The CALIPSO Integrated Thermal Control Subsystem

The Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) is a joint NASA-CNES mission to study the Earth's cloud and aerosol layers. The satellite is composed of a primary payload (built by Ball Aerospace) and a spacecraft platform bus (PROTEUS, built by Alcatel Alenia Space). The thermal control subsystem (TCS) for the CALIPSO satellite is a passive design utilizing radiators, multi-layer insulation (MLI) blankets, and both operational and survival surface heaters. The most temperature sensitive component within the satellite is the laser system. During thermal vacuum testing of the integrated satellite, the laser system's operational heaters were found to be inadequate in maintaining the lasers required set point. In response, a solution utilizing the laser system's survival heaters to augment the operational heaters was developed with collaboration between NASA, CNES, Ball Aerospace, and Alcatel-Alenia. The CALIPSO satellite launched from Vandenberg Air Force Base in California on April 26th, 2006. Evaluation of both the platform and payload thermal control systems show they are performing as expected and maintaining the critical elements of the satellite within acceptable limits

The Calipso Thermal Control Subsystem

The Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) is a joint NASA-CNES mission to study the Earth s cloud and aerosol layers. The satellite is composed of a primary payload (built by Ball Aerospace) and a spacecraft platform bus (PROTEUS, built by Alcatel Alenia Space). The thermal control subsystem (TCS) for the CALIPSO satellite is a passive design utilizing radiators, multi-layer insulation (MLI) blankets, and both operational and survival surface heaters. The most temperature sensitive component within the satellite is the laser system. During thermal vacuum testing of the integrated satellite, the laser system s operational heaters were found to be inadequate in maintaining the lasers required set point. In response, a solution utilizing the laser system s survival heaters to augment the operational heaters was developed with collaboration between NASA, CNES, Ball Aerospace, and Alcatel-Alenia. The CALIPSO satellite launched from Vandenberg Air Force Base in California on April 26th, 2006. Evaluation of both the platform and payload thermal control systems show they are performing as expected and maintaining the critical elements of the satellite within acceptable limits

M-protein diagnostics in multiple myeloma patients using ultra-sensitive targeted mass spectrometry and an off-the-shelf calibrator

Objectives: Minimal residual disease status in multiple myeloma is an important prognostic biomarker. Recently, personalized blood-based targeted mass spectrometry (MS-MRD) was shown to provide a sensitive and minimally invasive alternative to measure minimal residual disease. However, quantification of MS-MRD requires a unique calibrator for each patient. The use of patient-specific stable isotope labelled (SIL) peptides is relatively costly and time-consuming, thus hindering clinical implementation. Here, we introduce a simplification of MS-MRD by using an off-the-shelf calibrator. SILuMAB-based MS-MRD was performed by spiking a monoclonal stable isotope labeled IgG, Methods: SILuMAB-K1, in the patient serum. The abundance of both M-protein-specific peptides and SILuMAB-specific peptides were monitored by mass spectrometry. The relative ratio between M-protein peptides and SILuMAB peptides allowed for M-protein quantification. We assessed linearity, sensitivity and reproducibility of SILuMAB-based MS-MRD in longitudinally collected sera from the IFM-2009 clinical trial. Results: A linear dynamic range was achieved of over 5 log scales, allowing for M-protein quantification down to 0.001 » g/L. The inter-assay CV of SILuMAB-based MS-MRD was on average 11 » %. Excellent concordance between SIL- and SILuMAB-based MS-MRD was shown (R2&gt;0.985). Additionally, signal intensity of spiked SILuMAB can be used for quality control purpose to assess system performance and incomplete SILuMAB digestion can be used as quality control for sample preparation. Conclusion:Compared to SIL peptides, SILuMAB-based MS-MRD improves the reproducibility, turn-around-times and cost-efficacy of MS-MRD without diminishing its sensitivity and specificity. Furthermore, SILuMAB can be used as a MS-MRD quality control tool to monitor sample preparation efficacy and assay performance.</p

Analysis of a compartmental model of endogenous immunoglobulin G metabolism with application to multiple myeloma

Immunoglobulin G (IgG) metabolism has received much attention in the literature for two reasons: (i) IgG homeostasis is regulated by the neonatal Fc receptor (FcRn), by a pH-dependent and saturable recycling process, which presents an interesting biological system; (ii) the IgG-FcRn interaction may be exploitable as a means for extending the plasma half-life of therapeutic monoclonal antibodies, which are primarily IgG-based. A less-studied problem is the importance of endogenous IgG metabolism in IgG multiple myeloma. In multiple myeloma, quantification of serum monoclonal immunoglobulin plays an important role in diagnosis, monitoring and response assessment. In order to investigate the dynamics of IgG in this setting, a mathematical model characterizing the metabolism of endogenous IgG in humans is required. A number of authors have proposed a two-compartment nonlinear model of IgG metabolism in which saturable recycling is described using Michaelis-Menten kinetics; however it may be difficult to estimate the model parameters from the limited experimental data that are available. The purpose of this study is to analyse the model alongside the available data from experiments in humans and estimate the model parameters. In order to achieve this aim we linearize the model and use several methods of model and parameter validation: stability analysis, structural identifiability analysis, and sensitivity analysis based on traditional sensitivity functions and generalized sensitivity functions. We find that all model parameters are identifiable, structurally and taking into account parameter correlations, when several types of model output are used for parameter estimation. Based on these analyses we estimate parameter values from the limited available data and compare them with previously published parameter values. Finally we show how the model can be applied in future studies of treatment effectiveness in IgG multiple myeloma with simulations of serum monoclonal IgG responses during treatment

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Serum free light chains, not urine specimens, should be used to evaluate response in light-chain multiple myeloma

Guidelines for monitoring multiple myeloma (MM) patients expressing light chains only (light-chain MM [LCMM]) rely on measurements of monoclonal protein in urine. Alternatively, serum free light chain (sFLC) measurements have better sensitivity over urine methods, however, demonstration that improved sensitivity provides any clinical benefit is lacking. Here, we compared performance of serum and urine measurements in 113 (72κ, 41λ) newly diagnosed LCMM patients enrolled in the Intergroupe Francophone du Myélome (IFM) 2009 trial. All diagnostic samples (100%) had an abnormal κ:λ sFLC ratio, and involved (monoclonal) FLC (iFLC) expressed at levels deemed measurable for monitoring (≥100 mg/L). By contrast, only 64% patients had measurable levels of monoclonal protein (≥200 mg per 24 hours) in urine protein electrophoresis (UPEP). After 1 and 3 treatment cycles, iFLC remained elevated in 71% and 46% of patients, respectively, whereas UPEP reported a positive result in 37% and 18%; all of the patients with positive UPEP at cycle 3 also had elevated iFLC levels. Importantly, elevated iFLC or an abnormal κ:λ sFLC ratio after 3 treatment cycles associated with poorer progression-free survival (P = .006 and P < .0001, respectively), whereas positive UPEP or urine immunofixation electrophoresis (uIFE) did not. In addition, patients with an abnormal κ:λ sFLC ratio had poorer overall survival (P = .022). Finally, early normalization of κ:λ sFLC ratio but not negative uIFE predicted achieving negative minimal residual disease, as determined by flow cytometry, after consolidation therapy (100% positive predictive value). We conclude that improved sensitivity and prognostic value of serum over urine measurements provide a strong basis for recommending the former for monitoring LCMM patients.0SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Expression de TIMP-3 dans le cancer colorectal (à propos d'une série de 39 cas)

L'inhibiteur de métalloprotéases TIMP-3 présente des propriétés antiprolifératives, antiangiogéniques et anti-apoptotiques mises en évidence expérimentalement. Ce comportement de gène suppresseur de tumeur n'a pas été rapporté dans le cancer colorectal. Nous avons étudié l'expression de TIMP-3 au niveau transcritionnel et protéique, respectivement par PCR quantitative et immunohistochime en tissue Micro Array, sur une série d'adénocarcinomes colorectaux et leurs tissus sains appariés (n = 39). Nous mettons en évidence à la fois au niveau transcriptionnel (50 %) et protéique (88 %) une surexpression de TIMP-3 par les cellules tumorales par rapport au tissu sain. D'autre part, la fréquence très faible de l'hyperméthylation du promoteur de TIMP-3 retrouvée dans notre série de tumeurs, confirme ces résultats. Dans notre série, la surexpression de TIMP-3 n'est liée ni au stade TNM, ni à la présence de métastases. Enfin, l'hypothèse d'une surexpression de TIMP-3 associée à celle d'une de ces enzymes cibles ADAM-17, n'est pas confirmée dans notre cohorte.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Recommandations de l’IFM (Intergroupe francophone du myélome) pour l’harmonisation de l’analyse des électrophorèses des protéines sériques et urinaires dans le diagnostic et le suivi du myélome multiple [IFM (Intergroupe francophone du myelome) recommendations for uniform interpretation of serum and urine protein electrophoresis in multiple myeloma diagnosis and follow-up]

National audienceSerum and urine proteins electrophoresis take a major place in multiple myeloma management, at time of diagnosis, during follow-up for treatment response evaluation and also in detection of relapse. The Intergroupe francophone du myelome (IFM) suggests recommendations to clinicians and biologists, to perform and interpret these biochemical analysis, with the objective of harmonizing practices between laboratories and improving patients' follow-up

Phenotype and functions of B cells in patients with acute brain injuries

International audienceBackground: Brain injuries (BI) induce a state of systemic immunosuppression, leading to a high risk of pneumonia. In this pilot study, we investigated the status of B cell compartment in BI patients.Methods: A prospective observational study was performed in 2 intensive care units in a university hospital. Blood samples were collected in 14 patients at day 1 and day 7 after acute BI. The phenotype and the ability of B cells to secrete IL-10 were compared to 11 healthy volunteers (HV).Results: Among the circulating lymphocytes, the frequency of B cells was significantly higher in BI patients compared to HV (p < 0.001). B cells from BI patients displayed an activated profil on day 7 after BI, reflected by a significantly higher proportion of CD27 + memory (p = 0.01) and CD27 + IgD − switched memory B cells (p = 0.02), as well as a significantly higher blood level of IgA (p = 0.001) and IgM (p < 0.001) as compared to day 1. The frequency of IL-10 secreting B cells (IL-10 + B cells) on day 1 and day 7 was significantly lower in BI patients compared to HV (p < 0.05). Interestingly, we observed that all BI patients with high frequency of IL-10 + B cells on day 1 displayed an episode of pneumonia, and had a longer duration of mechanical ventilation and ICU stay compared to BI patients with low proportion of IL-10 + B cells.Conclusion: This study provides an extensive description of the phenotype and function of B cells in BI patients. Our results suggest that IL-10 + B cells could play a major role in immunosuppression after BI