Pre-launch radiometric calibration of the infrared spectrometer onboard SuperCam for the Mars2020 rover.

Near-infrared spectroscopy has become a well-known remote sensing technique for the surface characterization of planetary objects. Among them, Mars was observed in the past by three imaging spectrometers from orbit. The Infrared Spectrometer/SuperCam instrument performs near-infrared spectroscopy from the martian surface for the first time, with a 1.15 mrad field of view, in the 1.3 µm-2.6 µm range, enabling the identification of a variety of mafic and altered minerals. Before integration aboard the rover, the spectrometer underwent a calibration campaign. Here, we report the radiometric and linearity responses of the instrument, including the optical and thermal setups used to perform them over its nominal range of operations, in terms of instrument detector temperatures and spectral range. These responses were constrained by accuracy requirements (20% in absolute radiometry, 1% in relative). The derived instrument transfer function fits within these requirements (<15% in absolute and <0.8% in relative) and shall be used to calculate the expected instrumental signal-to-noise ratio for typical observation scenarios of mineral mixtures expected to be found in the Jezero crater, and ultimately to retrieve the spectral properties of the regions of interest observed by the rover.

[Outpatient expectations in dermatology consultations: A pilot study]. / Attente des patients consultant un dermatologue «de ville¼: une étude pilote.

BACKGROUND: Understanding patients' expectations with regard to medical care is critical as it guarantees an efficient therapeutic process. Our aim was to determine outpatients' expectations concerning clinical encounters in a dermatology clinic and to study how these matched the opinions of dermatologists regarding them. PATIENTS AND METHODS: Consecutive outpatients consulting in five dermatology centres in the Paris suburbs between February 2013 and March 2013 were prospectively included. For this pilot cross-sectional study, we used two standardized forms to collect data from patients and dermatologists. Patients' answers were compared to those of their dermatologist, and the degree of matching was calculated to assess the ability of dermatologists to accurately identify their patients' expectations. RESULTS: Two hundred and sixty-five patients were included, with a median age of 41 years (interquartile range: 25; 62), of whom 166 were women (65.4%). Patient's principal expectations concerned diagnosis (51.7%) and medication (40.8%), with 32.1% of patients requiring reassurance. The rates of matching between patients' and dermatologists' answers ranged from 33.3% to 65.7% according to the type of expectations. The highest rate concerned expectation with regard to medications, being only 52.6% and 58.8%, respectively for expectations regarding diagnosis and the need for reassurance. CONCLUSION: This study highlights the need for improved identification of outpatient expectations in dermatology consultations.

Assessing the clinical value of targeted massively parallel sequencing in a longitudinal, prospective population-based study of cancer patients.

INTRODUCTION: Recent discoveries in cancer research have revealed a plethora of clinically actionable mutations that provide therapeutic, prognostic and predictive benefit to patients. The feasibility of screening mutations as part of the routine clinical care of patients remains relatively unexplored as the demonstration of massively parallel sequencing (MPS) of tumours in the general population is required to assess its value towards the health-care system. METHODS: Cancer 2015 study is a large-scale, prospective, multisite cohort of newly diagnosed cancer patients from Victoria, Australia with 1094 patients recruited. MPS was performed using the Illumina TruSeq Amplicon Cancer Panel. RESULTS: Overall, 854 patients were successfully sequenced for 48 common cancer genes. Accurate determination of clinically relevant mutations was possible including in less characterised cancer types; however, technical limitations including formalin-induced sequencing artefacts were uncovered. Applying strict filtering criteria, clinically relevant mutations were identified in 63% of patients, with 26% of patients displaying a mutation with therapeutic implications. A subset of patients was validated for canonical mutations using the Agena Bioscience MassARRAY system with 100% concordance. Whereas the prevalence of mutations was consistent with other institutionally based series for some tumour streams (breast carcinoma and colorectal adenocarcinoma), others were different (lung adenocarcinoma and head and neck squamous cell carcinoma), which has significant implications for health economic modelling of particular targeted agents. Actionable mutations in tumours not usually thought to harbour such genetic changes were also identified. CONCLUSIONS: Reliable delivery of a diagnostic assay able to screen for a range of actionable mutations in this cohort was achieved, opening unexpected avenues for investigation and treatment of cancer patients.

In situ reconstruction in native and prosthetic aortic infections using cryopreserved arterial allografts.

OBJECTIVES: To evaluate overall survival and complications of cryopreserved arterial allografts in aortic graft infections and infected aortic aneurysms. METHODS: A retrospective review of consecutive patients was conducted with native or prosthetic aortic infections, who underwent local debridement and in situ implantation of a cryopreserved aortic allograft from September 2004 to June 2012 at the Henri Mondor University Hospital. Patient characteristics, indications for allograft implantation, perioperative events, bacteriological data, and events related to follow-up were identified. The primary outcome was overall survival. Overall survival was estimated using the Kaplan-Meier method. Predictors of postoperative mortality were identified using uni- and multivariate analysis with a Cox proportional hazard regression. RESULTS: During the study period, 54 patients (45 [83%] men, mean age 66.2 ± 10.2 years) underwent aortic reconstruction using cryopreserved allografts. Indications were native aortic infection in 17 patients and prosthetic graft infection in 37 patients, including seven aortoenteric fistulae. Twelve aortic reconstructions (22%) were performed as emergency procedures. The median duration of follow-up was 12.1 months (range 0.4-83.6). The 30-day mortality rate was 28%. The overall mortality rate was 39% at a median follow-up of 12.1 months. Early significant postoperative complications occurred in 52% of patients. The graft-related mortality rate was 7%. The graft-related complication rate was 19%. During follow-up, there were two recurrences of aortic infection and two recurrences of allograft limb occlusion. Multivariate survival analysis identified age, chronic renal disease, prosthetic infection, emergent procedure, and coronary disease as independent predictors for postoperative mortality. CONCLUSION: This experience with cryopreserved aortic allografts in aortic reconstructions shows an unsatisfactory 30-day survival rate, as well as a substantial early graft-related complication rate. Longer follow-up is needed in order to support the preferential use of cryopreserved allografts based on their long-term behavior.

Discovery of novel and potent benzhydryl-tropane trypanocides highly selective for Trypanosoma cruzi.

A benzhydryl tropinone oxime that is potently toxic to Trypanosoma cruzi has been previously identified. An SAR investigation determined that no part of the original compound was superfluous and all early SAR probes led to significant drops in activity. The only alteration that could be achieved without loss of activity was replacement of the aryl chloride substituent with chloro homologues. This led to the discovery of a trifluoromethyl-containing analogue with an EC(50) against T. cruzi of 30 nM and a cytotoxicity selectivity index of over 1000 relative to rat skeletal myoblast L-6 cells.

[Prediction of falls with performance on Timed "Up-and-Go" and one-leg-balance tests and additional cognitive tasks]. / Modification des performances au Timed "Up and Go" test et à l'appui monopodal par l'addition d'une charge cognitive: valeur discriminative des résultats.

OBJECTIVE: This study aimed to determine whether ordinary clinical performance on the timed "up-and-go" and one-leg-balance tests varied with additional cognitive tasks and the predictive value of this combination for future falls. METHODOLOGY: The sample comprised 95 women with osteoporosis who lived independently in the community and were older than 70 years (mean 73.4+/-1.7 years) who were randomized to perform the timed "up-and-go" (TUG) and one-leg-balance (OLB) tests. The tests were performed with or without an additional cognitive task (math task involving subtraction by 2 s or 5 s or addition by 3 s). RESULTS: For both TUG and OLB, performance decreased in the dual-task condition (P<0.05) but did not differ in older women with and without a history of falling, whatever the test, and with or without an additional cognitive load. CONCLUSION: Performance on the TUG and OLB tests was less efficient when patients simultaneously performed a cognitive task. Performance on these tests, without or with cognitive tasks, did not predict falls in a sample of women who lived independently.

MRP1 not MDR1 gene expression is the predominant mechanism of acquired multidrug resistance in two prostate carcinoma cell lines.

Multidrug resistant prostate cancer cell lines DU 0.03 and PC 0.03 were established from the parental prostate cancer cell lines DU145 and PC-3 respectively by stepwise selection in doxorubicin (DOX) from 0.001 to 0.03 &mgr;g/ml. As cells adapted to each concentration of DOX. the drug concentration was increased by 0.001 &mgr;g/ml. The chemosensitivity of each line was determined by growth inhibition assay. The DU 0.03 and PC 0.03 lines exhibit a 5-10-fold and 1.3-2.8-fold increase in resistance to anthracyclines, vinblastine (VLB) and mitozantrone (Mito), respectively. Verapamil (5 &mgr;M) partially reversed the resistance to the anthracycline and completely reversed the resistance to VLB and Mito. Drug kinetic studies measured by intracellular accumulation of (3)H-daunorubicin demonstrated a 3 fold decrease in the level of intracellular (3)H-daunorubicin in the PC 0.03 and DU 0.03 resistant lines compared with their respective parental line. This effect was partially reversed by 5 &mgr;M verapamil. The expression of MDR1 and MRP genes was analysed by Northern blotting and RT-PCR. P-glycoprotein (Pgp) and MRP protein were tested by immunocytochemistry staining using the monoclonal antibodies J-SB1. C219 and MRK16 (Pgp) and MRPm6 and MRPr1 (MRP). Neither Northern blot analysis nor the more sensitive RT-PCR demonstrated detectable MDR1 transcripts in any of the prostate cancer cell lines and the three Pgp monoclonal antibodies failed to reveal expression of Pgp. A 2-4-fold increase in MRP1 mRNA levels in the drug resistant DU 0.03 and PC 0.03 lines were demonstrated by both Northern blotting and RT-PCR consistent with the findings observed after staining by the two specific monoclonal antibodies, MRPm6 and MRPr1. Southern blot analysis demonstrated a 2-fold increase in the MRP1 gene copy number in the PC 0.03 line but not in the DU 0.03 line, suggesting that the overexpression of the MRP gene was regulated at the level of transcription in the latter line. We conclude that MRP1 not MDR1 overexpression. contributes to acquired drug resistance in these two prostate cancer cell lines. Prostate Cancer and Prostatic Diseases (2000) 3, 66-75

Induction of insulin-like growth factor binding protein expression by ICI 182,780 in a tamoxifen-resistant human breast cancer cell line.

Earlier studies in our laboratory demonstrated that the steroidal antiestrogen ICI 182,780 is very effective in abolishing the tamoxifen-resistant proliferation of MCF 7/5-23 cells. In addition, preliminary binding studies showed that ICI 182,780 increased the binding of insulin-like growth factor (IGF)-I to the MCF 7/5-23 cells, although this finding was not the result of an increase in the expression of the insulin-like growth factor-I receptor (IGF-IR). Hence, we reasoned that the inhibition of tamoxifen-resistant cell growth by ICI 182,780 might have been due to increased expression of insulin-like growth factor binding proteins (IGFBPs). We observed the up-regulation of non-insulin-suppressible IGF-I binding in both the tamoxifen-sensitive MCF 7/5-21 cell line (1.5-fold) and the tamoxifen-resistant MCF 7/5-23 cell line (2.5-fold) after 5 days of treatment with ICI 182,780 (10(-7) M) in serum-free medium, suggesting a role for cell-associated IGFBPs. Affinity cross-linking experiments confirmed the presence of an IGF-I:IGFBP complex of approximately 38-kDa in tamoxifen or ICI 182,780-treated cells. Western ligand blots showed higher levels of a soluble 30-kDa IGFBP in media conditioned by either of the subclones that had been treated with ICI 182,780, an effect consistently opposed by estrogen (E2: 10(-9) M). RT-PCR showed higher levels of IGFBP-5 mRNA than any of the other known IGFBPs, suggesting that this was the major IGFBP subtype. The protein was subsequently identified by Western immunoblotting as IGFBP-5. In conclusion, we postulate that this may be a mechanism contributing to the greater potency of ICI 182,780 in the growth inhibition of the MCF 7/5-23, tamoxifen-resistant cell line.

Altered expression of the IGF-1 receptor in a tamoxifen-resistant human breast cancer cell line.

The relationship between oestrogen (E2) and insulin-like growth factor-one (IGF-1) was examined in both tamoxifen-sensitive (MCF 7/5-21) and tamoxifen-resistant (MCF 7/5-23) subclones of the MCF 7 cell line. Both subclones were grown in defined, serum-free (SF) medium over a period of 7 days with the addition of E2 or IGF-1 or a combination of both agents. Growth of both MCF 7/5-21 and 7/5-23 cells was stimulated (245% and 350%, respectively) by E2. However, only the growth of MCF 7/5-23 cells was stimulated (266%) by IGF-1. A combination of E2 and IGF-1 significantly enhanced MCF 7/5-21 and 7/5-23 cell growth (581% and 695%, respectively). E2-induced IGF-1 receptor (IGF-1R) levels (as measured by 125I-IGF-1 binding and Northern analyses) in only MCF 7/5-23 cells. This effect was partially inhibited by tamoxifen. In medium containing serum, the growth of only the MCF 7/5-23 cells was significantly inhibited by the IGF-1R monoclonal antibody, alphaIR-3. The detection of E2-induced expression of IGF-2 using RT-PCR was demonstrated in the MCF 7/5-23 cells. These experiments indicate that E2 may sensitize tamoxifen-resistant MCF 7/5-23 cells to the growth stimulatory actions of IGF-2 via up-regulation of the IGF-1R and describes a cell-survival mechanism that may manifest itself as tamoxifen resistance.

The pure antiestrogen ICI 182,780 binds to a high-affinity site distinct from the estrogen receptor.

Both estrogen receptor-positive (ER+), tamoxifen-sensitive (5-21) and tamoxifen-resistant (5-23) subclones of the parental MCF-7 breast cancer cell line were used in competitive ligand binding studies involving either [3H]ICI 182,780 or 4-OH-[3H]tamoxifen (4OHT) displacement by unlabelled estradiol (E2) or the antiestrogens (AE) 4OHT and ICI 182,780. Neither radioligand was displaced significantly by E2 over a range of concentrations; binding was predominantly inhibited by the corresponding radio-inert ligand. Scatchard analysis of the data revealed that the binding capacities of both cell lines for ICI 182,780 were approximately 7-fold greater than the previously determined number of ER sites per cell, with the affinity being an order of magnitude less than that of E2 for ER. No difference was found between the TAM-sensitive and -resistant cells in their binding of either AE. When cells were preincubated with either E2, TAM or 4OHT at a high, fixed concentration to block the ER or AE binding sites (AEBS), respectively, displaceable binding of [3H]ICI 182,780 was still observed, indicating binding at a site other than the classical ER or previously described AEBS. Our results suggest that there is a specific, saturable and relatively high-affinity binding site for ICI 182,780 in MCF 5-21 and MCF 5-23 breast cancer cells. However, the physiological relevance of this binding site requires further clarification because in cell growth assays, E2 (at 1/10 the dose of ICI 182,780) overcame the inhibitory effect of the antiestrogen in both of the cell lines.

A study of chemical systems using signal flow graph theory: application to Neptune.

Photochemistry of giant planets and their satellites is characterized by numerous reactions involving many chemical species. In the present paper, chemical systems are modeled by signal flow graphs. Such a technique evaluates the transmission of any input into the system (solar flux, electrons...) and gives access to the identification of the most important mechanisms in the chemical system. For a given chemical system, we first evaluate rate coefficients. Then, in order to obtain concentrations of each compound, we integrate the set of continuity equations by Gear's method. Gear's method is chosen rather than another classical method because it is recommended for a system of stiff equations due to the existence of greatly differing time constants. Finally, the technique of signal flow graphs is used. This method is applied to the production of hydrocarbons in the atmospheres of giant planets. In particular, the production of C2H6 in the atmosphere of Neptune from the photodissociation of CH4 is investigated. Different paths of dissociation of CH4 are possible from L alpha radiations. A chemical system containing 14 species and 30 reactions including these different paths of dissociation is integrated. The main mechanism of production of C2H6 is identified and evaluated for each model of dissociation. The importance of various reaction paths as a function of time is discussed.

Photochemical modeling of Titan's atmosphere

We have developed a new photochemical model of Titan's atmosphere which includes all the important compounds and reactions in spherical geometry from the surface to 1240 km. Compared to the previous model of Yung et al. (1984, Astrophys. J. Suppl. 55, 465-506), the most significant recent change in the reactions used is the updated methane photodissociation scheme (Mordaunt et al. 1993, J. Chem. Phys. 98(3), 2054-2065). Moreover, the transfer of the solar radiation in the atmosphere and the photolysis rates have been calculated by using a Monte Carlo code. Finally, the eddy diffusion coefficient profile is adjusted in order to fit the mean vertical distribution of HCN retrieved from millimeter groundbased observations of Tanguy et al. (1990, Icarus, 85, 43-57) using new values for the boundary flux of atomic nitrogen (Strobel et al. 1992, Icarus 100, 512-526). We have run the model in both steady-state and diurnal modes, with 62 speices involved in 249 reactions. There is little difference between diurnal and steady-state results. Overall our results are in a closer agreement with the abundances inferred from the Voyager infrared measurements at the equator than the Yung et al. results. We find that the catalytic scheme for H recombination invoked by Yung et al. only slightly improves the model results and we conclude that this scheme is not essential to fit observations.

Numerical simulation of organic compounds formation in planetary atmospheres: comparison with laboratory experiments.

A numerical model of CH4 and CH4-NH3 photochemistry at 147 nm has been developed and results are directly compared with experimental simulations carried out for the same mixtures. Simulations with varying quantities of ammonia and hydrogen show how amines and nitriles can be produce in planetary atmospheres. These comparisons allow one to test schemes of reactions used in photochemical models. In particular, it is shown that the scheme of reactions of CH4 is fairly well consistent with experimental data. On the other hand, the photochemistry of NH3 should be improved.

A study of chemical systems using signal flow graph theory.

Photochemistry of giant planets and their satellites is characterized by numerous reactions involving a lot of chemical species. In the present paper, chemical systems are modeled by signal flow graphs. Such a technique evaluates the transmission of any input into the system (solar flux, electrons ... ) and gives access to the identification of the most important mechanisms in the chemical system. This method is applied to the production of hydrocarbons in the atmospheres of giant planets. In particular, the production of C2H6 in the atmosphere of Neptune from the photodissociation of CH4 is investigated. Different pathways of dissociation of CH4 are possible from L alpha radiation. A chemical system containing 14 species and 30 reactions including these different pathways of dissociation is integrated. The main mechanism of production of C2H6 is identified and evaluated for each model of dissociation. The importance of various reaction pathways as a function of time is presented.