Química de l'espín prohibit: la importància dels intermedis a capa oberta en l'activació d'enllaços C-H

Estudi realitzat a partir d’una estada a la School of Chemistry de la University of Bristol, Gran Bretanya, entre 2006 i 2008. La reacció d’activació del pre-catalitzador CH3-Fe(P(iPr)2CH2)3B-Ph, que es dóna en presència de H2 i P(CH3)3, és una reacció spin-prohibida ja que els reactius i els productes tenen diferents estat d’espín en el seu estat fonamental: el pre-catalitzador és quintet, mentre que el producte format després de l’eliminació de metà, PMe3(H3)-Fe[(P(iPr)2CH2)3B-Ph, és singlet. Un dels intermedis d’aquesta reacció és d’especial interès ja que catalitza la hidrogenació d’olefines. Intermedi que experimentalment s’ha proposat com a H-Fe[(P(iPr)2CH2)3B-Ph] o el Hx-Fe[(P(iPr)2CH2)3B-Ph]. Aquestes espècies han estat estudiades computacionalment, mitjançant la combinació de mètodes del funcional de la densitat calibrats mitjançant càlculs ab initio. Els resultats obtinguts mostren que les superfícies d’energia potencial singlet, triplet i quintet es creuen al llarg de les reaccions descrites. La reacció d’activació del pre-catalitzador és una reacció multi spin-prohibida (més d’un canvi d’espín), en la que el mecanisme preferit addiciona primer hidrogen i després la fosfina, el pas determinant de la velocitat és el creuament de la superfície d’energia potencial quintet a la triplet a la geometria del reactiu, que es produeix amb una barrera d’aproximadament 18 kcal/mol. La reacció d’hidrogenació d’olefines en canvi pot ser o no una reacció espín prohibida depenent de les condicions en que es dugui a terme. En cas de que la reacció es dugui a terme en un excés d’hidrogen, en el mecanisme principal l’espècie activa seria el (H2)H-Fe[(P(iPr)2CH2)3B-Ph] singlet en el seu estat fonamental que hidrogenaria l’olefina sense cap pas espín prohibit. Aquest mecanisme és el de barrera més baixa però s’espera que estigui més desafavorit entropicament. Si les condicions no són d’un important excés d’hidrogen, llavors l’espècie activa s’espera que sigui H-Fe[(P(iPr)2CH2)3B-Ph], la reacció llavors seria multi espín prohibida amb una barrera de unes 13 kcal/mol corresponents al creuament entre la superfície quintet i triplet a la geometria del H-Fe[(P(iPr)2CH2)3B-Ph].

Dominance Solvable Games with Multiple Payoff Criteria.

Two logically distinct and permissive extensions of iterative weak dominance are introduced for games with possibly vector-valued payoffs. The first, iterative partial dominance, builds on an easy-to check condition but may lead to solutions that do not include any (generalized) Nash equilibria. However, the second and intuitively more demanding extension, iterative essential dominance, is shown to be an equilibrium refinement. The latter result includes Moulin’s (1979) classic theorem as a special case when all players’ payoffs are real-valued. Therefore, essential dominance solvability can be a useful solution concept for making sharper predictions in multicriteria games that feature a plethora of equilibria.

Choice, Deferral and Consistency

In this paper we study decision making in situations where the individual’s preferences are not assumed to be complete. First, we identify conditions that are necessary and sufficient for choice behavior in general domains to be consistent with maximization of a possibly incomplete preference relation. In this model of maximally dominant choice, the agent defers/avoids choosing at those and only those menus where a most preferred option does not exist. This allows for simple explanations of conflict-induced deferral and choice overload. It also suggests a criterion for distinguishing between indifference and incomparability based on observable data. A simple extension of this model also incorporates decision costs and provides a theoretical framework that is compatible with the experimental design that we propose to elicit possibly incomplete preferences in the lab. The design builds on the introduction of monetary costs that induce choice of a most preferred feasible option if one exists and deferral otherwise. Based on this design we found evidence suggesting that a quarter of the subjects in our study had incomplete preferences, and that these made significantly more consistent choices than a group of subjects who were forced to choose. The latter effect, however, is mitigated once data on indifferences are accounted for.

Dynamic Relational Contracts under Complete Information

This paper considers a long-term relationship between two agents who both undertake a costly action or investment that together produces a joint benefit. Agents have an opportunity to expropriate some of the joint benefit for their own use. Two cases are considered: (i) where agents are risk neutral and are subject to limited liability constraints and (ii) where agents are risk averse, have quasi-linear preferences in consumption and actions but where limited liability constraints do not bind. The question asked is how to structure the investments and division of the surplus over time so as to avoid expropriation. In the risk-neutral case, there may be an initial phase in which one agent overinvests and the other underinvests. However, both actions and surplus converge monotonically to a stationary state in which there is no overinvestment and surplus is at its maximum subject to the constraints. In the risk-averse case, there is no overinvestment. For this case, we establish that dynamics may or may not be monotonic depending on whether or not it is possible to sustain a first-best allocation. If the first-best allocation is not sustainable, then there is a trade-off between risk sharing and surplus maximization. In general, surplus will not be at its constrained maximum even in the long run.

Choosing on Influence

Interaction, the act of mutual influence between two or more individuals, is an essential part of daily life and economic decisions. Yet, micro-foundations of interaction are unexplored. This paper presents a first attempt to this purpose. We study a decision procedure for interacting agents. According to our model, interaction occurs since individuals seek influence for those issues that they cannot solve on their own. Following a choice-theoretic approach, we provide simple properties that aid to detect interacting individuals. In this case, revealed preference analysis not only grants the underlying preferences but also the influence acquired. Our baseline model is based on two interacting individuals, though we extend the analysis to multi-individual environments.

Influence of age, risk factors, and cardiovascular and renal disease on arterial stiffness: clinical applications.

Age is the main clinical determinant of large artery stiffness. Central arteries stiffen progressively with age, whereas peripheral muscular arteries change little with age. A number of clinical studies have analyzed the effects of age on aortic stiffness. Increase of central artery stiffness with age is responsible for earlier wave reflections and changes in pressure wave contours. The stiffening of aorta and other central arteries is a potential risk factor for increased cardiovascular morbidity and mortality. Arterial stiffening with aging is accompanied by an elevation in systolic blood pressure (BP) and pulse pressure (PP). Although arterial stiffening with age is a common situation, it has now been confirmed that older subjects with increased arterial stiffness and elevated PP have higher cardiovascular morbidity and mortality. Increase in aortic stiffness with age occurs gradually and continuously, similarly for men and women. Cross-sectional studies have shown that aortic and carotid stiffness (evaluated by the pulse wave velocity) increase with age by approximately 10% to 15% during a period of 10 years. Women always have 5% to 10% lower stiffness than men of the same age. Although large artery stiffness increases with age independently of the presence of cardiovascular risk factors or other associated conditions, the extent of this increase may depend on several environmental or genetic factors. Hypertension may increase arterial stiffness, especially in older subjects. Among other cardiovascular risk factors, diabetes type 1 and 2 accelerates arterial stiffness, whereas the role of dyslipidemia and tobacco smoking is unclear. Arterial stiffness is also present in several cardiovascular and renal diseases. Patients with heart failure, end stage renal disease, and those with atherosclerotic lesions often develop central artery stiffness. Decreased carotid distensibility, increased arterial thickness, and presence of calcifications and plaques often coexist in the same subject. However, relationships between these three alterations of the arterial wall remain to be explored.

Predator-prey chemical warfare determines the expression of biocontrol genes by rhizosphere-associated Pseudomonas fluorescens.

Soil bacteria are heavily consumed by protozoan predators, and many bacteria have evolved defense strategies such as the production of toxic exometabolites. However, the production of toxins is energetically costly and therefore is likely to be adjusted according to the predation risk to balance the costs and benefits of predator defense. We investigated the response of the biocontrol bacterium Pseudomonas fluorescens CHA0 to a common predator, the free-living amoeba Acanthamoeba castellanii. We monitored the effect of the exposure to predator cues or direct contact with the predators on the expression of the phlA, prnA, hcnA, and pltA genes, which are involved in the synthesis of the toxins, 2,4-diacetylphloroglucinol (DAPG), pyrrolnitrin, hydrogen cyanide, and pyoluteorin, respectively. Predator chemical cues led to 2.2-, 2.0-, and 1.2-fold increases in prnA, phlA, and hcnA expression, respectively, and to a 25% increase in bacterial toxicity. The upregulation of the tested genes was related to the antiprotozoan toxicity of the corresponding toxins. Pyrrolnitrin and DAPG had the highest toxicity, suggesting that bacteria secrete a predator-specific toxin cocktail. The response of the bacteria was elicited by supernatants of amoeba cultures, indicating that water-soluble chemical compounds were responsible for induction of the bacterial defense response. In contrast, direct contact of bacteria with living amoebae reduced the expression of the four bacterial toxin genes by up to 50%, suggesting that protozoa can repress bacterial toxicity. The results indicate that predator-prey interactions are a determinant of toxin production by rhizosphere P. fluorescens and may have an impact on its biocontrol potential.

La programació al servei de la matemàtica

Treball de recerca realitzat per un alumne d'ensenyament secundari i guardonat amb un Premi CIRIT per fomentar l'esperit cientí­fic del Jovent l'any 2009. La programació al servei de la matemàtica és un programa informàtic fet amb Excel i Visual Basic. Resol equacions de primer grau, equacions de segon grau, sistemes d'equacions lineals de dues equacions i dues incògnites, sistemes d'equacions lineals compatibles determinats de tres equacions i tres incògnites i troba zeros de funcions amb el teorema de Bolzano. En cadascun dels casos, representa les solucions gràficament. Per a això, en el treball s'ha hagut de treballar, en matemàtiques, amb equacions, nombres complexos, la regla de Cramer per a la resolució de sistemes, i buscar la manera de programar un mètode iteratiu pel teorema de Bolzano. En la part gràfica, s'ha resolt com fer taules de valors amb dues i tres variables i treballar amb rectes i plans. Per la part informàtica, s'ha emprat un llenguatge nou per l'alumne i, sobretot, ha calgut saber decidir on posar una determinada instrucció, ja que el fet de variar-ne la posició una sola lí­nea ho pot canviar tot. A més d'això, s'han resolt altres problemes de programació i també s'ha realitzat el disseny de pantalles.

Estudi de la successió primària en esculls artificials en un port marítim

Treball de recerca realitzat per una alumna d'ensenyament secundari i guardonat amb un Premi CIRIT per fomentar l'esperit científic del Jovent l'any 2009. La llum i el temps són factors importants en tots els ecosistemes i especialment en ecosistemes aquàtics, ja que constitueixen variables ambientals que condicionen la seva evolució i equilibri. L’objectiu principal del treball de recerca és estudiar el desenvolupament de les successions primàries all llarg del temps en esculls artificials submergits en un ambient marí i observar les conseqüències de la incidència, directa o no, de la llum en aquests esculls pel que fa al desenvolupament de la successions primàries. Els resultats obtinguts demostren satisfactòriament que la incidència de la llum és un factor determinant en la constitució de les successions primàries en ambients marins. Per altra part, els resultats també demostren que el temps és un factor que actua condicionant la diversitat de les formes de vida que colonitzen aquests medis marins, concretament la diversitat s’incrementa amb el temps.

Inconsistency between different measures of sexual selection.

Measuring the intensity of sexual selection is of fundamental importance to the study of sexual dimorphism, population dynamics, and speciation. Several indices, pools of individuals, and fitness proxies are used in the literature, yet their relative performances are strongly debated. Using 12 independent common lizard populations, we manipulated the adult sex ratio, a potentially important determinant of the intensity of sexual selection at a particular time and place. We investigated differences in the intensity of sexual selection, as estimated using three standard indices of sexual selection-the standardized selection gradient (β'), the opportunity of selection (I), and the Bateman gradient (βss)--calculated for different pools of individuals and different fitness proxies. We show that results based on estimates of I were the opposite of those derived from the other indices, whereas results based on estimates of β' were consistent with predictions derived from knowledge about the species' mating system. In addition, our estimates of the strength and direction of sexual selection depended on both the fitness proxy used and the pool of individuals included in the analysis. These observations demonstrate inconsistencies in distinct measures of sexual selection and underscore the need for caution when comparing studies and species.

Estudi comparatiu del sòl d'una vinya de Sant Pere de Ribes

Treball de recerca realitzat per una alumna d'ensenyament secundari i guardonat amb un Premi CIRIT per fomentar l'esperit científic del Jovent l'any 2009. Anàlisi comparatiu de diferents propietats del sòl d’una vinya on s’ha observat que els peus presenten un creixement desigual. A partir d'una observació a simple vista de les plantes de la vinya i del sòl sobre el qual es desenvolupen, es proposa la hipòtesi de que el sòl pot ser un factor determinant per aquest creixement desigual. Després de fer una recerca bibliogràfica sobre l’edafologia, les propietats del sòl i els tipus de sòl que es poden trobar als voltants de Sant Pere de Ribes, l’autora ha fet una selecció de propietats físico-químiques que poden estar més relacionades amb el creixement de les plantes. Després de fer el mostreig i seguir els protocols de laboratori s’han analitzat els resultats i s’han redactat les conclusions. Les propietats estudiades han permès determinar els tipus de sòl, uns sòls de textures entre franco-arenoses i areno-franques. S’ha trobat també una correlació entre les diverses propietats estudiades: un sòl de porositat elevada, que presenta valors alts de velocitat d’infiltració i per tant amb baixa capacitat de retenció d’aigua disponible, no sembla el sòl ideal per al desenvolupament de les plantes de vinya. A partir del treball es plantegen noves incògnites sobre les adaptacions dels ceps a aquests tipus de sòl o sobre la qualitat del raïm que s'hi pot desenvolupar.

Metropolitan Areas in Spain and Italy

Metropolitan areas concentrate the main share of population, production and consumption in OECD countries. They are likely to be the most important units for economic, social and environmental analysis as well as for the development of policy strategies. However, one of the main problems that occur when adopting metropolitan areas as units of analysis and policy in European countries is the absence of widely accepted standards for identifying them. This severe problem appeared when we tried to perform comparative research between Spain and Italy using metropolitan areas as units of analysis. The aim of this paper is to identify metropolitan areas in Spain and Italy using similar methodologies. The results allow comparing the metropolitan realities of both countries as well as providing the metropolitan units that can be used in subsequent comparative researches. Two methodologies are proposed: the Cheshire-GEMACA methodology (FUR) and an iterative version of the USA-MSA algorithm, particularly adapted to deal with polycentric metropolitan areas (DMA). Both methods show a good approximation to the metropolitan reality and produce very similar results: 75 FUR and 67 DMA in Spain (75% of total population and employment), and 81 FUR and 86 DMA in Italy (70% of total population and employment).

Genetic survey of "spinturnix sp" (Acari, Mesostigmata) and their bat hosts in Western Palearctic

SUMMARY : The coevolution between two intimately associated organisms, like host and parasite, is a widely investigated theme in evolutionary biology. Recently, the use of genetic data in the study of host-parasite systems evidences that the genetic information from some parasites can complement genetic data from their hosts and thus may help to better understand their host's evolutionary history. Phylogenetic and population genetic aspects of bat parasites have been poorly investigated. Spinturnicid mites are highly specialized ectoparasites, exclusively associated with bats and therefore represent an ideal model to extant our knowledge on bat and parasite biology and on their coevolutionary history. In this thesis, I developed several molecular markers (mitochondrial DNA) to compare the genetic patterns of Spinturnix mites with their bat hosts at different levels. The molecular co-phylogeny between Spinturnix sp. and their bat hosts suggests a partial cospeciation and the occurrence of failure to speciate events and multiple host switches. Thus, Spinturnix mites do not exactly mirror the phylogenetic pattern of their hosts, despite their intimate association. Similar roosting habits of the hosts seem to promote host switches between different species, as far as ecological conditions are favourable. The phylogeographic study of the Maghrebian bat M. punicus in the Mediterranean area confirms the presence of M. punicus in North Africa, Corsica and Sardinia and highlights that islands and mainland are genetically highly divergent. The comparison between the parasitic mite S. myoti and the Maghrebian bat suggests that the phylogeographic pattern of the mite is moulded by its host, with open water as main barrier for host and parasite dispersal. Moreover, the unique presence of a European S. myoti lineage on M. punicus from Corsica strongly suggests the former presence of mouse-eared bats (M. myotis and/or M. blythii) in Corsica. By highlighting the probable presence of a nowadays locally extinct host species, S. myoti may represent a good proxy for inferring complex evolutionary history of bat hosts. Finally, population genetic surveys of S. myoti and S. bechsteinii suggest that these mites benefit from close contacts between individuals during the mating season and/or hibernation to disperse among remote colonies. The contrasted genetic patterns of these two distinct bat-mite systems evidence that bat social structure is a determinant factor of the genetic structure of mite populations. Altogether, this PhD thesis demonstrates the usefulness of parasites to gather information about their bat hosts. In addition, my results illustrate how different ecological and biological characteristics of bat species allow the emergence of a surprising diversity in the genetic patterns of the parasites, which may contribute to the diversification and speciation of parasites. RESUME : La co-évolution entre deux organismes intimement liés, comme un parasite et son hôte, fait partie des questions largement étudiées en biologie évolutive. Récemment, l'utilisation de données génétique dans l'étude des interactions hôte-parasite a montré que l'information génétique de certains parasites peut compléter les données génétiques de l'hôte et ainsi peut éclairer l'histoire évolutive de leur hôte. Très peu études ont étudié les interactions entre les chauves-souris et leurs parasites d'un point de vue moléculaire. Les acariens du genre Spinturnix sont des ectoparasites très spécialisés exclusivement associés aux chauves-souris. Ils représentent donc un model idéal pour élargir nos connaissances tant sur l'écologie des parasites de chauves-souris que sur leur coévolution. Durant cette thèse, plusieurs marqueurs moléculaires (ADN mitochondrial) ont été développés pour ainsi comparer la distribution de la variation génétique des parasites du genre Spinturnix avec celle de leurs hôtes, et ceci à différents niveaux. Tout d'abord, la co-phylogénie moléculaire entre les espèces de Spinturnix et les leurs hôtes révèle une co-spéciation partielle ainsi que la présence d'événement de non spéciation et de transferts horizontaux. Ces parasites ne reflètent donc pas entièrement l'histoire évolutive de leurs hôtes, malgré leurs intimes associations. La cohabitation de plusieurs espèces de chauves-souris dans un même gîte permet aux parasites un transfert entre différentes espèces, atténuant ainsi leur degré de co-spéciation. Deuxièmement, l'étude phylogéographique du marin du Maghreb dans le bassin Méditerranéen confirme sa présence en Afrique du Nord, en Corse et en Sardaigne. La comparaison avec un de ses parasites S. myoti suggère que la répartition génétique de S. myoti est façonnée par celle de leurs hôtes, avec les étendues d'eau comme barrière principale tant à la dispersion de l'hôte que de son parasite. De plus, la présence unique d'une lignée européenne de ces parasites sur des marins du Maghreb de Corse suggère fortement la présence du grand ou petit marin en Corse dans le passé. En reflétant la présence potentielle à un endroit donné d'une espèce de chauve-souris actuellement disparue, S. myoti peut représenter une bonne alternative pour comprendre l'histoire évolutive complexe des chauves-souris. Finalement, l'étude des structures génétiques des populations des parasites S. myoti et S. bechsteinii suggère que les contacts corporels entre chauves-souris durant la saison de reproduction ou l'hibernation peuvent permettre la dispersion des parasites entre des colonies éloignées géographiquement. La différence de structure génétique entre ces deux associations particulières montre que la structure génétique des populations de parasites dépend fortement des traits d'histoire de vie de son hôte. Dans l'ensemble, cette thèse démontre l'importance des parasites pour amener des informations sur leurs hôtes, les chauves-souris. Elle illustre aussi comment les différences écologique et biologique des différentes espèces de chauves-souris peuvent amener une étonnante diversité de structure génétique au sein de populations de parasites, ce qui peut peut-être contribuer à la diversification et à la spéciation des parasites.

Evaluation of the impact of a therapeutic drug monitoring program in a Swiss University Hospital

Background and objective: Therapeutic Drug Monitoring (TDM) has been introduced early 1970 in our hospital (CHUV). It represents nowadays an important routine activity of the Division of Clinical Pharmacology and Toxicology (PCL), and its impact and utility for clinicians required assessment. This study thus evaluated the impact of TDM recommendations in terms of dosage regimen adaptation. Design: A prospective observational study was conducted over 5 weeks. The primary objective was to evaluate the application of our TDM recommendations and to identify potential factors associated to variations in their implementation. The secondary objective was to identify pre-analytical problems linked to the collection and processing of blood samples. Setting: Four representative clinical units at CHUV. Main outcome measure: Clinical data, drug related data (intake, collection and processing) and all information regarding the implementation of clinical recommendations were collected and analyzed by descriptive statistics. Results: A total of 241 blood measurement requests were collected, among which 105 triggered a recommendation. 37% of the recommendations delivered were applied, 25 % partially applied and 34% not applied. In 4% it was not applicable. The factors determinant for implementation were the clinical unit and the mode of transmission of the recommendation (written vs oral). No clear difference between types of drugs could be detected. Pre-analytical problems were not uncommon, mostly related to completion of request forms and delays in blood sampling (equilibration or steady-state not reached). We have identified 6% of inappropriate and unusable drug level measurements that could cause a substantial cost for the hospital. Conclusion: This survey highlighted a better implementation of TDM recommendations in clinical units where this routine is well integrated and understood by the medical staff. Our results emphasize the importance of communication with the nurse or the physician in charge, either to transmit clinical recommendations or to establish consensual therapeutic targets in specific conditions. Development of strong partnerships between clinical pharmacists or pharmacologists and clinical units would be beneficial to improve the impact of this clinical activity.

Generic optimality conditions for semi-algebraic convex programs

We consider linear optimization over a nonempty convex semi-algebraic feasible region F. Semidefinite programming is an example. If F is compact, then for almost every linear objective there is a unique optimal solution, lying on a unique \active" manifold, around which F is \partly smooth", and the second-order sufficient conditions hold. Perturbing the objective results in smooth variation of the optimal solution. The active manifold consists, locally, of these perturbed optimal solutions; it is independent of the representation of F, and is eventually identified by a variety of iterative algorithms such as proximal and projected gradient schemes. These results extend to unbounded sets F.