Deux précurseurs français du pacifisme et de l'arbitrage international /

Author's autographed presentation copy to M. Lammasch.

Assimetria de informação no mercado de seguro de automóveis

Neste trabalho, estudaremos as possibilidades de existência de assimetria de informação relevante no mercado de seguros de automóveis brasileiro. Mais especificamente, estudaremos a relação entre o nsco empírico dos segurados, supostamente uma informação assimétrica, e sua demanda por cobertura. Utilizando uma extensa e detalhada base de dados, obtida junto a Superintendência de Seguros Privados (SUSEP), implementamos os principais testes econométricos existentes na literatura (paramétricas e semi­ paramétricas) para verificar a existência de assimetria de informação relevante no mercado de seguros de automóveis brasileiro. Inicialmente, replicamos os testes propostos por Chiappori e Salanié (2000) e Dionne, Gouriéroux e Vanasse (2001) e obtivemos o mesmo resultado: ausência de dependência condicional entre cobertura con­ tratada e risco empírico. Porém, constatamos que este resultado não é robusto a alterações marginais na metodologia de teste. Em seguida, estudamos uma característica peculiar dos contratos brasileiros: a não-monotonicidade das coberturas. Veremos que segurados mais arriscados terão incentivos em demandar contratos com franquias maiores (e, portanto, com menores coberturas). Após exaustivos testes, constatamos que tal característica inverte, de fato, o sinal da correlação entre cobertura e risco. Por fim, testamos se os prêmios dos contratos de seguro são funções lineares da cobertura. Constatamos que sim. Com isso, concluímos que as seguradoras não utilizam o par prêmio/ cobertura para separar os segurados de acordo com seu nsco (tal como prevê os modelos que consideram a existência de seleção adversa nesse mercado). Os resultados obtidos neste trabalho sugerem que, no mínimo, não devemos ignorar a possibilidade de existência de assimetria de informação relevante no mercado segurador brasileiro. Sendo assim, sugerimos que o apreçamento do risco nos contratos de seguro não deva se valer apenas de ferramentas atuariais, tal como é feito atualmente, mas deve considerar também os incentivos implícitos que os contratos de seguro exercem sobre o comportamento (arriscado) dos segurados.

Effects on school enrollment and performance of a conditional transfers program in Mexico

We study the effects of a conditional transfers program on school enrollment and performance in Mexico. We provide a theoretical framework for analyzing the dynamic educational decision and process inc1uding the endogeneity and uncertainty of performance (passing grades) and the effect of a conditional cash transfer program for children enrolled at school. Careful identification of the program impact on this model is studied. This framework is used to study the Mexican social program Progresa in which a randomized experiment has been implemented and allows us to identify the effect of the conditional cash transfer program on enrollment and performance at school. Using the mIes of the conditional program, we can explain the different incentive effects provided. We also derive the formal identifying assumptions needed to provide consistent estimates of the average treatment effects on enrollment and performance at school. We estimate empirically these effects and find that Progresa had always a positive impact on school continuation whereas for performance it had a positive impact at primary school but a negative one at secondary school, a possible consequence of disincentives due to the program termination after the third year of secondary school.

Microphotoluminescence investigation of InAs quantum dot active region in 1.3 mu m vertical cavity surface emitting laser structure

Microphotoluminescence (mu-PL) investigation has been performed at room temperature on InAs quantum dot (QD) vertical cavity surface emitting laser (VCSEL) structure in order to characterize the QD epitaxial structure which was designed for 1.3 mu m wave band emission. Actual and precise QD emission spectra including distinct ground state (GS) and excited state (ES) transition peaks are obtained by an edge-excitation and edge-emission (EEEE) mu-PL configuration. Conventional photoluminescence methods for QD-VCSELs structure analysis are compared and discussed, which indicate the EEEE mu-PL is a useful tool to determine the optical features of the QD active region in an as-grown VCSEL structure. Some experimental results have been compared with simulation results obtained with the aid of the plane-wave admittance method. After adjustment of epitaxial growth according to EEEE mu-PL measurement results, QD-VCSEL structure wafer with QD GS transition wavelength of 1300 nm and lasing wavelength of 1301 nm was obtained.

Chronic active hepatitis with high level of anti-ds-DNA detected by a solid phase radioimmunoassay

SCOPUS: ar.j

Analytical laboratory comparison of major and minor constituents in an active crater lake

info:eu-repo/semantics/published

Screening of electrophilic compounds yields an aziridinyl peptide as new active-site directed SARS-CoV main protease inhibitor.

The coronavirus main protease, Mpro, is considered a major target for drugs suitable to combat coronavirus infections including the severe acute respiratory syndrome (SARS). In this study, comprehensive HPLC- and FRET-substrate-based screenings of various electrophilic compounds were performed to identify potential Mpro inhibitors. The data revealed that the coronaviral main protease is inhibited by aziridine- and oxirane-2-carboxylates. Among the trans-configured aziridine-2,3-dicarboxylates the Gly-Gly-containing peptide 2c was found to be the most potent inhibitor.

Vasoactivity of AG014699, a clinically active small molecule inhibitor of poly(ADP-ribose) polymerase: a contributory factor to chemopotentiation in vivo?

Purpose: Poly(ADP-ribose) polymerase (PARP) plays an important role in DNA repair, and PARP inhibitors can enhance the activity of DNA-damaging agents in vitro and in vivo. AG014699 is a potent PARP inhibitor in phase II clinical development. However, the range of therapeutics with which AG014699 could interact via a DNA-repair based mechanism is limited. We aimed to investigate a novel, vascular-based activity of AG014699, underlying in vivo chemosensitization, which could widen its clinical application.

Experimental Design: Temozolomide response was analyzed in vitro and in vivo. Vessel dynamics were monitored using “mismatch” following the administration of perfusion markers and real-time analysis of fluorescently labeled albumin uptake in to tumors established in dorsal window chambers. Further mechanistic investigations used ex vivo assays of vascular smooth muscle relaxation, gut motility, and myosin light chain kinase (MLCK) inhibition.

Results: AG014699 failed to sensitize SW620 cells to temozolomide in vitro but induced pronounced enhancement in vivo. AG014699 (1 mg/kg) improved tumor perfusion comparably with the control agents nicotinamide (1 g/kg) and AG14361 (forerunner to AG014699; 10 mg/kg). AG014699 and AG14361 relaxed preconstricted vascular smooth muscle more potently than the standard agent, hydralazine, with no impact on gut motility. AG014699 inhibited MLCK at concentrations that relaxed isolated arteries, whereas AG14361 had no effect.

Conclusion: Increased vessel perfusion elicited by AG014699 could increase tumor drug accumulation and therapeutic response. Vasoactive concentrations of AG014699 do not cause detrimental side effects to gut motility and may increase the range of therapeutics with which AG014699 could be combined with for clinical benefit.

Identification of the mitochondrial ND3 subunit as a structural component involved in the active/deactive enzyme transition of respiratory complex I

Mitochondrial complex I (NADH: ubiquinone oxidoreductase) undergoes reversible deactivation upon incubation at 30-37 degrees C. The active/deactive transition could play an important role in the regulation of complex I activity. It has been suggested recently that complex I may become modified by S-nitrosation under pathological conditions during hypoxia or when the nitric oxide: oxygen ratio increases. Apparently, a specific cysteine becomes accessible to chemical modification only in the deactive form of the enzyme. By selective fluorescence labeling and proteomic analysis, we have identified this residue as cysteine-39 of the mitochondrially encoded ND3 subunit of bovine heart mitochondria. Cysteine-39 is located in a loop connecting the first and second transmembrane helix of this highly hydrophobic subunit. We propose that this loop connects the ND3 subunit of the membrane arm with the PSST subunit of the peripheral arm of complex I, placing it in a region that is known to be critical for the catalytic mechanism of complex I. In fact, mutations in three positions of the loop were previously reported to cause Leigh syndrome with and without dystonia or progressive mitochondrial disease.

Identification of Determinants of Glucose-Dependent Insulinotropic Polypeptide Receptor That Interact with N-Terminal Biologically Active Region of the Natural Ligand

Glucose-dependent insulinotropic polypeptide receptor (GIPR), a member of family B of the G-protein coupled receptors, is a potential therapeutic target for which discovery of nonpeptide ligands is highly desirable. Structure-activity relationship studies indicated that the N-terminal part of glucose-dependent insulinotropic polypeptide (GIP) is crucial for biological activity. Here, we aimed at identification of residues in the GIPR involved in functional interaction with N-terminal moiety of GIP. A homology model of the transmembrane core of GIPR was constructed, whereas a three-dimensional model of the complex formed between GIP and the N-terminal extracellular domain of GIPR was taken from the crystal structure. The latter complex was docked to the transmembrane domains of GIPR, allowing in silico identification of putative residues of the agonist binding/activation site. All mutants were expressed at the surface of human embryonic kidney 293 cells as indicated by flow cytometry and confocal microscopy analysis of fluorescent GIP binding. Mutation of residues Arg183, Arg190, Arg300, and Phe357 caused shifts of 76-, 71-, 42-, and 16-fold in the potency to induce cAMP formation, respectively. Further characterization of these mutants, including tests with alanine-substituted GIP analogs, were in agreement with interaction of Glu3 in GIP with Arg183 in GIPR. Furthermore, they strongly supported a binding mode of GIP to GIPR in which the N-terminal moiety of GIP was sited within transmembrane helices (TMH) 2, 3, 5, and 6 with biologically crucial Tyr1 interacting with Gln224 (TMH3), Arg300 (TMH5), and Phe357 (TMH6). These data represent an important step toward understanding activation of GIPR by GIP, which should facilitate the rational design of therapeutic agents.

Evidence for a Direct and Functional Interaction between the Regulators of G Protein Signaling-2 and Phosphorylated C Terminus of Cholecystokinin-2 Receptor

Signaling of G protein-coupled receptors (GPCRs) is regulated by different mechanisms. One of these involves regulators of G protein signaling (RGS), which are diverse and multifunctional proteins that bind to active G alpha subunits of G proteins and act as GTPase-activating proteins. Little is known about the molecular mechanisms that govern the selective use of RGS proteins in living cells. We first demonstrated that CCK2R-mediated inositol phosphate production, known to be G(q-)dependent, is more sensitive to RGS2 than to RGS4 and is insensitive to RGS8. Both basal and agonist-stimulated activities of the CCK2R are regulated by RGS2. By combining biochemical functional, and in silico structural approaches, we demonstrate that a direct and functional interaction occurs between RGS2 and agonist-stimulated cholecystokinin receptor-2 (CCK2R) and identified the precise residues involved: phosphorylated Ser434 and Thr439 located in the C-terminal tail of CCK2R and Lys62, Lys63, and Gln67, located in the N-terminal domain of RGS2. These findings confirm previous reports that RGS proteins can interact with GPCRs to modulate their signaling and provide a molecular basis for RGS2 recognition by the CCK2R.