Structural studies of the Ig58 domain of the giant muscle protein obscurin

Obscurin (720-900 kD) is a giant sarcomeric signaling protein that is the only known link between the cytoskeleton and the surrounding membrane structure. Mutations to obscurin and to obscurin binding partners have been linked to human muscle diseases such as hypertrophic cardiomyopathies and muscular dystrophy. These diseases likely occur due to the abrogation of specific molecular interactions necessary for suitable function. To more fully understand how specific mutations lead to disease, here we solve the highresolution structure of obscurin Ig58. The literature shows that an Arg8Gln mutation to the Ig58 domain of obscurin is associated with hypertrophic cardiomyopathy (HCM). Chemical shift changes of this mutation and MD simulations suggest that this mutation disrupts a large charge-charge surface of Ig58, perturbing the titin-binding interface

The Scrivener\u27s Error: How Bankruptcy Judges Overrule Health Experts on Medicare Decisions

There is a circuit split over the interpretation of 42 U.S.C. § 405(h), which requires providers to exhaust their remedies with the Department of Health and Human Services (HHS) before proceeding to court. This split originates from a recodification that omitted several jurisdictional grants from § 405(h), leaving courts to decide whether to continue interpreting the statute as Congress intended or begin interpreting the statute’s plain language. Complicating this split, a backlog of claims in HHS’s appeal systems prevents speedy adjudication. This delay leaves providers searching for other adjudicatory options for their Medicare claims, such as bankruptcy courts. As initially written, the statute intended to bar bankruptcy courts from hearing Medicare claims. After a recodification, Congress omitted several jurisdictional grants from the statute, leaving the plain text to support judicial adjudication of Medicare claims. Nonetheless, the recodification canon of statutory construction allows courts to continue using the pre-amended meaning of § 405(h). Congressional Medicare policy leans towards barring bankruptcy courts and allowing HHS to adjudicate these claims first. This Medicare policy supports a uniform and efficient Medicare law. On the contrary, congressional bankruptcy policy supports the court having jurisdiction over the entire bankruptcy estate, including Medicare claims. Nevertheless, bankruptcy jurisdiction is not expansive enough to cover claims clearly under HHS’s jurisdiction. Providers claim they need bankruptcy courts as an alternative to agency adjudication because of the backlog in the appeal systems. Subsequently, the agency is proactively speeding up the appeal process. Though providers may try to avoid the appeal system by asserting that their claim does not arise under Medicare law, § 405(h) encompasses the claims that providers are trying to file in bankruptcy court. Consequently, providers should appeal to the agency first. Therefore, Congress should amend the statute to explicitly bar bankruptcy jurisdiction to reflect the Act’s original intent since this will ensure uniformity and efficiency in Medicare law. Furthermore, barring bankruptcy jurisdiction ensures that the agency responsible for health law questions can fully apply its expertise to these questions by facilitating an effective internal agency appeals process

Top-of-the-line corrosion control by continuous chemical treatment

Top-of-the-Line (TOL) corrosion was investigated under different carbon dioxide partial pressures, acetic acid concentrations, and temperatures in order to understand the impact of these different parameters on TOL corrosion.16 generic amines were tested as possible volatile corrosion inhibitor (VCI) candidates in a variety of TOL corrosion test set-ups. Properties of a working TOL corrosion inhibitor were identified and TOL corrosion laboratory test methods were improved

An Analysis of the Substantive Effectiveness of the National Environmental Policy Act: Lessons from Ivanpah

Nearly 45 years ago, the National Environmental Policy Act (NEPA) was signed into law to become the first national policy for the environment of the United States. As it has evolved over time through implementation and litigation, numerous countries and states around the world have emulated NEPA with similar environmental impact assessment requirements. Many scholars have evaluated the success of the legislation in accomplishing its lofty goals. Most commonly, however, these studies address the procedural performance of agencies through the creation of environmental impact statements. This thesis examines the effectiveness of NEPA in accomplishing its substantive, rather than procedural, goals by identifying a set of values essential to meeting the fundamental intent of the Act. The values are then evaluated in the context of the Ivanpah Solar Electric Generating System Project to determine whether or not the NEPA process was effective in this case and to derive lessons for its future implementation

Fluid Expulsion, Habitability, and the Search for Life on Mars

Habitability assessments are critical for identifying settings in which potential biosignatures could exist in quantities large enough to be detected by rovers. Habitability depends on 1) the potential for long-lived liquid water, 2) conditions affording protection from surface processes destructive to organic biomolecules, and 3) a source of renewing nutrients and energy. Of these criteria, the latter is often overlooked. Here we present an analysis of a large "ghost" crater in northern Chryse Planitia [1] that appears to have satisfied each of these requirements, with several processes providing potential sources of nutrient/energy renewal [1-2]. This analysis can serve as a model for identifying other localities that could provide similarly favorable settings in which to seek evidence of life on Mars

Protein-mediated DNA Loop Formation and Breakdown in a Fluctuating Environment

Living cells provide a fluctuating, out-of-equilibrium environment in which genes must coordinate cellular function. DNA looping, which is a common means of regulating transcription, is very much a stochastic process; the loops arise from the thermal motion of the DNA and other fluctuations of the cellular environment. We present single-molecule measurements of DNA loop formation and breakdown when an artificial fluctuating force, applied to mimic a fluctuating cellular environment, is imposed on the DNA. We show that loop formation is greatly enhanced in the presence of noise of only a fraction of $k_B T$, yet find that hypothetical regulatory schemes that employ mechanical tension in the DNA--as a sensitive switch to control transcription--can be surprisingly robust due to a fortuitous cancellation of noise effects

Rover Exploration of Acidalia Mensa and Acidalia Planitia: Probing Mud Volcanoes to Sample Buried Sediments and Search for Ancient and Extant Life

Here we develop a plan to explore mud volcanoes near Acidalia Mensa with an MSL-class rover and propose a traverse based on geologic observations

Vernal Crater, SW Arabia Terra: MSL Candidate with Extensively Layered Sediments, Possible Lake Deposits, and a Long History of Subsurface Ice

Vernal Crater is a Mars Science Laboratory (MSL) landing site candidate providing relatively easy access to extensively layered sediments as well as potential lake deposits. Sediments of Vernal Crater are 400-1200 m below those being investigated by Opportunity in Meridiani Planum, and as such would allow study of significantly older geologic units, if Vernal Crater were selected for MSL. The location of Vernal Crater in SW Arabia Terra provides exceptional scientific interest, as rampart craters and gamma-ray spectrometer (GRS) data from the region suggest a long history of ice/fluids in the subsurface. The potential value of this MSL candidate is further enhanced by reports of atmospheric methane over Arabia, as any insight into the source of that methane would significantly increase our understanding of Mars. Finally, should MSL survive beyond its prime mission, the gentle slope within Vernal Crater would provide a route out of the crater for study of the once ice/fluid-rich plains

New Support for Hypotheses of an Ancient Ocean on Mars

A new analog for the giant polygons in the Chryse-Acidalia area suggests that those features may have formed in a major body of water - likely a Late Hesperian to Early Amazonian ocean. This analog -terrestrial polygons in subsea, passive margin basins derives from 3D seismic data that show similar-scale, polygonal fault systems in the subsurface of more than 50 terrestrial offshore basins. The terrestrial and martian polygons share similar sizes, basin-wide distributions, tectonic settings, and association with expected fine-grained sediments. Late Hesperian deposition from outflow floods may have triggered formation of these polygons, by providing thick, rapidly-deposited, fine-grained sediments necessary for polygonal fracturing. The restriction of densely occurring polygons to elevations below approx. -4000 m to -4100 m supports inferences that a body of water controlled their formation. Those same elevations appear to restrict occurrence of polygons in Utopia Planitia, suggesting that this analog may apply also to Utopia and that similar processes may have occurred across the martian lowlands

Mud Volcanoes in the Martian Lowlands: Potential Windows to Fluid-Rich Samples from Depth

The regional setting of the Chryse-Acidalia area augurs well for a fluid-rich subsurface, accumulation of diverse rock types reflecting the wide catchment area, astrobiological prospectivity, and mud volcanism. This latter provides a mechanism for transporting samples from relatively great depth to the surface. Since mud volcanoes are not associated with extreme heat or shock pressures, materials they transport to the surface are likely to be relatively unaltered; thus such materials could contain interpretable remnants of potential martian life (e.g., organic chemical biomarkers, mineral biosignatures, or structural remains) as well as unmetamorphosed rock samples. None of the previous landings on Mars was located in an area with features identified as potential mud volcanoes (Fig. 3), but some of these features may offer targets for future missions aimed at sampling deep fluid-rich strata with potential habitable zones