Immune Response Mechanisms against AAV Vectors in Animal Models

Early preclinical studies in rodents and other species did not reveal that vector or transgene immunity would present a significant hurdle for sustained gene expression. While there was early evidence of mild immune responses to adeno-associated virus (AAV) in preclinical studies, it was generally believed that these responses were too weak and transient to negatively impact sustained transduction. However, translation of the cumulative success in treating hemophilia B in rodents and dogs with an AAV2-F9 vector to human studies was not as successful. Despite significant progress in recent clinical trials for hemophilia, new immunotoxicities to AAV and transgene are emerging in humans that require better animal models to assess and overcome these responses. The animal models designed to address these immune complications have provided critical information to assess how vector dose, vector capsid processing, vector genome, difference in serotypes, and variations in vector delivery route can impact immunity and to develop approaches for overcoming pre-existing immunity. Additionally, a comprehensive dissection of innate, adaptive, and regulatory responses to AAV vectors in preclinical studies has provided a framework that can be utilized for development of immunomodulatory therapies to overcome or bypass immune responses and for developing strategic approaches toward engineering stealth AAV vectors that can circumvent immunity

Titanium Nitride and Nitrogen Ion Implanted Coated Dental Materials

Titanium nitride and/or nitrogen ion implanted coated dental materials have been investigated since the mid-1980s and considered in various applications in dentistry such as implants, abutments, orthodontic wires, endodontic files, periodontal/oral hygiene instruments, and casting alloys for fixed restorations. Multiple methodologies have been employed to create the coatings, but detailed structural analysis of the coatings is generally lacking in the dental literature. Depending on application, the purpose of the coating is to provide increased surface hardness, abrasion/wear resistance, esthetics, and corrosion resistance, lower friction, as well as greater beneficial interaction with adjacent biological and material substrates. While many studies have reported on the achievement of these properties, a consensus is not always clear. Additionally, few studies have been conducted to assess the efficacy of the coatings in a clinical setting. Overall, titanium nitride and/or nitrogen ion implanted coated dental materials potentially offer advantages over uncoated counterparts, but more investigation is needed to document the structure of the coatings and their clinical effectiveness

Io's polar volcanic thermal emission indicative of magma ocean and shallow tidal heating models

The distribution of Io's volcanic activity likely reflects the position and magnitude of internal tidal heating. We use new observations of Io's polar regions by the Juno spacecraft Jovian Infrared Auroral Mapper (JIRAM) to complete near-infrared global coverage, revealing the global distribution and magnitude of thermal emission from Io's currently erupting volcanoes. We show that the distribution of volcanic heat flow from 266 active hot spots is consistent with the presence of a global magma ocean, and/or shallow asthenospheric heating. We find that Io's polar volcanoes are less energetic but about the same in number per unit area than at lower latitudes. We also find that volcanic heat flow in the north polar cap is greater than that in the south. The low volcanic advection seen at Io's poles is therefore at odds with measurements of background temperature showing Io's poles are anomalously warm. We suggest that the differences in volcanic thermal emission from Io's poles compared to that at lower latitudes is indicative of lithospheric dichotomies that inhibit volcanic advection towards Io's poles, particularly in the south polar region.Comment: 17 pages, two tables, 7 figure

Preparing the water supply and water conservation management plan for Metro North Georgia: process and results

Population, water supply needs, and wastewater flows are expected to nearly double during the next 30 years in the 16 counties of Metropolitan North Georgia. The additional population will place increasing pressure on water managers to assure adequate quantity and quality of the water resources flowing into and from this 16-county region. With a backdrop of more than 4 years of serious drought, State and local water managers recognized the importance of developing plans to appropriately manage future needs and share water resources among the District governments. State legislation was passed in 2001 to establish the Metropolitan North Georgia Water Planning District (District), and work began to develop the first set of integrated water resource plans. The condensed two-year planning effort produced a comprehensive assessment of the existing and projected status of the region’s water resources. This process enabled the local governments to work together to determine how best to meet future needs and to produce the plans for sustainability of water resources in the region. The District adopted three distinct but linked long-term plans for water supply, wastewater, and watershed management in September, 2003.Sponsored by: Georgia Environmental Protection Division U.S. Geological Survey, Georgia Water Science Center U.S. Department of Agriculture, Natural Resources Conservation Service Georgia Institute of Technology, Georgia Water Resources Institute The University of Georgia, Water Resources Facult

Noise Impacts from Professional Dog Grooming Forced-Air Dryers

This study was designed to measure the sound output of four commonly used brands of forced-air dryers used by dog groomers in the United States. Many dog groomers have questions about the effect of this exposure on their hearing, as well as on the hearing of the dogs that are being groomed. Readings taken from each dryer at 1 meter (the likely distance of the dryer from the groomer and the dog) showed average levels ranging from 105.5 to 108.3 dB SPL or 94.8 to 108.0 dBA. Using the 90 dBA criterion required by the US Occupational Safety and Health Administration, dog groomers/bathers are at risk if exposure to the lowest intensity dryer (94.8 dBA) exceeds 4 hours per day. If the more stringent 85 dBA criterion and 3 dB tradeoff is applied, less than one hour of exposure is permissible in an 8 hour day. Cautions are recommended for any persons exposed to noise from forced-air dryers

Some old movies become classics - a case study determining the scientific value of ROV inspection footage on a platform on Australia's North West Shelf

© 2018 Thomson, Fowler, Davis, Pattiaratchi and Booth. The global oil and gas industry holds a vast archive of Remotely Operated Vehicle (ROV) inspection footage potentially containing useful long-term data on marine biological communities. With the upcoming era of decommissioning of oil and gas structures, it is timely to assess the usefulness of this footage for researching these communities. We used ROV inspection footage to characterize the sessile invertebrates and fishes associated with the Goodwyn Alpha Production Platform (GWA) on the North West Shelf of Australia between depths of 10 and 125 m during 2006 and 2008. Depth was a major driver of invertebrate assemblages, most likely due to specific requirements such as light, and differences between years were most likely from the physical detachment of species by cyclones and internal waves. Phototrophic species were mostly limited to the upper 50 m of the platform, including the hard coral Pocillopora sp. and the soft corals Nephthea sp. and Scleronephthya sp. In contrast, heterotrophic species including sponges, anemones, bryozoans, hydroids, bivalves such as Lopha folium and the hard coral Tubastrea spp., were distributed across all depths. We observed 1791 fish from at least 10 families and 19 species, including commercial species such as crimson seaperch (Lutjanus erythropterus), red emperor (L. sebae), saddle-tailed seaperch (L. malabaricus), mangrove jack (L. argentimaculatus) and trevally (Caranx spp.). Fish density increased significantly with depth during 2008, from a mean of 23 fish/50 m2 between 10 and 25 m to 3373 fish/50 m2 at 125 m, where small unidentified baitfish were abundant. The highest densities of commercial species occurred between 25 and 75 m depth, suggesting that mid-depth platform sections had high habitat value, a consideration when selecting decommissioning options. The greatest difficulties using the video were the poor lighting and resolution that inhibited our ability to identify sessile species with high taxonomic precision. However, the footage was useful for evaluating high-level biodiversity of the platform, understanding how fish and invertebrate communities changed with depth and comprehending the dynamic nature of the invertebrate community over time. Understanding the habitat value of structures will be necessary for making environmentally sound decommissioning decisions in the future

The effects of water temperature on the juvenile performance of two tropical damselfishes expatriating to temperate reefs

Ocean warming associated with global climate change is already inducing geographic range shifts of marine species. Juvenile coral reef fishes transported into temperate latitudes (termed 'vagrant' fishes) can experience winter water temperatures below their normal thermal minimum. Such environmental extremes may increase energetic costs for such fishes, resulting in reduced performance, which may be the governing factor that limits the potential for poleward range expansion of such fishes. This study compared the juvenile physiological performance and behaviour of two congeneric tropical damselfishes which settle during austral summer months within temperate eastern Australia: Abudefduf vaigiensis have an extended southern range, and lower threshold survival temperature than the congeneric A. whitleyi. Physiological and behavioural performance parameters that may be affected by cooler temperature regimes at higher latitudes were measured in aquaria. Lower water temperature resulted in reduced growth rates, feeding rates, burst escape speed and metabolic rates of both species, with significantly reduced performance (up to six-fold reductions) for fishes reared at 18°C relative to 22°C and 26°C. However, A. whitleyi exhibited lower growth rates than A. vaigiensis across all temperatures, and lower aerobic capacity at the lowest temperature (18°C). This difference between species in growth and metabolic capacity suggests that the extended southern distribution and greater overwintering success of A. vaigiensis, in comparison to A. whitleyi is related to thermal performance parameters which are critical in maintaining individual health and survival. Our results support previous findings in the region that water temperature below 22°C represents a critical physiological threshold for tropical Abudefduf species expatriating into temperate south-eastern Australia

Electrochemical control of calcium carbonate crystallization and dissolution in nanopipettes

Electrochemically-controlled nanopipettes are becoming increasingly versatile tools for a diverse range of sequencing, sizing and imaging applications. Herein, the use of nanopipettes to induce and monitor quantitatively crystallization and dissolution in real time is considered, using CaCO3 in aqueous solution as an exemplar system. The bias between a quasi-reference counter electrode (QRCE) in a nanopipette and one in a bulk solution, is used to mix (or de-mix) two different solutions by ion migration and drive either growth or dissolution depending on the polarity. Furthermore, Raman spectroscopy can be applied simultaneously to identify polymorphs formed in the nanopipette. The technique is supported with a robust finite element method (FEM) model that allows the extraction of time-dependent saturation levels and mixing characteristics at the nanoscale. The technique shows great promise as a tool for rapidly screening growth additives and inhibitors, allowing eight different additives to be ranked in order of efficacy for crystal growth rate inhibition