Cancer chronotherapeutics: experimental, theoretical, and clinical aspects.

The circadian timing system controls cell cycle, apoptosis, drug bioactivation, and transport and detoxification mechanisms in healthy tissues. As a consequence, the tolerability of cancer chemotherapy varies up to several folds as a function of circadian timing of drug administration in experimental models. Best antitumor efficacy of single-agent or combination chemotherapy usually corresponds to the delivery of anticancer drugs near their respective times of best tolerability. Mathematical models reveal that such coincidence between chronotolerance and chronoefficacy is best explained by differences in the circadian and cell cycle dynamics of host and cancer cells, especially with regard circadian entrainment and cell cycle variability. In the clinic, a large improvement in tolerability was shown in international randomized trials where cancer patients received the same sinusoidal chronotherapy schedule over 24h as compared to constant-rate infusion or wrongly timed chronotherapy. However, sex, genetic background, and lifestyle were found to influence optimal chronotherapy scheduling. These findings support systems biology approaches to cancer chronotherapeutics. They involve the systematic experimental mapping and modeling of chronopharmacology pathways in synchronized cell cultures and their adjustment to mouse models of both sexes and distinct genetic background, as recently shown for irinotecan. Model-based personalized circadian drug delivery aims at jointly improving tolerability and efficacy of anticancer drugs based on the circadian timing system of individual patients, using dedicated circadian biomarker and drug delivery technologies.

Working memory load improves early stages of independent visual processing.

Increasing evidence suggests that working memory and perceptual processes are dynamically interrelated due to modulating activity in overlapping brain networks. However, the direct influence of working memory on the spatio-temporal brain dynamics of behaviorally relevant intervening information remains unclear. To investigate this issue, subjects performed a visual proximity grid perception task under three different visual-spatial working memory (VSWM) load conditions. VSWM load was manipulated by asking subjects to memorize the spatial locations of 6 or 3 disks. The grid was always presented between the encoding and recognition of the disk pattern. As a baseline condition, grid stimuli were presented without a VSWM context. VSWM load altered both perceptual performance and neural networks active during intervening grid encoding. Participants performed faster and more accurately on a challenging perceptual task under high VSWM load as compared to the low load and the baseline condition. Visual evoked potential (VEP) analyses identified changes in the configuration of the underlying sources in one particular period occurring 160-190 ms post-stimulus onset. Source analyses further showed an occipito-parietal down-regulation concurrent to the increased involvement of temporal and frontal resources in the high VSWM context. Together, these data suggest that cognitive control mechanisms supporting working memory may selectively enhance concurrent visual processing related to an independent goal. More broadly, our findings are in line with theoretical models implicating the engagement of frontal regions in synchronizing and optimizing mnemonic and perceptual resources towards multiple goals.

A game theoretical approach to the algebraic counterpart of the Wagner hierarchy

La hiérarchie de Wagner constitue à ce jour la plus fine classification des langages ω-réguliers. Par ailleurs, l'approche algébrique de la théorie de langages formels montre que ces ensembles ω-réguliers correspondent précisément aux langages reconnaissables par des ω-semigroupes finis pointés. Ce travail s'inscrit dans ce contexte en fournissant une description complète de la contrepartie algébrique de la hiérarchie de Wagner, et ce par le biais de la théorie descriptive des jeux de Wadge. Plus précisément, nous montrons d'abord que le degré de Wagner d'un langage ω-régulier est effectivement un invariant syntaxique. Nous définissons ensuite une relation de réduction entre ω-semigroupes pointés par le biais d'un jeu infini de type Wadge. La collection de ces structures algébriques ordonnée par cette relation apparaît alors comme étant isomorphe à la hiérarchie de Wagner, soit un quasi bon ordre décidable de largeur 2 et de hauteur ω. Nous exposons par la suite une procédure de décidabilité de cette hiérarchie algébrique : on décrit une représentation graphique des ω-semigroupes finis pointés, puis un algorithme sur ces structures graphiques qui calcule le degré de Wagner de n'importe quel élément. Ainsi le degré de Wagner de tout langage ω-régulier peut être calculé de manière effective directement sur son image syntaxique. Nous montrons ensuite comment construire directement et inductivement une structure de n''importe quel degré. Nous terminons par une description détaillée des invariants algébriques qui caractérisent tous les degrés de cette hiérarchie. Abstract The Wagner hierarchy is known so far to be the most refined topological classification of ω-rational languages. Also, the algebraic study of formal languages shows that these ω-rational sets correspond precisely to the languages recognizable by finite pointed ω-semigroups. Within this framework, we provide a construction of the algebraic counterpart of the Wagner hierarchy. We adopt a hierarchical game approach, by translating the Wadge theory from the ω-rational language to the ω-semigroup context. More precisely, we first show that the Wagner degree is indeed a syntactic invariant. We then define a reduction relation on finite pointed ω-semigroups by means of a Wadge-like infinite two-player game. The collection of these algebraic structures ordered by this reduction is then proven to be isomorphic to the Wagner hierarchy, namely a well-founded and decidable partial ordering of width 2 and height $\omega^\omega$. We also describe a decidability procedure of this hierarchy: we introduce a graph representation of finite pointed ω-semigroups allowing to compute their precise Wagner degrees. The Wagner degree of every ω-rational language can therefore be computed directly on its syntactic image. We then show how to build a finite pointed ω-semigroup of any given Wagner degree. We finally describe the algebraic invariants characterizing every Wagner degree of this hierarchy.

Food traditions and landscape histories of the Indian Ocean World : theoretical and methodological reflections

Environmental histories of plant exchanges have largely centred on their eco- nomic importance in international trade and on their ecological and social impacts in the places where they were introduced. Yet few studies have at- tempted to examine how plants brought from elsewhere become incorporated over time into the regional cultures of material life and agricultural landscapes. This essay considers the theoretical and methodological problems in inves- tigating the environmental history, diversity and distribution of food plants transferred across the Indian Ocean over several millennia. It brings together concepts of creolisation, syncretism, and hybridity to outline a framework for understanding how biotic exchanges and diffusions have been translated into regional landscape histories through food traditions, ritual practices and articu- lation of cultural identity. We use the banana plant - which underwent early domestication across New Guinea, South-east Asia and peninsular India and reached East Africa roughly two thousand years ago - as an example for il- lustrating the diverse patterns of incorporation into the cultural symbolism, material life and regional landscapes of the Indian Ocean World. We show that this cultural evolutionary approach allows new historical insights to emerge and enriches ongoing debates regarding the antiquity of the plant's diffusion from South-east Asia to Africa.

Developing a theoretical framework using a nursing perspective to investigate perceived health in the "Sandwich Generation" group

Coexisting workloads from professional, household and family, and caregiving activities for frail parents expose middle-aged individuals, the so-called "Sandwich Generation", to potential health risks. Current trends suggest that this situation will continue or increase. Thus SG health promotion has become a nursing concern. Most existing research considers coexisting workloads a priori pathogenic. Most studies have examined the association of one, versus two, of these three activities with health. Few studies have used a nursing perspective. This article presents the development of a framework based on a nursing model. We integrated Siegrist's Effort-Reward Imbalance middle-range theory into "Neuman Systems Model". The latter was chosen for its salutogenic orientation, its attention to preventive nursing interventions and the opportunity it provides to simultaneously consider positive and negative perceptions of SG health and SG coexisting workloads. Finally, it facilitated a theoretical identification of health protective factors.

The local configuration of a science and innovation policy : a city into the nanoworld

Local trajectories and arrangements play a significant role because the development of a research field, such as nanoscience and nanotechnology, requires substantial investments in human and instrumental resources. But why are there often concentrated in a limited number of places? What dynamics lead to such concentration? The hypothesis is that there is an assemblage of heterogeneous resources through the action of local actors. The chapter will explore, from an Actor Network Theory (ANT) perspective, how the local emergence of research dynamics from: the revival of local traditions, the local and national action of institutional entrepreneurs, controversial dynamics, and researchers' arrangements to involve other actors. It will examine how they connect up with each other and mutually commit themselves to the development of new technologies. It will focus on the role of narratives in this assembling: how were the local narratives of the past mobilized and to what effect.