Página 1 dos resultados de 1938 itens digitais encontrados em 0.007 segundos

BCR-ABL-mediated upregulation of PRAME is responsible for knocking down TRAIL in CML patients

CARVALHO, D. D. De; BINATO, R.; PEREIRA, W. O.; LEROY, J. M. G.; COLASSANTI, M. D.; PROTO-SIQUEIRA, R.; BUENO-DA-SILVA, A. E. B.; ZAGO, M. A.; ZANICHELLI, M. A.; ABDELHAY, E.; CASTRO, F. A.; JACYSYN, J. F.; AMARANTE-MENDES, G. P.
Fonte: NATURE PUBLISHING GROUP Publicador: NATURE PUBLISHING GROUP
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
37.18%
Tumor necrosis factor-related apoptosis-inducing ligand-TNFSF10 (TRAIL), a member of the TNF-alpha family and a death receptor ligand, was shown to selectively kill tumor cells. Not surprisingly, TRAIL is downregulated in a variety of tumor cells, including BCR-ABL-positive leukemia. Although we know much about the molecular basis of TRAIL-mediated cell killing, the mechanism responsible for TRAIL inhibition in tumors remains elusive because (a) TRAIL can be regulated by retinoic acid (RA); (b) the tumor antigen preferentially expressed antigen of melanoma (PRAME) was shown to inhibit transcription of RA receptor target genes through the polycomb protein, enhancer of zeste homolog 2 (EZH2); and (c) we have found that TRAIL is inversely correlated with BCR-ABL in chronic myeloid leukemia (CML) patients. Thus, we decided to investigate the association of PRAME, EZH2 and TRAIL in BCR-ABL-positive leukemia. Here, we demonstrate that PRAME, but not EZH2, is upregulated in BCR-ABL cells and is associated with the progression of disease in CML patients. There is a positive correlation between PRAME and BCR-ABL and an inverse correlation between PRAME and TRAIL in these patients. Importantly, knocking down PRAME or EZH2 by RNA interference in a BCR-ABL-positive cell line restores TRAIL expression. Moreover...

STAT5 signaling is required for the efficient induction and maintenance of CML in mice

Ye, Dan; Wolff, Nicholas; Li, Li; Zhang, Shumin; Ilaria, Robert L.
Fonte: The American Society of Hematology Publicador: The American Society of Hematology
Tipo: Artigo de Revista Científica
Publicado em 15/06/2006 EN
Relevância na Pesquisa
27.34%
The role of signal transducers and activators of transcription 5 (STAT5) in chronic myelogenous leukemia (CML) is controversial. To clarify the role of STAT5 signaling in P210BCR/ABL leukemogenesis, P210 was introduced into primary murine STAT5A-deficient (STAT5A–/–) bone marrow (BM) cells, which, unlike STAT5A/5B double knockout BM cells, have no major intrinsic hematopoietic defects. Interestingly, only 21% of mice reconstituted with P210-transduced STAT5A–/– BM cells developed classic CML, compared with 80% to 100% of P210/STAT5A+/+ and P210/STAT5A+/–-reconstituted animals. The remainder of P210/STAT5A–/– animals died from an acute B-cell lymphoblastic leukemia (ALL)–like disease (32%) or a CML/ALL mix (47%), reflecting impairment in the induction and maintenance of CML, which normally predominates in this mouse model. Of mice that ultimately developed CML, P210/STAT5A–/– animals had prolonged survival and increased myeloid immaturity. Importantly, reconstitution of wild-type mice with BM cells coexpressing P210 and dominant-negative STAT5 also profoundly reduced the incidence of CML, without impairing the induction of ALL. Altogether, these findings indicate that STAT5 and STAT5A play an important role in the pathogenesis of the CML-like disease in mice. A greater understanding of the STAT5 target genes involved in CML induction may lead to new therapeutic targets that influence CML progenitor cell biology.

Human AQP5 Plays a Role in the Progression of Chronic Myelogenous Leukemia (CML)

Chae, Young Kwang; Kang, Sung Koo; Kim, Myoung Sook; Woo, Janghee; Lee, Juna; Chang, Steven; Kim, Dong-Wook; Kim, Myungshin; Park, Seonyang; Kim, Inho; Keam, Bhumsuk; Rhee, Jiyoung; Koo, Nam Hee; Park, Gyeongsin; Kim, Soo-Hyun; Jang, Se-Eun; Kweon, Il-You
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 09/07/2008 EN
Relevância na Pesquisa
27.34%
Aquaporins (AQPs) have previously been associated with increased expression in solid tumors. However, its expression in hematologic malignancies including CML has not been described yet. Here, we report the expression of AQP5 in CML cells by RT-PCR and immunohistochemistry. While normal bone marrow biopsy samples (n = 5) showed no expression of AQP5, 32% of CML patient samples (n = 41) demonstrated AQP5 expression. In addition, AQP5 expression level increased with the emergence of imatinib mesylate resistance in paired samples (p = 0.047). We have found that the overexpression of AQP5 in K562 cells resulted in increased cell proliferation. In addition, small interfering RNA (siRNA) targeting AQP5 reduced the cell proliferation rate in both K562 and LAMA84 CML cells. Moreover, by immunoblotting and flow cytometry, we show that phosphorylation of BCR-ABL1 is increased in AQP5-overexpressing CML cells and decreased in AQP5 siRNA-treated CML cells. Interestingly, caspase9 activity increased in AQP5 siRNA-treated cells. Finally, FISH showed no evidence of AQP5 gene amplification in CML from bone marrow. In summary, we report for the first time that AQP5 is overexpressed in CML cells and plays a role in promoting cell proliferation and inhibiting apoptosis. Furthermore...

Triptolide induces cell death independent of cellular responses to imatinib in blast crisis CML cells including quiescent CD34+ primitive progenitor cells

Mak, Duncan H.; Schober, Wendy D.; Chen, Wenjing; Konopleva, Marina; Cortes, Jorge; Kantarjian, Hagop M.; Andreeff, Michael; Carter, Bing Z.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
27.38%
The advent of Bcr-Abl tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of CML. However, resistance evolves due to BCR-ABL mutations and other mechanisms. Furthermore, patients with blast crisis (BC) CML are less responsive and quiescent CML stem cells are insensitive to these inhibitors. We found that triptolide, a diterpenoid, at nM concentrations, promoted equally significant death of KBM5 cells, a cell line derived from a Bcr-Abl-bearing BC CML patient and KBM5STI571 cells, an imatinib-resistant KBM5 subline bearing the T315I mutation. Similarly, Ba/F3 cells harboring mutated BCR-ABL were as sensitive as Ba/F3Bcr-Ablp210wt cells to triptolide. Importantly, triptolide induced apoptosis in primary samples from BC CML patients, who showed resistance to Bcr-Abl TKIs in vivo, with less toxicity to normal cells. Triptolide decreased XIAP, Mcl-1, and Bcr-Abl protein levels in K562, KBM5, KBM5STI571 cells and in cells from BC CML patients. It sensitized KBM5, but not KBM5STI571 cells to imatinib. More importantly, triptolide also induced death of quiescent CD34+ CML progenitor cells, a major problem in the therapy of CML with TKIs. Collectively, these results suggest that triptolide potently induces BC CML cell death independent of the cellular responses to Bcr-Abl TKIs...

GVL against mouse BC-CML and CP-CML: Shared mechanisms of T cell killing, but PD-ligands render CP-CML and not BC-CML GVL-resistant*

Matte-Martone, Catherine; Venkatesan, Srividhya; Tan, Hung Sheng; Athanasiadis, Ioanna; Chang, Julia; Pavisic, Jovana; Shlomchik, Warren
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
27.5%
GVL against chronic phase CML (CP-CML) is potent, but it is less efficacious against acute leukemias and blast crisis CML (BC-CML). The mechanisms underlying GVL-resistance are unknown. Previously, we found that alloreactive T cell targeting of GVL-sensitive bcr-abl-induced mouse CP-CML (mCP-CML) required TCR:MHC interactions and that multiple and redundant killing mechanisms were in play. To better understand why BC-CML is resistant to GVL, we performed a comprehensive analysis of GVL against mouse BC-CML (mBC-CML) induced by the retroviral transfer of the bcr-abl and NUP98/HOXA9 fusion cDNAs. Like human BC-CML, mBC-CML was GVL-resistant, and this was not due to accelerated kinetics or a greater leukemia burden. To study T cell recognition and killing mechanisms, we generated a panel of gene-deficient leukemias by transducing bone marrow from gene-deficient mice. T cell target recognition absolutely required that mBC-CML cells express MHC and GVL against both mCP-CML and mBC-CML required leukemia expression of ICAM-1. We hypothesized that mBC-CML would be resistant to some of the killing mechanisms sufficient to eliminate mCP-CML, but we found instead that the same mechanisms were effective against both types of leukemia as GVL was similar against wild type or mBC-CML genetically lacking Fas...

An investigation into the roles of CML15, CML16, and CML44, three calmodulin-like (CML) putative calcium sensors from Arabidopsis

Ogunrinde, Adenike
Fonte: Quens University Publicador: Quens University
Tipo: Tese de Doutorado
EN
Relevância na Pesquisa
37.18%
Plant cells use calcium (Ca2+) as a second messenger, exploiting Ca2+ gradients to facilitate rapid changes in cytosolic Ca2+ ( [ Ca2+]cyt) . Stimulus-specific spatio-temporal patterns of [Ca2+]cyt influx are interpreted by Ca2+-binding proteins such as the highly conserved calmodulin (CaM). In addition to CaM, Arabidopsis thaliana (Arabidopsis) possesses 50 CaM-like genes (CMLs) that are phylogenetically organized into 9 subfamilies. Very few CMLs have been studied to date and thus their biochemical properties and physiological roles remain largely unknown. Using a combination of molecular and biochemical analyses, the aim of this thesis was to provide insight into the cellular roles of CML15 and CML16 (within CML subfamily 4) and CML 44 (from subfamily 7). Using the beta-glucuronidase (GUS) reporter system, promoter analysis of CML15 and CML16 was performed to elucidate spatial patterns of promoter activity in Arabidopsis. Preliminary CML-promoter::GUS analysis suggested that CML15 promoter activity is either very weak or entirely absent from seedling tissues, and that CML16 promoter activity is broadly expressed in seedling tissues. These results are consistent with previous microarray studies. Using a reverse genetics approach...

Factors which impact on the response of CML patients to ABL kinase inhibitor therapy: a study of imatinib and nilotinib.

Harland, Deborah Lee
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2008
Relevância na Pesquisa
37.18%
The natural history of CML has been transformed in recent years by the introduction of Glivec[superscript TM] (imatinib mesylate), an ABL kinase inhibitor, which provides the new treatment paradigm for chronic phase CML. While the majority of patients with CP-CML respond very well to imatinib, there are approximately 15% of patients who fail to respond, or respond suboptimally. While the major cause of secondary imatinib resistance can be attributable to kinase domain mutations, the underlying cause of primary resistance is yet to be elucidated. Utilizing the phosphorylation of the adaptor protein Crkl, an immediate downstream partner of BCRABL, as a surrogate measure of BCR-ABL kinase activity, a large interpatient variation in the degree of imatinib induced kinase inhibition achieved in-vitro, was observed in previously untreated CP-CML patients. The observed in-vitro sensitivity was a good predictor of molecular response in patients treated with 600mg imatinib as front line therapy. Furthermore, analysis of the in-vivo reduction in p-Crkl mediated measured in blood cells in response to imatinib over the first 28 days of therapy, revealed that patients with higher % reductions respond significantly better over a two year period...

Harmonization of molecular monitoring of CML therapy in Europe

Muller, M.; Cross, N.; Erben, P.; Schenk, T.; Hanfstein, B.; Ernst, T.; Hehlmann, R.; Branford, S.; Saglio, G.; Hochhaus, A.
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em //2009 EN
Relevância na Pesquisa
36.87%
The high efficacy of the standard treatment of chronic myeloid leukemia (CML) with imatinib has prompted the need for accurate methods to monitor response at levels below the landmark of complete cytogenetic remission. Quantification of BCR–ABL transcripts has proven to be the most sensitive method available, and has shown prognostic impact with regard to progression-free survival. Until recently, variations in methods used to quantify BCR–ABL made it difficult to compare results between laboratories. An international program is now underway to harmonize the reporting of results according to an international scale (IS). In this review, we consider the background to the IS and the progress that has been made to date, with a particular focus on ongoing harmonization efforts in Europe. We provide recommendations for the propagation of the IS by national or regional laboratory networks.; MC Muller, NCP Cross, P Erben, T Schenk, B Hanfstein, T Ernst, R Hehlmann, S Branford, G Saglio and A Hochhaus

A Phase I/II study of nilotinib in Japanese patients with imatinib-resistant or -intolerant Ph plus CML or relapsed/refractory Ph plus ALL

Tojo, A.; Usuki, K.; Urabe, A.; Maeda, Y.; Kobayashi, Y.; Jinnai, I.; Ohyashiki, K.; Nishimura, M.; Kawaguchi, T.; Tanaka, H.; Miyamura, K.; Miyazaki, Y.; Hughes, T.; Branford, S.; Okamoto, S.; Ishikawa, J.; Okada, M.; Usui, N.; Tanii, H.; Amagasaki, T.;
Fonte: Garden Jennings Publ Co Ltd Publicador: Garden Jennings Publ Co Ltd
Tipo: Artigo de Revista Científica
Publicado em //2009 EN
Relevância na Pesquisa
37.27%
Nilotinib is a second-generation BCR-ABL kinase inhibitor with improved potency and selectivity compared to imatinib. A Phase I/II dose-escalation study was designed to evaluate the efficacy, safety, and pharmacokinetics of nilotinib in Japanese patients with imatinibresistant or -intolerant Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) or relapsed/ refractory Ph+ acute lymphoblastic leukemia (ALL). A total of 34 patients were evaluated in this analysis and had a median duration of drug exposure of 293 (range 13–615) days. All 6 CML-CP patients without complete hematologic response (CHR) at baseline rapidly achieved CHR. A major cytogenetic response was achieved in 94% of patients with CML-CP, including a complete cytogenetic response in 69%. A major molecular response was achieved by 56%. These responses were also observed in patients with CML in advanced stages and Ph+ ALL. Non-hematologic adverse events were mostly mild to moderate. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 50 and 28% of patients, respectively. Overall, the results of this study suggest that nilotinib induced significant responses inimatinib-resistant or -intolerant patients with CML-CP and CML in advanced stages and Ph+ ALL. The results of this study confirmed the efficacy and safety of nilotinib in Japanese patients.; Arinobu Tojo... Timothy Hughes... Susan Branford... et al.

TKI resistance in CML cell lines : investigating resistance pathways.

Tang, Carine
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2012
Relevância na Pesquisa
36.87%
Chronic myeloid leukaemia (CML) is characterised by the presence of the Philadelphia chromosome which harbours the Bcr-Abl oncogene. BCR-ABL is a constitutively active tyrosine kinase that can be inhibited by rationally designed tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib and dasatinib. Although TKI therapy is an effective treatment for many patients, resistance can arise. There are currently four identified resistance mechanisms. These are 1) overexpression of drug-efflux proteins (ABCB1 and ABCG2), 2) BCR-ABL kinase domain (KD) mutations, 3) increased BCR-ABL expression and 4) BCR-ABL independent mechanisms such as Lyn kinase expression. In this study the interplay between these four recognised modes of TKI resistance is investigated. Imatinib- and dasatinib-resistant cell lines were established and used to investigate TKI resistance in vitro. Viability and IC50 assays were used to demonstrate TKI sensitivity/resistance. Flow cytometry was used to screen for ABCB1 and ABCG2 cell surface expression, while conventional sequencing and the MassARRAY method were used to determine the mutation status of the BCR-ABL KD. Fluorescence in situ hybridisation (FISH) and quantitative DNA PCR were used to investigate Bcr-Abl DNA copy number...

Bone marrow engraftment: histopathology of hematopoietic reconstitution following allogeneic transplantation in CML patients

Thiele, J.; Kvasnicka, H.M.; Beelen, D.W.; Leder, L.D.; Schaefer, U.W.
Fonte: Murcia : F. Hernández Publicador: Murcia : F. Hernández
Tipo: Artigo de Revista Científica Formato: application/pdf
ENG
Relevância na Pesquisa
37.01%
Following myelo-ablative treatment and allogeneic bone marrow transplantation (BMT) in chronic myelogenous leukemia (CML) histopathological features assumed to exert a sienificant i m ~ a c ot n engraftment have been rarely inve;igated systekatically. This review is focused on immunohistochemical and morphometric techniques involving nucleated erythroid precursors, resident macrophages and their various subsets, megakaryocytes and finally argyrophilic (reticulin-collagen) fibers. Regarding standardized intervals of examination in the postgraft sequential trephine biopsies a pronounced reduction in cellularity was obvious and accompanied by a decrease in the quantity of erythro- and megakaryopoiesis. A significant correlation between the number of erythroid precursors and CD68+-macrophages could be determined in the areas of regenerating hematopoiesis. This finding is in keeping with the important functional role of the centrally localized mature macrophages during erythropoiesis. A relevant pretransplant reduction of the red cell lineage and an early to advanced reticulin fibrosis were correlated with a low hemoglobin leve1 (anemia) and splenomegaly and furthermore associated with a significant delay to reach transfusion independence. This result was supported by corresponding findings in biopsy specimens performed shortly after day 30 following BMT (standard interval for assessment of engraftment). Samples revealed an enhancement of fiber density and a conspicuous decrease in the amount of erythropoiesis in the small fraction of patients who did not conform with the usually accepted criteria for successful hematopoietic reconstitution. Considering the compartment of histiocytic reticular cells the recurrence of Pseudo-Gaucher cells (PCGs) in the engrafted donor marrow was remarkable and most prominently expressed in the first two months following BMT. This feature was presumed to be functionally linked with a pronounced degradation of cell debris in the seque1 of myelo-ablative therapy (scavenger macrophages). According to planimetric measurements in the postgraft bone marrow the atypical dwarf-like CD61+-megakaryocytes characteristic for CML disappeared. On the other hand...

Determinaci??n de carboximetillisina en alimentos tostados y horneados

Mes??as, M.; L??pez P??rez, N.; Guerra-Hern??ndez, E.; Garc??a-Villanova, Bel??n
Fonte: Universidad de Granada, Facultad de Farmacia Publicador: Universidad de Granada, Facultad de Farmacia
Tipo: Artigo de Revista Científica
SPA
Relevância na Pesquisa
27.43%
La carboximetillisina (CML) es un indicador de etapas avanzadas de la reacci??n de Maillard. Su formaci??n en los alimentos depender?? directamente de la composici??n de los mismos, pero tambi??n de la temperatura y tiempo de calentamiento al que se ven sometidos durante el procesado. Concretamente, se ve favorecida cuando el tratamiento t??rmico es m??s severo, de ah?? que est?? presente en alimentos tostados u horneados como los productos de panader??a o boller??a. En el presente trabajo se analiz?? el contenido de CML en 9 tipos de alimentos: pan integral, pan de molde tostado a diferentes tiempos, colines, torta de in??s rosales, palmera, caracola, suizo y medianoche y galleta integral m??s o menos horneadas. La determinaci??n de CML se realiz?? mediante cromatograf??a de gases acoplada a espectrometr??a de masas, previa reducci??n, hidr??lisis y derivatizaci??n. Los valores de CML determinados en las muestras del estudio oscilaron entre 1,38 mg/100 g muestra (palitos no integrales) y 10,4 mg/100 g de muestra (galleta m??s tostada). El pan de molde mostr?? un incremento en el contenido de CML paralelo al tiempo de tostado, pasando de 6,31 mg/100 g sin tostar, a 6,44 mg/100g con 1 minuto de tostado y a 8,95 mg/100 g con 6 minutos de tostado. En conclusi??n...

Defining CP-CML patient subsets associated with poor imatinib uptake and response.

Watkins, Dale Benjamin
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2014
Relevância na Pesquisa
27.42%
The introduction of tyrosine kinase inhibitor (TKI) therapy, specifically imatinib, has dramatically improved the treatment outcome for the majority of chronic phase chronic myeloid leukaemia (CP-CML) patients. Although most patients will achieve excellent clinical (haematological, cytogenetic and molecular) responses on imatinib, it is clear that a subset of patients will respond poorly, or fail imatinib therapy. Currently, up to 35% of patients treated with imatinib fit into this subset, displaying either primary or acquired resistance, leading to sub-optimal response or imatinib failure. The organic cation transport-1 (OCT-1) protein is the major active protein involved in imatinib transport. Measuring the function of OCT-1 in leukaemic mononuclear cells prior to imatinib therapy, expressed as OCT-1 activity (OA), has been demonstrated to be a strong prognostic indicator. Notably, low OA is strongly associated with patients at significant risk of poor molecular response, mutation development and leukaemic transformation during imatinib therapy. It is important to therefore determine what factors underlie the range of OA levels observed in CP-CML patients, and whether patients with very low OA and poor response to imatinib have different overall disease characteristics associated with alternative biological mechanisms. The present study sought to 1) determine the variation in CP-CML patient immunophenotype at diagnosis...

Blocking cytokine signaling along with intense Bcr-Abl kinase inhibition induces apoptosis in primary CML progenitors

Hiwase, D.; White, D.; Powell, J.; Saunders, V.; Zrim, S.; Frede, A.; Guthridge, M.; Lopez, A.; D'Andrea, R.; To, L.; Vaz de Melo, J.; Kumar, S.; Hughes, T.
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em //2010 EN
Relevância na Pesquisa
37.31%
In chronic myeloid leukemia (CML) cell lines, brief exposure to pharmacologically relevant dasatinib concentrations results in apoptosis. In this study, we assess the impact of intensity and duration of Bcr-Abl kinase inhibition on primary CD34(+) progenitors of chronic phase CML patients. As CML cells exposed to dasatinib in vivo are in a cytokine-rich environment, we also assessed the effect of cytokines (six growth factors cocktail or granulocyte-macrophage colony-stimulating factor (CSF) or granulocyte-CSF) in combination with dasatinib. In the presence of cytokines, short-term intense Bcr-Abl kinase inhibition (>or=90% p-Crkl inhibition) with 100 nM dasatinib did not reduce CD34(+) colony-forming cells (CFCs). In contrast, without cytokines, short-term exposure to dasatinib reduced CML-CD34(+) CFCs by 70-80%. When cytokines were added immediately after short-term exposure to dasatinib, CML-CD34(+) cells remained viable, suggesting that oncogene dependence of these cells can be overcome by concomitant or subsequent exposure to cytokines. Additional inhibition of Janus tyrosine kinase (Jak) activity re-established the sensitivity of CML progenitors to intense Bcr-Abl kinase inhibition despite the presence of cytokines. These findings support the contention that therapeutic strategies combining intense Bcr-Abl kinase inhibition and blockade of cytokine signaling pathways can be effective for eradication of CML progenitors.; D. K. Hiwase...

CMLLite: a design philosophy for CML

Townsend, Joseph A; Murray-Rust, Peter
Fonte: Murray-Rust group, Unilever Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge Publicador: Murray-Rust group, Unilever Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge
Tipo: Article; not applicable
EN
Relevância na Pesquisa
37.01%
CMLLite is a collection of definitions and processes which provide strong and flexible validation for a document in Chemical Markup Language (CML). It consists of an updated CML schema (schema3), conventions specifying rules in both human and machine-understandable forms and a validator available both online and offline to check conformance. This article explores the rationale behind the changes which have been made to the schema, explains how conventions interact and how they are designed, formulated, implemented and tested, and gives an overview of the validation service.; The Chem4Word project was supported by Microsoft External Research (http://research.microsoft.com/en-us/projects/chem4word/)

CML: Evolution and Design

Murray-Rust, Peter; Rzepa, Henry S
Fonte: Murray-Rust group, Unilever Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge Publicador: Murray-Rust group, Unilever Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge
Tipo: Article; not applicable
EN
Relevância na Pesquisa
36.87%
A retrospective view of the design and evolution of Chemical Markup Language (CML) is presented by its original authors.

The semantics of Chemical Markup Language (CML): dictionaries and conventions

Murray-Rust, Peter; Townsend, Joseph A; Adams, Sam; Phadungsukanan, Weerapong; Thomas, Jens
Fonte: Murray-Rust group, Unilever Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge Publicador: Murray-Rust group, Unilever Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge
Tipo: Article; not applicable
EN
Relevância na Pesquisa
37.01%
The semantic architecture of CML consists of conventions, dictionaries and units. The conventions conform to a top-level specification and each convention can constrain compliant documents through machine-processing (validation). Dictionaries conform to a dictionary specification which also imposes machine validation on the dictionaries. Each dictionary can also be used to validate data in a CML document, and provide human-readable descriptions. An additional set of conventions and dictionaries are used to support scientific units. All conventions, dictionaries and dictionary elements are identifiable and addressable through unique URIs.

The use of CML and CML in Computational Chemistry and Physics Programs

Wakelin, Jon; Garcia, A; Murray-Rust, Peter
Fonte: Universidade de Cambridge Publicador: Universidade de Cambridge
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
37.31%
Proceedings of the 2004 e-Science All Hands Meeting, 31st August - 3rd September, Nottingham UK; This work addresses problems associated with data exchange and data representation in the computational chemistry and physics communities. Recent computational developments, such as Condor and the Grid, have paved the way for new kinds of simulations that demand more rigorous data handling. To this end, the paper discusses the use of XML and the Chemical Markup Language (CML) in theoretical chemistry and physics. Extensions to the core CML language, known as CMLComp, are also discussed. However, the majority of atomic scale simulation software is written in Fortran. Fortran's lack of XML support represents a potential barrier to the adoption of CML in these fields. This has prompted the authors to develop XML and CML processing tools for Fortran, including native SAX and DOM implementations, as well as libraries for generating well formed XML and CML. These libraries have been used to extend existing simulation packages to work with the CML and CMLComp languages. Finally, we give a practical example that highlights how these XML aware applications can be effectively used as workflow components in complex chemical and physical simulations.

Capturing Chemistry in XML/CML

Townsend, Joseph A; Adams, Sam; Goodman, Jonathan M; Murray-Rust, Peter; Waudby, Chris A
Fonte: Universidade de Cambridge Publicador: Universidade de Cambridge
Tipo: Conferência ou Objeto de Conferência
EN
Relevância na Pesquisa
37.11%
ACS Spring Conference; Chemical Markup Language (CML) is an XML-conformant Schema that describes molecules, spectra, reactions, and computational chemistry. It is capable of capturing the chemistry in a variety of current publications and is becoming adopted by many organizations. We have developed tools for batch conversion of current chemical documents such as primary journal publications and theses into conformant CML. The parser reads many text and molecular formats and extracts chemical concepts into CML that are combined to give a single XML file. The process works well for methodology and analytical data in organic synthesis. The results are stored in an XML database where they can be queried on molecular identity and numeric quantities. Parsers can also capture the output of computational chemistry to extract essentially all of the information in the logfile. XML stylesheets can then be used to filter and display the results in an interactive manner.

Dietary intake increases serum levels of carboxymethil-lysine (CML) in diabetic patients

Jara,N.; Leal,M. J.; Bunout,D.; Hirsch,S.; Barrera,G.; Leiva,L.; de la Maza,M. P.
Fonte: Nutrición Hospitalaria Publicador: Nutrición Hospitalaria
Tipo: info:eu-repo/semantics/article; journal article; info:eu-repo/semantics/publishedVersion Formato: text/html; application/pdf
Publicado em 01/08/2012 ENG
Relevância na Pesquisa
37.23%
Introduction: Advanced glycation end products are produced endogenously, in association with hyperglycemia and oxidative stress. They can also be generated during cooking or food processing and, once absorbed, alter protein function and promote inflammation. Methods: We selected 40 healthy male subjects, 17 patients with type 2 diabetes of both sexes and 15 patients with type 1 diabetes of both sexes. Each participant underwent both a food frequency questionnaire (FFQ) and 24-hour dietary recall specially adapted for measuring CML intake, anthropometry, measurement of blood pressure and biochemical parameters in blood and urine. Results: Serum CML levels were significantly higher in patients with diabetes compared to healthy subjects (p 0.04), showing a direct relationship between dietary intake and serum levels of CML in T2D patients (r 0.53 p 0.03). sCML levels correlated positively with length of diabetes mellitus, and inversely with body mass index (BMI). The most important dietary factor contributing to raise CML levels in these patients with diabetes was the consumption of milk powder. Conclusion: Serum levels of CML were found to be higher among diabetic subjects, associated to length of diabetes as expected, but also with the ingestion of foods containing higher amounts of ML. The consumption of milk powder in this group is a major determinant of increased serum levels.