Subunit interactions influence the biochemical and biological properties of Hsp104

Point mutations in either of the two nucleotide-binding domains (NBD) of Hsp104 (NBD1 and NBD2) eliminate its thermotolerance function in vivo. In vitro, NBD1 mutations virtually eliminate ATP hydrolysis with little effect on hexamerization; analogous NBD2 mutations reduce ATPase activity and severely impair hexamerization. We report that high protein concentrations overcome the assembly defects of NBD2 mutants and increase ATP hydrolysis severalfold, changing V(max) with little effect on K(m). In a complementary fashion, the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate inhibits hexamerization of wild-type (WT) Hsp104, lowering V(max) with little effect on K(m). ATP hydrolysis exhibits a Hill coefficient between 1.5 and 2, indicating that it is influenced by cooperative subunit interactions. To further analyze the effects of subunit interactions on Hsp104, we assessed the effects of mutant Hsp104 proteins on WT Hsp104 activities. An NBD1 mutant that hexamerizes but does not hydrolyze ATP reduces the ATPase activity of WT Hsp104 in vitro. In vivo, this mutant is not toxic but specifically inhibits the thermotolerance function of WT Hsp104. Thus, interactions between subunits influence the ATPase activity of Hsp104, play a vital role in its biological functions, and provide a mechanism for conditionally inactivating Hsp104 function in vivo

Rigid open-cell polyurethane foam for cryogenic insulation

Lightweight polyurethane foam assembled in panels is effective spacer material for construction of self-evacuating multilayer insulation panels for cryogenic liquid tanks. Spacer material separates radiation shields with barrier that minimizes conductive and convective heat transfer between shields

Data Associated with A Simplified Approach to Stakeholder Engagement in Natural Resource Management: The Five-Feature Framework

This paper distills complex frameworks for stakeholder engagement to five main principles that scientists and natural resource managers can use in planning stakeholder engagement efforts. Many natural resource management professionals, including practitioners and scholars, increasingly recognize the need for and potential benefits of engaging stakeholders in complex decision-making processes, yet the implementation of these efforts varies wildly, reflecting great methodological and conceptual diversity. Given the dynamic and diverse natural resource management contexts in which engagement occurs and the often significant stakes involved in making decisions about natural resources, we argue that stakeholder engagement would benefit from a theoretical framework that is both agile and robust. To this end, five essential elements of stakeholder engagement are evaluated and organized to form the Five-Feature Framework, providing a functional and approachable platform with which to consider engagement processes. Aside from introducing and developing the Five-Feature Framework, this paper applies the framework as a measure to evaluate the empirical case-study literature involving SE in natural resource management in an effort to better understand the obstacles facing robust and genuine engagement in natural resource management. Our results suggest that the most basic principles of engagement are often absent from stakeholder engagement projects, confirming the need for a functional framework. The Five-Feature Framework can be used to plan flexible, adaptable, and rigorous engagement projects in a variety of contexts and with teams that have varying backgrounds and experience. By virtue of its simplicity and functionality, the framework demystifies stakeholder engagement in order to help natural resource professionals build opportunities for collaborative decision-making and integrate citizen values and knowledge into complex management issues

The binary black-hole problem at the third post-Newtonian approximation in the orbital motion: Static part

Post-Newtonian expansions of the Brill-Lindquist and Misner-Lindquist solutions of the time-symmetric two-black-hole initial value problem are derived. The static Hamiltonians related to the expanded solutions, after identifying the bare masses in both solutions, are found to differ from each other at the third post-Newtonian approximation. By shifting the position variables of the black holes the post-Newtonian expansions of the three metrics can be made to coincide up to the fifth post-Newtonian order resulting in identical static Hamiltonians up the third post-Newtonian approximation. The calculations shed light on previously performed binary point-mass calculations at the third post-Newtonian approximation.Comment: LaTeX, 9 pages, to be submitted to Physical Review

Heat shock factor 1 regulates lifespan as distinct from disease onset in prion disease

Prion diseases are fatal, transmissible, neurodegenerative diseases caused by the misfolding of the prion protein (PrP). At present, the molecular pathways underlying prion-mediated neurotoxicity are largely unknown. We hypothesized that the transcriptional regulator of the stress response, heat shock factor 1 (HSF1), would play an important role in prion disease. Uninoculated HSF1 knockout (KO) mice used in our study do not show signs of neurodegeneration as assessed by survival, motor performance, or histopathology. When inoculated with Rocky Mountain Laboratory (RML) prions HSF1 KO mice had a dramatically shortened lifespan, succumbing to disease ≈20% faster than controls. Surprisingly, both the onset of home-cage behavioral symptoms and pathological alterations occurred at a similar time in HSF1 KO and control mice. The accumulation of proteinase K (PK)-resistant PrP also occurred with similar kinetics and prion infectivity accrued at an equal or slower rate. Thus, HSF1 provides an important protective function that is specifically manifest after the onset of behavioral symptoms of prion disease

Dissipative fluids out of hydrostatic equilibrium

In the context of the M\"{u}ller-Israel-Stewart second order phenomenological theory for dissipative fluids, we analyze the effects of thermal conduction and viscosity in a relativistic fluid, just after its departure from hydrostatic equilibrium, on a time scale of the order of relaxation times. Stability and causality conditions are contrasted with conditions for which the ''effective inertial mass'' vanishes.Comment: 21 pages, 1 postscript figure (LaTex 2.09 and epsfig.sty required) Submitted to Classical and Quantum Gravit

Low-Density Granulocytes Are a Novel Immunopathological Feature in Both Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

Objective: To investigate whether low-density granulocytes (LDGs) are an immunophenotypic feature of patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD). Methods: Blood samples were collected from 20 patients with NMOSD and 17 patients with MS, as well as from 15 patients with Systemic Lupus Erythematosus (SLE) and 23 Healthy Donors (HD). We isolated peripheral blood mononuclear cells (PBMCs) with density gradient separation and stained the cells with antibodies against CD14, CD15, CD16, and CD45, and analyzed the cells by flow cytometry or imaging flow cytometry. We defined LDGs as CD14-CD15(high) and calculated their share in total PBMC leukocytes (CD45+) as well as the share of CD16(hi) LDGs. Clinical data on disease course, medication, and antibody status were obtained. Results: LDGs were significantly more common in MS and NMOSD than in HDs, comparable to SLE samples (median values HD 0.2%, MS 0.9%, NMOSD 2.1%, SLE 4.3%). 0/23 of the HDs, but 17/20 NMOSD and 11/17 MS samples as well as 13/15 SLE samples had at least 0.7 % LDGs. NMOSD patients without continuous immunosuppressive treatment had significantly more LDGs compared to their treated counterparts. LDG nuclear morphology ranged from segmented to rounded, suggesting a heterogeneity within the group. Conclusion: LDGs are a feature of the immunophenotype in some patients with MS and NMOSD

Inference with interference between units in an fMRI experiment of motor inhibition

An experimental unit is an opportunity to randomly apply or withhold a treatment. There is interference between units if the application of the treatment to one unit may also affect other units. In cognitive neuroscience, a common form of experiment presents a sequence of stimuli or requests for cognitive activity at random to each experimental subject and measures biological aspects of brain activity that follow these requests. Each subject is then many experimental units, and interference between units within an experimental subject is likely, in part because the stimuli follow one another quickly and in part because human subjects learn or become experienced or primed or bored as the experiment proceeds. We use a recent fMRI experiment concerned with the inhibition of motor activity to illustrate and further develop recently proposed methodology for inference in the presence of interference. A simulation evaluates the power of competing procedures.Comment: Published by Journal of the American Statistical Association at http://www.tandfonline.com/doi/full/10.1080/01621459.2012.655954 . R package cin (Causal Inference for Neuroscience) implementing the proposed method is freely available on CRAN at https://CRAN.R-project.org/package=ci

Stuffed Black Holes

Initial data corresponding to spacetimes containing black holes are considered in the time symmetric case. The solutions are obtained by matching across the apparent horizon different, conformally flat, spatial metrics. The exterior metric is the vacuum solution obtained by the well known conformal imaging method. The interior metric for every black hole is regular everywhere and corresponds to a positive energy density. The resulting matched solutions cover then the whole initial (Cauchy) hypersurface, without any singularity, and can be useful for numerical applications. The simpler cases of one black hole (Schwarzschild data) or two identical black holes (Misner data) are explicitly solved. A procedure for extending this construction to the multiple black hole case is also given, and it is shown to work for all time symmetric vacuum solutions obtained by the conformal imaging method. The numerical evolution of one such 'stuffed' black hole is compared with that of a pure vacuum or 'plain' black hole in the spherically symmetric case.Comment: 12 pages, Latex, 4 postscript figures, corrected some typos, new section about physical interpretatio