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High-field asymmetric waveform ion mobility spectrometry (FAIMS) has gained popularity in the proteomics field for its capability to improve mass spectrometry sensitivity and to decrease peptide co-fragmentation. The recent implementation of FAIMS on Tribrid Orbitrap instruments enhanced proteome coverage and increased the precision of quantitative measurements. However, the FAIMS interface has not been available on older generation Orbitrap mass spectrometers such as the Q-Exactive. Here, we report the integration of the FAIMS Pro device with embedded electrical and gas connections to a Q-Exactive HF mass spectrometer. Proteomic experiments performed on HeLa tryptic digests with the modified mass spectrometer improved signal to noise and reduced interfering ions, resulting in an increase of 42% in peptide identification. FAIMS was also combined with segmented ion fractionation where 100 m/z windows were obtained in turn to further increase the depth of proteome analysis by reducing the proportion of chimeric MS/MS spectra from 50 to 27%. We also demonstrate the application of FAIMS to improve quantitative measurements when using isobaric peptide labeling. FAIMS experiments performed on a two-proteome model revealed that FAIMS Pro provided a 65% improvement in quantification accuracy compared to conventional LC-MS/MS experiments.

The laser diode thermal desorption (LDTD) ionization source allows ultrafast and sensitive analysis of small molecules by mass spectrometry. Signal enhancement in LDTD has been observed when coating the surface of sample microwells with a solution of ethylenediaminetetraacetic acid (EDTA) or nitrilotriacetic acid. Here we present a quantitative analysis of signal enhancement using solutions of diverse commercial proteins (lysozyme, immunoglobulin G, albumin, and fibrinogen) as coatings. Results showed that compounds with polar chemical functions such as carboxylic acid, sulfonyl, and nitro had signal enhancement factors, in most cases higher than 10, when using any of the tested proteins as coating agent. Analysis of variance revealed that immunoglobulin G and fibrinogen gave the best results. However, the signal enhancement factors obtained with these proteins were not superior to those observed with EDTA. To explain the signal enhancement effect of proteins, analysis by scanning electron microscopy of dried samples on the microwell sample plates was carried out. Images showed that salicylic acid, one of the compounds with the highest observed signal enhancement, formed a thick layer when applied directly on the uncoated surface, but it formed small crystals (

Laser-diode thermal desorption (LDTD) is an ionization source usually coupled to triple quadrupole mass spectrometry (QqQMS) and specifically designed for laboratories requiring high-throughput analysis. It has been observed that surface coatings on LDTD microwell plates can improve the sensitivity of the analysis of small polar molecules. The objective of the present study is to understand and quantify the effect of microwell surface coatings on signal intensity of small organic molecules of clinical, environmental, and forensic interest. Experiments showed that the peak areas of diclofenac, chloramphenicol, salicylic acid, and 11-nor-9-carboxy-Δ9 -tetrahydrocannabinol obtained by LDTD-QqQMS increased by up to 3 orders of magnitude when using microwells coated with ethylenediaminetetraacetic acid (EDTA). Tests with different chelating agents and polytetrafluoroethylene as microwell surface coatings showed that nitrilotriacetic acid gave significantly higher peak areas for five out of the nine compounds that showed signal enhancement using chelating agents as coatings. Scanning electron microscopy studies of EDTA-coated and uncoated microwells showed that analytes deposited in the former formed more uniform and thinner films than in the latter. The enhancement effect of surface coatings in LDTD-QqQMS was explained mainly by the formation of homogenous and thinner layers of nanocrystals of analytes that are easier to desorb thermally than the layers formed when the analytes dry in direct contact with the bare stainless-steel surface. Chemisorption of some analytes to the stainless-steel surface of the microwell plate appeared to be a minor factor. Surface coatings widen the number of compounds analyzable by LDTD-QqQMS and can also improve sensitivity and limits of detection.

International audience; We analyze how insurance law can mitigate moral hazard by allowing insurers to reduce or cancel coverage in some circumstances. We consider an incomplete contract setting in which the insurer may obtain information related to the policyholder's behavior through a costly audit of the circumstances of the loss. Court decisions are based on a standard of proof such as the balance of probabilities. We show that an optimal insurance law brings efficiency gains compared to the no‐audit case. We also highlight the conditions under which the burden of proof should be on the insured, provided that insurers are threatened with sanctions for bad faith.; Les auteurs analysent comment le droit des assurances peut atténuer le risque moral en permettant aux assureurs de réduire ou d'annuler la couverture dans certaines circonstances. Ils considèrent un contrat incomplet dans lequel l'assureur peut obtenir des informations relatives au comportement de l'assuré par le biais d'un audit coûteux des circonstances du sinistre. Les décisions des tribunaux sont fondées sur une norme de preuve telle que la prépondérance des probabilités. Ils montrent alors qu'un droit des assurances optimal apporte des gains d'efficacité par rapport au cas sans audit. Les auteurs soulignent enfin également les conditions dans lesquelles la charge de la preuve devrait incomber à l'assuré, à condition que les assureurs soient menacés de sanctions pour mauvaise foi.

International audience; This work describes a process approach to study the oil leakage phenomenon in feeds for large Trout. Using a pilot vacuum coater, four experimental coating parameters were studied (stirring speed, pressure, filling rate, and time needed to restore atmospheric pressure) through an experimental design. The properties measured on the coated pellets were the oil leakage rate and three other important usage properties, i.e. durability, hardness, and floatability. The coating conditions had a significant influence on oil leakage rate, varying at 40 °C from 2.7 % to 1.2 % depending on the coating conditions used. Finally, the vacuum level was the most effective factor in reducing leakage. Indeed, a progressive reduction in oil leakage rate was observed as the pressure inside the coater was reduced during coating.

We analyze how pandemic business interruption coverage can be put in place by building on capitalization mechanisms. The pandemic risk cannot be mutualized since it affects simultaneously a large number of businesses, and furthermore, it has a systemic nature because it goes along with a severe decline in the real economy. However, as shown by COVID-19, pandemics affect economic sectors in a differentiated way: some of them are very severely affected because their activity is strongly impacted by travel bans and constraints on work organisation, while others are more resistant. This opens the door to risk coverage mechanisms based on a portfolio of financial securities, including long-short positions and options in stock markets. We show that such financial investment allow insurers to offer business interruption coverage in pandemic states, while simultaneously hedging the risks associated with the alternation of bullish and bearish non-pandemic states. These conclusions are derived from a theoretical model of corporate risk management, and they are illustrated by numerical simulations, using data from the French stock exchange.

Catastrophic risks are often characterised by a low probability , a high severity and a large number of affected individuals. Taking these specificities into account, we analyse the capacity of insurance contracts to provide coverage for those risks, independently from the market failures frequently observed in practice. On the demand side, we characterise individual preferences under which the willingness to pay for the coverage of large losses remains significant, although their occurrence probability is very small. On the supply side, the correlation between individual losses affects the insurance pricing through the insurers' cost of capital. Analysing the interaction between demand and supply yields the key determinants of insurability and of a socially optimal risk sharing strategy.

The aim of this work is to propose a new development of the fuel cell characterization tool based on Voltage Singularity Spectrum (VSS), a pattern that can advantageously be estimated from the "free" evolution of the stack voltage. A Polymer Electrolyte Membrane Fuel Cell (PEMFC) designed to operate in micro Combined Heat and Power units is investigated to create an experimental database made of normal and abnormal operating conditions. Some VSS signatures based on Wavelet Leader Multifractal Analysis (WLMA) are computed on low- and high-frequency filtered stack voltage signals reflecting different physical phenomena dynamics. The resulting low- and high-frequency VSS computed for six different operating conditions are then compared to the Electrochemical Impedance Spectra (EIS) recorded in the same conditions. In this way, we intend to establish some links between the VSS patterns and the EIS based on well-known physical analyses. We also show that the dominant singularity strengths of the low (and possibly also high) frequency VSS can be considered as relevant clustering features to identify various PEMFC operating states (linked with poorer / better air diffusion, with lower / higher MEA hydration), as it is usually done with the use of the characteristic resistances intercepted on the EIS graph x-axis.

We analyze the design of optimal medical insurance under ex post moral hazard, i.e., when illness severity cannot be observed by insurers and policyholders decide on their health expenditures. We characterize the trade-o§ between ex ante risk sharing and ex post incentive compatibility, in an optimal revelation mechanism under hidden information and risk aversion. We establish that the optimal contract provides partial insurance at the margin, with a deductible when insurersi rates are a§ected by a positive loading, and that it may also include an upper limit on coverage. We show that the potential to audit the health state leads to an upper limit on out-of-pocket expenses.

We analyze the insurance of nuclear liability risk, from theoretical and applied standpoints. Firstly, we characterize the optimal insurance scheme for a low-probability industrial accident, such as a nuclear catastrophe, in a model of collective risk-sharing. Using catastrophe bond data, we then evaluate the cost of capital sustaining such an insurance mechanism. Finally, we characterize the individual lotteries associated with the risk of a nuclear accident in France, and we estimate the optimal coverage. We conclude that the corporate liability limit currently in force is likely to be inferior to the socially optimal level.

Zeolite ZSM-12 with different Si:Al molar ratios and one-dimensional channels with 12 oxygen ring apertures (12R) was synthesized and characterized by different techniques such as: X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer-Emmett-Teller surface area (BET), elemental analysis by atomic absorption spectroscopy, Fourier transform infrared spectroscopy (FTIR) of adsorbed pyridine, and NH3 temperature-programmed desorption (TPD). The synthesized samples were tested as hydrocarbon (HC) trap adsorbents using toluene and ethylene as heavy and light probe molecules for HCs in the exhaust stream at engine cold-start. High heating rate desorption experiments were performed using the Phytronix Laser Diode Thermal Desorption system (S-960 LDTD) coupled with an Atmospheric Pressure Chemical Ionization (APCI) chamber (Phytronix Technologies, Canada) after adsorption of toluene-ethylene mixtures. Three heating rates, which reflect the actual heating rates of the catalytic muffler, were used for the desorption process: 3 °C/s, 5 °C/s, and 9 °C/s. For all solids considered in this study, the two HCs desorbed above 240 °C, which is the light-off temperature of the three-way catalyst. Ag-ZSM-12 with different Si:Al ratios was found the most appropriate HC trapping adsorbent in spite of its slightly lower adsorption capacity. A high desorption temperature for ethylene and toluene was associated with the large density of strong Lewis acid sites in this solid.

The move toward label-free screening in drug discovery has increased the demand for mass spectrometry (MS)-based analysis. Here we investigated the approach of coupling acoustic sample deposition (ASD) with laser diode thermal desorption (LDTD)-tandem mass spectrometry (MS/MS). We assessed its use in a cytochrome P450 (CYP) inhibition assay, where a decrease in metabolite formation signifies CYP inhibition. Metabolite levels for 3 CYP isoforms were measured as CYP3A4-1'-OH-midazolam, CYP2D6-dextrorphan, and CYP2C9-4'-OH-diclofenac. After incubation, samples (100 nL) were acoustically deposited onto a stainless steel 384-LazWell plate, then desorbed by an infrared laser directly from the plate surface into the gas phase, ionized by atmospheric pressure chemical ionization (APCI), and analyzed by MS/MS. Using this method, we achieved a sample analysis speed of 2.14 s/well, with bioanalytical performance comparable to the current online solid-phase extraction (SPE)-based MS method. An even faster readout speed was achieved when postreaction sample multiplexing was applied, where three reaction samples, one for each CYP, were transferred into the same well of the LazWell plate. In summary, LDTD coupled with acoustic sample deposition and multiplexing significantly decreased analysis time to 0.7 s/sample, making this MS-based approach feasible to support high-throughput screening (HTS) assays.

Audit mechanisms frequently take place in the context of repeated relationships between auditor and auditee. This paper focuses attention on the insurance fraud problem in a setting where insurers repeatedly verify claims satisfied by service providers (e.g., affiliated car repairers or members of managed care networks). We highlight a learning bias that leads insurers to over-audit service providers at the beginning of their relationship. The paper builds a bridge between the literature on optimal audit in insurance and the exploitation/exploration trade-off in multi-armed bandit problems.

ICEREGA 2017 -International Conference on Emerging and Renewable Energy: Generation and Automation, Belfort, FRANCE, 07-/07/2017 - 07/07/2017; The purpose of this article is to study the portability of a non-intrusive and free of any external / internal disturbance diagnosis tool devoted to the monitoring of the State of Health (SoH) of PEM Fuel Cell (PEMFC) stack. The tool is based on a thorough analysis of the stack voltage signal using a multifractal formalism and wavelet leaders. It offers well-suited signatures indicators on the SoH of the Fuel Cell. Some relevant descriptors extracted from these patterns (singularity features) are used in the frame of Machine Learning approaches to allow the PEMFC fault identification. The proposed diagnosis strategy is evaluated with two different PEMFC stacks. The first one is designed for automotive applications and the second one is dedicated to stationary use (micro combined heat and power - µCHP application). Framework of the 'Decentralized energy production' project, directed by EFFICACITY, the French R&D Institute for urban energy transition.

We characterize the design of insurance schemes when policyhold- ers face several insurable risks in a context of adverse selection. Split- ting risks emerges as a feature of second-best Pareto-optimal alloca- tions. This may take the form of risk-speci…c contracts, or of con- tracts where risks are bundled, but subject to di⁄erential coverage rules such as risk speci…c copayments, combined with a deductible, an out-of-pocket maximum or a cap on coverage.

In the last decade the quantitation of immunosuppressive drugs has seen vast improvements in analytical methods, optimizing time, accuracy of analysis and cost. Laser Diode Thermal Desorption (LDTD) coupled to Atmospheric Pressure Chemical ionization–tandem mass spectrometry (APCI-MS/MS) represents a technological breakthrough that removes the chromatographic separation step and thereby significantly increases the analytical throughput for the quantitation of cyclosporin A (CsA) in whole blood for therapeutic drug monitoring (TDM). A simple protein precipitation step was used prior to depositing 5 μL of the extract on a 96-well LazWell™ plate and CsA was quantified by LDTD-APCI-MS/MS. The laser pattern was set to ramp from 0 to 45% laser power within 2 s. The APCI parameters were set to negative needle voltage (−2 μA), carrier gas temperature (30 °C) and air flow rate (3 L min−1). The negative ion single reaction monitoring transitions for CsA and its internal standard cyclosporin D (CsD) were respectively m/z 1201.1/1088.9 and m/z 1214.8/1102.8; obtained with a collision energy of −40 V. The analysis was achieved within 9 s from sample to sample. The extraction procedure yielded high recovery (92%; RSD = 9.4%, n = 6). The lower limit of quantitation was fixed at the first level of calibration: 23.5 ng mL−1 (accuracy = 112.3%; RSD = 9.6%; n = 6) and a blank + 6 point linear regression up to 965 ng mL−1 was used. Using 4 levels of quality control (QC), intra-day assays (n = 6) ranged from 93.5 to 95.7% (bias) and from 3.4 to 13.1% (RSD) while inter-day assays (n = 6) ranged from 92.9 to 105.3% (bias) and from 4.9 to 7.5% (RSD). An inter-sample contamination of CsA of 2.3% was calculated that was considered negligible with respect to the range of CsA concentrations. Whole blood samples (120) from patients under CsA treatment were analyzed by LDTD-APCI-MS/MS and HPLC–ESI-MS/MS, the gold standard reference method for CsA quantification. Both methods agreed (P ≥ 0.99), with a coefficient of correlation of 0.99 (95% confidence interval 0.982–0.991). The Passing–Bablok regression revealed no significant deviation from linearity (Cusum test, P = 0.11). This method seems suitable for use in TDM of CsA.

A high-throughput, rapid, and reliable method based on laser diode thermal desorption (LDTD) and atmospheric pressure chemical ionization coupled to tandem MS (APCI-MS/MS) was used to identify and quantify chloramphenicol (CAP) residues in honey. Sample pretreatment consisted of a liquid–liquid extraction of diluted honey in water with ethyl acetate containing stearic acid. After extraction, a 2 μL aliquot of the organic phase was deposited into a 96-well plate prior to detection by LDTD-APCI-MS/MS. The total analysis time was less than 6 s compared to several minutes for traditional chromatographic methods used for CAP detection, since no chromatographic separation was necessary. The extraction and analysis were made with honey samples of different color grading ranging from extra white to dark amber. The method showed good linearity (R2 = 0.99995) within a concentration range of 0.1 to 500 ng/g for CAP with D5-CAP as an internal standard. The RSD varied between 8 and 24% over the calibration range (n = 4). The method LOD for CAP in honey was 0.19 ng/g. This work demonstrates that LDTD-APCI-MS/MS could be used for fast and effective quantification of CAP in honey samples.

A captive is an insurance or reinsurance company established by a parent group to finance its own risks. Captives mix internal risk pooling between the business units of the parent group and risk transfer toward the reinsurance market. We analyze captives from an optimal insurance contract perspective. The paper considers the vertical contractual chain that links firstly business units to insurance captives or to "fronters" through insurance contracts, secondly fronters to reinsurance captives through the cession of risks and thirdly insurance or reinsurance captives to reinsurers through cessions or retrocessions. In particular, the risk cession by fronters to a reinsurance captive trades o¤ the benefits derived from recouped premiums and from the risk sharing advantage of an "umbrella reinsurance policy", against the risks that result from the captive liabilities. The optimal captive scheme depends on the price of coverage in insurance and reinsurance markets and on the parent group's corporate capital. Since these variables fluctuate across time, the analysis developed in this paper corroborates the intertemporal variability of captives activity.

Degradation of bisphenol A (BPA), an endocrine disruptor from water has recently attracted great interest. The primary objective of this work was to prepare ZnO nanoparticles and to study the effect of these nanoparticles on changing the viscosity and zeta potential value of water and simultaneous degradation of BPA. Whey material was used as a dispersant for the preparation of nanoparticles. Analysis of BPA in water was carried out using the ultrafast method (15 s per sample) based on the Laser Diode Thermal Desorption/Atmospheric Pressure Chemical Ionization (LDTD/APCI) coupled to tandem Mass Spectrometry (MS/MS). The whey stabilized nanoparticles displayed lower agglomeration with higher BPA degradation power than those prepared without a stabilizer. The sample with whey stabilized nanoparticle showed lower viscosity and higher zeta potential value in the medium leading to higher degradation of BPA as compared to non-stabilized one. The whey stabilized ZnO nanoparticles were able to degrade 100% BPA from the medium as compared to 60% with the nonstabilized one. The application of a stabilizer for ZnO nanoparticles may substantially enhance the performance of nanoparticles for environmental applications.

We show that an equilibrium always exists in the Rothschild-Stiglitz insurance market model with adverse selection and an arbitrary number of risk types, when insurance contracts include policy dividend rules. The Miyazaki-WilsonSpence state-contingent allocation is an equilibrium allocation, and it is the only one when out-of-equilibrium beliefs satisfy a robustness criterion. It is shown that stock insurers and mutuals may coexist, with stock insurers o⁄ering insurance coverage at actuarial price and mutuals cross-subsidizing risks.

This paper considers the interaction between input sharing and labor market pooling in urban areas. In particular, it examines the impact of the size of a city and business risks on the organizational structures of firms located in urban agglomerations, and it also discusses the impact of organizational structure on incentives to insure workers against income risks. It is shown that manufacturing firms suffer from a coordination game in their decision to outsource production. The existence of idiosyncratic risks causes manufacturers to refrain from outsourcing. The incentives to offer wage and employment protection to workers are more pronounced when manufacturers outsource the production of their inputs to a local market, which mitigates the impact of labor market pooling.

Cet article examine les conséquences de l’hypothèse de rationalité approchée de Akerlof et Yellen, dans le cadre de la théorie des équilibres à prix fixes avec rationnements. Nous envisageons une économie soumise à des chocs monétaires transitoires où les prix restent fixés au niveau walrasien anticipé. Les agents forment des conjectures qui définissent les prix auxquels ils pensent pouvoir réaliser les échanges. Nous montrons que, quelles que soient ces conjectures, à l’équilibre à prix fixes le comportement des agents est approximativement rationnel : plus précisément, le gain individuel que les agents anticipent pouvoir réaliser en modifiant les prix est du second ordre par rapport aux chocs. Simultanément, ces chocs ont des effets du premier ordre sur les échanges réalisés., This paper investigates the consequences of the near-rationality assumption of Akerlof and Yellen, in the framework of the theory of fixed price equilibria with quantity rationing. We consider an economy with monetary transitory shocks where prices remain fixed at the expected walrasian equilibrium. Agents have conjectures about the prices at which trades can be realized. We show that, at the fixed price equilibria, the agents' behaviour is near-rational for all possible conjectures. More precisely, the individual welfare gains that agents expect to be able to realize by modifying prices is second order with respect to shocks. Simultaneously, the shocks exert first order effects on realized trades.

This paper investigates the role of private insurance in the prevention and mitigation of natural disasters. We characterize the equity-efficiency trade-off faced by the policymakers under imperfect information about individual prevention costs. It is shown that a competitive insurance market with actuarial ratemaking and compensatory tax-subsidy transfers is likely to dominate regulated uniform insurance pricing rules or state-funded assistance schemes. The model illustrates how targeted tax cuts on insurance contracts can improve the incentives to prevention, while compensating the individuales with high prevention costs. The paper also highlights the complementarity between individual incentives through tax cuts and collective incentives through grants to the local jurisdictions where risk management plans are enforced, Cet article analyse le rôle de l'assurance privée dans la prévention et la réduction des dommages des catastrophes naturelles. Nous caractérisons le dilemme équité-efficacité auquel sont confrontés les décideurs politiques dans un contexte d'information imparfaite sur les coûts individuels de prévention. Il est montré qu'un marché concurrentiel d'assurance avec une tarification actuarielle, associé à des transferts sous forme de taxe ou de subvention, domine vraisemblablement les règles de tarification uniforme de l'assurance ou les schémas d'indemnisation financée par l'Etat. Le modèle montre comment des taxes différentiées sur les contrats d'assurance peuvent accroître les incitations à la prévention, tout en faisant bénéficier d'un transfert compensateur les individus dont les coûts de prévention sont élevés. L'article met aussi l'accent sur la complémentarité entre les incitations individuelles par la fiscalité et les incitations collectives par l'attribution de subventions aux collectivités locales qui mettent en place des politiques de prévention des risques de catastrophes naturelle

Cigarette smoking is accepted as an important factor that increases the risk for the initiation and progress of chronic periodontitis. However, the effect of cigarette smoking on the recurrence of disease in patients undergoing regular maintenance therapy is less understood. Therefore, we set out to assess disease progression longitudinally in smoking and non-smoking subjects with chronic periodontitis undergoing periodontal maintenance therapy every 3 to 4 months.A total of 108 subjects undergoing regular maintenance therapy for chronic periodontitis were followed over a 3-year period. Self-reports of smoking status were confirmed by analysis of exhaled carbon monoxide concentrations. Clinical parameters (plaque index [PI], bleeding on probing [BOP], clinical attachment loss [CAL], probing depth [PD], and tooth loss) were recorded at yearly reevaluation visits. The study was carried out in a university hospital setting.Longitudinal measurements were obtained from 81 (75%) subjects. There were no differences in inflammatory indices at baseline or over time (PI and BOP; both P0.05) between smokers (N = 16; age: 54 +/- 6 years) and non-smokers (N = 65; age: 59 +/- 14 years). Likewise, there was no difference between the smoking groups with respect to disease progression (measured as changes in prevalence [number] and proportion [percentage] of progressing sites and as mean CAL, PD, and tooth loss; all P0.05).In this small population, regular maintenance treatment in a cross-section of highly motivated subjects with chronic periodontitis seemed to be equally successful in preventing progressive periodontal tissue destruction in current smokers and current non-smokers.

International audience; This paper provides a theoretical analysis of the benefits for an insurance company to develop its own network of service providers when insurance fraud is characterized by collusion between policyholders and providers. In a static framework without collusion, exclusive affiliation of providers allows insurance companies to recover some market power and to lessen competition on the insurance market. This entails a decrease in the insured's welfare. However, exclusive affiliation of providers may entail a positive effect on customers' surplus when insurers and providers are engaged in a repeated relationship. In particular, while insurers must cooperate to retaliate against a fraudulent provider under non-exclusive affiliation, no cooperation is needed under exclusive affiliation. In that case, an insurer is indeed able to reduce the profit of a malevolent provider by moving to collusion-proof contracts when collusion is detected, and this threat may act as a deterrent for fraudulent activities. This possibility may supplement an inefficient judicial system: it is thus a second-best optimal anti-fraud policy.

This paper describes the development of a high-throughput method for the analysis of cytochrome P450 (CYP) inhibition assay incubation samples using laser diode thermal desorption interfaced with atmospheric pressure chemical ionization mass spectrometry (LDTD-APCI-MS). Data for the CYP isoforms 3A4, 2D6, 2C9, and 1A2 from competitive inhibition assays are shown. The potential for inhibition of the CYP isoforms was measured by monitoring the level of the metabolites 6beta-hydroxytestosterone (3A4), dextrorphan (2D6), 4'-hydroxydiclofenac (2C9), and acetaminophen (1A2) formed in the presence of drug candidates using an eight-point titration. The analytical method involves plating of the inhibition samples on specially designed 96-well plates with stainless steel bottoms, followed by direct analysis using the LDTD source. Validation of the LDTD-MS method was performed by testing for interferences, reproducibility, dynamic range, ion suppression, and the ability of the source to produce comparable results to previously validated LC-MS methods. IC50 values for each CYP isoform using 33 different test compounds showed excellent agreement between LDTD-APCI-MS and LC-MS methods and literature values where available. Assay analysis time using the LDTD-APCI source is reduced to less than 30 min for a single 96-well plate compared to greater than 10 h using the LC-MS method. The LDTD-APCI-MS and LC-MS methods and results are compared and limitations and future potential for LDTD-APCI-MS are discussed.

Economic geography models predict the agglomeration of manufacturing activies only if the workforce is mobile. Still, as the E.U.'s experience shows, core-periphery patterns exist even though the workforce is rather immobile. The paper provides a theoretical explanation for such core-periphery patterns through the effect that unions have on firms' incentive to agglomerate in a region. The paper offers fully analytical results about location equilibria and some interesting welfare properties. (c) 2005 Elsevier B.V. All rights reserved.

It is sometimes argued that road safety measures or automobile safety standards fail to save lives because safer highways or safer cars induce more dangerous driving. A similar but less extreme view is that ignoring the behavioral adaptation of drivers would bias the cost-benefit analysis of a traffic safety measure. This article derives cost-benefit rules for automobile safety regulation when drivers may adapt their risk-taking behavior in response to changes in the quality of the road network. The focus is on the financial externalities induced by accidents because of the insurance system as well as on the consequences of drivers' risk aversion. We establish that road safety measures are Pareto improving if their monetary cost is lower than the difference between their (adjusted for risk aversion) direct welfare gain with unchanged behavior and the induced variation in insured losses due to drivers' behavioral adaptation. The article also shows how this rule can be extended to take other accident external costs into account.

The usual distinction between insurance risks and financial risks now become less marked in view of the transformation in the risks faced by individuals and firms. The boundaries of insurability are pushed away by risk transfer mechanisms, while firms’ self-insurance tends to associate insurance and finance within a global risk management industry. JEL classification : G22, La distinction habituelle entre risques d’assurance et risques financiers s’atténue aujourd’hui devant les transformations des risques auxquels sont confrontés individus et entreprises. Les techniques de transfert des risques repoussent les limites de l’assurabilité, tandis que se développent des formes d’auto-assurance des entreprises qui tendent à associer assurance et finance au sein d’une industrie globalisée de la gestion des risques. Classification JEL : G22, Picard Pierre. Risques d'assurance et risques financiers. In: Revue d'économie financière, n°80, 2005. L'industrie mondiale de l'assurance. pp. 15-25.

ABB’s commitment to adding value for customers includes a constant quest for innovation and improvement – new ideas, new thinking, new solutions and stronger customer relationships. FlexPlace is an example of that new thinking. Developed at ABB’s body‐in‐white facility in France, it is a software solution that will greatly improve efficiency and cost‐effectiveness in auto body assembly. Robots with FlexPlace use sensors and pattern recognition to automatically assemble the larger parts of a car, like the roof and the doors, with sub‐millimeter accuracy, and do away with the heavy and expensive tooling traditionally used.

By developing a class of dynamic stochastic general equilibrium models with nominal rigidities and assuming a two-country currency union with sovereign risk, we show that there is not necessarily a trade-off between the prevention of default risk and stabilizing inflation. Under optimal monetary and fiscal policy, comprising a de facto inflation stabilization policy, the tax rate as an optimal fiscal policy tool plays an important role in stabilizing inflation, although not completely because of the distorted steady state. Changes in the tax rate to minimize welfare costs via stabilizing inflation then improve the fiscal surplus, and because of this and the incompletely stabilized inflation, the default rate does not increase as much.

This paper studies the costs and benefits of the adoption of the policy of free movement for workers. For the countries to agree on uncontrolled movement of workers, the short run costs must be outweighed by the long term benefits that result from better labor market flexibility and income smoothing. We show that such policies are less likely to be adopted when workers are impatient and less risk averse workers, when production technologies display decreasing returns and when countries trade a share of their products.

We develop a model where workers both choose their residential location (geographical space) and social interactions (social space). In equilibrium, we show under which condition the majority group resides close to the job center while the minority group lives far away from it. Even though the two populations are ex ante totally identical, we find that the majority group experiences a lower unemployment rate than the minority group and tends to socially interact more with other workers of its own group. Within each group, we demonstrate that workers residing farther away from the job center tend to search less for a job and are less likely to be employed. This model is thus able to explain why ethnic minorities are segregated in the urban and social space and why this leads to adverse labor-market outcomes in the absence of any discrimination against the minority group.

We study how the level of trade costs and the intensity of competition interact to explain the nature and intensity of trade within a given industry and the location of firms across countries. As trade costs decrease from very high to very low values, the global economy moves from autarky to two-way trade, through one-way trade from the larger to the smaller region. By exploring the intensive and extensive margins of exports, we investigate how the intensity of trade reacts to the degree of competitiveness. Furthermore, when firms are free to change location, they flow from the small to the large country, and the larger country is always a net exported on the manufactured good. Firms located in the big country have a bigger size than those located in the small one. Under one-way trade, the relocation of firms changes their attitude toward export.

Insurers have the reputation of being bad payers who nitpick whenever an opportunity arises. However, this nitpicking activity has a positive impact on their auditing strategy since auditing may prove profitable when claimsare not fraudulent. We show that reducing the indemnity payments of audited claims induces a lower fraud rate at equilibrium and that some degree of nitpicking is socially optimal when insurance fraud is a concern. Itsremains optimal even if it induces adverse effects on policyholders' moral standards.; Les assureurs ont la réputation d'être de mauvais payeurs qui pinaillent chaque fois que l'occasion se présente. Cependant, ce pinaillage à un impact positif sur leur politique de vérification des demandes d'indemnisation car même en l'absence de fraude, l'information obtenue lors d'un audit peut permettre de réduire l'indemnité. Cette incitation à plus de contrôles réduit la (vraie) fraude à l'assurance et au final, les primes d'assurance. Les auteurs montrent qu'un certain degré de pinaillage est socialement optimal. Cela reste le cas même si la réputation de mauvais payeurs des assureurs réduit le scrupule des assurés à frauder.

This paper analyzes an irreversible “where-and-when” investment decision, in which a govern- ment must decide not only when to invest in income-increasing infrastructure but also where to make the investment, doing so under imperfect observability of the investment gains. The two models considered in the paper differ in the source of the imperfection. In the signal model, the imperfection comes from imperfect observability of initial income gains from the investment, while in the option model, it comes from the stochastic nature of the income gains in the second period. In addition to providing the first treatment of this type of problem, the analysis shows that the influences of underlying parameters on whether or not the government waits to invest are similar in the two models.

Background —Estrogen may increase the long-term survival of women who have suffered from a myocardial infarction (MI). We examined the acute and chronic influence of estrogen on MI in the rat left coronary artery ligation model. Methods and Results —Female Sprague-Dawley rats (10 to 12 weeks, n=93), divided into 3 groups (rats with intact ovaries, ovariectomized rats administered 17β-estradiol [17β-E 2 ] replacement, and ovariectomized rats administered placebo 2 weeks before MI), were randomized to left coronary artery ligation (n=66) or sham-operated (n=27) groups. Ten to 11 weeks after MI, rats were randomly assigned to either (1) assessment of left ventricular (LV) function and morphometric analysis or (2) measurement of cardiopulmonary mRNA expression of preproendothelin-1 and endothelin A and B receptors. Acutely, estrogen was associated with a trend toward increased mortality. Infarct size was increased in the 17β-E 2 group compared with the placebo group (42±2% versus 26±3%, respectively; P =0.01). Chronically, wall tension was normalized through a reduction in LV cavity size with estrogen treatment (419±41 mm Hg/mm for 17β-E 2 versus 946±300 mm Hg/mm for placebo, P =0.039). In the LV, there was a 2.5-fold increase in endothelin B mRNA expression after MI in placebo-treated rats ( P =0.004 versus sham-operated rats) that was prevented in the 17β-E 2 group ( P =NS versus sham-operated rats). Conclusions —These results suggest that estrogen is detrimental at the time of MI or early post-MI period, resulting in an increased size of infarct or infarct expansion, but chronically, it can normalize wall tension and inhibit LV dilatation, which may in turn lead to increased long-term survival. Regulation of the endothelin system, particularly the expression of the endothelin B receptor, may contribute to these estrogenic effects.