712 research outputs found

    Broadcast encryption with dealership

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    In this paper, we introduce a new cryptographic primitive called broadcast encryption with dealership. This notion, which has never been discussed in the cryptography literature, is applicable to many realistic broadcast services, for example subscription-based television service. Specifically, the new primitive enables a dealer to bulk buy the access to some products (e.g., TV channels) from the broadcaster, and hence, it will enable the dealer to resell the contents to the subscribers with a cheaper rate. Therefore, this creates business opportunity model for the dealer. We highlight the security consideration in such a scenario and capture the security requirements in the security model. Subsequently, we present a concrete scheme, which is proven secure under the decisional bilinear Diffie-Hellman exponent and the Diffie-Hellman exponent assumptions

    Quantitative analysis of videokymography in normal and pathological vocal folds: a preliminari study.

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    Videokymography (VKG) captures high-speed images of the vocal folds independently of the periodicity of the acoustic signal. The aim of this study was to preliminarily assess a software package that can objectively measure specific parameters of vocal fold vibration. From August 2009 until December 2010, we prospectively evaluated 40 subjects (Group A, 18 normal subjects; Group B, 14 patients with benign lesions of the middle third of the vocal fold, such as polyps and cysts; Group C, 8 patients treated by endoscopic excision of vocal fold benign lesions) by videoendoscopy, videolaryngostroboscopy, and VKG. A VKG camera was coupled to a 70 telescope and video was recorded during phonation. Images were objectively analyzed by a post-processing software tool (VKG-Analyser) with a user-friendly interface developed by our group. Different parameters were considered, including the ratio between the amplitude of the vibration of one vocal fold with respect to the contralateral (Ramp), the ratio between the period of one vocal fold vibration and the opposite one (Rper), and the ratio between the duration of the open and closed phase within a glottal cycle (Roc). Mean values for Ramp, Rper, and Roc in Group A were 1.05, 1.04, and 1.35, respectively; in Group B were 1.63, 0.92, and 0.97, respectively; and in Group C were 1.13, 0.91, and 1.85, respectively. Quantitative analysis of videokymograms by the herein presented tool, named VKG-Analyser, is useful for objective evaluation of the vibratory pattern in normal and pathologic vocal folds. Important future developments of this tool for the study of both physiologic and pathologic patterns of vocal fold vibration can be expected

    Novel bicistronic lentiviral vectors correct beta-Hexosaminidase deficiency in neural and hematopoietic stem cells and progeny: implications for in vivo and ex vivo gene therapy of GM2 gangliosidosis

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    The favorable outcome of in vivo and ex vivo gene therapy approaches in several Lysosomal Storage Diseases suggests that these treatment strategies might equally benefit GM2 gangliosidosis. Tay-Sachs and Sandhoff disease (the main forms of GM2 gangliosidosis) result from mutations in either the HEXA or HERB genes encoding, respectively, the alpha- or beta-subunits of the lysosomal beta-Hexosaminidase enzyme. In physiological conditions, alpha- and beta-subunits combine to generate beta-Hexosaminidase A (HexA, alpha beta) and beta-Hexosaminidase B (HexB, 1313). A major impairment to establishing in vivo or ex vivo gene therapy for GM2 gangliosidosis is the need to synthesize the alpha- and beta-subunits at high levels and with the correct stoichiometric ratio, and to safely deliver the therapeutic products to all affected tissues/organs. Here, we report the generation and in vitro validation of novel bicistronic lentiviral vectors (LVs) encoding for both the murine and human codon optimized Hexa and Hex!) genes. We show that these LVs drive the safe and coordinate expression of the alpha- and beta-subunits, leading to supranormal levels of beta-Hexosaminidase activity with prevalent formation of a functional HexA in SD murine neurons and glia, murine bone marrow-derived hematopoietic stem/progenitor cells (HSPCs), and human SD fibroblasts. The restoration/overexpression of beta-Hexosaminidase leads to the reduction of intracellular GM2 ganglioside storage in transduced and in cross-corrected SD murine neural progeny, indicating that the transgenic enzyme is secreted and functional. Importantly, bicistronic LVs safely and efficiently transduce human neurons/glia and CD34 + HSPCs, which are target and effector cells, respectively, in prospective in vivo and ex vivo GT approaches. We anticipate that these bicistronic LVs may overcome the current requirement of two vectors co-delivering the alpha- or beta-subunits genes. Careful assessment of the safety and therapeutic potential of these bicistronic LVs in the SD murine model will pave the way to the clinical development of LV-based gene therapy for GM2 gangliosidosis

    Transplantation of Skeletal Muscle-Derived Sca-1(+)/PW1(+)/Pax7(-) Interstitial Cells (PICs) Improves Cardiac Function and Attenuates Remodeling in Mice Subjected to Myocardial Infarction

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    We have previously shown that skeletal muscle-derived Sca-1+/PW1+/Pax7− interstitial cells (PICs) are multi-potent and enhance endogenous repair and regeneration. Here, we investigated the regenerative potential of PICs following intramyocardial transplantation in mice subjected to an acute myocardial infarction (MI). MI was induced through the ligation of the left anterior descending coronary artery in 8-week old male C57BL/6 mice. 5 × 105 eGFP-labelled PICs (MI + PICs; n = 7) or PBS (MI-PBS; n = 7) were injected intramyocardially into the border zone. Sham mice (n = 8) were not subjected to MI, or the transplantation of PICs or PBS. BrdU was administered via osmotic mini-pump for 14 days. Echocardiography was performed prior to surgery (baseline), and 1-, 3- and 6-weeks post-MI and PICs transplantation. Mice were sacrificed at 6 weeks post-MI + PICs transplantation, and heart sections were analysed for fibrosis, hypertrophy, engraftment, proliferation, and differentiation of PICs. A significant (p < 0.05) improvement in ejection fraction (EF) and fractional shortening was observed in the MI-PICs group, compared to MI + PBS group at 6-weeks post MI + PICs transplantation. Infarct size/fibrosis of the left ventricle significantly (p < 0.05) decreased in the MI-PICs group (14.0 ± 2.5%), compared to the MI-PBS group (32.8 ± 2.2%). Cardiomyocyte hypertrophy in the border zone significantly (p < 0.05) decreased in the MI-PICs group compared to the MI-PBS group (330.0 ± 28.5 µM2 vs. 543.5 ± 26.6 µm2), as did cardiomyocyte apoptosis (0.6 ± 0.9% MI-PICs vs. 2.8 ± 0.8% MI-PBS). The number of BrdU+ cardiomyocytes was significantly (p < 0.05) increased in the infarct/border zone of the MI-PICs group (7.0 ± 3.3%), compared to the MI-PBS group (1.7 ± 0.5%). The proliferation index (total BrdU+ cells) was significantly increased in the MI-PICs group compared to the MI-PBS group (27.0 ± 3.4% vs. 7.6 ± 1.0%). PICs expressed and secreted pro-survival and reparative growth factors, supporting a paracrine effect of PICs during recovery/remodeling. Skeletal muscle-derived PICs show significant reparative potential, attenuating cardiac remodelling following transplantation into the infarcted myocardium. PICs can be easily sourced from skeletal muscle and therefore show promise as a potential cell candidate for supporting the reparative and regenerative effects of cell therapies

    Dropout from cognitive behavioural treatment in a case of bulimia nervosa: The role of the therapeutic alliance

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    Despite the refinement of the cognitive treatment for eating disorders, relatively high dropout rates represent a major problem for therapists and researchers. This study investigated the case of a patient with a diagnosis of bulimia nervosa, who dropped out of outpatient CBT after 28 weekly sessions. In addition to standard clinical outcome assessment, we examined how patient's psychological functioning and therapeutic alliance changed across sessions by applying observer-rating scales to the therapy transcripts. Although the patient reported some improvement at the six-month retest, observer ratings showed persistence of impaired functioning and frequent ruptures in the patient-therapist relationship throughout the treatment. We concluded that a thorough examination of the therapy process might help to understand the factors that lead to premature treatment termination

    Transplantation of Skeletal Muscle-Derived Sca-1âș/PW1âș/Pax7⁻ Interstitial Cells (PICs) Improves Cardiac Function and Attenuates Remodeling in Mice Subjected to Myocardial Infarction

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    We have previously shown that skeletal muscle-derived Sca-1âș/PW1âș/Pax7⁻ interstitial cells (PICs) are multi-potent and enhance endogenous repair and regeneration. Here, we investigated the regenerative potential of PICs following intramyocardial transplantation in mice subjected to an acute myocardial infarction (MI). MI was induced through the ligation of the left anterior descending coronary artery in 8-week old male C57BL/6 mice. 5 × 10⁔ eGFP-labelled PICs (MI + PICs; n = 7) or PBS (MI-PBS; n = 7) were injected intramyocardially into the border zone. Sham mice (n = 8) were not subjected to MI, or the transplantation of PICs or PBS. BrdU was administered via osmotic mini-pump for 14 days. Echocardiography was performed prior to surgery (baseline), and 1-, 3- and 6-weeks post-MI and PICs transplantation. Mice were sacrificed at 6 weeks post-MI + PICs transplantation, and heart sections were analysed for fibrosis, hypertrophy, engraftment, proliferation, and differentiation of PICs. A significant (\u1d631 < 0.05) improvement in ejection fraction (EF) and fractional shortening was observed in the MI-PICs group, compared to MI + PBS group at 6-weeks post MI + PICs transplantation. Infarct size/fibrosis of the left ventricle significantly (\u1d631 < 0.05) decreased in the MI-PICs group (14.0 ± 2.5%), compared to the MI-PBS group (32.8 ± 2.2%). Cardiomyocyte hypertrophy in the border zone significantly (\u1d631 < 0.05) decreased in the MI-PICs group compared to the MI-PBS group (330.0 ± 28.5 ”M2 vs. 543.5 ± 26.6 ”m2), as did cardiomyocyte apoptosis (0.6 ± 0.9% MI-PICs vs. 2.8 ± 0.8% MI-PBS). The number of BrdU+ cardiomyocytes was significantly (\u1d631 < 0.05) increased in the infarct/border zone of the MI-PICs group (7.0 ± 3.3%), compared to the MI-PBS group (1.7 ± 0.5%). The proliferation index (total BrdU+ cells) was significantly increased in the MI-PICs group compared to the MI-PBS group (27.0 ± 3.4% vs. 7.6 ± 1.0%). PICs expressed and secreted pro-survival and reparative growth factors, supporting a paracrine effect of PICs during recovery/remodeling. Skeletal muscle-derived PICs show significant reparative potential, attenuating cardiac remodelling following transplantation into the infarcted myocardium. PICs can be easily sourced from skeletal muscle and therefore show promise as a potential cell candidate for supporting the reparative and regenerative effects of cell therapie

    Blood Chemistry, Acid- Base, Electrolyte, Blood Lactate Metabolism and Sleep at 3480 m in Mountain Marathon Runners

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    Altered blood chemistry, acid-base and electrolyte are suggested determinants of sleep disturbance, with frequent arousal at high altitude even in well and long-trained altitude marathon runners. In this sample of experienced altitude marathon runners with maximal aerobic power at sea level of 61.4 \ub1 2.7 ml/kg 121\u387min 121 we found that pO2 and percent of oxygen saturation (%SO2) were lower at 2050 m and 3480 m than at sea level; pO2 was higher after 38 - 41 hours than after 30 - 31 hours of acclimatization at 3480 m (P < 0.05). After ascent to 3480 m %SO2 decreased (P < 0.003). Compared to sea level values, pH increased at high altitude (P < 0.05) consistent with changes in pCO2 and [HCO3-] (P < 0.05). Nocturnal %SpaO2 at a sleeping altitude of 3480 m was lower (P < 0.05) than at sea level. At high altitude, the percent of wake (W) time and delay falling asleep (DFA) increased, whereas non-rapid eye movement sleep (N-REM), REM sleep and total sleep time (TST) decreased (P < 0.05). Simple regression analysis disclosed a significant correlation between the changes in TST and the percent of REM sleep and the changes in %SpaO2 recorded during sleep (P < 0.05). Simple regression analysis showed a positive correlation between the changes in pO2 at higher altitude and the percent of W and of TST (P < 0.05). The changes in pO2, tCO2 and [HCO3-] correlated negatively and significantly with the percent of REM sleep changes at high altitude (P < 0.05). The TST changes at high altitude correlated positively with the changes in pO2 and pH and correlated negatively with the changes in %SO2, pCO2, tCO2, and [HCO3-] (P < 0.05). The changes in the percent of W at high altitude correlated significantly and positively with the changes in bases excess [BE] at high altitude (P < 0.05). The changes in the percent of REM sleep correlated significantly and positively with the changes in [iCa++] and [BE] and negatively with the changes in buffered bases [BB] and [BEeffective] (P < 0.05). The change in the percent of NREM + REM sleep at high altitude correlated significantly and positively with the changes in [BE] and [BB] concentration (P < 0.05). The increase in DFA at high altitude correlated significantly and negatively with the changes in pCO2 and significantly and negatively with the changes in [K+] (P < 0.05). Simple regression analysis demonstrated that the changes in pH at high altitude correlated positively and significantly with the percent of W and the DFA and negatively with the percent of changes in NREM sleep, REM sleep, NREM + REM sleep (P < 0.05). The decrease in the TST at high altitude correlated significantly and negatively with the changes in pCO2, tCO2, [HCO3-]and [K+] (P < 0.05). Our data demonstrate that the arterialized ear lobe techniques we used for evaluating most of the changes in blood chemistry, acid-base, electrolyte and blood lactate metabolism are suitable for clinical and laboratory assessment and are important predictors of the quality and quantity of acclimatization and sleep at high altitude

    A workflow for patient-specific fluid-structure interaction analysis of the mitral valve: A proof of concept on a mitral regurgitation case

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    The mechanics of the mitral valve (MV) are the result of the interaction of different anatomical structures complexly arranged within the left heart (LH), with the blood flow. MV structure abnormalities might cause valve regurgitation which in turn can lead to heart failure. Patient-specific computational models of the MV could provide a personalised understanding of MV mechanics, dysfunctions and possible interventions. In this study, we propose a semi-automatic pipeline for MV modelling based on the integration of state-of-the-art medical imaging, i.e. cardiac magnetic resonance (CMR) and 3D transoesophageal-echocardiogram (TOE) with fluid-structure interaction (FSI) simulations. An FSI model of a patient with MV regurgitation was implemented using the finite element (FE) method and smoothed particle hydrodynamics (SPH). Our study showed the feasibility of combining image information and computer simulations to reproduce patient-specific MV mechanics as seen on medical images, and the potential for efficient in-silico studies of MV disease, personalised treatments and device design
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