759 research outputs found

    Why compatibilist intuitions are not mistaken: a reply to Feltz and Millan

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    In the past decade, a number of empirical researchers have suggested that laypeople have compatibilist intuitions. In a recent paper, Feltz and Millan (2015) have challenged this conclusion by claiming that most laypeople are only compatibilists in appearance and are in fact willing to attribute free will to people no matter what. As evidence for this claim, they have shown that an important proportion of laypeople still attribute free will to agents in fatalistic universes. In this paper, we first argue that Feltz and Millan’s error-theory rests on a conceptual confusion: it is perfectly acceptable for a certain brand of compatibilist to judge free will and fatalism to be compatible, as long as fatalism does not prevent agents from being the source of their actions. We then present the results of two studies showing that laypeople’s intuitions are best understood as following a certain brand of source compatibilism rather than a “free-will-no-matter-what” strategy

    Diffusion-weighted MRI in the evaluation of renal lesions:preliminary results

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    The purpose of this study was to evaluate the capability and the reliability of diffusion-weighted MRI in the evaluation of normal kidney and different renal lesions. 39 patients (10 normal volunteers and 29 patients with known renal lesions) underwent MRI of the kidneys by using a 1.5 T superconducting magnet. Axial fat suppressed turbo spin echo (TSE) T2 and coronal fast field echo (FFE) T1 or TSE T1 weighted images were acquired for each patient. Diffusion-weighted (DW) images were obtained in the axial plane during breath-hold (17 s) with a spin-echo echo planar imaging (SE EPI) single shot sequence (repetition time (TR)52883 ms, echo time (TE)561 ms, flip angle590°), with b value of 500 s mm22. 16 slices were produced with slice thickness of 7 mm and interslice gap of 1 mm. An apparent diffusion coefficient (ADC) map was obtained at each slice position. The ADC was measured in an approximately 1 cm region of interest (ROI) within the normal renal parenchyma, the detected renal lesions and the collecting system if dilated. ADC values in normal renal parenchyma ranged from 1.7261023 mm2 s21 to 2.6561023 mm2 s21, while ADC values in simple cysts (n513) were higher (2.8761023 mm2 s21 to 4.0061023 mm2 s21). In hydronephrotic kidneys (n56) the ADC values of renal pelvis ranged from 3.3961023 mm2 s21 to 4.0061023 mm2 s21. In cases of pyonephrosis (n53) ADC values of the renal pelvis were found to be lower than those of renal pelvis of hydronephrotic kidneys (0.7761023 mm2 s21 to 1.0761023 mm2 s21). Solid benign and malignant renal tumours (n57) showed ADC values ranging between 1.2861023 mm2 s21 and 1.8361023 mm2 s21. In conclusion diffusion-weighted MR imaging of the kidney seems to be a reliable way to differentiate normal renal parenchyma and different renal diseases. Clinical experience with this method is still preliminary and further studies are required

    Aptamer-peptide conjugates as a new strategy to modulate human α-thrombin binding affinity

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    Aptamers are single-stranded RNA or DNA molecules that specifically recognize their targets and have proven valuable for functionalizing sensitive biosensors. α-thrombin is a trypsin-like serine proteinase which plays a crucial role in haemostasis and thrombosis. An abnormal activity or overexpression of this protein is associated with a variety of diseases. A great deal of attention was devoted to the construction of high-throughput biosensors for accurately detect thrombin for the early diagnosis and treatment of related diseases. Herein, we propose a new approach to modulate the interaction between α-thrombin and the aptamer TBA. To this end, TBA was chemically conjugated to two peptide sequences (TBA-GFIE-Ac and TBA-GEIF-Ac) corresponding to a short fragment of the acidic region of the human factor V, which is known to interact directly with exosite I. Surface Plasmon Resonance (SPR) results showed enhanced analytical performances of thrombin with TBA-GEIF-Ac than with TBA wild-type, reaching a limit of detection as low as 44.9 pM. Electrophoresis mobility shift assay (EMSA) corroborated the SPR results. Molecular dynamics (MD) simulations support experimental evidences and provided further insight into thrombin/TBA-peptide interaction. Our findings demonstrate that the combination of TBA with key interacting peptides offers good opportunities to produce sensitive devices for thrombin detection and potential candidates to block thrombin activity

    Doxorubicin and congo red effectiveness on prion infectivity in golden Syrian hamster

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    The effect of doxorubicin and Congo Red on prion protein (PrP) infectivity in experimental scrapie was studied to better understand the effect of these compounds in prion diseases and to establish whether a dose-response correlation exists for Congo Red. This was performed in order to test the effectiveness of compounds that may easily be used in human prion diseases. Brain homogenate containing membrane bound PrPSc monomers was used as inoculum and was previously incubated with doxorubicin 10(-3) M and with increasing concentrations of Congo Red ranging from 10(-7) to 10(-2) M. This study shows for the first time that doxorubicin, and confirms that Congo Red, may interact with pathological PrP monomers modifying their infectious properties. Pre-incubation of infected brain homogenate with Congo Red resulted in prolonged incubation time and survival, independently of Congo Red concentration (p<0.05). Doxorubicin and Congo Red effects do not depend upon interaction with PrP amyloid material

    Noninvasive near-infrared live imaging of human adult mesenchymal stem cells transplanted in a rodent model of Parkinson’s disease

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    Background: We have previously shown that human mesenchymal stem cells (hMSCs) can reduce toxin-induced neurodegeneration in a well characterized rodent model of Parkinson's disease. However, the precise mechanisms, optimal cell concentration required for neuroprotection, and detailed cell tracking need to be defined. We exploited a near-infrared imaging platform to perform noninvasive tracing following transplantation of tagged hMSCs in live parkinsonian rats.Methods: hMSCs were labeled both with a membrane intercalating dye, emitting in the near-infrared 815 nm spectrum, and the nuclear counterstain, Hoechst 33258. Effects of near-infrared dye on cell metabolism and proliferation were extensively evaluated in vitro. Tagged hMSCs were then administered to parkinsonian rats bearing a 6-hydroxydopamine-induced lesion of the nigrostriatal pathway, via two alternative routes, ie, intrastriatal or intranasal, and the cells were tracked in vivo and ex vivo using near-infrared technology.Results: In vitro, NIR815 staining was stable in long-term hMSC cultures and did not interfere with cell metabolism or proliferation. A significant near-infrared signal was detectable in vivo, confined around the injection site for up to 14 days after intrastriatal transplantation. Conversely, following intranasal delivery, a strong near-infrared signal was immediately visible, but rapidly faded and was completely lost within 1 hour. After sacrifice, imaging data were confirmed by presence/absence of the Hoechst signal ex vivo in coronal brain sections. Semiquantitative analysis and precise localization of transplanted hMSCs were further performed ex vivo using near-infrared imaging.Conclusion: Near-infrared technology allowed longitudinal detection of fluorescent-tagged cells in living animals giving immediate information on how different delivery routes affect cell distribution in the brain. Near-infrared imaging represents a valuable tool to evaluate multiple outcomes of transplanted cells, including their survival, localization, and migration over time within the host brain. This procedure considerably reduces the number of animal experiments needed, as well as interindividual variability, and may favor the development of efficient therapeutic strategies promptly applicable to patients

    High fidelity numerical fracture mechanics assisted by RBF mesh morphing

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    The study and design of cyclically loaded structures cannot neglect the evaluation of their fatigue behavior. Today numerical prediction tools allow adopting, in various industrial fields, refined and consolidated procedures for the assessment of cracked parts through analyses based on fracture mechanics. An high level of detail can be obtained through the use of well consolidated FEM methods, allowing an accurate and reliable calculation of the flaw Stress Intensity Factor (SIF) and its resulting prediction in terms of crack propagation. A challenging step for this computational workflow remains, however, the generation and update of the computational grid during crack evolution. It is in this context that radial basis functions (RBF) mesh morphing is emerging as a viable solution to replace the complex and time-consuming remeshing operation. The flaw front is updated, according to its propagation, by automatically deforming the numerical grid obtaining an evolutionary workflow suitable to be used for industrially-sized numerical meshes (many millions of nodes). A review of applications, obtained by exploiting FEA (Ansys Mechanical) and mesh morphing (RBF Morph) state of-the-art tools, is presented in this work. At first the proposed workflow is applied on a circular notched bar with a defect controlled by a two-parameters evolution. The same approach is then refined and demonstrated for a Multi Degree of Freedom (MDoF) case on the same geometry and on the vacuum vessel port stub from the fusion nuclear reactor Iter

    Content and Feedback Analysis of YouTube Videos: Football Clubs and Fans as Brand Communities

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    The use of Web 2.0 tools has been transforming the interaction between companies and their clients, especially for those that are selling emotional products. Consumers are generating and sharing contents concerning their favourite products on the web. Even if this process has been widely acknowledged, only a few studies have been specifically devoted to the analysis of both the contents and the feedback the consumers receive from other users. This article analyzes the online presence of sport brands through contents that are generated by sport clubs (official contents) and their fans (User Generated Content, UGC) on YouTube. After a description and classification of video contents, it examines the factors that influence the performance of the videos in terms of passive (videos views) and active behaviour (any kinds of interaction with videos) among the viewers. In order to carry out this analysis, 125 YouTube channels were considered thereby accounting for a total of 375 videos. Results show that official contents are those preferred by the users/consumers and that if the video displays a passive/purely informative content, the chance of getting an active behaviour from the users tends to decrease. These findings may help companies manage their online presence, creating awareness about contents and information that should be spread and shared on the web
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