19 research outputs found

    The Reverse Transcriptase Encoded by LINE-1 Retrotransposons in the Genesis, Progression, and Therapy of Cancer

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    In higher eukaryotic genomes, Long Interspersed Nuclear Element 1 (LINE-1) retrotransposons represent a large family of repeated genomic elements. They transpose using a reverse transcriptase (RT), which they encode as part of the ORF2p product. RT inhibition in cancer cells, either via RNA interference-dependent silencing of active LINE-1 elements, or using RT inhibitory drugs, reduces cancer cell proliferation, promotes their differentiation and antagonizes tumor progression in animal models. Indeed, the nonnucleoside RT inhibitor efavirenz has recently been tested in a phase II clinical trial with metastatic prostate cancer patients. An in-depth analysis of ORF2p in a mouse model of breast cancer showed ORF2p to be precociously expressed in precancerous lesions and highly abundant in advanced cancer stages, while being barely detectable in normal breast tissue, providing a rationale for the finding that RT-expressing tumours are therapeutically sensitive to RT inhibitors. We summarise mechanistic and gene profiling studies indicating that highly abundant LINE-1-derived RT can sequester RNA substrates for reverse transcription in tumor cells, entailing the formation of RNA:DNA hybrid molecules and impairing the overall production of regulatory miRNAs, with a global impact on the cell transcriptome. Based on these data, LINE-1-ORF2 encoded RT has a tumor-promoting potential that is exerted at an epigenetic level. We propose a model whereby LINE1-RT drives a previously unrecognized global regulatory process, the deregulation of which drives cell transformation and tumorigenesis and possibly implicated in cancer cell heterogeneity

    Adaptation of an i-voting scheme to Italian Elections for Citizens Abroad

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    We adapt the Ara´ujo-Traor´e protocol to Italian elections, with emphasis on anti-coercion measures. In this short paper we focus on a new method for managing anti-coercion credentials for each voter

    Amun: Securing E-Voting Against Over-the-Shoulder Coercion

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    In an election where each voter may express PP preferences among MM possible choices, the Amun protocol allows to secure vote casting against over-the-shoulder adversaries, retaining privacy, fairness, end-to-end verifiability, and correctness. Before the election, each voter receives a ballot containing valid and decoy tokens: only valid tokens contribute in the final tally, but they remain indistinguishable from the decoys. Since the voter is the only one who knows which tokens are valid (without being able to prove it to a coercer), over-the-shoulder attacks are thwarted. We prove the security of the construction under the standard Decisional Diffie Hellman assumption in the random oracle model

    Coercion-Resistant Blockchain-Based E-Voting Protocol

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    Coercion resistance is one of the most important features of a secure voting procedure. Because of the properties such as transparency, decentralization, and non-repudiation, blockchain is a fundamental technology of great interest in its own right, and it also has large potential when integrated into many other areas. Here we propose a decentralized e-voting protocol that is coercion-resistant and vote-selling resistant, while being also completely transparent and not receipt-free. We prove the security of the protocol under the standard DDH assumption

    Approach to leg edema

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    Edema is defined as a palpable swelling caused by an increase in interstitial fluid volume. Leg edema is a common problem with a wide range of possible causes and is the result of an imbalance in the filtration system between the capillary and interstitial spaces. Major causes of edema include venous obstruction, increased capillary permeability and increased plasma volume secondary to sodium and water retention. In both hospital and general practice, the patient with a swollen leg presents a common dilemma in diagnosis and treatment. The cause may be trivial or life-threatening and it is often difficult to determine the clinical pathway. The diagnosis can be narrowed by categorizing the edema according to its duration, distribution (unilateral or bilateral) and accompanying symptoms. This work provides clinically oriented recommendations for the management of leg edema in adults

    Antonio Gramsci e le interazioni con il pragmatismo europeo e statunitense

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    Dottorato di ricerca in Modelli di formazione, analisi teorica e comparazione, XXI ciclo, A.a. 2007-2008Università della Calabria, Dipartimento di scienze dell'educazion
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