657 research outputs found
Cms gem detector material study for the hl-lhc
A study on the Gaseous Electron Multiplier (GEM) foil material is performed to determine the moisture diffusion rate, moisture saturation level and the effects on its mechanical properties. The study is focused on the foil contact with ambient air and moisture to determine the value of the diffusion coefficient of water in the foil material. The presence of water inside the detector foil can determine the changes in its mechanical and electrical properties. A simulated model is developed with COMSOL Multiphysics v. 4.3 [1] by taking into account the real GEM foil (hole dimensions, shapes and material), which describes the adsorption of water. This work describes the model, its experimental verification, the water diffusion within the entire sheet geometry of the GEM foil, thus gaining concentration profiles and the time required to saturate the system and the effects on the mechanical properties
Defining disease modification in myelofibrosis in the era of targeted therapy
The development of targeted therapies for the treatment of myelofibrosis highlights a unique issue in a field that has historically relied on symptom relief, rather than survival benefit or modification of disease course, as key response criteria. There is, therefore, a need to understand what constitutes disease modification of myelofibrosis to advance appropriate drug development and therapeutic pathways. Here, the authors discuss recent clinical trial data of agents in development and dissect the potential for novel end points to act as disease modifying parameters. Using the rationale garnered from latest clinical and scientific evidence, the authors propose a definition of disease modification in myelofibrosis. With improved overall survival a critical outcome, alongside the normalization of hematopoiesis and improvement in bone marrow fibrosis, there will be an increasing need for surrogate measures of survival for use in the early stages of trials. As such, the design of future clinical trials will require re-evaluation and updating to incorporate informative parameters and end points with standardized definitions and methodologies
Characterization of the water diffusion in GEM foil material
Systematic studies on the GEM foil material are performed to measure the moisture diffusion rate and saturation level.These studies are important because the presence of this compound inside the detectorâs foil can possibly change its mechanical and electrical properties,and in such a way,the detector performance can be affected.To understand this phenomenon,a model is developed with COMSOL Multiphysicsv.4.3 which described the adsorption and diffusion within the geometry of GEM foil,the concentration profiles and the time required to saturate the foil.The COMSOL model is verified by experimental observations on a GEM foil sample.This note will describe the model and its experimental verification results
Blast phase myeloproliferative neoplasm: Mayo-AGIMM study of 410 patients from two separate cohorts
A total of 410 patients with blast phase myeloproliferative neoplasm (MPN-BP) were retrospectively reviewed: 248 from the
Mayo Clinic and 162 from Italy. Median survival was 3.6 months, with no improvement over the last 15 years. Multivariable
analysis performed on the Mayo cohort identified high risk karyotype, platelet count < 100 Ăâ 109
/L, age > 65 years and
transfusion need as independent risk factors for survival. Also in the Mayo cohort, intensive chemotherapy resulted in complete
remission (CR) or CR with incomplete count recovery (CRi) rates of 35 and 24%, respectively; treatment-specified 3-year/5-year
survival rates were 32/10% for patients receiving allogeneic stem cell transplant (AlloSCT) (n = 24), 19/13% for patients
achieving CR/CRi but were not transplanted (n = 24), and 1/1% in the absence of both AlloSCT and CR/CRi (n = 200) (p <
0.01). The survival impact of AlloSCT (HR 0.2, 95% CI 0.1ââŹâ0.3), CR/CRi without AlloSCT (HR 0.3, 95% CI 0.2ââŹâ0.5), high risk
karyotype (HR 1.6, 95% CI 1.1ââŹâ2.2) and platelet count < 100 Ăâ 109
/L (HR 1.6, 95% CI 1.1ââŹâ2.2) were confirmed to be interindependent. Similar observations were made in the Italian cohort. The current study identifies the setting for improved short-term
survival in MPN-BP, but also highlights the limited value of current therapy, including AlloSCT, in securing long-term survival
Structural Analysis of a Peptide Fragment of Transmembrane Transporter Protein Bilitranslocase
Using a combination of genomic and post-genomic approaches is rapidly altering the number of identified human influx carriers. A transmembrane protein bilitranslocase (TCDB 2.A.65) has long attracted attention because of its function as an organic anion carrier. It has also been identified as a potential membrane transporter for cellular uptake of several drugs and due to its implication in drug uptake, it is extremely important to advance the knowledge about its structure. However, at present, only the primary structure of bilitranslocase is known. In our work, transmembrane subunits of bilitranslocase were predicted by a previously developed chemometrics model and the stability of these polypeptide chains were studied by molecular dynamics (MD) simulation. Furthermore, sodium dodecyl sulfate (SDS) micelles were used as a model of cell membrane and herein we present a high-resolution 3D structure of an 18 amino acid residues long peptide corresponding to the third transmembrane part of bilitranslocase obtained by use of multidimensional NMR spectroscopy. It has been experimentally confirmed that one of the transmembrane segments of bilitranslocase has alpha helical structure with hydrophilic amino acid residues oriented towards one side, thus capable of forming a channel in the membrane
MARIMO cells harbor a CALR mutation but are not dependent on JAK2/STAT5 signaling.
Work in the Green lab is supported by
Leukemia and Lymphoma Research, Cancer Research UK, the NIHR Cambridge
Biomedical Research Centre, the Cambridge Experimental Cancer Medicine Centre,
and the Leukemia and Lymphoma Society of America. WW is supported by the
Austrian Science Foundation (J 3578-B21). JN is supported by a Kay Kendall
Leukaemia Clinical Fellowship.This is the final published version. It first appeared at http://www.nature.com/leu/journal/vaop/ncurrent/full/leu2014285a.html
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