Designing Vibrotactile Widgets with Printed Actuators and Sensors

Physical controls are fabricated through complicated assembly of parts requiring expensive machinery and are prone to mechanical wear. One solution is to embed controls directly in interactive surfaces, but the proprioceptive part of gestural interaction that makes physical controls discoverable and usable solely by hand gestures is lost and has to be compensated, by vibrotactile feedback for instance. Vibrotactile actuators face the same aforementioned issues as for physical controls. We propose printed vibrotactile actuators and sensors. They are printed on plastic sheets, with piezoelectric ink for actuation, and with silver ink for conductive elements, such as wires and capacitive sensors. These printed actuators and sensors make it possible to design vibrotactile widgets on curved surfaces, without complicated mechanical assembly

Tests of achromatic phase shifters performed on the SYNAPSE test bench: a progress report

The achromatic phase shifter (APS) is a component of the Bracewell nulling interferometer studied in preparation for future space missions (viz. Darwin/TPF-I) focusing on spectroscopic study of Earth-like exo-planets. Several possible designs of such an optical subsystem exist. Four approaches were selected for further study. Thales Alenia Space developed a dielectric prism APS. A focus crossing APS prototype was developed by the OCA, Nice, France. A field reversal APS prototype was prepared by the MPIA in Heidelberg, Germany. Centre Spatial de Li\`ege develops a concept based on Fresnel's rhombs. This paper presents a progress report on the current work aiming at evaluating these prototypes on the SYNAPSE test bench at the Institut d'Astrophysique Spatiale in Orsay, France

GPU-based ultra-fast direct aperture optimization for online adaptive radiation therapy

Online adaptive radiation therapy (ART) has great promise to significantly reduce normal tissue toxicity and/or improve tumor control through real-time treatment adaptations based on the current patient anatomy. However, the major technical obstacle for clinical realization of online ART, namely the inability to achieve real-time efficiency in treatment re-planning, has yet to be solved. To overcome this challenge, this paper presents our work on the implementation of an intensity modulated radiation therapy (IMRT) direct aperture optimization (DAO) algorithm on graphics processing unit (GPU) based on our previous work on CPU. We formulate the DAO problem as a large-scale convex programming problem, and use an exact method called column generation approach to deal with its extremely large dimensionality on GPU. Five 9-field prostate and five 5-field head-and-neck IMRT clinical cases with 5\times5 mm2 beamlet size and 2.5\times2.5\times2.5 mm3 voxel size were used to evaluate our algorithm on GPU. It takes only 0.7~2.5 seconds for our implementation to generate optimal treatment plans using 50 MLC apertures on an NVIDIA Tesla C1060 GPU card. Our work has therefore solved a major problem in developing ultra-fast (re-)planning technologies for online ART

Could we identify hot Ocean-Planets with CoRoT, Kepler and Doppler velocimetry?

Planets less massive than about 10 MEarth are expected to have no massive H-He atmosphere and a cometary composition (50% rocks, 50% water, by mass) provided they formed beyond the snowline of protoplanetary disks. Due to inward migration, such planets could be found at any distance between their formation site and the star. If migration stops within the habitable zone, this will produce a new kind of planets, called Ocean-Planets. Ocean-planets typically consist in a silicate core, surrounded by a thick ice mantle, itself covered by a 100 km deep ocean. The existence of ocean-planets raises important astrobiological questions: Can life originate on such body, in the absence of continent and ocean-silicate interfaces? What would be the nature of the atmosphere and the geochemical cycles ? In this work, we address the fate of Hot Ocean-Planets produced when migration ends at a closer distance. In this case the liquid/gas interface can disappear, and the hot H2O envelope is made of a supercritical fluid. Although we do not expect these bodies to harbor life, their detection and identification as water-rich planets would give us insight as to the abundance of hot and, by extrapolation, cool Ocean-Planets.Comment: 47 pages, 6 Fugures, regular paper. Submitted to Icaru

Bcl-2 protein family: Implications in vascular apoptosis and atherosclerosis

Apoptosis has been recognized as a central component in the pathogenesis of atherosclerosis, in addition to the other human pathologies such as cancer and diabetes. The pathophysiology of atherosclerosis is complex, involving both apoptosis and proliferation at different phases of its progression. Oxidative modification of lipids and inflammation differentially regulate the apoptotic and proliferative responses of vascular cells during progression of the atherosclerotic lesion. Bcl-2 proteins act as the major regulators of extrinsic and intrinsic apoptosis signalling pathways and more recently it has become evident that they mediate the apoptotic response of vascular cells in response to oxidation and inflammation either in a provocative or an inhibitory mode of action. Here we address Bcl-2 proteins as major therapeutic targets for the treatment of atherosclerosis and underscore the need for the novel preventive and therapeutic interventions against atherosclerosis, which should be designed in the light of molecular mechanisms regulating apoptosis of vascular cells in atherosclerotic lesions

Transiting exoplanets from the CoRoT space mission VIII. CoRoT-7b: the first Super-Earth with measured radius

We report the discovery of very shallow (DF/F = 3.4 10-4), periodic dips in the light curve of an active V = 11.7 G9V star observed by the CoRoT satellite, which we interpret as due to the presence of a transiting companion. We describe the 3-colour CoRoT data and complementary ground-based observations that support the planetary nature of the companion. Methods. We use CoRoT color information, good angular resolution ground-based photometric observations in- and out- of transit, adaptive optics imaging, near-infrared spectroscopy and preliminary results from Radial Velocity measurements, to test the diluted eclipsing binary scenarios. The parameters of the host star are derived from optical spectra, which were then combined with the CoRoT light curve to derive parameters of the companion. We examine carefully all conceivable cases of false positives, and all tests performed support the planetary hypothesis. Blends with separation larger than 0.40 arcsec or triple systems are almost excluded with a 8 10-4 risk left. We conclude that, as far as we have been exhaustive, we have discovered a planetary companion, named CoRoT-7b, for which we derive a period of 0.853 59 +/- 3 10-5 day and a radius of Rp = 1.68 +/- 0.09 REarth. Analysis of preliminary radial velocity data yields an upper limit of 21 MEarth for the companion mass, supporting the finding. CoRoT-7b is very likely the first Super-Earth with a measured radius.Comment: Accepted in Astronomy and Astrophysics; typos and language corrections; version sent to the printer w few upgrade

Combination Therapies Targeting Alk-Aberrant Neuroblastoma in Preclinical Models.

BACKGROUND: ALK activating mutations are identified in approximately 10% of newly diagnosed neuroblastomas and ALK amplifications in a further 1-2% of cases. Lorlatinib, a third generation ALK inhibitor, will soon be given alongside induction chemotherapy for children with ALK-aberrant neuroblastoma. However, resistance to single agent treatment has been reported and therapies that improve the response duration are urgently required. We studied the preclinical combination of lorlatinib with chemotherapy, or with the MDM2 inhibitor, idasanutlin, as recent data has suggested that ALK inhibitor resistance can be overcome through activation of the p53-MDM2 pathway. AIMS: To study the preclinical activity of ALK inhibitors alone and combined with chemotherapy or idasanutlin. METHODS: We compared different ALK inhibitors in preclinical models prior to evaluating lorlatinib in combination with chemotherapy or idasanutlin. We developed a triple chemotherapy (CAV: cyclophosphamide, doxorubicin and vincristine) in vivo dosing schedule and applied this to both neuroblastoma genetically engineered mouse models (GEMM) and patient derived xenografts (PDX). RESULTS: Lorlatinib in combination with chemotherapy was synergistic in immunocompetent neuroblastoma GEMM. Significant growth inhibition in response to lorlatinib was only observed in the ALK-amplified PDX model with high ALK expression. In this PDX lorlatinib combined with idasanutlin resulted in complete tumor regression and significantly delayed tumor regrowth. CONCLUSION: In our preclinical neuroblastoma models, high ALK expression was associated with lorlatinib response alone or in combination with either chemotherapy or idasanutlin. The synergy between MDM2 and ALK inhibition warrants further evaluation of this combination as a potential clinical approach for children with neuroblastoma

Multi-omics comparison of malignant and normal uveal melanocytes reveals molecular features of uveal melanoma.

Uveal melanoma (UM) is a rare cancer resulting from the transformation of melanocytes in the uveal tract. Integrative analysis has identified four molecular and clinical subsets of UM. To improve our molecular understanding of UM, we performed extensive multi-omics characterization comparing two aggressive UM patient-derived xenograft models with normal choroidal melanocytes, including DNA optical mapping, specific histone modifications, and DNA topology analysis using Hi-C. Our gene expression and cytogenetic analyses suggest that genomic instability is a hallmark of UM. We also identified a recurrent deletion in the BAP1 promoter resulting in loss of expression and associated with high risk of metastases in UM patients. Hi-C revealed chromatin topology changes associated with the upregulation of PRAME, an independent prognostic biomarker in UM, and a potential therapeutic target. Our findings illustrate how multi-omics approaches can improve our understanding of tumorigenesis and reveal two distinct mechanisms of gene expression dysregulation in UM

Example-based wrinkle synthesis for clothing animation

This paper describes a method for animating the appearance of clothing, such as pants or a shirt, that fits closely to a figure's body. Compared to flowing cloth, such as loose dresses or capes, these types of garments involve nearly continuous collision contact and small wrinkles, that can be troublesome for traditional cloth simulation methods. Based on the observation that the wrinkles in closefitting clothing behave in a predominantly kinematic fashion, we have developed an example-based wrinkle synthesis technique. Our method drives wrinkle generation from the pose of the figure's kinematic skeleton. This approach allows high quality clothing wrinkles to be combined with a coarse cloth simulation that computes the global and dynamic aspects of the clothing motion. While the combined results do not exactly match a high-resolution reference simulation, they do capture many of the characteristic fine-scale features and wrinkles. Further, the combined system runs at interactive rates, making it suitable for applications where high-resolution offline simulations would not be a viable option. The wrinkle synthesis method uses a precomputed database built by simulating the high-resolution clothing as the articulated figure is moved over a range of poses. In principle, the space of poses is exponential in the total number of degrees of freedom; however clothing wrinkles are primarily affected by the nearest joints, allowing each joint to be processed independently. During synthesis, mesh interpolation is used to consider the influence of multiple joints, and combined with a coarse simulation to produce the final results at interactive rates

Benchmarked performance charts using principal components analysis to improve the effectiveness of feedback for audit data in HIV care

Abstract Background Feedback tools for clinical audit data that compare site-specific results to average performance over all sites can be useful for quality improvement. Proposed tools should be simple and clearly benchmark the site’s performance, so that a relevant action plan can be directly implemented to improve patient care services. We aimed to develop such a tool in order to feedback data to UK HIV clinics participating in the 2015 British HIV Association (BHIVA) audit assessing compliance with the 2011 guidelines for routine investigation and monitoring of adult HIV-1- infected individuals. Methods HIV clinic sites were asked to provide data on a random sample of 50–100 adult patients attending for HIV care during 2014 and/or 2015 by completing a self-audit spreadsheet. Outcomes audited included the proportion of patients with recorded resistance testing, viral load monitoring, adherence assessment, medications, hepatitis testing, vaccination management, risk assessments, and sexual health screening. For each outcome we benchmarked the proportion for a specific site against the average performance. We produced performance charts for each site using boxplots for the outcomes. We also used the mean and differences from the mean performance to produce a dashboard for each site. We used principal components analysis to group correlated outcomes and simplify the dashboard. Results The 106 sites included in the study provided information on a total of 7768 patients. Outcomes capturing monitoring of treatment of HIV-infection showed high performance across the sites, whereas testing for hepatitis, and risk assessment for cardiovascular disease and smoking, management of flu vaccination, sexual health screening, and cervical cytology for women were very variable across sites. The principal components analysis reduced the original 12 outcomes to four factors that represented HIV care, hepatitis testing, other screening tests, and resistance testing. These provided simplified measures of adherence to guidelines which were presented as a 4 bar dashboard of performance. Conclusion Our dashboard performance charts provide easily digestible visual summaries of locally relevant audit data that are benchmarked against the overall mean and can be used to improve feedback to HIV services. Feedback from clinicians indicated that they found these charts acceptable and useful