7,747 research outputs found

    Regression on fixed-rank positive semidefinite matrices: a Riemannian approach

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    The paper addresses the problem of learning a regression model parameterized by a fixed-rank positive semidefinite matrix. The focus is on the nonlinear nature of the search space and on scalability to high-dimensional problems. The mathematical developments rely on the theory of gradient descent algorithms adapted to the Riemannian geometry that underlies the set of fixed-rank positive semidefinite matrices. In contrast with previous contributions in the literature, no restrictions are imposed on the range space of the learned matrix. The resulting algorithms maintain a linear complexity in the problem size and enjoy important invariance properties. We apply the proposed algorithms to the problem of learning a distance function parameterized by a positive semidefinite matrix. Good performance is observed on classical benchmarks

    Human and bovine respiratory syncytial virus vaccine research and development

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    Human (HRSV) and bovine (BRSV) respiratory syncytial viruses (RSV) are two closely related viruses, which are the most important causative agents of respiratory tract infections of young children and calves, respectively. BRSV vaccines have been available for nearly 2 decades. They probably have reduced the prevalence of RSV infection but their efficacy needs improvement. In contrast, despite decades of research, there is no currently licensed vaccine for the prevention of HRSV disease. Development of a HRSV vaccine for infants has been hindered by the lack of a relevant animal model that develops disease, the need to immunize immunologically immature young infants, the difficulty for live vaccines to find the right balance between attenuation and immunogenicity, and the risk of vaccine-associated disease. During the past 15 years, intensive research into a HRSV vaccine has yielded vaccine candidates, which have been evaluated in animal models and, for some of them, in clinical trials in humans. Recent formulations have focused on subunit vaccines with specific CD4+ Th-1 immune response-activating adjuvants and on genetically engineered live attenuated vaccines. It is likely that different HRSV vaccines and/or combinations of vaccines used sequentially will be needed for the various populations at risk. This review discusses the recent advances in RSV vaccine development

    In vivo evidence for quasispecies distributions in the bovine respiratory syncytial virus genome

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    We analyzed the genetic evolution of bovine respiratory syncytial virus (BRSV) isolate W2-00131, from its isolation in bovine turbinate (BT) cells to its inoculation in calves. Results showed that the BRSV genomic region encoding the highly variable glycoprotein G remains genetically stable after virus isolation and over 10 serial infections in BT cells, as well as following experimental inoculation in calves. This remarkable genetic stability led us to examine the mutant spectrum of several populations derived from this field isolate. Sequence analysis of molecular clones revealed an important genetic heterogeneity in G coding region of each population, with mutation frequencies ranging from 6.8 to 10.1 10-4 substitutions/nucleotide. The non-synonymous mutations of the mutant spectrum mapped preferentially within the two variable antigenic regions of the ectodomain or close to the highly conserved domain. These results suggest that RSV populations may evolve as complex and dynamic mutant swarms, despite apparent genetic stability

    It is Worth More When It is Shared: Exploring Values Related to Shared-Use New Products

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    Recent research has shown that exchange value goes beyond utilitarian and functional aspects of goods or services. Value can be considered as symbolic, social or emotional. Postmodernism resurgence enhances significantly the appearance of new value categories. The growing importance of new behaviors shed a new light on a specific consumption way: shared consumption, i.e. simultaneous and coordinated consumption of the same product by more than one person. However, literature has brought mainly an individualistic response by identifying values for the sake of the individual consumer. Therefore, our research aims at investigating dimensions of value creation in case of innovative products linked to sharedusage. Three focus groups have been conducted. Subjects were asked to give their perceptions about three products concepts whit inherent shared-use characteristics. We ask them to imagine themselves in a real situation of concept use. Content analysis has revealed the categorization of news values, namely Synergy, Shared Expertise; Accuracy/Shared Contemplative Sensitivity, Conviviality, Integration/Domination, Reassurance, Tribalism and Communion. From a theoretical standpoint, this typology completes the individualistic Holbrookian model. Managerial contribution remains in the fact that this new typology can help R&D managers to explore shared-use values in new product development and use it in the different steps of new product elaboration

    Preferred antiretroviral drugs for the next decade of scale up

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    Global commitments aim to provide antiretroviral therapy (ART) to 15 million people living with HIV by 2015, and recent studies have demonstrated the potential for widespread ART to prevent HIV transmission. Increasingly, countries are adapting their national guidelines to start ART earlier, for both clinical and preventive benefits. To maximize the benefits of ART in resource-limited settings, six key principles need to guide ART choice: simplicity, tolerability and safety, durability, universal applicability, affordability and heat stability. Currently available drugs, combined with those in late-stage clinical development, hold great promise to simplify treatment in the short term. Over the longer-term, newer technologies, such as long-acting formulations and nanotechnology, could radically alter the treatment paradigm. This commentary reviews recommendations made in an expert consultation on treatment scale up in resource-limited settings

    A new subunit vaccine based on nucleoprotein nanoparticles confers partial clinical and virological protection in calves against bovine respiratory syncytial virus

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    Human and bovine respiratory syncytial viruses (HRSV and BRSV) are two closely related, worldwide prevalent viruses that are the leading cause of severe airway disease in children and calves, respectively. Efficacy of commercial bovine vaccines needs improvement and no human vaccine is licensed yet. We reported that nasal vaccination with the HRSV nucleoprotein produced as recombinant ringshaped nanoparticles (NSRS) protects mice against a viral challenge with HRSV. The aim of this work was to evaluate this new vaccine that uses a conserved viral antigen, in calves, natural hosts for BRSV. Calves, free of colostral or natural anti-BRSV antibodies, were vaccinated with NSRS either intramuscularly, or both intramuscularly and intranasally using MontanideTM ISA71 and IMS4132 as adjuvants and challenged with BRSV. All vaccinated calves developed anti-N antibodies in blood and nasal secretions and N-specific cellular immunity in local lymph nodes. Clinical monitoring post-challenge demonstrated moderate respiratory pathology with local lung tissue consolidations for the non vaccinated calves that were significantly reduced in the vaccinated calves. Vaccinated calves had lower viral loads than the nonvaccinated control calves. Thus NSRS vaccination in calves provided cross-protective immunity against BRSV infection without adverse inflammatory reaction

    Rethinking business models for innovation

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    One of the major challenges confronted by those in charge of technological innovation involves anticipating the value creation model sufficiently early on,in a highly uncertain context both as far as the technology itself is concerned and the potential market. Today, in many industrial sectors, the innovation boundaries have moved towards projects that are more and more exploratory and fuzzy. The simple optimisation of linear processes of the "stage-gate" type is no longer sufficient to build sustainable competitive advantages. The notion of Business Models, when applied to innovation, enables us to describe how a company creates value through innovation, generally within a business ecosystem, and how the value will be distributed between the actors involved. The authors of this book believe that the notions of Business Modelling and value creation are key to all the dimensions of successful innovation, whether technology, marketing, organisational or economically based. Rethinking Business Models for Innovation: this title describes the relationship between thinking, modelling, and also field-testing. The book is based on a series of nine recent cases of innovation involving company managers, often assisted by researchers (the co-authors of each chapter), and how they built and formalised their Business Models and then tested their strategies. After having discovered the variety of the cases, the reader will understand that every innovation situation generates specific questions about Business Models. However, we feel that we can identify three key issues that arise, more or less, in each of these projects. The chapters in this book build on these issues: the identification of sources of value and revenue models (the notion of value creation), the position of the company in the value-network or ecosystem (the sharing of value) and finally the evolution of Business MoDdels over time (the sustainability and the competitiveness of the company). The last chapter goes over all the contributions, exploring the notion of value in the Business Model approach.business model ; innovation ; value ; entrepreneurial project

    Successes and challenges of the APP Coronagraph

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    The Apodizing Phase Plate (APP) coronagraph has been used to image the exoplanet β Pictoris b and the protoplanet candidate around HD 100546, and is currently in use in surveys with NaCo at the VLT. Its success is due to its tolerance to tip-tilt pointing errors in current AO systems, which degrade the performance of nearly all other coronagraphs. Currently the sensitivity of the APP is limited by non-common path errors in the science camera systems and by its chromatic behaviour. We present the achromatized Vector APP coronagraph and address how we will measure and minimise non-common path errors with Focal Plane Wavefront Sensing algorithm
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