Optimal marketing decision in a duopoly: a stochastic approach

Let us consider two new perfect substitute durable products which are produced and sold in a market by two competing firms. Looking at a potential buyer, we build a stochastic rule by which she purchases the good from one of the two firms (so that she becomes an adopter). The model is considered discrete in time and space. The probability of transition from the non adopter state to the adopter one depends on an imitation mechanism (word-ofmouth) as well as on the pricing and advertising policies of the producers/sellers. It is assumed that only actual information about the market determine the evolution in the subsequent time step so that a Markov process arises. Both firms maximize their expected discounted profits by choosing optimal marketing strategies. Suitable equilibria are characterized and, because of the lack of convexity in the model, the simulated annealing algorithm is proposed to compute them.

Optimal Control Problems Arising In Marketing Models

The diffusion in time of a new product in a monopolistic or oligopolistic market can be described by a system of evolution equations (PDE, ODE, DDE) containing one or more control parameters (advertising, prices, plant locations, ...). The productors choose the control parameters in order to maximize their (discounted) prots. Hence an optimal control problems (in the case of a monopoly) or a dynamic game (in the case of an oligopoly) has to be solved. A specic model is proposed and an exhaustive description of its solution is given.

Coinfection by Ureaplasma spp., Photobacterium damselae and an Actinomyces-like microorganism in a bottlenose dolphin (Tursiops truncatus) with pleuropneumonia stranded along the Adriatic coast of Italy

A case of pleuropneumonia is reported in an adult male bottlenose dolphin (Tursiops truncatus) found stranded in 2014 along the Central Adriatic coast of Italy. A severe pyogranulomatous pneumonia and thoracic lymphadenopathy were present at necropsy. Numerous Splendore-Hoeppli bodies were found microscopically scattered throughout the lung. Histochemical evidence of Actinomyces-like organisms was obtained from the pulmonary parenchyma, with a strain of Photobacterium damselae subsp. piscicida and Ureaplasma spp. being also isolated from the same tissue. For the latter, a genome fragment of approximately 1400 bp from the 16s rDNA was amplified and sequenced. BLAST analysis revealed 100% identity with an uncultured Ureaplasma spp. (JQ193826.1)

Co-selection of antibiotic and heavy metal resistance in freshwater bacteria

Antibiotic resistant bacteria are found in most environments, especially in highly anthropized waters. A direct correlation between human activities (e.g., pollution) and spread and persistence of antibiotic resistant bacteria (ARB) and resistance genes (ARGs) within the resident bacterial communities appears more and more obvious. Furthermore, the threat posed for human health by the presence of ARB and ARGs in these environments is enhanced by the risk of horizontal gene transfer of resistance genes to human pathogens. Although the knowledge on the spread of antibiotic resistances in waters is increasing, the understanding of the driving factors determining the selection for antibiotic resistance in the environment is still scarce. Antibiotic pollution is generally coupled with contamination by heavy metals (HMs) and other chemicals, which can also promote the development of resistance mechanisms, often through co-selecting for multiple resistances. The co-selection of heavy metal resistance genes and ARGs in waters, sediments, and soils, increases the complexity of the ecological role of ARGs, and reduces the effectiveness of control actions. In this mini-review we present the state-of-the-art of the research on antibiotic- and HM-resistance and their connection in the environment, with a focus on HM pollution and aquatic environments. We review the spread and the persistence of HMs and/or ARB, and how it influences their respective gene co-selection. In the last chapter, we propose Lake Orta, a system characterized by an intensive HM pollution followed by a successful restoration of the chemistry of the water column, as a study-site to evaluate the spread and selection of HMs and antibiotic resistances in heavily disturbed environments

Financial sector pro-cyclicality: lessons from the crisis

We analyze the main forces affecting financial system pro-cyclicality (the fact that developments in the financial sector can amplify business cycle fluctuations). We first review some major structural developments in financial markets that may influence pro-cyclicality and that have been overlooked in earlier analyses. We then examine three issues that are center stage in the current debate: capital regulation, accounting standards and managers’ incentives. After reviewing the institutional set-up and the key mechanisms at work, we critically examine a series of proposals designed to mitigate pro-cyclicality.pro-cyclicality, financial accelerator, capital requirements, leverage, accounting standards, incentives

Zooplankton as refuge for invading bacteria

Nonetheless, studies on the impact of non-parasitic bacteria are still scarce. In this study we analysed the consequences of this colonisation on the distribution of potentially pathogenic and antibiotic resistant bacteria in freshwater systems. This is based on the hypothesis that potential pathogens have a selective advantage when growing in biofilms, as has been shown in clinical settings. Thus we postulate that attaching to animals might allow potential pathogens, e.g. deriving from the efflux of a waste water treatment plant (WWTP), to survive in freshwaters. Additionally the movement of the animal transports the bacteria away from the point-contamination to more pristine waters. We experimentally show that, if added to a natural bacterial community, Escherichia coli attaches to daphnids and derives particularly well in the gut of the animals, where they naturally do not form part of their microflora, whilst decreasing in abundance in the surrounding water. Moreover, the presence of daphnids decreased the abundance of a tetracycline resistance gene (tetA) in the surrounding water, whilst a higher number of tetA gene copies were detected in the animals. In addition we tested whether zooplankton species form a surface for the horizontal gene transfer, of e.g. antibiotic resistant genes, from one E. coli strain to another. In order to expand our hypothesis to natural environment we sampled Lake Maggiore at three points with increasing distance to an inflow of a WWTP and compared the microbial community on various zooplankton species as well as on stones and in the sediment. Whereas similar relationships have been described in marine systems, e.g. Vibrio cholera and Copepods, this is the first study that confronts the potential role of zooplankton in the spread of potential pathogens in freshwater systems

Enhancement of radiosensitivity by the novel anticancer quinolone derivative vosaroxin in preclinical glioblastoma models

Purpose: Glioblastoma multiforme (GBM) is the most aggressive brain tumor. The activity of vosaroxin, a first-in-class anticancer quinolone derivative that intercalates DNA and inhibits topoisomerase II, was investigated in GBM preclinical models as a single agent and combined with radiotherapy (RT). Results: Vosaroxin showed antitumor activity in clonogenic survival assays, with IC50 of 10-100 nM, and demonstrated radiosensitization. Combined treatments exhibited significantly higher γH2Ax levels compared with controls. In xenograft models, vosaroxin reduced tumor growth and showed enhanced activity with RT; vosaroxin/RT combined was more effective than temozolomide/RT. Vosaroxin/ RT triggered rapid and massive cell death with characteristics of necrosis. A minor proportion of treated cells underwent caspase-dependent apoptosis, in agreement with in vitro results. Vosaroxin/RT inhibited RT-induced autophagy, increasing necrosis. This was associated with increased recruitment of granulocytes, monocytes, and undifferentiated bone marrow-derived lymphoid cells. Pharmacokinetic analyses revealed adequate blood-brain penetration of vosaroxin. Vosaroxin/RT increased disease-free survival (DFS) and overall survival (OS) significantly compared with RT, vosaroxin alone, temozolomide, and temozolomide/RT in the U251-luciferase orthotopic model. Materials and Methods: Cellular, molecular, and antiproliferative effects of vosaroxin alone or combined with RT were evaluated in 13 GBM cell lines. Tumor growth delay was determined in U87MG, U251, and T98G xenograft mouse models. (DFS) and (OS) were assessed in orthotopic intrabrain models using luciferasetransfected U251 cells by bioluminescence and magnetic resonance imaging. Conclusions: Vosaroxin demonstrated significant activity in vitro and in vivo in GBM models, and showed additive/synergistic activity when combined with RT in O6- methylguanine methyltransferase-negative and -positive cell lines

Presenza e distribuzione di batteri antibiotico-resistenti nelle acque del Lago Maggiore

Not availableRicerche sull\u27evoluzione del Lago Maggiore. Aspetti limnologici. Programma triennale 2013-2015. Campagna 2013. Presenza e distribuzione di batteri antibiotico-resistenti nelle acque del Lago Maggiore. Valutazione della presenza di geni di antibiotico-resistenza (ABR). Quantificazione dei geni di resistenza alle tetracicline

The impact of sovereign credit risk on bank funding conditions

The financial crisis and the ensuing recession have caused a sharp deterioration in public finances across advanced economies, raising investor concerns about sovereign risk. The concerns have so far mainly affected the euro area, where some countries have seen their credit ratings downgraded during 2009−11 and their funding costs rise sharply. Other countries have also been affected, but to a much lesser extent. Greater sovereign risk is already having adverse effects on banks and financial markets. Looking forward, sovereign risk concerns may affect a broad range of countries. In advanced economies, government debt levels are expected to rise over coming years, due to high fiscal deficits and rising pension and health care costs. In emerging economies, vulnerability to external shocks and political instability may have periodic adverse effects on sovereign risk. Overall, risk premia on government debt will likely be higher and more volatile than in the past. In some countries, sovereign debt has already lost its risk-free status; in others, it may do so in the future. The challenge for authorities is to minimise the negative consequences for bank funding and the flow-on effects on the real economy. This report outlines the impact of sovereign risk concerns on the cost and availability of bank funding over recent years. It then describes the channels through which sovereign risk affects bank funding. The last section summarises the main conclusions and discusses some implications for banks and the official sector. Two caveats are necessary before discussing the main findings. First, the analysis focuses on causality going from sovereigns to banks, as is already the case in some countries, and, looking forward, is a possible scenario for other economies. But causality may clearly also go from banks to sovereigns. However, even in this second case, sovereign risk eventually acquires its own dynamics and compounds the problems of the banking sector. Second, the report examines the link between sovereign risk and bank funding in general terms, based on recent experience and research. It does not assess actual sovereign risk and its impact on bank stability in individual countries at the present juncture.Sovereign debt; banks; financial turmoil

Mitotic cell death induction by targeting the mitotic spindle with tubulin-inhibitory indole derivative molecules

Tubulin-targeting molecules are widely used cancer therapeutic agents. They inhibit microtubule-based structures, including the mitotic spindle, ultimately preventing cell division. The final fates of microtubule-inhibited cells are however often heterogeneous and difficult to predict. While recent work has provided insight into the cell response to inhibitors of microtubule dynamics (taxanes), the cell response to tubulin polymerization inhibitors remains less well characterized. Arylthioindoles (ATIs) are recently developed tubulin inhibitors. We previously identified ATI members that effectively inhibit tubulin polymerization in vitro and cancer cell growth in bulk cell viability assays. Here we characterise in depth the response of cancer cell lines to five selected ATIs. We find that all ATIs arrest mitotic progression, yet subsequently yield distinct cell fate profiles in time-lapse recording assays, indicating that molecules endowed with similar tubulin polymerization inhibitory activity in vitro can in fact display differential efficacy in living cells. Individual ATIs induce cytological phenotypes of increasing severity in terms of damage to the mitotic apparatus. That differentially triggers MCL-1 down-regulation and caspase-3 activation, and underlies the terminal fate of treated cells. Collectively, these results contribute to define the cell response to tubulin inhibitors and pinpoint potentially valuable molecules that can increase the molecular diversity of tubulin-targeting agents