Inclusion of a degron reduces levelsof undesired inteins after AAV-mediated proteintrans-splicing in the retina

Split intein-mediated protein trans-splicing expands AAV transfer capacity, thus overcoming the limited AAV cargo. However, non-mammalian inteins persist as trans-splicing by-products, and this could raise safety concerns for AAV intein clinical applications. In this study, we tested the ability of several degrons to selectively decrease levels of inteins after protein trans-splicing and found that a version of E. coli dihydrofolate reductase, which we have shortened to better fit into the AAV vector, is the most effective. We show that subretinal administration of AAV intein armed with this short degron is both safe and effective in a mouse model of Stargardt disease (STGD1), which is the most common form of inherited macular degeneration in humans. This supports the use of optimized AAV intein for gene therapy of both STGD1 and other conditions that require transfer of large genes

Angular Resolution of the Pachmarhi Array of Cerenkov Telescopes

The Pachmarhi Array of Cerenkov Telescopes consists of a distributed array of 25 telescopes that are used to sample the atmospheric Cerenkov Photon showers. Each telescope consists of 7 parabolic mirrors each viewed by a single photo-multiplier tube. Reconstruction of photon showers are carried out using fast timing information on the arrival of pulses at each PMT. The shower front is fitted to a plane and the direction of arrival of primary particle initiating the shower is obtained. The error in the determination of the arrival direction of the primary has been estimated using the {\it split} array method. It is found to be $\sim 2.4^\prime ~$ for primaries of energy $> 3 \~TeV$. The dependence of the angular resolution on the separation between the telescopes and the number of detectors are also obtained from the data.Comment: 26 pages, 11 Postscript figures; uses elsart.cls. To appear in Astroparticle Physic

Temperature-dependent nonlinear analysis of shallow shells: A theoretical approach

The paper presents a theoretical formulation for the computation of temperature-dependent nonlinear response of shallow shells with single and double curvatures subjected to transverse mechanical loads while being exposed to through-depth non-uniform heating regimes such as those resulting from a fire. The material nonlinearity arises from taking into consideration the degradation of the material elastic behaviour at elevated temperatures under quasi-static conditions. Two types of boundary conditions are considered, both of which constrain the transverse deflections and allow the rotations about the edge axis to be free. One of the boundary conditions permits lateral translation (laterally unrestrained) and the other one does not (laterally restrained). A number of examples are solved for shallow shells under different types of loading conditions including: an exponential "short hot" fire leading to a high temperature over a relatively short duration; and an exponential "long cool" fire of lower temperature over a longer duration. The limits of the shallow shell equations are investigated through comparison studies. Results show that while current numerical approaches for analysis of laterally restrained shallow shells are often computationally intensive, the proposed approach offers an adequate level of accuracy with a rapid convergence rate for such structures.The Edinburgh Research Partnership in Engineering (ERPE)

Columbus crater and other possible groundwater-fed paleolakes of Terra Sirenum, Mars

Columbus crater in the Terra Sirenum region of the Martian southern highlands contains light-toned layered deposits with interbedded sulfate and phyllosilicate minerals, a rare occurrence on Mars. Here we investigate in detail the morphology, thermophysical properties, mineralogy, and stratigraphy of these deposits; explore their regional context; and interpret the crater's aqueous history. Hydrated mineral-bearing deposits occupy a discrete ring around the walls of Columbus crater and are also exposed beneath younger materials, possibly lava flows, on its floor. Widespread minerals identified in the crater include gypsum, polyhydrated and monohydrated Mg/Fe-sulfates, and kaolinite; localized deposits consistent with montmorillonite, Fe/Mg-phyllosilicates, jarosite, alunite, and crystalline ferric oxide or hydroxide are also detected. Thermal emission spectra suggest abundances of these minerals in the tens of percent range. Other craters in northwest Terra Sirenum also contain layered deposits and Al/Fe/Mg-phyllosilicates, but sulfates have so far been found only in Columbus and Cross craters. The region's intercrater plains contain scattered exposures of Al-phyllosilicates and one isolated mound with opaline silica, in addition to more common Fe/Mg-phyllosilicates with chlorides. A Late Noachian age is estimated for the aqueous deposits in Columbus, coinciding with a period of inferred groundwater upwelling and evaporation, which (according to model results reported here) could have formed evaporites in Columbus and other craters in Terra Sirenum. Hypotheses for the origin of these deposits include groundwater cementation of crater-filling sediments and/or direct precipitation from subaerial springs or in a deep (∼900 m) paleolake. Especially under the deep lake scenario, which we prefer, chemical gradients in Columbus crater may have created a habitable environment at this location on early Mars

A mission control architecture for robotic lunar sample return as field tested in an analogue deployment to the Sudbury impact structure

A Mission Control Architecture is presented for a Robotic Lunar Sample Return Mission which builds upon the experience of the landed missions of the NASA Mars Exploration Program. This architecture consists of four separate processes working in parallel at Mission Control and achieving buy-in for plans sequentially instead of simultaneously from all members of the team. These four processes were: Science Processing, Science Interpretation, Planning and Mission Evaluation. Science Processing was responsible for creating products from data downlinked from the field and is organized by instrument. Science Interpretation was responsible for determining whether or not science goals are being met and what measurements need to be taken to satisfy these goals. The Planning process, responsible for scheduling and sequencing observations, and the Evaluation process that fostered inter-process communications, reporting and documentation assisted these processes. This organization is advantageous for its flexibility as shown by the ability of the structure to produce plans for the rover every two hours, for the rapidity with which Mission Control team members may be trained and for the relatively small size of each individual team. This architecture was tested in an analogue mission to the Sudbury impact structure from June 6-17, 2011. A rover was used which was capable of developing a network of locations that could be revisited using a teach and repeat method. This allowed the science team to process several different outcrops in parallel, downselecting at each stage to ensure that the samples selected for caching were the most representative of the site. Over the course of 10 days, 18 rock samples were collected from 5 different outcrops, 182 individual field activities - such as roving or acquiring an image mosaic or other data product - were completed within 43 command cycles, and the rover travelled over 2,200 m. Data transfer from communications passes were filled to 74%. Sample triage was simulated to allow down-selection to 1kg of material for return to Earth

Propulsion Investigation for Zero and Near-Zero Emissions Aircraft

As world emissions are further scrutinized to identify areas for improvement, aviation s contribution to the problem can no longer be ignored. Previous studies for zero or near-zero emissions aircraft suggest aircraft and propulsion system sizes that would perform propulsion system and subsystems layout and propellant tankage analyses to verify the weight-scaling relationships. These efforts could be used to identify and guide subsequent work on systems and subsystems to achieve viable aircraft system emissions goals. Previous work quickly focused these efforts on propulsion systems for 70- and 100-passenger aircraft. Propulsion systems modeled included hydrogen-fueled gas turbines and fuel cells; some preliminary estimates combined these two systems. Hydrogen gas-turbine engines, with advanced combustor technology, could realize significant reductions in nitrogen emissions. Hydrogen fuel cell propulsion systems were further laid out, and more detailed analysis identified systems needed and weight goals for a viable overall system weight. Results show significant, necessary reductions in overall weight, predominantly on the fuel cell stack, and power management and distribution subsystems to achieve reasonable overall aircraft sizes and weights. Preliminary conceptual analyses for a combination of gas-turbine and fuel cell systems were also performed, and further studies were recommended. Using gas-turbine engines combined with fuel cell systems can reduce the fuel cell propulsion system weight, but at higher fuel usage than using the fuel cell only