346 research outputs found

    Ineffective Assistance of Counsel: A Plea Bargain Lost

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    GATE simulation for medical physics with genius Web portal

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    présenté par C. ThiamPCSV team of the LPC laboratory in Clermont-Ferrand is involved in the deployment of biomedical applications on the grid architecture. One of these applications deals with the deployment of GATE (Geant4 Application for Tomographic Emission) for medical physics application. The aim of the developments actually performed is to enable an application of the GATE platform in clinical routine. However, this perspective is only possible if the computing time and user time are highly reduced. The new grid architecture, developed within the framework of the European project Enabling Grid for E-sciencE (EGEE) is there to answer this requirement. The use of the grid resources must be transparent easy and rapid for the medical physicists. For this perpose, we adapted the GENIUS web portal in order to facilitate the GATE simulations planning on the grid. We will present a demonstration of the GENIUS portal which integrates all the functionalities of EGEE: to create, to submit and manage GATE jobs on the grid architecture. Our GATE activities for dosimetry application entered in to direct phase of evaluation by the cancer treatment center of Clermont Ferrand (Centre Jean perrin).A work station is currently available in this center to test the use of GATE application on the grid through GENIUS. This portal will allow in a long term to use GATE application in brachytherapy and radiotherapy treatment planning using medical data (medical images, DICOM, binary data dose calculation in the heterogeneous mediums) and to analyze the results obtained in visual form. Other functionalities are under development and will make possible to register medical data on grid storages elements and to manage them. However, these data must be anonymised before their recording on the grid. Their access via the GENIUS portal must be made safe and fast (compared simulation computing time). In order to be sure that the medical data are accessible for calculations, their replication on various storage element (SE) should be possible. The grid services give the possibility of managing this information in a free way and transparently. Operations of data handling and catalogues on the grid are ensured by the Replica Manager system which integrates all tools making it possible to manage data on the grid. The computing grid give promising results and meet a definite need: reach acceptable computing time for a future use of Monte Carlo simulations for treatment planning in brachytherapy and radiotherapy

    Dopamine D 4 Receptor-Deficient Mice Display Cortical Hyperexcitability

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    The dopamine D(4) receptor (D(4)R) is predominantly expressed in the frontal cortex (FC), a brain region that receives dense input from midbrain dopamine (DA) neurons and is associated with cognitive and emotional processes. However, the physiological significance of this dopamine receptor subtype has been difficult to explore because of the slow development of D(4)R agonists and antagonists the selectivity and efficacy of which have been rigorously demonstrated in vivo. We have attempted to overcome this limitation by taking a multidimensional approach to the characterization of mice completely deficient in this receptor subtype. Electrophysiological current and voltage-clamp recordings were performed in cortical pyramidal neurons from wild-type and D(4)R-deficient mice. The frequency of spontaneous synaptic activity and the frequency and duration of paroxysmal discharges induced by epileptogenic agents were increased in mutant mice. Enhanced synaptic activity was also observed in brain slices of wild-type mice incubated in the presence of the selective D(4)R antagonist PNU-101387G. Consistent with greater electrophysiological activity, nerve terminal glutamate density associated with asymmetrical synaptic contacts within layer VI of the motor cortex was reduced in mutant neurons. Taken together, these results suggest that the D(4)R can function as an inhibitory modulator of glutamate activity in the FC.Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Cepeda, Carlos. University of California at Los Angeles; Estados UnidosFil: Hurst, Raymond S.. University of California at Los Angeles; Estados UnidosFil: Flores Hernandez, Jorge. University of California at Los Angeles; Estados UnidosFil: Ariano, Marjorie A.. The Chicago Medical School; Estados UnidosFil: Falzone, Tomas Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Kozell, Laura B.. Oregon Health Sciences University; Estados UnidosFil: Meshul, Charles K.. Oregon Health Sciences University; Estados UnidosFil: Bunzow, James R.. Oregon Health Sciences University; Estados UnidosFil: Low, Malcolm J.. Oregon Health Sciences University; Estados UnidosFil: Levine, Michael S.. University of California at Los Angeles; Estados UnidosFil: Grandy, David K.. Oregon Health Sciences University; Estados Unido

    EXTENDING A MOBILE DEVICE WITH LOW-COST 3D MODELING AND BUILDING-SCALE MAPPING CAPABILITIES, FOR APPLICATION IN ARCHITECTURE AND ARCHAEOLOGY

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    One of the most challenging problem in architecture is the automated construction of 3D (and 4D) digital models of cultural objects with the aim of implementing open data repositories, scientifically authenticated and responding to well accepted standards of validation, evaluation, preservation, publication, updating and dissemination. The realization of such an ambitious objective requires the adoption of special technological instruments. In this paper we plan to use portable devices (i.e. smartphones, tablets or PDAs eventually extended to wearable ones), extended with a small plug-in, for automatically extracting 3D models of single objects and building-scale mapping of the surrounding environment. At the same time, the device will provide the capability of inserting notes and observations. Where the instrument cannot be directly applied, for example for exploring the top of a complex building, we consider mounting our device, or using equivalent existing equipment, on a drone, in a modular approach for obtaining data de-facto interchangeable. The approach based on the expansion packs has the advantage of anticipating (or even promoting) future extensions of new mobile devices, when the spectrum of possible applications justify the corresponding increased costs. In order to experiment and verify this approach we plan to test it in two specific scenarios of the cultural heritage domain in which such devices seem particularly promising: Strada Nuova in Genoa and Palazzo Ducale in Urbino, both located in Italy

    Mobile phone radiation does not induce pro-apoptosis effects in human spermatozoa

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    Recent reports suggest that mobile phone radiation may diminish male fertility. However, the effects of this radiation on human spermatozoa are largely unknown. The present study examined effects of the radiation on induction of apoptosisrelated properties in human spermatozoa. Ejaculated, densitypurified, highly motile human spermatozoa were exposed to mobile phone radiation at specific absorption rates (SARs) of 2.0 and 5.7 W/kg. At various times after exposure, flow cytometry was used to examine caspase 3 activity, externalization of phosphatidylserine (PS), induction of DNA strand breaks, and generation of reactive oxygen species. Mobile phone radiation had no statistically significant effect on any of the parameters studied. This suggests that the impairment of fertility reported in some studies was not caused by the induction of apoptosis in spermatozoa.This research was funded by the National Research Foundation (NRF), Pretoria, South Africa (Grant No: 2054206), NRF mobility fund, the South African Bureau of Standards (SABS), Pretoria, South Africa and the Finnish Radiation and Nuclear Safety Authority (STUK), Helsinki, Finland

    Mobile phone radiation does not induce pro-apoptosis effects in human spermatozoa

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    Recent reports suggest that mobile phone radiation may diminish male fertility. However, the effects of this radiation on human spermatozoa are largely unknown. The present study examined effects of the radiation on induction of apoptosisrelated properties in human spermatozoa. Ejaculated, densitypurified, highly motile human spermatozoa were exposed to mobile phone radiation at specific absorption rates (SARs) of 2.0 and 5.7 W/kg. At various times after exposure, flow cytometry was used to examine caspase 3 activity, externalization of phosphatidylserine (PS), induction of DNA strand breaks, and generation of reactive oxygen species. Mobile phone radiation had no statistically significant effect on any of the parameters studied. This suggests that the impairment of fertility reported in some studies was not caused by the induction of apoptosis in spermatozoa.This research was funded by the National Research Foundation (NRF), Pretoria, South Africa (Grant No: 2054206), NRF mobility fund, the South African Bureau of Standards (SABS), Pretoria, South Africa and the Finnish Radiation and Nuclear Safety Authority (STUK), Helsinki, Finland

    Current molecular and clinical insights into uveal melanoma (Review)

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    Uveal melanoma (UM) represents the most prominent primary eye cancer in adults. With an incidence of approximately 5 cases per million individuals annually in the United States, UM could be considered a relatively rare cancer. The 90.95% of UM cases arise from the choroid. Diagnosis is based mainly on a clinical examination and ancillary tests, with ocular ultrasonography being of greatest value. Differential diagnosis can prove challenging in the case of indeterminate choroidal lesions and, sometimes, monitoring for documented growth may be the proper approach. Fine needle aspiration biopsy tends to be performed with a prognostic purpose, often in combination with radiotherapy. Gene expression profiling has allowed for the grading of UMs into two classes, which feature different metastatic risks. Patients with UM require a specialized multidisciplinary management. Primary tumor treatment can be either enucleation or globe preserving. Usually, enucleation is reserved for larger tumors, while radiotherapy is preferred for small/medium melanomas. The prognosis is unfavorable due to the high mortality rate and high tendency to metastasize. Following the development of metastatic disease, the mortality rate increases to 80% within one year, due to both the absence of an effective treatment and the aggressiveness of the condition. Novel molecular studies have allowed for a better understanding of the genetic and epigenetic mechanisms involved in UM biological activity, which differs compared to skin melanomas. The most commonly mutated genes are GNAQ, GNA11 and BAP1. Research in this field could help to identify effective diagnostic and prognostic biomarkers, as well as novel therapeutic targets

    Immune-checkpoint inhibitors from cancer to COVID‑19: A promising avenue for the treatment of patients with COVID‑19

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    The severe acute respiratory syndrome associated coronavirus‑2 (SARS‑CoV‑2) poses a threat to human life worldwide. Since early March, 2020, coronavirus disease 2019 (COVID‑19), characterized by an acute and often severe form of pneumonia, has been declared a pandemic. This has led to a boom in biomedical research studies at all stages of the pipeline, from the in vitro to the clinical phase. In line with this global effort, known drugs, currently used for the treatment of other pathologies, including antivirals, immunomodulating compounds and antibodies, are currently used off‑label for the treatment of COVID‑19, in association with the supportive standard care. Yet, no effective treatments have been identified. A new hope stems from medical oncology and relies on the use of immune‑checkpoint inhibitors (ICIs). In particular, amongst the ICIs, antibodies able to block the programmed death‑1 (PD‑1)/PD ligand-1 (PD‑L1) pathway have revealed a hidden potential. In fact, patients with severe and critical COVID‑19, even prior to the appearance of acute respiratory distress syndrome, exhibit lymphocytopenia and suffer from T‑cell exhaustion, which may lead to viral sepsis and an increased mortality rate. It has been observed that cancer patients, who usually are immunocompromised, may restore their anti‑tumoral immune response when treated with ICIs. Moreover, viral-infected mice and humans, exhibit a T‑cell exhaustion, which is also observed following SARS‑CoV‑2 infection. Importantly, when treated with anti‑PD‑1 and anti‑PD‑L1 antibodies, they restore their T‑cell competence and efficiently counteract the viral infection. Based on these observations, four clinical trials are currently open, to examine the efficacy of anti‑PD‑1 antibody administration to both cancer and non‑cancer individuals affected by COVID‑19. The results may prove the hypothesis that restoring exhausted T‑cells may be a winning strategy to beat SARS‑CoV‑2 infection

    Adattamento precoce dell’impianto cocleare in età pediatrica

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    L’impianto cocleare costituisce una valida opportunità per fornire l’accesso alla stimolazione uditiva nei casi di ipoacusia severa o profonda di origine cocleare. E’ stato ampiamente dimostrato che l’impianto cocleare è una soluzione sicura ed efficace e che la precocità nell’attivazione è associata a risultati migliori. E’ importante studiare le variabili e gli aspetti che possono interferire con un adattamento precoce e un adeguato accesso al mondo sonoro: caratteristiche del bambino, alleanza terapeutica con la famiglia, aspetti tecnici, medici e organizzativi. Obiettivo di questo lavoro è quello di proporre raccomandazioni utili per gli aspetti organizzativi-pratici relativi alle attivazioni precoci di impianto cocleare, attraverso un particolare modello di analisi SWOT e TOWS
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