Muon spin rotation measurements of the superfluid density in fresh and aged superconducting PuCoGa5_5

We have measured the temperature dependence and magnitude of the superfluid density $\rho_{\rm s}(T)$ via the magnetic field penetration depth $\lambda(T)$ in PuCoGa$_5$ (nominal critical temperature $T_{c0} = 18.5$ K) using the muon spin rotation technique in order to investigate the symmetry of the order parameter, and to study the effects of aging on the superconducting properties of a radioactive material. The same single crystals were measured after 25 days ($T_c = 18.25$ K) and 400 days ($T_c = 15.0$ K) of aging at room temperature. The temperature dependence of the superfluid density is well described in both materials by a model using d-wave gap symmetry. The magnitude of the muon spin relaxation rate $\sigma$ in the aged sample, $\sigma\propto 1/\lambda^2\propto\rho_s/m^*$, where $m^*$ is the effective mass, is reduced by about 70% compared to fresh sample. This indicates that the scattering from self-irradiation induced defects is not in the limit of the conventional Abrikosov-Gor'kov pair-breaking theory, but rather in the limit of short coherence length (about 2 nm in PuCoGa$_5$) superconductivity.Comment: 11 page

The informed road map to prevention of Alzheimer disease: A call to arms

Alzheimer disease (AD) prevention trials hold the promise to delay or prevent cognitive decline and dementia onset by intervening before significant neuronal damage occurs. In recent years, the first AD prevention trials have launched and are yielding important findings on the biology of targeting asymptomatic AD pathology. However, there are limitations that impact the design of these prevention trials, including the translation of animal models that recapitulate key stages and multiple pathological aspects of the human disease, missing target validation in asymptomatic disease, uncertain causality of the association of pathophysiologic changes with cognitive and clinical symptoms, and limited biomarker validation for novel targets. The field is accelerating advancements in key areas including the development of highly specific and quantitative biomarker measures for AD pathology, increasing our understanding of the course and relationship of amyloid and tau pathology in asymptomatic through symptomatic stages, and the development of powerful interventions that can slow or reverse AD amyloid pathology. We review the current status of prevention trials and propose key areas of needed research as a call to basic and translational scientists to accelerate AD prevention. Specifically, we review (1) sporadic and dominantly inherited primary and secondary AD prevention trials, (2) proposed targets, mechanisms, and drugs including the amyloid, tau, and inflammatory pathways and combination treatments, (3) the need for more appropriate prevention animal models and experiments, and (4) biomarkers and outcome measures needed to design human asymptomatic prevention trials. We conclude with actions needed to effectively move prevention targets and trials forward

Peptidoglycan Remodeling and Conversion of an Inner Membrane into an Outer Membrane during Sporulation

Two hallmarks of the Firmicute phylum, which includes the Bacilli and Clostridia classes, are their ability to form endospores and their “Gram-positive” single-membraned, thick-cell-wall envelope structure. Acetonema longum is part of a lesser-known family (the Veillonellaceae) of Clostridia that form endospores but that are surprisingly “Gram negative,” possessing both an inner and outer membrane and a thin cell wall. Here, we present macromolecular resolution, 3D electron cryotomographic images of vegetative, sporulating, and germinating A. longum cells showing that during the sporulation process, the inner membrane of the mother cell is inverted and transformed to become the outer membrane of the germinating cell. Peptidoglycan persists throughout, leading to a revised, “continuous” model of its role in the process. Coupled with genomic analyses, these results point to sporulation as a mechanism by which the bacterial outer membrane may have arisen and A. longum as a potential “missing link” between single- and double-membraned bacteria

miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential.

We have shown that antagomiR inhibition of miRNA miR-21 and miR-196b activity is sufficient to ablate MLL-AF9 leukemia stem cells (LSC) in vivo. Here, we used an shRNA screening approach to mimic miRNA activity on experimentally verified miR-196b targets to identify functionally important and therapeutically relevant pathways downstream of oncogenic miRNA in MLL-r AML. We found Cdkn1b (p27Kip1) is a direct miR-196b target whose repression enhanced an embryonic stem cell–like signature associated with decreased leukemia latency and increased numbers of leukemia stem cells in vivo. Conversely, elevation of p27Kip1 significantly reduced MLL-r leukemia self-renewal, promoted monocytic differentiation of leukemic blasts, and induced cell death. Antagonism of miR-196b activity or pharmacologic inhibition of the Cks1-Skp2–containing SCF E3-ubiquitin ligase complex increased p27Kip1 and inhibited human AML growth. This work illustrates that understanding oncogenic miRNA target pathways can identify actionable targets in leukemia

Extensions of tempered representations

Let $\pi, \pi'$ be irreducible tempered representations of an affine Hecke algebra H with positive parameters. We compute the higher extension groups $Ext_H^n (\pi,\pi')$ explicitly in terms of the representations of analytic R-groups corresponding to $\pi$ and $\pi'$. The result has immediate applications to the computation of the Euler-Poincar\'e pairing $EP(\pi,\pi')$, the alternating sum of the dimensions of the Ext-groups. The resulting formula for $EP(\pi,\pi')$ is equal to Arthur's formula for the elliptic pairing of tempered characters in the setting of reductive p-adic groups. Our proof applies equally well to affine Hecke algebras and to reductive groups over non-archimedean local fields of arbitrary characteristic. This sheds new light on the formula of Arthur and gives a new proof of Kazhdan's orthogonality conjecture for the Euler-Poincar\'e pairing of admissible characters.Comment: This paper grew out of "A formula of Arthur and affine Hecke algebras" (arXiv:1011.0679). In the second version some minor points were improve

Kinetic Characterization of Salmonella FliK-FlhB Interactions Demonstrates Complexity of the Type III Secretion Substrate-Specificity Switch

The bacterial flagellum is a complex macromolecular machine consisting of more than 20000 proteins, most of which must be exported from the cell via a dedicated Type III secretion apparatus. At a defined point in flagellar morphogenesis, hook completion is sensed and the apparatus switches substrate specificity type from rod and hook proteins to filament ones. How the switch works is a subject of intense interest. FIiK and F1hBs play central roles. In the present study, two optical biosensing methods were used to characterize FIiK-F1hB interactions using wild-type and two variant FlhBs from mutants with severe flagellar structural defects. Binding was found to be complex with fast and slow association and dissociation components. Surprisingly, wild-type and variant FlhBs had similar kinetic profiles and apparent affinities, which ranged between I and 10.5 μM, suggesting that the specificity switch is more complex than presently understood. Other binding experiments provided evidence for a conformational change after binding. Liquid chromatography-mass spectrometry (LC-MS) and NMR experiments were performed to identify a cyclic intermediate product whose existence supports the mechanism of autocatalytic cleavage at FlhB residue N269. The present results show that while autocatalytic cleavage is necessary for proper substrate specificity switching, it does not result in an altered interaction with FIiK. strongly suggesting the involvement of other proteins in the mechanism

Summary of CPAS Gen II Parachute Analysis

The Orion spacecraft is currently under development by NASA and Lockheed Martin. Like Apollo, Orion will use a series of parachutes to slow its descent and splashdown safely. The Orion parachute system, known as the CEV Parachute Assembly System (CPAS), is being designed by NASA, the Engineering and Science Contract Group (ESCG), and Airborne Systems. The first generation (Gen I) of CPAS testing consisted of thirteen tests and was executed in the 2007-2008 timeframe. The Gen I tests provided an initial understanding of the CPAS parachutes. Knowledge gained from Gen I testing was used to plan the second generation of testing (Gen II). Gen II consisted of six tests: three singleparachute tests, designated as Main Development Tests, and three Cluster Development Tests. Gen II required a more thorough investigation into parachute performance than Gen I. Higher fidelity instrumentation, enhanced analysis methods and tools, and advanced test techniques were developed. The results of the Gen II test series are being incorporated into the CPAS design. Further testing and refinement of the design and model of parachute performance will occur during the upcoming third generation of testing (Gen III). This paper will provide an overview of the developments in CPAS analysis following the end of Gen I, including descriptions of new tools and techniques as well as overviews of the Gen II tests