Towards the Knowledge-based Design of Universal Influenza Epitope Ensemble Vaccines

Motivation: Influenza A viral heterogeneity remains a significant threat due to unpredictable antigenic drift in seasonal influenza and antigenic shifts caused by the emergence of novel subtypes. Annual review of multivalent influenza vaccines targets strains of influenza A and B likely to be predominant in future influenza seasons. This does not induce broad, cross protective immunity against emergent subtypes. Better strategies are needed to prevent future pandemics. Cross-protection can be achieved by activating CD8+ and CD4+ T cells against highly-conserved regions of the influenza genome. We combine available experimental data with informatics-based immunological predictions to help design vaccines potentially able to induce cross-protective T-cells against multiple influenza subtypes. Results: To exemplify our approach we designed two epitope ensemble vaccines comprising highlyconserved and experimentally-verified immunogenic influenza A epitopes as putative non-seasonal influenza vaccines; one specifically targets the US population and the other is a universal vaccine. The USA-specific vaccine comprised 6 CD8+ T cell epitopes (GILGFVFTL, FMYSDFHFI, GMDPRMCSL, SVKEKDMTK, FYIQMCTEL, DTVNRTHQY) and 3 CD4+ epitopes (KGILGFVFTLTVPSE, EYIMKGVYINTALLN, ILGFVFTLTVPSERG). The universal vaccine comprised 8 CD8+ epitopes: (FMYSDFHFI, GILGFVFTL, ILRGSVAHK, FYIQMCTEL, ILKGKFQTA, YYLEKANKI, VSDGGPNLY, YSHGTGTGY) and the same 3 CD4+ epitopes. Our USA-specific vaccine has a population protection coverage (portion of the population potentially responsive to one or more component epitopes of the vaccine, PPC) of over 96% and 95% coverage of observed influenza subtypes. The universal vaccine has a PPC value of over 97% and 88% coverage of observed subtypes.

Zig-zagging in geometrical reasoning in technological collaborative environments: a Mathematical Working Space-framed study concerning cognition and affect

This study highlights the importance of cognition-affect interaction pathways in the construction of mathematical knowledge. Scientific output demands further research on the conceptual structure underlying such interaction aimed at coping with the high complexity of its interpretation. The paper discusses the effectiveness of using a dynamic model such as that outlined in the Mathematical Working Spaces (MWS) framework, in order to describe the interplay between cognition and affect in the transitions from instrumental to discursive geneses in geometrical reasoning. The results based on empirical data from a teaching experiment at a middle school show that the use of dynamic geometry software favours students’ attitudinal and volitional dimensions and helps them to maintain productive affective pathways, affording greater intellectual independence in mathematical work and interaction with the context that impact learning opportunities in geometric proofs. The reflective and heuristic dimensions of teacher mediation in students’ learning is crucial in the transition from instrumental to discursive genesis and working stability in the Instrumental-Discursive plane of MWS.

Analysis of the genome content of Lactococcus garvieae by genomic interspecies microarray hybridization

BACKGROUND Lactococcus garvieae is a bacterial pathogen that affects different animal species in addition to humans. Despite the widespread distribution and emerging clinical significance of L. garvieae in both veterinary and human medicine, there is almost a complete lack of knowledge about the genetic content of this microorganism. In the present study, the genomic content of L. garvieae CECT 4531 was analysed using bioinformatics tools and microarray-based comparative genomic hybridization (CGH) experiments. Lactococcus lactis subsp. lactis IL1403 and Streptococcus pneumoniae TIGR4 were used as reference microorganisms. RESULTS The combination and integration of in silico analyses and in vitro CGH experiments, performed in comparison with the reference microorganisms, allowed establishment of an inter-species hybridization framework with a detection threshold based on a sequence similarity of >or= 70%. With this threshold value, 267 genes were identified as having an analogue in L. garvieae, most of which (n = 258) have been documented for the first time in this pathogen. Most of the genes are related to ribosomal, sugar metabolism or energy conversion systems. Some of the identified genes, such as als and mycA, could be involved in the pathogenesis of L. garvieae infections. CONCLUSIONS In this study, we identified 267 genes that were potentially present in L. garvieae CECT 4531. Some of the identified genes could be involved in the pathogenesis of L. garvieae infections. These results provide the first insight into the genome content of L. garvieae.

Diseño y estudio de situaciones didácticas que favorecen el trabajo con registros semióticos

What’s behind the mistakes and difficulties that appear on the students to understand and study mathematics?are only related to the cognitive complexity of the content or such difficulties are also related to the possible ways to access the different mathematical objects? The mathematical activity generated in many students learning difficulties that are not manifested in cognitive processes related to other areas of knowledge. If something characterizes the processes of teaching and learning of mathematics is that, unlike what happens with the objects of study in the experimental sciences, the only way to access to them is through its different semiotic representations. The coordination among the different systems of representation that refer to the same mathematical concept, needs to move from one register to another (D’Amore, 1998, 2001, 2003, 2004, 2006; Duval, 1993, 1994, 1995, 1996, 2000, 2003, 2004, 2005, 2007, 2008, 2011, 2012; Godino, 2002, 2003, 2012, 2014; Kaput, 1989a, 1989b,1992, 1998; Radford, 1998, 2004a, 2004b, 2004c, 2006a, 2008,2009, 2011, 2013, 2014a). Therefore, the treatments that can be realized within a given register and the conversion of one register into another, play an essential role in the grasp of the object and mathematical concepts. Through this work with representations, students give meanings to the objects of study and are able to understand the underlying mathematical structures, which is the main educational interest of this issue...