Selling to consumers with endogenous types

For many goods (such as experience goods or addictive goods), consumers preferences may change over time. In this paper, we examine a monopolist s optimal pricing schedule when current consumption can affect a consumer s valuation in the future and valuations are unobservable. We assume that consumers are anonymous, i.e. the monopolist can t observe a consumer s past consumption history. For myopic consumers, the optimal consumption schedule is distorted upwards, involving substantial discounts for low valuation types. This pushes low types into higher valuations, from which rents can be extracted.For forward looking consumers, there may be a further upward distortion of consumption due to a reversal of the adverse selection effect; low valuation consumers now have a strong interest in consumption in order to increase their valuations. Firms will find it profitable to educate consumers and encourage forward looking behavior.

Histological behavior of glutaraldehyde cross-linked bovine collagen injected into the human bladder for the treatment of vesicoureteral reflux

Endoscopic subureteral collagen injection has become an accepted means for the treatment of vesicoureteral reflux in children. The aim of this study was to evaluate the histological behavior of glutaraldehyde cross-linked bovine collagen implants. The specimens were harvested from 29 patients who underwent reimplant surgery 2 to 30 months (mean 9.5) after unsuccessful subureteral injection therapy. In addition to routine hematoxylin and eosin staining, a new staining method (solophenyl red 3BL) able to demonstrate selectively neoformation of types I and III human collagen, was applied. Invasion of host fibroblasts into the bovine implant and the formation of endogenous types I and III collagen were demonstrated in all 29 cases. Adverse histological reactions were rare and, if present, they were predominantly of an inflammatory nature.

Asymmetric dimethylarginine endogenous inhibition of nitric oxide synthase causes differential vasculature effects

Background: Asymmetric dimethylarginine (ADMA), produced during protein metabolism, is an endogenous inhibitor of nitric oxide synthase, but little is known about its direct vasoactive properties in different arterial beds. Material/Methods: Segments of canine coronary, renal, and femoral arteries were pretreated with increasing concentrations of ADMA, and endothelial function was evaluated in organ chambers. Results: In precontracted canine coronary arteries, the highest concentrations of ADMA inhibited endothelium-dependent relaxation mediated by acetylcholine (n=7), but no concentration of ADMA inhibited receptor-independent relaxation mediated by calcium ionophore (n=7) (P<.001). The effect of ADMA on acetylcholine-mediated relaxation was shown to be competitive inhibition of the nitric oxide synthase pathway, because the addition of L-arginine (10(-3) M), but not D-arginine (101 M), reversed the effect produced by 10(-5) M ADMA. Further, ADMA did not alter endothelium-independent relaxation mediated by sodium nitroprusside (10(-9) to 10(-6) M; n=7). Femoral arteries (n=7) and renal arteries (n=7) were more sensitive to ADMA than were coronary arteries, and they demonstrated significant ADMA inhibition to receptor dependent relaxation induced by acetylcholine (P=.03 and P=.01, respectively) and to receptor-independent relaxation induced by calcium ionophore (P=.02 and P=.01, respectively). Conclusions: Endothelium-dependent relaxation mediated by ADMA is more marked in femoral and renal arteries than in coronary arteries. The response in coronary arteries may be overall protective. Considering these different effects in various artery types, the role of ADMA as a confiable and specific cardiovascular risk factor is questioned.

Redistributive taxation with endogenous sentiments

We present a model in which an individual's sentiments towards others are determined endogenously on the basis of how they perform relative to the societal average. This, in turn, affects the individual's own behavior and hence other agents' sentiments toward her. We focus on stationary patterns of utility interdependence. To demonstrate the effects of such endogeneity, we consider an example of a production economy with redistributive taxation. There are two types of stationary equilibria: one in which all agents conform to the societal norm, into two or three groups. The main conclusion is that the tax structure, in that it affects behavior which in turn affects sentiments, plays a crucial role in determining which type of equilibrium occurs and its characteristics as well as the extent of altruism and social cohesion in society.

Research policy and endogenous growth

This paper studies the effects of different types of research policy on economic growth. We find that while tax incentives to private research, public funding of private projects, and basic research performed at public institutions have unambiguously positive effects on economic growth, performing applied research at public institutions could have negative growth effects. This is due to the large crowding out of private research caused by public R\&D when it competes with private firms in the "patent race". Concerning the effects of these policies on welfare, it is found that research policy can either improve or reduce consumer welfare depending on the characteristics of the policy and that an excessively high research subsidy will reduce it.

The Social contract with endogenous sentiments

Moral values infuence individual behavior and social interactions. A specially signif- cant instance is the case of moral values concerning work e¤ort. Individuals determine what they take to be proper behaviour and judge the others, and themselves, accordingly. They increase their esteem -and self-esteem- for those who perform in excess of the standard and decrease their esteem for those who work less. These changes in self-esteem result from the self-regulatory emotions of guilt or pride extensively studied in Social Psychology. We examine the interactions between sentiments, individual behaviour and the social contract in a model of rational voting over redistribution where individual self-esteem and relative es-teem for others are endogenously determined. Individuals di¤er in their productivities. The desired extent of redistribution depends both on individual income and on individual attitudes toward others. We characterize the politico-economic equilibria in which sentiments, labor supply and redistribution are simultaneously determined. The model has two types of equilibria. In "cohesive" equilibria, all individuals conform to the standard of proper behav- iour, income inequality is low and social esteem is not biased toward any particular type. Under these conditions equilibrium redistribution increases in response to larger inequality. In a "clustered" equilibrium skilled workers work above the mean while unskilled workers work below. In such an equilibrium, income inequality is large and sentiments are biased in favor of the industrious. As inequality increases, this bias may eventually overtake the egoistic demand for greater taxation and equilibrium redistribution decreases. The type of equilibrium that emerges crucially depends on inequality. We contrast the predictions of the model with data on inequality, redistribution, work values and attitudes toward work and toward the poor for a set of OECD countries.

Unemployment and Endogenous Reallocation over the Business Cycle

This paper studies unemployed workers’ decisions to change occupations, and their impact on fluctuations in aggregate unemployment and its underlying duration distribution. We develop an analytically and computationally tractable stochastic equilibrium model with heterogenous labor markets. In this model three different types of unemployment arise: search, rest and reallocation unemployment. We document new evidence on unemployed workers’ gross occupational mobility and use it to calibrate the model. We show that rest unemployment is the main driver of unemployment fluctuations over the business cycle and causes cyclical unemployment to be highly volatile. The resulting unemployment duration distribution generated by the model responds realistically to the business cycle, creating substantial longer-term unemployment in downturns. Finally, rest unemployment also makes our model simultaneously consistent with procyclical occupational mobility of the unemployed, countercyclical job separations into unemployment and a negatively-sloped Beveridge curve.

Analysis of the transcriptional activity of endogenous NFAT5 in primary cells using transgenic NFAT-luciferase reporter mice

Background: The transcription factor NFAT5/TonEBP regulates the response of mammalian cells to hypertonicity. However, little is known about the physiopathologic tonicity thresholds that trigger its transcriptional activity in primary cells. Wilkins et al. recently developed a transgenic mouse carrying a luciferase reporter (9xNFAT-Luc) driven by a cluster of NFAT sites, that was activated by calcineurin-dependent NFATc proteins. Since the NFAT site of this reporter was very similar to an optimal NFAT5 site, we tested whether this reporter could detect the activation of NFAT5 in transgenic cells.Results: The 9xNFAT-Luc reporter was activated by hypertonicity in an NFAT5-dependent manner in different types of non-transformed transgenic cells: lymphocytes, macrophages and fibroblasts. Activation of this reporter by the phorbol ester PMA plus ionomycin was independent of NFAT5 and mediated by NFATc proteins. Transcriptional activation of NFAT5 in T lymphocytes was detected at hypertonic conditions of 360–380 mOsm/kg (isotonic conditions being 300 mOsm/kg) and strongly induced at 400 mOsm/kg. Such levels have been recorded in plasma in patients with osmoregulatory disorders and in mice deficient in aquaporins and vasopressin receptor. The hypertonicity threshold required to activate NFAT5 was higher in bone marrow-derived macrophages (430 mOsm/kg) and embryonic fibroblasts (480 mOsm/kg). Activation of the 9xNFAT-Luc reporter by hypertonicity in lymphocytes was insensitive to the ERK inhibitor PD98059, partially inhibited by the PI3-kinase inhibitor wortmannin (0.5 μM) and the PKA inhibitor H89, and substantially downregulated by p38 inhibitors (SB203580 and SB202190) and by inhibition of PI3-kinase-related kinases with 25 μM LY294002. Sensitivity of the reporter to FK506 varied among cell types and was greater in primary T cells than in fibroblasts and macrophages.Conclusion: Our results indicate that NFAT5 is a sensitive responder to pathologic increases in extracellular tonicity in T lymphocytes. Activation of NFAT5 by hypertonicity in lymphocytes was mediated by a combination of signaling pathways that differed from those required in other cell types. We propose that the 9xNFAT-Luc transgenic mouse model might be useful to study the physiopathological regulation of both NFAT5 and NFATc factors in primary cells.

Endogenous spillovers, increased competition and re-organization waves

We consider an entrepreneur that is the sole producer of a costreducing skill, but the entrepreneur that hires a team to usethe skill cannot prevent collusive trade for the innovation related knowledge between employees and competitors. We showthat there are two types of diffusion avoiding strategies forthe entrepreneur to preempt collusive communication i) settingup a large productive capacity (the traditional firm) and ii)keeping a small team (the lean firm). The traditional firm ischaracterized by its many "marginal" employees that work shortdays, receive flat wages and are incompletely informed about the innovation. The lean firm is small in number of employees,engages in complete information sharing among members, that are paid with stock option schemes. We find that the lean firm is superior to the traditional firm when technological entry costsare low and when the sector is immature.

Endogenous and exogenous regulation of monocyte responses

Mononuclear phagocytes are essential for the innate response to pathogens and for the repair of injured tissue. The cells - which can be broadly divided into circulating monocytes and tissue-resident macrophages and dendritic cells - are selectively equipped to protect the host by mediating pleiotropic and tissue-specific functions. The properties of some mononuclear phagocytes, however, also contribute to the development and the progression of inflammatory diseases. Consequently, current research investigates mononuclear phagocytes into greater detail with the aim to clarify their contributions to pathophysiologic inflammation. Recent studies indicate that circulating monocytes can be divided into distinct populations, which differ in their tissue tropism and functional commitment. Also, tissue macrophages and dendritic cells have been found to adopt context-dependent phenotypes, which can range from "pro-" to "anti-" inflammatory. These findings have markedly contributed to our understanding of the functional heterogeneity of mononuclear phagocyte populations. Yet, in many cases, the factors that control the quantity and/or quality of phagocyte responses in vivo remain largely unknown. The goal of this thesis was to identify cell endogenous and cell exogenous factors that dictate the fate of mononuclear phagocyte populations. To this end we made use of the recent identification of phenotypic markers, which permit to track mononuclear cell types and their lineage precursors. A main approach consisted to define candidate regulatory factors of certain types of mononuclear phagocytes and then to manipulate the expression of these factors in mice so as to address their functions and causal contributions on mononuclear phagocyte lineages in vivo. Human patient material was further used to validate findings. First, we investigated a microRNA and a transcription factor as candidate cell endogenous co- regulators of monocyte subset responses. Second, we studied a tumor-derived hormone as a candidate exogenous factor that amplifies the production of a population of mononuclear phagocytes with tumor-promoting functions. The endogenous and exogenous factors identified in this research appear to act as effective regulators of mononuclear phagocyte responses in vivo and thus may be exploited in future therapeutic approaches to regulate disease-associated inflammation. - Les phagocytes mononucléaires sont essentiels pour la réponse innée aux pathogènes et pour la réparation des tissus lésés. Ces cellules - qui peuvent être largement divisées en deux groupes, les monocytes circulant dans le sang et les macrophages et cellules dendritiques résidant dans les tissus - sont capables de protéger l'hôte en exerçant des fonctions pléiotropiques. Cependant, les propriétés de certains phagocytes mononucléaires contribuent également au développement et à la progression des maladies inflammatoires. Par conséquent, la recherche actuelle étudie les phagocytes mononucléaires plus en détail afin de clarifier leurs contributions à l'inflammation pathophysiologique. Des études récentes indiquent que les monocytes circulants peuvent être divisés en populations distinctes, qui diffèrent dans leur tropisme tissulaire et dans leurs fonctions biologiques. En outre, les macrophages et les cellules dendritiques peuvent adopter des phénotypes dépendants de l'environnement dans lequel ils se trouvent; ces phénotypes peuvent aller du type "pro-" au type "anti-" inflammatoire. Ces récentes découvertes ont contribué à notre compréhension sur l'hétérogénéité fonctionnelle des phagocytes mononucléaires. Pourtant, dans de nombreux cas, les facteurs qui contrôlent la quantité et/ou la qualité des réponses produites par ces cellules restent encore largement inconnus. L'objectif de cette thèse a consisté à identifier de nouveaux facteurs (endogènes ou exogènes) qui contrôlent les phagocytes mononucléaires. Dans ce but, nous avons fait usage de l'identification récente de marqueurs qui permettent d'identifier différents types de phagocytes mononucléaires ainsi que des cellules (souches) dont ils sont issus. Notre approche a consisté à définir des facteurs candidats qui pourraient contrôler certains phagocytes mononucléaires, puis à manipuler l'expression de ces facteurs chez la souris de manière à tester leurs fonctions et leur contributions in vivo. Nous avons également utilisé des échantillons biologiques de patients pour vérifier nos résultats chez l'homme. Tout d'abord, nous avons étudié un microARN et un facteur de transcription pour déterminer si ces deux facteurs opèrent en tant que co-régulateurs d'un certain type de monocytes. Deuxièmement, nous avons considéré une hormone produite par certaines tumeurs afin d'examiner son rôle dans la production d'une population de macrophages qui favorisent la progression des tumeurs. Les facteurs endogènes et exogènes identifiés dans cette recherche semblent agir comme régulateurs dominants de réponses produites par certains phagocytes mononucléaires et pourraient donc être exploités dans de futures approches thérapeutiques afin de contrôler les réponses immunitaires inflammatoires associées a certaines maladies.

In vivo activation of melanoma-specific CD8(+) T cells by endogenous tumor antigen and peptide vaccines. A comparison to virus-specific T cells.

Many new types of vaccines against infectious or malignant diseases are currently being proposed. Careful characterization of the induced immune response is required in assessing their efficiency. While in most studies human tumor antigen-specific T cells are analyzed after in vitro re-stimulation, we investigated these T cells directly ex vivo using fluorescent tetramers. In peripheral blood lymphocytes from untreated melanoma patients with advanced disease, a fraction of tumor antigen (Melan-A/MART-1)-specific T cells were non-naive, thus revealing tumor-driven immune activation. After immunotherapy with synthetic peptides plus adjuvant, we detected tumor antigen-specific T cells that proliferated and differentiated to memory cells in vivo in some melanoma patients. However, these cells did not present the features of effector cells as found in cytomegalovirus specific T cells analyzed in parallel. Thus, peptide plus adjuvant vaccines can lead to activation and expansion of antigen specific CD8(+) T cells in PBL. Differentiation to protective CD8(+) effector cells may, however, require additional vaccine components that stimulate T cells more efficiently, a major challenge for the development of future immunotherapy.

Signal transduction by the cloned glucagon-like peptide-1 receptor: comparison with signaling by the endogenous receptors of beta cell lines.

Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone that potentiates glucose-induced insulin secretion by pancreatic beta cells. The mechanisms of interaction between GLP-1 and glucose signaling pathways are not well understood. Here we studied the coupling of the cloned GLP-1 receptor, expressed in fibroblasts or in COS cells, to intracellular second messengers and compared this signaling with that of the endogenous receptor expressed in insulinoma cell lines. Binding of GLP-1 to the cloned receptor stimulated formation of cAMP with the same dose dependence and similar kinetics, compared with the endogenous receptor of insulinoma cells. Compared with forskolin-induced cAMP accumulation, that induced by GLP-1 proceeded with the same initial kinetics but rapidly reached a plateau, suggesting fast desensitization of the receptor. Coupling to the phospholipase C pathway was assessed by measuring inositol phosphate production and variations in the intracellular calcium concentration. No GLP-1-induced production of inositol phosphates could be measured in the different cell types studied. A rise in the intracellular calcium concentration was nevertheless observed in transfected COS cells but was much smaller than that observed in response to norepinephrine in cells also expressing the alpha 1B-adrenergic receptor. Importantly, no such increase in the intracellular calcium concentration could be observed in transfected fibroblasts or insulinoma cells, which, however, responded well to thrombin or carbachol, respectively. Together, our data show that interaction between GLP-1 and glucose signaling pathways in beta cells may be mediated uniquely by an increase in the intracellular cAMP concentration, with the consequent activation of protein kinase A and phosphorylation of elements of the glucose-sensing apparatus or of the insulin granule exocytic machinery.

Detection of transgenic and endogenous plant DNA fragments in the blood, tissues, and digesta of broilers

The aim was to determine the fate of transgenic and endogenous plant DNA fragments in the blood, tissues, and digesta of broilers. Male broiler chicks (n = 24) were allocated at 1 day old to each of four treatment diets designated T1-T4. T1 and T2 contained the near isogenic nongenetically modified (GM) maize grain, whereas T3 and T4 contained GM maize grain [cry1a(b) gene]; T1 and T3 also contained the near isogenic non-GM soybean meal, whereas T2 and T4 contained GM soybean meal (cp4epsps gene). Four days prior to slaughter at 39-42 days old, 50% of the broilers on T2-T4 had the source(s) of GM ingredients replaced by their non-GM counterparts. Detection of specific DNA sequences in feed, tissue, and digesta samples was completed by polymerase chain reaction analysis. Seven primer pairs were used to amplify fragments (similar to 200 bp) from single copy genes (maize high mobility protein, soya lectin, and transgenes in the GM feeds) and multicopy genes (poultry mitochondrial cytochrome b, maize, and soya rubisco). There was no effect of treatment on the measured growth performance parameters. Except for a single detection of lectin (nontransgenic single copy gene; unsubstantiated) in the extracted DNA from one bursa tissue sample, there was no positive detection of any endogenous or transgenic single copy genes in either blood or tissue DNA samples. However, the multicopy rubisco gene was detected in a proportion of samples from all tissue types (23% of total across all tissues studied) and in low numbers in blood. Feed-derived DNA was found to survive complete degradation up to the large intestine. Transgenic DNA was detected in gizzard digesta but not in intestinal digesta 96 h after the last feeding of treatment diets containing a source of GM maize and/or soybean meal.

Endogenous collateral

We study an economy where there are two types of assets. Consumers’ promises are the primitive defaultable assets secured by collateral chosen by the consumers themselves. The purchase of these personalized assets by financial intermediaries is financed by selling back derivatives to consumers. We show that nonarbitrage prices of primitive assets are strict submartingales, whereas nonarbitrage prices of derivatives are supermartingales. Next we establish existence of equilibrium, without imposing bounds on short sales. The nonconvexity of the budget set is overcome by considering a continuum of agents.

Exogenous expectations on endogenous uncertainty: recursive equilibrium and survival

This paper analyses general equilibrium models with finite heterogeneous agents having exogenous expectations on endogenous uncertainty. It is shown that there exists a recursive equilibrium with the state space consisting of the past aggregate portfolio distribution and the current state of the nature and that it implements the sequential equilibrium. We establish conditions under which the recursive equilibrium is continuous. Moreover, we use the continuous recursive relation of the aggregate variables to prove that if the economy has two types of agents, the one who commits persistent mistakes on the expectation rules of the future endogenous variables is driven out of the market by the others with correct anticipations of the variables, that is, the rational expectations agents.