gebhart/patrepeval huggingface dataset:
Mechanism and Activity of Ruthenium Olefin Metathesis Catalysts:  The Role of Ligands and Substrates from a Theoretical Perspective (2004)

The reaction mechanism of olefin metathesis by ruthenium carbene catalysts is studied by gradient-corrected density functional calculations (BP86). Alternative reaction mechanisms for the reaction of the "first-generation" Grubbs-type catalyst (PCy(3))(2)Cl(2)Ru=CH(2) (1) for the reaction with ethylene are studied. The most likely dissociative mechanism with trans olefin coordination is investigated for the metathesis reaction between the "first-" and the "second-generation" Grubbs-type catalysts 1 and (H(2)IMes)(PCy(3))Cl(2)Ru=CH(2) (2) with different substrates, ethylene, ethyl vinyl ether, and norbornene, and a profound influence of the substrate is found. In contrast to the degenerate reaction with ethylene, the reactions with ethyl vinyl ether and norbornene are strongly exergonic by 8-15 kcal/mol, and this excess energy is released after passing through the metallacyclobutane structure. While the metallacyclobutane is in a deep potential minimum for degenerate metathesis reactions, the energy barrier for the [2+2] cycloreversion vanishes for the most exergonic reactions. On the free energy surface under typical experimental conditions, the rate-limiting steps for the overall reactions are then either metallacyclobutane formation for 1 or phosphane ligand dissociation for 2.
BRANCH DUCT INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMS OF THE PANCREAS (IPMNS) (2006)

IPMNs arising in branch ducts are thought to be less aggressive than those involving the main pancreatic duct, and guidelines for their conservative management were recently proposed following the Sendai consensus conference on IPMNs. The purpose of this study is to describe the combined experiences of two large pancreatic centers with this entity in order to validate these recommendations. Patients with resected, pathologically confirmed IPMNs between January 1990 to December 2005 were identified from prospectively collected databases. Of 363 patients (203 MGH and 160 UV), 145 (40%) were determined to have branch duct IPMNs, with the remaining being main duct or combined type. Adenomas were found in 66 of these patients (45.5%); 47 had borderline tumors (32%); 16 carcinoma in situ (11%) and 16 invasive carcinoma (11%), of whom only 3 had positive lymph nodes. Median age was similar between benign and malignant subgroups (66 vs. 68 years) with a slight preponderance of women (57%). Jaundice was more frequent in patients with cancer (12.5% vs. 1.8%, P = 0.022) and abdominal pain in patients with benign tumors (45% vs. 25%, P = 0.025). Forty percent of tumors were discovered incidentally. Mean radiologic diameter of the lesions differed significantly between benign and malignant tumors (27.9 mm vs. 40.6 mm, P < 0.001) and multifocality was present in 21 patients (14.5%). Significant pathologic findings associated with malignancy were the presence of a thick wall (P < 0.001), nodules (P < 0.001) and a diameter equal to or greater than 30 mm (P < 0.001). All branch duct IPMNs with cancer were either larger than 30 mm in size or had nodules or symptoms. There were no operative deaths, and with a mean follow up of 45 months, the 5 and 10 year survival was 91% and 72%. The 5-year disease-specific survival for branch duct IPMN with invasive cancer was 58%, whereas there were no deaths from recurrent disease in the 129 patients with non-invasive neoplasms. Conclusions: This large cohort of resected branch duct IPMNs shows that cancer is present in 22% of cases, but validates the Sendai recommendations based on absence of malignancy in tumors < 30 mm, without symptoms or mural nodules.
Perspectives on General Management in the National Health Service (1989)

If general managers experience problems in establishing a dialogue with their various constituencies both inside and outside the NHS, they are not alone. Researchers of health policy and management experience similar difficulties in trying to engage in a mutually useful exchange of views with health service managers. Attempts to bring the two groups together in order to interweave their respective experience and knowledge have rarely been successful. The reasons are manifold but the chief problem is the existence of suspicion on each side: researchers suspect managers of being intellectual philistines or of being unduly defensive about perceived criticism of their activities; for their part, managers accuse academics of indulging in ‘intellectual mystification’ and peddling useless models or of making unwarranted generalisations on the basis of small and unrepresentative samples. The upshot of this divide is that each group tolerates the other but, with few exceptions, warily and without any real or shared comprehension.
The use of 4‐methylumbelliferyl and other chromophoric glycosides in the study of cellulolytic enzymes (1982)

HPLC‐analysis of the reaction products of a series of 4‐methylumbelliferyl glycosides from cello‐oligosaccharides, used as substrates of a cellobiohydrolase from Trichoderma reesei , proves the lack of specificity for terminal cellobiosyl groups. Also, different reaction patterns are observed for this CBHI and for an endocellulase, when acting on these same substrates. 4‐Methylumbelliferyl β‐D‐lactoside is an unexpected substrate for CBHI, yielding only lactose and phenol as reaction products. The binding characteristics of p ‐nitrobenzyl 1‐thio‐β‐D‐lactoside for this enzyme are determined by a dia‐filtration technique, yielding 1 binding site and an association constant of 4.0 × 10 4 M −1 .
UnyLinker: An Efficient and Scaleable Synthesis of Oligonucleotides Utilizing a Universal Linker Molecule: A Novel Approach To Enhance the Purity of Drugs (2008)

A novel universal linker (UnyLinker) molecule which has a conformationally rigid and chemically stable bridge head ring oxygen atom carrying a conventional 4,4′-dimethoxytrityl (DMT) and succinyl groups locked in a syn orientation has been developed to carry out oligonucleotide synthesis efficiently and smoothly. The geometry of the vicinal syn oxygen functionalized group allows fast and clean cleavage under standard aqueous ammonia deprotection conditions to afford high-quality oligonucleotides. No base modification is observed, based on the ion-pair HPLC−UV−MS (IP-HPLC−UV−MS) method with detection limit of <0.1%. A class of impurities formed by branching from the exocyclic amino group of nucleosides loaded onto a solid support has been eliminated by the use of this method. Examples demonstrating the versatile nature of this molecule are shown by syntheses of different chemistries such as 2′-deoxy, 2′-O-methyl, 2′-O-methoxyethyl, Lock nucleic acids (LNA), 2′-α-fluoro nucleic acids (FANA), conjugates such as 5′-phosphate monoester and biotin, and phosphate diester and phosphorothioate backbone modifications. This molecule was loaded onto several commercial solid supports and used in both gas-sparged and packed-bed automated DNA/RNA synthesizers. Large-scale syntheses (up to 700 mmol) of multiple phosphorothioate first- and second-generation antisense drugs on GE-Amersham’s OligoProcess synthesizer are demonstrated further, showing that this chemistry could be used for efficient synthesis of multiple oligonucleotide drugs using a single raw material, thereby eliminating a difficult to characterize nucleoside-loaded polymer matrix used as a starting material. A mechanism for deprotection and cleavage of the linker molecule to liberate the free oligonucleotide is proposed. Characterization of the cyclic byproduct formed during release of the oligonucleotide is presented. The exo-syn configuration of the dihydroxy structure of the UnyLinker molecule is conclusively established by X-ray crystallography studies. A novel method to remove the last traces of osmium used during the synthesis of the UnyLinker molecule to reach undetectable levels (<1 ppm) is also described.
Structural and dynamic insights into the energetics of activation loop rearrangement in FGFR1 kinase (2015)

Protein tyrosine kinases differ widely in their propensity to undergo rearrangements of the N-terminal Asp-Phe-Gly (DFG) motif of the activation loop, with some, including FGFR1 kinase, appearing refractory to this so-called 'DFG flip'. Recent inhibitor-bound structures have unexpectedly revealed FGFR1 for the first time in a 'DFG-out' state. Here we use conformationally selective inhibitors as chemical probes for interrogation of the structural and dynamic features that appear to govern the DFG flip in FGFR1. Our detailed structural and biophysical insights identify contributions from altered dynamics in distal elements, including the αH helix, towards the outstanding stability of the DFG-out complex with the inhibitor ponatinib. We conclude that the αC-β4 loop and 'molecular brake' regions together impose a high energy barrier for this conformational rearrangement, and that this may have significance for maintaining autoinhibition in the non-phosphorylated basal state of FGFR1.
Domain-Boundary Structure of Styrene-Isoprene Block Copolymer Films Cast from Solution. 4. Molecular-Weight Dependence of Lamellar Microdomains (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDomain-Boundary Structure of Styrene-Isoprene Block Copolymer Films Cast from Solution. 4. Molecular-Weight Dependence of Lamellar MicrodomainsTakeji Hashimoto, Mitsuhiro Shibayama, and Hiromichi KawaiCite this: Macromolecules 1980, 13, 5, 1237–1247Publication Date (Print):September 1, 1980Publication History Published online1 May 2002Published inissue 1 September 1980https://pubs.acs.org/doi/10.1021/ma60077a040https://doi.org/10.1021/ma60077a040research-articleACS PublicationsRequest reuse permissionsArticle Views2561Altmetric-Citations401LEARN 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
Cloning and nucleotide sequences of the two 130kDa insecticidal protein genes of Bacillus thuringiensis var. israelensis. (1988)

Two types of 130kDa insecticidal protein genes isolated from large plasmid DNAs of Bacillus thuringiensis var. israelensis HD522 were cloned in an Escherichia coli plasmid vector. Analysis of the nucleotide sequences revealed that the two genes encoded a 127, 500-dalton protein (ISRH3) consisting of 1, 135 amino acids and a 134, 400-dalton protein (ISRH4) consisting of 1, 180 amino acids. The two insecticidal proteins were identical in a region of the C-terminal 467 amino acids.
Nerve agent stereoisomers: analysis, isolation and toxicology (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNerve agent stereoisomers: analysis, isolation and toxicologyH. P. Benschop and L. P. A. De JongCite this: Acc. Chem. Res. 1988, 21, 10, 368–374Publication Date (Print):October 1, 1988Publication History Published online1 May 2002Published inissue 1 October 1988https://pubs.acs.org/doi/10.1021/ar00154a003https://doi.org/10.1021/ar00154a003research-articleACS PublicationsRequest reuse permissionsArticle Views1175Altmetric-Citations181LEARN 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
TSG-6: An IL-1 /TNF-inducible protein with anti-inflammatory activity (1997)

The pro-inflammatory cytokines IL-1 and TNF-alpha are primary mediators of the acute phase response, the complex reaction of the mammalian organism to infection and injury. Among the genes activated by TNF-alpha and IL-1 in a variety of cells is TNF-stimulated gene 6 (TSG-6). The TSG-6 cDNA encodes a secreted 35 kDa glycoprotein which is abundant in synovial fluids of patients with various forms of arthritis and detectable in serum of patients with different inflammatory or autoimmune disorders. TSG-6 protein consists of two structural domains: a hyaluronan-binding link module, the characteristic domain of the hyaladherin family of proteins, and a C-terminal CUB domain, present in a variety of diverse proteins. TSG-6 forms a stable complex with components of the plasma protein inter-alpha-inhibitor (I[alpha]I), a Kunitz-type serine protease inhibitor. TSG-6 and I(alpha)I synergize to inhibit plasmin, a serine protease involved in the activation of matrix metalloproteinases which are part of the proteolytic cascade associated with inflammation. Recombinant human TSG-6 protein exerts a potent anti-inflammatory effect in a murine model of acute inflammation. Modulation of the proteolytic network associated with inflammatory processes may be a mechanism whereby TSG-6, in cooperation with I(alpha)I, inhibits inflammation. Activation of the TSG-6 gene by pro-inflammatory cytokines, presence of TSG-6 protein in inflammatory lesions and its anti-inflammatory effect suggest a role for TSG-6 in a negative feed-back control of the inflammatory response.
Protamine-induced fatal anaphylaxis. Prevalence of antiprotamine immunoglobulin E antibody. (1985)

Protamine is used widely to reverse the anticoagulant effects of heparin and to delay the absorption of insulin. Although adverse reactions to protamine are reported infrequently and are usually mild, we recently observed the first fatal case of type I anaphylaxis resulting from protamine. This patient had previously been sensitized to protamine during cardiac catheterization and had high levels of protamine-specific immunoglobulin E in the serum. In a prospective study, we found that 10 of 19 diabetic patients (53%) who had received insulin containing insulin also had high levels of antiprotamine immunoglobulin E. In contrast, none of 27 nondiabetic healthy normal controls or 10 diabetics who had never received protamine or protamine-containing insulin had levels of antiprotamine immunoglobulin E over background. This study underscores the risks of routinely administering protamine to susceptible individuals and the need for alternative therapies.
Electrocatalytic CO2 reduction with a membrane supported manganese catalyst in aqueous solution (2014)

[Mn(bpy)(CO)3Br] cast in a Nafion membrane is an active heterogeneous electrocatalyst with good selectivity for CO2 reduction to CO in neutral aqueous electrolyte. Addition of multi-walled carbon nanotubes (MWCNT) leads to a ∼10 fold current enhancement and stable CO : H2 yields (1 : 2) at -1.4 V vs. Ag/AgCl at pH 7.
Purification and properties of bacterially synthesized human granulocyte-macrophage colony stimulating factor (1987)

Human granulocyte-macrophage colony stimulating factor (GM-CSF) has been synthesized in high yield using a temperature inducible plasmid in Escherichia coli. The human GM-CSF is readily isolated from the bacterial proteins because of its differential solubility and chromatographic properties. The bacterially synthesized form of the human GM-CSF contains an extra methionine residue at position 1, but otherwise it is identical to the polypeptide predicted from the cDNA sequence. The specific activity of 2.9 X 10(7) units/mg of protein for purified bacterially synthesized human GM-CSF indicates that despite the lack of glycosylation, the molecule is substantially in its native conformation. This molecule stimulated the same number and type of both seven- and 14-day human bone marrow colonies as the CSF alpha preparation from human placental conditioned medium. Human GM-CSF had no activity on murine bone marrow or murine leukemic cells. There was no detectable, direct stimulation of adult human erythroid burst forming units (BFU-E) by the bacterially synthesized human GM-CSF. Although impure preparations containing native human GM-CSF (eg, human placental conditioned medium) stimulated the formation of mixed colonies, even in the presence of erythropoietin, the bacterially synthesized human GM-CSF failed to stimulate the formation of mixed colonies from adult human bone marrow cells. The bacterially synthesized human GM-CSF increased N-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced superoxide production and lysozyme secretion. Antibody-dependent cytotoxicity and phagocytosis by human neutrophils was stimulated by the bacterially synthesized human GM-CSF and eosinophils were also activated in the antibody-dependent cytotoxicity assay.
Towards an Example-Based Image Compression Architecture for Video-Conferencing (1994)

Very-low bandwidth video-conferencing, which is the simultaneous transmission of speech and pictures (face-to-face communication) of the communicating parties, is a challenging application requiring an integrated effort of computer vision and computer graphics. This paper consists of two major parts. First, we present the outline of a simple approach to video-conferencing relying on an example-based hierarchical image compression scheme. In particular, we discuss the use of example images as a model, the number of required examples, faces as a class of semi-rigid objects, a hierarchical model based on decomposition into different time-scales, and the decomposition of face images into patches of interest. In the second part, we present several algorithms for image processing and animation as well as their experimental evaluation. Among the original contributions of this paper is an automatic algorithm for pose estimation and normalization. Experiments suggest interesting estima...
Heparanase accelerates wound angiogenesis and wound healing in mouse and rat models (2005)

Orchestration of the rapid formation and reorganization of new tissue observed in wound healing involves not only cells and polypeptides but also the extracellular matrix (ECM) microenvironment. The ability of heparan sulfate (HS) to interact with major components of the ECM suggests a key role for HS in maintaining the structural integrity of the ECM. Heparanase, an endoglycosidase-degrading HS in the ECM and cell surface, is involved in the enzymatic machinery that enables cellular invasion and release of HS-bound polypeptides residing in the ECM. Bioavailabilty and activation of multitude mediators capable of promoting cell migration, proliferation, and neovascularization are of particular importance in the complex setting of wound healing. We provide evidence that heparanase is normally expressed in skin and in the wound granulation tissue. Heparanase stimulated keratinocyte cell migration and wound closure in vitro. Topical application of recombinant heparanase significantly accelerated wound healing in a flap/punch model and markedly improved flap survival. These heparanase effects were associated with enhanced wound epithelialization and blood vessel maturation. Similarly, a marked elevation in wound angiogenesis, evaluated by MRI analysis and histological analyses, was observed in heparanase-overexpressing transgenic mice. This effect was blocked by a novel, newly developed, heparanase-inhibiting glycol-split fragment of heparin. These results clearly indicate that elevation of heparanase levels in healing wounds markedly accelerates tissue repair and skin survival that are mediated primarily by an enhanced angiogenic response.-Zcharia, E., Zilka, R., Yaar, A., Yacoby-Zeevi, O., Zetser, A., Metzger, S., Sarid, R., Naggi, A., Casu, B., Ilan, N., Vlodavsky, I., Abramovitch, R. Heparanase accelerates wound angiogenesis and wound healing in mouse and rat models.
The Effect of Mating System Differences on Nucleotide Diversity at the Phosphoglucose Isomerase Locus in the Plant Genus Leavenworthia (1999)

To test the theoretical prediction that highly inbreeding populations should have low neutral genetic diversity relative to closely related outcrossing populations, we sequenced portions of the cytosolic phosphoglucose isomerase (PgiC) gene in the plant genus Leavenworthia, which includes both self-incompatible and inbreeding taxa. On the basis of sequences of intron 12 of this gene, the expected low diversity was seen in both populations of the selfers Leavenworthia uniflora and L. torulosa and in three highly inbreeding populations of L. crassa, while high diversity was found in self-incompatible L. stylosa, and moderate diversity in L. crassa populations with partial or complete self-incompatibility. In L. stylosa, the nucleotide diversity was strongly structured into three haplotypic classes, differing by several insertion/deletion sequences, with linkage disequilibrium between sequences of the three types in intron 12, but not in the adjacent regions. Differences between the three kinds of haplotypes are larger than between sequences of this gene region from different species. The haplotype divergence suggests the presence of a balanced polymorphism at this locus, possibly predating the split between L. stylosa and its two inbreeding sister taxa, L. uniflora and L. torulosa. It is therefore difficult to distinguish between different potential causes of the much lower sequence diversity at this locus in inbreeding than outcrossing populations. Selective sweeps during the evolution of these populations are possible, or background selection, or merely loss of a balanced polymorphism maintained by overdominance in the populations that evolved high selfing rates.
Uncoupling signal transducers from oncogenic MET mutants abrogates cell transformation and inhibits invasive growth (1998)

The assumption that genes encoding tyrosine kinase receptors could play a role in human cancers has been confirmed by the identification of oncogenic mutations in the kinase domain of RET and KIT. Recently, homologous residues were found mutated in MET, in papillary renal carcinomas (PRCs). The link coupling these genetic lesions to cellular transformation is still unclear. METPRC mutations result in increased kinase activity and-in some instances, i.e., M1250T substitution-in changes in substrate specificity. A direct correlation occurs between the transforming potential of METPRC mutants and their ability to constitutively associate with signal transducers through two phosphorylated tyrosines (Y1349VHVNATY1356VNV) located in the receptor tail. Substitution of these "docking tyrosines" with phenylalanines leaves unaffected the altered properties of the kinase but abrogates transformation and invasiveness in vitro. Uncoupling the receptor from signal transducers with a tyrosine-phosphorylated peptide derivative (YpVNV) inhibits invasive growth induced by METPRC mutants. These data indicate that constitutive receptor coupling to downstream signal transducers is a key mechanism in neoplastic transformation driven by mutated MET and suggest a therapeutic strategy to target neoplastic diseases associated with this oncogene.