Anti-Melanoma immunity and local regression of cutaneous metastases in melanoma patients treated with monobenzone and imiquimod; a phase 2 a trial

Vitiligo development in melanoma patients during immunotherapy is a favorable prognostic sign and indicates breakage of tolerance against melanocytic/melanoma antigens. We investigated a novel immunotherapeutic approach of the skin-depigmenting compound monobenzone synergizing with imiquimod in inducing antimelanoma immunity and melanoma regression. Stage III-IV melanoma patients with non-resectable cutaneous melanoma metastases were treated with monobenzone and imiquimod (MI) therapy applied locally to cutaneous metastases and adjacent skin during 12 weeks, or longer. Twenty-one of 25 enrolled patients were evaluable for clinical assessment at 12 weeks. MI therapy was well-tolerated. Partial regression of cutaneous metastases was observed in 8 patients and stable disease in 1 patient, reaching the statistical endpoint of treatment efficacy. Continued treatment induced clinical response in 11 patients, including complete responses in three patients. Seven patients developed vitiligo-like depigmentation on areas of skin that were not treated with MI therapy, indicating a systemic effect of MI therapy. Melanoma-specific antibody responses were induced in 7 of 17 patients tested and melanoma-specific CD8+T-cell responses in 11 of 15 patients tested. These systemic immune responses were significantly increased during therapy as compared to baseline in responding patients. This study shows that MI therapy induces local and systemic anti-melanoma immunity and local regression of cutaneous metastases in 38% of patients, or 52% during prolonged therapy. This study provides proof-of-concept of MI therapy, a low-cost, broadly applicable and well-tolerated treatment for cutaneous melanoma metastases, attractive for further clinical investigation

Rigorous Polynomial Approximation using Taylor Models in Coq

International audienceOne of the most common and practical ways of representing a real function on machines is by using a polynomial approximation. It is then important to properly handle the error introduced by such an approximation. The purpose of this work is to offer guaranteed error bounds for a specific kind of rigorous polynomial approximation called Taylor model. We carry out this work in the Coq proof assistant, with a special focus on genericity and efficiency for our implementation. We give an abstract interface for rigorous polynomial approximations, parameter- ized by the type of coefficients and the implementation of polynomials, and we instantiate this interface to the case of Taylor models with inter- val coefficients, while providing all the machinery for computing them. We compare the performances of our implementation in Coq with those of the Sollya tool, which contains an implementation of Taylor models written in C. This is a milestone in our long-term goal of providing fully formally proved and efficient Taylor models

Nomad DNA — A model for movement and duplication of DNA sequences in plant genomes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43425/1/11103_2004_Article_BF00019160.pd

Computed Tomography of Flake Graphite Ore: Data Acquisition and Image Processing

A solid knowledge of the mineralogical properties (e.g., flake size, flake size distribution, purity, shape) of graphite ores is necessary because different graphite classes have different product uses. To date, these properties are commonly examined using well-established optical microscopy (OM), scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS) and SEM-based automated image analysis. However, these 2D methods may be subject to sampling errors and stereological effects that can adversely affect the quality of the analysis. X-ray microcomputed tomography (CT) is a nondestructive imaging technique allowing for examination of the interior and exterior of solid materials such as rocks and ores in 3D. This study aimed to explore whether CT can provide additional mineralogical information for the characterisation of graphite ores. CT was used in combination with traditional techniques (XRD, SEM-EDS, OM) to examine a flake graphite ore in 3D. A scanning protocol for the examined graphite ore was established to acquire high-quality CT data. Quantitative mineralogical information on key properties of graphite was obtained by developing a deep learning-based image processing strategy. The results demonstrate that CT allows for the 3D visualisation of graphite ores and provides valid and reliable quantitative information on the quality-determining properties that currently cannot be obtained by other analytical tools. CT allows improved assessment of graphite deposits and their beneficiation

Computed Tomography of Scheelite Ore, Kara, Australia: Morphological Characterisation and Modal Mineralogy

Metal ores are mineralogically characterised to understand their genesis in order to allow informed decisions on mineral processing and to recognise likely environmental risks upon mining. However, standard mineralogical techniques generate only two-dimensional information at best, which in addition may be subject to sampling and stereological errors. By contrast, computed tomography (CT) is a non-destructive imaging technique that allows three-dimensional analysis of solid materials. In the present study, two ore types of the Kara Fe-W deposit (Australia) were characterised using CT to examine their mineral texture and modal mineralogy as well as scheelite distribution and ore grade (WO3). The results show that scheelite is primarily associated with hydrous phases (e.g., epidote, chlorite, amphibole) and occurs as massive or disseminated mineral as well as vein-fill at minor and trace concentrations. This study demonstrates that CT of scheelite ore enables accurate 3D texture visualisation (volume, grain size distribution) and yields valid quantitative data on modal mineralogy and WO3 grade of individual ore samples. Consequently, CT analysis of scheelite-bearing ore provides information relevant for ore genesis studies and comminution strategies for the possible recovery of scheelite as a by-product from metalliferous ores

Response competition between neurons and antineurons in the mushroom body

The mushroom bodies of Drosophila contain circuitry compatible with race models of perceptual choice. When flies discriminate odor intensity differences, opponent pools of cci3 core Kenyon cells (on and off cci3c KCs) accumulate evidence for increases or decreases in odor concentration. These sensory neurons and "antineurons"connect to a layer of mushroom body output neurons (MBONs) which bias behavioral intent in opposite ways. All-to-all connectivity between the competing integrators and their MBON partners allows for correct and erroneous decisions; dopaminergic reinforcement sets choice probabilities via reciprocal changes to the efficacies of on and off KC synapses; and pooled inhibition between cci3c KCs can establish equivalence with the drift-diffusion formalism known to describe behavioral performance. The response competition network gives tangible form to many features envisioned in theoretical models of mammalian decision making, but it differs from these models in one respect: the principal variables-the fill levels of the integrators and the strength of inhibition between them-are represented by graded potentials rather than spikes. In pursuit of similar computational goals, a small brain may thus prioritize the large information capacity of analog signals over the robustness and temporal processing span of pulsatile codes