MyHits: improvements to an interactive resource for analyzing protein sequences.

The MyHits web site (http://myhits.isb-sib.ch) is an integrated service dedicated to the analysis of protein sequences. Since its first description in 2004, both the user interface and the back end of the server were improved. A number of tools (e.g. MAFFT, Jacop, Dotlet, Jalview, ESTScan) were added or updated to improve the usability of the service. The MySQL schema and its associated API were revamped and the database engine (HitKeeper) was separated from the web interface. This paper summarizes the current status of the server, with an emphasis on the new services.

Coparenting and Toddler's Interactive Styles in Family Coalitions

The current study examined the coparenting and toddler's interactive styles in family coalitions. According to structural family theory, boundaries between generations are clear in alliances, but disturbed in coalitions: the parents look to the child to regulate their conflictual relationship and the child attempts to meet this need. In a normative sample studied longitudinally during the Lausanne Trilogue Play situation (LTP, N=38), 15 coalition cases were detected. Styles of coparenting and of child's interactions were determined and compared in coalition and alliance cases at 18 months. Findings confirm the structural family model by showing the specific ways in which the coparenting and the toddler's interactive styles are associated in 3 different patterns of coalitions: binding, detouring, and triangulation. They illustrate how the child's triangular capacity, or her ability to simultaneously communicate with both parents, is used to regulate the parents' relationship. They suggest that the LTP observational paradigm is a promising assessment method of early family interactions. They point to the importance of assessing early the child's contribution to family coalitions.

Implementing interactive computing in an object-oriented environment

Statistical computing when input/output is driven by a Graphical User Interface is considered. A proposal is made for automatic control ofcomputational flow to ensure that only strictly required computationsare actually carried on. The computational flow is modeled by a directed graph for implementation in any object-oriented programming language with symbolic manipulation capabilities. A complete implementation example is presented to compute and display frequency based piecewise linear density estimators such as histograms or frequency polygons.

Interactive local bandwidth choice

A tool for user choice of the local bandwidth function for a kernel density estimate is developed using KDE, a graphical object-oriented package for interactive kernel density estimation written in LISP-STAT. The bandwidth function is a cubic spline, whose knots are manipulated by the user in one window, while the resulting estimate appears in another window. A real data illustration of this method raises concerns, because an extremely large family of estimates is available.

Iowa Department of Transportation Fiscal Year 2008 Report of Savings by Using Video Conferencing Through Iowa Communications Network to the Iowa General Assembly Pursuant to Iowa Code § II 84 Acts and Joint Resolutions Enacted at the 1994 Regular Session of the 75th General Assembly of the State of Iowa Iowa Code §8D.10 Report of Savings by State Agencies

Iowa Code § 8D.10 requires certain state agencies prepare an annual report to the General Assembly certifying the identified savings associated with that state agency’s use of the Iowa Communications Network (ICN). This report covers estimated cost savings related to video conferencing via ICN for the Iowa Department of Transportation (DOT). In FY 2008, the DOT did not conduct any sessions utilizing ICN’s video conferencing system. Therefore, no cost savings were calculated for this report.

c-Myc acts downstream of IL-15 in the regulation of memory CD8 T-cell homeostasis.

A subset of CD8 T cells in normal mice, expressing high levels of activation markers such as CD44, shares many properties with antigen-specific memory CD8 T cells. Homeostasis of CD44(high) CD8 T cells depends upon cytokines such as interleukin-15 (IL-15); however, the downstream signaling pathways regulating IL-15-dependent homeostatic proliferation are poorly defined. Surprisingly, we show here that haploinsufficiency of the protooncogene c-myc leads to a highly selective decrease in CD44(high) CD8 T cells in mice. Although steady-state proliferation and survival of CD44(high) CD8 T cells appeared not to be dependent on c-Myc, homeostatic proliferation of c-myc(+/-) CD44(high) CD8 T cells in lymphopenic hosts was strongly reduced, and the residual homeostatic proliferation of these cells appeared to occur independently of IL-15. Moreover, c-myc(+/-) CD44(high) CD8 T cells responded very poorly to purified IL-15 in vitro. Backcrossing of c-myc(+/-) mice to IL-15(-/-) mice revealed that the number of CD44(high) CD8 T cells decreased in an additive fashion in mice heterozygous for c-myc and IL-15. Finally homeostatic proliferation of antigen-specific memory CD44(high) CD8 T cells was also impaired in c-myc(+/-) mice. Collectively, our data identify c-Myc as a novel downstream component of the IL-15-dependent pathway controlling homeostatic proliferation of memory CD44(high) CD8 T cells.

Meropenem prevents levofloxacin-induced resistance in penicillin-resistant pneumococci and acts synergistically with levofloxacin in experimental meningitis.

The aim of the present study was to investigate the potential synergy between meropenem and levofloxacin in vitro and in experimental meningitis and to determine the effect of meropenem on levofloxacin-induced resistance in vitro. Meropenem increased the efficacy of levofloxacin against the penicillin-resistant pneumococcal strain KR4 in time-killing assays in vitro and acted synergistically against a second penicillin-resistant strain WB4. In the checkerboard, only an additive effect (FIC indices: 1.0) was observed for both strains. In cycling experiments in vitro, levofloxacin alone led to a 64-fold increase in the MIC for both strains after 12 cycles. Addition of meropenem in sub-MIC concentrations (0.25 x MIC) completely inhibited the selection of levofloxacin-resistant mutants in WB4 after 12 cycles. In KR4, the addition of meropenem led to just a twofold increase in the MIC for levofloxacin after 12 cycles. Mutations detected in the genes encoding for topoisomerase IV (parC) and gyrase (gyrA) confirmed the levofloxacin-induced resistance in both strains. Addition of meropenem was able to completely suppress levofloxacin-induced mutations in WB4 and led to only one mutation in parE in KR4. In experimental meningitis, meropenem, given in two doses (2 x 125 mg/kg), produced a good bactericidal activity (-0.45 Deltalog10 cfu/ml.h) comparable to one dose (1 x 10 mg/kg) of levofloxacin (-0.44 Deltalog10 cfu/ml.h) against the penicillin-resistant strain WB4. Meropenem combined with levofloxacin acted synergistically (-0.93 Deltalog10 cfu/ml.h), sterilizing the CSF of all rabbits.

Evaluation of an online, case-based interactive approach to teaching pathophysiology

Rapport de synthèse : L'article qui fait l'objet de ma thèse évalue une nouvelle approche pédagogique pour l'apprentissage de certains chapitres de physiopathologie. Le dispositif pédagogique se base sur l'alternance d'apprentissage ex-cathedra et de l'utilisation d'un site web comprenant des vignettes cliniques. Lors de la consultation de ces-dernières, l'étudiant est invité à demander des examens de laboratoire dont il pourrait justifier la pertinence selon le cas clinique étudié. La nouveauté du procédé réside dans le fait que, préalablement à son cours ex-cathedra, l'enseignant peut consulter les statistiques de demandes de laboratoire et ainsi orienter son cours selon les éléments mal compris par les étudiants. A la suite du cours ex-cathedra, les étudiants peuvent consulter sur internet la vignette clinique complète avec des explications. A l'issue de tout le cours, une évaluation auprès des étudiants a été conduite. Le procédé a été mis en place durant deux années consécutives et l'article en discute notamment les résultats. Nous avons pu conclure que cette méthode innovatrice d'enseignement amène les étudiants à mieux se préparer pour les cours ex-cathedra tout en permettant à l'enseignant d'identifier plus précisément quelles thématiques étaient difficiles pour les étudiants et donc d'ajuster au mieux son cours. Mon travail de thèse a consisté à créer ce dispositif d'apprentissage, à créer l'application web des vignettes cliniques et à l'implanter durant deux années consécutives. J'ai ensuite analysé les données des évaluations et écrit l'article que j'ai présenté à la revue 'Medical Teacher'. Après quelques corrections et précisions demandées par le comité de lecture, l'article a été accepté et publié. Ce travail a débouché sur une seconde version de l'application web qui est actuellement utilisée lors du module 3.1 de 3è année à l'Ecole de Médecine à Lausanne. Summary : Since the early days of sexual selection, our understanding of the selective forces acting on males and females during reproduction has increased remarkably. However, despite a long tradition of experimental and theoretical work in this field and relentless effort, numerous questions remain unanswered and many results are conflicting. Moreover, the interface between sexual selection and conservation biology has to date received little attention, despite existing evidence for its importance. In the present thesis, I first used an empirical approach to test various sexual selection hypotheses in a population of whitefish of central Switzerland. This precise population is characterized by a high prevalence of gonadal alterations in males. In particular, I challenged the hypothesis that whitefish males displaying peculiar gonadal features are of lower genetic quality than other seemingly normal males. Additionally, I also worked on identifying important determinant of sperm behavior. During a second theoretical part of my work, which is part of a larger project on the evolution of female mate preferences in harvested fish populations, I developed an individual-based simulation model to estimate how different mate discrimination costs affect the demographical behavior of fish populations and the evolutionary trajectories of female mate preferences. This latter work provided me with some insight on a recently published article addressing the importance of sexual selection for harvesting-induced evolution. I built upon this insight in a short perspective paper. In parallel, I let some methodological questions drive my thoughts, and wrote an essay about possible synergies between the biological, the philosophical and the statistical approach to biological questions.

The discourse on political pluralism in early eighteenth-century England : a conceptual study with special reference to terminology of religious origin

Doctoral dissertation, University of Jyväskylä