1st National Accessiblity Plan 2004-2012: achieving equal opportunities and full participation through design for all

According to official statistics, disabled people in Spain number 3.5 million and make up 8.8% of the Spanish population. This group of people are increasingly being recognised as members of society with equal rights, and many of their demands are gradually being transformed into solutions that benefit society as a whole. One example is improved accessibility. Accessible built environments are more human and inclusive places, as well as being easier to get around. Improved accessibility is now recognised as a requirement shared by all members of society, although it is achieved thanks to the demands of disabled people and their representatives. The 1st National Accessibility Plan is a strategic framework for action aimed at ensuring that new products, services and built environments are designed to be accessible for as many people as possible (Design for All) and that existing ones are gradually duly adapted.

Rational design of an organometallic glutathione transferase inhibitor.

Double trouble: A hybrid organic-inorganic (organometallic) inhibitor was designed to target glutathione transferases. The metal center is used to direct protein binding, while the organic moiety acts as the active-site inhibitor (see picture). The mechanism of inhibition was studied using a range of biophysical and biochemical methods.

In vitro cell activating properties of the composite ribosomal vaccine D53

D53 (RibomuntyR) is a composite vaccine made of immunogenic ribosomes from 4 bacterial species (Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pyogenes and Streptococcus pneumoniae) associated with a membrane proteoglycan from a non encapsulated strain of Klebsiella pneumoniae. D53 is a potent inducer of interleukin-1 production by mouse BALB/c spleen cells as shown by the C3H/HeJ thymocyte co-stimulation assay. Furthermore D53 triggers DNA synthesis by mouse spleen cells and induces the maturation of B lymphocytes into immunoglobulin secreting cells. Polyclonal B cell activation by D53 was readily achieved in the C3H/HeJ strain which is deficient in its response to E. coli lipopolysaccharide. The proliferative response to D53 was abrogated by removal of B cells from the spleen cell suspension, but it was not altered after depletion of T cells or adherent cells. D53 induced polyclonal B cell activation of spleen cells from athymic nude mice and from CBA/N mice. Each component of D53 induced polyclona B cell activation except ribosomes from Streptococcus pneumoniae. Each triggered Interleukin-1 synthesis except ribosomes from Klebsiella penumoniae. These in vitro properties may account for some of the in vivo immunostimulating properties of this composite vaccine.

GP38, P28-I and P28-II: candidates for a vaccine against Schistosomiasis

Three antigens protective against Schistosoma mansoni have been extensively characterized. The schistosomulum surface antigen GP38 possesses an immunodominant carbohydrate epitope of which the structure has been defined. Protection can be achieved via the transfer of monoclonal antibodies recognizing the epitope or by immunization with anti-idiotype monoclonal antibodies. The glycan epitope is shared with the intermediate host, Biomphalaria glabrata as well as being present on other molluscs, including the Keyhole Limpet. A group of molecules at 28 kDa were initially characterized in adult worms and shown to protect rats and mice against a challenge infection. One of these molecules, P28-I, was cloned and expressed in E. coli, yeast and vaccinia virus. The recombinant antigen significantly protected rats, hamsters and baboons against a challenge infection. P28-I is a glutathione-S-transferase and the recombinant antigen produced in yeast exhibits the enzyme activity and has been purified to homogeneity by affinity chromatography. A second P28 antigen, P28-II, has also been cloned, fully sequenced and expressed. This recombinant antigen also protects against S. mansoni infection.

Prospects for a nonliving vaccine against Schistosomiasis based on cell-mediated immune resistance mechanisms

We have designed a vaccine model based on induction of cell-mediated immunity and shown that it protects mice against Schistosoma mansoni infection. Mice are immunized by intradermal injection with schistosome antigens plus BCG. Resistance is dependent on the route of antigen presentation and the adjuvant chosen. The pattern of resistance correlates with sensitization of T lymphocytes for production of gamma interferon, a macrophage activating lymphokine that stimulates the cellular effector mechanism of protection. Purified schistosome paramyosin, a muscle cell component present in soluble parasite antigenic preparations, is immunogenic for T lymphocytes and induces resistance when given intradermally with BCG. It is likely that this protein, and possibly other soluble molecules that are released by the parasites of a challenge infection, induce a cellular inflammatory response resulting in larval trapping and/or killing by activated macrophages. These results verify the feasibility of a vaccine against schistosomiasis based on induction of cell-mediated immune resistance mechanisms.

From creative ideas to new emerging ventures: the process of identification and exploitation among finnish design entrepreneurs

This study focuses on identification and exploitation processes among Finnish design entrepreneurs (i.e. selfemployed industrial designers). More specifically, this study strives to find out what design entrepreneurs do when they create new ventures, how venture ideas are identified and how entrepreneurial processes are organized to identify and exploit such venture ideas in the given industrial context. Indeed, what does educated and creative individuals do when they decide to create new ventures, where do the venture ideas originally come from, and moreover, how are venture ideas identified and developed into viable business concepts that are introduced on the markets? From an academic perspective: there is a need to increase our understanding of the interaction between the identification and exploitation of emerging ventures, in this and other empirical contexts. Rather than assuming that venture ideas are constant in time, this study examines how emerging ideas are adjusted to enable exploitation in dynamic market settings. It builds on the insights from previous entrepreneurship process research. The interpretations from the theoretical discussion build on the assumption that the subprocesses of identification and exploitation interact, and moreover, they are closely entwined with each other (e.g. McKelvie & Wiklund, 2004, Davidsson, 2005). This explanation challenges the common assumption that entrepreneurs would first identify venture ideas and then exploit them (e.g. Shane, 2003). The assumption is that exploitation influences identification, just as identification influences exploitation. Based on interviews with design entrepreneurs and external actors (e.g. potential customers, suppliers and collaborators), it appears as identification and exploitation of venture ideas are carried out in close interaction between a number of actors, rather than alone by entrepreneurs. Due to their available resources, design entrepreneurs have a desire to focus on identification related activities and to find external actors that take care of exploitation related activities. The involvement of external actors may have a direct impact on decisionmaking and various activities along the processes of identification and exploitation, which is something that previous research does not particularly emphasize. For instance, Bhave (1994) suggests both operative and strategic feedback from the market, but does not explain how external parties are actually involved in the decisionmaking, and in carrying out various activities along the entrepreneurial process.

Using active learning for monitoring networks design: The example of wind power plants sites evaluation

Locating new wind farms is of crucial importance for energy policies of the next decade. To select the new location, an accurate picture of the wind fields is necessary. However, characterizing wind fields is a difficult task, since the phenomenon is highly nonlinear and related to complex topographical features. In this paper, we propose both a nonparametric model to estimate wind speed at different time instants and a procedure to discover underrepresented topographic conditions, where new measuring stations could be added. Compared to space filling techniques, this last approach privileges optimization of the output space, thus locating new potential measuring sites through the uncertainty of the model itself.

Simultaneous CD8+ T cell responses to multiple tumor antigen epitopes in a multipeptide melanoma vaccine.

The recent identification and molecular characterization of tumor-associated antigens recognized by tumor-reactive CD8+ T lymphocytes has led to the development of antigen-specific immunotherapy of cancer. Among other approaches, clinical studies have been initiated to assess the in vivo immunogenicity of tumor antigen-derived peptides in cancer patients. In this study, we have analyzed the CD8+ T cell response of an ocular melanoma patient to a vaccine composed of four different tumor antigen-derived peptides administered simultaneously in incomplete Freund's adjuvant (IFA). Peptide NY-ESO-1(157-165) was remarkably immunogenic and induced a CD8+ T cell response detectable ex vivo at an early time point of the vaccination protocol. A CD8+ T cell response to the peptide analog Melan-A(26-35 A27L) was also detectable ex vivo at a later time point, whereas CD8+ T cells specific for peptide tyrosinase(368-376) were detected only after in vitro peptide stimulation. No detectable CD8+ T cell response to peptide gp100(457-466) was observed. Vaccine-induced CD8+ T cell responses declined rapidly after the initial response but increased again after further peptide injections. In addition, tumor antigen-specific CD8+ T cells were isolated from a vaccine injection site biopsy sample. Importantly, vaccine-induced CD8+ T cells specifically lysed tumor cells expressing the corresponding antigen. Together, these data demonstrate that simultaneous immunization with multiple tumor antigen-derived peptides can result in the elicitation of multiepitope-directed CD8+ T cell responses that are reactive against antigen-expressing tumors and able to infiltrate antigen-containing peripheral sites.

Determinants of hepatitis A vaccine immunity in a cohort of human immunodeficiency virus-infected children living in Switzerland.

Vaccination in HIV-infected children is often less effective than in healthy children. The goal of this study was to assess vaccine responses to hepatitis A virus (HAV) in HIV-infected children. Children of the Swiss Mother and Child HIV Cohort Study (MoCHiV) were enrolled prospectively. Recommendations for initial, catch-up, and additional HAV immunizations were based upon baseline antibody concentrations and vaccine history. HAV IgG was assessed by enzyme-linked immunosorbent assay (ELISA) with a protective cutoff value defined as ≥10 mIU/ml. Eighty-seven patients were included (median age, 11 years; range, 3.4 to 21.2 years). Forty-two patients were seropositive (48.3%) for HAV. Among 45 (51.7%) seronegative patients, 36 had not received any HAV vaccine dose and were considered naïve. Vaccine responses were assessed after the first dose in 29/35 naïve patients and after the second dose in 33/39 children (25 initially naïve patients, 4 seronegative patients, and 4 seropositive patients that had already received 1 dose of vaccine). Seroconversion was 86% after 1 dose and 97% after 2 doses, with a geometric mean concentration of 962 mIU/ml after the second dose. A baseline CD4(+) T cell count below 750 cells/μl significantly reduced the post-2nd-dose response (P = 0.005). Despite a high rate of seroconversion, patients with CD4(+) T cell counts of <750/μl had lower anti-HAV antibody concentrations. This may translate into a shorter protection time. Hence, monitoring humoral immunity may be necessary to provide supplementary doses as needed.

Study on thermostabilizers for trivalent oral poliomyelitis vaccine

Different formulations of trivalent oral poliomyelitis vaccine were tested, in order to obtain better thermostability, reduce corrosion of machinery and improve production costs. Magnesium chloride, sucrose, arginine and 199-Hank's medium were used in the formulations. The most appropriate formulation was a mixture of MgCl2 and arginine, which was highly thermostable, and had low production costs. The low corrosive formulation was rejected, due to low thermostability on storage.

Malaria vaccine development using synthetic peptides as a technical platform.

The review covers the development of synthetic peptides as vaccine candidates for Plasmodium falciparum- and Plasmodium vivax-induced malaria from its beginning up to date and the concomitant progress of solid phase peptide synthesis (SPPS) that enables the production of long peptides in a routine fashion. The review also stresses the development of other complementary tools and actions in order to achieve the long sought goal of an efficacious malaria vaccine.