Human-based approaches to pharmacology and cardiology: an interdisciplinary and intersectorial workshop

Both biomedical research and clinical practice rely on complex datasets for the physiological and genetic characterization of human hearts in health and disease. Given the complexity and variety of approaches and recordings, there is now growing recognition of the need to embed computational methods in cardiovascular medicine and science for analysis, integration and prediction. This paper describes a Workshop on Computational Cardiovascular Science that created an international, interdisciplinary and inter-sectorial forum to define the next steps for a human-based approach to disease supported by computational methodologies. The main ideas highlighted were (i) a shift towards human-based methodologies, spurred by advances in new in silico, in vivo, in vitro, and ex vivo techniques and the increasing acknowledgement of the limitations of animal models. (ii) Computational approaches complement, expand, bridge, and integrate in vitro, in vivo, and ex vivo experimental and clinical data and methods, and as such they are an integral part of human-based methodologies in pharmacology and medicine. (iii) The effective implementation of multi- and interdisciplinary approaches, teams, and training combining and integrating computational methods with experimental and clinical approaches across academia, industry, and healthcare settings is a priority. (iv) The human-based cross-disciplinary approach requires experts in specific methodologies and domains, who also have the capacity to communicate and collaborate across disciplines and cross-sector environments. (v) This new translational domain for human-based cardiology and pharmacology requires new partnerships supported financially and institutionally across sectors. Institutional, organizational, and social barriers must be identified, understood and overcome in each specific setting

Human-based approaches to pharmacology and cardiology: an interdisciplinary and intersectorial workshop.

Both biomedical research and clinical practice rely on complex datasets for the physiological and genetic characterization of human hearts in health and disease. Given the complexity and variety of approaches and recordings, there is now growing recognition of the need to embed computational methods in cardiovascular medicine and science for analysis, integration and prediction. This paper describes a Workshop on Computational Cardiovascular Science that created an international, interdisciplinary and inter-sectorial forum to define the next steps for a human-based approach to disease supported by computational methodologies. The main ideas highlighted were (i) a shift towards human-based methodologies, spurred by advances in new in silico, in vivo, in vitro, and ex vivo techniques and the increasing acknowledgement of the limitations of animal models. (ii) Computational approaches complement, expand, bridge, and integrate in vitro, in vivo, and ex vivo experimental and clinical data and methods, and as such they are an integral part of human-based methodologies in pharmacology and medicine. (iii) The effective implementation of multi- and interdisciplinary approaches, teams, and training combining and integrating computational methods with experimental and clinical approaches across academia, industry, and healthcare settings is a priority. (iv) The human-based cross-disciplinary approach requires experts in specific methodologies and domains, who also have the capacity to communicate and collaborate across disciplines and cross-sector environments. (v) This new translational domain for human-based cardiology and pharmacology requires new partnerships supported financially and institutionally across sectors. Institutional, organizational, and social barriers must be identified, understood and overcome in each specific setting

SAIR - Social-Aware IMS-Enabled Recommender

The ever-increasing people demand for mobile communications has widely been satisfied by novel socially-enabled services and communication styles, starting from the advent of instant messaging to Voice over IP (VoIP), from Web 2.0 to social networks, and beyond. Most people agree that now the new challenge is to explore the potential of that immense information and service deposit already collected, ever-increasing, and easy-to-access to promote a socially-aware recommendation and to foster a more efficient delivery of mobile services. The article addresses the above issues, still unexplored in literature, by focusing on integration problems and describing a practical design experience derived from the development of a socio-technical aware support for the management of mobile services based on the widely diffused and interoperable IP Multimedia Subsystem (IMS) session control platform. Our proposal is organized along three main original technical guidelines: an innovative support to monitor and describe via social, physical, and computation information the sociotechnical context where services and user interact; a recommendation system to automate and facilitate dynamic selection of the mobile services most suitable from both final user and operator perspectives; and a new IMS-based management platform to ease the composition of existing IMS mobile services and the monitoring and control of their usage at runtime. We believe that we contribute with a first step to the understanding of how full awareness of socio and technical information allows improving overall Quality of Experience (QoE) for the final users

Activity recognition for Smart City scenarios: Google Play Services vs. MoST facilities

The ever increasing diffusion of smartphones today equipped with several physical and virtual sensors allow to directly collect information about surrounding physical and logical context that range from monitoring current social pulse of individuals and entire communities to detecting user current physical activity. Enabling those advanced sensing capabilities requires complex signal processing, machine learning, and resource management algorithms that are often beyond the skills of many mobile app developers. This paper describes the relevance of these facilities for mobile crowdsensing applications in Smart City scenarios and presents our solution for activity detection, comparing it with the reference implementations provided by Google as part of the Google Play Services library

Crowdsensing in Urban areas for city-scale mass gathering management: Geofencing and activity recognition

The widespread availability of smartphones today equipped with several physical and virtual sensors allows to directly collect various information about surrounding physical and logical context for different purposes that range from detecting user's current physical activity and also user presence in a designated area, often referred to as geofencing, to determining current social pulse of individuals and entire communities. Mobile crowdsensing seems a promising solution for enabling the design/development and deployment of a wide range of advanced applications in various fields. In particular, public safety, transportation, and energy monitoring and management in urban environments can benefit from mobile crowdsensing in terms of advanced provisioned applications as well as savings of investments in the urban sensing infrastructure. However, enabling those advanced smart urban applications requires complex signal processing, machine learning, and resource management algorithms that are often beyond the skills of many mobile app developers. This paper describes the pivotal relevance of these facilities for mobile crowdsensing applications and presents our open-source solution, called Mobile Sensing Technology (MoST), for activity detection and geofencing, comparing it with the reference implementations provided by Google as part of the Google Play Services library. Experimental results within the testbed framework of a crowd-management application scenario validate MoST design guidelines and demonstrate the general-purpose, unintrusive, and power-efficient characteristics of MoST sensing capabilities

Suppression of a Morphogenic Mutant in Rous Sarcoma Virus Capsid Protein by a Second-Site Mutation: a Cryoelectron Tomography Study▿ †

Retrovirus assembly is driven by polymerization of the Gag polyprotein as nascent virions bud from host cells. Gag is then processed proteolytically, releasing the capsid protein (CA) to assemble de novo inside maturing virions. CA has N-terminal and C-terminal domains (NTDs and CTDs, respectively) whose folds are conserved, although their sequences are divergent except in the 20-residue major homology region (MHR) in the CTD. The MHR is thought to play an important role in assembly, and some mutations affecting it, including the F167Y substitution, are lethal. A temperature-sensitive second-site suppressor mutation in the NTD, A38V, restores infectivity. We have used cryoelectron tomography to investigate the morphotypes of this double mutant. Virions produced at the nonpermissive temperature do not assemble capsids, although Gag is processed normally; moreover, they are more variable in size than the wild type and have fewer glycoprotein spikes. At the permissive temperature, virions are similar in size and spike content as in the wild type and capsid assembly is restored, albeit with altered polymorphisms. The mutation F167Y-A38V (referred to as FY/AV in this paper) produces fewer tubular capsids than wild type and more irregular polyhedra, which tend to be larger than in the wild type, containing ∼30% more CA subunits. It follows that FY/AV CA assembles more efficiently in situ than in the wild type and has a lower critical concentration, reflecting altered nucleation properties. However, its infectivity is lower than that of the wild type, due to a 4-fold-lower budding efficiency. We conclude that the wild-type CA protein sequence represents an evolutionary compromise between competing requirements for optimization of Gag assembly (of the immature virion) and CA assembly (in the maturing virion)

The Asymmetric Structure of an Icosahedral Virus Bound to Its Receptor Suggests a Mechanism for Genome Release

Simple, spherical RNA viruses have well-understood, symmetric protein capsids, but little structural information is available for their asymmetric components, such as minor proteins and their genomes, which are vital for infection. Here, we report an asymmetric structure of bacteriophage MS2, attached to its receptor, the F-pilus. Cryo-electron tomography and subtomographic averaging of such complexes result in a structure containing clear density for the packaged genome, implying that the conformation of the genome is the same in each virus particle. The data also suggest that the single-copy viral maturation protein breaks the symmetry of the capsid, occupying a position that would be filled by a coat protein dimer in an icosahedral shell. This capsomere can thus fulfill its known biological roles in receptor and genome binding and suggests an exit route for the genome during infection

Dinamiche del ricordo e della rimozione. L’eccidio delle Fosse Ardeatine nelle opere documentarie e cinegiornalistiche italiane (1945-1955)

Il contributo si concentra sul cinema di non fiction che tratta dell’eccidio delle Fosse Ardeatine. Dai documentari Giorni di gloria (Serandrei, Visconti, De Santis, Pagliero, 1945) e Dieci anni della nostra vita (Marcellini, 1953) ai cinegiornali. L’intento è riflettere sul ruolo che queste produzioni ricoprono nel modellare la memoria culturale e le narrazioni traumatiche. I film documentari del dopo-guerra assumono la forma di mediatori tra storia, memoria e politica, strumenti atti a contribuire alla definizione e ridefinizione dei caratteri identitari degli italiani

Imeglimin lowers glucose primarily by amplifying glucose-stimulated insulin secretion in high-fat-fed rodents

Imeglimin is a promising new oral antihyperglycemic agent that has been studied in clinical trials as a possible monotherapy or add-on therapy to lower fasting plasma glucose and improve hemoglobin A(1c) (1–3, 9). Imeglimin was shown to improve both fasting and postprandial glycemia and to increase insulin secretion in response to glucose during a hyperglycemic clamp after 1-wk of treatment in type 2 diabetic patients. However, whether the β-cell stimulatory effect of imeglimin is solely or partially responsible for its effects on glycemia remains to be fully confirmed. Here, we show that imeglimin directly activates β-cell insulin secretion in awake rodents without affecting hepatic insulin sensitivity, body composition, or energy expenditure. These data identify a primary amplification rather than trigger the β-cell mechanism that explains the acute, antidiabetic activity of imeglimin