Development of LaRC 160/NR150B2 polyimide graphite hybrid composites

A method for co-curing NR150B2 and LaRC 160 prepregs into hybrid composites was developed. The processing characteristics and the properties of the hybrid composites were compared with those of laminates fabricated from the individual component prepregs. Resin forms were selected and optimized and a new NR150 formulation was investigated. The new formulation greatly facilitated the processing and the performance of this system. Quality control techniques were evaluated and developed, high quality laminates were fabricated from both individual resin systems, and hybrid laminates were successfully co-cured. Optimum hybrid forms were investigated and several novel approaches were explored. An optimum hybrid system was developed that utilizes a LaRC curing schedule but shows no degradation of mechanical properties after aging 500 hr in air at 260 C

UTILIZING THE RIGHT MIX OF ENVIRONMENTAL CLEANUP TECHNOLOGIES

The Savannah River Site (SRS) Figure 1 is a 310-square-mile United States Department of Energy nuclear facility located along the Savannah River near Aiken, South Carolina. During operations, which started in 1951, hazardous substances (chemicals and radionuclides) were released to the environment. The releases occurred as a result of inadvertent spills and waste disposal in unlined pits and basins which was common practice before environmental regulations existed. The hazardous substances have migrated to the vadose zone and groundwater in many areas of the SRS, resulting in 515 waste units that are required by environmental regulations, to undergo characterization and, if needed, remediation. In the initial years of the SRS environmental cleanup program (early 1990s), the focus was to use common technologies (such as pump and treat, air stripping, excavation and removal) that actively and tangibly removed contamination. Exclusive use of these technologies required continued and significant funding while often failing to meet acceptable clean-up goals and objectives. Recognizing that a more cost-effective approach was needed, SRS implemented new and complementary remediation methods focused on active and passive technologies targeted to solve specific remediation problems. Today, SRS uses technologies such as chemical/pH-adjusting injection, phytoremediation, underground cutoff walls, dynamic underground stripping, soil fracturing, microbial degradation, baroballs, electrical resistance heating, soil vapor extraction, and microblowers to more effectively treat contamination at lower costs. Additionally, SRS's remediation approach cost effectively maximizes cleanup as SRS works proactively with multiple regulatory agencies. Using GIS, video, animation, and graphics, SRS is able to provide an accurate depiction of the evolution of SRS groundwater and vadose zone cleanup activities to convince stakeholders and regulators of the effectiveness of various cleanup technologies. Remediating large, complex groundwater plumes using state of-the art technologies and approaches is a hallmark of years of experience and progress. Environmental restoration at SRS continues to be a challenging and dynamic process as new cleanup technologies and approaches are adopted

Differential requirements of androgen receptor in luminal progenitors during prostate regeneration and tumor initiation

Master regulatory genes of tissue specification play key roles in stem/progenitor cells and are often important in cancer. In the prostate, androgen receptor (AR) is a master regulator essential for development and tumorigenesis, but its specific functions in prostate stem/progenitor cells have not been elucidated. We have investigated AR function in CARNs (CAstration-Resistant Nkx3.1-expressing cells), a luminal stem/progenitor cell that functions in prostate regeneration. Using genetically--engineered mouse models and novel prostate epithelial cell lines, we find that progenitor properties of CARNs are largely unaffected by AR deletion, apart from decreased proliferation in vivo. Furthermore, AR loss suppresses tumor formation after deletion of the Pten tumor suppressor in CARNs; however, combined Pten deletion and activation of oncogenic Kras in AR-deleted CARNs result in tumors with focal neuroendocrine differentiation. Our findings show that AR modulates specific progenitor properties of CARNs, including their ability to serve as a cell of origin for prostate cancer

A computational systems approach identifies synergistic specification genes that facilitate lineage conversion to prostate tissue

To date, reprogramming strategies for generating cell types of interest have been facilitated by detailed understanding of relevant developmental regulatory factors. However, identification of such regulatory drivers often represents a major challenge, as specific gene combinations may be required for reprogramming. Here we show that a computational systems approach can identify cell type specification genes (master regulators) that act synergistically, and demonstrate its application for reprogramming of fibroblasts to prostate tissue. We use three such master regulators (FOXA1, NKX3.1 and androgen receptor, AR) in a primed conversion strategy starting from mouse fibroblasts, resulting in prostate tissue grafts with appropriate histological and molecular properties that respond to androgen-deprivation. Moreover, generation of reprogrammed prostate does not require traversal of a pluripotent state. Thus, we describe a general strategy by which cell types and tissues can be generated even with limited knowledge of the developmental pathways required for their specification in vivo

The Updated version of SF Box: A method for soil quality classification as a basis for applicable site-specific environmental risk assessment of contaminated soils

This technical note summarises major changes in the updated version of SF Box, which is part of the SCORE – the Multi-Criteria Decision Analysis method for decision support in soil remediation projects. SCORE stands for the Sustainable Choice Of REmediation and SF Box stands for Soil Function toolBox. The SF Box tool has been developed for soil function assessment to complement environmental risk assessments, in order to increase awareness of decision-makers for inherent soil qualities other than concentration of contaminants and their availability/mobility, which are critical for proper soil functioning, e.g. availability of water and nutrients for soil organisms, but often ignored in remediation projects (driven by protection of the soil environment with ambition to recover ecosystem functions) in Sweden. The tool is based on a scoring method using soil quality indicators (SQIs) for assessing (I) the soil’s capacity to perform its functions in its own reference state of being ‘clean’, i.e. “what can this soil do and can it perform its functions well, assuming that it is free of contaminants?”, and (II) the effects of the remedial actions themselves on soil functions, i.e. “can the remediated soil continue to perform these functions well?”. The earlier version of SF Box addresses the soil functions associated with Primary Production. By (i) taking into consideration the perspectives of soil microbiology, soil fauna and vegetation, (ii) slightly modifying the set of SQIs (consisting of soil texture, content of coarse material, organic carbon/matter, available water, C/N ratio, pH and available phosphorus), and (iii) revisiting the curves for scoring of soil performances on each SQI, the SF Box tool has been updated to assess the soils’ capacity to function as a basis for Life and Habitat of flora and fauna. This updated version is therefore aimed to provide an improved basis for site-specific environmental risk assessment by means of (1) differentiating between the effects of contamination on soil biota and the effects of soil capability to function as a host to these species in its own reference state free from contaminants, and (2) classification of the soils (usually characterized by heterogeneity at contaminated sites) in accordance with their overall performance on the selected SQIs for further analysis of ecotoxicological risks in each soil class

Cell Rep

The identification of cell types of origin for cancer has important implications for tumor stratification and personalized treatment. For prostate cancer, the cell of origin has been intensively studied, but it has remained unclear whether basal or luminal epithelial cells, or both, represent cells of origin under physiological conditions in vivo. Here, we use a novel lineage-tracing strategy to assess the cell of origin in a diverse range of mouse models, including Nkx3.1(+/-); Pten(+/-), Pten(+/-), Hi-Myc, and TRAMP mice, as well as a hormonal carcinogenesis model. Our results show that luminal cells are consistently the observed cell of origin for each model in situ; however, explanted basal cells from these mice can generate tumors in grafts. Consequently, we propose that luminal cells are favored as cells of origin in many contexts, whereas basal cells only give rise to tumors after differentiation into luminal cells

Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects

The human sodium channel family includes seven neuronal channels that are essential for the initiation and propagation of action potentials in the CNS and PNS. In view of their critical role in neuronal firing and their strong sequence conservation during evolution, it is not surprising that mutations in the sodium channel genes are responsible for a growing spectrum of channelopathies. Nearly 700 mutations of the SCN1A gene have been identified in patients with Dravet's syndrome (severe myoclonic epilepsy of infancy), making this the most commonly mutated gene in human epilepsy. A small number of mutations have been found in SCN2A , SCN3A and SCN9A , and studies in the mouse suggest that SCN8A may also contribute to seizure disorders. Interactions between genetic variants of SCN2A and KCNQ2 in the mouse and variants of SCN1A and SCN9A in patients provide models of potential genetic modifier effects in the more common human polygenic epilepsies. New methods for generating induced pluripotent stem cells and neurons from patients will facilitate functional analysis of amino acid substitutions in channel proteins. Whole genome sequencing and exome sequencing in patients with epilepsy will soon make it possible to detect multiple variants and their interactions in the genomes of patients with seizure disorders.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79388/1/jphysiol.2010.188482.pd

Discovery and Characterization of Bukakata orbivirus (\u3ci\u3eReoviridae:Orbivirus\u3c/i\u3e), a Novel Virus from a Ugandan Bat

While serological and virological evidence documents the exposure of bats to medically important arboviruses, their role as reservoirs or amplifying hosts is less well-characterized. We describe a novel orbivirus (Reoviridae:Orbivirus) isolated from an Egyptian fruit bat (Rousettus aegyptiacus leachii) trapped in 2013 in Uganda and named Bukakata orbivirus. This is the fifth orbivirus isolated from a bat, however genetic information had previously only been available for one bat-associated orbivirus. We performed whole-genome sequencing on Bukakata orbivirus and three other bat-associated orbiviruses (Fomede, Ife, and Japanaut) to assess their phylogenetic relationship within the genus Orbivirus and develop hypotheses regarding potential arthropod vectors. Replication kinetics were assessed for Bukakata orbivirus in three different vertebrate cell lines. Lastly, qRT-PCR and nested PCR were used to determine the prevalence of Bukakata orbivirus RNA in archived samples from three populations of Egyptian fruit bats and one population of cave-associated soft ticks in Uganda. Complete coding sequences were obtained for all ten segments of Fomede, Ife, and Japanaut orbiviruses and for nine of the ten segments for Bukakata orbivirus. Phylogenetic analysis placed Bukakata and Fomede in the tick-borne orbivirus clade and Ife and Japanaut within the Culicoides/phlebotomine sandfly orbivirus clade. Further, Bukakata and Fomede appear to be serotypes of the Chobar Gorge virus species. Bukakata orbivirus replicated to high titers (106–107 PFU/mL) in Vero, BHK-21 [C-13], and R06E (Egyptian fruit bat) cells. Preliminary screening of archived bat and tick samples do not support Bukakata orbivirus presence in these collections, however additional testing is warranted given the phylogenetic associations observed. This study provided complete coding sequence for several bat-associated orbiviruses and in vitro characterization of a bat-associated orbivirus. Our results indicate that bats may play an important role in the epidemiology of viruses in the genus Orbivirus and further investigation is warranted into vector-host associations and ongoing surveillance efforts

Discovery and Characterization of Bukakata orbivirus (\u3ci\u3eReoviridae:Orbivirus\u3c/i\u3e), a Novel Virus from a Ugandan Bat

While serological and virological evidence documents the exposure of bats to medically important arboviruses, their role as reservoirs or amplifying hosts is less well-characterized. We describe a novel orbivirus (Reoviridae:Orbivirus) isolated from an Egyptian fruit bat (Rousettus aegyptiacus leachii) trapped in 2013 in Uganda and named Bukakata orbivirus. This is the fifth orbivirus isolated from a bat, however genetic information had previously only been available for one bat-associated orbivirus. We performed whole-genome sequencing on Bukakata orbivirus and three other bat-associated orbiviruses (Fomede, Ife, and Japanaut) to assess their phylogenetic relationship within the genus Orbivirus and develop hypotheses regarding potential arthropod vectors. Replication kinetics were assessed for Bukakata orbivirus in three different vertebrate cell lines. Lastly, qRT-PCR and nested PCR were used to determine the prevalence of Bukakata orbivirus RNA in archived samples from three populations of Egyptian fruit bats and one population of cave-associated soft ticks in Uganda. Complete coding sequences were obtained for all ten segments of Fomede, Ife, and Japanaut orbiviruses and for nine of the ten segments for Bukakata orbivirus. Phylogenetic analysis placed Bukakata and Fomede in the tick-borne orbivirus clade and Ife and Japanaut within the Culicoides/phlebotomine sandfly orbivirus clade. Further, Bukakata and Fomede appear to be serotypes of the Chobar Gorge virus species. Bukakata orbivirus replicated to high titers (106–107 PFU/mL) in Vero, BHK-21 [C-13], and R06E (Egyptian fruit bat) cells. Preliminary screening of archived bat and tick samples do not support Bukakata orbivirus presence in these collections, however additional testing is warranted given the phylogenetic associations observed. This study provided complete coding sequence for several bat-associated orbiviruses and in vitro characterization of a bat-associated orbivirus. Our results indicate that bats may play an important role in the epidemiology of viruses in the genus Orbivirus and further investigation is warranted into vector-host associations and ongoing surveillance efforts