Retinal gene therapy with a large MYO7A cDNA using adeno-associated virus.

Usher 1 patients are born profoundly deaf and then develop retinal degeneration. Thus they are readily identified before the onset of retinal degeneration, making gene therapy a viable strategy to prevent their blindness. Here, we have investigated the use of adeno-associated viruses (AAVs) for the delivery of the Usher 1B gene, MYO7A, to retinal cells in cell culture and in Myo7a-null mice. MYO7A cDNA, under control of a smCBA promoter, was packaged in single AAV2 and AAV5 vectors and as two overlapping halves in dual AAV2 vectors. The 7.9-kb smCBA-MYO7A exceeds the capacity of an AAV vector; packaging of such oversized constructs into single AAV vectors may involve fragmentation of the gene. Nevertheless, the AAV2 and AAV5 single vector preparations successfully transduced photoreceptor and retinal pigment epithelium cells, resulting in functional, full-length MYO7A protein and correction of mutant phenotypes, suggesting successful homologous recombination of gene fragments. With discrete, conventional-sized dual AAV2 vectors, full-length MYO7A was detected, but the level of protein expression was variable, and only a minority of cells showed phenotype correction. Our results show that MYO7A therapy with AAV2 or AAV5 single vectors is efficacious; however, the dual AAV2 approach proved to be less effective

Strengths-based Programming for First Nations Youth in Schools: Building Engagement Through Healthy Relationships and Leadership Skills

FirstNationsyouthinCanadademonstratedisproportionatelyhighratesofnegative behaviors such as violence, substance abuse, and leaving school early. An understanding of historical context and current environment helps explain these patterns. Providing culturally relevant opportunities for youth to build healthy relationships and leadership skills has the potential to increase youth engagement. Over the past four years our multidisciplinary team of researchers, educators, program developers, and community leaders have worked together to develop a number of school-based initiatives that focus on increasing youth engagement through building on strengths and the promotion of healthy relationships. Specific strategies include peer mentoring, a credit-based academic course, and transition conferences for grade 8 students. This article describes these initiatives and some of the early successes and challenges we have faced in the design and implementation of them. Preliminary evidence is presented to support the contention that these initiatives increase youth engagement

Syzygies of torsion bundles and the geometry of the level l modular variety over M_g

We formulate, and in some cases prove, three statements concerning the purity or, more generally the naturality of the resolution of various rings one can attach to a generic curve of genus g and a torsion point of order l in its Jacobian. These statements can be viewed an analogues of Green's Conjecture and we verify them computationally for bounded genus. We then compute the cohomology class of the corresponding non-vanishing locus in the moduli space R_{g,l} of twisted level l curves of genus g and use this to derive results about the birational geometry of R_{g, l}. For instance, we prove that R_{g,3} is a variety of general type when g>11 and the Kodaira dimension of R_{11,3} is greater than or equal to 19. In the last section we explain probabilistically the unexpected failure of the Prym-Green conjecture in genus 8 and level 2.Comment: 35 pages, appeared in Invent Math. We correct an inaccuracy in the statement of Prop 2.

Effects of Arctic ozone on the stratospheric spring onset and its surface response

Ozone in the Arctic stratosphere is subject to large interannual variability, driven by both chemical ozone depletion and dynamical variability. Anomalies in Arctic stratospheric ozone become particularly important in spring, when returning sunlight allows them to alter stratospheric temperatures via shortwave heating, thus modifying atmospheric dynamics. At the same time, the stratospheric circulation undergoes a transition in spring with the final stratospheric warming (FSW), which marks the end of winter. A causal link between stratospheric ozone anomalies and FSWs is plausible and might increase the predictability of stratospheric and tropospheric responses on sub-seasonal to seasonal timescales. However, it remains to be fully understood how ozone influences the timing and evolution of the springtime vortex breakdown. Here, we contrast results from chemistry climate models with and without interactive ozone chemistry to quantify the impact of ozone anomalies on the timing of the FSW and its effects on surface climate. We find that ozone feedbacks increase the variability in the timing of the FSW, especially in the lower stratosphere. In ozone-deficient springs, a persistent strong polar vortex and a delayed FSW in the lower stratosphere are partly due to the lack of heating by ozone in that region. High-ozone anomalies, on the other hand, result in additional shortwave heating in the lower stratosphere, where the FSW therefore occurs earlier. We further show that FSWs in high-ozone springs are predominantly followed by a negative phase of the Arctic Oscillation (AO) with positive sea level pressure anomalies over the Arctic and cold anomalies over Eurasia and Europe. These conditions are to a significant extent (at least 50 %) driven by ozone. In contrast, FSWs in low-ozone springs are not associated with a discernible surface climate response. These results highlight the importance of ozone–circulation coupling in the climate system and the potential value of interactive ozone chemistry for sub-seasonal to seasonal predictability

energy performance of chp system integrated with citrus peel air steam gasification a comparative study

Abstract The aim of this work is to exploit the potential of residual biomass, different from the traditional wood feedstock, by thermochemical gasification process. In particular, citrus peels waste of the juice extraction process, was selected since it is a typical local Sicilian residue. The citrus peel conversion performances in air-steam gasification process were evaluated and compared with those obtained with pinewood as feedstock. Experimental activities of air-steam gasification were carried out in a bench-scale fluidized bed reactor at 1023 K, for both citrus peel and pinewood, varying the steam to biomass ratio (S/B). A simulation model of the experimental facility was developed in order to find a useful tool to realize the virtual scale-up of the system with downstream syngas utilization. The cold gas efficiency (CGE) and the net cold gas efficiency (CGE net ) were calculated to define the best gasification conditions. Results showed that using pinewood a very low reactivity can be observed, showing a very low net CGE. The highest net CGE for citrus peel was observed at S/B = 0.5, while for pinewood the addition of water did not improve the net CGE. Finally, an integration of the citrus peel gasification system with a commercial CHP unit was proposed and the efficiencies were evaluated

Analysis of Reforming Gas Combustion in Internal Combustion Engine

Abstract The present paper deals with the study of the combustion of reforming gas in a small size Internal Combustion Engine. Therefore, mathematical models of both reforming process and internal combustion engine were implemented. In particular, steams reforming of glycerol to produce synthesis gas and spark ignition four strokes ICE were studied. The reforming process mathematical model was verified using experimental data. Synthesis gas was used to feed the ICE with different syngas and engine configuration. On the basis of the comparison with the experimental results, it is possible to state that the mathematical model is validated. Engine performance and pollutant emission evaluation was carried out using the integrated mathematical models with reference to the engine running on standard commercial fuel. The results highlight a reduction in engine performance and, at the same time a reduction of pollutant emissions in terms of CO and CO 2

Emerging giant resonant exciton induced by Ta-substitution in anatase TiO2_{2}: a tunable correlation effect

Titanium dioxide (TiO$_2$) has rich physical properties with potential implications in both fundamental physics and new applications. Up-to-date, the main focus of applied research is to tune its optical properties, which is usually done via doping and/or nano-engineering. However, understanding the role of $d$-electrons in materials and possible functionalization of $d$-electron properties are still major challenges. Herewith, within a combination of an innovative experimental technique, high energy optical conductivity, and of the state-of-the-art {\it ab initio} electronic structure calculations, we report an emerging, novel resonant exciton in the deep ultraviolet region of the optical response. The resonant exciton evolves upon low concentration Ta-substitution in anatase TiO$_{2}$ films. It is surprisingly robust and related to strong electron-electron and electron-hole interactions. The $d$- and $f$- orbitals localization, due to Ta-substitution, plays an unexpected role, activating strong electronic correlations and dominating the optical response under photoexcitation. Our results shed light on a new optical phenomenon in anatase TiO$_{2}$ films and on the possibility of tuning electronic properties by Ta substitution

Landau-Ginzburg/Calabi-Yau correspondence, global mirror symmetry and Orlov equivalence

We show that the Gromov-Witten theory of Calabi-Yau hypersurfaces matches, in genus zero and after an analytic continuation, the quantum singularity theory (FJRW theory) recently introduced by Fan, Jarvis and Ruan following ideas of Witten. Moreover, on both sides, we highlight two remarkable integral local systems arising from the common formalism of Gamma-integral structures applied to the derived category of the hypersurface {W=0} and to the category of graded matrix factorizations of W. In this setup, we prove that the analytic continuation matches Orlov equivalence between the two above categories.Comment: 72pages, v2: Appendix B and references added. Typos corrected, v3: several mistakes corrected, final versio