321 research outputs found

    Let the Buyer Beware: A Comparison of Flood-Related Real Estate Disclosure Laws of Virginia and Other States

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    This white paper examines the state of flood disclosure laws for residential real estate transactions in Virginia and compares them to those of other states that have much more rigorous disclosure laws. Part II explores the history behind Virginia’s current “buyer beware” laws and examines previous attempts at establishing stricter real estate disclosure laws surrounding “special flood hazard areas”. Part III surveys a number of disclosure laws from other states that have successfully required sellers to disclose the risk of flooding in some capacity, and examines the events or circumstances that led to the enactment of those laws. Finally, Part IV concludes with an examination of the policy implications of implementing more stringent disclosure requirements in the Commonwealth. This abstract has been adapted from the author\u27s introduction

    Congestive heart failure: therapeutics--chronic CHF

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    This issue of eMedRef provides information to clinicians on the therapeutics of chronic congestive heart failure

    ACSVL3 is a Novel Therapeutic Target in Glioblastoma: Drug Discovery and Role in Protein Lipidation

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    Glioblastoma is an aggressive form of brain cancer with a five-year survival rate after diagnosis of less than 6%. More efficacious treatments are needed to improve patient prognosis. Very long-chain acyl-CoA synthetase (ACSVL3) is not detected in healthy glial cells, but is highly expressed in gliomas. Knockout of ACSVL3 in glioblastoma cells in culture decreases tumorigenicity and disrupts growth-factor induced cell signaling. However, the mechanism through which ACSVL3 promotes malignancy is not known. To address this question, lipid-based post-translational modifications were studied in wild-type and ACSVL3-knockout glioblastoma lines in cell culture. No significant differences were found in levels of protein palmitoylation or GPI anchors between wild-type and knockout cells. However, a global decrease in protein stearoylation was observed with ACSVL3 knockout, and mass spectrometry revealed several individual proteins that exhibited increased or decreased stearoylation with ACSVL3 knockout. From this we conclude that ACSVL3 is partially responsible for mediating stearoylation in glioblastoma cells. Next, we searched for inhibitors of ACSVL3. Inhibitors are desired both as tools to study the mechanism of ACSVL3-promoted malignancy and as potential therapeutic agents in glioblastoma. Two methods were established to screen for inhibitors of ACSVL3. The first was a small screen of known inhibitors of the homologous enzyme ACSVL1. This screen determined whether these drugs and compounds inhibited the activation of the 18-carbon fatty acid stearate by glioblastoma cells. The second was development of a screen to evaluate the ability of an ACSVL3/ACSVL1 hybrid enzyme to uptake fluorescent fatty-acid analogs. In the first screen, the small molecule CB5 was found to greatly inhibit activation of stearate. When glioblastoma cells in culture were treated with CB5, the compound slowed the rate of cell proliferation, induced differentiation, and decreased β-oxidation of long-chain fatty acids. Growth of subcutaneous xenografts produced from U87, but not Mayo-22, glioblastoma cells implanted subcutaneously in mice was significantly slowed by CB5 treatment. We conclude that the small molecule CB5 inhibits ACSVL3 activity in vitro and in vivo, and ACSVL3 is a promising novel therapeutic target in glioblastoma. The second screen shows high potential for conducting a high-throughput screen for additional inhibitors

    Assimilation of NUCAPS Retrieved Profiles in GSI for Unique Forecasting Applications

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    Hyperspectral IR profiles can be assimilated in GSI as a separate observation other than radiosondes with only changes to tables in the fix directory. Assimilation of profiles does produce changes to analysis fields and evidenced by: Innovations larger than +/-2.0 K are present and represent where individual profiles impact the final temperature analysis.The updated temperature analysis is colder behind the cold front and warmer in the warm sector. The updated moisture analysis is modified more in the low levels and tends to be drier than the original model background Analysis of model output shows: Differences relative to 13-km RAP analyses are smaller when profiles are assimilated with NUCAPS errors. CAPE is under-forecasted when assimilating NUCAPS profiles, which could be problematic for severe weather forecasting Refining the assimilation technique to incorporate an error covariance matrix and creating a separate GSI module to assimilate satellite profiles may improve results

    Persistent Diaper Need Identified During the COVID-19 Pandemic

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    Diaper need refers to the lack of a sufficient supply of diapers to keep an infant or child clean, dry, and healthy. More than 1 in 3 households (36%) experienced diaper need in the first year of the COVID-19 pandemic

    Identification of Preferred DNA-Binding Sites for the Thermus thermophilus Transcriptional Regulator SbtR by the Combinatorial Approach REPSA

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    One of the first steps towards elucidating the biological function of a putative transcriptional regulator is to ascertain its preferred DNA-binding sequences. This may be rapidly and effectively achieved through the application of a combinatorial approach, one involving very large numbers of randomized oligonucleotides and reiterative selection and amplification steps to enrich for high-affinity nucleic acid-binding sequences. Previously, we had developed the novel combinatorial approach Restriction Endonuclease Protection, Selection and Amplification (REPSA), which relies not on the physical separation of ligand-nucleic acid complexes but instead selects on the basis of ligand-dependent inhibition of enzymatic template inactivation, specifically cleavage by type IIS restriction endonucleases. Thus, no prior knowledge of the ligand is required for REPSA, making it more amenable for discovery purposes. Here we describe using REPSA, massively parallel sequencing, and bioinformatics to identify the preferred DNA-binding sites for the transcriptional regulator SbtR, encoded by the TTHA0167 gene from the model extreme thermophile Thermus thermophilus HB8. From the resulting position weight matrix, we can identify multiple operons potentially regulated by SbtR and postulate a biological role for this protein in regulating extracellular transport processes. Our study provides a proof-of-concept for the application of REPSA for the identification of preferred DNA-binding sites for orphan transcriptional regulators and a first step towards determining their possible biological roles
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