Performance of AAV8 vectors expressing human factor IX from a hepatic-selective promoter following intravenous injection into rats

Background: Vectors based on adeno-associated virus-8 (AAV8) have shown efficiency and efficacy for liver-directed gene therapy protocols following intravascular injection, particularly in relation to haemophilia gene therapy. AAV8 has also been proposed for gene therapy targeted at skeletal and cardiac muscle, again via intravascular injection. It is important to assess vector targeting at the level of virion accumulation and transgene expression in multiple species to ascertain potential issues relating to species variation in infectivity profiles. Methods: We used AAV8 vectors expressing human factor IX (FIX) from the liver-specific LP-1 promoter and administered this virus via the intravascular route of injection into 12 week old Wistar Kyoto rats. We assessed FIX levels in serum by ELISA and transgene expression at sacrifice by immunohistochemistry using anti-FIX antibodies. Vector DNA levels in organs we determined by real time PCR. Results: Administration of 1 × 1011 or 5 × 1011 scAAV8-LP1-hFIX vector particles/rat resulted in efficient production of physiological hFIX levels, respectively in blood assessed 4 weeks post-injection. This was maintained for the 4 month duration of the study. At 4 months we observed liver persistence of vector with minimal non-hepatic distribution. Conclusion: Our results demonstrate that AAV8 is a robust vector for delivering therapeutic genes into rat liver following intravascular injection

Multi-site mean-field theory for cold bosonic atoms in optical lattices

We present a detailed derivation of a multi-site mean-field theory (MSMFT) used to describe the Mott-insulator to superfluid transition of bosonic atoms in optical lattices. The approach is based on partitioning the lattice into small clusters which are decoupled by means of a mean field approximation. This approximation invokes local superfluid order parameters defined for each of the boundary sites of the cluster. The resulting MSMFT grand potential has a non-trivial topology as a function of the various order parameters. An understanding of this topology provides two different criteria for the determination of the Mott insulator superfluid phase boundaries. We apply this formalism to $d$-dimensional hypercubic lattices in one, two and three dimensions, and demonstrate the improvement in the estimation of the phase boundaries when MSMFT is utilized for increasingly larger clusters, with the best quantitative agreement found for $d=3$. The MSMFT is then used to examine a linear dimer chain in which the on-site energies within the dimer have an energy separation of $\Delta$. This system has a complicated phase diagram within the parameter space of the model, with many distinct Mott phases separated by superfluid regions.Comment: 30 pages, 23 figures, accepted for publication in Phys. Rev.

Critiquing Variational Theories of the Anderson-Hubbard Model: Real-Space Self-Consistent Hartree-Fock Solutions

A simple and commonly employed approximate technique with which one can examine spatially disordered systems when strong electronic correlations are present is based on the use of real-space unrestricted self-consistent Hartree-Fock wave functions. In such an approach the disorder is treated exactly while the correlations are treated approximately. In this report we critique the success of this approximation by making comparisons between such solutions and the exact wave functions for the Anderson-Hubbard model. Due to the sizes of the complete Hilbert spaces for these problems, the comparisons are restricted to small one-dimensional chains, up to ten sites, and a 4x4 two-dimensional cluster, and at 1/2 filling these Hilbert spaces contain about 63,500 and 166 million states, respectively. We have completed these calculations both at and away from 1/2 filling. This approximation is based on a variational approach which minimizes the Hartree-Fock energy, and we have completed comparisons of the exact and Hartree-Fock energies. However, in order to assess the success of this approximation in reproducing ground-state correlations we have completed comparisons of the local charge and spin correlations, including the calculation of the overlap of the Hartree-Fock wave functions with those of the exact solutions. We find that this approximation reproduces the local charge densities to quite a high accuracy, but that the local spin correlations, as represented by , are not as well represented. In addition to these comparisons, we discuss the properties of the spin degrees of freedom in the HF approximation, and where in the disorder-interaction phase diagram such physics may be important

The Impact of New EUV Diagnostics on CME-Related Kinematics

We present the application of novel diagnostics to the spectroscopic observation of a Coronal Mass Ejection (CME) on disk by the Extreme Ultraviolet Imaging Spectrometer (EIS) on the Hinode spacecraft. We apply a recently developed line profile asymmetry analysis to the spectroscopic observation of NOAA AR 10930 on 14-15 December 2006 to three raster observations before and during the eruption of a 1000km/s CME. We see the impact that the observer's line-of-sight and magnetic field geometry have on the diagnostics used. Further, and more importantly, we identify the on-disk signature of a high-speed outflow behind the CME in the dimming region arising as a result of the eruption. Supported by recent coronal observations of the STEREO spacecraft, we speculate about the momentum flux resulting from this outflow as a secondary momentum source to the CME. The results presented highlight the importance of spectroscopic measurements in relation to CME kinematics, and the need for full-disk synoptic spectroscopic observations of the coronal and chromospheric plasmas to capture the signature of such explosive energy release as a way of providing better constraints of CME propagation times to L1, or any other point of interest in the heliosphere.Comment: Accepted to appear in Solar Physics Topical Issue titled "Remote Sensing of the Inner Heliosphere". Manuscript has 14 pages, 5 color figures. Movies supporting the figures can be found in http://download.hao.ucar.edu/pub/mscott/papers/Weathe

Comparison of H alpha synoptic charts with the large-scale solar magnetic field as observed at Stanford

Two methods of observing the neutral line of the large-scale photospheric magnetic field are compared: (1) neutral line positions inferred from H alpha photographs and (2) observations of the photospheric magnetic field made with low spatial resolution (3 arc min.) and high sensitivity using the Stanford magnetograph. The comparison is found to be very favorable

Using ³⁶Cl exposure dating to date mass movement and assess land stability on the Nicholas Range, Tasmania

Detailed mapping of dolerite slope deposits overlying sedimentary Triassic rocks on the northern slopes of the Nicholas Range in northeastern Tasmania has revealed an extensive mass movement complex. Landforms north of the summit plateau of the Nicholas Range include the following: (1) a cliff of dolerite columns with associated scree slopes at its base; (2) a topple landscape consisting of several topples that have fallen in a north-easterly direction; (3) a ripple landscape consisting of a series of long boulder ridges aligned approximately east-west. Exposure dates were obtained for three large boulders (collapsed dolerite columns) from a ridge within the ripple landscape. The two youngest dates gave a mean age of 52.1 ± 1.9 ka using36Cl. This is the estimated age for collapse of the dated columns from the cliff face c. 750 m to the south. Boulder ages and landscape morphology indicate that the ripple landscape developed by physical and chemical degradation and concurrent northern displacement of topples over a slip plane formed at the contact between dolerite colluvium and underlying Triassic sedimentary rocks. There is no evidence of movement today, other than localised debris flows associated with knickpoints in streams, and it is deduced that movement on the slip plane occurred under a cooler climate than that prevailing today, possibly under the influence of melting of winter snow during the last glacial cycle. As there is no evidence of significant recent mass movement and forests in the area are likely to have experienced many stand-destroying forest fires in the Holocene, forest harvest is not considered to pose a risk to landscape stability

Tidal effects and the Proximity decay of nuclei

We examine the decay of the 3.03 MeV state of $^8$Be evaporated from an excited projectile-like fragment following a peripheral heavy-ion collision. The relative energy of the daughter $\alpha$ particles exhibits a dependence on the decay angle of the $^8$Be$^*$, indicative of a tidal effect. Comparison of the measured tidal effect with a purely Coulomb model suggests the influence of a measurable nuclear proximity interaction.Comment: 5 pages, 4 figure

The role of sustainability knowledge-action platforms in advancing multi-stakeholder engagement on sustainability

Within the last decade, online sustainability knowledge-action platforms have proliferated. We surveyed 198 sustainability-oriented sites and conducted a review of 41 knowledge-action platforms, which we define as digital tools that advance sustainability through organized activities and knowledge dissemination. We analyzed platform structure and functionality through a systematic coding process based on key issues identified in three bodies of literature: (a) the emergence of digital platforms, (b) the localization of the sustainable development goals (SDGs), and (c) the importance of multi-level governance to sustainability action. While online collaborative tools offer an array of resources, our analysis indicates that they struggle to provide context-sensitivity and higher-level analysis of the trade-offs and synergies between sustainability actions. SDG localization adds another layer of complexity where multi-level governance, actor, and institutional priorities may generate tensions as well as opportunities for intra- and cross-sectoral alignment. On the basis of our analysis, we advocate for the development of integrative open-source and dynamic global online data management tools that would enable the monitoring of progress and facilitate peer-to-peer exchange of ideas and experience among local government, community, and business stakeholders. We argue that by showcasing and exemplifying local actions, an integrative platform that leverages existing content from multiple extant platforms through effective data interoperability can provide additional functionality and significantly empower local actors to accelerate local to global actions, while also complex system change

Hinode/EIS observations of propagating low-frequency slow magnetoacoustic waves in fan-like coronal loops

We report the first observation of multiple-periodic propagating disturbances along a fan-like coronal structure simultaneously detected in both intensity and Doppler shift in the Fe XII 195 A line with the EUV Imaging Spectrometer (EIS) onboard Hinode. A new application of coronal seismology is provided based on this observation. We analyzed the EIS sit-and-stare mode observation of oscillations using the running difference and wavelet techniques. Two harmonics with periods of 12 and 25 min are detected. We measured the Doppler shift amplitude of 1-2 km/s, the relative intensity amplitude of 3%-5% and the apparent propagation speed of 100-120 km/s. The amplitude relationship between intensity and Doppler shift oscillations provides convincing evidence that these propagating features are a manifestation of slow magnetoacoustic waves. Detection lengths (over which the waves are visible) of the 25 min wave are about 70-90 Mm, much longer than those of the 5 min wave previously detected by TRACE. This difference may be explained by the dependence of damping length on the wave period for thermal conduction. Based on a linear wave theory, we derive an inclination of the magnetic field to the line-of-sight about 59$\pm$8 deg, a true propagation speed of 128$\pm$25 km/s and a temperature of 0.7$\pm$0.3 MK near the loop's footpoint from our measurements.Comment: 4 pages and 4 figures, with 3 online figures and 1 online table; Astron & Astrophys Letter, in pres