gebhart/patrepeval huggingface dataset:
Human liver arylacetamide deacetylase. Molecular cloning of a novel esterase involved in the metabolic activation of arylamine carcinogens with high sequence similarity to hormone-sensitive lipase. (1994)

Microsomal arylacetamide deacetylase (DAC) competes against the activity of cytosolic arylamine N-acetyltransferase, which catalyzes one of the initial biotransformation pathways for arylamine and heterocyclic amine carcinogens in many species and tissues. Activity determination and immunoblot analysis of DAC in human target tissues for arylamine carcinogens revealed that in extrahepatic tissues, additional enzymes are responsible for any deacetylation activity, whereas a single enzyme predominantly catalyzes this hydrolytic reaction in liver. We isolated and characterized a full-length cDNA from a human liver lambda gt11 library. This clone encodes an open reading frame of 400 amino acids with a deduced molecular mass of 45.7 kDa and contains two putative glycosylation sites. The 3'-untranslated region contains two putative polyadenylation signals. The cDNA was confirmed to be that for DAC in tryptic peptides from the purified human liver protein. Highest sequence similarity of DAC was found in a series of prokaryotic esterases encompassing the putative active site. Two extended regions of significant sequence homology with hormone-sensitive lipase and with lipase 2 from Moraxella TA144 were identified, whereas similarity to carboxyl esterases was restricted to the region encompassing the putative active site, indicating that DAC should be classified as esterase. This cDNA provides an important tool to study deacetylation and its effects on the metabolic activation of arylamine and heterocyclic amine carcinogens.
USING ENZYME STRUCTURE-ENVIRONMENT-ACTIVITY RELATIONSHIPS TO ENHANCE BIOCATALYST UTILITY (2007)

The overall objective of this work was to probe the fundamental relationship between enzyme structure, environment, and activity. These relationships were in turn exploited as the basis for developing effective strategies for stabilizing and thus improving the efficiency of biocatalysts. Initially, the utility of ionic liquids, which represent an environmentally green alternative to conventional solvents, as reaction media for anhydrous enzymatic reactions was explored. Solvatochromic and partition coefficient analysis suggest that ionic liquids are considerably more polar and hydrophilic than organic solvents. In model transesterification reactions, the enzyme lipase was found to be highly active in 1-butyl-3-methylimidazolium hexafluorophosphate, but inactive in more hydrophilic ionic liquids. Conventional approaches to preventing deactivating conformational changes in non-aqueous environments were ineffective in improving lipase activity in ionic liquids. Moreover, stability studies indicated that lipase are significantly more stable in ionic liquids compared to in organic solvents.To effectively control the pH of essential enzyme-bound water molecules, which is critical even in anhydrous enzymology, a novel buffering approach was developed. This approach was based on the hypothesis that simultaneous biocatalytic reactions that produce acid and base will create a dynamic pH equilibrium. The concept of biocatalytic pH control was successfully demonstrated by employing urease-catalyzed urea hydrolysis, which forms ammonia, to neutralize acid produced by the enzymatic degradation of organophosphorous toxins. Based on the pH-dependent activity profiles of the enzymes, the pH of the combined enzyme system is predictable and can be controlled by adjusting the relative ratio of enzyme activities.Lastly, poly(ethylene glycol)-modification was investigated as a method of enhancing the stability of therapeutic proteases in in vivo settings. Matrix metalloproteinase-1 (MMP-1), which has considerable therapeutic potential in the treatment of fibrotic conditions, was employed as a model protease for these studies. Comparison of the efficacy of native full-length enzyme, the truncated active enzyme, and a poly(ethylene glycol)-modified form of the truncated active enzyme in a laceration model in mice showed that the truncated active enzyme produced the greatest reduction in interfibrillar collagen. Structural characterization of the modified enzyme suggests that site-specific modification are key to retaining activity and to improving the enzyme's stability.
Thalidomide and a Thalidomide Analogue Drug Costimulate Virus‐Specific CD8+T Cells In Vitro (2003)

CD8(+) T cell immunity is critical for protection from viral disease, such as that caused by the human immunodeficiency virus (HIV) or cytomegalovirus (CMV). It is therefore important to identify therapies that can boost antiviral immunity. The recent finding that thalidomide acts as a T cell costimulator suggested that this drug may boost antiviral CD8(+) T cell responses. In this in vitro study, in a human autologous CD8(+) T cell/dendritic cell (DC) coculture system, thalidomide and a potent thalidomide analogue were shown to enhance virus-specific CD8(+) T cell cytokine production and cytotoxic activity. The drug-enhanced antiviral activity was noted in cells from both healthy donors and persons chronically coinfected with HIV and CMV. This stimulatory effect was directed at CD8(+) T cells, and not DCs. These results suggest an application for thalidomide and the thalidomide analogue as a novel immune-adjuvant therapy in chronic viral infections.
Computationally Efficient Moving Object Tracking with CAMSHIFT Embedded Kalman Filter Theory (2012)

In this paper we propose a computationally efficient moving object tracking algorithm with CAMSHIFT Embedded Kalman Filter technique. Object tracking using CAMSHIFT still is suffering from fundamental problems such as cluttered background, occlusion and dynamic movement of objects. In order to cope with these problems, the Kalman filter is applied in CAMSHIFT to predict the location of object for efficient object tracking. As Kalman Filter is a set of mathematical equation, so it increases the computational complexity of our propose system. We solve this problem by using random frame selection procedure. We randomly select some frame instead of processing every frame for reducing the computational complexity. The experimental results are shown to prove the robustness, computational efficient and validity of the propose algorithm using various video sequences of moving object.
Three cases of PICU sedation with isoflurane delivered by the ‘AnaConDa®’ (2005)

Prolonged sedation in the pediatric intensive care unit may be difficult because of tolerance, drug dependence and withdrawal, drug interactions and unwanted drug effects. We present three patients sedated with isoflurane via the Anesthetic Conserving Device, AnaConDa. AnaConDa is a modified heat and moisture exchanger that allows evaporation and delivery of inhalational anesthetics without an anesthesia machine, vaporizer or adapted ventilator. Two patients with abdominal complications and prolonged sedation for mechanical ventilation were converted to isoflurane sedation for several days. The third patient with refractory status epilepticus received isoflurane to treat epileptiform electroencephalogram activity. Patients weighing 40 and 30 kg were treated with AnaConDa placed at the Y-piece, while the patient weighing 20 kg was treated with AnaConDa in the inspiratory limb of the respiratory circuit. Adequate sedation was achieved with endtidal isoflurane concentration of 0.3-0.4%, while antiepileptic effect was achieved at a higher dose, 0.9%. Intravenous sedatives could be reduced or discontinued during isoflurane sedation. Inhaled sedation of isoflurane with AnaConDa was effective in these patients. It may provide an alternative in difficult cases needing prolonged sedation and should be evaluated further.
Chemoprevention of colon carcinogenesis by concurrent administration of piroxicam, a nonsteroidal antiinflammatory drug with D,L-alpha-difluoromethylornithine, an ornithine decarboxylase inhibitor, in diet. (1990)

The effect of three levels of piroxicam and three levels of D,L-alpha-difluoromethylornithine (DFMO) fed individually and in combination during the postinitiation phase of carcinogenesis was studied in male F344 rats to generate a data base on the efficacy and synergistic and additive effects of these compounds as inhibitors of colon carcinogenesis. The maximum tolerated dose of DFMO was determined in male F344 rats and found to be 5000 ppm in the AIN-76A diet. Piroxicam at levels of 25, 75, and 150 ppm and DFMO at concentrations of 400, 1000, and 4000 ppm (20, 50, and 80% maximum tolerated dose) in AIN-76 diet were tested individually and in combinations. At 7 weeks of age, while the rats were consuming the control diet (AIN-76A), all animals except the vehicle (saline)-treated controls were given a single s.c. injection of azoxymethane (CAS: 25843-45-2) at a dose level of 29.6 mg/kg body weight to induce intestinal tumors. One week after azoxymethane injection, animals were transferred to their respective experimental diets containing piroxicam and DFMO. Fifty-six weeks after azoxymethane injection, all animals were necropsied and colon and small intestinal tumor incidences and multiplicity were compared among the various dietary groups. Feeding of diets containing 75 and 150 ppm piroxicam or 1000 and 4000 ppm DFMO significantly inhibited the incidence (percentage of animals with tumors) of colon adenocarcinomas compared to that of control diet. The multiplicity (number of tumors/rat) of adenocarcinomas was significantly inhibited in animals fed the 25, 75, and 150 ppm piroxicam or 400, 1000, and 4000 ppm DFMO diets. Results analyzed by the linear regression method suggested a dose-dependent inhibition in colon adenocarcinoma incidence with increasing levels of piroxicam or DFMO. The incidence and multiplicity of colon adenocarcinomas were significantly inhibited in animals fed the diets containing combinations of 25, 75, and 150 ppm piroxicam and 400, 1000, and 4000 ppm DFMO. Piroxicam and DFMO administered together had a stronger inhibitory effect than did those given individually. Piroxicam and DFMO when administered individually had no significant inhibitory effect on colon adenoma incidence and multiplicity; in contrast, combinations of these compounds significantly inhibited colon adenomas. No consistent differences were found in the incidence and multiplicity of small intestinal tumors among the dietary groups.(ABSTRACT TRUNCATED AT 400 WORDS)
In-resonator variation of waveguide cross-sections for dispersion control of aluminum nitride micro-rings (2015)

We propose and demonstrate a dispersion control technique by combination of different waveguide cross sections in an aluminum nitride micro-ring resonator. Narrow and wide waveguides with normal and anomalous dispersion, respectively, are linked with tapering waveguides and enclosed in a ring resonator to produce a total dispersion near zero. The mode-coupling in multimoded waveguides is also effectively suppressed. This technique provides new degrees of freedom and enhanced flexibility in engineering the dispersion of microcomb resonators.
Changes in coagulation factor activity and content of di(2‐ethylhexyl)phthalate in frozen plasma units during refrigerated storage for up to five days after thawing (2011)

The bulk of coagulation factor activity losses during storage occurred in the first 24 hours. Coagulation factor activities remaining in FP after 5 days did not differ from those previously reported in similar products frozen within 24 hours of phlebotomy. While DEHP levels in 5-day-thawed FP are not of concern for adult patients, for infants, DEHP levels can be minimized by using FP refrigerated for no more than 24 hours.
Monodisperse core-shell chitosan microcapsules for pH-responsive burst release of hydrophobic drugs (2011)

Monodisperse core-shell microcapsules based on crosslinked chitosan membrane with acid-triggered burst release properties are successfully developed. The microcapsules are fabricated from double emulsion precursors that are prepared with a microfluidic approach. In neutral medium (pH 7.1), the microcapsules maintain a good spherical shape and structural integrity; while, in acidic medium (pH 1.5 ∼ 4.7), the microcapsules decompose rapidly and release the encapsulated contents completely in short periods varying from 39 s to 22 min. The acid-triggered burst release pattern from the proposed chitosan microcapsules may make them capable for stomach-specific drug delivery systems with quick and complete release characteristics in a controllable pH-responsive manner.
Capillary electrophoresis and the clinical laboratory (2006)

Over the past 15 years, CE as an analytical tool has shown great promise in replacing many conventional clinical laboratory methods, such as electrophoresis and HPLC. CE's appeal was that it was fast, used very small amounts of sample and reagents, was extremely versatile, and was able to separate large and small analytes, whether neutral or charged. Because of this versatility, numerous methods have been developed for analytes that are of clinical interest. Other than molecular diagnostic and forensic laboratories CE has not been able to make a major impact in the United States. In contrast, in Europe and Japan an increasing number of clinical laboratories are using CE. Now that automated multicapillary instruments are commercially available along with cost-effective test kits, CE may yet be accepted as an instrument that will be routinely used in the clinical laboratories. This review will focus on areas where CE has the potential to have the greatest impact on the clinical laboratory. These include analyses of proteins found in serum and urine, hemoglobin (A1c and variants), carbohydrate-deficient transferrin, forensic and therapeutic drug screening, and molecular diagnostics.
Further studies of polymers as carcinogenic agents in animals. (1955)

Summary 1.Malignant tumors were induced in rodents by subcutaneously imbedding the following polymer films: Cellophane, Dacron, polyethylene, polyvinyl chloride, Silastic, Pliofilm, Nylon, polymethyl methacrylate, polystyrene, Saran, Ivalon, Kel-F, Teflon, and silk. 2.The polymer films were always found encpsulated in a pocket of connective tissue, except when a tumor was induced. 3.It does not appear that the carcinogenic activity is a result of the presence of impurities, since tumors were induced by pure polymers as well as by commercial products. 4.The monomers, styrene, methyl methacrylate, and hexamethylene diamine, were not carcinogenic in rodents when painted on the skin. 5.Studies with tagged polymers showed that they decomposed at a minute rate when left in the organism. 6.A possible mechanism by which polymers may exert their carcinogenic activity, based on the observed degradation, is suggested.
GENETICALLY‐INDUCED SUSCEPTIBILITY TO MALATHION IN TRIBOLIUM CASTANEUM DESPITE SELECTION FOR RESISTANCE (1980)

Immigration of malathion‐susceptible males into resistant populations of Tribolium castaneum considerably increased mortality despite selection for resistance every generation. It is suggested that this method may prevent the appearance of resistance with continuous use of chemicals. Its use with warehouse populations of stored‐products insects seems to be feasible. ZUSAMMENFASSUNG GENETISCHE VERLANGSAMUNG DER ENTWICKLUNG VON RESISTENZ GEGEN MALATHION BEI TRIBOLIUM CASTANEUM TROTZ SELEKTION Die Einwanderung von Malathion‐sensiblen Männchen in resistenten Populationen von Tribolium castaneum erhöhte die Mortalität beträchtlich, trotzdem eine Selektion auf Resistenz in jeder Generation erfolgte. Es wird vermutet, dass diese Methode das Auftreten von Resistenz bei dauernder Insektizidanwendung verhindern könnte. Die Anwendung in Lagerhauspopulationen von Vorratsschädlingen erscheint möglich.
Effect of TGF-β<sub>1</sub> Antisense S-Oligonucleotide on Synthesis and Accumulation of Matrix Proteoglycans in Balloon Catheter-Injured Neointima of Rabbit Carotid Arteries (2000)

Arterial matrix proteoglycans (PG) are necessary for the maintenance of viscoelastic properties of the vessel wall, but excess levels, particularly of versican and biglycan in primary and restenotic intimal thickenings, are correlated with increased tissue volume and with atherogenicity. There is good evidence that the primary stimulus to increased PG synthesis, including versican and biglycan, is transforming growth factor-beta(1) (TGF-beta(1)). The aim of this study was to determine the effects of reducing endogenous TGF-beta(1) on rates and patterns of PG synthesis and on versican, biglycan and decorin accumulation in vivo. Rabbit common carotid arteries subjected to balloon catheter injury were treated with a TGF-beta(1) antisense phosphorothioate oligonucleotide applied in a pluronic gel to the adventitia. Control animals received a nonsense oligonucleotide or gel alone. TGF-beta(1) antisense (1) significantly (p < 0.005) inhibited, at day 2, the balloon catheter-induced increase in TGF-beta(1) mRNA relative to beta-actin mRNA; (2) inhibited intimal thickening at 23 days by approximately 40% (p < 0.05); (3) inhibited (p < 0.05) PG synthesis, measured by autoradiographic detection of [(3)H]glucosamine, in the media of day 2 ballooned carotids and in the subendothelial zone of day 23 neointima, and (4) decreased immunostaining intensity for versican (p < 0.03) and TGF-beta(1) (p < 0.001) in the neointima. Biglycan was reduced to a lesser extent but not significantly and decorin was not affected. Proliferating cell nuclear antigen indices were variable and not significantly changed. These findings confirm a role for TGF-beta(1) in developing neointima and demonstrate a specific effect on the synthesis, distribution, and accumulation of matrix PG, particularly versican.
Equilibrium conformational dynamics in an RNA tetraloop from massively parallel molecular dynamics (2010)

Conformational equilibrium within the ubiquitous GNRA tetraloop motif was simulated at the ensemble level, including 10 000 independent all-atom molecular dynamics trajectories totaling over 110 micros of simulation time. This robust sampling reveals a highly dynamic structure comprised of 15 conformational microstates. We assemble a Markov model that includes transitions ranging from the nanosecond to microsecond timescales and is dominated by six key loop conformations that contribute to fluctuations around the native state. Mining of the Protein Data Bank provides an abundance of structures in which GNRA tetraloops participate in tertiary contact formation. Most predominantly observed in the experimental data are interactions of the native loop structure within the minor groove of adjacent helical regions. Additionally, a second trend is observed in which the tetraloop assumes non-native conformations while participating in multiple tertiary contacts, in some cases involving multiple possible loop conformations. This tetraloop flexibility can act to counterbalance the energetic penalty associated with assuming non-native loop structures in forming tertiary contacts. The GNRA motif has thus evolved not only to readily participate in simple tertiary interactions involving native loop structure, but also to easily adapt tetraloop secondary conformation in order to participate in larger, more complex tertiary interactions.
Isoprenoid (phosphinylmethyl)phosphonates as inhibitors of squalene synthetase (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIsoprenoid (phosphinylmethyl)phosphonates as inhibitors of squalene synthetaseScott A. Biller, Cornelia Forster, Eric M. Gordon, Thomas Harrity, William A. Scott, and Carl P. Ciosek Jr.Cite this: J. Med. Chem. 1988, 31, 10, 1869–1871Publication Date (Print):October 1, 1988Publication History Published online1 May 2002Published inissue 1 October 1988https://pubs.acs.org/doi/10.1021/jm00118a001https://doi.org/10.1021/jm00118a001research-articleACS PublicationsRequest reuse permissionsArticle Views526Altmetric-Citations65LEARN 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
Role of native disulfide bonds in the structure and activity of insulin-like growth factor 1: Genetic models of protein-folding intermediates (1993)

Insulin and insulin-related proteins contain three motif-specific disulfide bonds. Here we examine the role of these disulfide bonds in the folding and function of one family member, human insulin-like growth factor 1 (IGF-1). Analogues containing pariwise Cys-->Ser or Cys-->Ala substitutions were expressed in Escherichia coli, purified, and analyzed with respect to receptor-binding, solution structure, and thermodynamic stability. An analogue lacking all three disulfide bonds (designated des-Cys-IGF-1) is inactive and unfolded. Introduction of the [18-61] disulfide bond, previously shown to occur in an early intermediate in oxidative refolding [Miller, J. A., Owers-Narhi, L., Hua, Q. X., Rosenfeld, R., Arakawa, T., Rohde, M., Prestrelski, S., Lauren, S., S. Stoney, K. S., Tsai, L., & Weiss, M. A. (1993) Biochemistry (preceding paper in this issue)], results in a compact partially folded state with low but significant biological activity. Additional but incomplete structural organization and biological activity are observed following introduction of either the [6-48] or the [47-52] disulfide bonds. Native function, structure, and stability require the presence of all three disulfide bonds. These analogues provide genetic models of IGF-1 protein-folding intermediates. Their characterization suggests that bifurcation of the IGF-1 folding pathway reflects alternative late steps in the folding of a molten-globule intermediate.