Duplication and concerted evolution in a master sex determiner under balancing selection.

The transformer (tra) gene is a key regulator in the signalling hierarchy controlling all aspects of somatic sexual differentiation in Drosophila and other insects. Here, we show that six of the seven sequenced ants have two copies of tra. Surprisingly, the two paralogues are always more similar within species than among species. Comparative sequence analyses indicate that this pattern is owing to the ongoing concerted evolution after an ancestral duplication rather than independent duplications in each of the six species. In particular, there was strong support for inter-locus recombination between the paralogues of the ant Atta cephalotes. In the five species where the location of paralogues is known, they are adjacent to each other in four cases and separated by only few genes in the fifth case. Because there have been extensive genomic rearrangements in these lineages, this suggests selection acting to conserve their synteny. In three species, we also find a signature of positive selection in one of the paralogues. In three bee species where information is available, the tra gene is also duplicated, the copies are adjacent and in at least one species there was recombination between paralogues. These results suggest that concerted evolution plays an adaptive role in the evolution of this gene family.

The Point system of selection of immigrants in Quebec

The present paper is aimed at identifying what are the effects of the Point System of Selection of immigrants in Quebec. I defend that the distribution of points results in a different composition of immigrant stocks in terms of origin mix and not in terms of labour skills. To do so, I carry out a longitudinal descriptive analysis on the national composition of immigrants in Quebec and two other significant provinces (Ontario and British Columbia), as well as an analysis of the distribution of points in Quebec and in the rest of Canada.

Thymic lineage commitment rather than selection causes genetic variations in size of CD4 and CD8 compartments.

During their development, immature CD4+ CD8+ thymocytes become committed to either the CD4 or CD8 lineage. Subsequent complete maturation of CD4+ and CD8+ cells requires a molecular match of the expressed coreceptor and the MHC specificity of the TCR. The final size of the mature CD4+ and CD8+ thymic compartments is therefore determined by a combination of lineage commitment and TCR-mediated selection. In humans and mice, the relative size of CD4+ and CD8+ peripheral T cell compartments shows marked genetic variability. We show here that genetic variations in thymic lineage commitment, rather than TCR-mediated selection processes, are responsible for the distinct CD4/CD8 ratios observed in common inbred mouse strains. Genetic variations in the regulation of lineage commitment open new ways to analyze this process and to identify the molecules involved.

Sélection et suivi prétransplantation des patients candidats à la greffe cardiaque en Suisse romande [Selection and preoperative follow-up of heart transplantation candidates in the French part of Switzerland].

Heart transplantation (HTx) started in 1987 at two university hospitals (CHUV, HUG) in the western part of Switzerland, with 223 HTx performed at the CHUV until December 2010. Between 1987 and 2003, 106 HTx were realized at the HUG resulting in a total of 329 HTx in the western part of Switzerland. After the relocation of organ transplantation activity in the western part of Switzerland in 2003, the surgical part and the early postoperative care of HTx remained limited to the CHUV. However, every other HTx activity are pursued at the two university hospitals (CHUV, HUG). This article summarizes the actual protocols for selection and pre-transplant follow-up of HTx candidates in the western part of Switzerland, permitting a uniform structure of pretransplant follow-up in the western part of Switzerland.

An adult thymic stromal-cell suspension model for in vitro positive selection.

Presented here is a cell-suspension model for positive selection using thymocytes from alphabeta-TCR (H-2Db-restricted) transgenic mice specific to the lymphocytic choriomeningitis virus (LCMV) on a nonselecting MHC background (H-2d or TAP-1 -/-), cocultured with freshly isolated adult thymus stromal cells of the selecting MHC type. The thymic stromal cells alone induced positive selection of functional CD4- CD8+ cells whose kinetics and efficiency were enhanced by nominal peptide. Fibroblasts expressing the selecting MHC alone did not induce positive selection; however, together with nonselecting stroma and nominal peptide, there was inefficient positive. These results suggest multiple signaling in positive selection with selection events able to occur on multiple-cell types. The ease with which this model can be manipulated should greatly facilitate the resolution of the mechanisms of positive selection in normal and pathological states.

A limited role for beta-selection during gamma delta T cell development.

T cells belong to two distinct lineages expressing either alpha beta or gamma delta TCR. During alpha beta T cell development, it is clearly established that productive rearrangement at the TCR beta locus in immature precursor cells leads to the expression of a pre-TCR complex. Signaling through the pre-TCR results in the selective proliferation and maturation of TCR beta+ cells, a process that is known as beta-selection. However, the potential role of beta-selection during gamma delta T cell development is controversial. Whereas PCR-RFLP and sequencing techniques have provided evidence for a bias toward in-frame VDJ beta rearrangements in gamma delta cells (consistent with beta-selection), gamma delta cells apparently develop normally in mice that are unable to assemble a pre-TCR complex due to a deficiency in TCR beta or pT alpha genes. In this report, we have directly addressed the physiologic significance of beta-selection during gamma delta cell development in normal mice by quantitating intracellular TCR beta protein in gamma delta cells and correlating its presence with cell cycle status. Our results indicate that beta-selection plays a significant (although limited) role in gamma delta cell development by selectively amplifying a minor subset of gamma delta precursor cells with productively rearranged TCR beta genes.

The automatic selection of ventilation parameters during the initial phase of mechanical ventilation.

OBJECTIVE: To test a method that allows automatic set-up of the ventilator controls at the onset of ventilation. DESIGN: Prospective randomized crossover study. SETTING: ICUs in one adult and one children's hospital in Switzerland. PATIENTS: Thirty intubated stable, critically ill patients (20 adults and 10 children). INTERVENTIONS: The patients were ventilated during two 20-min periods using a modified Hamilton AMADEUS ventilator. During the control period the ventilator settings were chosen immediately prior to the study. During the other period individual settings were automatically determined by the ventilatior (AutoInit). MEASUREMENTS AND RESULTS: Pressure, flow, and instantaneous CO2 concentration were measured at the airway opening. From these measurements, series dead space (V(DS)), expiratory time constant (RC), tidal volume (VT, total respiratory frequency (f(tot), minute ventilation (MV), and maximal and mean airway pressure (Paw, max and Paw, mean) were calculated. Arterial blood gases were analyzed at the end of each period. Paw, max was significantly less with the AutoInit ventilator settings while f(tot) was significantly greater (P < 0.05). The other values were not statistically significant. CONCLUSIONS: The AutoInit ventilator settings, which were automatically derived, were acceptable for all patients for a period of 20 min and were not found to be inferior to the control ventilator settings. This makes the AutoInit method potentially useful as an automatic start-up procedure for mechanical ventilation.

Endogenous Credit Cycles and Financial Dampening in an Adverse Selection Economy

We propose an adverse selection framework in which the financial sector has a dual role. It amplifies or dampens exogenous shocks and also generates endogenous fluctuations. We fully characterize constrained optimal contracts in a setting in which entrepreneurs need to borrow and are privately informed about the quality of their projects. Our characterization is novel in analyzing pooling and separating allocations in a context of multi-dimensional screening: specifically, the amounts of investment undertaken and of entrepreneurial net worth are used to screen projects. We then embed these results in a dynamic competitive economy. First, we show how endogenous regime switches in financial contracts may generate fluctuations in an economy that exhibits no dynamics under full information. Unlike previous models of endogenous cycles, our result does not rely on entrepreneurial net worth being counter-cyclical or inconsequential for determining investment. Secondly, the model shows the different implications of adverse selection as opposed to pure moral hazard. In particular, and contrary to standard results in the macroeconomic literature, the financial system may dampen exogenous shocks in the presence of adverse selection.

Adverse Selection, Credit, and Efficiency: the Case of the Missing Market

We analyze a standard environment of adverse selection in credit markets. In our envi- ronment, entrepreneurs who are privately informed about the quality of their projects need to borrow from banks. As is generally the case in economies with adverse selection, the competitive equilibrium of our economy is shown to be ine¢ cient. Under adverse selection, the choices made by one type of agents limit what can be o¤ered to other types in an incentive-compatible manner. This gives rise to an externality, which cannot be internalized in a competitive equilibrium. We show that, in this type of environment, the ine¢ ciency associated to adverse selection is the consequence of one implicit assumption: entrepreneurs can only borrow from banks. If an additional market is added (say, a .security market.), in which entrepreneurs can obtain funds beyond those o¤ered by banks, we show that the e¢ cient allocation is an equilibrium of the economy. In such an equilibrium, all entrepreneurs borrow at a pooling rate in the security market. When they apply to bank loans, though, only entrepreneurs with good projects pledge these additional funds as collateral. This equilibrium thus simultaneously entails cross- subsidization and separation between di¤erent types of entrepreneurs.

On Certain Greedoid Polyhedra, Partially Indexable Scheduling Problems, and Extended Restless Bandit Allocation Indices

We present a polyhedral framework for establishing general structural properties on optimal solutions of stochastic scheduling problems, where multiple job classes vie for service resources: the existence of an optimal priority policy in a given family, characterized by a greedoid (whose feasible class subsets may receive higher priority), where optimal priorities are determined by class-ranking indices, under restricted linear performance objectives (partial indexability). This framework extends that of Bertsimas and Niño-Mora (1996), which explained the optimality of priority-index policies under all linear objectives (general indexability). We show that, if performance measures satisfy partial conservation laws (with respect to the greedoid), which extend previous generalized conservation laws, then the problem admits a strong LP relaxation over a so-called extended greedoid polytope, which has strong structural and algorithmic properties. We present an adaptive-greedy algorithm (which extends Klimov's) taking as input the linear objective coefficients, which (1) determines whether the optimal LP solution is achievable by a policy in the given family; and (2) if so, computes a set of class-ranking indices that characterize optimal priority policies in the family. In the special case of project scheduling, we show that, under additional conditions, the optimal indices can be computed separately for each project (index decomposition). We further apply the framework to the important restless bandit model (two-action Markov decision chains), obtaining new index policies, that extend Whittle's (1988), and simple sufficient conditions for their validity. These results highlight the power of polyhedral methods (the so-called achievable region approach) in dynamic and stochastic optimization.

Adverse selection, credit, and efficiency: the case of the missing market

We analyze a standard environment of adverse selection in credit markets. In our environment, entrepreneurs who are privately informed about the quality of their projects need to borrow in order to invest. Conventional wisdom says that, in this class of economies, the competitive equilibrium is typically inefficient. We show that this conventional wisdom rests on one implicit assumption: entrepreneurs can only access monitored lending. If a new set of markets is added to provide entrepreneurs with additional funds, efficiency can be attained in equilibrium. An important characteristic of these additional markets is that lending in them must be unmonitored, in the sense that it does not condition total borrowing or investment by entrepreneurs. This makes it possible to attain efficiency by pooling all entrepreneurs in the new markets while separating them in the markets for monitored loans.

Optimal Contracts, Adverse Selection, and Social Preferences: An Experiment

It has long been standard in agency theory to search for incentive-compatible mechanisms on the assumption that people care only about their own material wealth. However, this assumption is clearly refuted by numerous experiments, and we feel that it may be useful to consider nonpecuniary utility in mechanism design and contract theory. Accordingly, we devise an experiment to explore optimal contracts in an adverse-selection context. A principal proposes one of three contract menus, each of which offers a choice of two incentive-compatible contracts, to two agents whose types are unknown to the principal. The agents know the set of possible menus, and choose to either accept one of the two contracts offered in the proposed menu or to reject the menu altogether; a rejection by either agent leads to lower (and equal) reservation payoffs for all parties. While all three possible menus favor the principal, they do so to varying degrees. We observe numerous rejections of the more lopsided menus, and approach an equilibrium where one of the more equitable contract menus (which one depends on the reservation payoffs) is proposed and agents accept a contract, selecting actions according to their types. Behavior is largely consistent with all recent models of social preferences, strongly suggesting there is value in considering nonpecuniary utility in agency theory.

Monoclonal antibodies to carcinoembryonic antigen: ionic strength as a factor in the selection of antibodies for immunoscintigraphy.

As part of an ongoing effort to improve the technique of immunoscintigraphy for the detection of human carcinomas with radiolabeled monoclonal antibodies (MABs) to carcinoembryonic antigen (CEA), we have developed a series of MABs to CEA and have studied the effects of low- and physiological molarity buffers on their CEA binding and affinity, as well as their cross-reactivity with granulocyte glycoprotein(s). These in vitro results in different buffer systems were then correlated with the use of these MABs to CEA in the detection of human colon carcinoma grafts in nude mice. Our results show that the binding of CEA by some MABs is influenced by ionic strength and that this may be an important factor in their successful use for the immunolocalization of carcinomas in vivo.

A Model of Collateral, Investment, and Adverse Selection

This paper characterizes the relationship between entrepreneurial wealth and aggregate investment under adverse selection. Its main finding is that such a relationship need not be monotonic. In particular, three results emerge from the analysis: (i) pooling equilibria, in which investment is independent of entrepreneurial wealth, are more likely to arise when entrepreneurial wealth is relatively low; (ii) separating equilibria, in which investment is increasing in entrepreneurial wealth, are most likely to arise when entrepreneurial wealth is relatively high and; (iii) for a given interest rate, an increase in entrepreneurial wealth may generate a discontinuous fall in investment.

Pheomelanin-based colouration is correlated with indices of flying strategies in the barn owl

Resource polymorphism refers to individuals from the same population foraging in alternative habitats or on alternative food. Food specialization can be associated with adaptations such as colour polymorphism, with pale and dark colours conferring differential camouflage in different habitats. Pale and dark-reddish pheomelanic Barn Owls (Tyto alba) forage on different prey species in closed and open habitats, respectively. We show here that darker-reddish owls have heavier stomach content when found dead, and their 5th secondary wing feather is more deeply anchored inside the integument. These correlations suggest that their feathers bend less when flying, and that darker-reddish Barn Owls are able sustain more intense flying than their paler conspecifics.