Global instability of currencies: reasons and perspectives according to the state-corporation hegemonic stability theory

This paper analyses reasons of the instability of the world monetary system. The author considers this problem from historical and contemporary perspectives. According to presented point of view banknotes and electronic money which replaced gold and silver coins in popular circulation are the most important reason of the instability. There are also proven positive and negative consequences of money instability. Reforms of the world monetary system need agreement within the global collective hegemony of state-powers and transnational corporations.

Isolation and characterization of genomic DNA sequences that enhance the stability of plasmid DNA in mammalian cells /

The ease of production and manipulation has made plasmid DNA a prime target for its use in gene transfer technologies such as gene therapy and DNA vaccines. The major drawback of plasmid however is its stability within mammalian cells. Plasmid DNA is usually lost by cellular mechanisms or as a result of mitosis by simple dilution. This study set out to search for mammalian genomic DNA sequences that would enhance the stability of plasmid DNA in mammalian cells.Creating a plasmid based genomic DNA library, we were able to screen the human genome by transfecting the library into Human Embryonic Kidney (HEK 293) Cells. Cells that contained plasmid DNA were selected, using G418 for 14 days. The resulting population was then screened for the presence of biologically active plasmid DNA using the process of transformation as a detector.A commercially available plasmid DNA isolation kit was modified to extract plasmid DNA from mammalian cells. The standardized protocol had a detection limit of -0.6 plasmids per cell in one million cells. This allowed for the detection of 45 plasmids that were maintained for 32 days in the HEK 293 cells. Sequencing of selected inserts revealed a significantly higher thymine content in comparison to the human genome. Sequences with high A/T content have been associated with Scaffold/Matrix Attachment Region (S/MAR) sequences in mammalian cells. Therefore, association with the nuclear matrix might be required for the stability of plasmids in mammalian cells.

Investigating the role of apoptosis regulator EndoG on exogenous DNA uptake, stability, replication and recombination

Endonuclease G (EndoG) is a well conserved mitochondrial nuclease with dual lethal and vital roles in the cell. It non-specifically cleaves endogenous DNA following apoptosis induction, but is also active in non-apoptotic cells for mitochondrial DNA (mtDNA) replication and may also be important for replication, repair and recombination of genomic DNA. The aim of our study was to examine whether EndoG exerts similar activities on exogenous DNA substrates such as plasmid DNA (pDNA) and viral DNA vectors, considering their importance in gene therapy applications. The effects of EndoG knockdown on pDNA stability and levels of encoded reporter gene expression were evaluated in the cervical carcinoma HeLa cells. Transfection of pDNA vectors encoding short-hairpin RNAs (shRNAs) reduced levels of EndoG mRNA and nuclease activity in HeLa cells. In physiological circumstances, EndoG knockdown did not have an effect on the stability of pDNA or the levels of encoded transgene expression as measured over a four day time-course. However, when endogenous expression of EndoG was induced by an extrinsic stimulus (a cationic liposome transfection reagent), targeting of EndoG by shRNA improved the perceived stability and transgene expression of pDNA vectors. Therefore, EndoG is not a mediator of exogenous DNA clearance, but in non-physiological circumstances it may non-specifically cleave intracellular DNA regardless of its origin. To investigate possible effects of EndoG on viral DNA vectors, we constructed and evaluated AdsiEndoG, a first generation adenovirus (Ad5 ΔE1) vector encoding a shRNA directed against EndoG mRNA, along with appropriate Ad5 ΔE1 controls. Infection of HeLa cells with AdsiEndoG at a multiplicity of infection (MOI) of 10 p.f.u./cell resulted in an early cell proliferation defect, absent from cells infected at equivalent MOI with control Ad5 ΔE1 vectors. Replication of Ad5 ΔE1 DNA was detected for all vectors, but AdsiEndoG DNA accumulated to levels that were 50 fold higher than initially, four days after infection, compared to 14 fold for the next highest control Ad5 ΔE1 vector. Deregulation of the cell cycle by EndoG depletion, which is characterized by an accumulation of cells in the G2/M transition, is the most likely reason for the observed cell proliferation defect. The enhanced replication of AdsiEndoG is consistent with this conclusion, as Ad5 ΔE1 DNA replication is intimately related to cell cycling and prolongation or delay in G2/M greatly enhances this process. Furthermore, infection of HeLa with AdsiEndoG at MOI of 50 p.f.u./cell resulted in an almost complete disappearance of viable, adherent tumour cells from culture, whereas almost a third of the cells were still adherent after infection with control Ad5 ΔE1 vectors, relative to the non-infected control. Therefore, targeting of EndoG by RNAi is a viable strategy for improving the oncolytic properties of first generation adenovirus vectors. In addition, AdsiEndoG-mediated knockdown of EndoG reduced homologous recombination between pDNA substrates in HeLa cells. The effect was modest but, nevertheless demonstrated that the proposed role of EndoG in homologous recombination of cellular DNA also extends to exogenous DNA substrates.

Information Sharing and the Stability of Cooperation in Research Joint Ventures.

The model studies information sharing and the stability of cooperation in cost reducing Research Joint Ventures (RJVs). In a four-stage game-theoretic framework, firms decide on participation in a RJV, information sharing, R&D expenditures, and output. An important feature of the model is that voluntary information sharing between cooperating firms increases information leakage from the RJV to outsiders. It is found that it is the spillover from the RJV to outsiders which determines the decision of insiders whether to share information, while it is the spillover affecting all firms which determines the level of information sharing within the RJV. RJVs representing a larger portion of firms in the industry are more likely to share information. It is also found that when sharing information is costless, firms never choose intermediate levels of information sharing : they share all the information or none at all. The size of the RJV is found to depend on three effects : a coordination effect, an information sharing effect, and a competition effect. Depending on the relative magnitudes of these effects, the size of the RJV may increase or decrease with spillovers. The effect of information sharing on the profitability of firms as well as on welfare is studied.

Simulation-Based Finite-Sample Tests for Heteroskedasticity and ARCH Effects.

A wide range of tests for heteroskedasticity have been proposed in the econometric and statistics literature. Although a few exact homoskedasticity tests are available, the commonly employed procedures are quite generally based on asymptotic approximations which may not provide good size control in finite samples. There has been a number of recent studies that seek to improve the reliability of common heteroskedasticity tests using Edgeworth, Bartlett, jackknife and bootstrap methods. Yet the latter remain approximate. In this paper, we describe a solution to the problem of controlling the size of homoskedasticity tests in linear regression contexts. We study procedures based on the standard test statistics [e.g., the Goldfeld-Quandt, Glejser, Bartlett, Cochran, Hartley, Breusch-Pagan-Godfrey, White and Szroeter criteria] as well as tests for autoregressive conditional heteroskedasticity (ARCH-type models). We also suggest several extensions of the existing procedures (sup-type of combined test statistics) to allow for unknown breakpoints in the error variance. We exploit the technique of Monte Carlo tests to obtain provably exact p-values, for both the standard and the new tests suggested. We show that the MC test procedure conveniently solves the intractable null distribution problem, in particular those raised by the sup-type and combined test statistics as well as (when relevant) unidentified nuisance parameter problems under the null hypothesis. The method proposed works in exactly the same way with both Gaussian and non-Gaussian disturbance distributions [such as heavy-tailed or stable distributions]. The performance of the procedures is examined by simulation. The Monte Carlo experiments conducted focus on : (1) ARCH, GARCH, and ARCH-in-mean alternatives; (2) the case where the variance increases monotonically with : (i) one exogenous variable, and (ii) the mean of the dependent variable; (3) grouped heteroskedasticity; (4) breaks in variance at unknown points. We find that the proposed tests achieve perfect size control and have good power.

Candidate Stability and Nonbinary Social Choice

A desirable property of a voting procedure is that it be immune to the strategic withdrawal of a candidate for election. Dutta, Jackson, and Le Breton (Econometrica, 2001) have established a number of theorems that demonstrate that this condition is incompatible with some other desirable properties of voting procedures. This article shows that Grether and Plott's nonbinary generalization of Arrow's Theorem can be used to provide simple proofs of two of these impossibility theorems.

Asymptotic Approximations in the Near-Integrated Model with a Non-Zero Initial Condition

This paper considers various asymptotic approximations in the near-integrated firstorder autoregressive model with a non-zero initial condition. We first extend the work of Knight and Satchell (1993), who considered the random walk case with a zero initial condition, to derive the expansion of the relevant joint moment generating function in this more general framework. We also consider, as alternative approximations, the stochastic expansion of Phillips (1987c) and the continuous time approximation of Perron (1991). We assess how these alternative methods provide or not an adequate approximation to the finite-sample distribution of the least-squares estimator in a first-order autoregressive model. The results show that, when the initial condition is non-zero, Perron's (1991) continuous time approximation performs very well while the others only offer improvements when the initial condition is zero.

Asymptotic Distribution of a Simple Linear Estimator for VARMA Models in Echelon Form

In this paper, we study the asymptotic distribution of a simple two-stage (Hannan-Rissanen-type) linear estimator for stationary invertible vector autoregressive moving average (VARMA) models in the echelon form representation. General conditions for consistency and asymptotic normality are given. A consistent estimator of the asymptotic covariance matrix of the estimator is also provided, so that tests and confidence intervals can easily be constructed.

Inférence doublement robuste en présence de données imputées dans les enquêtes

L'imputation est souvent utilisée dans les enquêtes pour traiter la non-réponse partielle. Il est bien connu que traiter les valeurs imputées comme des valeurs observées entraîne une sous-estimation importante de la variance des estimateurs ponctuels. Pour remédier à ce problème, plusieurs méthodes d'estimation de la variance ont été proposées dans la littérature, dont des méthodes adaptées de rééchantillonnage telles que le Bootstrap et le Jackknife. Nous définissons le concept de double-robustesse pour l'estimation ponctuelle et de variance sous l'approche par modèle de non-réponse et l'approche par modèle d'imputation. Nous mettons l'emphase sur l'estimation de la variance à l'aide du Jackknife qui est souvent utilisé dans la pratique. Nous étudions les propriétés de différents estimateurs de la variance à l'aide du Jackknife pour l'imputation par la régression déterministe ainsi qu'aléatoire. Nous nous penchons d'abord sur le cas de l'échantillon aléatoire simple. Les cas de l'échantillonnage stratifié et à probabilités inégales seront aussi étudiés. Une étude de simulation compare plusieurs méthodes d'estimation de variance à l'aide du Jackknife en terme de biais et de stabilité relative quand la fraction de sondage n'est pas négligeable. Finalement, nous établissons la normalité asymptotique des estimateurs imputés pour l'imputation par régression déterministe et aléatoire.

Implications of banking regulation for banking sector stability and welfare

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

Importance of the HSP90 molecular chaperoning pathway for antibody diversification by determining AID stability

La protéine AID (déaminase induite par l’activation) joue un rôle central dans la réponse immunitaire adaptative. En désaminant des désoxycytidines en désoxyuridines au niveau des gènes immunoglobulines, elle initie l’hypermutation somatique (SHM), la conversion génique (iGC) et la commutation isotypique (CSR). Elle est essentielle à une réponse humorale efficace en contribuant à la maturation de l’affinité des anticorps et au changement de classe isotypique. Cependant, son activité mutagénique peut être oncogénique et causer une instabilité génomique propice au développement de cancers et de maladies autoimmunes. Il est donc critique de réguler AID, en particulier ses niveaux protéiques, pour générer une réponse immunitaire efficace tout en minimisant les risques de cancer et d’autoimmunité. Un élément de régulation est le fait qu’AID transite du cytoplasme vers le noyau mais reste majoritairement cytoplasmique à l’équilibre. AID est par ailleurs plus stable dans le cytoplasme que dans le noyau, ce qui contribue à réduire sa présence à proximité de l’ADN. Le but de cette thèse était d’identifier de nouveaux partenaires et déterminants d’AID régulant sa stabilité et ses fonctions biologiques. Dans un premier temps, nous avons identifié AID comme une nouvelle protéine cliente d’HSP90. Nous avons montré qu’HSP90 interagit avec AID dans le cytoplasme, ce qui empêche la poly-ubiquitination d’AID et sa dégradation par le protéasome. En conséquence, l’inhibition d’HSP90 résulte en une diminution significative des niveaux endogènes d’AID et corrèle avec une réduction proportionnelle de ses fonctions biologiques dans la diversification des anticorps mais aussi dans l’introduction de mutations aberrantes. Dans un second temps, nous avons montré que l’étape initiale dans la stabilisation d’AID par la voie de chaperonnage d’HSP90 dépend d’HSP40 et d’HSP70. En particulier, la protéine DnaJa1, qui fait partie de la famille des protéines HSP40s, limite la stabilisation d’AID dans le cytoplasme. La farnésylation de DnaJa1 est importante pour l’interaction entre DnaJa1 et AID et moduler les niveaux de DnaJa1 ou son état de farnésylation impacte à la fois les niveaux endogènes d’AID mais aussi la diversification des anticorps. Les souris DNAJA1-/- présentent une réponse immunitaire compromise en cas d’immunisation, qui est dûe à des niveaux réduits d’AID et un défaut de commutation de classe. Dans un troisième temps, nous avons montré que la protéine AID est intrinsèquement plus instable que sesprotéines paralogues APOBEC. Nous avons identifié l’acide aspartique en seconde position d’AID ainsi qu’un motif semblable au PEST comme des modulateurs de la stabilité d’AID. La modification de ces motifs augmente la stabilité d’AID et résulte en une diversification des anticorps plus efficace. En conclusion, l’instabilité intrinsèque d’AID est un élément de régulation de la diversification des anticorps. Cette instabilité est en partie compensée dans le cytoplasme par l’action protective de la voie de chaperonnage DnaJa1-HSP90. Par ailleurs, l’utilisation d’inhibiteurs d’HSP90 ou de farnésyltransférases pourrait être un outil intéressant pour la modulation indirecte des niveaux d’AID et le traitement de lymphomes/leucémies et de maladies auto-immunes causés par AID.