gebhart/patrepeval huggingface dataset:
Heparanase Is Involved in the Pathogenesis of Proteinuria as a Result of Glomerulonephritis (2004)

The beta-D-endoglycosidase heparanase has been proposed to be important in the pathogenesis of proteinuria by selectively degrading the negatively charged side chains of heparan sulfate proteoglycans within the glomerular basement membrane. A loss of negatively charged heparan sulfate proteoglycans may result in alteration of the permselective properties of the glomerular basement membrane, loss of glomerular epithelial and endothelial cell anchor points, and liberation of growth factors. In this study, therefore, the role of heparanase in passive Heymann nephritis (PHN) was examined. Normal glomeruli showed low-level heparanase expression as determined by immunohistochemistry and Western blot analysis. Days 5, 14, and 28 of PHN were associated with an increase in endothelial and glomerular epithelial cell heparanase. Reverse transcription-PCR confirmed a significant increase in mRNA at day 21 of disease (P < 0.0004). Furthermore, urinary and glomerular heparanase activities were significantly increased at days 5 and 21 of disease, respectively. Western blot analysis of isolated glomeruli separated into membrane- and cytosol-enriched protein fractions showed that the active 58-kD heparanase species was increased but restricted to the cytosol of diseased glomeruli at day 21. The inactive 65-kD precursor, however, was found in membrane and cytosol-diseased fractions, suggesting cell membrane processing. Complement depletion prevented glomerular heparanase expression; in addition, administration of a polyclonal anti-heparanase antibody significantly reduced urinary protein excretion at day 5 of disease to 62 +/- 11 mg/d compared with 203 +/- 43 and 159 +/- 18 mg/d in the normal rabbit serum- and normal saline-treated experimental groups, respectively (P < 0.002). Proteinuria was reduced in the absence of any altered glomerular C5b-9 activity, sheep IgG deposition, or rat anti-sheep antibody titers. These data suggest that heparanase contributes to the pathogenesis of proteinuria in PHN.
Notch1 activation contributes to tumor cell growth and proliferation in human hepatocellular carcinoma HepG2 and SMMC7721 cells (2012)

Notch signaling controls cellular differentiation and proliferation. Recent studies have shown that Notch signaling plays an important role in the carcinogenesis and progression of a growing number of malignant tumors. We investigated the effect of Notch1 activation on human hepatocellular carcinoma (HCC). In five human HCC cell lines, it was found that SMMC7721 had relatively high while HepG2 relatively low expression of Notch1 and the activity of Notch signaling. Notch1 activation by transfection of active intracellular region of Notch1 (ICN1) into HCC HepG2 cells enhanced cell growth and proliferation, including in vitro single cell colony formation, anchorage-independent proliferation, and in vivo tumorigenicity. Notch1 activation also promoted HepG2 cell cycle progression. Suppression of Notch1 activation by RNAi of Notch1 or by γ-secretase inhibitor (GSI) in HCC SMMC7721 cells decreased cell growth capability and blocked cell cycle progression. Moreover, it was found that suppression of Notch1 activation induced SMMC7721 cell apoptosis, as demonstrated by apoptosis assays. These findings indicate that Notch1 activation promotes human HCC cell growth and proliferation, which may contribute to the progression of this type of malignant carcinoma.
Circulating tumor cells as prognostic marker in metastatic breast cancer (2010)

Testing for circulating tumor cells has emerged as a new and promising tool for stratifying and monitoring patients with metastatic disease. Appropriate risk and biologic stratification in breast cancer is important for the development of more effectively tailored targeted therapies. To optimize patient care, it is important for the clinicians to rely on validated and robust tools able to provide accurate predictive and prognostic information for each patient at any time during treatment. The recent demonstration that the presence of circulating tumor cells predicts the prognosis at any time during the treatment of patients with metastatic breast cancer raises the possibility that this approach will allow for a true 'biologic staging' of the disease. Important questions regarding the biological characteristics of cells and the reasons for the reduced capacity of systemic treatments to arrest or eradicate the cancer were raised. A further study suggests that comprehensive analysis of circulating tumor cells is likely to provide new insights into the biology of breast cancer and contribute to defining novel treatments and better prediction of clinical benefit. Efforts are being made to genotype and phenotype micrometastatic cells. Considerable progress has been already accomplished which should lead to further noninvasive, real-time monitoring of these rare events in the adjuvant and metastatic settings.
Learning from E-commerce for E-learning (2007)

Both e-learning and e-commerce are increasingly of interest to researchers in recent years. A body of research has emerged regarding the two trends. It was considered that e-learning could be taken as a special type of e-commerce, in which the education service provided online is, in fact, the product that being purchased and delivered online from an e-commerce system. Based on this concept, some lessons or findings drawn from e-commerce researches should also be useful for e-learning system design. The purpose of this paper is to carry out a preliminary investigation on the e-learning system design considerations from users' (students') point of view by referring to some of the e-shop designing considerations. With literature reviewed and the author's previous study on e-commerce, the characteristics of e-learning systems were highlighted and compared with their counterparts in e-commerce systems. It was found that the characteristics of a product affect customers' preference of online shopping for that particular product. By the same token, an inference was made with this study that the content features of a particular course would influence students' acceptance of the e-learning approach. Content feature and its suitableness for online delivery may provide a new perspective when designing an e-course, and could be an early signal for the success of the service.
Nobilamides A–H, Long-Acting Transient Receptor Potential Vanilloid-1 (TRPV1) Antagonists from Mollusk-Associated Bacteria (2011)

New compounds nobilamides A-H and related known compounds A-3302-A and A-3302-B were isolated based upon their suppression of capsaicin-induced calcium uptake in a mouse dorsal root ganglion primary cell culture assay. Two of these compounds, nobilamide B and A-3302-A, were shown to be long-acting antagonists of mouse and human TRPV1 channels, abolishing activity for >1 h after removal of drug presumably via a covalent attachment. Other derivatives also inhibited the TRPV1 channel, albeit with low potency, affording a structure-activity profile to support the proposed mechanism of action. While the activities were modest, we propose a new mechanism of action and a new site of binding for these inhibitors that may spur development of related analogues for treatment of pain.
A chloroplast lipoxygenase is required for wound-induced jasmonic acid accumulation in Arabidopsis. (1995)

Plant lipoxygenases are thought to be involved in the biosynthesis of lipid-derived signaling molecules. The potential involvement of a specific Arabidopsis thaliana lipoxygenase isozyme, LOX2, in the biosynthesis of the plant growth regulators jasmonic acid (JA) and abscisic acid was investigated. Our characterization of LOX2 indicates that the protein is targeted to chloroplasts. The physiological role of this chloroplast lipoxygenase was analyzed in transgenic plants where cosuppression reduced LOX2 accumulation. The reduction in LOX2 levels caused no obvious changes in plant growth or in the accumulation of abscisic acid. However, the wound-induced accumulation of JA observed in control plants was absent in leaves of transgenic plants that lacked LOX2. Thus, LOX2 is required for the wound-induced synthesis of the plant growth regulator JA in leaves. We also examined the expression of a wound- and JA-inducible Arabidopsis gene, vsp, in transgenic and control plants. Leaves of transgenic plants lacking LOX2 accumulated less vsp mRNA than did control leaves in response to wounding. This result suggests that wound-induced JA (or some other LOX2-requiring component of the wound response pathway) is involved in the wound-induced regulation of this gene.
Antibody response of dairy cattle experimentally infected with Listeria monocytogenes. (1990)

The purpose of our study was to monitor the humoral immune response of 34 lactating dairy cattle experimentally infected with Listeria monocytogenes (strain Scott A, serotype 4b). Twenty-seven animals were inoculated with 10(6) to 10(7) c.f.u./ml of L. monocytogenes via the intramammary route at ten day intervals for one month and 7 were inoculated with 4 x 10(2) to 4 x 10(3) c.f.u./ml. Preinfection and weekly-post infection serum and whey samples were prepared during acute infection. Antibody titres of serum and whey were evaluated in agglutination tests using whole-cell formalin-fixed L. monocytogenes suspensions. Preinfection agglutination titres ranged from 1:20 to 1:320. At least four-dilution increase over pre-infection titres were apparent by the 8th week of infection. Eighty per cent of the bovine sera (26/34) exhibited titres of greater than or equal to 1:20, 480. Whey titres, which reflected the local humoral response to L. monocytogenes, rarely exceeded 1:256 which may be ascribed in part to the lower immunoglobulin concentration in milk vs. blood. Antibody levels indicate active listeriosis but could not be used to predict the magnitude of the recovery of Listeria (c.f.u./ml) in milk.
Towards securing network management agent distribution and communication (2003)

Network management applications using distributed software agents require secure techniques for agent distribution and communication. Although there are several popular mobile agent environments written in the Java programming language that contend to offer these functions, these packages are generally heavyweight and do not provide a framework for authenticating agent responsibilities within agent systems. This paper describes an agent distribution and communication framework for Java-based software agents. The framework has several key features: (1) a secure mechanism for dispatching agents to selected nodes from secured agent repositories; (2) an operating environment for each agent that depends upon its role-based authenticated security level; (3) object-based, peer-to-peer and peer-to-many communication; (4) provision for encrypted communication; (5) a low-overhead distributed naming directory of agents populating the network; (6) proactive agent monitoring for secure operations; (7) tools for reflective monitoring of agent contents and communication; (8) a lightweight environment that is easy to use while keeping the agents small in size.
A monoclonal antibody against human thrombospondin inhibits platelet aggregation. (1985)

A monoclonal antibody (C6.7) has been generated against the calcium-replete form of human platelet thrombospondin (TSP). C6.7 is specific for TSP as determined by both competitive radioimmunoassay and immunoprecipitation. This antibody inhibits both thrombin- and A23187-induced aggregation of gel-filtered platelets in a concentration-dependent manner without affecting the secretion of serotonin. The epitope on TSP recognized by C6.7 has been localized to an 18-kDa fragment that is present in mild chymotryptic digests of TSP. This fragment is disulfide-linked to a 120- to 140-kDa fragment in unreduced digests, and both reduction and denaturation are required to separate the 18-kDa peptide from the larger fragments. A 25-kDa heparin binding domain is also present in the chymotryptic digest. However, the 18-kDa peptide is distinct from the heparin binding domain. The amino acid sequence at the NH2 terminus of the 18-kDa fragment is Asp-Thr-Asn-Pro-Thr-Arg-Ala-Gln-Gly-Tyr-.
Neural differentiation of mouse embryonic stem cells grown in monolayer (2002)

To drive neural differentiation of mouse embryonic stem (ES) cells, various culture protocols have been previously developed that all require the formation of embryoid bodies, usually combined with a treatment by all-trans retinoic acid (aRA). Here, we investigated whether or not neural differentiation can also occur in a simplified monolayer culture. Mouse ES cells were plated in serum-containing DMEM media with and without aRA and grown under these conditions for 2 days. Then, the cells were transferred to fresh serum-containing DMEM media and/or to serum-free DMEM/F12 media supplemented with a mixture of insulin, transferrin, selenium, and fibronectin (ITSF) for further culture. The changes in cell morphology and in the expression of selected molecular markers were monitored. Generally, in contrast to all the others, the protocol consisting of a 2-day culture in serum-containing DMEM followed by continuous exposure to the ITSF supplement in DMEM/F12 drove a vast majority of ES cells to generate phenotypic signs of neural lineage. Altogether, neural differentiation can be achieved in vitro without the step involving the formation of embryoid bodies as well as the treatment by aRA.
Evidence for two enzymatic pathways for ω-oxidation of docosanoic acid in rat liver microsomes (2005)

We studied the omega-oxidation of docosanoic acid (C22:0) in rat liver microsomes. C22:0 and 22-hydroxy-docosanoic acid (omega-hydroxy-C22:0) were used as substrates, and the reaction products were analyzed by electrospray ionization mass spectrometry. In the presence of NADPH, omega-oxidation of C22:0 produced not only the hydroxylated product, omega-hydroxy-C22:0, but also the dicarboxylic acid of C22:0, docosanedioic acid (C22:0-DCA). When rat liver microsomes were incubated with omega-hydroxy-C22:0 in the presence of either NAD+ or NADPH, C22:0-DCA was formed readily. Formation of C22:0-DCA from either C22:0 or omega-hydroxy-C22:0 with NADPH as cofactor was inhibited strongly by miconazole and disulfiram, whereas no inhibition was found with NAD+ as cofactor. Furthermore, omega-oxidation of C22:0 was reduced significantly when molecular oxygen was depleted. The high sensitivity toward the more specific cytochrome P450 inhibitors ketoconazole and 17-octadecynoic acid suggests that hydroxylation of C22:0 and omega-hydroxy-C22:0 may be catalyzed by one or more cytochrome P450 hydroxylases belonging to the CYP4A and/or CYP4F subfamily. This study demonstrates that C22:0 is a substrate for the omega-oxidation system in rat liver microsomes and that the product of the first hydroxylation step, omega-hydroxy-C22:0, may undergo further oxidation via two distinct pathways driven by NAD+ or NADPH.
Phase 2 study of CEP-701, an orally available JAK2 inhibitor, in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis (2009)

Few treatment options exist for patients with myelofibrosis (MF), and their survival is significantly shortened. Activating mutation of the JAK2 tyrosine kinase (JAK2(V617F)) is found in approximately 50% of MF patients. CEP-701 is a tyrosine kinase inhibitor that inhibits JAK2 in in vitro and in vivo experiments. We conducted a phase 2 clinical study of CEP-701 in 22 JAK2(V617F)-positive MF patients (80 mg orally twice daily), and 6 (27%) responded by International Working Group criteria (clinical improvement in all cases): reduction in spleen size only (n = 3), transfusion independency (n = 2), and reduction in spleen size with improvement in cytopenias (n = 1). Median time to response was 3 months, and duration of response was more than or equal to 14 months. No improvement was seen in bone marrow fibrosis or JAK2(V617F) allele burden. Phosphorylated STAT3 levels decreased from baseline in responders while on therapy. Eight patients (36%) experienced grade 3 or 4 toxicity, and 6 (27%) required dose reduction. Main side effects were myelosuppression (grade 3 or 4 anemia, 14%; and thrombocytopenia, 23%) and gastrointestinal disturbances (diarrhea, any grade, 72%; grade 3 or 4, 9%; nausea, grade 1 or 2 only, 50%; vomiting, grade 1 or 2 only, 27%). In conclusion, CEP-701 resulted in modest efficacy and mild but frequent gastrointestinal toxicity in MF patients. The study was registered at http://clinicaltrials.gov as NCT00494585.
Toward Understanding of Electrical Limitations (Electronic, Ionic) in LiMPO[sub 4] (M=Fe, Mn) Electrode Materials (2005)

To better understand the factors responsible for the poor electrochemical performances of the olivine-type , various experiments such as chemical delithiation, galvanostatic charge and discharge, cyclic voltamperometry, and impedance conductivity, were carried out on both and . Chemical delithiation experiments confirmed a topotactic two-phase electrochemical mechanism between and the fully delithiated phase (, , and ). We conclude that the limiting factor in the / electrochemical reaction is nested mostly in the ionic and/or electronic transport within the particles themselves rather than in charge transfer kinetics or structural instability of the phase. For instance, the electrical conductivity of ( at 573 K, ) was found to be several orders of magnitude lower than that of ( at 298 K, ).
Kinetic mechanism of p53 oncogenic mutant aggregation and its inhibition (2012)

Aggregation of destabilized mutants of the tumor suppressor p53 is a major route for its loss of activity. In order to assay drugs that inhibit aggregation of p53, we established the basic kinetics of aggregation of its core domain, using the mutant Y220C that has a mutation-induced, druggable cavity. Aggregation monitored by light scattering followed lag kinetics. Electron microscopy revealed the formation of small aggregates that subsequently grew to larger amorphous aggregates. The kinetics of aggregation produced surprising results: progress curves followed either by the binding of Thioflavin T or the fluorescence of the protein at 340 nm fitted well to simple two-step sequential first-order lag kinetics with rate constants k(1) and k(2) that were independent of protein concentration, and not to classical nucleation-growth. We suggest a mechanism of first-order formation of an aggregation competent state as being rate determining followed by rapid polymerization with the higher order kinetics. By measuring the inhibition kinetics of k(1) and k(2), we resolved that the process with the higher rate constant followed that of the lower. Further, there was only partial inhibition of k(1) and k(2), which showed two parallel pathways of aggregation, one via a state that requires unfolding of the protein and the other of partial unfolding with the ligand still bound. Inhibition kinetics of ligands provides a useful tool for probing an aggregation mechanism.
Role of Promyelocytic Leukemia (Pml) Sumolation in Nuclear Body Formation, 11s Proteasome Recruitment, and as2O3-Induced Pml or Pml/Retinoic Acid Receptor α Degradation (2001)

Promyelocytic leukemia (PML) is the organizer of nuclear matrix domains, PML nuclear bodies (NBs), with a proposed role in apoptosis control. In acute promyelocytic leukemia, PML/retinoic acid receptor (RAR) alpha expression disrupts NBs, but therapies such as retinoic acid or arsenic trioxide (As2O3) restore them. PML is conjugated by the ubiquitin-related peptide SUMO-1, a process enhanced by As2O3 and proposed to target PML to the nuclear matrix. We demonstrate that As2O3 triggers the proteasome-dependent degradation of PML and PML/RARalpha and that this process requires a specific sumolation site in PML, K160. PML sumolation is dispensable for its As2O3-induced matrix targeting and formation of primary nuclear aggregates, but is required for the formation of secondary shell-like NBs. Interestingly, only these mature NBs harbor 11S proteasome components, which are further recruited upon As2O3 exposure. Proteasome recruitment by sumolated PML only likely accounts for the failure of PML-K160R to be degraded. Therefore, studying the basis of As2O3-induced PML/RARalpha degradation we show that PML sumolation directly or indirectly promotes its catabolism, suggesting that mature NBs could be sites of intranuclear proteolysis and opening new insights into NB alterations found in viral infections or transformation.
Studies toward a Synthesis of Epothilone A:  Stereocontrolled Assembly of the Acyl Region and Models for Macrocyclization (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTStudies toward a Synthesis of Epothilone A: Stereocontrolled Assembly of the Acyl Region and Models for MacrocyclizationPeter Bertinato, Erik J. Sorensen, Dongfang Meng, and Samuel J. DanishefskyView Author Information Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10021, and Department of Chemistry, Columbia University, Havemeyer Hall, New York, New York 10027 Cite this: J. Org. Chem. 1996, 61, 23, 8000–8001Publication Date (Web):November 15, 1996Publication History Received30 August 1996Published online15 November 1996Published inissue 15 November 1996https://pubs.acs.org/doi/10.1021/jo961674ohttps://doi.org/10.1021/jo961674orapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views1246Altmetric-Citations98LEARN 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:Alcohols,Aldehydes,Alkyls,Hydrocarbons,Olefin metathesis Get e-Alerts
A free-text retrieval system using hash codes (1975)

An algorithm is presented for efficient serial searching of files whose records have arbitrary length free-text retrieval keys. It is most applicable when a batch of enquiries is to search a given file once only, which is an implicit feature of the SDI application for which it was designed. Unlike some other serial systems, an arbitrary number of enquiries can be handled with a single pass of the search file, and the algorithm is simple in concept, and straightforward to implement. Specimen performance figures are quoted in the appendix.