gebhart/patrepeval huggingface dataset:
Chronic liver disease: current concepts of disease mechanisms (1999)

Optimal management of chronic liver disease requires an understanding of aetiological factors or conditions initiating and sustaining tissue damage. Injury may derive initially from toxin or xenobiotic exposure (direct, biotransformation adducts, hypersensitivity responses or immune-mediated mechanisms), infectious organisms, inborn errors of metabolism, or pathological accumulations of transition metals (iron or copper), endotoxins or membranocytolytic bile acids. Secondarily, cells and mediators associated with inflammation, pathological expression of major histocompatibility foci on hepatocytes and biliary epithelia, aberrant initiation of apoptosis, modification of the extracellular matrix, and depletion of natural antioxidants can each play pivotal roles. Cholestatic liver injury derived from extrahepatic mechanical obstruction or intrahepatic cholestasis (many causes) can induce membrane damage subsequent to accumulation of membranocytolytic bile acids, copper retention, and membrane peroxidation. This paper reviews contemporary issues of chronic hepatocellular injury and hepatic fibrosis with the aim of broadening the clinical perspective of treatment strategies.
Activation and activities of the p53 tumour suppressor protein (2001)

The p53 tumour suppressor protein inhibits malignant progression by mediating cell cycle arrest, apoptosis or repair following cellular stress. One of the major regulators of p53 function is the MDM2 protein, and multiple forms of cellular stress activate p53 by inhibiting the MDM2-mediated degradation of p53. Mutations in p53, or disruption of the pathways that allow activation of p53, seem to be a general feature of all cancers. Here we review recent advances in our understanding of the pathways that regulate p53 and the pathways that are induced by p53, as well as their implications for cancer therapy.
Synthesis of Glycoproteins (2002)

ADVERTISEMENT RETURN TO ISSUEPREVArticleSynthesis of GlycoproteinsBenjamin G. DavisView Author Information Dyson Perrins Laboratory, University of Oxford, South Parks Road, Oxford, OX1 3QY, U.K. Cite this: Chem. Rev. 2002, 102, 2, 579–602Publication Date (Web):January 29, 2002Publication History Received9 August 2001Published online29 January 2002Published inissue 1 February 2002https://pubs.acs.org/doi/10.1021/cr0004310https://doi.org/10.1021/cr0004310research-articleACS PublicationsCopyright © 2002 American Chemical SocietyRequest reuse permissionsArticle Views5342Altmetric-Citations454LEARN 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 SUBJECTS:Carbohydrates,Chemical biology,Monomers,Peptides and proteins,Post-translational modification Get e-Alerts
A Virus-Encoded RNA Polymerase Purified from Baculovirus-Infected Cells (1998)

A DNA-dependent RNA polymerase was purified to homogeneity, starting from insect cells infected with the baculovirus Autographa californica nuclear polyhedrosis virus (AcNPV). The purified polymerase supported accurate and specific transcription from late and very late promoters but was not active on viral early promoters. Thus, promoter recognition is an integral function of the purified enzyme. The purified RNA polymerase was composed of only four equimolar subunits, which makes it the simplest DNA-directed RNA polymerase from a eukaryotic source described so far. Amino-terminal protein sequencing, peptide fingerprinting, and immunochemical analyses were used to identify the four subunits, all of which are virus encoded. Overexpression of the four viral proteins (LEF-8, LEF-4, LEF-9, and p47) in baculovirus-infected cells resulted in a significant increase in the levels of RNA polymerase produced in the infected cells. Thus, the overexpression data are consistent with our identification of the RNA polymerase subunits.
Effects of Ammonium and Lactate on Growth and Metabolism of a Recombinant Chinese Hamster Ovary Cell Culture (1997)

A Chinese hamster ovary (CHO) cell line producing a recombinant glycoprotein was cultured in batch mode with different initial concentrations of ammonium chloride (0-10 mM), sodium lactate (0-60 mM), or sodium chloride (0-60 mM). High ammonium concentrations did not inhibit cell growth and productivity or glucose and glutamine consumption. In contrast, specific ammonia and alanine production decreased by 55% and 40%, respectively. There were also significant increases in specific aspartate and glutamate consumption in high ammonium concentrations. These observations indicated a shift in glutamine catabolic pathways in response to the effects of ammonium. The influence of lactate on growth and metabolism were the combined effects of lactate concentration and osmolarity. After "correcting" for osmolarity effects, lactate was found to inhibit growth by 25% but to increase specific productivity slightly (10%). Lactate had profound effects not only on glycolysis but also on glutaminolysis. While specific glucose and glutamine consumptions decreased by 15-20%, the effects of lactate on their metabolic products were far more significant. Lactate production was halted, and specific ammonia and alanine productions decreased by 64% and 70% at high lactate concentration. Theories on how ammonium and lactate affected the metabolic pathways of glucose and glutamine are presented.
Transcriptional activation of mucin by Pseudomonas aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease (1997)

An unresolved question in cystic fibrosis (CF) research is how mutations of the CF transmembrane conductance regulator, a Cl ion channel, cause airway mucus obstruction leading to fatal lung disease. Recent evidence has linked the CF transmembrane conductance regulator mutation to the onset and persistence of Pseudomonas aeruginosa infection in the airways, and here we provide evidence directly linking P. aeruginosa infection to mucus overproduction. We show that P. aeruginosa lipopolysaccharide profoundly upregulates transcription of the mucin gene MUC 2 in epithelial cells via inducible enhancer elements and that this effect is blocked by the tyrosine kinase inhibitors genistein and tyr-phostin AG 126. These findings improve our understanding of CF pathogenesis and suggest that the attenuation of mucin production by lipopolysaccharide antagonists and tyrosine kinase inhibitors could reduce morbidity and mortality in this disease.
Evaluation of an α synuclein sensitized dendritic cell based vaccine in a transgenic mouse model of Parkinson disease (2015)

In order to develop a cell-based vaccine against the Parkinson disease (PD) associated protein α-synuclein (α-Syn) 3 peptides were synthesized based upon predicted B cell epitopes within the full length α-Syn protein sequence. These peptide fragments as well as the full length recombinant human α-Syn (rh- α-Syn) protein were used to sensitize mouse bone marrow-derived dendritic cells (DC) ex vivo, followed by intravenous delivery of these sensitized DCs into transgenic (Tg) mice expressing the human A53T variant of α-Syn. ELISA analysis and testing of behavioral locomotor function by rotometry were performed on all mice after the 5th vaccination as well as just prior to euthanasia. The results indicated that vaccination with peptide sensitized DCs (PSDC) as well as DCs sensitized by rh-α-Syn induced specific anti-α-Syn antibodies in all immunized mice. In terms of rotometry performance, a measure of locomotor activity correlated to brain dopamine levels, mice vaccinated with PSDC or rh- α-Syn sensitized DCs performed significantly better than non-vaccinated Tg control mice during the final assessment (i.e. at 17 months of age) before euthanasia. As well, measurement of levels of brain IL-1α, a cytokine hypothesized to be associated with neuroinflammation, demonstrated that this proinflammatory molecule was significantly reduced in the PSDC and rh- α-Syn sensitized DC vaccinated mice compared to the non-vaccinated Tg control group. Overall, α-Syn antigen-sensitized DC vaccination was effective in generating specific anti- α-Syn antibodies and improved locomotor function without eliciting an apparent general inflammatory response, indicating that this strategy may be a safe and effective treatment for PD.
Synthetic aperture pulse-echo imaging with rectangular boundary arrays (acoustic imaging) (1993)

The effectiveness of a square boundary array in finite-range, pulse-echo imaging is investigated. The images produced by such an array are quite poor when no additional signal processing is used. It is demonstrated through simulations that a synthetic-aperture signal processing technique called image addition can be used to reduce the sidelobes associated with the square boundary array, thereby improving the image quality. Image addition was originally proposed for narrowband imaging of far-field scenes, but it is also useful for finite-range, pulse-echo imaging. The conclusions are expected to apply to other, nonsquare boundary array geometries.
Error concealment of still image and video streams with multi-directional recursive nonlinear filters (2002)

A novel approach for error concealment in block-based image and video coding systems over the ATM networks is presented. This new approach aims at reconstructing the lost pixels in the intra-coded frames by spatial interpolation of the nearest undamaged pixels with a recursive multi-directional nonlinear filtering scheme. The lost interframe information are also reconstructed by using robust nonlinear filtering of the adjacent and previous motion vector blocks. We assume that the important synchronization and header information of the compressed bit streams are packed into high priority ATM cells and an integral number of macroblocks are packed into normal cells for efficient transmission. Finally, simulation results are provided to illustrate the effectiveness of the proposed method.
Knee forces during the activity of getting out of a chair with and without the aid of arms. (1976)

This is a preliminary study of the knee forces during the activity of getting out of a chair with and without the aid of arms. The equipment limited the study to the phase of the activity where no contact occurred between the subject and the chair seat. The model of the knee considered was two-dimensional, and quasi-static. Analysis showed that the forces acting in both compartments of the knee were comparable with those occurring during other non-strenuous activities such as level walking. It was also shown that the use of arms to aid rising from a chair causes considerable reduction in both joint and muscle forces.
Structural characteristics of interferons from mouse Ehrlich ascites tumor cells. (1979)

An improved procedure for the isolation of interferons produced by mouse Ehrlich ascites tumor cells infected with Newcastle disease virus provides interferons of three size classes (33,000, 26,000, and 20,000 daltons) with specific activities between 2 and 3 x 10(9) units/mg of protein and a yield of 11 to 20%. The tryptic peptide maps of the two larger species are very similar; that of the smallest species is different, at least in part. The amino acid compositions of the three species are very close. Their NH2-terminal amino acids are identical and so are the amino acids released by carboxypeptidase A treatment. These data are consistent with the possibility that the differences in size between the three species may be due, at least in part, to unequal glycosylation.
A specification environment for configuring a discrete-part manufacturing system simulation infrastructure (2002)

A well-designed graphical environment that supports model specification has the potential of enabling the modeler to make better use of the modeling constructs and architecture. We describe on-going research in creating a graphical environment that supports model specification in OOSIM (Object-Oriented Simulation in Manufacturing), a high fidelity manufacturing system simulator.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Rate-Constrained Contour-Representation for Region-Based Motion Compensation (1996)

A new region-based coding scheme is introduced. It uses generalized parabolic blending curves for contour coding which lead to visually preferable smooth contours and support good local controllability. A rate-distortion criterion is applied to decide which regions should be used for motion compensation and for optimizing the region contours. The conditions for optimal regions in a rate-distortion sense are derived. Simulation results are presented. A gain of about 2 dB in PSNR for region-based motion compensation with optimized regions over block-based motion compensation at very low bit-rates is reported. Keywords: very low bit-rate video coding, optimal contours, rate-distortion theory, region-based coding, generalized parabolic blending 1 INTRODUCTION SPIE Symposium on Visual Communications and Image Processing 96, March 96, Orlando Region-based video coding schemes are expected to yield better compression ratios and a better visual quality than existing block-based video compres...
Protonated cyclopropane intermediates in the reactions of cyclopropanecarboxylic acids (1970)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProtonated cyclopropane intermediates in the reactions of cyclopropanecarboxylic acidsNorman C. Deno, Wilbur E. Billups, Daniel LaVietes, Philip C. Scholl, and Samuel SchneiderCite this: J. Am. Chem. Soc. 1970, 92, 12, 3700–3703Publication Date (Print):June 1, 1970Publication History Published online1 May 2002Published inissue 1 June 1970https://pubs.acs.org/doi/10.1021/ja00715a027https://doi.org/10.1021/ja00715a027research-articleACS PublicationsRequest reuse permissionsArticle Views312Altmetric-Citations10LEARN 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
Synthesis and Pharmacokinetics of Valopicitabine (NM283), an Efficient Prodrug of the Potent Anti-HCV Agent 2‘-C-Methylcytidine (2006)

In our search for new therapeutic agents against chronic hepatitis C, a ribonucleoside analogue, 2‘-C-methylcytidine, was discovered to be a potent and selective inhibitor in cell culture of a number of RNA viruses, including the pestivirus bovine viral diarrhea virus, a surrogate model for hepatitis C virus (HCV), and three flaviviruses, namely, yellow fever virus, West Nile virus, and dengue-2 virus. However, pharmacokinetic studies revealed that 2‘-C-methylcytidine suffers from a low oral bioavailability. To overcome this limitation, we have synthesized the 3‘-O-l-valinyl ester derivative (dihydrochloride form, valopicitabine, NM283) of 2‘-C-methylcytidine. We detail herein for the first time the chemical synthesis and physicochemical characteristics of this anti-HCV prodrug candidate, as well as a comparative study of its pharmacokinetic parameters with those of its parent nucleoside analogue, 2‘-C-methylcytidine.
Antithrombotic effects of combining activated protein C and urokinase in nonhuman primates. (1991)

A combination of intermediate-dose APC and u-PA produce substantial and efficient antithrombotic effects without impairing hemostatic function.
The Chemistry of Nitroacetic Acid and its Esters. I. The Alkylation of Alkylnitroacetates with Gramine (1947)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Chemistry of Nitroacetic Acid and its Esters. I. The Alkylation of Alkylnitroacetates with GramineD. A. Lyttle and D. I. WeisblatCite this: J. Am. Chem. Soc. 1947, 69, 9, 2118–2119Publication Date (Print):September 1, 1947Publication History Published online1 May 2002Published inissue 1 September 1947https://pubs.acs.org/doi/10.1021/ja01201a015https://doi.org/10.1021/ja01201a015research-articleACS PublicationsRequest reuse permissionsArticle Views320Altmetric-Citations32LEARN 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
A microfabricated atomic clock (2004)

Fabrication techniques usually applied to microelectromechanical systems (MEMS) are used to reduce the size and operating power of the core physics assembly of an atomic clock. With a volume of 9.5mm3, a fractional frequency instability of 2.5×10−10 at 1s of integration, and dissipating less than 75mW of power, the device has the potential to bring atomically precise timing to hand-held, battery-operated devices. In addition, the design and fabrication process allows for wafer-level assembly of the structures, enabling low-cost mass-production of thousands of identical units with the same process sequence, and easy integration with other electronics.
Synthesis of (R)-1,3-Butanediol by Enantioselective Oxidation Using Whole RecombinantEscherichia coliCells Expressing (S)-Specific Secondary Alcohol Dehydrogenase (2002)

The synthesis of (R)-1,3-butanediol (BDO) from its racemate was studied using whole cells of recombinant Escherichia coli expressing an (S)-specific secondary alcohol dehydrogenase (CpSADH) from Candida parapsilosis by enantioselective oxidation. Under the optimized conditions, the yield of (R)-1,3-BDO reached 72.6 g/l, with a molar recovery yield of 48.4% from a racemate of 15% and an optical purity of 95% ee.
Investigation of (Oxodioxolenyl)methyl Carbamates as Nonchiral Bioreversible Prodrug Moieties for Chiral Amines (1996)

The preparation of (oxodioxolenyl)methyl carbamates and their evaluation as novel nonchiral prodrug moieties for chiral primary and secondary amino functional drugs are described. 4-(Carbamoylmethyl)-2-oxo-1,3-dioxolene derivatives of 3,4-dimethoxyphenethylamine with 5-methyl, 5-phenyl, and 5-anisyl substitution (5a, 5b, and 5c) on the dioxolenone ring were prepared as model amine prodrugs by a one step process involving displacement of p-nitrophenol from appropriately substituted ring opening of these carbamates led to a cascade reaction resulting in the rapid and quantitative regeneration of the parent amine drug. Aryl substitution did not significantly alter the hydrolysis rates of these dioxolenone carbamates in buffers at pH 1 and 7.4 or in rat plasma, although the hydrolysis rates of 5-phenyl- (1b) and 5-anisyl- 4-methyl-1,3-dioxol-4-en-2-one (1c) in pH 7.4 phosphate buffer were 2-3 fold faster than that of the 5-methyl-substituted analog (1a). Application of this prodrug strategy to the chiral fibrinogen receptor antagonist L-734,217 resulted in a prodrug that gave quantitative reconversion in rat and dog plasma in vitro and oral bioavailability of 23 +/- 6% in dogs for the parent drug.
Artemin promotes oncogenicity, metastasis and drug resistance in cancer cells (2017)

Artemin (ARTN) is a member of glial cell line-derived neurotrophic factor (GDNF) family of ligands, and its signaling is mediated via a multi-component receptor complex including the glycosylphosphatidylinositol-anchored GDNF family receptors a (GFRa1, GFRa3) and RET receptor tyrosine kinase. The major mechanism of ARTN action is via binding to a non-signaling co-receptor. The major function of ARTN is to drive the molecule to induce migration and axonal projection from sympathetic neurons. It also promotes the survival, proliferation and neurite outgrowth of sympathetic neurons in vitro. ARTN triggers oncogenicity and metastasis by the activation of the AKT signaling pathway. Recent studies have reported that the expression of ARTN in hepatocellular carcinoma is associated with increased tumor size, quick relapse and shorter survival. Furthermore, ARTN promotes drug resistance such as antiestrogens, doxorubicin, fulvestrant, paclitaxel, tamoxifen and trastuzumab. Moreover, ARTN also stimulates the radio-therapeutic resistance. This review highlights the proposed roles of ARTN in cancer cells and discusses recent results supporting its emerging role as an oncogenic, metastatic and drug-resisting agent with a special focus on how these new insights may facilitate rational development of ARTN for targeted therapies in the future.
Advanced Cutting Structure Improves PDC Bit Performance in Hard and Abrasive Drilling Environments (2003)

The performances of PDC bits in hard formations, especially when these formations are also abrasive, still lack effectiveness and consistency. In such applications, the industry has usually resorted to the use of