19 research outputs found
Modeling the triple-GEM detector response to background particles for the CMS Experiment
An estimate of environmental background hit rate on triple-GEM chambers is
performed using Monte Carlo (MC) simulation and compared to data taken by test
chambers installed in the CMS experiment (GE1/1) during Run-2 at the Large
Hadron Collider (LHC). The hit rate is measured using data collected with
proton-proton collisions at 13 TeV and a luminosity of 1.5
cm s. The simulation framework uses a combination of the FLUKA
and Geant4 packages to obtain the hit rate. FLUKA provides the radiation
environment around the GE1/1 chambers, which is comprised of the particle flux
with momentum direction and energy spectra ranging from to
MeV for neutrons, to MeV for 's, to
MeV for , and to MeV for charged hadrons.
Geant4 provides an estimate of detector response (sensitivity) based on an
accurate description of detector geometry, material composition and interaction
of particles with the various detector layers. The MC simulated hit rate is
estimated as a function of the perpendicular distance from the beam line and
agrees with data within the assigned uncertainties of 10-14.5%. This simulation
framework can be used to obtain a reliable estimate of background rates
expected at the High Luminosity LHC.Comment: 16 pages, 9 figures, 6 table
Immunoglobulin M myeloma: evaluation of molecular features and cytokine expression
Immunoglobulin (Ig) M myeloma is a distinct entity with features of multiple myeloma (MM) and Waldenström’s macroglobulinemia (WM). The malignant cells in IgM myeloma have a distinctive chromosomal translocation that differentiates them from WM. These cells are postgerminal–center in origin with isotype-switch transcripts. They appear to be arrested at a point of maturation between that of WM and MM. Preliminary data indicate that a pattern of osteoclast-activating factor and osteoprotegerin expression similar to that observed in classic MM is present in IgM myeloma. Additional studies on patients with this rare tumor may provide further insight into the pathogenesis of bone disease in plasma cell dyscrasias
Vaccine based immunotherapy as a strategy to bypass drug resistance in multiple myeloma
Clonal evolution under therapy leads to drug resistance and relapse in multiple myeloma (MM), requiring new treatment mo- dalities to control disease. Immunotherapy and specifically vacci- nation to induce anti-tumor CD8+ cytotoxic T-cells (CTLs) provides one such strategy, but susceptibility of drug resistant MM cells to CTL attack is as yet not defined. To examine this, a first requirement is identification of tumour-associated antigens in drug refractory MM. To this end, we had previously specifically evaluated cancer testis antigens (CTAs) in MM for retention at relapse post- therapy, and identified SPAG9 and MAGEC1 as frontline antigen targets for vaccines. Of these, SPAG9 is generic to relapse MM (expressed in w100% of cases) and MAGEC1 is essentially tumour-specific (expressed w60% of cases). An optimal strategy for vaccination as therapy is in disease remission to attack re-emerging MM cells that escape drug therapy. A second requirement is to model drug resistance in MM, and accordingly we have now generated derivatives of the XG2 MM cell line that are resistant to melphalan (XG2 M) or Bortezomib (XG2 600R3); the RPMI8226-derivative R5 line with multiple drug resistance was also available. A third requirement is to show effective lysis of drug resistant MM cells by antigen specific CTLs. To generate antigen-specific CTLs, we utilized pDOM-CTAepitope DNA vaccine delivery in HLA-A2 transgenic HHD mice. We examined two epitopes in respective vaccines, pDOM-SPAG9p1 and pDOM-MAGEC1p2. Both vac- cines elicited epitope specific T-cell responses in HHD measured by IFN release assays following prime and boost with electroporation. Significantly, using MM cell lines made chimeric for HHD MHC class I as targets, both vaccines induced CTLs in HHD mice that were able to effectively lyse primary (XG2 and others) and drug resistant MM cell lines (XG2M, XG2 600R3, R5) effectively. These data demonstrate that drug resistant MM cells are susceptible to CTL killing, substantiating a role for vaccination in MM to over- come drug resistance and hence prevent relapse