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Ying Lu,
Bing Chen,
Jun-Hong Song,
Tao Zhen,
Bai-Yan Wang,
Xin Li,
Ping Liu,
Xin Yang,
Qun-Ling Zhang,
Xiao-Dong Xi,
Sheng-Di Chen,
Jian-Ping Zuo,
Zhu Chen,
Sai-Juan Chen
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ABSTRACT: Eriocalyxin B (EriB), a diterpenoid isolated from Isodon eriocalyx, was previously reported to have antitumor effects via multiple pathways, and these pathways are related to immune responses. In this study, we demonstrated that EriB was efficacious in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. Treatment with EriB led to amelioration of EAE, which correlated with reduced spinal cord inflammation and demyelination. EriB treatment abolished encephalitogenic T-cell responses to myelin oligodendrocyte glycoprotein in an adoptive transfer EAE model. The underlying mechanism of EriB-induced effects involved inhibition of T helper (Th) 1 and Th17 cell differentiation through Janus Kinase/Signal Transducer and Activator Of Transcription and Nuclear factor-κB signaling pathways as well as elevation of reactive oxygen species. These findings indicate that EriB exerts potent antiinflammatory effects through selective modulation of pathogenic Th1 and Th17 cells by targeting critical signaling pathways. The study provides insights into the role of EriB as a unique therapeutic agent for the treatment of autoimmune diseases.
Proceedings of the National Academy of Sciences 01/2013; · 9.68 Impact Factor
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ABSTRACT: To explore the expression and clinical significance of Caudal-type homeobox transcription factor 2 (CDX2) gene in acute myeloid leukemia (AML) patients.
Real time quantitative PCR (RQ-PCR) was used to test the expression level of CDX2 gene in 108 de novo AML patients and the clinical features of these patients were analyzed.
CDX2 gene transcript levels were detectable in bone marrow mononuclear cells from 108 AML patients and 7 healthy donors, the median expression level were 1179.44 (range 14.15 - 867 961.10) and 105.30 (range 22.30 - 453.11). There was a statistically significant difference in expression level of CDX2 gene between the AML patients and normal donor (P < 0.01). All 14 patients with FLT3-ITD(+) were in CDX2 gene higher expression group (P = 0.018), including 10 patients with normal karyotype. In the 83 treated AML patients (P = 0.046) and 57 higher WBC count (≥ 10×10(9)/L, P = 0.048) patients, the higher expression level of CDX2 gene was associated with lower complete remission (CR) rates.
Higher expression level of CDX2 gene was seen mostly in AML patients with FLT3-ITD mutation and with lower CR rates. CDX2 gene might be a prognostic molecular marker in AML patients with normal karyotype.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 10/2012; 33(10):835-8.
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ABSTRACT: To establish a stable, rapid multiplex PCR assay combined with PAGE gel electrophoresis for simultaneously detecting FLT3-ITD and NPM1 mutations in acute myeloid leukemia (AML).
Capillary electrophoresis (CE) and PAGE gel electrophoresis were simultaneously used to analyze FLT3-ITD and NPM1 mutations in 117 de novo AML patients with normal cytogenetic findings.
For certain mutations, the length of mutated double-stranded DNA is longer than wild-type DNA. Since FLT3-mut (420 bp) is longer than FLT3-wt (327-332 bp), and NPM1-mut (172 bp) is longer than NPM1-wt (168 bp), heteroduplex will move more slowly during PAGE gel electrophoresis than homoduplex. Therefore the mutations may be detected. A total of 117 CN-AML patients were analyzed with CE and PAGE gel electrophoresis, and the results were identical, which included 18 (15.4%) patients with FLT3-ITD+/NPM1-, 19 (16.2%) patients with FLT3-ITD+/NPM1+, 25 (21.4%) patients with FLT3-ITD-/NPM1+, and 55 (47.0%) patients with FLT3-ITD-/NPM1-.
Both types of electrophoresis assays may provide a rapid and handy assay for simultaneous detection of FLT3-ITD and NPM1 mutations. CE is relatively sensitive, stable; while PAGE electrophoresis is relatively simple, cheap, and reliable, which may be suitable for primary hospitals and preliminary screening.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 04/2012; 29(2):163-6.
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ABSTRACT: To explore the expression and clinical significance of ID1 gene in acute myeloid leukemia (AML) patients.
Real-time quantitative PCR (RQ-PCR) was used to test the expression level of ID1 gene in 114 de novo adult AML patients, and the clinical features of these patients were analyzed.
ID1 gene transcript levels were detectable in BM mononuclear cells from 114 patients with AML, the median expression level of all samples was 8525 (range: 57 - 11 233 238). There was a statistically significant difference on expression level of ID1 gene among the three different cytogenetic prognosis groups, and the poor prognosis group (median: 36 840, range: 336 - 11 233 238) harbored the significantly higher level of ID1 gene than the intermediate prognosis group (Median: 6630, range: 66 - 1 840 798) (P = 0.006). The expression level of ID1 gene was positively associated with older age (age ≥ 60 years vs < 60 years, P = 0.002) and higher WBC count (WBC ≥ 10×10(9)/L vs < 10×10(9)/L, P = 0.005). Young patients (age < 60 years) who were not obtained the complete remission (non-CR) after the first cycle of chemotherapy harbored the high level of ID1 gene (Median: 9537 of non-CR vs 1268 of CR, P = 0.010).
High expression level of ID1 gene was mostly seen in AML patients with adverse cytogenetics and older age (age ≥ 60 years), and may be associated with poor prognosis of AML. ID1 gene might be a prognostic molecular marker of AML.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 04/2012; 33(4):278-81.
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Tao Zhen,
Chuan-Feng Wu,
Ping Liu,
Hai-Yan Wu,
Guang-Biao Zhou, Ying Lu,
Jian-Xiang Liu,
Yang Liang,
Keqin Kathy Li,
Yue-Ying Wang,
Yin-Yin Xie,
Miao-Miao He,
Huang-Ming Cao,
Wei-Na Zhang,
Li-Min Chen,
Kevin Petrie,
Sai-Juan Chen,
Zhu Chen
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ABSTRACT: Nearly 60% of acute myeloid leukemia (AML) patients with the t(8;21)(q22;q22) translocation fail to achieve long-term disease-free survival. Our previous studies demonstrated that oridonin selectively induces apoptosis of t(8;21) leukemia cells and causes cleavage of AML1-ETO oncoprotein resulting from t(8;21), but the underlying mechanisms remain unclear. We show that oridonin interacted with glutathione and thioredoxin/thioredoxin reductase to increase intracellular reactive oxygen species, which in turn activated caspase-3 in t(8;21) cells. Moreover, oridonin bound AML1-ETO, directing the enzymatic cleavage at aspartic acid 188 via caspase-3 to generate a truncated AML1-ETO (ΔAML1-ETO) and preventing the protein from further proteolysis. ΔAML1-ETO interacted with AML1-ETO and interfered with the trans-regulatory functions of remaining AML1-ETO oncoprotein, thus acting as a tumor suppressor that mediates the anti-leukemia effect of oridonin. Furthermore, oridonin inhibited the activity of c-Kit(+) leukemia-initiating cells. Therefore, oridonin is a potential lead compound for molecular target-based therapy of leukemia.
Science translational medicine 03/2012; 4(127):127ra38. · 7.80 Impact Factor
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ABSTRACT: The International Dual-Photon X-Ray Absorptiometry (DXA) Standardization Committee (IDSC) conducted a cross-calibration study among three models of DXA machines from three different manufacturers. In that study, 100 subjects were scanned on all three machines. A set of equations were derived to convert bone mineral density (BMD) on each machine to a “standardized BMD” (sBMD) such that sBMD from the same subject derived from different machines would be approximately the same. In a reanalysis of the cross-calibration data, we showed that the conversion method used in the IDSC study did not achieve several optimal properties desirable in such conversions. We derived new conversion equations to sBMD based on minimizing differences among sBMD from the three machines. More important is that the new conversions have no residual bias that was present in the IDSC conversions. The performance of the methods were compared on the cross-calibration data as well as an external data set. We conclude that the IDSC conversions are adequate for clinical use on other machines worldwide, but that researchers should standardize their own machines in a laboratory using the new method.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 08/1997; 12(9):1463 - 1470. · 6.04 Impact Factor
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ABSTRACT: Previous studies demonstrated that DBA/2J (DBA) mice performed poorly while C57BL/6J (C57) mice performed normally on a number of complex learning and memory tasks. Chronic oxiracetam treatment dramatically improved the performance of DBA mice but not that of C57 mice on the Morris water task and in contextual fear conditioning. The present study demonstrates that acute treatment with nootropics, oxiracetam (10–1000 mg/kg) or aniracetam (10–100 mg/kg), and N-methyl-d-Aspartate (NMDA) antagonists, (+)-MK-801 (0.1–3 μg/kg), CPP (0.01–0.3 mg/kg), and (+)-HA-966 (0.1–3 mg/kg), administered prior to training and testing, reversed the contextual learning impairment in DBA mice in a dose-dependent manner without affecting auditory cue conditioning. These effects appeared to be independent of testing order (context vs. auditory cue tests) and were not due to state-dependent learning. The inactive stereoisomers, (−)-MK-801 and (−)-HA-966, were incapable of increasing contextual freezing in DBA mice. In DBA mice, the effects of 30 mg/kg oxiracetam and 100 mg/kg aniracetam were inhibited by the (±)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonists, NBQX, and GYKI-52466. The combined administration of 30 mg/kg oxiracetam and 1 μg/kg (+)-MK-801 produced an additive response. None of the pharmacological treatments altered performance in C57 mice at doses that were effective in DBA mice. These results suggest that DBA mice may be learning impaired due to altered glutamatergic receptor function.
Brain Research.
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ABSTRACT: The paper presents an inclusion relation which is used to verify the process of controller synthesis based on incompletely specified finite state machine model. State transition graph is adopted to describe the behavior of controller. State transition graph STG_org was abstract behavior description of controller synthesis generated before synthesized and state transition graph STG_ext was reversely extracted from structure realization of controller synthesis. If STG_org contains STG_ext then corresponding process of controller synthesis was correct. The paper gives a formal verification algorithm of controller synthesis with time complexity. In order to further improve time complexity of algorithm, a verifying algorithm with synthetic information guidance was proposed.
Intelligent Information Technology Applications, 2007 Workshop on. 3:593-597.
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Vardan Khachatryan,
Albert M. Sirunyan,
Armen Tumasyan,
Wolfgang Adam,
Thomas Bergauer,
Marko Dragicevic,
Janos Erö,
Christian Fabjan,
Markus Friedl,
Rudolf Fruehwirth, [......],
Jessica Leonard,
David Lomidze,
Richard Loveless,
Ajit Mohapatra,
Don Reeder,
Ian Ross,
Alexander Savin,
Wesley H. Smith,
Joshua Swanson,
Marc Weinberg
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ABSTRACT: A search for pair production of first-generation scalar leptoquarks is performed in the final state containing two electrons and two jets using proton-proton collision data at sqrt(s)=7 TeV. The data sample used corresponds to an integrated luminosity of 33 inverse picobarns collected with the CMS detector at the CERN LHC. The number of observed events is in good agreement with the predictions for the standard model background processes, and an upper limit is set on the leptoquark pair production cross section times beta^2 as a function of the leptoquark mass, where beta is the branching fraction of the leptoquark decay to an electron and a quark. A 95% confidence level lower limit is set on the mass of a first-generation scalar leptoquark at 384 GeV for beta=1, which is the most stringent direct limit to date.
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Vardan Khachatryan,
Albert M. Sirunyan,
Armen Tumasyan,
Wolfgang Adam,
Thomas Bergauer,
Marko Dragicevic,
Janos Erö,
Christian Fabjan,
Markus Friedl,
Rudolf Fruehwirth, [......],
Christos Lazaridis,
Jessica Leonard,
Richard Loveless,
Ajit Mohapatra,
Don Reeder,
Ian Ross,
Alexander Savin,
Wesley H. Smith,
Joshua Swanson,
Marc Weinberg
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ABSTRACT: A measurement of the b-hadron production cross section in proton-proton collisions at sqrt(s)=7 TeV is presented. The dataset, corresponding to 85 inverse nanobarns, was recorded with the CMS experiment at the LHC using a low-threshold single-muon trigger. Events are selected by the presence of a muon with transverse momentum greater than 6 GeV with respect to the beam direction and pseudorapidity less than 2.1. The transverse momentum of the muon with respect to the closest jet discriminates events containing b hadrons from background. The inclusive b-hadron production cross section is presented as a function of muon transverse momentum and pseudorapidity. The measured total cross section in the kinematic acceptance is sigma(pp to b+X to mu + X') =1.32 +/- 0.01 (stat) +/- 0.30 (syst) +/- 0.15 (lumi) microbarns.
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Serguei Chatrchyan,
Vardan Khachatryan,
Albert M. Sirunyan,
Armen Tumasyan,
Wolfgang Adam,
Thomas Bergauer,
Marko Dragicevic,
Janos Erö,
Christian Fabjan,
Markus Friedl, [......],
Christos Lazaridis,
Jessica Leonard,
Richard Loveless,
Ajit Mohapatra,
Don Reeder,
Ian Ross,
Alexander Savin,
Wesley H. Smith,
Joshua Swanson,
Marc Weinberg
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ABSTRACT: A search is presented for physics beyond the standard model (SM) in final states with opposite-sign isolated lepton pairs accompanied by hadronic jets and missing transverse energy. The search is performed using LHC data recorded with the CMS detector, corresponding to an integrated luminosity of 34 inverse picobarns. No evidence for an event yield beyond SM expectations is found. An upper limit on the non-SM contribution to the signal region is deduced from the results. This limit is interpreted in the context of the constrained minimal supersymmetric model. Additional information is provided to allow testing the exclusion of specific models of physics beyond the SM.
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Vardan Khachatryan,
Albert M. Sirunyan,
Armen Tumasyan,
Wolfgang Adam,
Thomas Bergauer,
Marko Dragicevic,
Janos Erö,
Christian Fabjan,
Markus Friedl,
Rudolf Fruehwirth, [......],
Jessica Leonard,
David Lomidze,
Richard Loveless,
Ajit Mohapatra,
Don Reeder,
Ian Ross,
Alexander Savin,
Wesley H. Smith,
Joshua Swanson,
Marc Weinberg
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ABSTRACT: Measurements of inclusive W and Z boson production cross sections in pp collisions at sqrt(s) = 7 TeV are presented, based on 2.9 pb-1 of data recorded by the CMS detector at the LHC. The measurements, performed in the electron and muon decay channels, are combined to give sigma(pp --> WX) X B(W--> ln) = 9.95 +/- 0.07 (stat.) +/- 0.28 (syst.) +/- 1.09 (lumi.) nb and sigma(pp --> ZX) X B(Z --> ll) = 0.931 +/- 0.026 (stat.) +/- 0.023 (syst.) +/- 0.102 (lumi.) nb, where l stands for either e or mu. Theoretical predictions, calculated at the next-to-next-to-leading order in QCD using recent parton distribution functions, are in agreement with the measured cross sections. Ratios of cross sections, which incur an experimental systematic uncertainty of less than 4%, are also reported.
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Vardan Khachatryan,
Albert M. Sirunyan,
Armen Tumasyan,
Wolfgang Adam,
Thomas Bergauer,
Marko Dragicevic,
Janos Erö,
Christian Fabjan,
Markus Friedl,
Rudolf Fruehwirth, [......],
Jessica Leonard,
David Lomidze,
Richard Loveless,
Ajit Mohapatra,
Don Reeder,
Ian Ross,
Alexander Savin,
Wesley H. Smith,
Joshua Swanson,
Marc Weinberg
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ABSTRACT: A search for pair production of second-generation scalar leptoquarks in the final state with two muons and two jets is performed using proton-proton collision data at sqrt(s) = 7 TeV collected by the CMS detector at the LHC. The data sample used corresponds to an integrated luminosity of 34 inverse picobarns. The number of observed events is in good agreement with the predictions from the standard model processes. An upper limit is set on the second-generation leptoquark cross section times beta^2 as a function of the leptoquark mass, and leptoquarks with masses below 394 GeV are excluded at a 95% confidence level for beta = 1, where beta is the leptoquark branching fraction into a muon and a quark. These limits are the most stringent to date.
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Vardan Khachatryan,
Albert M. Sirunyan,
Armen Tumasyan,
Wolfgang Adam,
Thomas Bergauer,
Marko Dragicevic,
Janos Erö,
Christian Fabjan,
Markus Friedl,
Rudolf Fruehwirth, [......],
Jessica Leonard,
David Lomidze,
Richard Loveless,
Ajit Mohapatra,
Don Reeder,
Ian Ross,
Alexander Savin,
Wesley H. Smith,
Joshua Swanson,
Marc Weinberg
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ABSTRACT: Hadronic event shapes have been measured in proton-proton collisions at sqrt(s)=7 TeV, with a data sample collected with the CMS detector at the LHC. The sample corresponds to an integrated luminosity of 3.2 inverse picobarns. Event-shape distributions, corrected for detector response, are compared with five models of QCD multijet production.
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Vardan Khachatryan,
Albert M. Sirunyan,
Armen Tumasyan,
Wolfgang Adam,
Thomas Bergauer,
Marko Dragicevic,
Janos Erö,
Christian Fabjan,
Markus Friedl,
Rudolf Fruehwirth, [......],
Christos Lazaridis,
Jessica Leonard,
Richard Loveless,
Ajit Mohapatra,
Don Reeder,
Ian Ross,
Alexander Savin,
Wesley H. Smith,
Joshua Swanson,
Marc Weinberg
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ABSTRACT: Bose-Einstein correlations between identical particles are measured in samples of proton-proton collisions at 0.9 and 7 TeV centre-of-mass energies, recorded by the CMS experiment at the LHC. The signal is observed in the form of an enhancement of number of pairs of same-sign charged particles with small relative momentum. The dependence of this enhancement on kinematic and topological features of the event is studied.
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Serguei Chatrchyan,
Vardan Khachatryan,
Albert M. Sirunyan,
Armen Tumasyan,
Wolfgang Adam,
Thomas Bergauer,
Marko Dragicevic,
Janos Erö,
Christian Fabjan,
Markus Friedl, [......],
Christos Lazaridis,
Jessica Leonard,
Richard Loveless,
Ajit Mohapatra,
Don Reeder,
Ian Ross,
Alexander Savin,
Wesley H. Smith,
Joshua Swanson,
Marc Weinberg
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ABSTRACT: A new heavy gauge boson, W', decaying to a muon and a neutrino, is searched for in pp collisions at a centre-of-mass of 7 TeV. The data, collected with the CMS detector at the LHC, correspond to an integrated luminosity of 36 inverse picobarns. No significant excess of events above the standard model expectation is found in the transverse mass distribution of the muon-neutrino system. Masses below 1.40 TeV are excluded at the 95% confidence level for a sequential standard-model-like W'. The W' mass lower limit increases to 1.58 TeV when the present analysis is combined with the CMS result for the electron channel.
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Serguei Chatrchyan,
Vardan Khachatryan,
Albert M. Sirunyan,
Armen Tumasyan,
Wolfgang Adam,
Thomas Bergauer,
Marko Dragicevic,
Janos Erö,
Christian Fabjan,
Markus Friedl, [......],
Jessica Leonard,
Richard Loveless,
Ajit Mohapatra,
Francesco Palmonari,
Don Reeder,
Ian Ross,
Alexander Savin,
Wesley H. Smith,
Joshua Swanson,
Marc Weinberg
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ABSTRACT: A search for large extra spatial dimensions via virtual-graviton exchange in the diphoton channel has been carried out with the CMS detector at the LHC. No excess of events above the standard model expectations is found using a data sample collected in proton-proton collisions at sqrt(s) = 7 TeV and corresponding to an integrated luminosity of 36 inverse picobarns. New lower limits on the effective Planck scale in the range of 1.6-2.3 TeV at the 95% confidence level are set, providing the most restrictive bounds to date on models with more than two large extra dimensions.
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Vardan Khachatryan,
Albert M. Sirunyan,
Armen Tumasyan,
Wolfgang Adam,
Thomas Bergauer,
Marko Dragicevic,
Janos Erö,
Christian Fabjan,
Markus Friedl,
Rudolf Fruehwirth, [......],
Jessica Leonard,
David Lomidze,
Richard Loveless,
Ajit Mohapatra,
Don Reeder,
Ian Ross,
Alexander Savin,
Wesley H. Smith,
Joshua Swanson,
Marc Weinberg
[show abstract]
[hide abstract]
ABSTRACT: A search for a heavy gauge boson W' has been conducted by the CMS experiment at the LHC in the decay channel with an electron and large transverse energy imbalance, using proton-proton collision data corresponding to an integrated luminosity of 36 inverse picobarns. No excess above standard model expectations is seen in the transverse mass distribution of the electron-(missing E_T) system. Assuming standard-model-like couplings and decay branching fractions, a W' boson with a mass less than 1.36 TeV/$c^2$ is excluded at 95% confidence level.
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Vardan Khachatryan,
Albert M. Sirunyan,
Armen Tumasyan,
Wolfgang Adam,
Thomas Bergauer,
Marko Dragicevic,
Janos Erö,
Christian Fabjan,
Markus Friedl,
Rudolf Fruehwirth, [......],
Jessica Leonard,
David Lomidze,
Richard Loveless,
Ajit Mohapatra,
Don Reeder,
Ian Ross,
Alexander Savin,
Wesley H. Smith,
Joshua Swanson,
Marc Weinberg
[show abstract]
[hide abstract]
ABSTRACT: The result of a search at the LHC for heavy stable charged particles produced in pp collisions at sqrt(s) = 7 TeV is described. The data sample was collected with the CMS detector and corresponds to an integrated luminosity of 3.1 inverse picobarns. Momentum and ionization-energy-loss measurements in the inner tracker detector are used to identify tracks compatible with heavy slow-moving particles. Additionally, tracks passing muon identification requirements are also analyzed for the same signature. In each case, no candidate passes the selection, with an expected background of less than 0.1 events. A lower limit at the 95% confidence level on the mass of a stable gluino is set at 398 GeV/c2, using a conventional model of nuclear interactions that allows charged hadrons containing this particle to reach the muon detectors. A lower limit of 311 GeV/c2 is also set for a stable gluino in a conservative scenario of complete charge suppression, where any hadron containing this particle becomes neutral before reaching the muon detectors.
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Vardan Khachatryan,
Albert M. Sirunyan,
Armen Tumasyan,
Wolfgang Adam,
Thomas Bergauer,
Marko Dragicevic,
Janos Erö,
Christian Fabjan,
Markus Friedl,
Rudolf Fruehwirth, [......],
Jessica Leonard,
David Lomidze,
Richard Loveless,
Ajit Mohapatra,
Giovanni Polese,
Don Reeder,
Alexander Savin,
Wesley H. Smith,
Joshua Swanson,
Marc Weinberg
[show abstract]
[hide abstract]
ABSTRACT: The first LHC pp collisions at centre-of-mass energies of 0.9 and 2.36 TeV were recorded by the CMS detector in December 2009. The trajectories of charged particles produced in the collisions were reconstructed using the all-silicon Tracker and their momenta were measured in the 3.8 T axial magnetic field. Results from the Tracker commissioning are presented including studies of timing, efficiency, signal-to-noise, resolution, and ionization energy. Reconstructed tracks are used to benchmark the performance in terms of track and vertex resolutions, reconstruction of decays, estimation of ionization energy loss, as well as identification of photon conversions, nuclear interactions, and heavy-flavour decays.
