A human immune data-informed vaccine concept elicits strong and broad T-cell specificities associated with HIV-1 control in mice and macaques

Background: None of the HIV T-cell vaccine candidates that have reached advanced clinical testing have been able to induce protective T cell immunity. A major reason for these failures may have been suboptimal T cell immunogen designs. Methods: To overcome this problem, we used a novel immunogen design approach that is based on functional T cell response data from more than 1,000 HIV-1 clade B and C infected individuals and which aims to direct the T cell response to the most vulnerable sites of HIV-1. Results: Our approach identified 16 regions in Gag, Pol, Vif and Nef that were relatively conserved and predominantly targeted by individuals with reduced viral loads. These regions formed the basis of the HIVACAT T-cell Immunogen (HTI) sequence which is 529 amino acids in length, includes more than 50 optimally defined CD4+ and CD8+ T-cell epitopes restricted by a wide range of HLA class I and II molecules and covers viral sites where mutations led to a dramatic reduction in viral replicative fitness. In both, C57BL/6 mice and Indian rhesus macaques immunized with an HTI-expressing DNA plasmid (DNA.HTI) induced broad and balanced T-cell responses to several segments within Gag, Pol, and Vif. DNA.HTI induced robust CD4+ and CD8+ T cell responses that were increased by a booster vaccination using modified virus Ankara (MVA.HTI), expanding the DNA.HTI induced response to up to 3.2% IFN-γ T-cells in macaques. HTI-specific T cells showed a central and effector memory phenotype with a significant fraction of the IFN-γ+ CD8+ T cells being Granzyme B+ and able to degranulate (CD107a+). Conclusions: These data demonstrate the immunogenicity of a novel HIV-1 T cell vaccine concept that induced broadly balanced responses to vulnerable sites of HIV-1 while avoiding the induction of responses to potential decoy targets that may divert effective T-cell responses towards variable and less protective viral determinants.

Endogeneizing know-how flows through the nature of R&D investments

In this paper we carefully link knowledge flows to and from a firms innovation process with this firms investment decisions. Three types of investments are considered: investments in applied research, investments in basic research, and investments in intellectual property protection. Only when basic research is performed, can the firm effectively access incoming knowledge flows and these incoming spillovers serve to increase the efficiency of own applied research.. The firm can at the same time influence outgoing knowledge flows, improving appropriability of its innovations, by investing in protection. Our results indicate that firms with small budgets for innovation will not invest in basic research. This occurs in the short run, when the budget for know-how creation is restricted, or in the long-run, when market opportunities are low, when legal protection is not very important, or, when the pool of accessible and relevant external know-how is limited. The ratio! of basic to applied research is non-decreasing in the size of the pool of accessible external know-how, the size and opportunity of the market, and, the effectiveness of intellectual property rights protection. This indicates the existence of economies of scale in basic research due to external market related factors. Empirical evidence from a sample of innovative manufacturing firms in Belgium confirms the economies of scale in basic research as a consequence of the firms capacity to access external knowledge flows and to protect intellectual property, as well as the complementarity between legal and strategic investments.

Generalized property R and the Schoenflies Conjecture

There is a relation between the generalized Property R Conjecture and the Schoenflies Conjecture that suggests a new line of attack on the latter. The new approach gives a quick proof of the genus 2 Schoenflies Conjecture and suffices to prove the genus 3 case, even in the absence of new progress on the generalized Property R Conjecture.

Firm strategies in R&D: cooperation and participation in R&D programs

This paper presents empirical evidence on firms’ decisions to cooperate in R&D and the extent to which government sponsored R&D programs increase cooperation. Using a sample of firms from the Spanish innovation survey we jointly estimate the determinants of firm participation in R&D programs and of choice of cooperation partners. We find that (i) firms participating in national and European programs have different profiles, suggesting program complementarity; (ii) private-private and publicprivate cooperation are associated on average with firms with different characteristics, and (iii) national R&D programs seem to have a positive effect on all types of cooperation, but especially on public-private partnerships.

Who participates in R&D subsidy programs? The case of spanish manufacturing firms.

Empirical evidence on the effectiveness of R&D subsidies to firms has produced mixed results so far. One possible explanation is that firms and project selection rules may be quite heterogeneous both across agencies and across industries, leading to different outcomes in terms of the induced additional private effort. Here we focus on the participation stage. Using a sample of Spanish firms, we test for differences across agencies and industries. Our results suggest that firms in the same industry face different hurdles to participate in different agencies’ programs, that participation patterns may reflect a combination of agency goals, and that patterns differ across high-tech and low-tech industries.

Assessing the assignation of public subsidies: Do the experts choose the most efficient R&D projects?

The implementation of public programs to support business R&D projects requires the establishment of a selection process. This selection process faces various difficulties, which include the measurement of the impact of the R&D projects as well as selection process optimization among projects with multiple, and sometimes incomparable, performance indicators. To this end, public agencies generally use the peer review method, which, while presenting some advantages, also demonstrates significant drawbacks. Private firms, on the other hand, tend toward more quantitative methods, such as Data Envelopment Analysis (DEA), in their pursuit of R&D investment optimization. In this paper, the performance of a public agency peer review method of project selection is compared with an alternative DEA method.

Innovation, R&D spillovers and productivity: the role of knowledge-intensive services

This paper analyses the performance of companies’ R&D and innovation and the effects of intra- and inter-industry R&D spillover on firms’ productivity in Catalonia. The paper deals simultaneously with the performance of manufacturing and service firms, with the aim of highlighting the growing role of knowledge-intensive services in promoting innovation and productivity gains. We find that intra-industry R&D spillovers have an important effect on the productivity level of manufacturing firms, and the inter-industrial R&D spillovers related to computer and software services also play an important role, especially in high-tech manufacturing industries. The main conclusion is that the traditional classification of manufactured goods and services no longer makes sense in the ‘knowledge economy’ and in Catalonia the regional policy makers will have to design policies that favour inter-industrial R&D flows, especially from high-tech services.

Ciencia, industria e ideología en la Cataluña del siglo XX: el Instituto Ravetllat-Pla en Sudamérica entre 1924 y 1936

En 1923, Ramón Plá i Armengol (1880-1958) fundó el Instituto Ravetllat-Pla para la comercialización y producción de dos productos antituberculosos (Hemo-Antitoxina y Suero Ravetllat-Pla) fundamentados en una teoría heterodoxa postulada por el veterinario Joaquim Ravetllat i Estech (1871-1923). A través del instituto creó una gran red internacional científico-comercial principalmente en Latinoamérica. Plá i Armengol fue doctor en medicina y participó activamente en la lucha antituberculosa en Cataluña sin dejar de lado su militancia socialista. A través de estos dos productos, logró crear un mercado que se sustentaba en una teoría heterodoxa que integraban sus principios e ideología.

Does Internationalization Alter the R&D-Productivity Relationship?

R&D investment is an important driver of productivity gains. However, firms differ in their ability to appropiate the returns to their R&D efforts. This paper analyses to what extent firm's internationalization influences the endogenous relation between R&D and productivity. In particular, we assess the contribution of R&D to productivity for a panel of UK firms that differ in their degree of internationalization. We find that, on average, multinationals obtain higher gains from their investment in R&D. However, the influence of internationalization on the contribution of R&D to productivity varies along the distribution of the returns to R&D. Keywords: R&D, Multinationals, Productivity. JEL Codes: C14, D24, F23.

A doubling measure on R(d) can charge a rectifiable curve

"Vegeu el resum a l'inici del document del fitxer adjunt"

Determinación cualitativa de los componentes del cemento portland CEM I 52,5-R endurecido

Se pretende contribuir al esclarecimiento de la causa o causas de la importante disminución de la resistencia de las pastas de cemento portland sometidas a altas temperaturas. Para ello el primer paso y el que desarrolla este trabajo final de carrera es la determinación de los diferentes componentes de las pastas de cemento portland y más concretamente las fases en las que se encuentran los C-S-H a diferentes edades ya que son los responsables de las principales resistencias mecánicas de los materiales realizados con cemento portland, como los morteros y los hormigones.

Revisió de la Guia d’avaluació del testimoni en violència de gènere (GAT-VIG-R)

Nou document produït pels professionals dels equips d’assessorament tècnic penal de Catalunya (EAT penal) en l’àmbit de la jurisdicció d’adults, elaborat en el context del programa Compartim del Centre d’Estudis Juridics i Formació Especialitzada del Departament de Justícia. En aquest cas, es tracta de la revisió de la Guia d’avaluació del testimoni en violència de gènere (GAT-VIG-R) amb mostres dels EAT penal de Catalunya. Transcrivim una part de la presentació de l’obra on els mateixos autors ens expliquen els motius de la seva elaboració: “És dins els peritatges psicològics on se’ns encomana una de les tasques més delicades i complexes que duem a terme els psicòlegs dels EAT penal: l’anàlisi de la credibilitat dels testimonis. És en aquest camp que decidim, l’any 2009, donar un pas més enllà i analitzar en profunditat les tècniques que hi ha actualment sobre l’anàlisi de la credibilitat del testimoni adult en violència de gènere per tal de valorar la seva possible eficàcia i la seva posterior administració. El present document suposa el primer pas per millorar l’avaluació del testimoni en violència de gènere dins dels equips d’assessorament tècnic penal mitjançant la revisió de la Guia d’avaluació del testimoni en violència de gènere, instrument publicat al nostre país el 2007 per Juárez, J.R.; Mateu, A. i Sala, E. Així el present treball és el punt de partida per tal d’obtenir un primer perfil sociodemogràfic, psicològic i del testimoni en casos de violència de gènere creïbles amb l’objectiu que en properes recerques puguem arribar a obtenir criteris objectius per tal de discernir els testimonis creïbles en violència de gènere d’aquells que no ho són.”