Hawks and doves in segmented markets : a formal approach to competitive aggressiveness

Competitive aggressiveness is analyzed in a simple spatial oligopolistic competition model, where each one of two firms supplies two connected markets segments, one captive the other contested. To begin with, firms are simply assumed to maximize profit subject to two constraints, one related to competitiveness, the other to market feasibility. The competitive aggressiveness of each firm, measured by the relative implicit price of the former constraint, is then endogenous and may be taken as a parameter to characterize the set of equilibria. A further step consists in supposing that competitive aggressiveness is controlled by each firm through its manager hiring decision, in a preliminary stage of a delegation game. When competition is exogenously intensified, through higher product substitutability or through larger relative size of the contested market segment, competitive aggressiveness is decreased at the subgame perfect equiibrium. This decrease partially compensates for the negative effect on profitability of more intense competition

Hawks and doves in segmented markets: a formal approach to competitive aggressiveness

Competitive aggressiveness is analyzed in a simple spatial oligopolistic competition model, where each one of two firms supplies two connected market segments, one captive the other contested. To begin with, firms are simply assumed to maximize profit subject to two constraints, one related to competitiveness, the other to market feasibility. The competitive aggressiveness of each firm, measured by the relative implicit price of the former constraint, is then endogenous and may be taken as a parameter to characterize the set of equilibria. A further step consists in supposing that competitive aggressiveness is controlled by each firm through its manager hiring decision, in a preliminary stage of a delegation game. When competition is exogenously intensified, through higher product substitutability or through larger relative size of the contested market segment, competitive aggressiveness is decreased at the subgame perfect equilibrium. This decrease partially compensates for the negative effect on profitability of more intense competition.

Cumul de mandats d’administrateur et risques anticoncurrentiels: Un vide juridique en Europe?

Souvent occultée par les situations de prises de participations minoritaires, la pratique des cumuls de mandats d’administrateur entre concurrents n’est pas sans susciter un risque d’effets anticoncurrentiels. Cette contribution s’attache, à partir d’une analyse systématique des instruments existants, à déterminer si le droit des sociétés et les principes de gouvernance d’entreprise peuvent efficacement suppléer le droit de la concurrence dans le traitement des effets négatifs induits par les cumuls, et à mettre ainsi en lumière l’existence d’un vide juridique en Europe. = Interlocking directorates between competitors may raise significant anti-competitive risks, which attract little attention in comparison to that posed by other structural links, such as minority shareholdings. This article provides a systematic analysis of the ability of current legal tools of competition law, as well as of company law and corporate governance to address those anti-competitive risks, and thereby, highlights the existence of an enforcement gap in Europe

Decitabine encapsulation in nanovector to improve acute myeloid leukemia treatment

Acute myeloid leukemia (AML) mainly affects adult patients, and for older ones unfit for intensive chemotherapy only few therapies are available. Hypomethylating agents, as decitabine, is a labeled option but its plasma half-life is short whereas a long cell exposure time improves response rate. Only intravenous administration is available, whereas an oral route is generally preferred by patients. Consequently, to enhance plasma half-life and to develop an oral decitabine formulation, in this work decitabine was encapsulated in nanoparticles. Two different strategies were tested: decitabine loaded into lipid nanocapsules (DAC-LNC), and a decitabine-prodrug synthesis [3’(OH)-5’(OH)-(lauroyl)2-modified DAC] encapsulated into LNC (DAC-(C12)2-LNC). DAC-LNC and DAC-(C12)2-LNC particles were obtained with sizes of 26.5 ± 0.5 nm and 27.45 ± 0.05 nm respectively, and drug payloads of 0.47 ± 0.06 mg/mL and 5.8 ± 0.5 mg/mL (corresponding to 2.3 ± 0.2 mg/mL of decitabine). Both formulations were able to increase in vitro human plasma half-life by protecting decitabine from degradations. Compared to free-decitabine solutions, both nanoparticle formulations were able to preserve decitabine cytotoxicity on an AML cell line (HEL). Moreover, permeability studies across an adenocarcinoma cell model (Caco-2 cells) demonstrated that DAC-LNC improve decitabine’s intestinal permeability whereas DAC-(C12)2-LNC decreased it. However, this drawback could be countered by the enhanced decitabine’s stability in gastrointestinal fluids thanks to DAC-(C12)2-LNC, leading to more available drug for absorption. Globally, both formulation have demonstrated their ability to improve DAC plasma half-life in vitro and their potential for oral administration. In vivo pharmacokinetics evaluations may now confirm interests of such strategies

Cumul de mandats d’administrateur et risques anticoncurrentiels: Un vide juridique en Europe?

Souvent occultée par les situations de prises de participations minoritaires, la pratique des cumuls de mandats d’administrateur entre concurrents n’est pas sans susciter un risque d’effets anticoncurrentiels. Cette contribution s’attache, à partir d’une analyse systématique des instruments existants, à déterminer si le droit des sociétés et les principes de gouvernance d’entreprise peuvent efficacement suppléer le droit de la concurrence dans le traitement des effets négatifs induits par les cumuls, et à mettre ainsi en lumière l’existence d’un vide juridique en Europe. = Interlocking directorates between competitors may raise significant anti-competitive risks, which attract little attention in comparison to that posed by other structural links, such as minority shareholdings. This article provides a systematic analysis of the ability of current legal tools of competition law, as well as of company law and corporate governance to address those anti-competitive risks, and thereby, highlights the existence of an enforcement gap in Europe

From Ideotypes to Genotypes: Approaches to Adapt Wheat Phenology to Climate Change

AbstractIntroductionSimulations using crop models can assist in designing ideotypes for current and future agricultural conditions. This approach has been often in recent years to identify avenues for adapting wheat to climate change. However, this approach has rarely been used to guide commercial breeding programs. We hypothesize that the lack of link between models and the available tools for breeding, i.e. available genetic variability and selection methods.Materials and methods- We use a modified ARCWHEAT2 phenology model and future climate data from the ARPEGE global circulation model to identify targets for future phenologies-We genotyped over 400 French cultivars for known phenology genes and confronted the genetic make-up of these varieties to their success in France over the past 25 years- We developed a methodology to link model parameters to underlying marker data. We tested the performance of the methodology against circa 60 varietiesResultsEarlier phenology may be an avenue for stress avoidance in the future.Current photoperiod sensitivity of early cultivars already poses problems in terms of adaptation, as exemplified by the interaction between Ppd-D1 and Vrn-A3We show that a gene-based model can be used to predict wheat phenology without a significant loss in predictive performance.DiscussionAnalyzing current phenology genes of existing cultivars and their adaptation allowed us to identify a limit to past breeding efforts in obtaining early cultivars. This requires that a more knowledge based approach be taken. Gene-based modelling of phenology is possible on a collection of elite, adapted varieties and provides the tools for constructing genotypes with specific allelic combinations leading to more appropriate constructions of earliness

Outcome of Ph negative myeloproliferative neoplasms transforming to accelerated or leukemic phase

Myeloproliferative neoplasms (MPN) are chronic disorders that can sometimes evolve into accelerated or leukemic phases. We retrospectively identified 122 patients with such blastic phases. The overall median survival was four months: 10.2 months for patients treated with intensive treatments compared to three months for best supportive care (p = .005). Azacytidine, intensive chemotherapies, or allogeneic stem cell transplantation gave the highest median survivals with 9, 10.2, and 19.4 months, respectively. Accelerated phases (AP) had a longer median survival compared to acute leukemia (4.8 months vs. 3.1 months; p = .02). In this retrospective and observational study, we observe that the longest survivals are seen in patients eligible for intensive treatments. Azacytidine shows interesting results in patients non-fit for intensive chemotherapy. Supportive care should probably be restricted to elderly patients and those with unfavorable karyotype. An early diagnosis of AP could also result in a better survival rate

Dynamics of DNA Replication Factories in Living Cells

DNA replication occurs in microscopically visible complexes at discrete sites (replication foci) in the nucleus. These foci consist of DNA associated with replication machineries, i.e., large protein complexes involved in DNA replication. To study the dynamics of these nuclear replication foci in living cells, we fused proliferating cell nuclear antigen (PCNA), a central component of the replication machinery, with the green fluorescent protein (GFP). Imaging of stable cell lines expressing low levels of GFP-PCNA showed that replication foci are heterogeneous in size and lifetime. Time-lapse studies revealed that replication foci clearly differ from nuclear speckles and coiled bodies as they neither show directional movements, nor do they seem to merge or divide. These four dimensional analyses suggested that replication factories are stably anchored in the nucleus and that changes in the pattern occur through gradual, coordinated, but asynchronous, assembly and disassembly throughout S phase

AP-1 Transcription Factor JunD Confers Protection from Accelerated Nephrotoxic Nephritis and Control Podocyte-Specific Vegfa Expression

Genetic investigation of crescentic glomerulonephritis (Crgn) susceptibility in the Wistar Kyoto rat, a strain uniquely susceptible to nephrotoxic nephritis (NTN), allowed us to positionally clone the activator protein-1 transcription factor Jund as a susceptibility gene associated with Crgn. To study the influence of Jund deficiency (Jund-/-) on immune-mediated renal disease, susceptibility to accelerated NTN was examined in Jund-/- mice and C57BL/6 wild-type (WT) controls. Jund-/- mice showed exacerbated glomerular crescent formation and macrophage infiltration, 10 days after NTN induction. Serum urea levels were also significantly increased in the Jund-/- mice compared with the WT controls. There was no evidence of immune response differences between Jund-/- and WT animals because the quantitative immunofluorescence for sheep and mouse IgG deposition in glomeruli was similar. Because murine Jund was inactivated by replacement with a bacterial LacZ reporter gene, we then investigated its glomerular expression by IHC and found that the Jund promoter is mainly active in Jund-/- podocytes. Furthermore, cultured glomeruli from Jund-/- mice showed relatively increased expression of vascular endothelial growth factor A (Vegfa), Cxcr4, and Cxcl12, well-known HIF target genes. Accordingly, small-interfering RNA–mediated JUND knockdown in conditionally immortalized human podocyte cell lines led to increased VEGFA and HIF1A expression. Our findings suggest that deficiency of Jund may cause increased oxidative stress in podocytes, leading to altered VEGFA expression and subsequent glomerular injury in Crgn