The SUMO Ligase Protein Inhibitor of Activated STAT 1 (PIAS1) is a constituent PML-NB protein that contributes to the intrinsic antiviral immune response to herpes simplex virus 1 (HSV-1)

Aspects of intrinsic antiviral immunity are mediated by promyelocytic leukaemia (PML)-nuclear body (PML-NB) constituent proteins. During herpesvirus infection, these antiviral proteins are independently recruited to nuclear domains that contain infecting viral genomes to cooperatively promote viral genome silencing. Central to the execution of this particular antiviral response is the small ubiquitin-like modifier (SUMO) signalling pathway. However, the participating SUMOylation enzymes are not fully characterized. We identify the SUMO ligase Protein Inhibitor of Activated STAT1 (PIAS1) as a constituent PML-NB protein. We show that PIAS1 localizes at PML-NBs in a SUMO interaction motif (SIM)-dependent manner that requires SUMOylated or SUMOylation competent PML. Following infection with herpes simplex virus 1 (HSV-1), PIAS1 is recruited to nuclear sites associated with viral genome entry in a SIM-dependent manner, consistent with the SIM-dependent recruitment mechanisms of other well characterized PML-NB proteins. In contrast to Daxx and Sp100, however, the recruitment of PIAS1 is enhanced by PML. PIAS1 promotes the stable accumulation of SUMO1 at nuclear sites associated with HSV-1 genome entry, whereas the accumulation of other evaluated PML-NB proteins occurs independently of PIAS1. We show that PIAS1 cooperatively contributes to HSV-1 restriction through mechanisms that are additive to those of PML and cooperative with those of PIAS4. The antiviral mechanisms of PIAS1 are counteracted by ICP0, the HSV-1 SUMO-targeted ubiquitin ligase, which disrupts the recruitment of PIAS1 to nuclear domains that contain infecting HSV-1 genomes through mechanisms that do not directly result in PIAS1 degradation

Monitoring and Modeling of Emissions from Concentrated Animal Feeding Operations: Overview of Methods

Accurate monitors are required to determine ambient concentration levels of contaminants emanating from concentrated animal feeding operations (CAFOs), and accurate models are required to indicate the spatial variability of concentrations over regions affected by CAFOs. A thorough understanding of the spatial and temporal variability of concentration levels could then be associated with locations of healthy individuals or subjects with respiratory ailments to statistically link the presence of CAFOs to the prevalence of ill health effects in local populations. This workgroup report, which was part of the Conference on Environmental Health Impacts of Concentrated Animal Feeding Operations: Anticipating Hazards—Searching for Solutions, describes instrumentation currently available for assessing contaminant concentration levels in the vicinity of CAFOs and reviews plume dispersion models that may be used to estimate concentration levels spatially. Recommendations for further research with respect to ambient air monitoring include accurately determining long-term average concentrations for a region under the influence of CAFO emissions using a combination of instruments based on accuracy, cost, and sampling duration. In addition, development of instruments capable of accurately quantifying adsorbed gases and volatile organic compounds is needed. Further research with respect to plume dispersion models includes identifying and validating the most applicable model for use in predicting downwind concentrations from CAFOs. Additional data are needed to obtain reliable emission rates from CAFOs

Global Patterns of Terrestrial Biological Nitrogen (N2) Fixation in Natural Ecosystems

Human activities have clearly caused dramatic alterations of the terrestrial nitrogen cycle, and analyses of the extent and effects of such changes are now common in the scientific literature. However, any attempt to evaluate N cycling processes within ecosystems, as well as anthropogenic influences on the N cycle, requires an understanding of the magnitude of inputs via biological nitrogen fixation (BNF). Although there have been many studies addressing the microbiology, physiology, and magnitude of N fixation at local scales, there are very few estimates of BNF over large scales. We utilized \u3e100 preexisting published estimates of BNF to generate biome- and global-level estimates of biological N fixation. We also used net primary productivity (NPP) and evapotranspiration (ET) estimates from the Century terrestrial ecosystem model to examine global relationships between these variables and BNF as well as to compare observed and Century-modeled BNF. Our data-based estimates showed a strong positive relationship between ecosystem ET and BNF, and our analyses suggest that while the model\u27s simple relationships for BNF predict broad scale patterns, they do not capture much of the variability or magnitude of published rates. Patterns of BNF were also similar to patterns of ecosystem NPP. Our “best estimate” of potential nitrogen fixation by natural ecosystems is ∼195 Tg N yr−1, with a range of 100–290 Tg N yr−1. Although these estimates do not account for the decrease in natural N fixation due to cultivation, this would not dramatically alter our estimate, as the greatest reductions in area have occurred in systems characterized by relatively low rates of N fixation (e.g., grasslands). Although our estimate of BNF in natural ecosystems is similar to previously published estimates of terrestrial BNF, we believe that this study provides a more documented, constrained estimate of this important flux

Integration of Women Veterans into VA Quality Improvement Research Efforts: What Researchers Need to Know

The Department of Veterans Affairs (VA) and other federal agencies require funded researchers to include women in their studies. Historically, many researchers have indicated they will include women in proportion to their VA representation or pointed to their numerical minority as justification for exclusion. However, women’s participation in the military—currently 14% of active military—is rapidly changing veteran demographics, with women among the fastest growing segments of new VA users. These changes will require researchers to meet the challenge of finding ways to adequately represent women veterans for meaningful analysis. We describe women veterans’ health and health-care use, note how VA care is organized to meet their needs, report gender differences in quality, highlight national plans for women veterans’ quality improvement, and discuss VA women’s health research. We then discuss challenges and potential solutions for increasing representation of women veterans in VA research, including steps for implementation research

Modeling Multi-factor Binding of the Genome

<p>Hundreds of different factors adorn the eukaryotic genome, binding to it in large number. These DNA binding factors (DBFs) include nucleosomes, transcription factors (TFs), and other proteins and protein complexes, such as the origin recognition complex (ORC). DBFs compete with one another for binding along the genome, yet many current models of genome binding do not consider different types of DBFs together simultaneously. Additionally, binding is a stochastic process that results in a continuum of binding probabilities at any position along the genome, but many current models tend to consider positions as being either binding sites or not.</p><p>Here, we present a model that allows a multitude of DBFs, each at different concentrations, to compete with one another for binding sites along the genome. The result is an 'occupancy profile', a probabilistic description of the DNA occupancy of each factor at each position. We implement our model efficiently as the software package COMPETE. We demonstrate genome-wide and at specific loci how modeling nucleosome binding alters TF binding, and vice versa, and illustrate how factor concentration influences binding occupancy. Binding cooperativity between nearby TFs arises implicitly via mutual competition with nucleosomes. Our method applies not only to TFs, but also recapitulates known occupancy profiles of a well-studied replication origin with and without ORC binding.</p><p>We then develop a statistical framework for tuning our model concentrations to further improve its predictions. Importantly, this tuning optimizes with respect to actual biological data. We take steps to ensure that our tuned parameters are biologically plausible.</p><p>Finally, we discuss novel extensions and applications of our model, suggesting next steps in its development and deployment.</p>Dissertatio

Application of Radio Control Cars as Intelligent Unmanned Ground Vehicles with Collaborative and

Simple radio control cars commonly sold as toys can provide a viable starting platform for the development of low-cost intelligent Unmanned Ground Vehicles (UGVs) for the study of robot collectives. In a collaborative effort, Sandia National Labs and New Mexico Tech have successfully demonstrated proof-of-concept by utilizing low-cost radio control cars manufactured by Nikko. Initial tests have involved using a small number (two to ten) of these UGVs to successfully demonstrate both collaborative and independent behavior simultaneously. In the tests individuals share their locations with the collective to cover an area, thus demonstrating collaborative behavior. Independent behavior is demonstrated as each member of the collective maintains a desired compass heading while simultaneously avoiding obstacles in its path. These UGVs are powered by high-capacity rechargeable batteries and equipped with a custom-designed microcontroller board with a stackable modular interface and wireless communication. The initial modular sensor configuration includes a digital compass and GPS unit for navigation as well as ultrasonic sensors for obstacle avoidance. This paper describes the design and operations of these UGVs, their possible uses, and the advantages of using a radio control car platform as a low-cost starting point for the development of intelligent UGV collectives

Monitoring and Modeling of Emissions from Concentrated Animal Feeding Operations: Overview of Methods

Accurate monitors are required to determine ambient concentration levels of contaminants emanating from concentrated animal feeding operations (CAFOs), and accurate models are required to indicate the spatial variability of concentrations over regions affected by CAFOs. A thorough understanding of the spatial and temporal variability of concentration levels could then be associated with locations of healthy individuals or subjects with respiratory ailments to statistically link the presence of CAFOs to the prevalence of ill health effects in local populations. This workgroup report, which was part of the Conference on Environmental Health Impacts of Concentrated Animal Feeding Operations: Anticipating Hazards—Searching for Solutions, describes instrumentation currently available for assessing contaminant concentration levels in the vicinity of CAFOs and reviews plume dispersion models that may be used to estimate concentration levels spatially. Recommendations for further research with respect to ambient air monitoring include accurately determining long-term average concentrations for a region under the influence of CAFO emissions using a combination of instruments based on accuracy, cost, and sampling duration. In addition, development of instruments capable of accurately quantifying adsorbed gases and volatile organic compounds is needed. Further research with respect to plume dispersion models includes identifying and validating the most applicable model for use in predicting downwind concentrations from CAFOs. Additional data are needed to obtain reliable emission rates from CAFOs.This article is from Environmental Health Perspectives 115, no. 2 (February 2007): 303–307, doi:10.1289/ehp.8838. Posted with permission.</p

Aussermotorische Verschleisspruefung zur Einstufung von Werkstoffen fuer Kolbenring-Zylinder-Paarungen Abschlussbericht

Available from TIB Hannover: RA 1581(401) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Broad-Scale Non-indigenous Species Monitoring along the West Coast in National Marine Sanctuaries and National Estuarine Research Reserves

Nonindigenous species have caused substantial environmental and economic damage to coastal areas. Moreover, the extent and impacts of nonindigenous species are increasing over time. To develop predictive models and to identify which areas should be targeted for impact mitigation or early detection, we need a basic foundation of knowledge about the spatial and temporal patterns of invasions. This project was developed because we lacked the necessary data to rigorously evaluate the patterns of coastal invasions. This collaborative project, between the Smithsonian Environmental Research Center, the National Estuarine Research Reserve System (NERRS) and the National Marine Sanctuary Program (NMSP), established a rigorous, largescale monitoring and research program for invasive species in nine protected coastal areas along the US West Coast from San Diego, CA, to Kachemak Bay, AK. Our research included two components, broad-scale and site-specific projects. The broad-scale component focused on using standardized protocols to collect data on the composition of fouling communities and nearshore fish and crabs. We collected data from 310 settling plates and 140 traps across nine NERRS Reserves and NMSP Sanctuaries. The four most common taxa on the settling plates were Bryozoa, Tunicata, Cirripedia, and Hydrozoa. We identified these four taxa and also Nudibranchia, a mobile molluscan taxa often associated with fouling organisms, to species and noted which were nonindigenous. We found 132 species in the 5 taxa under study. NIS accounted for over one quarter of the diversity in these taxa, with 31 NIS identified. Over half of tunicate species were non-native. The documented NIS included two new US west coast sitings plus 3 other range extensions. We documented two patterns in NIS, a latitudinal pattern and differences between NIS impacts in marinas versus non-marina sites; research on salinity differences is still underway. Both the number and percent of NIS decreased with increasing latitude. Tijuana River had the most, 21, NIS and Monterey Bay had the highest proportion of NIS (57%). The same pattern of decreasing NIS with increasing latitude was observed when we examined Tunicata only and Bryozoa only. Across latitudes, plates in marinas were more impacted by NIS than were plates in more natural areas. All NIS but one were found at marinas, whereas only half the NIS were found at the non-marina sites. In addition, NIS at marinas accounted for almost 80% of the NIS per site. Therefore, we were able to provide information on the relative risk of invasions for different taxonomic groups and geographic regions. The spatial and habitat patterns can be used for future predictions and will be of even more value once they are confirmed with additional taxonomic groups and hypothesis-driven studies that will continue from this initial study. Our broad-scale trapping study illustrated how recently-introduced NIS quickly can become numerically dominant. Although we only found Carcinus maenas at Elkhorn Slough NERR, this recently introduced nonindigenous crab was very common at this Reserve and was the most abundant crab in our traps at 3 of 7 Elkhorn sites. The site-specific projects were conducted at each Reserve plus Olympic Coast and Monterey Bay Sanctuaries. Several are serving as the first important step in longer term research, such as examining whether a change in shipping policy in Kachemak Bay will increase NIS. Others, such as the South Slough project examining the effect of a salinity cline on the number and proportion of NIS, will be expanded to test hypotheses across several protected areas. Many of these site-specific projects still need further analyses, and analysis is underway