Psychosis in Alzheimer's Disease in the National Alzheimer's Disease Coordinating Center Uniform Data Set: Clinical Correlates and Association with Apolipoprotein E

Approximately 50% of late-onset Alzheimer's disease (AD) patients develop psychosis (AD+P), a heritable phenotype associated with more rapid cognitive decline. Prior studies conflict regarding whether apolipoprotein E (APOE) ϵ4 alleles are associated with AD+P, possibly due to small sample sizes, inconsistent diagnostic criteria, and different methodologies to assess psychosis. We used the National Alzheimer's Coordinating Center Uniform Data Set to evaluate the largest uniformly characterized sample of AD+P subjects studied to date for the association of APOE ϵ4 genotype, along with other demographic and clinical variables. Greater cognitive impairment and depressive symptoms were associated with AD+P, while the Caucasian race was protective. Neither APOE ϵ4 carrier status nor allele number was associated with psychosis. The AD+P phenotype is not associated with the APOE ϵ4 genotype. AD+P may represent a useful phenotype for the discovery of non-APOE ϵ4 genetic variation contributing to the risk of AD

Database Search Strategies for Proteomic Data Sets Generated by Electron Capture Dissociation Mass Spectrometry

Large data sets of electron capture dissociation (ECD) mass spectra from proteomic experiments are rich in information; however, extracting that information in an optimal manner is not straightforward. Protein database search engines currently available are designed for low resolution CID data, from which Fourier transform ion cyclotron resonance (FT-ICR) ECD data differs significantly. ECD mass spectra contain both z-prime and z-dot fragment ions (and c-prime and c-dot); ECD mass spectra contain abundant peaks derived from neutral losses from charge-reduced precursor ions; FT-ICR ECD spectra are acquired with a larger precursor m/z isolation window than their low-resolution CID counterparts. Here, we consider three distinct stages of postacquisition analysis: (1) processing of ECD mass spectra prior to the database search; (2) the database search step itself and (3) postsearch processing of results. We demonstrate that each of these steps has an effect on the number of peptides identified, with the postsearch processing of results having the largest effect. We compare two commonly used search engines: Mascot and OMSSA. Using an ECD data set of modest size (3341 mass spectra) from a complex sample (mouse whole cell lysate), we demonstrate that search results can be improved from 630 identifications (19% identification success rate) to 1643 identifications (49% identification success rate). We focus in particular on improving identification rates for doubly charged precursors, which are typically low for ECD fragmentation. We compare our presearch processing algorithm with a similar algorithm recently developed for electron transfer dissociation (ETD) data

Magnetic Reconnection with Radiative Cooling. I. Optically-Thin Regime

Magnetic reconnection, a fundamental plasma process associated with a rapid dissipation of magnetic energy, is believed to power many disruptive phenomena in laboratory plasma devices, the Earth magnetosphere, and the solar corona. Traditional reconnection research, geared towards these rather tenuous environments, has justifiably ignored the effects of radiation on the reconnection process. However, in many reconnecting systems in high-energy astrophysics (e.g., accretion-disk coronae, relativistic jets, magnetar flares) and, potentially, in powerful laser plasma and z-pinch experiments, the energy density is so high that radiation, in particular radiative cooling, may start to play an important role. This observation motivates the development of a theory of high-energy-density radiative magnetic reconnection. As a first step towards this goal, we present in this paper a simple Sweet--Parker-like theory of non-relativistic resistive-MHD reconnection with strong radiative cooling. First, we show how, in the absence of a guide magnetic field, intense cooling leads to a strong compression of the plasma in the reconnection layer, resulting in a higher reconnection rate. The compression ratio and the layer temperature are determined by the balance between ohmic heating and radiative cooling. The lower temperature in the radiatively-cooled layer leads to a higher Spitzer resistivity and hence to an extra enhancement of the reconnection rate. We then apply our general theory to several specific astrophysically important radiative processes (bremsstrahlung, cyclotron, and inverse-Compton) in the optically thin regime, for both the zero- and strong-guide-field cases. We derive specific expressions for key reconnection parameters, including the reconnection rate. We also discuss the limitations and conditions for applicability of our theory.Comment: 31 pages, 1 figur

Current sheet bifurcation and collapse in electron magnetohydrodynamics

Inertial effects in nonlinear magnetic reconnection are studied within the context of 2D electron magnetohydrodynamics (EMHD) with resistive and viscous dissipation. Families of nonlinear solutions for relevant current sheet parameters are predicted and confirmed numerically in all regimes of interest. Electron inertia becomes important for current sheet thicknesses $\delta$ below the inertial length $d_{e}$. In this case, in the absence of electron viscosity, the sheet thickness experiences a nonlinear collapse. Viscosity regularizes solutions at small scales. Transition from resistive to viscous regimes shows a nontrivial dependence on resistivity and viscosity, featuring a hysteresis bifurcation. In all accessible regimes, the nonlinear reconnection rate is found to be explicitly independent of the electron inertia and dissipation coefficients.Comment: submitted to publicatio

Collisionless Magnetic Reconnection via Alfven Eigenmodes

We propose an analytic approach to the problem of collisionless magnetic reconnection formulated as a process of Alfven eigenmodes' generation and dissipation. Alfven eigenmodes are confined by the current sheet in the same way that quantum mechanical waves are confined by the tanh^2 potential. The dynamical time scale of reconnection is the system scale divided by the eigenvalue propagation velocity of the n=1 mode. The prediction of the n=1 mode shows good agreement with the in situ measurement of the reconnection-associated Hall fields

Rhetoric in the language of real estate marketing

“Des. Res.”, “rarely available”, “viewing essential” – these are all part of the peculiar parlance of housing advertisements which contain a heady mix of euphemism, hyperbole and superlative. Of interest is whether the selling agent’s penchant for rhetoric is spatially uniform or whether there are variations across the urban system. We are also interested in how the use of superlatives varies over the market cycle and over the selling season. For example, are estate agents more inclined to use hyperbole when the market is buoyant or when it is flat, and does it matter whether a house is marketed in the summer or winter? This paper attempts to answer these questions by applying textual analysis to a unique dataset of 49,926 records of real estate transactions in the Strathclyde conurbation over the period 1999 to 2006. The analysis opens up a new avenue of research into the use of real estate rhetoric and its interaction with agency behaviour and market dynamics

Design and fabrication of a long-life Stirling cycle cooler for space application. Phase 3: Prototype model

A second-generation, Stirling-cycle cryocooler (cryogenic refrigerator) for space applications, with a cooling capacity of 5 watts at 65 K, was recently completed. The refrigerator, called the Prototype Model, was designed with a goal of 5 year life with no degradation in cooling performance. The free displacer and free piston of the refrigerator are driven directly by moving-magnet linear motors with the moving elements supported by active magnetic bearings. The use of clearance seals and the absence of outgassing material in the working volume of the refrigerator enable long-life operation with no deterioration in performance. Fiber-optic sensors detect the radial position of the shafts and provide a control signal for the magnetic bearings. The frequency, phase, stroke, and offset of the compressor and expander are controlled by signals from precision linear position sensors (LVDTs). The vibration generated by the compressor and expander is cancelled by an active counter balance which also uses a moving-magnet linear motor and magnetic bearings. The driving signal for the counter balance is derived from the compressor and expander position sensors which have wide bandwidth for suppression of harmonic vibrations. The efficiency of the three active members, which operate in a resonant mode, is enhanced by a magnetic spring in the expander and by gas springs in the compressor and counterbalance. The cooling was achieved with a total motor input power of 139 watts. The magnetic-bearing stiffness was significantly increased from the first-generation cooler to accommodate shuttle launch vibrations

Effects of the tat and nef gene products of human immunodeficiency virus type 1 (HIV-1) on transcription controlled by the HIV-1 long terminal repeat and on cell growth in macrophages

The RAW264 murine macrophage cell line was used as a model to examine the role of the tat and nef gene products in the transcription regulation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in macrophages. Contrary to claims that the activity of the HIV-1 LTR responds poorly in rodent cells to trans activation by the viral tat gene product, cotransfection of RAW264 cells with a tat expression plasmid in transient transfection assays caused a > 20-fold increase in reporter gene expression that was inhibited by mutations in the TAR region. RAW264 cells stably transfected with the tat plasmid displayed similarly elevated HIV-1 LTR-driven reporter gene activity. By contrast to previous reports indicating a negative role for nef in HIV transcription, cotransfection of RAW264 cells with a nef expression plasmid trans activated the HIV-1 LTR driving either a chloramphenicol acetyltransferase or a luciferase reporter gene. The action of nef was specific to the LTR, as expression of nef had no effect on the activity of the simian virus 40, c-fms, urokinase plasminogen activator, or type 5 acid phosphatase promoter. trans-activating activity was also manifested by a frameshift mutant expressing only the first 35 amino acids of the protein. The effects of nef were multiplicative with those of tat gene product and occurred even in the presence of bacterial lipopolysaccharide, which itself activated LTR-directed transcription. Examination of the effects of selected mutations in the LTR revealed that neither the kappa B sites in the direct repeat enhancer nor the TAR region was required as a cis-acting element in nef action. The action of nef was not species restricted; it was able to trans activate in the human monocyte-like cell line Mono Mac 6. The presence of a nef expression cassette in a neomycin phosphotransferase gene expression plasmid greatly reduced the number of G418-resistant colonies generated in stable transfection of RAW264 cells, and many of the colonies that were formed exhibited very slow growth. The frameshift mutant was also active in reducing colony generation. Given the absence of any effect of the frameshift mutation on nef function, its actions on macrophage growth and HIV transcription are discussed in terms of the role of the N-terminal 30 amino acids and of stable secondary structures in the mRNA

Threading, Stitching, and Storytelling: Using CBPR and Blackfoot Knowledge and Cultural Practices to Improve Domestic Violence Services for Indigenous Women

This article discusses a community-based participatory research (CBPR) project at two women’s emergency shelters in rural southwestern Alberta. The CBPR project aimed to improve shelter services on and off reserve in our area by engaging the voices of Indigenous women who had experienced domestic violence. The project’s methods were participatory appraisal and arts-based work re-imagined through Blackfoot cultural practices of storytelling and shawl making. The project created a rare safe space where thirteen Blackfoot women emphasised DV services should provide opportunities to connect with family and community and role model Blackfoot knowledge. Role modelling traditional knowledges aids developing life and parenting skills, opening up pathways for Indigenous women to more positive, secure futures. These women’s recommendations impelled this article to challenge the individualized case management model and discourses of cultural competence dominating Canadian DV services, which isolate and marginalize Indigenous women when they seek help. We highlight resources existing in Blackfoot communities to manage and prevent violence by protecting and facilitating Indigenous women’s connections to their communities and cultures, and offer ways to utilize these more effectively in service settings