Supervised Nonlinear Unmixing of Hyperspectral Images Using a Pre-image Methods

This book is a collection of 19 articles which reflect the courses given at the Collège de France/Summer school “Reconstruction d'images − Applications astrophysiques“ held in Nice and Fréjus, France, from June 18 to 22, 2012. The articles presented in this volume address emerging concepts and methods that are useful in the complex process of improving our knowledge of the celestial objects, including Earth

Spores of Clostridium engineered for clinical efficacy and safety cause regression and cure of tumors in vivo.

Spores of some species of the strictly anaerobic bacteria Clostridium naturally target and partially lyse the hypoxic cores of tumors, which tend to be refractory to conventional therapies. The anti-tumor effect can be augmented by engineering strains to convert a non-toxic prodrug into a cytotoxic drug specifically at the tumor site by expressing a prodrug-converting enzyme (PCE). Safe doses of the favored prodrug CB1954 lead to peak concentrations of 6.3 μM in patient sera, but at these concentration(s) known nitroreductase (NTR) PCEs for this prodrug show low activity. Furthermore, efficacious and safe Clostridium strains that stably express a PCE have not been reported. Here we identify a novel nitroreductase from Neisseria meningitidis, NmeNTR, which is able to activate CB1954 at clinically-achievable serum concentrations. An NmeNTR expression cassette, which does not contain an antibiotic resistance marker, was stably localized to the chromosome of Clostridium sporogenes using a new integration method, and the strain was disabled for safety and containment by making it a uracil auxotroph. The efficacy of Clostridium-Directed Enzyme Prodrug Therapy (CDEPT) using this system was demonstrated in a mouse xenograft model of human colon carcinoma. Substantial tumor suppression was achieved, and several animals were cured. These encouraging data suggest that the novel enzyme and strain engineering approach represent a promising platform for the clinical development of CDEPT

Modulation of cell death in the tumor micro environment

The microenvironment of solid human tumors is characterized by heterogeneity in oxygenation. Hypoxia arises early in the process of tumor development because rapidly proliferating tumor cells outgrow the capacity of the host vasculature. Formation of solid tumors thus requires coordination of angiogenesis with continued tumor cell proliferation. However, despite such neovascularization, hypoxia is persistent and frequently found in tumors at the time of diagnosis. Tumors with low oxygenation have a poor prognosis, and strong evidence suggests this is because of the effects of hypoxia on malignant progression, angiogenesis, metastasis, and therapy resistance. The presence of viable hypoxic cells is likely a reflection of the development of hypoxia tolerance resulting from modulation of cell death in the microenvironment. This acquired feature has been explained on the basis of clonal selection-the hypoxic microenvironment selects cells capable of surviving in the absence of normal oxygen availability. However, the persistence and frequency of hypoxia in solid tumors raises a second potential explanation. We suggest that stable microregions of hypoxia may play a positive role in tumor growth. Although hypoxia inhibits cell proliferation and in tumor cells will eventually induce cell death, hypoxia also provides angiogenic and metastatic signals. The development of hypoxia tolerance will thus allow prolonged survival in the absence of oxygen and generation of a persistent angiogenic signal. We will discuss the concept of hypoxia tolerance and review mechanisms used by cancer cells to acquire this phenotype. The concept of hypoxia tolerance has important implications for current and future therapeutic approaches. Most therapeutic efforts to combat hypoxia have focused on targeting the presence of hypoxia itself. Our hypothesis predicts that targeting the biological responses to hypoxia and the pathways leading to hypoxia tolerance may also be attractive therapeutic strategies.Copyright 2003, Elsevier Science (USA). All rights reserved

Decreasing population selection rates of resistance mutation K65R over time in HIV-1 patients receiving combination therapy including tenofovir

Objectives The use of tenofovir is highly associated with the emergence of mutation K65R, which confers broad resistance to nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs), especially when tenofovir is combined with other NRTIs also selecting for K65R. Although recent HIV-1 treatment guidelines discouraging these combinations resulted in reduced K65R selection with tenofovir, updated information on the impact of currently recommended regimens on the population selection rate of K65R is presently lacking. Methods In this study, we evaluated changes over time in the selection rate of resistance mutation K65R in a large population of 2736 HIV-1-infected patients failing combination antiretroviral treatment between 2002 and 2010. Results The K65R resistance mutation was detected in 144 patients, a prevalence of 5.3%. A large majority of observed K65R cases were explained by the use of tenofovir, reflecting its wide use in clinical practice. However, changing patterns over time in NRTIs accompanying tenofovir resulted in a persistent decreasing probability of K65R selection by tenofovir-based therapy. The currently recommended NRTI combination tenofovir/emtricitabine was associated with a low probability of K65R emergence. For any given dual NRTI combination including tenofovir, higher selection rates of K65R were consistently observed with a non-nucleoside reverse transcriptase inhibitor than with a protease inhibitor as the third agent. Discussion Our finding of a stable time trend of K65R despite elevated use of tenofovir illustrates increased potency of current HIV-1 therapy including tenofovi

Les enjeux de la conférence de Paris : penser autrement la question climatique

International audienc

Diffusion tensor imaging and resting-state functional MRI-scanning in 5- and 6-year-old children: Training protocol and motion assessment

Advanced Magnetic Resonance Imaging (MRI) techniques such as Diffusion Tensor Imaging (DTI) and resting-state functional MRI (rfMRI) are widely used to study structural and functional neural connectivity. However, as these techniques are highly sensitive to motion artifacts and require a considerable amount of time for image acquisition, successful acquisition of these images can be challenging to complete with certain populations. This is especially true for young children. This paper describes a new approach termed the 'submarine protocol', designed to prepare 5- and 6-year-old children for advanced MRI scanning. The submarine protocol aims to ensure that successful scans can be acquired in a time- and resource-efficient manner, without the need for sedation. This manuscript outlines the protocol and details its outcomes, as measured through the number of children who completed the scanning procedure and analysis of the degree of motion present in the acquired images. Seventy-six children aged between 5.8 and 6.9 years were trained using the submarine protocol and subsequently underwent DTI and rfMRI scanning. After completing the submarine protocol, 75 of the 76 children (99%) completed their DTI-scan and 72 children (95%) completed the full 35-minute scan session. Results of diffusion data, acquired in 75 children, showed that the motion in 60 of the scans (80%) did not exceed the threshold for excessive motion. In the rfMRI scans, this was the case for 62 of the 71 scans (87%). When placed in the context of previous studies, the motion data of the 5- and 6-year-old children reported here were as good as, or better than those previously reported for groups of older children (i.e., 8-year-olds). Overall, this study shows that the submarine protocol can be used successfully to acquire DTI and rfMRI scans in 5 and 6-year-old children, without the need for sedation or lengthy training procedures. © 2014 Theys et al

Understanding Uncertainty

A way to assess the information decrease uncertainty and project risk was described. Incorporating the method into real-time evaluation programs allowed continual updating of prognoses, such as the distance to a drilling target. Three case studies showed uncertainty analysis for geosteering into a thin pay section, a shaly-sand petrophysical analysis and a walkaway vertical seismic profile (VSP)