Abstract
Mesenchymal Stromal/Stem Cells (MSC) are currently being explored in diverse clinical applications, including regenerative therapies. Their contribution to regeneration of bone fractures is dependent on their capacity to proliferate, undergo osteogenesis and induce angiogenesis. This study aimed to uncover microRNAs capable of concomitantly regulate these mechanisms. Following microRNA array results, we identified miR-195 and miR-497 as downregulated in human primary MSC under osteogenic differentiation. Overexpression of miR-195 or miR-497 in human primary MSC leads to a decrease in osteogenic differentiation and proliferation rate. Conversely, inhibition of miR-195 increased alkaline phosphatase expression and activity and cells proliferation. Then, miR-195 was used to study MSC capacity to recruit blood vessels in vivo. We provide evidence that the paracrine effect of MSC on angiogenesis is diminished when cells over-express miR-195. VEGF may partially mediate this effect, as its expression and secreted protein levels are reduced by miR195, while increased by anti-miR-195, in human MSC. Luciferase reporter assays revealed a direct interaction between miR-195 and VEGF 3'-UTR in bone cancer cells. In conclusion, our results suggest that miR-195 regulates important mechanisms for bone regeneration, specifically MSC osteogenic differentiation, proliferation and control of angiogenesis; therefore, it is a potential target for clinical bone regenerative therapies.

Abstract
The paradigm of metallic ions as exclusive toxic agents is changing. During the last 60 years, knowledge about toxicological and immunological reactions to metal particles and ions has advanced considerably. Hip prostheses, namely metal-on-metal bearings, have prompted studies about excessive and prolonged exposure to prosthetic debris. In that context, the interactions of metal particles and ions with cells and tissues are mostly harmful, inducing immune responses that lead to osteolysis and implant failure. However, in the last decade, new strategies to promote immunomodulation and healing have emerged based on the unique properties of metallic ions. The atom-size and charge enable ions to interact with key macromolecules (e.g. proteins, nucleic acids) that affect cellular function. Moreover, these agents are inexpensive, stable and can be integrated in biomaterials, which may open new avenues for a novel generation of medical devices. Herein, orthopedic devices are discussed as models for adverse responses to metal ions, and debated together with the potential to use metal ions-based therapies, thus bridging the gap between unmet clinical needs and cutting-edge research. In summary, this review addresses the two "faces" of metallic ions, from pathological responses to innovative research strategies that use metal ions for regenerative medicine.

Abstract
This paper deals with dynamic price competition in markets in which the perception of consumers regarding the value of goods depends on the choices of other consumers in the market. In particular, we consider the case in which consumers exhibit conformist preferences, which leads them to imitate their peers. In the context of a finite horizon model, we show that conformity based behavior creates new channels of dynamic interaction between firms, changing the nature of price competition. We focus on the case of high network effects for which we obtain V-shaped equilibrium price paths and oscillating trajectories of market shares. We provide also a new rationale for the inversion of fashion trends.

Abstract
We merge the two-sided markets duopoly model of Armstrong (2006) with the nested vertical and horizontal differentiation model of Gabszewicz and Wauthy (2012), which consists of a linear city with different consumer densities on the left and on the right side of the city. In equilibrium, the high-quality platform sells at a higher price and captures a greater market share than the low-quality platform, despite the indifferent consumer being closer to the high-quality platform. The difference between market shares is lower than socially optimal. A perturbation that introduces a negligible difference between the consumer density on the left and on the right side of the city may disrupt existence of equilibrium in the model of Armstrong (2006).

Abstract
In this paper, we develop a theoretical model that enriches the literature on the pros and cons of ownership unbundling vis-A -vis lighter unbundling frameworks in the natural gas markets. For each regulatory framework, we compute equilibrium outcomes when an incumbent firm and a new entrant compete A la Cournot in the final gas market. We find that the entrant's contracting conditions in the upstream market and the transmission tariff are key determinants of the market structure in the downstream gas market (both with ownership and with legal unbundling). We also study how the regulator must optimally set transmission tariffs in each of the two unbundling regimes. We conclude that welfare maximizing tariffs often require free access to the transmission network (in both regulatoy regimes). However, when the regulator aims at promoting the break-even of the regulated transmission system operator, the first-best tariff is unfeasible in both regimes. Hence, we study a more realistic set-up, in which the regulator's action is constrained by the break-even of the regulated firm (the transmission system operator). In this set-up, we find that, for a given transmission tariff, final prices in the downstream market are always higher with ownership unbundling than with legal unbundling.

Abstract
This paper examines how firms should allocate their advertising budgets between consumers who have a high preference for their products (i.e., strong segment) and those who prefer competing products (i.e., weak segment). Targeted advertising transmits relevant information to otherwise uninformed consumers and it is used as a price discrimination device. With targeted advertising and price discrimination, we find that, when the attractiveness of the weak segment is low, each firm advertises more intensively in its strong segment. The same result arises when the attractiveness of the weak segment is high and advertising is sufficiently expensive. Interestingly, when the attractiveness of the weak segment is high but advertising costs are sufficiently low, it is optimal for each firm to advertise more intensively in its weak segment. The paper also investigates how advertising strategies and equilibrium profits are affected by price discrimination. Compared with uniform pricing, firms can increase or reduce the intensity of advertising targeted to each segment when price discrimination is allowed. Furthermore, when the attractiveness of the weak market is high, price discrimination boosts firms' profits provided that advertising costs are sufficiently low. The reverse happens when advertising costs are high.