gebhart/patrepeval huggingface dataset:
Mechanism of anti-HIV action of masked alaninyl d4T-MP derivatives. (1996)

So324 is a 2',3'-dideoxy-2',3'-didehydrothymidine-5'-monophosphate (d4T-MP) prodrug containing at the phosphate moiety a phenyl group and the methylester of alanine linked to the phosphate through a phosphoramidate linkage. So324 has anti-HIV activity in human CEM, MT4, and monocyte/macrophage cells that is superior to that of d4T. In contrast to d4T, So324 is also able to inhibit HIV replication in thymidine kinase-deficient CEM cells. After uptake of So324 by intact human lymphocytes, d4T-MP is released and subsequently converted intracellularly to d4T-TP. In addition, accumulation of substantial amounts of a novel d4T derivative has been found. This d4T metabolite has been characterized as alaninyl d4T-MP. The latter metabolite accumulates at approximately 13- to 200-fold higher levels than d4T-TP depending the experimental conditions. Alaninyl d4T-MP should be considered as an intra- and/or extracellular depot form of d4T and/or d4T-MP. These findings may explain the superior anti-retroviral activity of So324 over d4T in cell culture.
Cross-linking analysis of the outer membrane proteins of Neisseria gonorrhoeae (1980)

The organization of outer membrane proteins of Neisseria gonorrhoeae was investigated by using two-dimensional dodecyl sulfate-polyacrylamide gel electrophoresis and cross-linking agents. A naturally occurring protein aggregate, which may be composed of two proteins of 50,000 molecular weight, was detected in all strains. Treatment of whole cells with cross-linking agents yielded several additional complexes, suggesting that other proteins are arranged in the outer membrane as near neighbors. The principal outer membrane protein (molecular weight, 34,000) cross-linked (i) to itself to form a complex whch appeared to be trimeric, (ii) to the 28,000-molecular-weight outer membrane protein to form a bimolecular comlex, and (iii) to the 28,000-molecular-weight outer membrane protein in a 3:1 ratio. The formation of these complexes was independent of (i) colony type, (ii) colony opacity, (iii) pH during growth, and (iv) presence of markers for drug resistance or hypersensitivity.
THE SOCIETAL COSTS OF SEVERE TO PROFOUND HEARING LOSS IN THE UNITED STATES (2000)

Results indicate that an additional $4.6 billion will be spent over the lifetime of persons who acquired their impairment in 1998. The particularly high costs associated with prelingual onset of severe to profound hearing impairment suggest interventions aimed at children, such as early identification and/or aggressive medical intervention, may have a substantial payback.
Fibroblast growth factor‐2 converts PACAP growth action on embryonic hindbrain precursors from stimulation to inhibition (2002)

Pituitary adenylyl cyclase activating peptide (PACAP) has been shown either to stimulate or to inhibit neural cell proliferation depending on the origin of the cell population. We show here that, depending on the presence or absence of fibroblast growth factor-2 (FGF-2, also called basic FGF), PACAP may either stimulate or inhibit DNA synthesis in neural precursors isolated from embryonic day 10.5 mouse hindbrain. In the absence of FGF-2, PACAP stimulated 3H-thymidine incorporation in a dose-dependent manner. This stimulatory action was unaffected by antagonists of protein kinases A and C but was abolished in the presence of the MEK1/2 antagonist PD98059. In contrast, when FGF-2 was present, PACAP inhibited DNA synthesis. This inhibitory action was insensitive to PD98059 but was fully blocked by the protein kinase A (PKA) inhibitor H89. The differential blockades by MEK1/2 and PKA inhibitors indicate that the FGF-2-induced switch in PACAP action on DNA synthesis was accomplished by a change in PACAP signaling pathways. We hypothesize that the actions of PACAP in the specific parts of the developing nervous system are determined in part by the presence or absence of FGFs and other growth factors.
TNT003, an inhibitor of the serine protease C1s, prevents complement activation induced by cold agglutinins (2014)

Activation of the classical pathway (CP) of complement is often associated with autoimmune disorders in which disease pathology is linked to the presence of an autoantibody. One such disorder is cold agglutinin disease (CAD), an autoimmune hemolytic anemia in which autoantibodies (cold agglutinins) bind to red blood cells (RBCs) at low temperatures. Anemia occurs as a result of autoantibody-mediated CP activation on the surface of the erythrocyte, leading to the deposition of complement opsonins that drive extravascular hemolysis in the liver. Here we test the effects of TNT003, a mouse monoclonal antibody targeting the CP-specific serine protease C1s, on CP activity induced by cold agglutinins on human RBCs. We collected 40 individual CAD patient samples and showed that TNT003 prevented cold agglutinin-mediated deposition of complement opsonins that promote phagocytosis of RBCs. Furthermore, we show that by preventing CP activation, TNT003 also prevents cold agglutinin-driven generation of anaphylatoxins. Finally, we provide evidence that CP activity in CAD patients terminates prior to activation of the terminal cascade, supporting the hypothesis that the primary route of RBC destruction in these patients occurs via extravascular hemolysis. Our results support the development of a CP inhibitor for the treatment of CAD.
Ordered assembly of the asymmetrically branched lipid-linked oligosaccharide in the endoplasmic reticulum is ensured by the substrate specificity of the individual glycosyltransferases (1999)

The assembly of the lipid-linked core oligosaccharide Glc3Man9GlcNAc2, the substrate for N-linked glycosylation of proteins in the endoplasmic reticulum (ER), is catalyzed by different glycosyltransferases located at the membrane of the ER. We report on the identification and characterization of the ALG12 locus encoding a novel mannosyltransferase responsible for the addition of the alpha-1,6 mannose to dolichol-linked Man7GlcNAc2. The biosynthesis of the highly branched oligosaccharide follows an ordered pathway which ensures that only completely assembled oligosaccharide is transferred from the lipid anchor to proteins. Using the combination of mutant strains affected in the assembly pathway of lipid-linked oligosaccharides and overexpression of distinct glycosyltransferases, we were able to define the substrate specificities of the transferases that are critical for branching. Our results demonstrate that branched oligosaccharide structures can be specifically recognized by the ER glycosyltransferases. This substrate specificity of the different transferases explains the ordered assembly of the complex structure of lipid-linked Glc3Man9GlcNAc2 in the endoplasmic reticulum.
Pharmacological characterization of the seven human NOX isoforms and their inhibitors (2019)

Our findings indicate that experimental results obtained with widely used NOX inhibitors must be carefully interpreted and highlight the challenge of developing reliable pharmacological inhibitors of these key molecular targets.
PD-1 Inhibits Antiviral Immunity at the Effector Phase in the Liver (2003)

Unlike naive T cells, effector T cells can be activated by either T cell receptor signal or costimulatory signal alone and therefore the absence of costimulatory molecules on tissue cells cannot explain the tolerance mechanism at the effector phase. Here we report that PD-L1, the ligand for the immunoinhibitory receptor PD-1, was expressed on vascular endothelium in peripheral tissues. Liver nonparenchymal cells including sinusoidal endothelial cells and Kupffer cells constitutively expressed PD-L1 and inhibited proliferation and cell division of activated T cells expressing PD-1. The absence of PD-1 induced proliferation of effector T cells in the adenovirus-infected liver and resulted in rapid clearance of the virus. These results indicate that PD-1 plays an important role in T cell tolerance at the effector phase and the blockade of the PD-1 pathway can augment antiviral immunity.
Alteration of surfactant function due to protein leakage: special interaction with fibrin monomer (1985)

In isolated rabbit lungs standardized amounts of edema were induced. Stimulation with the Ca ionophore A23187, leukotriene C4, Pseudomonas aeruginosa cytotoxin and human serum (activated complement) all resulted in protein leakage into the alveolar space with no change in the total phospholipid content. The pressure-volume characteristics of the lungs and the characteristics of the lavage surfactant (Wilhelmy balance) were markedly altered, correlating to the lavage protein content. The surfactant alterations were reproduced by addition of perfusion fluid protein to control surfactant in vitro. All changes were far less expressed or even missing in isolated lungs developing the same amount of edema due to omittance of proteins from the perfusion liquid. Different proteins added to control surfactant in the Wilhelmy balance showed a marked rank order of potency in interfering with surfactant function: immunoglobulins G and M and elastin less than albumin less than fibrinogen less than fibrin monomers. The fibrin monomer effect was reproduced by addition of thrombin to a surfactant fibrinogen mixture and was partly reversed by subsequent incubation with plasmin. In conclusion, high-permeability edema induced by different means results in alterations of lung mechanics and surface activity of lavaged surfactant, presumably due to protein surfactant interaction. Among different proteins, fibrin monomers are especially effective in interfering with surfactant function.
Hormone-sensitive cyclic GMP-inhibited cyclic AMP phosphodiesterase in rat adipocytes. Regulation of insulin- and cAMP-dependent activation by phosphorylation (1991)

In 32PO4-labeled adipocytes, isoproterenol (ISO) or physiologically relevant concentrations of insulin rapidly increased phosphorylation of a particulate 135-kDa protein which has been identified as a cGMP-inhibited "low Km" cAMP phosphodiesterase (CGI-PDE) by several criteria, including selective immunoprecipitation with anti-CGI-PDE IgG (Degerman, E., Smith, C.J., Tornqvist, H., Vasta, V., Belfrage, P., and Manganiello, V.C. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 533-537). The time courses and concentration dependences for phosphorylation of CGI-PDE by ISO and insulin correlated with CGI-PDE activation in the presence of these agents; effects of ISO were somewhat more rapid than those of insulin. Adenosine deaminase, which metabolizes the adenylate cyclase inhibitor adenosine, also rapidly induced phosphorylation and activation of CGI-PDE. Phenylisopropyladenosine (an adenosine deaminase-resistant adenosine analog) prevented or reversed both adenosine deaminase-stimulated phosphorylation and activation of CGI-PDE (IC50 approximately 0.2 nM). Incubation of adipocytes with 0.1 nM insulin in the presence of ISO rapidly produced 30-200% greater activation and phosphorylation of CGI-PDE than the expected added effects of insulin and ISO individually; both effects preceded the insulin-induced decreases in protein kinase A activity and inhibition of lipolysis. These and other results indicate that CGI-PDE can be phosphorylated at distinct sites and activated by cAMP-dependent and insulin-dependent serine kinase(s), that the activation state of CGI-PDE reflects its relative phosphorylation state, and that synergistic phosphorylation/activation of CGI-PDE may be important in the antilipolytic action of insulin.
Finding circles by an array of accumulators (1975)

We describe an efficient procedure for detecting approximate circles and approximately circular arcs of varying gray levels in an edge-enhanced digitized picture. This procedure is an extension and improvement of the circle-finding concept sketched by Duda and Hart [2] as an extension of the Hough straight-line finder [6].
A Novel Strategy for Encapsulation and Release of Proteins:  Hydrogels and Microgels with Acid-Labile Acetal Cross-Linkers (2002)

A new acid-labile acetal cross-linker was synthesized and used to prepare protein-loaded hydrogels and microgels. This cross-linker undergoes an acid-catalyzed degradation with a half-life of 5.5 min at pH 5.0 and 24 h at pH 7.4. Protein-loaded hydrogels were synthesized with this cross-linker, and their release profiles were measured as a function of pH. Hydrogels made with the acetal cross-linker release their contents in a pH-dependent manner. The acetal cross-linker was also used to synthesize microgels with sizes between 1 and 10 mum, a range suitable for phagocytosis. The unique acid sensitivity of the acetal cross-linker should make it a useful synthetic intermediate in the design of acid-sensitive drug or gene delivery systems.
Automatic Metaphor Recognition Based on Semantic Relation Patterns (2010)

Focusing on Chinese subject-predicate constructions, this paper analyzes the limitations of Selectional-Preference based metaphor recognition and proposes a new metaphor recognition model which is based on Semantic Relation Patterns. The model constructs Semantic Relation Pattern by integrating six types of semantic relations between a subject head and other subject heads in a subject-predicate cluster which share the same predicate head, and then employs a SVM classifier for metaphor recognition. Experiments show that the model outperforms the Selectional-Preference based metaphor recognition model to a great extent, achieving an F-1 of 89% in metaphor recognition, about 37% higher than Selectional-Preference based model. Analysis shows that the model is able to account for lexicalized metaphors, truth-condition literality and other types of literality and metaphor failed in Selectional-Preference based models. More importantly, the model can be generalized to unknown predicate heads. Theoretically, the semantic-relation-pattern model can also be applied in all endocentric constructions such as verb-objects and adjective-nouns.
Improved Alkaline Oxidation Process for the Production of Aldehydes (Vanillin and Syringaldehyde) from Steam-Explosion Hardwood Lignin (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTImproved Alkaline Oxidation Process for the Production of Aldehydes (Vanillin and Syringaldehyde) from Steam-Explosion Hardwood LigninGuoxiong Wu, Michele Heitz, and Esteban ChornetCite this: Ind. Eng. Chem. Res. 1994, 33, 3, 718–723Publication Date (Print):March 1, 1994Publication History Published online1 May 2002Published inissue 1 March 1994https://pubs.acs.org/doi/10.1021/ie00027a034https://doi.org/10.1021/ie00027a034research-articleACS PublicationsRequest reuse permissionsArticle Views1225Altmetric-Citations97LEARN 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
BCR/ABL-mediated increased expression of multiple known and novel genes that may contribute to the pathogenesis of chronic myelogenous leukemia. (2003)

The BCR/ABL chimeric protein plays a central role in the pathogenesis of chronic myelogenous leukemia (CML). Intensive research has elucidated many signal transduction pathways activated by BCR/ABL. However, few studies addressed BCR/ABL-dependent alterations in gene expression that may contribute to the pathobiology of CML. To additionally define such downstream genes, we performed a subtractive hybridization between cord blood (CB) CD34(+) cells transduced with an MSCV-retrovirus vector containing either enhanced green fluorescent protein (eGFP) alone or p210(BCR/ABL)-internal ribosome entry site-eGFP. Thirty-four subtracted clones expressed in p210-eGFP but not eGFP-transduced CD34(+) cells have been confirmed by Northern blot and sequenced. Fifty-nine percent represent novel proteins, and 41% are homologous to known genes. Quantitative real-time PCR analysis confirmed that 14 of 14 genes tested were also overexpressed in additional populations of p210(BCR/ABL)-transduced CB CD34(+) cells, as well as in CD34(+) cells from primary newly diagnosed CML patients versus GFP-transduced CB or samples from normal donors. Western blot analysis showed that the known sequences were also overexpressed at the protein level. Treatment of BCR/ABL(+) cells with the Abl-specific tyrosine kinase inhibitor STI571 decreased expression at the mRNA as well as protein level of some but not all of the gene products. This suggests that increased gene expression is in some cases tyrosine kinase-independent. Some of the overexpressed genes are implicated in cellular processes known to be disturbed in CML, including the mitogen-activated protein kinase or the ubiquitin pathway, whereas overexpression of other genes, including RAN and NUP98, may implicate new cellular pathways involved in CML. Additional characterization of downstream genes activated by BCR/ABL may lead to important new insights in the molecular mechanisms underlying CML and identify potentially novel therapeutic targets for CML.
A standard numbering scheme for the class A β-lactamases (1991)

peer reviewed
GOToolBox: functional analysis of gene datasets based on Gene Ontology (2004)

We have developed methods and tools based on the Gene Ontology (GO) resource allowing the identification of statistically over- or under-represented terms in a gene dataset; the clustering of functionally related genes within a set; and the retrieval of genes sharing annotations with a query gene. GO annotations can also be constrained to a slim hierarchy or a given level of the ontology. The source codes are available upon request, and distributed under the GPL license.
Kinase Inhibitor Profiling Reveals Unexpected Opportunities to Inhibit Disease-Associated Mutant Kinases (2016)

Small-molecule kinase inhibitors have typically been designed to inhibit wild-type kinases rather than the mutant forms that frequently arise in diseases such as cancer. Mutations can have serious clinical implications by increasing kinase catalytic activity or conferring therapeutic resistance. To identify opportunities to repurpose inhibitors against disease-associated mutant kinases, we conducted a large-scale functional screen of 183 known kinase inhibitors against 76 recombinant mutant kinases. The results revealed lead compounds with activity against clinically important mutant kinases, including ALK, LRRK2, RET, and EGFR, as well as unexpected opportunities for repurposing FDA-approved kinase inhibitors as leads for additional indications. Furthermore, using T674I PDGFRα as an example, we show how single-dose screening data can provide predictive structure-activity data to guide subsequent inhibitor optimization. This study provides a resource for the development of inhibitors against numerous disease-associated mutant kinases and illustrates the potential of unbiased profiling as an approach to compound-centric inhibitor development.
Synthesis, In Vitro Evaluation, and In Vivo Metabolism of Fluor/Quencher Compounds Containing IRDye 800CW and Black Hole Quencher-3 (BHQ-3) (2011)

Protease-cleavable peptides containing a suitable fluor/quencher (Fl/Q) pair are optically dark until cleaved by their target protease, generating fluorescence. This approach has been used with many Fl/Q pairs, but little has been reported with IRDye 800CW, a popular near-infrared (NIR) fluor. We explored the use of the azo-bond-containing Black Hole Quencher 3 (BHQ-3) as a quencher for IRDye 800CW and found that IRDye 800CW/BHQ-3 is a suitable Fl/Q pair, despite the lack of proper spectral overlap for fluorescence resonance energy transfer (FRET) applications. Cleavage of IRDye 800CW-PLGLK(BHQ-3)AR-NH(2) (8) and its D-arginine (Darg) analogue (9) by matrix metalloproteinases (MMPs) in vitro yielded the expected cleavage fragments. In vivo, extensive metabolism was found. Significant decomposition of a "non-cleavable" control IRDye 800CW-(1,13-diamino-4,7,10-trioxatridecane)-BHQ-3 (10) was evident in plasma of normal mice by 3 min post injection. The major metabolite showed a m/z and UV/vis spectrum consistent with azo bond cleavage in the BHQ-3 moiety. Preparation of an authentic standard of this metabolite (11) confirmed the assignment. Although the IRDye 800CW/BHQ-3 constructs showed efficient contact quenching prior to enzymatic cleavage, BHQ-3 should be used with caution in vivo, due to instability of its azo bond.
From SAC to SAOC—Recent Developments in Parametric Coding of Spatial Audio (2007)

One of the most remarkable innovations in low bitrate audio coding during the recent years was the arrival of 'Spatial Audio Coding' (SAC) technology. Exploiting the human perception of spatial sound, these coding schemes are capable of transmitting high quality surround sound using bitrates that have been used for carrying traditional two-channel stereo audio so far. Following the recent finalization of the MPEG Surround specification, a next technology generation is envisaged for standardization within ISO/MPEG allowing bitrate-efficient and backward compatible coding of several sound objects. On the receiving side, such a 'Spatial Audio Object Coding' (SAOC) system renders the objects interactively into a sound scene on a reproduction setup of choice. The paper reviews the principles and current status of Spatial Audio Coding schemes and discusses their evolution towards Spatial Audio Object Coding with particular focus on the ongoing ISO/MPEG Audio standardization activities in this field. Entnommen aus &lt;a href="http://www.fiz-technik.de/db/b_tema.htm" target="_blank"&gt;TEMA&lt;/a&gt;
Neural transplantation using temperaturesensitive immortalized neural cells: A preliminary report (1990)

Current approaches to neural transplantation--adrenal medullary and fetal brain--suffer from limitations in tissue availability, cellular uniformity, and general applicability. The system described here uses temperature-sensitive immortalized clonal neural cells to address these limitations. Cerebellar cells, immortalized with a temperature-sensitive tumor virus, are transformed at 34 degrees C, but differentiate at 38 degrees C. The cells were genetically engineered to express beta-galactosidase, providing a tag to study their fate in the host. The cells were then successfully transplanted to the cerebellum of adult rats.
Identification of mRNA Markers for Molecular Staging of Lymph Nodes in Colorectal Cancer (2006)

Several mRNA markers are capable of providing exceptionally accurate characterization of lymph node status in colorectal cancer. An automated, multimarker, quantitative reverse transcription-PCR assay for characterization of lymph nodes from colorectal cancer patients may be useful for improved staging and therapeutic decision making in colorectal cancer.