Some organisms have shown the ability to naturally survive in extreme environments, even outer space. Some of these have natural mechanisms to resist severe DNA damage from conditions such as ionizing and non-ionizing radiation, extreme temperatures, and low pressures or vacuum. A good example can be found in Deinococcus radiodurans, which was exposed to severe conditions such as those listed in the Exposure Facility of the International Space Station (ISS) for up to three years. Another example are tardigrades (Ramazzottius varieornatus) which are some of the most resilient animals known. In this study, the survival under simulated Low earth Orbit (LEO) environmental conditions was tested in Escherichia coli. The radiation resistance of this bacteria was enhanced using the Dsup gene from R. varieornatus, and two more genes from D. radiodurans involved in DNA damage repair, RecA and uvrD. The enhanced survival to wide ranges of temperatures and low pressures was then tested in the new strains. This research constitutes a first step in the creation of new bacterial strains engineered to survive severe conditions and adapting existing species for their survival in remote environments, including extra-terrestrial habitats. These strains could be key for the development of environments hospitable to life and could be of use for ecological restoration and space exploration. In addition, studying the efficacy and the functioning of the DNA repair mechanisms used in this study could be beneficial for medical and life sciences engineering.

The aim of this paper is to analyse empirically entry decisions by generic firms into markets with tough regulation. Generic drugs might be a key driver of competition and cost containment in pharmaceutical markets. The dynamics of reforms of patents and pricing across drug markets in Spain are useful to identify the impact of regulations on generic entry. Estimates from a count data model using a panel of 86 active ingredients during the 1999-2005 period show that the drivers of generic entry in markets with price regulations are similar to less regulated markets: generic firms entries are positively affected by the market size and time trend, and negatively affected by the number of incumbent laboratories and the number of substitutes active ingredients. We also find that contrary to what policy makers expected, the system of reference pricing restrains considerably the generic entry. Short run brand name drug price reductions are obtained by governments at the cost of long run benefits from fostering generic entry and post-patent competition into the markets.

<p>Some organisms have shown to be able to naturally survive environments which we consider extreme, including the Low Earth Orbit, or even Outer Space. These microorganisms have natural mechanisms to repair severe DNA damage, such as the caused by ionizing and non-ionizing radiation or extreme temperatures and pressures. Some examples are <em>Deinococcus radiodurans</em>, which proved to be capable of surviving in the Exposure Facility of the International Space Station (ISS) for up to three years, and tardigrade species, such as <em>Ramazzottius varieornatus</em>, which are some of the most resilient known organisms. In this study, performed at the Barcelona Biomedical Research Park in collaboration with Hospital del Mar, survival under simulated Low Earth Orbit environmental conditions was tested in engineered and wild-type <em>Escherichia coli</em> strains. Ionizing radiation resistance was enhanced by transforming the Dsup gene from <em>R. varieornatus</em> and two genes from <em>D. radiodurans</em> involved in DNA damage repair, RecA and uvrD. This enhancement, together with a directed evolution process, resulted in a significant increase in the surviving fraction of the <em>E. coli</em> strain protected with the Dsup gene after a high dose, up to 3000 Gy, of ionizing radiation exposure in the form of a continuous spectrum of X-ray photons. Additionally, the survival to wide ranges of temperatures and low pressures was tested for the same strains, revealing a lack of relevance of cell aggregation for survival under the mentioned conditions in contrast with the case of <em>D. radiodurans</em>. However, survival rates showed no enhancement for any of the new <em>E. coli</em> strains. In a new collaboration with the Subterranean Laboratory of Canfranc, both the absence of radiation and extreme levels of radiation will be further studied. Additionally, an extreme environments analogue for several environmental conditions will be built, allowing for more specific testing on a controlled environment. This research represents a first step in the creation of new bacterial strains engineered to survive severe conditions and adapting existing species for their survival in remote environments, like extra-terrestrial habitats. These species could pave the road for future human expeditions, helping develop environments hospitable to life. In addition, studying the efficacy and the functioning of the genetic mechanisms used in this study could be beneficial for fields such as ecological restoration and medical and life sciences engineering, addressing treatments and/or diseases caused or related to radiation and DNA damage. Space is believed to be the last frontier, but the truth is, we are still a frontier to ourselves.</p>