Mitochondrial Membrane Permeability Inhibitors in Acute Myocardial Infarction Still Awaiting Translation

Despite therapeutic advances, acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. One potential limitation of the current treatment paradigm is the lack of effective therapies to optimize reperfusion after ischemia and prevent reperfusion-mediated injury. Experimental studies indicate that this process accounts for up to 50% of the final infarct size, lending it importance as a potential target for cardioprotection. However, multiple therapeutic approaches have shown potential in pre-clinical and early phase trials but a paucity of clear clinical benefit when expanded to larger studies. Here we explore this history of trials and errors of the studies of cyclosporine A and other mitochondrial membrane permeability inhibitors, agents that appeared to have a promising pre-clinical record yet provided disappointing results in phase III clinical trials

Cartografie di rischio d’inquinamento ambientale: l’area carsica di Prizzi (Monti Sicani, Sicilia)

Il presente lavoro riporta uno studio eseguito in un’area della Sicilia, quella di Prizzi, inclusa nella regione geologica dei Monti Sicani, dove è stata redatta una cartografia di rischio d’inquinamento per acquiferi ancora poco contaminati. L’intendimento è quello di superare il concetto di vulnerabilità intrinseca ove applicato alle aree carsiche e di privilegiare così il pericolo di contaminazione degli acquiferi in relazione con le minacce d’inquinamento in ambiente carsico. Sono stati, di conseguenza, raccolti gli elementi di rischio legati alla presenza nel territorio dei centri di pericolo, redigendo un database ed elaborando un gruppo di mappe di pericolo territoriale. Queste, unitamente alle altre informazioni, possono fornire un’opportunità alle Pubbliche Amministrazioni al fine di poter indirizzare precauzionalmente la localizzazione o lo spostamento di infrastrutture o di insediamenti potenzialmente inquinanti (reti fognarie, discariche, aree industriali...). L’obiettivo finale, quindi, è quello di tener conto della possibilità di accadimento di incidenti o addirittura di catastrofi idrogeologiche, consentendo l’opportuna ubicazione delle stesse fonti di approvvigionamento idrico.This paper resumes an experience of evaluation, in a karst inland area of Sicily, of the danger contamination of groundwater characterizing the investigated territories, trying to connect them with the potential and real occurring menaces of pollution. A protection tool is conveniently represented by territory mapping performed in GIS environment, collecting also records of contamination sources spread in the territory and through the application of special standards for the estimation of the various risk elements. The final proposal is to furnish a useful opportunity to local administrations (municipalities, provinces, regional governments) for a reliable policy and management of their territories: in fact, they can precautionarily select suitable zones to locate or also shift particular infrastructures or settlements (sewerage networks, landfills, industrial poles…), with reference to dangerous events potentially occurring close to water supply sources. In this paper, a Sicily test-site will be depicted, located in the mountainous Sicani belt, where karst aquifers show till now a relative good groundwater quality, together with a likely danger of an increasing contamination risk. In the selected zone, a mapping of territorial danger has been performed in GIS environment

Stream programming framework for global ilumination techniques using a GPU

Los procesadores de streams están comenzando a ser una alternativa accesible para implementar técnicas de rendering asistidas por hardware que habitualmente estaban relegadas al uso offline. Nosotros elaboramos un marco de trabajo para procesamiento de streams basado en los conceptos del modelo de Stream Programming, seleccionamos el algoritmo de Photon Mapping y una GPU (Graphics Processing Unit) Nvidia para una implementación de un caso de prueba. Definimos un conjunto de clases en C++ para encapsular los componentes (kernels y streams) de este nuevo paradigma, usando OpenGL y el lenguaje Cg. Nuestra aplicación combina el método de Photon Mapping y una estructura de aceleración BVH (Bounding Volumes Hierarchy) en un pipeline de renderizado basado casi completamente en la GPU. Finalmente, evaluamos su desempeño usando un modelo de caja de Cornell.Stream processors are becoming an affordable alternative to implement hardware assisted rendering techniques which were usually relegated to offline usage. We built a stream processing framework based on the Stream Programming Model concepts, selected the Photon Mapping algorithm and an NVIDIA GPU (Graphics Processing Unit) as a test case implementation of a Global Illumination technique. We defined a set of C++ classes to encapsulate the components (kernels and streams) of this new paradigm, using OpenGL and Cg language. Our application combines the Photon Splatting method and the BVH (Bounding Volumes Hierarchy) acceleration structure into a rendering pipeline relying almost entirely on the GPU. Finally, we evaluated its performance using a Cornell Box model.V Workshop de Computación Gráfica, Imágenes Y VisualizaciónRed de Universidades con Carreras en Informática (RedUNCI

Business Model Innovation and exaptation: a new way of innovating in SMEs

Although research underlines the need for SMEs to innovate their Business Model, they face considerable challenges in exploring external business opportunities and experimenting/developing their available resources in unexpected ways. We posit that one way that SMEs can innovate their Business Model is through exaptation, a discontinuous evolutionary process that allows utilizing and adapting existing resources in new application domains. Using a case study approach, we investigate the case of a SME that has successfully innovated its Business Model through exaptation. We then discuss how three key exaptation processes lead to value creation, delivery and capturing, thus supporting Business Model Innovation in SMEs

Impaired myocardial relaxation with exercise determines peak aerobic exercise capacity in heart failure with preserved ejection fraction

Background Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by impaired exercise capacity due to shortness of breath and/or fatigue. Assessment of diastolic dysfunction at rest and with exercise may provide insight into the pathophysiology of exercise intolerance in HFpEF. Aims To measure echocardio-Doppler-derived parameters of diastolic function as they relate to various indices of aerobic exercise capacity in HFpEF. Methods We selected 16 subjects with clinically stable HFpEF, no evidence of volume overload, but impaired functional capacity by cardiopulmonary exercise testing [peak oxygen consumption (VO2)]. We measured the transmitral E and A flow velocities, E/A ratio, and E deceleration time (DT) and tissue Doppler E′ velocity. We also indexed the E′ to the DT, as additional measure of impaired relaxation (E′DT), and calculated the diastolic functional reserve index (DFRI), as the product of E′ at rest and change in E′ with exercise. Results E′ velocity, at rest and peak exercise, as well as the DFRI positively correlated with peak VO2, whereas DT, E′DT, and E/E′ with exercise inversely correlated with peak VO2. Of note, the E′DT at rest also significantly predicted E′ velocity at peak exercise (R = +0.81, P \u3c 0.001). Exercise E′ was the only independent predictor of peak VO2 at multivariable analysis (R = +0.67, P = 0.005). Conclusions The E′ velocity at peak exercise is a strong and independent predictor of aerobic exercise capacity as measured by peak VO2 in patients with HFpEF, providing the link between abnormal myocardial relaxation with exercise and impaired aerobic exercise capacity in HFpEF

Circularly polarized luminescence of natural products lycorine and narciclasine: role of excited-state intramolecular proton-transfer and test of pH sensitivity

: Circularly polarized luminescence (CPL) is increasingly gaining interest not only for its applicative potentialities but also for providing an understanding of the excited state properties of chiral molecules. However, applications of CPL are mainly in the field of materials science: special organic molecules and polymers, metal (lanthanide) complexes, and organic dyes are actively and intensely studied. So far natural compounds have not been investigated much. We fill the gap here by measuring circular dichroism (CD) and CPL of lycorine and narciclasine, the most abundant known alkaloid and isocarbostyril from Amaryllidaceae, which exhibit a large spectrum of biological activities and are promising anticancer compounds. Dual fluorescence detection in narciclasine led us to unveil an occurring excited-state intramolecular proton transfer (ESIPT) process, this mechanism well accounts for the Stokes shift and CPL spectra observed in narciclasine. The same molecule is interesting also as a pH chiroptical switch. Both in absorption and emission, lycorine and narciclasine are also studied computationally via density functional theory (DFT) calculations further shedding light on their properties

Self-Supervised Prediction of the Intention to Interact with a Service Robot

A service robot can provide a smoother interaction experience if it has the ability to proactively detect whether a nearby user intends to interact, in order to adapt its behavior e.g. by explicitly showing that it is available to provide a service. In this work, we propose a learning-based approach to predict the probability that a human user will interact with a robot before the interaction actually begins; the approach is self-supervised because after each encounter with a human, the robot can automatically label it depending on whether it resulted in an interaction or not. We explore different classification approaches, using different sets of features considering the pose and the motion of the user. We validate and deploy the approach in three scenarios. The first collects $3442$ natural sequences (both interacting and non-interacting) representing employees in an office break area: a real-world, challenging setting, where we consider a coffee machine in place of a service robot. The other two scenarios represent researchers interacting with service robots ($200$ and $72$ sequences, respectively). Results show that, even in challenging real-world settings, our approach can learn without external supervision, and can achieve accurate classification (i.e. AUROC greater than $0.9$) of the user's intention to interact with an advance of more than $3$s before the interaction actually occurs.Comment: Paper under revision for Robotics and Autonomous Systems journa

Interleukin-1 blockade in recently decompensated systolic heart failure: study design of the recently decompensated heart failure anakinra response trial (RED-HART)

Heart Failure (HF) is a clinical syndrome characterized by dyspnea, fatigue, and poor exercise capacity due to impaired cardiac function. The incidence of HF is increasing and represents the leading cause of hospitalization in the United States among patients > 65 years of age. Neurohormonal blockade has proven to reduce morbidity and mortality; however the persistent toll of HF demonstrates the urgent need to continue to develop novel drugs that target other pathophysiological paradigms. The presence of inflammation in cardiovascular disease has been well-established and interleukin-1 (IL-1), the prototypical proinflammatory agent, has been shown in preclinical animal models to induce cardiac dysfunction. The current study will investigate the role of IL-1 as an inflammatory mediator of HF progression and investigate whether IL-1 blockade with anakinra, recombinant human IL-1 receptor antagonist, improves aerobic exercise performance in patients with recently decompensated systolic HF. This study will be composed of 3 treatment arms (20 patients each): 1) anakinra 100mg daily for 12 weeks; 2) anakinra 100mg daily for 2 weeks followed by placebo for 10 weeks; or 3) placebo for 12 weeks. All patients will be followed for at least 24 weeks. The co-primary endpoints will be placebo-corrected interval changes in peak oxygen consumption (VO2) and ventilatory efficiency (VE/VCO2 slope) measured by Cardiopulmonary Exercise Testing (CPX) after 2 weeks of anakinra treatment. Secondary endpoints will include interval changes in 1) CPX variables at 4, 12 and 24 weeks; 2) echocardiographic measures of cardiac dimension/function; 3) quality of life assessments; 4) inflammatory biomarkers; and 5) clinical outcome including days alive outside of the hospital and survival free of re-hospitalization for HF. The RED-HART study will be the first study to address the potential benefits of IL-1 blockade on aerobic exercise performance in patients with recently decompensated HF