gebhart/patrepeval huggingface dataset:
Carbocycle Synthesis via Carbopalladation of Nitriles (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTCarbocycle Synthesis via Carbopalladation of NitrilesRichard C. Larock, Qingping Tian, and Alexandre A. PletnevView Author Information Department of Chemistry, Iowa State University Ames, Iowa 50011 Cite this: J. Am. Chem. Soc. 1999, 121, 13, 3238–3239Publication Date (Web):March 19, 1999Publication History Received30 November 1998Published online19 March 1999Published inissue 1 April 1999https://pubs.acs.org/doi/10.1021/ja984086whttps://doi.org/10.1021/ja984086wrapid-communicationACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views2900Altmetric-Citations193LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Hydrocarbons,Ketones,Nitrogen compounds,Palladium,Solvents Get e-Alerts
Hyperglycemia-induced beta-cell apoptosis in pancreatic islets of Psammomys obesus during development of diabetes. (1999)

The gerbil Psammomys obesus develops nutrition-dependent diabetes associated with moderate obesity. The disease is characterized by initial hyperinsulinemia, progressing to hypoinsulinemia associated with depleted pancreatic insulin stores. The contribution of changes in beta-cell turnover to insulin deficiency was investigated in vivo during transition to overt diabetes. Normo glycemic diabetes-prone P. obesus animals who were given a high-calorie diet developed hyperglycemia within 4 days, which was found to be associated with a progressive decline in pancreatic insulin content. This was accompanied by a transient increase in beta-cell proliferative activity and by a prolonged increase in the rate of beta-cell death, culminating in disruption of islet architecture. The hypothesis that "glucotoxicity" was responsible for these in vivo changes was investigated in vitro in primary islet cultures. Exposure of islets from diabetes-prone P. obesus to high glucose levels resulted in a dose-dependent increase in beta-cell DNA fragmentation. In contrast, high glucose levels did not induce DNA fragmentation in rat islets, whereas islets from a diabetes-resistant P. obesus line exhibited a reduced and delayed response. Aminoguanidine did not prevent glucose-induced beta-cell DNA fragmentation in vitro, suggesting that formation of nitric oxide and/or advanced glycation end products plays no major role. Elevated glucose concentrations stimulated beta-cell proliferation in both rat and P. obesus islets. However, unlike the marked long-lasting effect in rat islets, only a transient and reduced proliferative response was observed in P. obesus islets; furthermore, beta-cell proliferation was inhibited after prolonged exposure to elevated glucose levels. These results suggest that hyperglycemia-induced beta-cell death coupled with reduced proliferative capacity may contribute to the insulin deficiency and deterioration of glucose homeostasis in P. obesus. Similar adverse effects of hyperglycemia could play a role in the evolution of type 2 diabetes in genetically susceptible individuals.
Comparison of Naturally Occurring Vitamin K-Dependent Proteins:  Correlation of Amino Acid Sequences and Membrane Binding Properties Suggests a Membrane Contact Site (1997)

Membrane-binding properties of human and bovine forms of vitamin K-dependent proteins Z, S, and C were characterized. Each of these proteins showed unique properties and interspecies differences that correlated with specific amino acid sequence variations in the amino-terminal 45 residues. Protein Z showed 100-fold slower membrane binding and dissociation kinetics relative to other vitamin K-dependent proteins that have been tested. This property seemed to correlate with an extra gamma-carboxyglutamic acid (Gla) residue at position 11 of protein Z. The interspecies difference for protein Z consisted of a higher packing density for the bovine protein on the membrane and a 9-fold slower dissociation rate. Higher affinity correlated with Asp at position 34 of bovine protein Z, where the human protein contains Asn. While both protein S species showed high affinity for the membrane, it was significantly greater for the human protein versus bovine protein S. Again, higher affinity correlated with an Asp (vs Asn) at position 34. Protein C was characterized by binding affinities that were 100-1000-fold lower than the other proteins. Low affinity appeared to be related to loss of Gla-32 (homologous to Gla-33 of protein Z). Interspecies differences of protein C appeared to be related to proline at position 10 (homologous to position 11 of protein Z) of bovine protein C, which produced at least 10-fold lower affinity than the human protein. Comparable substitutions at positions homologous to 11, 33, and 34 of protein Z may also underlie membrane binding behaviors of other vitamin K-dependent proteins. The three-dimensional structure of strontium-prothrombin fragment 1 [Seshadri et al. (1994) Biochemistry 33, 1087] shows that these positions are clustered on the protein surface near strontium-8, another possible candidate for membrane contact. A membrane contact mechanism consisting of an isolated protein-lipid ion pair is proposed. Comparison of naturally occurring vitamin K-dependent proteins has provided possible bases for divergent membrane binding and suggested future approaches to determine biological function.
Semisynthesis and degradation of the tubulin inhibitors epothilone and tubulysin (2003)

Abstract The structure-activity relationships of epothilones indicate that major modifications are only tolerated in the western ring segment. In particular, C2 methyl of the thiazole ring appears to be most flexible. Its broad modification started from epothilone F, which was obtained from natural epothilone B by hydroxylation via the N -oxide. Some of the prepared derivatives exhibit improved esterase stability in addition to high cytotoxic activity. For these and other favorable properties, amine (BMS-310705) was recently introduced in clinical trials. In an alternative approach, modified side chains were introduced by replacement of the C12,C15 ring segment via ring-opening olefin metathesis (ROM) of epothilone C in the presence of ethylene to 12,13- seco -epothilone C, introduction of a synthetic building block followed by ring-closing olefin metathesis (RCM), and epoxidation to the 16-alkyne analog of epothilone A. The structure of the tetrapeptide tubulysin D was confirmed by total hydrolysis to N -methyl d-pipecolic acid, l-isoleucine, tubuvaline (Tuv), tubuphenylalanine (Tup), formaldehyde, and 3-methylbutyric acid. Mild acidic hydrolysis to cyclo-tubulysin andoxidative degradation to l-valine allowed the assignment of the stereocenters of Tuv, hydrazinolysis, and comparison with synthetic reference samples to that of Tup. The absolute configuration of tubulysin D is: ( R )-Mep, (2,3 S )-Ile, (1' R ,3' R )-Tuv, and (2 S ,4 R )-Tup.
Characterization of and human serologic response to proteins in Helicobacter pylori broth culture supernatants with vacuolizing cytotoxin activity (1990)

Helicobacter pylori infection is strongly associated with histologic gastritis and peptic ulcer disease. Broth culture supernatants from a subset of H. pylori strains induce vacuolization in cultured cells, a phenomenon that has been attributed to cytotoxin activity. Concentrated culture supernatants from 15 of 28 (53.6%) H. pylori strains tested induced vacuolization in HeLa cells in titers ranging from 1:10 to 1:180. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining of supernatants from these 28 strains and 2 control strains demonstrated an 82-kilodalton (kDa) protein band in 3 of 16 supernatants with vacuolizing activity, but in none of 14 supernatants without vacuolizing activity. By immunoblotting with human sera, a 128-kDa band was recognized in all 16 supernatants with vacuolizing activity, compared with 9 of 14 (64%) supernatants without vacuolizing activity (P = 0.014). Serologic recognition of the 128-kDa band in H. pylori culture supernatants was more prevalent among persons infected with vacuolizing H. pylori strains than among persons infected with nonvacuolizing strains, but the difference was not statistically significant (80 versus 45%; P = 0.079); human serologic recognition of the 82-kDa band was less common. The 128-kDa band was recognized by 100% of 31 serum samples from H. pylori-infected patients with duodenal ulcer disease, compared with 60.8% of 74 serum samples from H. pylori-infected persons without peptic ulcer disease (P = 0.0001). These data indicate that antigenic 128- and 82-kDa proteins are present in H. pylori broth culture supernatants with vacuolizing activity and that serologic responses to the 128-kDa protein are more prevalent among H. pylori-infected persons with duodenal ulceration than among infected persons without peptic ulceration.
A Rotating Ball Inlet for On-Line MALDI Mass Spectrometry (1999)

The rotating ball inlet (ROBIN) is presented in a new design for on-line matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). This method uses a capillary to deliver a matrix and analyte solution to the surface of a rotating ball upon which MALDI is carried out. The ball is in contact with a polymer gasket surrounding the capillary. Sample adhering to the surface of the ball is dragged past the gasket into the vacuum of the mass spectrometer where it is irradiated by a pulsed UV laser, and the resulting ions are mass-separated in a linear time-of-flight mass spectrometer. The mechanical sample introduction prevents clogging of the vacuum interface by matrix crystals or frozen solvent. Preliminary results from flow injection analysis (FIA) suggest that the new interface does not introduce a significant peak-tailing or memory effect. The system is capable of 20-30 h of continuous operation with a flow rate of 2 microL/min before cleaning of the ball is needed. With the prototype inlet, concentration detection limits are at the low micromolar level.
Das Diazo‐chinon von PQQ als mögliches Reagenz für die Kartierung von Chinoproteinen mittels Photoaffinitätsmarkierung (1993)

The Diazo‐quinone of PQQ as a Possible Reagent for Mapping Quinoproteins by Photo‐affinity Labeling PQQ is an organic redox cofactor found in a class of enzymes called quinoproteins. The synthesis and the photochemistry of the diazo‐quinones of PQQ and PQQ ‐triester are described. The photogenerated Wolff ‐rear‐rangement products have been caught with water and methanol as model nucleophiles. The products show a strong fluorescence. The diazoquinone of PQQ may be considered as possible reagent for mapping quinoproteins by photo‐affinity labeling.
Electrically-pumped vertical-cavity lasers with AlxOy-GaAs reflectors (1996)

We have fabricated the first electrically-pumped vertical-cavity surface-emitting lasers (VCSELs) which use oxide-based distributed Bragg reflectors (DBRs) on both sides of the gain region. They require a third the epitaxial growth time of VCSELs with semiconductor DBRs. We obtain threshold currents as low as 160 μA in VCSELs with an active area of 8 μm×8 μm using a two quantum well InGaAs-GaAs active region. By etching away mirror pairs from the top reflector, quantum efficiencies as high as 61% are attained, while still maintaining a low threshold current of 290 μA.
Hydrogen production from natural gas and biomethane with carbon capture and storage – A techno-environmental analysis (2020)

We quantify the technical and environmental performance of clean hydrogen production (with CCS) by linking detailed process simulation with LCA.
Monitoring of biotransformation of hop aroma compounds in an in vitro digestion model (2012)

An in vitro digestion procedure followed by gas chromatography-mass spectrometry analysis has been applied to assess the stability of aroma compounds from hop oil in the human gastrointestinal tract. Hop oil is used in phytotherapy as a sedative, yet the bioactive substances responsible for this effect have not been conclusively clarified. Therefore, the focus of this study was placed on hop aroma substances that: (i) have been previously described to possess sedative properties, (ii) are suspected to have these properties due to structural features, or (iii) that are present in hop oil in high concentrations. While some compounds remained unchanged under the simulated physiological conditions, others underwent transformations to a great extent. Particularly interesting was the formation of α-terpineol and linalool from several different aroma compounds. α-Terpineol has been previously described as a bioactive compound with anti-inflammatory properties. Linalool is a well-known sedative compound and its formation during digestion could enhance the sedative effect of hop oil. The results of this study show that gastrointestinal processes can modulate the chemical composition of ingested aroma constituents and might even influence the bioactivity of essential oils.
Assays for the Evaluation of HIV-1 Integrase Inhibitors (2003)

Integration is an essential step in the replication cycle of a retrovirus, such as the human immunodeficiency virus type 1 (HIV-1) (for a review, see ref. 1). After reverse transcription of the RNA genome, the DNA copy is transported into the nucleus and integrated in the host chromosome. The only viral enzyme required for HIV-1 integration is integrase (IN), a protein of 32 kDa encoded by the 3′-end of the pol gene. The enzyme is produced by protease-mediated cleavage of the gag-pol precursor during virion maturation. Integrase can be considered a site-specific endonuclease; the removal of two nucleotides creates a hydroxyl residue at each 3′-end of the viral DNA that will carry out a nucleophilic attack on the phosphodiester backbone of the host DNA.
Sensing Arrays Constructed from Nanoparticle Thin Films and Interdigitated Microelectrodes (2006)

This paper describes the results of a study of a few design parameters influencingthe performance of sensor arrays constructed from nanostructured thin films andinterdigitated microelectrodes (IMEs). The nanostructured thin films on the IME deviceswere prepared from nonanedithiol (NDT) and mercaptoundecanoic acid (MUA) linkedassemblies of 2-nm sized gold nanoparticles. The sensor array data in response to volatileorganic compounds were collected and analyzed using fractional factorial experimentaldesign and analysis of variance for understanding effects of the design parameters on thesensitivity. While the smaller value for the microelectrode space, width, and lengthgenerally led to higher response sensitivity, a strong dependence on the nature of thenanostructured thin films was found. The microelectrode space was the most importantdesign parameter for NDT-based thin films. However, the microelectrode space, width, andlength were found to play almost equally important roles for MUA-based thin films. Theprincipal component analysis results for classification performances of the arrays consistingof a set of thin films have demonstrated the possibility of optimizing sensor arrays byappropriate selections of microelectrode parameters and nanostructured sensing films.
Identification of Ald6p as the target of a class of small-molecule suppressors of FK506 and their use in network dissection (2004)

FK506 inhibits the Ca2+/calmodulin-dependent protein phosphatase calcineurin, which plays a critical role in yeast subjected to salt stress. A chemical genetic screen for small molecules that suppress growth inhibition by high NaCl plus FK506 identified a structurally related class of suppressors of FK506 (SFKs) named SFKs 2-4. To identify possible protein targets for these small molecules, a genome-wide screen of approximately 4,700 haploid yeast deletion strains was undertaken for strains showing resistance to high NaCl plus FK506. This screen yielded a number of genes not previously implicated in salt stress, including ALD6, which encodes an NADP(+)-dependent aldehyde dehydrogenase, and UTR1, which encodes an NAD+ kinase. Transcriptional profiling of yeast treated with SFK2 indicated that the SFKs target the Ald6p pathway. In addition, screening of the deletion strains for hypersensitivity to SFK2 yielded ZWF1, encoding glucose-6-phosphate dehydrogenase, which has been shown to play an overlapping role with Ald6p in NADPH production. Furthermore, the SFKs inhibited the activity of Ald6p in vitro. Having established that the SFKs target Ald6p, they were used as tools to implicate systematically other gene products in the Ald6p pathway, including Utr1p, which may function by supplying Ald6p with its NADP+ cofactor. Furthermore, growth improvement by the SFKs on high NaCl plus FK506 was shown to require GPD1, which encodes an NADH-dependent glycerol-3-phosphate dehydrogenase that is important for the production of glycerol in response to osmotic stress.
Automated Image Analysis Method for Detecting and Quantifying Macrovesicular Steatosis in Hematoxylin and Eosin–Stained Histology Images of Human Livers (2013)

Large-droplet macrovesicular steatosis (ld-MaS) in more than 30% of liver graft hepatocytes is a major risk factor for liver transplantation. An accurate assessment of the ld-MaS percentage is crucial for determining liver graft transplantability, which is currently based on pathologists' evaluations of hematoxylin and eosin (H&E)-stained liver histology specimens, with the predominant criteria being the relative size of the lipid droplets (LDs) and their propensity to displace a hepatocyte's nucleus to the cell periphery. Automated image analysis systems aimed at objectively and reproducibly quantifying ld-MaS do not accurately differentiate large LDs from small-droplet macrovesicular steatosis and do not take into account LD-mediated nuclear displacement; this leads to a poor correlation with pathologists' assessments. Here we present an improved image analysis method that incorporates nuclear displacement as a key image feature for segmenting and classifying ld-MaS from H&E-stained liver histology slides. 52,000 LDs in 54 digital images from 9 patients were analyzed, and the performance of the proposed method was compared against the performance of current image analysis methods and the ld-MaS percentage evaluations of 2 trained pathologists from different centers. We show that combining nuclear displacement and LD size information significantly improves the separation between large and small macrovesicular LDs (specificity = 93.7%, sensitivity = 99.3%) and the correlation with pathologists' ld-MaS percentage assessments (linear regression coefficient of determination = 0.97). This performance vastly exceeds that of other automated image analyzers, which typically underestimate or overestimate pathologists' ld-MaS scores. This work demonstrates the potential of automated ld-MaS analysis in monitoring the steatotic state of livers. The image analysis principles demonstrated here may help to standardize ld-MaS scores among centers and ultimately help in the process of determining liver graft transplantability.
Review on self micro emulsifying drug delivery systems (2011)

In modern drug discovery techniques, there has been a consistent increase in the number of poor water soluble drug candidate compounds, and currently more than 50% of new pharmacologically active chemical entities are lipophilic and exhibit poor water solubility. Self-micro emulsifying drug delivery (SMEDDS) is the one of the method for the improvement of oral bioavailability. SMEDDS are the isotropic mixtures of oils, surfactants, solvents and co-solvents. This review article tries to describe the formulation of SMEDDS and also talks about the construction of the phase diagram for SMEDDS. It describes the mechanism involved in self emulsification and the biopharmaceutical aspects involved. The advantages of SMEDDS over conventional emulsions are listed. Some of the marketed preparations of SMEDDS are listed in detail. A few drug delivery systems which show the scope for usage of the SMEDDS are also described.
Regulation of endothelial derived nitric oxide in health and disease (2005)

Endothelial nitric oxide synthase (eNOS) is the primary physiological source of nitric oxide (NO) that regulates cardiovascular homeostasis. Historically eNOS has been thought to be a constitutively expressed enzyme regulated by calcium and calmodulin. However, in the last five years it is clear that eNOS activity and NO release can be regulated by post-translational control mechanisms (fatty acid modification and phosphorylation) and protein-protein interactions (with caveolin-1 and heat shock protein 90) that direct impinge upon the duration and magnitude of NO release. This review will summarize this information and apply the post-translational control mechanisms to disease states.
Plasma DNA aberrations in systemic lupus erythematosus revealed by genomic and methylomic sequencing (2014)

We performed a high-resolution analysis of the biological characteristics of plasma DNA in systemic lupus erythematosus (SLE) patients using massively parallel genomic and methylomic sequencing. A number of plasma DNA abnormalities were found. First, aberrations in measured genomic representations (MGRs) were identified in the plasma DNA of SLE patients. The extent of the aberrations in MGRs correlated with anti-double-stranded DNA (anti-dsDNA) antibody level. Second, the plasma DNA of active SLE patients exhibited skewed molecular size-distribution profiles with a significantly increased proportion of short DNA fragments. The extent of plasma DNA shortening in SLE patients correlated with the SLE disease activity index (SLEDAI) and anti-dsDNA antibody level. Third, the plasma DNA of active SLE patients showed decreased methylation densities. The extent of hypomethylation correlated with SLEDAI and anti-dsDNA antibody level. To explore the impact of anti-dsDNA antibody on plasma DNA in SLE, a column-based protein G capture approach was used to fractionate the IgG-bound and non-IgG-bound DNA in plasma. Compared with healthy individuals, SLE patients had higher concentrations of IgG-bound DNA in plasma. More IgG binding occurs at genomic locations showing increased MGRs. Furthermore, the IgG-bound plasma DNA was shorter in size and more hypomethylated than the non-IgG-bound plasma DNA. These observations have enhanced our understanding of the spectrum of plasma DNA aberrations in SLE and may provide new molecular markers for SLE. Our results also suggest that caution should be exercised when interpreting plasma DNA-based noninvasive prenatal testing and cancer testing conducted for SLE patients.