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.

Government information transparency

This paper studies a model of announcements by a privately informed government about the future state of the economic activity in an economy subject to recurrent shocks and with distortions due to income taxation. Although transparent communication would ex ante be desirable, we find that even a benevolent government may ex-post be non-informative, in an attempt to countervail the tax distortion with a "second best" compensating distortion in information. This result provides a rationale for independent national statistical offices, committed to truthful communication. We also find that whether inequality in income distribution favors or harms government transparency depends on labor supply elasticity.

Information Design

There are two ways of creating incentives for interacting agents to behave in a desired way. One is by providing appropriate payoff incentives, which is the subject of mechanism design. The other is by choosing the information that agents observe, which we refer to as information design. We consider a model of symmetric information where a designer chooses and announces the information structure about a payoff relevant state. The interacting agents observe the signal realizations and take actions which affect the welfare of both the designer and the agents. We characterize the general finite approach to deriving the optimal information structure for the designer - the one that maximizes the designer's ex ante expected utility subject to agents playing a Bayes Nash equilibrium. We then apply the general approach to a symmetric two state, two agent, and two actions environment in a parameterized underlying game and fully characterize the optimal information structure: it is never strictly optimal for the designer to use conditionally independent private signals; the optimal information structure may be a public signal or may consist of correlated private signals. Finally, we examine how changes in the underlying game affect the designer's maximum payoff. This exercise provides a joint mechanism/information design perspective.

Positive solutions of nonlinear problems involving the square root of the Laplacian

We consider nonlinear elliptic problems involving a nonlocal operator: the square root of the Laplacian in a bounded domain with zero Dirichlet boundary conditions. For positive solutions to problems with power nonlinearities, we establish existence and regularity results, as well as a priori estimates of Gidas-Spruck type. In addition, among other results, we prove a symmetry theorem of Gidas-Ni-Nirenberg type.

99mTc-sestamibi imaging and bone marrow karyotyping in the assessment of multiple myeloma and MGUS

AIM: The first pathogenetic step in multiple myeloma is the emergence of a limited number of clonal plasma cells, clinically known as monoclonal gammopathy of undetermined significance (MGUS). Patients with MGUS do not have symptoms or end-organ damage but they do have a 1% annual risk of progression to multiple myeloma or related malignant disorders. With progression of MGUS to multiple myeloma, complex genetic events occur in the neoplastic plasma cell. Karyotyping and fluorescence in-situ hybridization (FISH) were shown to be of prognostic value in patients with multiple myeloma. Tc-sestamibi imaging reflects myeloma disease activity in bone marrow with very high sensitivity and specificity predicting disease evolution. This study was undertaken to evaluate the role of Tc-sestamibi imaging and cytogenetic analysis in prognosis prediction of MGUS and multiple myeloma. METHODS: We enrolled 30 consecutive patients with a confirmed diagnosis of multiple myeloma or MGUS. Bone marrow biopsy and biochemical staging according to the International Staging System (ISS) were performed in all cases. Karyotype analysis and FISH were performed in 11 of 12 patients with MGUS and in 17 of 18 patients with multiple myeloma having adequate metaphases. RESULTS: The karyotype was abnormal in four of 11 MGUS and in six of 17 multiple myeloma. Abnormalities of chromosome 13 were present in one case of MGUS and in six cases of multiple myeloma whereas the involvement of immunoglobulin was observed in one case of multiple myeloma. An abnormal FISH panel was found in four MGUS and nine multiple myeloma patients. All patients with MGUS showed a normal MIBI scan (score 0). Among patients with multiple myeloma only three, all with ISS stage I, showed a normal scan while a positive scan was obtained in others (score range, 1-7). The MIBI uptake was strongly related to the bone marrow plasma cell infiltration and to cytogenetic abnormalities. Particularly, a MIBI uptake score above 5 identified patients with poor prognosis encompassing all stage III multiple myeloma and three of seven stage II multiple myeloma. On the other hand all stage I and II patients having a MIBI score less than 5 showed a good prognosis. CONCLUSION: Both cytogenetic analysis and a MIBI scan add no relevant prognostic information to the ISS in patients with stage I and III multiple myeloma. The MIBI scan was of prognostic value in stage II multiple myeloma patients. Additionally, MIBI imaging may be useful to guide bone marrow biopsy in order to obtain adequate samples for cytogenetic analysis.

The Optimal Degree of Monetary-Discretion in a New Keynesian Model with Private Information

This paper considers the optimal degree of discretion in monetary policy when the central bank conducts policy based on its private information about the state of the economy and is unable to commit. Society seeks to maximize social welfare by imposing restrictions on the central bank's actions over time, and the central bank takes these restrictions and the New Keynesian Phillips curve as constraints. By solving a dynamic mechanism design problem we find that it is optimal to grant "constrained discretion" to the central bank by imposing both upper and lower bounds on permissible inflation, and that these bounds must be set in a history-dependent way. The optimal degree of discretion varies over time with the severity of the time-inconsistency problem, and, although no discretion is optimal when the time-inconsistency problem is very severe, our numerical experiment suggests that no-discretion is a transient phenomenon, and that some discretion is granted eventually.

Superfamily of steroid nuclear receptors: positive and negative regulators of gene expression.

The nuclear hormone receptor superfamily is characterized by an impressive functional diversity of its members despite a remarkable overall structural unity. A variety of ligands bind specifically to them and these receptors control gene networks that have profound effects on growth, development, and homeostasis. The ligand-receptor complexes recognize transcriptional enhancer DNA sequences, the hormone response elements, resulting in induction or repression of gene activity. The similarity between all these hormone response enhancer elements, as well as between the receptors themselves, indicates a conserved general strategy for the hormonal control of transcription by steroids. The activated receptors bind to responsive promoters and most likely mediate the assembly of stage- and tissue-specific transcription factor complexes that stimulate or inhibit gene expression.

Skeletal Muscle Mitochondrial and Lipid Droplet Volume Density: Validity of Electron Microscopy Point-counting Measurements

Mitochondrial (M) and lipid droplet (L) volume density (vd) are often used in exercise research. Vd is the volume of muscle occupied by M and L. The means of calculating these percents are accomplished by applying a grid to a 2D image taken with transmission electron microscopy; however, it is not known which grid best predicts these values. PURPOSE: To determine the grid with the least variability of Mvd and Lvd in human skeletal muscle. METHODS: Muscle biopsies were taken from vastus lateralis of 10 healthy adults, trained (N=6) and untrained (N=4). Samples of 5-10mg were fixed in 2.5% glutaraldehyde and embedded in EPON. Longitudinal sections of 60 nm were cut and 20 images were taken at random at 33,000x magnification. Vd was calculated as the number of times M or L touched two intersecting grid lines (called a point) divided by the total number of points using 3 different sizes of grids with squares of 1000x1000nm sides (corresponding to 1µm2), 500x500nm (0.25µm2) and 250x250nm (0.0625µm2). Statistics included coefficient of variation (CV), 1 way-BS ANOVA and spearman correlations. RESULTS: Mean age was 67 ± 4 yo, mean VO2peak 2.29 ± 0.70 L/min and mean BMI 25.1 ± 3.7 kg/m2. Mean Mvd was 6.39% ± 0.71 for the 1000nm squares, 6.01% ± 0.70 for the 500nm and 6.37% ± 0.80 for the 250nm. Lvd was 1.28% ± 0.03 for the 1000nm, 1.41% ± 0.02 for the 500nm and 1.38% ± 0.02 for the 250nm. The mean CV of the three grids was 6.65% ±1.15 for Mvd with no significant differences between grids (P>0.05). Mean CV for Lvd was 13.83% ± 3.51, with a significant difference between the 1000nm squares and the two other grids (P<0.05). The 500nm squares grid showed the least variability between subjects. Mvd showed a positive correlation with VO2peak (r = 0.89, p < 0.05) but not with weight, height, or age. No correlations were found with Lvd. CONCLUSION: Different size grids have different variability in assessing skeletal muscle Mvd and Lvd. The grid size of 500x500nm (240 points) was more reliable than 1000x1000nm (56 points). 250x250nm (1023 points) did not show better reliability compared with the 500x500nm, but was more time consuming. Thus, choosing a grid with square size of 500x500nm seems the best option. This is particularly relevant as most grids used in the literature are either 100 points or 400 points without clear information on their square size.

Testing low-altitude infrared digital photography from a mini-UAV to retrieve information for biological conservation

Satellite remote sensing imagery is used for forestry, conservation and environmental applications, but insufficient spatial resolution, and, in particular, unavailability of images at the precise timing required for a given application, often prevent achieving a fully operational stage. Airborne remote sensing has the advantage of custom-tuned sensors, resolution and timing, but its price prevents using it as a routine technique for the mentioned fields. Some Unmanned Aerial Vehicles might provide a “third way” solution as low-cost techniques for acquiring remotely sensed information, under close control of the end-user, albeit at the expense of lower quality instrumentation and instability. This report evaluates a light remote sensing system based on a remotely-controlled mini-UAV (ATMOS-3) equipped with a color infra-red camera (VEGCAM-1) designed and operated by CATUAV. We conducted a testing mission over a Mediterranean landscape dominated by an evergreen woodland of Aleppo pine (Pinus halepensis) and (Holm) oak (Quercus ilex) in the Montseny National Park (Catalonia, NE Spain). We took advantage of state-of-the-art ortho-rectified digital aerial imagery (acquired by the Institut Cartogràfic de Catalunya over the area during the previous year) and used it as quality reference. In particular, we paid attention to: 1) Operationality of flight and image acquisition according to a previously defined plan; 2) Radiometric and geometric quality of the images; and 3) Operational use of the images in the context of applications. We conclude that the system has achieved an operational stage regarding flight activities, although with meteorological limits set by wind speed and turbulence. Appropriate landing areas can be sometimes limiting also, but the system is able to land on small and relatively rough terrains such as patches of grassland or short matorral, and we have operated the UAV as far as 7 km from the control unit. Radiometric quality is sufficient for interactive analysis, but probably insufficient for automated processing. A forthcoming camera is supposed to greatly improve radiometric quality and consistency. Conventional GPS positioning through time synchronization provides coarse orientation of the images, with no roll information.

Traitement de l'information sensorielle chez la souris HeCo

L'hétérotopie sous-corticale en bandes ou double-cortex est une malformation cérébrale causée par une interruption de la migration des neurones du néocortex pendant sa formation. La souris HeCo est un modèle murin de cette affection, caractérisée par un amas de neurones corticaux dans la substance blanche sous-corticale. Les signes cliniques de cette maladie sont le plus souvent une épilepsie réfractaire, un retard développemental et mental. Chez l'homme, l'hétérotopie se trouve en partie en profondeur du cortex somatotopique moteur et sensitif et semble participer à leurs fonctions. L'IRM fonctionnelle a montré lors d'une tâche motrice (taper des doigts), l'activation en plus du cortex moteur controlatéral du cortex hétérotopique sous-jacent. La pathogenèse des malformations corticales est toujours mal comprise, c'est pourquoi il est important d'avoir plusieurs modèles animaux. Jusqu'il a peu, il n'existait que le rat TISH, découvert en 1997, dont la génétique n'est pas connue à ce jour. La souris HeCo est un nouveau modèle animal de malformation corticale dont le gène muté impliquant une protéine associée aux microtubules a été découvert récemment. Elle partage avec les cas humains un seuil épileptique abaissé et un certain retard développemental. Objectif : Déterminer si le cortex hétérotopique de la souris HeCo est activé lors d'une tâche sensitive (exploration de l'environnement à l'aide des vibrisses du museau). Méthode : Chez la souris, les vibrisses sont des organes sensitifs essentiels dans l'exploration de l'environnement. Pour déterminer si le cortex hétérotopique est actif lors d'une tâche sensitive, on utilisera donc un exercice de découverte d'une cage enrichie en stimulus. Afin de visualiser les régions du cerveau actives, on utilisera plusieurs méthodes: l'autoradiographie ([14C]2- deoxyglucose, 2-DG) et l'immunohistochimie c-Fos. Le 2-DG est un analogue du glucose qui se fixe dans les régions cérébrales métaboliquement actives, ici impliquées dans la sensibilité. Il est injecté dans le péritoine de la souris à jeun avant l'exploration. Le contrôle négatif se fera en coupant les vibrisses d'un côté avant la tâche sensitive. A la fin de la tâche, on prélève des coupes du cerveau pour mesurer l'autoradioactivité. L'immunohistochimie c-Fos est réalisée sur les cerveaux de souris ayant effectué la même tâche sensitive et détecte une protéine d'activation neuronale. Afin de détecter une activation de l'hétérotopie à plus long terme, on utilisera la cytochrome oxydase, une enzyme qui met en évidence les régions contenant beaucoup de mitochondries, donc métaboliquement très actives. Résultats : La cytochrome oxydase a marqué de façon égale le cortex homotopique de la souris HeCo et le cortex des souris contrôle. Par ailleurs, chez le mutant, elle a montré un faible marquage dans la partie médiale de l'hétérotopie et des zones de marquage plus intenses dans sa partie latérale. L'autoradiographie 2-DG a montré un pattern classique d'activation du cortex homotopique du côté stimulé, avec une intensité plus marquée dans la couche IV. Du même côté, l'hétérotopie latérale montre une intensité similaire à celui de la couche IV. Du côté non stimulé, on note une intensité faible, tant dans le cortex homotopique que dans le cortex hétérotopique. L'immunohistochimie c-Fos a montré une nette différence entre l'hémisphère stimulé et l'hémisphère non stimulé dans la couche IV comme dans l'hétérotopie. Il existe, tant du côté stimulé que du côté non stimulé, un gradient dans l'hétérotopie, le marquage latéral étant du même ordre que dans la couche IV alors qu'il est moins intense médialement. Conclusion : l'hétérotopie corticale latérale, située en particulier sous le cortex somatosensoriel, semble traiter l'information périphérique controlatérale dans le même ordre que le cortex homotopique.

Quality of web-based information on bipolar disorder

Rapport de synthèse : Introduction : Internet est une source importante d'information sur la santé mentale. Le trouble bipolaire est communément associé à un handicap, des comorbidités, un faible taux d'introspection et une mauvaise compliance au traitement. Le fardeau de la maladie, de par les épisodes dépressifs et maniaques, peut conduire les personnes (dont le diagnostic de trouble bipolaire a été déjà posé ou non), ainsi que leur famille à rechercher des informations sur Internet. De ce fait, il est important que les sites Web traitant du sujet contiennent de l'information de haute qualité, basée sur les évidences scientifiques. Objectif.: évaluer la qualité des informations consultables sur Internat au sujet du trouble bipolaire et identifier des indicateurs de qualité. Méthode: deux mots-clés : « bipolar disorder » et « manic depressive illness » ont été introduits dans les moteurs de recherche les plus souvent utilisés sur Internet. Les sites Internet ont été évalués avec un formulaire standard conçu pour noter les sites sur la base de l'auteur (privé, université, entreprise,...), la présentation, l'interactivité, la lisibilité et la qualité du contenu. Le label de qualité « Health On the Net» (HON), et l'outil DISCERN ont été utilisés pour vérifier leur efficacité comme indicateurs de la qualité. Résultats: sur les 80 sites identifiés, 34 ont été inclus. Sur la base de la mesure des résultats, la qualité du contenu des sites s'est avérée être bonne. La qualité du contenu des sites Web qui traitent du trouble bipolaire est expliquée de manière significative par la lisibilité, la responsabilité et l'interactivité aussi bien que par un score global. Conclusions: dans l'ensemble, la qualité du contenu de l'étude des sites Web traitant du trouble bipolaire est de bonne qualité.

Mitochondrial targeting adaptation of the hominoid-specific glutamate dehydrogenase driven by positive Darwinian selection.

Many new gene copies emerged by gene duplication in hominoids, but little is known with respect to their functional evolution. Glutamate dehydrogenase (GLUD) is an enzyme central to the glutamate and energy metabolism of the cell. In addition to the single, GLUD-encoding gene present in all mammals (GLUD1), humans and apes acquired a second GLUD gene (GLUD2) through retroduplication of GLUD1, which codes for an enzyme with unique, potentially brain-adapted properties. Here we show that whereas the GLUD1 parental protein localizes to mitochondria and the cytoplasm, GLUD2 is specifically targeted to mitochondria. Using evolutionary analysis and resurrected ancestral protein variants, we demonstrate that the enhanced mitochondrial targeting specificity of GLUD2 is due to a single positively selected glutamic acid-to-lysine substitution, which was fixed in the N-terminal mitochondrial targeting sequence (MTS) of GLUD2 soon after the duplication event in the hominoid ancestor approximately 18-25 million years ago. This MTS substitution arose in parallel with two crucial adaptive amino acid changes in the enzyme and likely contributed to the functional adaptation of GLUD2 to the glutamate metabolism of the hominoid brain and other tissues. We suggest that rapid, selectively driven subcellular adaptation, as exemplified by GLUD2, represents a common route underlying the emergence of new gene functions.