gebhart/patrepeval huggingface dataset:
Posttranslational modifications of recombinant myotube-synthesized human factor IX (2001)

Recent data demonstrate that the introduction into skeletal muscle of an adeno-associated viral (AAV) vector expressing blood coagulation factor IX (F.IX) can result in long-term expression of the transgene product and amelioration of the bleeding diathesis in animals with hemophilia B. These data suggest that biologically active F.IX can be synthesized in skeletal muscle. Factor IX undergoes extensive posttranslational modifications in the liver, the normal site of synthesis. In addition to affecting specific activity, these posttranslational modifications can also affect recovery, half-life in the circulation, and the immunogenicity of the protein. Before initiating a human trial of an AAV-mediated, muscle-directed approach for treating hemophilia B, a detailed biochemical analysis of F.IX synthesized in skeletal muscle was carried out. As a model system, human myotubes transduced with an AAV vector expressing F.IX was used. F.IX was purified from conditioned medium using a novel strategy designed to purify material representative of all species of rF.IX in the medium. Purified F.IX was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), N-terminal sequence analysis, chemical gamma-carboxyglutamyl analysis, carbohydrate analysis, assays for tyrosine sulfation, and serine phosphorylation, and for specific activity. Results show that myotube-synthesized F.IX has specific activity similar to that of liver-synthesized F.IX. Posttranslational modifications critical for specific activity, including removal of the signal sequence and propeptide, and gamma-carboxylation of the N-terminal glutamic acid residues, are also similar, but carbohydrate analysis and assessment of tyrosine sulfation and serine phosphorylation disclose differences. In vivo experiments in mice showed that these differences affect recovery but not half-life of muscle-synthesized F.IX.
Emergence of Sequence Type 779 Methicillin-Resistant Staphylococcus aureus Harboring a Novel Pseudo Staphylococcal Cassette Chromosome mec (SCC mec )-SCC-SCC CRISPR Composite Element in Irish Hospitals (2012)

Methicillin-resistant Staphylococcus aureus (MRSA) has been a major cause of nosocomial infection in Irish hospitals for 4 decades, and replacement of predominant MRSA clones has occurred several times. An MRSA isolate recovered in 2006 as part of a larger study of sporadic MRSA exhibited a rare spa (t878) and multilocus sequence (ST779) type and was nontypeable by PCR- and DNA microarray-based staphylococcal cassette chromosome mec (SCCmec) element typing. Whole-genome sequencing revealed the presence of a novel 51-kb composite island (CI) element with three distinct domains, each flanked by direct repeat and inverted repeat sequences, including (i) a pseudo SCCmec element (16.3 kb) carrying mecA with a novel mec class region, a fusidic acid resistance gene (fusC), and two copper resistance genes (copB and copC) but lacking ccr genes; (ii) an SCC element (17.5 kb) carrying a novel ccrAB4 allele; and (iii) an SCC element (17.4 kb) carrying a novel ccrC allele and a clustered regularly interspaced short palindromic repeat (CRISPR) region. The novel CI was subsequently identified by PCR in an additional 13 t878/ST779 MRSA isolates, six from bloodstream infections, recovered between 2006 and 2011 in 11 hospitals. Analysis of open reading frames (ORFs) carried by the CI showed amino acid sequence similarity of 44 to 100% to ORFs from S. aureus and coagulase-negative staphylococci (CoNS). These findings provide further evidence of genetic transfer between S. aureus and CoNS and show how this contributes to the emergence of novel SCCmec elements and MRSA strains. Ongoing surveillance of this MRSA strain is warranted and will require updating of currently used SCCmec typing methods.
Rapid single flux quantum T-flip flop operating up to 770 GHz (1999)

Rapid Single Flux Quantum (RSFQ) T-flip flops (TFFs) operating up to 770 GHz have been demonstrated at 4.2 K. The devices, consisting of either resistively shunted or unshunted Josephson junctions, are fabricated using a planarized Nb/AlO/sub x//Nb trilayer process. Electron beam lithography is used to pattern all levels with a minimum junction area less than 0.1 /spl mu/m/sup 2/. Critical current densities of 0.5 mA//spl mu/m/sup 2/ and 2.5 mA//spl mu/m/sup 2/ are used for the shunted (tested at 1.8 K) and unshunted devices (tested at 4.2 K) respectively. The input and output frequencies of the TFFs are obtained from the input and output voltages by the Josephson relation. The output voltage is exactly half of the input voltage when the divide-by-two operation is correct.
Diagnostic neuroimaging across diseases (2011)

Fully automated classification algorithms have been successfully applied to diagnose a wide range of neurological and psychiatric diseases. They are sufficiently robust to handle data from different scanners for many applications and in specific cases outperform radiologists. This article provides an overview of current applications taking structural imaging in Alzheimer's disease and schizophrenia as well as functional imaging to diagnose depression as examples. In this context, we also report studies aiming to predict the future course of the disease and the response to treatment for the individual. This has obvious clinical relevance but is also important for the design of treatment studies that may aim to include a cohort with a predicted fast disease progression to be more sensitive to detect treatment effects. In the second part, we present our own opinions on i) the role these classification methods can play in the clinical setting; ii) where their limitations are at the moment and iii) how those can be overcome. Specifically, we discuss strategies to deal with disease heterogeneity, diagnostic uncertainties, a probabilistic framework for classification and multi-class classification approaches.
The branched-chain fatty acids of mutton fat. 3. The isolation of 16-methylheptadecanoic acid (isostearic acid) (1956)

Research Article| October 01 1956 The branched-chain fatty acids of mutton fat. 3. The isolation of 16-methylheptadecanoic acid (isostearic acid)* R. P. Hansen; R. P. Hansen 1Fats Research Laboratory, Department of Scientific and Industrial Research, Wellington, New Zealand Search for other works by this author on: This Site PubMed Google Scholar F. B. Shorland; F. B. Shorland 1Fats Research Laboratory, Department of Scientific and Industrial Research, Wellington, New Zealand Search for other works by this author on: This Site PubMed Google Scholar N. J. Cooke N. J. Cooke 1Fats Research Laboratory, Department of Scientific and Industrial Research, Wellington, New Zealand Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1956) 64 (2): 214–216. https://doi.org/10.1042/bj0640214 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation R. P. Hansen, F. B. Shorland, N. J. Cooke; The branched-chain fatty acids of mutton fat. 3. The isolation of 16-methylheptadecanoic acid (isostearic acid). Biochem J 1 October 1956; 64 (2): 214–216. doi: https://doi.org/10.1042/bj0640214 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1956 CAMBRIDGE UNIVERSITY PRESS1956 Article PDF first page preview Close Modal You do not currently have access to this content.
Regioselective Ring-Opening/Cross-Metathesis Reactions of Norbornene Derivatives with Electron-Rich Olefins (2004)

This manuscript describes facile ring-opening/cross-metathesis (ROCM) reactions between unsymmetrical norbornene derivatives and electron-rich olefins in the presence of the second-generation Grubbs' catalyst to generate highly substituted furans and pyrroles.
Identification and Characterization of the Human Set1B Histone H3-Lys4 Methyltransferase Complex (2007)

We previously identified a mammalian Set1A complex analogous to the yeast Set1/COMPASS histone H3-Lys4 methyltransferase complex (Lee, J.-H., and Skalnik, D. G. (2005) J. Biol. Chem. 280, 41725-41731). Data base analysis indicates that human Set1A protein shares 39% identity with an uncharacterized SET domain protein, KIAA1076, hereafter denoted Set1B. Immunoprecipitation and mass spectrometry reveal that Set1B associates with a approximately 450 kDa complex that contains all five non-catalytic components of the Set1A complex, including CFP1, Rbbp5, Ash2, Wdr5, and Wdr82. These data reveal two human protein complexes that differ only in the identity of the catalytic histone methyltransferase. In vitro assays demonstrate that the Set1B complex is a histone methyltransferase that produces trimethylated histone H3 at Lys(4). Both Set1A and Set1B are widely expressed. Inducible expression of the carboxyl terminus of either Set1A or Set1B decreases steady-state levels of both endogenous Set1A and Set1B protein, but does not alter the expression of the non-catalytic components of the Set1 complexes. A 123-amino acid fragment upstream of the Set1A SET domain is necessary for interaction with CFP1, Ash2, Rbbp5, and Wdr5. This protein domain is also required to mediate feedback inhibition of Set1A and Set1B expression, which is a consequence of reduced Set1A and Set1B stability when not associated with the methyltransferase complex. Confocal microscopy reveals that Set1A and Set1B each localize to a largely non-overlapping set of euchromatic nuclear speckles, suggesting that Set1A and Set1B each bind to a unique set of target genes and thus make non-redundant contributions to the epigenetic control of chromatin structure and gene expression.
Biochemical characterization of mutant EGF receptors expressed in the hemopoietic cell line BaF/3 (1998)

The Epidermal Growth Factor (EGF) receptor appears to require a fully active tyrosine kinase domain to transmit mitogenic signals. However, waved-2 mice carrying a mutation in the alpha-helix C of their EGF-R, which abolishes tyrosine kinase activity, only display a mild phenotype and are fully viable. This suggests that the mutant EGF-R signals through heterodimerization with endogenous, kinase active members of the EGF-R family such as ErbB-2 or ErbB-4. We have examined the biochemistry of EGF-Rs carrying mutations in the alpha-helix C of the human EGF-R (V741G and Y740F), in the ATP binding site (K721R) and at the C-terminus (CT957), by expression in BaF/3 cells which are devoid of EGF-R family members. The in vitro kinase activity of the alpha-helix C EGF-R mutants was severely impaired as a result of reduced phosphotransfer activity without appreciable changes in the affinity for either ATP or peptide substrate. Surprisingly, EGF stimulation of cells carrying the different mutant or wild type EGF-Rs resulted in tyrosine phosphorylation of EGF-R proteins; this phosphorylation was abolished in crude plasma membrane preparations, and appears to be due to activation of a membrane-associated or a cytosolic kinase. Receptor-mediated internalization of EGF was profoundly suppressed in the V741G, K721R and CT957 receptor mutant, and high affinity EGF binding was undetectable in the V741G and K721R receptors. We conclude that specific residues in the C-helix of the EGF-R kinase are essential for full kinase activity; mutations in this region do not affect ATP binding, but impair the receptors' phosphotransfer ability. High affinity binding of EGF is not dependent on tyrosine kinase activity or sequences in the C-terminus.
Anti-TNF-&#945; Antibody Therapies in Autoimmune Diseases (2006)

Autoimmune diseases affect about 3% of the world population, more frequently women than men, and their incidence is attributed to an immune response of a genetically predisposed individual to an environmental pathogen, under the influence of inadequate immuno-regulatory mechanisms. Advances in understanding the cellular activity pathways and cytokine expression profiles have led to new therapeutic regiments, like soluble receptors, monoclonal antibodies and molecular mimetics that have been employed to enhance or replace conventional immunosuppressive therapies. Among new biologicals that have been developed to target defined pathways of the adaptive immune response are TNF-alpha inhibitors. TNF-alpha is a proinflammatory cytokine elevated in many autoimmune lesions, and its deregulation characterizes many autoimmune diseases. TNF-alpha seems to exhibit an immunoregulatory role that can alter the balance of T regulatory cells and orchestrate acute immunological responses. More than half a million autoimmune patients have received therapy with anti-TNF-alpha antibodies, usually because they were refractory to conventional treatments. This review offers an update on TNF-alpha-targeted therapies used in patients suffering from various autoimmune diseases, based on the current knowledge of disease pathogenesis, with emphasis on the efficacy and safety that clinical trials have shown until now.
18F-fluoroacetate: a potential acetate analog for prostate tumor imaging--in vivo evaluation of 18F-fluoroacetate versus 11C-acetate. (2007)

All of these data indicate that (18)F-FAC may be a useful alternative to (11)C-ACE tracer for the detection of prostate tumors by PET.
Effect of Downhole Pressure Conditions on High-Power Laser Perforation (2005)

Abstract Researchers at Gas Technology Institute (GTI) have been exploring the use of high power laser energy as a non-damaging alternative to conventional explosive perforation methods. All previous laser/rock interaction tests were performed on samples in the lab at atmospheric pressure. To determine the effect of downhole pressure conditions, a sophisticated tri-axial cell was designed and tested. For the first time, Berea sandstone, limestone and clad core samples were lased under various combinations of confining, axial and pore pressures. Clad core samples consisted of steel cemented to rock in an effort to represent material penetrated in a cased hole. The results of this experiment will assist in the development of a downhole laser perforation prototype tool. In the past, several combinations of laser and rock variables were investigated at standard conditions and reported in the literature. More recent experiments determined the technical feasibility of laser perforation with a 5.34 kW Ytterbium-doped multiclad fiber laser exposed to multiple samples of rock, cement and steel. The fiber laser was capable of penetrating these materials under a variety of conditions, to an appropriate depth, and with reasonable energy requirements. It was determined that fiber lasers are capable of cutting rock without causing damage to flow properties. Furthermore, the laser perforation resulted in permeability improvements on the exposed rock surface. This paper will discuss the design and development of a customized laser pressure cell; experimental design and procedures, and the resulting data on pressure-charged samples exposed to the laser beam. An analysis will provide the resulting effect of downhole pressure conditions on the laser/rock interaction process.
Alternative Pathway Evaluation (1994)

The alternative pathway of complement shares its terminal components (C3 and C5 through 9) with the classical pathway, but has several unique components, including factors D, B, and P (properdin). This unit presents methods for assaying total alternative pathway activity and the activity of factors B and D. Radial immunodiffusion (RID) can also be used to measure factor D, B, and P concentrations.
Chelating Activity of Advanced Glycation End-product Inhibitors (2001)

The advanced glycation end-product (AGE) hypothesis proposes that accelerated chemical modification of proteins by glucose during hyperglycemia contributes to the pathogenesis of diabetic complications. The two most commonly measured AGEs, N(epsilon)-(carboxymethyl)lysine and pentosidine, are glycoxidation products, formed from glucose by sequential glycation and autoxidation reactions. Although several compounds have been developed as AGE inhibitors and are being tested in animal models of diabetes and in clinical trials, the mechanism of action of these inhibitors is poorly understood. In general, they are thought to function as nucleophilic traps for reactive carbonyl intermediates in the formation of AGEs; however alternative mechanisms of actions, such as chelation, have not been rigorously examined. To distinguish between the carbonyl trapping and antioxidant activity of AGE inhibitors, we have measured the chelating activity of the inhibitors by determining the concentration required for 50% inhibition of the rate of copper-catalyzed autoxidation of ascorbic acid in phosphate buffer. All AGE inhibitors studied were chelators of copper, as measured by inhibition of metal-catalyzed autoxidation of ascorbate. Apparent binding constants for copper ranged from approximately 2 mm for aminoguanidine and pyridoxamine, to 10-100 microm for carnosine, phenazinediamine, OPB-9195 and tenilsetam. The AGE-breakers, phenacylthiazolium and phenacyldimethylthiazolium bromide, and their hydrolysis products, were among the most potent inhibitors of ascorbate oxidation. We conclude that, at millimolar concentrations of AGE inhibitors used in many in vitro studies, inhibition of AGE formation results primarily from the chelating or antioxidant activity of the AGE inhibitors, rather than their carbonyl trapping activity. Further, at therapeutic concentrations, the chelating activity of AGE inhibitors and AGE-breakers may contribute to their inhibition of AGE formation and protection against development of diabetic complications.
Impact of p53 loss on reversal and recurrence of conditional Wnt-induced tumorigenesis (2003)

Aberrant activation of Wnt signaling is oncogenic and has been implicated in a variety of human cancers. We have developed a doxycycline-inducible Wnt1 transgenic mouse model to determine the dependence of established mammary adenocarcinomas on continued Wnt signaling. Using this model we show that targeted down-regulation of the Wnt pathway results in the rapid disappearance of essentially all Wnt-initiated invasive primary tumors as well as pulmonary metastases. Tumor regression does not require p53 and occurs even in highly aneuploid tumors. However, despite the dependence of primary mammary tumors and metastases on continued Wnt signaling and the dispensability of p53 for tumor regression, we find that a substantial fraction of tumors progress to a Wnt-independent state and that p53 suppresses this process. Specifically, loss of one p53 allele dramatically facilitates the progression of mammary tumors to a Wnt1-independent state both by impairing the regression of primary tumors following doxycycline withdrawal and by promoting the recurrence of fully regressed tumors in the absence of doxycycline. Thus, although p53 itself is dispensable for tumor regression, it nevertheless plays a critical role in the suppression of tumor recurrence. Our findings demonstrate that although even advanced stages of epithelial malignancy remain dependent upon continued Wnt signaling for maintenance and growth, loss of p53 facilitates tumor escape and the acquisition of oncogene independence.
Towards the automatic generation of software diagrams (1991)

The authors formulate the criteria for drawing dataflow diagrams and describe the placement and routing algorithms used in a system called MONDRIAN. A generalized approach to the question of software diagrams is proposed based on the authors' experience with MONDRIAN and a metasystem approach to the creation of CASE (computer-aided software engineering) environments. A formal approach to the definition of software objects and their graphical representation is given. The use of location constraints as a basis for generalized layout algorithms is discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Modification of triantennary glycopeptide into probes for the asialoglycoprotein receptor of hepatocytes. (1990)

Triantennary glycopeptide was oxidized with galactose oxidase to convert the -CH2OH group on terminal galactose residues to the aldehyde group (oxo-form). Kinetic profiling by reverse phase high performance liquid chromatography allowed termination of the reaction when intermediate mono-oxo- and di-oxo-triantennary glycopeptides had been produced. The mixture of the oxo-glycopeptides was derivatized with 2,4-dinitrophenylhydrazine for efficient separation, and each isomeric triantennary hydrazone was separated by reverse phase high performance liquid chromatography. The purified hydrazones were reverted to three original isomeric mono-oxo- and di-oxo-glycopeptides, and a single tri-oxo-glycopeptide. Each of these isomers was characterized by proton NMR by a downfield shift in the anomeric signals of 6-oxo-Gal residue(s). The functionalized glycopeptides were successively modified with dansyl and naphthyl groups through the 6-oxo-Gal residue and the amino terminus of the peptide to prepare three isomeric glycopeptide probes suitable for conformation studies by fluorescence energy transfer measurements. Alternatively, glycopeptides were derivatized by attaching t-butyloxycarbonyl-L-tyrosine to the amino terminus of the peptide, and reductive amination of the 6-oxo-Gal residue, provided three isomeric triantennary photoaffinity probes which allow photolyzable groups to be attached to the newly introduced 6-amino-Gal residue.
Nitric Oxide Production and Signaling in Inflammation (2005)

Nitric oxide (NO) is recognized as a mediator and regulator of inflammatory responses. It possesses cytotoxic properties that are aimed against pathogenic microbes, but it can also have damaging effects on host tissues. NO reacts with soluble guanylate cyclase to form cyclic guanosine monophosphate (cGMP), which mediates many of the effects of NO. NO can also interact with molecular oxygen and superoxide anion to produce reactive nitrogen species that can modify various cellular functions. These indirect effects of NO have a significant role in inflammation, where NO is produced in high amounts by inducible nitric oxide synthase (iNOS) and reactive oxygen species are synthesized by activated inflammatory cells. The present review deals with NO production and signaling in inflammation, especially in relation to human neutrophils and eosinophils.