Tenure, Experience, Human Capital and Wages:A Tractable Equilibrium Search Model of Wage Dynamics

We develop and estimate an equilibrium job search model of worker careers, allowing for human capital accumulation, employer heterogeneity and individual-level shocks. Wage growth is decomposed into contributions of human capital and job search, within and between jobs. Human capital accumulation is largest for highly educated workers. The contribution from job search to wage growth, both within- and between-job, declines over the first ten years of a career – the ‘job-shopping’ phase of a working life – after which workers settle into high-quality jobs using outside offers to generate gradual wage increases, thus reaping the benefits from competition between employers

Ab initio calculation of effective work functions for a TiN/HfO(2)/SiO(2)/Si transistor stack

International audienceClose Ab initio techniques are used to calculate the effective work function (Weff) of a TiN/HfO2/SiO2/Si stack representing a metal-oxide-semiconductor (MOS) transistor gate taking into account first order many body effects. The required band offsets were calculated at each interface varying its composition. Finally, the transitivity of local density approximation (LDA) calculated bulk band lineups were used and completed by many body perturbation theory (MBPT) bulk corrections for the terminating materials (Si and TiN) of the MOS stack. With these corrections the ab initio calculations predict a Weff of a TiN metal gate on HfO2 to be close to 5.0 eV

NMscatt: a program for calculating inelastic scattering from large biomolecular systems using classical force-field simulations

Computational tools for normal mode analysis, which are widely used in physics and materials science problems, are designed here in a single package called NMscatt (Normal Modes & scattering) that allows arbitrarily large systems to be handled. The package allows inelastic neutron and X-ray scattering observables to be calculated, allowing comparison with experimental data produced at large scale facilities. Various simplification schemes are presented for analysing displacement vectors, which are otherwise too complicated to understand in very large systems.Comment: 13 pages, 5 figures, preprint submitted to Computer Physics Communication

Fast 3D shape screening of large chemical databases through alignment-recycling

<p>Abstract</p> <p>Background</p> <p>Large chemical databases require fast, efficient, and simple ways of looking for similar structures. Although such tasks are now fairly well resolved for graph-based similarity queries, they remain an issue for 3D approaches, particularly for those based on 3D shape overlays. Inspired by a recent technique developed to compare molecular shapes, we designed a hybrid methodology, alignment-recycling, that enables efficient retrieval and alignment of structures with similar 3D shapes.</p> <p>Results</p> <p>Using a dataset of more than one million PubChem compounds of limited size (< 28 heavy atoms) and flexibility (< 6 rotatable bonds), we obtained a set of a few thousand diverse structures covering entirely the 3D shape space of the conformers of the dataset. Transformation matrices gathered from the overlays between these diverse structures and the 3D conformer dataset allowed us to drastically (100-fold) reduce the CPU time required for shape overlay. The alignment-recycling heuristic produces results consistent with <it>de novo </it>alignment calculation, with better than 80% hit list overlap on average.</p> <p>Conclusion</p> <p>Overlay-based 3D methods are computationally demanding when searching large databases. Alignment-recycling reduces the CPU time to perform shape similarity searches by breaking the alignment problem into three steps: selection of diverse shapes to describe the database shape-space; overlay of the database conformers to the diverse shapes; and non-optimized overlay of query and database conformers using common reference shapes. The precomputation, required by the first two steps, is a significant cost of the method; however, once performed, querying is two orders of magnitude faster. Extensions and variations of this methodology, for example, to handle more flexible and larger small-molecules are discussed.</p

Using Pharmacokinetic and Viral Kinetic Modeling To Estimate the Antiviral Effectiveness of Telaprevir, Boceprevir, and Pegylated Interferon during Triple Therapy in Treatment-Experienced Hepatitis C Virus-Infected Cirrhotic Patients.: Effectiveness of triple therapy in cirrhotic patients

International audienceTriple therapy combining a protease inhibitor (PI) (telaprevir or boceprevir), pegylated interferon (PEG-IFN), and ribavirin (RBV) has dramatically increased the chance of eradicating hepatitis C virus (HCV). However, the efficacy of this treatment remains suboptimal in cirrhotic treatment-experienced patients. Here, we aimed to better understand the origin of this impaired response by estimating the antiviral effectiveness of each drug. Fifteen HCV genotype 1-infected patients with compensated cirrhosis, who were nonresponders to prior PEG-IFN/RBV therapy, were enrolled in a nonrandomized study. HCV RNA and concentrations of PIs, PEG-IFN, and RBV were frequently assessed in the first 12 weeks of treatment and were analyzed using a pharmacokinetic/viral kinetic model. The two PIs achieved similar levels of molar concentrations (P = 0.5), but there was a significant difference in the 50% effective concentrations (EC50) (P = 0.008), leading to greater effectiveness for telaprevir than for boceprevir in blocking viral production (99.8% versus 99.0%, respectively, P = 0.002). In all patients, the antiviral effectiveness of PEG-IFN was modest (43.4%), and there was no significant contribution of RBV exposure to the total antiviral effectiveness. The second phase of viral decline, which is attributed to the loss rate of infected cells, was slow (0.19 day(-1)) and was higher in patients who subsequently eradicated HCV (P = 0.03). The two PIs achieved high levels of antiviral effectiveness. However, the suboptimal antiviral effectiveness of PEG-IFN/RBV and the low loss of infected cells suggest that a longer treatment duration might be needed in cirrhotic treatment-experienced patients and that a future IFN-free regimen may be particularly beneficial in these patients

AFM Imaging of SWI/SNF action: mapping the nucleosome remodeling and sliding

We propose a combined experimental (Atomic Force Microscopy) and theoretical study of the structural and dynamical properties of nucleosomes. In contrast to biochemical approaches, this method allows to determine simultaneously the DNA complexed length distribution and nucleosome position in various contexts. First, we show that differences in the nucleo-proteic structure observed between conventional H2A and H2A.Bbd variant nucleosomes induce quantitative changes in the in the length distribution of DNA complexed with histones. Then, the sliding action of remodeling complex SWI/SNF is characterized through the evolution of the nucleosome position and wrapped DNA length mapping. Using a linear energetic model for the distribution of DNA complexed length, we extract the net wrapping energy of DNA onto the histone octamer, and compare it to previous studies.Comment: 25 pages,5 figures, to appear in Biophysical Journa

Spleen-Resident CD4+ and CD4− CD8α− Dendritic Cell Subsets Differ in Their Ability to Prime Invariant Natural Killer T Lymphocytes

One important function of conventional dendritic cells (cDC) is their high capacity to capture, process and present Ag to T lymphocytes. Mouse splenic cDC subtypes, including CD8α+ and CD8α− cDC, are not identical in their Ag presenting and T cell priming functions. Surprisingly, few studies have reported functional differences between CD4− and CD4+ CD8α− cDC subsets. We show that, when loaded in vitro with OVA peptide or whole protein, and in steady-state conditions, splenic CD4− and CD4+ cDC are equivalent in their capacity to prime and direct CD4+ and CD8+ T cell differentiation. In contrast, in response to α-galactosylceramide (α-GalCer), CD4− and CD4+ cDC differentially activate invariant Natural Killer T (iNKT) cells, a population of lipid-reactive non-conventional T lymphocytes. Both cDC subsets equally take up α-GalCer in vitro and in vivo to stimulate the iNKT hybridoma DN32.D3, the activation of which depends solely on TCR triggering. On the other hand, and relative to their CD4+ counterparts, CD4− cDC more efficiently stimulate primary iNKT cells, a phenomenon likely due to differential production of co-factors (including IL-12) by cDC. Our data reveal a novel functional difference between splenic CD4+ and CD4− cDC subsets that may be important in immune responses

Tax law and competition

Les rapports entre concurrence et droit fiscal, en tant que technique de mise en oeuvre du prélèvement fiscal, sont multiples et complexes. Il apparaît sans peine que la concurrence est affectée par le droit fiscal, dans la mesure où tant les dépenses fiscales que les normes fiscales peuvent dénaturer le rapport concurrentiel. En pratique un tel biais concurrentiel résulte de critères d’imposition ratione materiae ou personae qui décorrèlent la charge fiscale de l’avantage concurrentiel, lequel détermine à lui seul l’issue du jeu concurrentiel, et est réductible à l’avantage en valeur ajoutée. Dit de manière plus analytique, le droit fiscal est distorsif de concurrence lorsqu’il traite certains concurrents ou actes concurrents de manière différenciée, soit de jure, soit de facto, c’est-à-dire en fonction de leurs caractéristiques économiques, dans la mesure où une telle différenciation ne recoupe pas les différences de valeur ajoutée. Le jeu concurrentiel est par ailleurs un instrument du droit fiscal, qui définit un principe dit « de pleine concurrence » pour déterminer objectivement la base imposable d’échanges intragroupes. Ce principe, qui emporte des effets importants en droit commercial et en droit de la concurrence, permet en outre d’exposer empiriquement les distorsions de concurrence naissant d’une méconnaissance de la valeur ajoutée propre à chaque contribuable. Au final, la distorsion fiscale de concurrence apparaît bien comme une affaire de critère d’imposition ; cette dimension juridique pose nécessairement la question de la réception de cette distorsion par le droit positif. magistère de fait dessine ainsi une norme matérielle de concurrence qui affecte le droit fiscal. Ainsi, en droit interne, la teneur et la mise en oeuvre du principe d’égalité devant l’impôt repose de manière croissante sur des analyses concurrentielles spontanées du juge de l’impôt et du juge constitutionnel, dont la seule limite paraît être une approche abstraite de l’égalité et une grande latitude d’appréciation laissée par ces derniers au pouvoir fiscal. Ce rapport d’influence se double d’une véritable instrumentalisation du droit fiscal sur le terrain du droit économique, qui subordonne la fiscalité à sa propre finalité concurrentielle. En effet, le droit de l’Union européenne recourt de manière étendue et explicite à l’analyse concurrentielle dans son contrôle de conventionalité du droit fiscal, en s’opposant aux mesures fiscales internes susceptibles, par une atteinte à l’obligation de traitement national ou une concurrence fiscale déloyale, de mettre en échec l’intégration économique européenne. Appliquant au droit fiscal un prisme purement économique ne présentant que des égards très limités pour les objectifs et méthodes fiscales, le droit de l’Union européenne porte en germe la censure de toute politique fiscale, même indistinctement applicable, à raison de son objet mais plus encore de ses effets anticoncurrentiels. L’expression ultime de l’instrumentalisation du droit fiscal par la concurrence réside dans la jurisprudence qui commande l’imposition au seul regard des distorsions de concurrence naissant de son absence, faisant de la concurrence une source d’imposition.The relationship between competition and tax law, defined as a means of setting the tax burden for corporations, is far-reaching and complex. Competition is undoubtedly shaped by tax law, insofar as tax expenditures and regular tax provisions may adversely affect the outcome of competition on a given market. Specifically, competition may be distorted by tax criteria that unalign the tax burden from the competitive advantage which determines the market outcome, and which can be defined as the difference in added value between competitors. A more analytical expression of this would be that the criteria setting the tax burden distort competition - either de jure or de facto - when they provide for a specific tax treatment of certain competitors or competing operations. Furthermore, pursuant to the arm’s length principle, competition can be considered as an instrument for tax law, insofar as it is used as a tool for setting intragroup tax bases. The arm’s length principle, which falls under anticompetitive pricing rules, evidences the distorsion of competition that stems from disregarding taxpayers’ respective added values, thereby empirically confirming that tax capacity and added value should be aligned in order for tax law to be competition-neutral. Accordingly, tax distorsions of competition are a question of tax criteria; this legal dimension begs the question of whether such distorsions are characterized and regulated by statute and /or case law.A first observation would be that competition increasingly applies to tax law, marginally via competition law (which is a paradox), but more profoundly and widely as the defining influence behind a number of provisions and principles that govern tax law. That competition is accordingly instrumental for these norms would tend to make of competition a substantive norm for tax law. The French principle of equality before tax increasingly factors full-fledged competition analyses in the tax and constitutional courts’ appreciation of the competitive effects of tax provisions, but its scope is curtailed by an overly abstract conception of equality and, overall, a reluctance to challenge the legislator’s policy decisions. This influence, characterized in French law and conducive to tax being affected by the objective of free competition, also entails the instrumentalization of tax law in the field of economic law, which imposes on tax law its own competitive objectives. Indeed, EU law provides a wider and more explicit use of competition analysis in its appreciation of the lawfulness of tax law, by precluding provisions which, through discrimination on the grounds of nationality or unfair tax competition, conflict with the European economic integration. Specifically, tax provisions are tested for anticompetitive object and / or effects, with their fiscal objectives or methods being mostly disregarded in this respect, to the extent that anticompetitive effects can be viewed as the ultimate governing principle for tax law. This is conducive to the instrumentalization of tax law by competition, with far-reaching implications for tax policies and their underlying criteria. Ultimately, tax law is instrumentalized by competition in the case-law that warrants taxation on the grounds of the distortions of competition that would arise from its absence, effectively making competition a source of taxatio