gebhart/patrepeval huggingface dataset:
Initial Cleavage of the Human Immunodeficiency Virus Type 1 GagPol Precursor by Its Activated Protease Occurs by an Intramolecular Mechanism (2004)

Processing of the GagPol polyprotein precursor of human immunodeficiency virus type 1 (HIV-1) is a critical step in viral assembly and replication. The HIV-1 protease (PR) is translated as part of GagPol and is both necessary and sufficient for precursor processing. The PR is active only as a dimer; enzyme activation is initiated when the PR domains in two GagPol precursors dimerize. The precise mechanism by which the PR becomes activated and the subsequent initial steps in precursor processing are not well understood. However, it is clear that processing is initiated by the PR domain that is embedded within the precursor itself. We have examined the earliest events in precursor processing using an in vitro assay in which full-length GagPol is cleaved by its embedded PR. We demonstrate that the embedded, immature PR is as much as 10,000-fold less sensitive to inhibition by an active-site PR inhibitor than is the mature, free enzyme. Further, we find that different concentrations of the active-site inhibitor are required to inhibit the processing of different cleavage sites within GagPol. Finally, our results indicate that the first cleavages carried out by the activated PR within GagPol are intramolecular. Overall, our data support a model of virus assembly in which the first cleavages occur in GagPol upstream of the PR. These intramolecular cleavages produce an extended form of PR that completes the final processing steps accompanying the final stages of particle assembly by an intermolecular mechanism.
Therapeutics for Alzheimer's disease (2002)

Conference Abstract| June 01 2002 Therapeutics for Alzheimer's disease T. Wisniewski T. Wisniewski 1NYU Sch Med, Dept. Neurol and Pathol., Rm HN419 Millhauser Lab, 550 1st Avenue, New York, NY 10016 USA Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (2002) 30 (3): A71. https://doi.org/10.1042/bst030a071a Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation T. Wisniewski; Therapeutics for Alzheimer's disease. Biochem Soc Trans 1 June 2002; 30 (3): A71. doi: https://doi.org/10.1042/bst030a071a Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu nav search search input Search input auto suggest search filter All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 2002 Biochemical Society2002 Article PDF first page preview Close Modal You do not currently have access to this content.
Myostatin Gene Deletion Prevents Glucocorticoid-Induced Muscle Atrophy (2006)

Glucocorticoids mediate muscle atrophy in many catabolic states. Myostatin expression, a negative regulator of muscle growth, is increased by glucocorticoids and myostatin overexpression is associated with lower muscle mass. This suggests that myostatin is required for the catabolic effects of glucocorticoids. We therefore investigated whether myostatin gene disruption could prevent muscle atrophy caused by glucocorticoids. Male myostatin knockout (KO) and wild-type mice were subjected to dexamethasone treatment (1 mg/kg.d for 10 d or 5 mg/kg.d for 4 d). In wild-type mice, daily administration of low-dose dexamethasone for 10 d resulted in muscle atrophy (tibialis anterior: -15%; gastrocnemius: -13%; P < 0.01) due to 15% decrease in the muscle fiber cross-sectional area (1621 +/- 31 vs. 1918 +/- 64 microm(2), P < 0.01). In KO mice, there was no reduction of muscle mass nor fiber cross-sectional area after dexamethasone treatment. Muscle atrophy after 4 d of high-dose dexamethasone was associated with increased mRNA of enzymes involved in proteolytic pathways (atrogin-1, muscle ring finger 1, and cathepsin L) and increased chymotrypsin-like proteasomal activity. In contrast, the mRNA of these enzymes and the proteasomal activity were not significantly affected by dexamethasone in KO mice. Muscle IGF-I mRNA was paradoxically decreased in KO mice (-35%, P < 0.05); this was associated with a potentially compensatory increase of IGF-II expression in both saline and dexamethasone-treated KO mice (2-fold, P < 0.01). In conclusion, our results show that myostatin deletion prevents muscle atrophy in glucocorticoid-treated mice, by blunting the glucocorticoid-induced enhanced proteolysis, and suggest an important role of myostatin in muscle atrophy caused by glucocorticoids.
PatMatch: a program for finding patterns in peptide and nucleotide sequences (2005)

Here, we present PatMatch, an efficient, web-based pattern-matching program that enables searches for short nucleotide or peptide sequences such as cis-elements in nucleotide sequences or small domains and motifs in protein sequences. The program can be used to find matches to a user-specified sequence pattern that can be described using ambiguous sequence codes and a powerful and flexible pattern syntax based on regular expressions. A recent upgrade has improved performance and now supports both mismatches and wildcards in a single pattern. This enhancement has been achieved by replacing the previous searching algorithm, scan_for_matches [D'Souza et al. (1997), Trends in Genetics, 13, 497-498], with nondeterministic-reverse grep (NR-grep), a general pattern matching tool that allows for approximate string matching [Navarro (2001), Software Practice and Experience, 31, 1265-1312]. We have tailored NR-grep to be used for DNA and protein searches with PatMatch. The stand-alone version of the software can be adapted for use with any sequence dataset and is available for download at The Arabidopsis Information Resource (TAIR) at ftp://ftp.arabidopsis.org/home/tair/Software/Patmatch/. The PatMatch server is available on the web at http://www.arabidopsis.org/cgi-bin/patmatch/nph-patmatch.pl for searching Arabidopsis thaliana sequences.
Preclinical Evidence for the Therapeutic Potential of CD38-Targeted Immuno-Chemotherapy in Multiple Myeloma Patients Refractory to Lenalidomide and Bortezomib (2014)

Our results provide the first preclinical evidence for the benefit of daratumumab plus lenalidomide combination for lenalidomide- and bortezomib-refractory patients.
Modular Functionalization of Carbon Nanotubes and Fullerenes (2009)

A series of highly efficient, modular zwitterion-mediated transformations have been developed which enable diverse functionalization of carbon nanotubes (CNTs, both single-walled and multi-walled) and fullerenes. Three functionalization strategies are demonstrated. (1) Trapping the charged zwitterion intermediate with added nucleophiles allows a variety of functional groups to be installed on the fullerenes and carbon nanotubes in a one-pot reaction. (2) Varying the electrophile from dimethyl acetylenedicarboxylate to other disubstituted esters provides CNTs functionalized with chloroethyl, allyl, and propargyl groups, which can further undergo S(N)2 substitution, thiol addition, or 1,3-dipolar cycloaddition reactions. (3) Postfunctionalization transformations on the cyclopentenones (e.g., demethylation and saponification) of the CNTs lead to demethylated or hydrolyzed products, with high solubility in water (1.2 mg/mL for MWCNTs). CNT aqueous dispersions of the latter derivatives are stable for months and have been successfully utilized in preparation of CNT-poly(ethylene oxide) nanocomposite via electrospinning. Large-scale MWCNT (10 g) functionalization has also been demonstrated to show the scalability of the zwitterion reaction. In total we present a detailed account of diverse CNT functionalization under mild conditions (60 degrees C, no strong acids/bases, or high pressure) and with high efficiency (1 functional group per 10 carbon atoms for SWCNTs), which expand the utility of these materials.
Robust nanogenerators based on graft copolymers via control of dielectrics for remarkable output power enhancement (2017)

A robust nanogenerator based on poly(<i>tert</i>-butyl acrylate) (PtBA)-grafted polyvinylidene difluoride (PVDF) copolymers via dielectric constant control through an atom-transfer radical polymerization technique, which can markedly increase the output power, is demonstrated. The copolymer is mainly composed of α phases with enhanced dipole moments due to the π-bonding and polar characteristics of the ester functional groups in the PtBA, resulting in the increase of dielectric constant values by approximately twice, supported by Kelvin probe force microscopy measurements. This increase in the dielectric constant significantly increased the density of the charges that can be accumulated on the copolymer during physical contact. The nanogenerator generates output signals of 105 V and 25 μA/cm<sup>2</sup>, a 20-fold enhancement in output power, compared to pristine PVDF-based nanogenerator after tuning the surface potential using a poling method. The markedly enhanced output performance is quite stable and reliable in harsh mechanical environments due to the high flexibility of the films. On the basis of these results, a much faster charging characteristic is demonstrated in this study.
Bacterial Quorum-Sensing Network Architectures (2009)

Quorum sensing is a cell-cell communication process in which bacteria use the production and detection of extracellular chemicals called autoinducers to monitor cell population density. Quorum sensing allows bacteria to synchronize the gene expression of the group, and thus act in unison. Here, we review the mechanisms involved in quorum sensing with a focus on the Vibrio harveyi and Vibrio cholerae quorum-sensing systems. We discuss the differences between these two quorum-sensing systems and the differences between them and other paradigmatic bacterial signal transduction systems. We argue that the Vibrio quorum-sensing systems are optimally designed to precisely translate extracellular autoinducer information into internal changes in gene expression. We describe how studies of the V. harveyi and V. cholerae quorum-sensing systems have revealed some of the fundamental mechanisms underpinning the evolution of collective behaviors.
Proteus: an adaptable presentation system for a software development and multimedia document environment (1995)

Proteus: An Adaptable Presentation System for a Software Development and Multimedia Document Environment by Ethan Vincent Munson Doctor of Philosophy in Computer Science University of California at Berkeley Professor Michael A. Harrison, Chair The many different documents produced by a large software project are typically created and maintained by a variety of incompatible software tools, such as programming environments, document processing systems, and specialized editors for non-textual media. The incompatibility of these tools hinders communication within the project by making it difficult to share the documents that record the project&amp;apos;s plans, design history, implementations, and experiences. An important factor underlying this incompatibility is the diversity of presentation models that have been adopted. Each system&amp;apos;s presentation model is well-suited to the document types and media it supports, but is difficult to adapt to other types and media. This dissertation describes a ne...
Purification and characterization of a novel soluble receptor for interleukin 1. (1991)

Affinity chromatography and reverse-phase high-performance liquid chromatography was used to purify a soluble interleukin 1 beta (IL-1 beta) specific binding protein from the supernatant of a human B cell line, Raji. The purified protein specifically bound 125I IL-1 beta forming a 60-kD complex in nonreducing conditions and a 70-kD complex in reducing conditions. Binding was found to be displaceable by mature human and murine IL-1 beta and human 31-kD IL-1 beta propeptide, but not displaceable by human and murine IL-1 alpha or human IL-1 receptor (IL-1R) antagonist. Ligand blotting revealed a 47-kD molecule that specifically bound IL-1 beta. Measurement of binding affinity of the cell surface Raji IL-1R (Kd = 2.2 nm) and the Raji soluble (s)IL-1R (Kd = 2.7 nm) demonstrated a similar affinity for 125I IL-1 beta. Purified sIL-1R inhibited binding of IL-1 beta to cell lines with both type I (80 kD) and type II (65 kD) IL-1Rs, but did not interfere with IL-1 alpha binding. This natural sIL-1R may function as an important regulatory molecule of IL-1 beta in vivo.
Premedication with dexmedetomidine in pediatric patients: a systematic review and meta-analysis (2014)

Premedication is important in pediatric anesthesia. This meta-analysis aimed to investigate the role of dexmedetomidine as a premedicant for pediatric patients. A systematic literature search was conducted to identify randomized controlled trials comparing dexmedetomidine premedication with midazolam or ketamine premedication or placebo in children. Two reviewers independently performed the study selection, quality assessment and data extraction. The original data were pooled for the meta-analysis with Review Manager 5. The main parameters investigated included satisfactory separation from parents, satisfactory mask induction, postoperative rescue analgesia, emergence agitation and postoperative nausea and vomiting. Thirteen randomized controlled trials involving 1190 patients were included. When compared with midazolam, premedication with dexmedetomidine resulted in an increase in satisfactory separation from parents (RD = 0.18, 95% CI: 0.06 to 0.30, p = 0.003) and a decrease in the use of postoperative rescue analgesia (RD = -0.19, 95% CI: -0.29 to -0.09, p = 0.0003). Children treated with dexmedetomidine had a lower heart rate before induction. The incidence of satisfactory mask induction, emergence agitation and PONV did not differ between the groups. Dexmedetomidine was superior in providing satisfactory intravenous cannulation compared to placebo. This meta-analysis suggests that dexmedetomidine is superior to midazolam premedication because it resulted in enhanced preoperative sedation and decreased postoperative pain. Additional studies are needed to evaluate the dosing schemes and long-term outcomes of dexmedetomidine premedication in pediatric anesthesia.
SMILEE: Symmetric Multi-modal Interactions with Language-gesture Enabled (AI) Embodiment (2018)

Sujeong Kim, David Salter, Luke DeLuccia, Kilho Son, Mohamed R. Amer, Amir Tamrakar. Proceedings of the 2018 Conference of the North American Chapter of the Association for Computational Linguistics: Demonstrations. 2018.
The Role of the C-terminal Domain of IκBα in Protein Degradation and Stabilization (1996)

In the present study, the role of the I kappa B alpha C terminus in NF-kappa B/I kappa B alpha regulation was examined in NIH 3T3 cells engineered to inducibly express wild type or mutated human I kappa B alpha proteins under the control of the tetracycline responsive promoter. Deletion studies demonstrated that the last C-terminal 30 amino acids (amino acids (aa) 288 to aa 317, deleted in I kappa B alpha delta 3), including most of the PEST domain, were dispensable for I kappa B alpha function. However, deletions from aa 261 to 317 or aa 269 to 317 (I kappa B alpha delta 1 and I kappa B alpha delta 2 respectively), lacked the ability to dissociate NF-kappa B/DNA complexes in vitro and were unable to inhibit NF-kappa B dependent transcription. Moreover, I kappa B alpha delta 1 and I kappa B alpha delta 2 mutants were resistant to inducer-mediated degradation. Analysis of I kappa B alpha deletions in the presence of protein synthesis inhibitors revealed that, independently of stimulation, I kappa B alpha delta 1 and I kappa B alpha delta 2 had a half-life four times shorter than wild type I kappa B alpha and the interaction of I kappa B alpha delta 1 and I kappa B alpha delta 2 with p65 was dramatically decreased in vivo as measured by co-immunoprecipitation. Interestingly, protease inhibitors which blocked inducer-mediated degradation of I kappa B alpha also stabilized the turnover of I kappa B alpha delta 1 and I kappa B alpha delta 2. Based on these studies, we propose that in the absence of stimulation, the C-terminal domain between aa 269 and 287 may play a role to protect I kappa B alpha from a constitutive protease activity.
Observation of a Second Substrate Radical Intermediate in the Reaction of Lysine 2,3-Aminomutase: A Radical Centered on the .beta.-Carbon of the Alternative Substrate, 4-Thia-L-lysine (1995)

Lysine 2,3-aminomutase from Clostridia catalyzes the interconversion of lysine and beta-lysine by a mechanism in which four organic radicals are postulated as intermediates. One of the intermediates has been identified as the alpha-radical of beta-lysine in imine linkage to pyridoxal phosphate (PLP) [Ballinger, M. D., Frey, P. A., & Reed, G. H. (1992) Biochemistry 31, 10782-10788]. We report here the observation of another of the four putative radical intermediates in the reaction of the alternative substrate, 4-thia-L-lysine (S-2-aminoethyl-L-cysteine). 4-Thialysine is a substrate for lysine 2,3-aminomutase. The Km of 4-thialysine is similar to that for lysine, and the Vm is approximately 3% of that for lysine. Upon mixing 4-thialysine with the activated enzyme in the presence of the required cofactor S-adenosylmethionine, followed by freeze-quenching with liquid N2 in the steady state, a strong EPR signal centered at g = 2.003 is observed. This signal exhibits strong hyperfine splitting due to the presence of 13C at carbon-3 of 4-thialysine, and the EPR pattern is narrowed upon the substitution of deuterium at carbon-3. The hyperfine interactions show that the unpaired electron is centered on carbon-3 of 4-thialysine. The hyperfine pattern in the EPR spectrum is also simplified by the use of 4-thia[5,6-2H4]lysine as the substrate, showing either that the spin is partially delocalized through the sulfur intervening between carbons-3 and -5 or that the conformation is such that protons at carbon-6 are close to carbon-3.(ABSTRACT TRUNCATED AT 250 WORDS)
Enantioselective Nucleophilic Catalysis with “Planar-Chiral” Heterocycles (2000)

Although Lewis bases (e.g., tertiary phosphines, tertiary amines, and pyridines) serve as nucleophilic catalysts for a wide array of reactions, there have been relatively few reports of enantioselective nucleophilic catalysts. In this Account, we describe the design and synthesis of a new family of chiral nucleophilic catalysts, specifically, planar-chiral heterocycles. These complexes provide good levels of enantiomeric excess in the addition of alcohols to ketenes, the rearrangement of O-acylated azlactones, and the kinetic resolution of secondary alcohols.
Phosphorylation of cellular proteins in Rous sarcoma virus-infected cells: analysis by use of anti-phosphotyrosine antibodies. (1988)

The protein substrates for the tyrosine protein kinases in cells transformed by avian sarcoma viruses were analyzed by gel electrophoresis in combination with immunoblotting or immunoprecipitation by antibodies against phosphotyrosine. We found that greater than 90% of phosphotyrosine-containing cellular proteins can be immunoprecipitated by these antibodies. The level of phosphotyrosine-containing cellular proteins detectable by this method markedly increased upon transformation with Rous sarcoma virus, and more than 20 distinct bands of such proteins were found in lysates of Rous sarcoma virus-transformed cells. Most of these phosphotyrosine-containing proteins had not been identified by other methods, and their presence appeared to correlate with morphological transformation in cells infected with various Rous sarcoma virus mutants and Y73, PRCII, and Fujinami sarcoma viruses. However, considerably different patterns were obtained with cells infected with nontransforming Rous sarcoma virus mutants that encode nonmyristylated src kinases, indicating that most substrates that correlate with transformation can only be recognized by p60v-src associated with the plasma membrane.
Glucocorticoid Effects on Memory Retrieval Require Concurrent Noradrenergic Activity in the Hippocampus and Basolateral Amygdala (2004)

Previous findings indicate that administration of abeta-adrenoceptor antagonist systemically blocks glucocorticoid impairment of memory retrieval. Here, we report that beta-adrenoceptor activation in the hippocampus and the basolateral complex of the amygdala (BLA) is implicated in the impairing effects of glucocorticoids on memory retrieval. The specific glucocorticoid receptor (GR) agonist 11beta,17beta-dihydroxy-6,21-dimethyl-17alpha-pregna-4,6-trien-20yn-3-one (RU 28362) (15 ng) infused into the hippocampus of male Sprague Dawley rats 60 min before water maze retention testing, 24 hr after training, impaired probe trial retention performance, as assessed by quadrant search time and initial latency to cross the platform location. Because we found previously that RU 28362 infused into the hippocampus does not affect water maze acquisition or immediate recall, the findings suggest that the GR agonist-induced retention impairment was attributable to a selective influence on long-term memory retrieval. Likewise, systemic injections of the beta1-adrenoceptor partial agonist xamoterol (3.0 or 10.0 mg/kg, s.c.) 60 min before the probe trial dose-dependently impaired retention performance. The beta-adrenoceptor antagonist propranolol (2.0 mg/kg) administered subcutaneously before retention testing did not affect retention performance alone, but blocked the memory retrieval impairment induced by concurrent intrahippocampal infusions of RU 28362. Pretest infusions of the beta1-adrenoceptor antagonist atenolol into either the hippocampus (1.25 microg in 0.5 microl) or the BLA (0.5 microg in 0.2 microl) also prevented the GR agonist-induced memory retrieval impairment. These findings suggest that glucocorticoids impair retrieval of long-term spatial memory by facilitating noradrenergic mechanisms in the hippocampus, and additionally, that norepinephrine-mediated BLA activity is critical in enabling hippocampal glucocorticoid effects on memory retrieval.
General Approaches To Mask Design For Binary Optics (1989)

The fabrication of binary optics using high quality lithographic processes requires binary masks with constant phase contours. Parameter driven software for the development of these masks has been developed at Perkin-Elmer. Applications include zone plates, aspheric lenses, and optics described using Zernike polynomials, arbitrary phase functions, and sampled phase arrays.
A G Protein-coupled Receptor Responsive to Bile Acids (2003)

So far some nuclear receptors for bile acids have been identified. However, no cell surface receptor for bile acids has yet been reported. We found that a novel G protein-coupled receptor, TGR5, is responsive to bile acids as a cell-surface receptor. Bile acids specifically induced receptor internalization, the activation of extracellular signal-regulated kinase mitogen-activated protein kinase, the increase of guanosine 5'-O-3-thio-triphosphate binding in membrane fractions, and intracellular cAMP production in Chinese hamster ovary cells expressing TGR5. Our quantitative analyses for TGR5 mRNA showed that it was abundantly expressed in monocytes/macrophages in human and rabbit. Treatment with bile acids was found to suppress the functions of rabbit alveolar macrophages including phagocytosis and lipopolysaccharide-stimulated cytokine productions. We prepared a monocytic cell line expressing TGR5 by transfecting a TGR5 cDNA into THP-1 cells that did not express TGR5 originally. Treatment with bile acids suppressed the cytokine productions in the THP-1 cells expressing TGR5, whereas it did not influence those in the original THP-1 cells, suggesting that TGR5 is implicated in the suppression of macrophage functions by bile acids.