CRISPR/Cas9‐mediated genome editing: from basic research to translational medicine

The recent development of the CRISPR/Cas9 system as an efficient and accessible programmable genome-editing tool has revolutionized basic science research. CRISPR/Cas9 system-based technologies have armed researchers with new powerful tools to unveil the impact of genetics on disease development by enabling the creation of precise cellular and animal models of human diseases. The therapeutic potential of these technologies is tremendous, particularly in gene therapy, in which a patient-specific mutation is genetically corrected in order to treat human diseases that are untreatable with conventional therapies. However, the translation of CRISPR/Cas9 into the clinics will be challenging, since we still need to improve the efficiency, specificity and delivery of this technology. In this review, we focus on several in vitro, in vivo and ex vivo applications of the CRISPR/Cas9 system in human disease-focused research, explore the potential of this technology in translational medicine and discuss some of the major challenges for its future use in patients.Portuguese Foundation for Science and Technology: UID/BIM/04773/2013 1334 Spanish Ministry of Science, Innovation and Universities RTI2018-094629-B-I00 Portuguese Foundation for Science and Technology SFRH/BPD/100434/2014 European Union (EU) 748585 LPCC-NRS/Terry Fox grantsinfo:eu-repo/semantics/publishedVersio

Credible Equilibria in Games with Utility Changing during the Play

Publicado por Tilburg Center Economic Research 1992Whenever one deals with an interactive decision situation of long duration, one has to take into account that priorities of the participants may change during the conflicto In this paper we propose an extensiveform game model to handle such situations and suggest and study a solution concept, called credible equilibrium, which generalizes the concept of Nash equilibrium. We also discuss possible variants to this concept and applications of the model to other types of games

Higher spins on AdS3_{3} from the worldsheet

It was recently shown that the CFT dual of string theory on ${\rm AdS}_3 \times {\rm S}^3 \times T^4$, the symmetric orbifold of $T^4$, contains a closed higher spin subsector. Via holography, this makes precise the sense in which tensionless string theory on this background contains a Vasiliev higher spin theory. In this paper we study this phenomenon directly from the worldsheet. Using the WZW description of the background with pure NS-NS flux, we identify the states that make up the leading Regge trajectory and show that they fit into the even spin ${\cal N}=4$ Vasiliev higher spin theory. We also show that these higher spin states do not become massless, except for the somewhat singular case of level $k=1$ where the theory contains a stringy tower of massless higher spin fields coming from the long string sector.Comment: 29+8 pages, 3 figure

Excitation of trapped oscillations in discs around black holes

High-frequency quasi-periodic oscillations detected in the light curves of black hole candidates can, according to one model, be identified with hydrodynamic oscillations of the accretion disc. We describe a non-linear coupling mechanism, suggested by Kato, through which inertial waves trapped in the inner regions of accretion discs around black holes are excited. Global warping and/or eccentricity of the disc have a fundamental role in this coupling: they combine with trapped modes, generating negative energy waves, that are damped as they approach the inner edge of the disc or their corotation resonance. As a result of this damping, inertial oscillations are amplified. We calculate the resulting eigenfunctions and their growth rates.Comment: 6 pages, 2 figures; accepted for inclusion in the proceedings of "Cool Discs, Hot Flows: The Varying Faces of Accreting Compact Objects," ed. M. Axelsson (New York: AIP

Warped and eccentric discs around black holes

Accretion discs around black holes in X-ray binary stars are warped if the spin axis of the black hole is not perpendicular to the binary orbital plane. They can also become eccentric through an instability involving a resonance with the binary orbit. Depending on the thickness of the disc and the efficiency of dissipative processes, these global deformations may be able to propagate into the innermost part of the disc in the form of stationary bending or density waves. We describe the solutions in the linear regime and discuss the conditions under which a warp or eccentricity is likely to produce significant activity in the inner region, which may include the excitation of quasi-periodic oscillations.Comment: 6 pages, 3 figures; accepted for inclusion in the proceedings of "Cool Discs, Hot Flows: The Varying Faces of Accreting Compact Objects," ed. M. Axelsson (New York: AIP

Are Magnetic Wind-Driving Disks Inherently Unstable?

There have been claims in the literature that accretion disks in which a centrifugally driven wind is the dominant mode of angular momentum transport are inherently unstable. This issue is considered here by applying an equilibrium-curve analysis to the wind-driving, ambipolar diffusion-dominated, magnetic disk model of Wardle & Konigl (1993). The equilibrium solution curves for this class of models typically exhibit two distinct branches. It is argued that only one of these branches represents unstable equilibria and that a real disk/wind system likely corresponds to a stable solution.Comment: 5 pages, 2 figures, to be published in ApJ, vol. 617 (2004 Dec 20). Uses emulateapj.cl