gebhart/patrepeval huggingface dataset:
Synthesis of Deoxy, Dideoxy and Didehydrodideoxy Analogs of 9-(4-C-Hydroxymethyl-α-L-pentofuranosyl)adenine (1994)

Condensation of 1,2-di- O -acetyl-3,5-di- O -benzoyl-4- C -benzoyloxymethyl-L-arabinofuranose with N 6 -benzoyladenine, catalyzed with tin tetrachloride, afforded nucleoside I , which upon partial deacetylation and subsequent mesylation was converted into 9-(3,5-di- O -benzoyl-4- C -benzoyloxymethyl-2- O -methanesulfonyl-α-L-arabinofuranosyl)adenine ( III ). 9-(2,5,6-Tri- O -acetyl-4- C -acetoxymethyl-3- O -methanesulfonyl-α-L-arabinofuranosyl)- N 6 -benzoyladenine ( V ) was obtained by condensation of 1,2,5-tri- O -acetyl-4- C -acetoxymethyl-3- O -methanesulfonyl-L-arabinose with N 6 -benzoyladenine. Reaction of mesyl derivatives III and V with methanolic sodium methoxide afforded 2',3'-anhydro nucleosides VIa and VIIa , which were acetylated to give 9-(5- O -acetyl-4- C -acetoxymethyl-2,3-anhydro-α-L-ribofuranosyl)adenine ( VIb ) and 9-(5- O -acetyl-4- C -acetoxymethyl-2,3-anhydro-α-L-lyxofuranosyl)adenine ( VIIb ). Epoxy derivative VIb was cleaved with bromotrimethylsilane to 9-(5- O -acetyl-4- C -acetoxymethyl-2-bromo-2-deoxy-α-L-arabinofuranosyl)adenine ( VIIIa ); the same reaction with epoxy derivative VIIb afforded a mixture of 9-(5- O -acetyl-4- C -acetoxymethyl- 2-bromo-2-deoxy-α-L-xylofuranosyl)adenine ( IXa ) and 9-(5- O -acetyl-4- C -acetoxymethyl-3-bromo- 3-deoxy-α-L-arabinofuranosyl)adenine ( Xa ). Their dehalogenation with tributylstannane and subsequent deacetylation led to 9-(2-deoxy-4- C -hydroxymethyl-α-L- erythro -pentofuranosyl)adenine ( VIIIc ), 9-(2-deoxy-4- C -hydroxymethyl- α-L- threo -pentofuranosyl)adenine ( IXc ) and 9-(3-deoxy-4- C -hydroxymethyl-α-L- threo -pentofuranosyl)adenine ( Xc ). 9-(2,5-Di- O -acetyl-4- C -acetoxymethyl-2-bromo-2-deoxy-α-L-arabinofuranosyl)adenine ( VIIId ), prepared by acetylation of VIIIa , on reductive elimination with Cu/Zn couple and subsequent deacetylation afforded 9-(2,3-dideoxy-4- C -hydroxymethyl-α-L- glycero -pent-2-enofuranosyl)adenine ( XIb ). 9-(2,3-Dideoxy-4- C -hydroxymethyl-α-L- glycero -pentofuranosyl)adenine ( XIIb ) was obtained either by catalytic hydrogenation of bromo derivative VIIId , followed by deacetylation, or by catalytic hydrogenation of didehydro derivative XIb . The nucleosides synthesized were tested for antiviral activity.
Optimizing Preparative LC/MS Configurations and Methods for Parallel Synthesis Purification (2003)

Preparative LC/MS is widely employed to address the high-throughput purification demands of parallel synthesis. However, conflicting chromatography requirements and the complexities of applying MS-directed fractionation can limit its effectiveness in high-throughput parallel synthesis schemes. We report here an at-column dilution small-scale preparative LC configuration which satisfies the mass loading (>20 mg) and small fraction volume (<1.5 mL) requirements of discovery parallel synthesis schemes employing plate mapping. We also present a protocol for compound-specific optimization of the preparative gradient LC method and MS threshold for fractionation from a “prepreparative” LC/MS analysis of the crude material. We will demonstrate significantly improved preparative separations (relative to “universal” prep LC methods) and the selection of reliable and effective fraction threshold methods for diverse libraries. The methods and configurations are simple to implement and are equally suited for “open access” and “expert” applications of preparative LC/MS purification.
Comparison of safety and tolerability with continuous (exenatide once weekly) or intermittent (exenatide twice daily) GLP ‐1 receptor agonism in patients with type 2 diabetes (2012)

Both exenatide formulations were generally safe and well-tolerated, with ExQW associated with less nausea and vomiting but more injection-site AEs. Continuous vs. intermittent exposure did not impact the overall tolerability profile of exenatide, with no evidence of prolonged duration or worsened intensities of AEs with continuous exposure.
Stretch-induced membrane type matrix metalloproteinase and tissue plasminogen activator in cardiac fibroblast cells (1998)

In the normal heart, cardiomyocytes are surrounded by extracellular matrix (ECM) and latent matrix metalloproteinases (MMPs), which are produced primarily by cardiac fibroblasts. An activator of latent MMPs might be induced by ischemic conditions or pressure-induced stretching. To test the hypothesis that an activator of latent MMP is induced in the ischemic heart during transformation of a compensatory hypertrophic response to a decompensatory failing response in cardiac fibroblast cells, we stretched the human cardiac fibroblasts at 25 cycles/min in serum-free or 5% serum culture condition. The membrane type (MT)-MMP activity in stretched cells was measured by zymography and immuno-blot analyses using MT-MMP-2 antibody. The MT-MMP activity was further characterized by transverse-urea gradient (TUG)-zymography. The results suggested that stretch induced a membrane MMP in the fibroblasts that was similar to the MT-MMP induced in ischemic heart. Furthermore, we observed that membrane MMP has distinct mobility in TUG-zymography. To localize the MT-MMP and tissue plasminogen activator (tPA) of latent MMPs, the membrane and cytosol were separated by a method employing a detergent and sedimentation. The MT-MMP and tPA activities of cytosol and membrane fractions were measured by gelatin- and plasminogen-zymography, respectively. Differential-display mRNA analysis was performed on control and stretched cells. In situ immuno-labelling was performed to localize the MT-MMP. The results indicate that induction of MT-MMP occurred in the membrane fractions. The secretion of tPA was elevated in the stretched cells. The MT-MMP activity was inhibited by prior incubation with an antibody generated to membrane MMP. The tPA activity was inhibited by using tPA antibody. These results suggest that, under stretched conditions, neutral transmembrane matrix proteinases are induced in the cardiac fibroblasts. This may lead to activation of adverse ECM remodeling, cardiac dilatation, and failure.
1 - Einleitung (2018)

Der Leitzins ist das zentrale Instrument der Geldpolitik. Dieser wird von den Zentralbanken festgelegt und lenkt maßgeblich die allgemeine Zinsentwicklung. Die US-Notenbank Federal Reserve legt großen Wert darauf, ihre Absichten klar und frühzeitig an die Finanzmärkte zu signalisieren, um Verwerfungen an den Märkten kleinzuhalten. Ein Ereignis im Sinne dieses Buches ist eine Zusammenkunft der Mitglieder des Federal Open Market Committe (FOMC), um über den weiteren Verlauf der Leitzinsen abzustimmen. Robert Köck zeigt in seinem dargestellten Modell ein Werkzeug, mit Hilfe dessen sich mögliche Änderungen des Leitzinssatzes frühzeitig abschätzen lassen.
Steady State Kinetics of Spleen Tyrosine Kinase Investigated by a Real Time Fluorescence Assay (2007)

Spleen tyrosine kinase (Syk) is a cytoplasmic tyrosine kinase that plays an important signaling role in several types of immune cells. To improve our understanding of the enzymology and activation mechanism of Syk, we characterized the steady state kinetics of Syk substrate phosphorylation. A new real time fluorescence kinase assay was employed that utilizes a nonnatural amino acid in the peptide substrate which undergoes an enhancement in fluorescence following phosphorylation. Characterizing the steady state kinetics using a Syk kinase domain construct [Syk(360-635)] revealed that Syk employs a ternary complex kinetic mechanism involving little cooperativity between substrate binding sites and a Km(ATP) of 36 +/- 5 microM and a Km(peptide substrate) of 4.4 +/- 0.9 microM. The order of substrate binding was determined to be either random or ordered with ATP binding first, as determined in substrate analogue inhibitor studies. Utilizing the real time capabilities of the fluorescence assay, we established that Syk demonstrates no lag phase in product formation. Furthermore, a Syk mutant lacking tyrosine in the activation loop (Syk Y525F,Y526F) exhibited activity identical to that of wild-type Syk. These two findings indicate that autophosphorylation of the activation loop of Syk does not regulate Syk(360-635) activity. We also compared the activity of Syk(360-635) to that of full-length Syk and revealed that Syk(360-635) is 10-fold more active, suggesting that residues outside the catalytic domain of Syk suppress kinase activity. The findings presented here provide the first kinetic description of the Syk enzyme mechanism.
Cloning and expression of the beta- and gamma-subunits of the human epithelial sodium channel (1995)

Amiloride-sensitive Na+ channels are an important component of the Na+ reabsorption pathway in a number of epithelia. Here we report the cloning and characterization of cDNAs encoding two subunits of the human kidney epithelial Na+ channel (beta- and gamma-hENaC). Their predicted amino acid sequences were highly homologous (83-85% identical) to the corresponding subunits reported from rat colon (beta- and gamma-rENaC). Both beta- and gamma-hENaC mapped to human chromosome 16. Northern blot analysis showed high expression of beta- and gamma-hENaC in kidney and lung and differential expression of the three subunits in other tissues. Coexpression of beta- and gamma-hENaC with alpha-hENaC in Xenopus oocytes produced Na+ channels with high selectivity for Na+ and high sensitivity to amiloride. In addition, human subunits were able to substitute for the corresponding rat subunits in forming functional Na+ channels, suggesting conservation of function and suggesting that differences in sequence do not disrupt interactions between subunits. These results suggest that human alpha-, beta-, and gamma-ENaC together form Na+ channels with properties that are similar to those observed in epithelia, and will allow further investigation into the role that these channels may play in human disease.
Cd1-Reactive Natural Killer T Cells Are Required for Development of Systemic Tolerance through an Immune-Privileged Site (1999)

Systemic tolerance can be elicited by introducing antigen into an immune-privileged site, such as the eye, or directly into the blood. Both routes of immunization result in a selective deficiency of systemic delayed type hypersensitivity. Although the experimental animal model of anterior chamber-associated immune deviation (ACAID) occurs in most mouse strains, ACAID cannot be induced in several mutant mouse strains that are coincidentally deficient in natural killer T (NKT) cells. Therefore, this model for immune-privileged site-mediated tolerance provided us with an excellent format for studying the role of NKT cells in the development of tolerance. The following data show that CD1-reactive NKT cells are required for the development of systemic tolerance induced via the eye as follows: (a) CD1 knockout mice were unable to develop ACAID unless they were reconstituted with NKT cells together with CD1(+) antigen-presenting cells; (b) specific antibody depletion of NKT cells in vivo abrogated the development of ACAID; and (c) anti-CD1 monoclonal antibody treatment of wild-type mice prevented ACAID development. Significantly, CD1-reactive NKT cells were not required for intravenously induced systemic tolerance, thereby establishing that different mechanisms mediate development of tolerance to antigens inoculated by these routes. A critical role for NKT cells in the development of systemic tolerance associated with an immune-privileged site suggests a mechanism involving NKT cells in self-tolerance and their defects in autoimmunity.
Guide for the mechanistic-empirical design of new and rehabilitated pavement structures: materials characterization: is your agency ready? (2004)

The implementation of the Guide for the Mechanistic-Empirical Design of New and Rehabilitated Pavement Structures (Design Guide) as a standard design practice will also require significant changes to pavement design procedures, testing procedures and equipment, traffic data input, climatic data input, performance criteria, and others. The Design Guide performance models are calibrated using data from the Strategic Highway Research Program (SHRP) Long Term Pavement Performance (LTPP) Program. To maximize the benefits of the Design Guide, agencies will need to embark on an implementation process to ensure that all of the input parameters are acceptable and practical for their location. The Design Guide provides a hierarchical methodology with three levels of design ranging from Level 1 (detailed project specific inputs) to Level 3 (default regional inputs). This paper presents the material characterization input and testing required for use in the Design Guide.
Reconstructive Knee Surgery (1995)

Operating room environment, Peter R. Kurzweil and Lois C. McCauley. Part 1 Extensor mechanism - patellofemoral problems: arthroscopic lateral release of the patella with electrocautery, Seth I. Gasser and Douglas W. Jackson anteromedial tibial tubercle transfer, John P. Fulkerson patellectomy, Christopher S. Proctor and Dougles W. Jackson. Part 2 Meniscus surgery: meniscus repair - the outside-in technique, Lanny L. Johnson meniscus repair - the inside-out technique, Mark F. Money and Thomas D. Rosenberg meniscus repair - the all-inside arthroscopic technique, Craig D. Morgan. Part 3 Ligament injuries and instability: anterior cruciate ligament reconstruction, Douglas W. Jackson and Peter R. Kurzweil arthroscopic-assisted posterior cruciate ligament repair/reconstruction, Mark F. Mooney and Lonnie E. Paulos posterolateral corner collateral ligament reconstruction, William G. Clancy et al surgical and reconstructive technique for knee dislocations, Michael J. Maynard and Russell F. Warren high tibial posteotomy in knees with associated chronic ligament deficiencies, Frank R. Noyes and Craig S. Roberts. Part 4 Intraarticular fractures of the tibia and patella: arthroscopic management of intraarticular tibial fractures, Jerome E. Jennings arthroscopically-assisted fixation of patella fractures, Peter R. Kurzweil open reduction internal fixation of intraarticular fractures of the tibia, Robert C. Schenck, Jr and James D. Heckman. Part 5 Articular cartilage and synovium: arthroscopic chondroplasty, J. Whit Ewing osteochondritis dissecans, S. Terry Canale arthroscopic synovectomy, Dinesh Patel et al.
Histones, protamine, and polylysine but not poly(E:K) enhance transfection efficiency (1997)

Liposomal gene delivery has a great potential for the treatment of cancer and other human diseases. In this work we have investigated the optimal conditions for liposome-mediated transfer of the luciferase gene to human erythroleukemia K562 cells. DDAB:DOPE liposomes were more efficient than lysyl-DOPE:DOPE (1:2) and DDAB:cholesterol for transfection. Total histones from bovine thymus, salmon sperm protamine, and polylysine at an optimal ratio of 0.5 mg protein/mg DNA enhanced up to 7-fold the transfection efficiency of luciferase plasmids; on the contrary, the synthetic polymer poly(E:K), containing glutamic acid and lysine residues in a random order at a ratio 1:4, diminished luciferase expression. Transfection was nearly zero at high histone:DNA ratio by reversal of the charge of the particle from negative to positive leading:to its inability to interact with cationic liposomes. The increase in luciferase gene expression by DNA-binding proteins might arise from an increased transfer across the cell membrane of the liposome-DNA-protein complex but also by an increase in nuclear import of the DNA-protein complex because of the presence of nuclear localization signals on the protein molecule used for DNA condensation.
Eosinophilic bronchitis: clinical manifestations and implications for treatment (2002)

Airway inflammation with eosinophils is now reported to occur not only in asthma but in other airway diseases such as cough variant asthma, chronic cough, atopic cough, episodic symptoms without asthma, allergic rhinitis, and COPD. Although the prevalence of eosinophilic bronchitis (EB) is less than in asthma, the causes, mechanisms and treatment of EB in these conditions appears to be similar to asthma where allergen induced IL-5 secretion and symptoms are readily responsive to inhaled corticosteroids. The prognosis of EB without asthma is not known but it may be a precursor for asthma and, if so, recognition of this syndrome may permit effective treatment and reduction in the rising prevalence of asthma. Induced sputum analysis allows recognition of EB in clinical practice. The place of the asthma treatment paradigm with early and sustained corticosteroid treatment needs to be defined in EB without asthma. Airway wall remodelling can occur in rhinitis, COPD, and cough variant asthma with EB. The mechanisms and long term implications of this complication in EB without asthma need to be clarified.
Correlation of integrin β3 mRNA and vascular endothelial growth factor protein expression profiles with the clinicopathological features and prognosis of gastric carcinoma (2008)

Integrin beta3 and VEGF expression can synergistically enhance tumor angiogenesis, and may play a crucial role in invasion and metastasis of gastric carcinoma. Therefore, they may be prognostic biomarkers and novel molecular therapeutic targets.
Probabilistic Latent Semantic Indexing (2017)

Probabilistic Latent Semantic Indexing is a novel approach to automated document indexing which is based on a statistical latent class model for factor analysis of count data. Fitted from a training corpus of text documents by a generalization of the Expectation Maximization algorithm, the utilized model is able to deal with domain{specific synonymy as well as with polysemous words. In contrast to standard Latent Semantic Indexing (LSI) by Singular Value Decomposition, the probabilistic variant has a solid statistical foundation and defines a proper generative data model. Retrieval experiments on a number of test collections indicate substantial performance gains over direct term matching methods as well as over LSI. In particular, the combination of models with different dimensionalities has proven to be advantageous.
The Use of Albendazole in Patients with Single Lesions Enhanced on Contrast CT (1993)

To the Editor: Single lesions that are enhanced during computed tomography (CT) with a contrast agent are frequently found in patients with partial seizures. Reports from the Indian subcontinent su...
The Hydrogenation of Esters to Alcohols at 25-150° (1948)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Hydrogenation of Esters to Alcohols at 25-150°Homer Adkins and Harry R. BillicaCite this: J. Am. Chem. Soc. 1948, 70, 9, 3121–3125Publication Date (Print):September 1, 1948Publication History Published online1 May 2002Published inissue 1 September 1948https://pubs.acs.org/doi/10.1021/ja01189a085https://doi.org/10.1021/ja01189a085research-articleACS PublicationsRequest reuse permissionsArticle Views1615Altmetric-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
[Diabetic neuropathy: clinical and experimental progress in its pathogenesis and treatment]. (1999)

Diabetic symmetrical polyneuropathy have been known to arise from metabolic alteration such as accelerated polyol pathway and/or from neurovascular deficit. Recently, two other hypotheses were confirmed. Decreased neurotrophic supports were reported in diabetic neuropathy. Subcutaneous injection of recombinant human nerve growth factor ameliorated sensory symptoms and cooling detection threshold. The most common adverse effect was injection site hyperalagesia. Brain-derived neurotrophic factor, neurotrophin-3 and insulin-like growth factors are under clinical trials. The excessive oxidative stresses are also associated with diabetic neuropathy. Increased production and decreased scavenge system of free radicals enhance their cytotoxic effects. Alpha-lipoic acid, gliclazide and troglitazone have been reported to be effective for diabetic neuropathy.
Mechanism of Cobalt(II) Porphyrin-Catalyzed C–H Amination with Organic Azides: Radical Nature and H-Atom Abstraction Ability of the Key Cobalt(III)–Nitrene Intermediates (2011)

The mechanism of cobalt(II) porphyrin-catalyzed benzylic C-H bond amination of ethylbenzene, toluene, and 1,2,3,4-tetrahydronaphthalene (tetralin) using a series of different organic azides [N(3)C(O)OMe, N(3)SO(2)Ph, N(3)C(O)Ph, and N(3)P(O)(OMe)(2)] as nitrene sources was studied by means of density functional theory (DFT) calculations and electron paramagnetic resonance (EPR) spectroscopy. The DFT computational study revealed a stepwise radical process involving coordination of the azide to the metal center followed by elimination of dinitrogen to produce unusual "nitrene radical" intermediates (por)Co(III)-N(•)Y (4) [Y = -C(O)OMe, -SO(2)Ph, -C(O)Ph, -P(O)(OMe)(2)]. Formation of these nitrene radical ligand complexes is exothermic, predicting that the nitrene radical ligand complexes should be detectable species in the absence of other reacting substrates. In good agreement with the DFT calculations, isotropic solution EPR signals with g values characteristic of ligand-based radicals were detected experimentally from (por)Co complexes in the presence of excess organic azide in benzene. They are best described as nitrene radical anion ligand complexes (por)Co(III)-N(•)Y, which have their unpaired spin density located almost entirely on the nitrogen atom of the nitrene moiety. These key cobalt(III)-nitrene radical intermediates readily abstract a hydrogen atom from a benzylic position of the organic substrate to form the intermediate species 5, which are close-contact pairs of the thus-formed organic radicals R'(•) and the cobalt(III)-amido complexes (por)Co(III)-NHY ({R'(•)···(por)Co(III)-NHY}). These close-contact pairs readily collapse in a virtually barrierless fashion (via transition state TS3) to produce the cobalt(II)-amine complexes (por)Co(II)-NHYR', which dissociate to afford the desired amine products NHYR' (6) with regeneration of the (por)Co catalyst. Alternatively, the close-contact pairs {R'(•)···(por)Co(III)-NHY} 5 may undergo β-hydrogen-atom abstraction from the benzylic radical R'(•) by (por)Co(III)-NHY (via TS4) to form the corresponding olefin and (por)Co(III)-NH(2)Y, which dissociates to give Y-NH(2). This process for the formation of olefin and Y-NH(2) byproducts is also essentially barrierless and should compete with the collapse of 5 via TS3 to form the desired amine product. Alternative processes leading to the formation of side products and the influence of different porphyrin ligands with varying electronic properties on the catalytic activity of the cobalt(II) complexes have also been investigated.