78 research outputs found

    Chronotherapy of Janus Kinase Inhibitor against Complete Freund’s Adjuvant-Induced Rheumatoid Arthritis in Wistar Rats

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    INTRODUCTION: Rheumatoid arthritis (RA) is a chronic systemic auto immune disease that arises more frequently in females than males, being predominantly observed in the elderly. The prevalence rate reported in 2002 ranged from 0.5% to 1% of the population and had regional variation. RA primarily affects the lining of the synovial joints and can cause progressive disability, premature death, and socioeconomic burdens. The clinical manifestations of symmetrical joint involvement include arthralgia, swelling, redness, and even limiting the range of motion. Early diagnosis is considered as the key improvement index for the most desirable outcomes (i.e., reduced joint destruction, less radiologic progression, no functional disability, and disease modifying antirheumatic drugs (DMARD)-free remission) as well as cost effectiveness as the first 12 weeks after early symptoms occur is regarded as the optimal therapeutic window. AIM OF THE STUDY: To explore the circadian rhythm of serum CRP in complete Freund’s adjuvant (CFA) rats and effectiveness of tofacitinib administered via chronotherapy. METHODS: CFA rat models were immunized with mycobacterium butyricum. Serum CRP levels in normal and CFA rats were measured at 4,10,16, or 22 h ZT0/ZT12.Tofacitinib was administered to ZT8/ZT20 experimental groups of Wistar rats once daily according to the circadian rhythm. The positive control was given with methotrexate, for ZT0 and ZT12 was given with tofacitinib and normal control given (0.5% CMC) once daily simultaneously. Arthritis score, paw volume, body weight was measured on 1st, 5th ,7th ,14th and 21st. Rheumatoid factor and C reactive protein (CRP) levels in the serum were measured by semiauto-analyser using turbilatex method. Histological changes in the ankle joint were analyzed. RESULTS: After 3 weeks of treatment, arthritis scores in the experimental group were lower than in the Negative control group. The expression of CRP was lower in the ZT0 treated group than in the negative control or ZT12 treated groups. Histopathology scores in the experimental groups shows less inflammatory cells than in the control group. CONCLUSION: The serum CRP levels in CFA rats were higher than in normal rats and showed significant circadian rhythm. Daily dose time dependent administration of tofacitinib is more potent than traditional administration. The therapeutic index of rheumatoid arthritis (RA) may be improved with tofacitinib therapy based on the serum CRP circadian rhythm

    Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-Adjusted life-years for 29 cancer groups, 1990 to 2017 : A systematic analysis for the global burden of disease study

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    Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-Adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs). Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care. © 2019 American Medical Association. All rights reserved.Peer reviewe

    Measurement of the azimuthal anisotropy of Y(1S) and Y(2S) mesons in PbPb collisions at root s(NN)=5.02 TeV

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    The second-order Fourier coefficients (v(2)) characterizing the azimuthal distributions of Y(1S) and Y(2S) mesons produced in PbPb collisions at root s(NN) = 5.02 TeV are studied. The Y mesons are reconstructed in their dimuon decay channel, as measured by the CMS detector. The collected data set corresponds to an integrated luminosity of 1.7 nb(-1). The scalar product method is used to extract the v2 coefficients of the azimuthal distributions. Results are reported for the rapidity range vertical bar y vertical bar < 2.4, in the transverse momentum interval 0 < pT < 50 GeV/c, and in three centrality ranges of 10-30%, 30-50% and 50-90%. In contrast to the J/psi mesons, the measured v(2) values for the Y mesons are found to be consistent with zero. (C) 2021 The Author(s). Published by Elsevier B.V.Peer reviewe

    Reconstruction of signal amplitudes in the CMS electromagnetic calorimeter in the presence of overlapping proton-proton interactions

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    A template fitting technique for reconstructing the amplitude of signals produced by the lead tungstate crystals of the CMS electromagnetic calorimeter is described. This novel approach is designed to suppress the contribution to the signal of the increased number of out-of-time interactions per beam crossing following the reduction of the accelerator bunch spacing from 50 to 25 ns at the start of Run 2 of the LHC. Execution of the algorithm is sufficiently fast for it to be employed in the CMS high-level trigger. It is also used in the offline event reconstruction. Results obtained from simulations and from Run 2 collision data (2015-2018) demonstrate a substantial improvement in the energy resolution of the calorimeter over a range of energies extending from a few GeV to several tens of GeV.Peer reviewe

    Observation of the Production of Three Massive Gauge Bosons at root s=13 TeV

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    The first observation is reported of the combined production of three massive gauge bosons (VVV with V = W, Z) in proton-proton collisions at a center-of-mass energy of 13 TeV. The analysis is based on a data sample recorded by the CMS experiment at the CERN LHC corresponding to an integrated luminosity of 137 fb(-1). The searches for individualWWW, WWZ, WZZ, and ZZZ production are performed in final states with three, four, five, and six leptons (electrons or muons), or with two same-sign leptons plus one or two jets. The observed (expected) significance of the combinedVVV production signal is 5.7 (5.9) standard deviations and the corresponding measured cross section relative to the standard model prediction is 1.02(-0.23)(+0.26). The significances of the individual WWW and WWZ production are 3.3 and 3.4 standard deviations, respectively. Measured production cross sections for the individual triboson processes are also reported

    Search for a light pseudoscalar Higgs boson in the boosted mu mu tau tau final state in proton-proton collisions at root s=13 TeV

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    A search for a light pseudoscalar Higgs boson (a) decaying from the 125 GeV (or a heavier) scalar Higgs boson (H) is performed using the 2016 LHC proton-proton collision data at root s = 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), collected by the CMS experiment. The analysis considers gluon fusion and vector boson fusion production of the H, followed by the decay H -> aa -> mu mu tau tau, and considers pseudoscalar masses in the range 3.6 aa -> mu mu tau tau, down to 1.5 (2.0)x10(-4) for m(H) = 125 (300) GeV. Model-dependent limits on B(H -> aa) are set within the context of two Higgs doublets plus singlet models, with the most stringent results obtained for Type-III models. These results extend current LHC searches for heavier a bosons that decay to resolved lepton pairs and provide the first such bounds for an H boson with a mass above 125 GeV.Peer reviewe

    Influence of the genetic background and carrier protein on the antibody response to GnRH

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    A vaccine against the gonadotropin releasing hormone (GnRH) is being developed as an immunological method for the treatment of prostatic enlargement. The work described here was aimed at investigating the influence of the genetic background on immune responses to GnRH conjugated to diphtheria toxoid (DT). Mice of different strains were injected with the conjugate and the antibody levels against GnRH and DT quantitated in order to examine the effect of genetic background on immune responses to the hapten and the carrier. All immunized animals produced antibodies to DT. Anti-GnRH antibodies were generated by all strains of mice except 129. The low anti-GnRH response in the 129 strain mice did not appear to be MHC-linked, as C57BL/6 mice, which bear the same MHC haplotype as 129 mice, were able to generate a strong anti-GnRH response. The non-responsiveness to the hapten (GnRH) in 129 strain mice was overcome by the use of an 'alternate carrier' approach

    Re-Engineering Towed Arrays for Quality Enhancement - Network Based Towed Array

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    The Towed Array electronics is a multi-channel simultaneous real time high speed data acquisition system. Since its assembly is highly manpower intensive, the costs of arrays are prohibitive and therefore any attempt to reduce the manufacturing, assembly, testing and maintenance costs is a welcome proposition. The Network Based Towed Array is an innovative concept and its implementation has remarkably simplified the fabrication, assembly and testing and revolutionised the Towed Array scenario. The focus of this paper is to give a good insight into the Reliability aspects of Network Based Towed Array. A case study of the comparison between the conventional array and the network based towed array is also dealt withCochin University of Science and TechnologyOcean Electronics (SYMPOL), 201

    Ethernet Telemetry for Towed Arrays

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    The towed array electronics is essentially a multichannel real time data acquisition system. The major challenges involved in it are the simultaneous acquisition of data from multiple channels, telemetry of the data over tow cable (several kilometres in some systems) and synchronization with the onboard receiver for accurate reconstruction. A serial protocol is best suited to transmit the data to onboard electronics since number of wires inside the tow cable is limited. The best transmission medium for data over large distances is the optical fibre. In this a two step approach towards the realization of a reliable telemetry scheme for the sensor data using standard protocols is described. The two schemes are discussed in this paper. The first scheme is for conversion of parallel, time-multiplexed multi-sensor data to Ethernet. Existing towed arrays can be upgraded to ethernet using this scheme. Here the last lap of the transmission is by Ethernet over Fibre. For the next generation of towed arrays it is required to digitize and convert the data to ethernet close to the sensor. This is the second scheme. At the heart of this design is the Analog-to-Ethernet node. In addition to a more reliable interface, this helps in easier fault detection and firmware updates in the field for the towed arrays. The design challenges and considerations for incorporating a network of embedded devices within the array are highlightedCochin University of Science and TechnologyOcean Electronics (SYMPOL), 2009 International Symposium o
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