Thermodynamic Field Theory with the Iso-Entropic Formalism

A new formulation of the thermodynamic field theory (TFT) is presented. In this new version, one of the basic restriction in the old theory, namely a closed-form solution for the thermodynamic field strength, has been removed. In addition, the general covariance principle is replaced by Prigogine's thermodynamic covariance principle (TCP). The introduction of TCP required the application of an appropriate mathematical formalism, which has been referred to as the iso-entropic formalism. The validity of the Glansdorff-Prigogine Universal Criterion of Evolution, via geometrical arguments, is proven. A new set of thermodynamic field equations, able to determine the nonlinear corrections to the linear ("Onsager") transport coefficients, is also derived. The geometry of the thermodynamic space is non-Riemannian tending to be Riemannian for hight values of the entropy production. In this limit, we obtain again the same thermodynamic field equations found by the old theory. Applications of the theory, such as transport in magnetically confined plasmas, materials submitted to temperature and electric potential gradients or to unimolecular triangular chemical reactions can be found at references cited herein.Comment: 35 page

Fostering collaborative research for rare genetic disease: The example of Niemann-Pick type C disease

Rare disease represents one of the most significant issues facing the medical community and health care providers worldwide, yet the majority of these disorders never emerge from their obscurity, drawing little attention from the medical community or the pharmaceutical industry. The challenge therefore is how best to mobilize rare disease stakeholders to enhance basic, translational and clinical research to advance understanding of pathogenesis and accelerate therapy development. Here we describe a rare, fatal brain disorder known as Niemann-Pick type C (NPC) and an innovative research collaborative known as Support of Accelerated Research for NPC (SOAR-NPC) which illustrates one pathway through which knowledge of a rare disease and its possible treatments are being successfully advanced. Use of the “SOAR” mechanism, we believe, offers a blueprint for similar advancement for many other rare disorders

Mycobacterium pseudoshottsii sp nov., a slowly growing chromogenic species isolated from Chesapeake Bay striped bass (Morone saxatilis)

A group of slowly growing photochromogenic mycobacteria was isolated from Chesapeake Bay striped bass (Morone saxatilis) during an epizootic of mycobacteriosis. Growth characteristics, acid-fastness and 16S rRNA gene sequencing results were consistent with those of the genus Mycobacterium, Biochemical reactions, growth characteristics and mycolic acid profiles (HPLC) resembled those of Mycobacterium shottsii, a non-pigmented mycobacterium also isolated during the same epizootic. Sequencing of the 16S rRNA genes, the gene encoding the exported repeated protein (erp) and the gene encoding the 65 kDa heat-shock protein (hsp65) and restriction enzyme analysis of the hsp65 gene demonstrated that this group of isolates is unique. Insertion sequences associated with Mycobacterium ulcerans, IS2404 and IS2606, were detected by PCR. These isolates could be differentiated from other slowly growing pigmented mycobacteria by their inability to grow at 37 degrees C, production of niacin and urease, absence of nitrate reductase, negative Tween 80 hydrolysis and resistance to isoniazid (1 mu g ml(-1)), p-nitrobenzoic acid, thiacetazone and thiophene-2-carboxylic hydrazide. On the basis of this polyphasic study, it is proposed that these isolates represent a novel species, Mycobacterium pseudoshottsii sp. nov. The type strain, L15(T), has been deposited in the American Type Culture Collection as ATCC BAA-883(T) and the National Collection of Type Cultures (UK) as NCTC 13318(T)

A novel cell immunoassay to measure survival of motor neurons protein in blood cells

BACKGROUND: The motor neuron degenerative disease spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality and is caused by mutations in the survival of motor neurons (SMN) gene that reduce the expression levels of the SMN protein. A major goal of current therapeutic approaches is to increase SMN levels in SMA patients. The purpose of this study was to develop a reliable assay to measure SMN protein levels from peripheral blood samples. METHODS: We developed a novel cell immunoassay to quantitatively measure SMN levels from peripheral blood mononuclear cells (PBMCs) using a single anti-SMN antibody. RESULTS: SMN levels determined by the cell immunoassay are comparable to levels determined by Western blot, but in contrast, the immunoassay does not involve cell lysis, requires a small amount of patient material, and can be done on a large number of samples simultaneously. SMN levels from PBMCs are not influenced by cell type heterogeneity. CONCLUSION: SMN levels measured from total PBMCs provide an important snapshot of SMN protein expression, which should be a useful aid in SMA diagnosis, and a surrogate marker of efficacy of treatment in SMA clinical trials

Test plan for the irradiation of nonmetallic materials.

A comprehensive test program to evaluate nonmetallic materials use in the Hanford Tank Farms is described in detail. This test program determines the effects of simultaneous multiple stressors at reasonable conditions on in-service configuration components by engineering performance testing

Insights into the Second Law of Thermodynamics from Anisotropic Gas-Surface Interactions

Thermodynamic implications of anisotropic gas-surface interactions in a closed molecular flow cavity are examined. Anisotropy at the microscopic scale, such as might be caused by reduced-dimensionality surfaces, is shown to lead to reversibility at the macroscopic scale. The possibility of a self-sustaining nonequilibrium stationary state induced by surface anisotropy is demonstrated that simultaneously satisfies flux balance, conservation of momentum, and conservation of energy. Conversely, it is also shown that the second law of thermodynamics prohibits anisotropic gas-surface interactions in "equilibrium", even for reduced dimensionality surfaces. This is particularly startling because reduced dimensionality surfaces are known to exhibit a plethora of anisotropic properties. That gas-surface interactions would be excluded from these anisotropic properties is completely counterintuitive from a causality perspective. These results provide intriguing insights into the second law of thermodynamics and its relation to gas-surface interaction physics.Comment: 28 pages, 11 figure

Commercial experience with facility deactivation to safe storage

The Department of Energy (DOE) has shutdown many production reactors; the Department has begun a major effort to also shutdown a wide variety of other nuclear facilities. Because so many facilities are being closed, it is necessary to place many of them into a safe- storage status, i.e., deactivation, before conducting decommissioning- for perhaps as long as 20 years. The challenge is to achieve this safe-storage condition in a cost-effective manner while remaining in compliance with applicable regulations. The DOE Office of Environmental Management, Office of Transition and Management, commissioned a lessons-learned study of commercial experience with safe storage and decommissioning. Although the majority of the commercial experience has been with reactors, many of the lessons learned presented in this document can provide insight into transitioning challenges that Will be faced by the DOE weapons complex

RNA polymerase II stalling promotes nucleosome occlusion and pTEFb recruitment to drive immortalization by Epstein-Barr virus

Epstein-Barr virus (EBV) immortalizes resting B-cells and is a key etiologic agent in the development of numerous cancers. The essential EBV-encoded protein EBNA 2 activates the viral C promoter (Cp) producing a message of ~120 kb that is differentially spliced to encode all EBNAs required for immortalization. We have previously shown that EBNA 2-activated transcription is dependent on the activity of the RNA polymerase II (pol II) C-terminal domain (CTD) kinase pTEFb (CDK9/cyclin T1). We now demonstrate that Cp, in contrast to two shorter EBNA 2-activated viral genes (LMP 1 and 2A), displays high levels of promoter-proximally stalled pol II despite being constitutively active. Consistent with pol II stalling, we detect considerable pausing complex (NELF/DSIF) association with Cp. Significantly, we observe substantial Cp-specific pTEFb recruitment that stimulates high-level pol II CTD serine 2 phosphorylation at distal regions (up to +75 kb), promoting elongation. We reveal that Cp-specific pol II accumulation is directed by DNA sequences unfavourable for nucleosome assembly that increase TBP access and pol II recruitment. Stalled pol II then maintains Cp nucleosome depletion. Our data indicate that pTEFb is recruited to Cp by the bromodomain protein Brd4, with polymerase stalling facilitating stable association of pTEFb. The Brd4 inhibitor JQ1 and the pTEFb inhibitors DRB and Flavopiridol significantly reduce Cp, but not LMP1 transcript production indicating that Brd4 and pTEFb are required for Cp transcription. Taken together our data indicate that pol II stalling at Cp promotes transcription of essential immortalizing genes during EBV infection by (i) preventing promoter-proximal nucleosome assembly and ii) necessitating the recruitment of pTEFb thereby maintaining serine 2 CTD phosphorylation at distal regions