in AD and other neurodegenerative diseases, the direct molecular link between pathogenic forms of tau and deficits in axonal transport remain unclear. Recently, we demonstrated that filamentous, but not soluble, forms of wild-type tau inhibit anterograde, kinesin-based fast axonal transport (FAT) by activating axonal protein phosphatase 1 (PP1) and glycogen synthase kinase 3 (GSK3), independent of microtubule binding. Here, we demonstrate that amino acids 2-18 of tau, comprising a phosphatase-activating domain (PAD), are necessary and sufficient for activation of this pathway in axoplasms isolated from squid giant axons. Various pathogenic forms of tau displaying increased exposure of PAD inhibited anterograde FAT in squid axoplasm. Importantly, immunohistochemical studies using a novel PAD-specific monoclonal antibody in human postmortem tissue indicated that increased PAD exposure represents an early pathogenic event in AD that closely associates in time with AT8 immunoreactivity, an early marker of pathological tau. We propose a model of pathogenesis in which disease-associated changes in tau conformation lead to increased exposure of PAD, activation of PP1-GSK3, and inhibition of FAT. Results from these studies reveal a novel role for tau in modulating axonal phosphotransferases and provide a molecular basis for a toxic gain-of-function associated with pathogenic forms of tau.
Combined Peritoneal Dialysis and Hemodialysis: Our Experience Compared to Others (2003)

Hemodialysis and PD are not mutually exclusive. They can be used in combination to achieve targeted solute clearances, to improve certain clinical conditions, and to control volume and blood pressure in a subset of patients. Further evaluation is needed to better establish the long-term outcomes of using combined modality. Total solute clearance goals and methods for determining total solute clearance need to be standardized.
Direct binding of a synthetic multichain polypeptide to class II major histocompatibility complex molecules on antigen-presenting cells and stimulation of a specific T-cell line require processing of the polypeptide. (1991)

T-cell activation involves the recognition of foreign antigens as a complex with self-major histocompatibility complex (MHC) proteins on the surface of antigen-presenting cells (APC). Protein antigens usually require uptake by the APC and processing that results in the generation of peptide fragments. The branched synthetic polypeptide (Tyr, Glu)-Ala--Lys was chosen as a model antigen to follow the processing requirements, leading to T-cell activation. It has been demonstrated, by using fixed APC and various inhibitors of proteases, that (Tyr, Glu)-Ala--Lys has to be processed to stimulate a (Tyr, Glu)-Ala--Lys-specific T-cell line of C3H.SW (H-2b) origin to proliferate. To determine whether processing of (Tyr,Glu)-Ala--Lys is required to allow its association with the MHC class II molecules, biotin was covalently attached to it. Binding of the biotinylated (Tyr,Glu)-Ala--Lys to MHC class II gene products on the surface of intact normal APC was directly detected by phycoerythrin-streptavidin. The specificity of the binding was confirmed by its inhibition with anti-I-Ab antibodies as well as with excess of nonlabeled (Tyr,Glu)-Ala--Lys. Furthermore, introducing several inhibitors of proteases to the binding assay, we could substantiate that the proteolysis of (Tyr,Glu)-Ala--Lys is required to allow association of the resulting peptidyl T-cell epitopes with the MHC class II molecules themselves. The presence of the biotin moiety in the resulting peptides suggests that the T-cell epitopes of (Tyr,Glu)-Ala--Lys contain the N-terminal portion of the side chains of the branched polypeptide. An apparent Kd of 8.05 x 10(-8) M was determined, and optimal binding was detected after 10 hr of incubation with the antigen. The latter phenomenon is not due to slow uptake, since uptake of (Tyr,Glu)-Ala--Lys occurs mainly during the first 30 min of incubation, but rather reflects the events of processing that precede MHC interaction.
Effect of carbohydrate moieties on the folate hydrolysis activity of the prostate specific membrane antigen (2003)

N-linked carbohydrate structures are important for the folate hydrolase function of the protein. Removal of sugars partially or completely causes PSMA to be enzymatically inactive, improperly folded, resulting in increased rate of degradation.
Evidence for intracellular association of the glucocorticoid receptor with the 90-kDa heat shock protein. (1988)

We have investigated the association of the glucocorticoid receptor in S49 mouse lymphoma cells with the 90-kDa heat shock protein, HSP 90. Proteins were synthetically labeled by culturing cells with [35S]methionine and immunoadsorbed to protein A-Sepharose using monoclonal antireceptor antibody (BuGR-2). HSP 90 coimmunoadsorbed with the receptor when cytosol was incubated with antireceptor antibody for 1 h in the absence of molybdate, indicating that molybdate is not required for either formation or recovery of HSP 90-receptor complexes. Molybdate stabilized HSP 90-receptor complexes during prolonged incubation in vitro and rendered the complexes resistant to dissociation by 500 mM NaCl. In pulse-chase experiments, cells were incubated with [35S]methionine for 30 min (pulse label) and then cultured with excess unlabeled methionine (chase). At different times in the chase, cytosol was prepared from cells, and labeled proteins were immunoadsorbed by antireceptor antibody. The amount of labeled receptor recovered from cytosol decreased during the chase with a half-life of about 4 h. Labeled HSP 90 coimmunoadsorbed with the receptor at 4 h into the chase but not at the beginning of the chase or at 2 h into the chase, indicating that newly synthesized HSP 90 associated with the receptor in a time-dependent manner during the chase. Labeled HSP 90 did not associate with the receptor when dexamethasone was added to cells at the beginning of the chase. These findings support the hypothesis that HSP 90 associates with the glucocorticoid receptor in intact cells rather than in cytosol and indicates that dexamethasone promotes dissociation of HSP 90-receptor complexes in vivo.
Biomedical applications of micro- and nanoengineering : 16-18 December 2002, Melbourne, Australia (2002)

Part of SPIE's 2002 International Symposium on Smart Materials, Nano-, and Micro-Smart Systems, held at RMIT University--P. xi.
Two New Enzymes of Rosmarinic Acid Biosynthesis from Cell Cultures of Coleus blumei: Hydroxyphenylpyruvate Reductase and Rosmarinic Acid Synthase (1988)

Rosmarinic acid biosynthesis can be stimulated in cell cultures of Coleus blumei by culturing the cells in medium with 4% sucrose. In enzyme extracts of these cells two new enzymes of rosmarinic acid biosynthesis were discovered. Hydroxyphenylpyruvate reductase reduces 4-hydroxyphenylpyruvate and 3,4-dihydroxyphenylpyruvate to 4-hydroxyphenyllactate and 3,4-dihydroxyphenyllactate, respectively, using NADH. Rosmarinic acid synthase transfers the caffeoyl moiety of caffeoyl-CoA to the non-phenolic OH-group of 3,4-dihydroxyphenyllactic acid, in course of which rosmarinic acid is formed.