905 research outputs found

    Coherent Control of Photoelectron Wavepacket Angular Interferograms

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    Coherent control over photoelectron wavepackets, via the use of polarization-shaped laser pulses, can be understood as a time and polarization-multiplexed process. In this work, we investigate this multiplexing via computation of the observable photoelectron angular interferograms resulting from multi-photon atomic ionization with polarization-shaped laser pulses. We consider the polarization sensitivity of both the instantaneous and cumulative continuum wavefunction; the nature of the coherent control over the resultant photoelectron interferogram is thus explored in detail. Based on this understanding, the use of coherent control with polarization-shaped pulses as a methodology for a highly multiplexed coherent quantum metrology is also investigated, and defined in terms of the information content of the observable.Comment: 9 pages, 5 figure

    SMAD About Hepatitis C Virus Cell Entry and Liver Disease

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    Hepatitis C virus cell entry: a target for novel antiviral strategies to address limitations of direct acting antivirals

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    Hepatitis C virus (HCV) infection remains a major global health problem, with 130-170 million chronically infected individuals at risk to develop severe liver disease, including hepatocellular carcinoma. Although the development of direct-acting antivirals offers cure for a large majority of patients, there are still a number of clinical challenges. These include DAA failure in a significant subset of patients, difficult-to-treat genotypes and limited access to therapy due to high costs. Moreover, recent data indicate that the risk for liver cancer persists in patients with advanced fibrosis. These challenges highlight the need for continued efforts towards novel therapeutic strategies for HCV. Over the past two decades, advances in HCV model systems have enabled a detailed understanding of HCV entry and its clinical impact. Many of the virus-host interactions involved in HCV entry have now been identified and explored as antiviral targets. Furthermore, viral entry is recognized as an important factor for graft reinfection and establishment of persistent infection. HCV entry inhibitors, therefore, offer promising opportunities to address the limitations of DAAs. Here, we summarize recent advances in the field of HCV entry and discuss perspectives towards the prevention and cure of HCV infection and virus-induced liver disease

    Hepatitis C virus infection and related liver disease: the quest for the best animal model

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    Hepatitis C virus (HCV) is a major cause of cirrhosis and hepatocellular carcinoma (HCC) making the virus the most common cause of liver failure and transplantation. HCV is estimated to chronically affect 130 million individuals and to lead to more than 350,000 deaths per year worldwide. A vaccine is currently not available. The recently developed direct acting antivirals (DAAs) have markedly increased the efficacy of the standard of care but are not efficient enough to completely cure all chronically infected patients and their toxicity limits their use in patients with advanced liver disease, co-morbidity or transplant recipients. Because of the host restriction, which is limited to humans and non-human primates, in vivo study of HCV infection has been hampered since its discovery more than 20 years ago. The chimpanzee remains the most physiological model to study the innate and adaptive immune responses, but its use is ethically difficult and is now very restricted and regulated. The development of a small animal model that allows robust HCV infection has been achieved using chimeric liver immunodeficient mice, which are therefore not suitable for studying the adaptive immune responses. Nevertheless, these models allowed to go deeply in the comprehension of virus-host interactions and to assess different therapeutic approaches. The immunocompetent mouse models that were recently established by genetic humanization have shown an interesting improvement concerning the study of the immune responses but are still limited by the absence of the complete robust life cycle of the virus. In this review, we will focus on the relevant available animal models of HCV infection and their usefulness for deciphering the HCV life cycle and virus-induced liver disease, as well as for the development and evaluation of new therapeutics. We will also discuss the perspectives on future immunocompetent mouse models and the hurdles to their development

    Medida de la capacidad innovadora de las Comunidades Autónomas españolas : construcción de un índice regional de la innovación

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    El documento presenta un nuevo índice (el Índice IAIF de la Innovación Regional) que permite cuantificar en un solo valor la capacidad innovadora de las regiones españolas. El índice se compone de cuatro índices parciales, que permiten medir el nivel de innovación de las Comunidades Autónomas en los factores Entorno regional y productivo de la innovación, y Universidad, Administración Pública y Empresas innovadoras como agentes del sistema regional de I+D. Se detalla la metodología empleada en la construcción del índice y sus componentes, y se estudian los resultados que de los mismos se derivan

    Initiation of hepatitis C virus infection is dependent on cholesterol and cooperativity between CD81 and scavenger receptor B type I.

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    In the past several years, a number of cellular proteins have been identified as candidate entry receptors for hepatitis C virus (HCV) by using surrogate models of HCV infection. Among these, the tetraspanin CD81 and scavenger receptor B type I (SR-BI), both of which localize to specialized plasma membrane domains enriched in cholesterol, have been suggested to be key players in HCV entry. In the current study, we used a recently developed in vitro HCV infection system to demonstrate that both CD81 and SR-BI are required for authentic HCV infection in vitro, that they function cooperatively to initiate HCV infection, and that CD81-mediated HCV entry is, in part, dependent on membrane cholesterol

    Status of Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection and Remaining Challenges

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    PMC6446912Chronic infection with hepatitis C virus is a major cause of liver disease and hepatocellular carcinoma worldwide. After the discovery of hepatitis C virus 3 decades ago, the identification of the structure of the viral proteins, combined with high-throughput replicon models, enabled the discovery and development of direct-acting antivirals. These agents have revolutionized patient care, with cure rates of more than 90%. We review the status of direct-acting antiviral therapies for hepatitis C virus infection and discuss remaining challenges. We highlight licensed compounds, discuss the potential to shorten therapy even further, and review different options for treatment failure and resistance. We also provide an overview of clinical experience with generic agents and evidence for their efficacy. Finally, we discuss the need for new drugs and outline promising targets for future therapies

    Nota de prensa

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    Un estudio publicado por la Cátedra de Economía del Terrorismo revela que las bombas de Boston tuvieron un impacto significativo sobre las bolsas mundiales. El estudio destaca que ese impacto fue transitorio, de manera que los mercados se recuperaron en el mismo día del atentado. Asimismo, se muestra que el falso anuncio de The Associated Press, según el cual el presidente de los Estados Unidos, Barack Obama, había sido herido en un atentado a la Casa Blanca, provocó una caída del índice Dow Jones similar a la del atentado de Boston. Los autores del estudio consideran que ello abre nuevas incógnitas sobre las posibilidades del ciberterrorismo para las organizaciones terroristas
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