241 research outputs found

    The structure and dynamics of carbon dioxide and water containing ices investigated via THz and mid-IR spectroscopy

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    Icy dust grains play a key role in the chemistry of the interstellar medium. The cumulative outcome of recent observations, laboratory studies, and astrochemical models indicates that solid-phase reaction mechanisms may dominate the formation of complex organic molecules such as amino acids and sugars in space. Consequently, the composition and structure of the icy grain mantle may significantly influence solid-phase reaction pathways. In this work, we present a new experimental setup capable of studying astrochemical ice analogs in both the TeraHertz (THz), or far-Infrared (far-IR), region (0.3–7.5 THz; 10–250 cm^(−1)) and the mid-IR (400–4000 cm^(−1)). The instruments are capable of performing a variety of spectroscopic studies that can provide especially relevant laboratory data to support astronomical observations from telescopes such as Herschel, SOFIA, and ALMA. Experimental spectra of astrochemical ice analogs of water and carbon dioxide in pure, mixed, and layered ices were collected at different temperatures under high vacuum conditions with the goal of investigating the structure of the ice. We tentatively observe a new feature in both amorphous solid water and crystalline water at 33 cm^(−1) (1 THz). In addition, our studies of mixed and layered ices show how it is possible to identify the location of carbon dioxide as it segregates within the ice by observing its effect on the THz spectrum of water ice. The THz spectra of mixed and layered ices are further analyzed by fitting their spectral features to those of pure amorphous solid water and crystalline water ice to quantify the effects of temperature changes on structure. From the results of this work, it appears that THz spectroscopy is potentially well suited to study thermal transformations within the ice

    Transverse lipid organization dictates bending fluctuations in model plasma membranes

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    © 2020 The Royal Society of Chemistry. Membrane undulations play a vital role in many biological processes, including the regulation of membrane protein activity. The asymmetric lipid composition of most biological membranes complicates theoretical description of these bending fluctuations, yet experimental data that would inform any such a theory is scarce. Here, we used neutron spin-echo (NSE) spectroscopy to measure the bending fluctuations of large unilamellar vesicles (LUV) having an asymmetric transbilayer distribution of high- and low-melting lipids. The asymmetric vesicles were prepared using cyclodextrin-mediated lipid exchange, and were composed of an outer leaflet enriched in egg sphingomyelin (ESM) and an inner leaflet enriched in 1-palmitoyl-2-oleoyl-phosphoethanolamine (POPE), which have main transition temperatures of 37 °C and 25 °C, respectively. The overall membrane bending rigidity was measured at three temperatures: 15 °C, where both lipids are in a gel state; 45 °C, where both lipids are in a fluid state; and 30 °C, where there is gel-fluid co-existence. Remarkably, the dynamics for the fluid asymmetric LUVs (aLUVs) at 30 °C and 45 °C do not follow trends predicted by their symmetric counterparts. At 30 °C, compositional asymmetry suppressed the bending fluctuations, with the asymmetric bilayer exhibiting a larger bending modulus than that of symmetric bilayers corresponding to either the outer or inner leaflet. We conclude that the compositional asymmetry and leaflet coupling influence the internal dissipation within the bilayer and result in membrane properties that cannot be directly predicted from corresponding symmetric bilayers

    What is Financial Therapy? Discovering Mechanisms and Aspects of an Emerging Field

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    Very little research currently exists specifically on the topic of financial therapy. In this emerging field, it is important to lay the groundwork for future practice and study. The purpose of this study was to answer the question, “What are the mechanisms and aspects of financial therapy?” Using qualitative methods, eighteen members of the Financial Therapy Association were interviewed by members of the research team. The participants included six financial professionals, six mental health professions, and six researchers/educators all engaged in financial therapy. Six categories emerged from the analysis of data, including: (a) integration, (b) complexity, (c) help seeker issues, (d) helper issues, (e) process, and (f) research. The analysis resulted in a conceptual framework and ten theoretical assumptions of financial therapy

    The antioxidant vitamin E as a membrane raft modulator: Tocopherols do not abolish lipid domains

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    © 2020 Elsevier B.V. The antioxidant vitamin E is a commonly used vitamin supplement. Although the multi-billion dollar vitamin and nutritional supplement industry encourages the use of vitamin E, there is very little evidence supporting its actual health benefits. Moreover, vitamin E is now marketed as a lipid raft destabilizing anti-cancer agent, in addition to its antioxidant behaviour. Here, we studied the influence of vitamin E and some of its vitamers on membrane raft stability using phase separating unilamellar lipid vesicles in conjunction with small-angle scattering techniques and fluorescence microscopy. We find that lipid phase behaviour remains unperturbed well beyond physiological concentrations of vitamin E (up to a mole fraction of 0.10). Our results are consistent with a proposed line active role of vitamin E at the domain boundary. We discuss the implications of these findings as they pertain to lipid raft modification in native membranes, and propose a new hypothesis for the antioxidant mechanism of vitamin E

    APP Regulates Microglial Phenotype in a Mouse Model of Alzheimer\u27s Disease

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    Prior work suggests that amyloid precursor protein (APP) can function as a proinflammatory receptor on immune cells, such as monocytes and microglia. Therefore, we hypothesized that APP serves this function in microglia during Alzheimer\u27s disease. Although fibrillar amyloid β (Aβ)-stimulated cytokine secretion from both wild-type and APP knock-out (mAPP−/−) microglial cultures, oligomeric Aβ was unable to stimulate increased secretion from mAPP−/− cells. This was consistent with an ability of oligomeric Aβ to bind APP. Similarly, intracerebroventricular infusions of oligomeric Aβ produced less microgliosis in mAPP−/− mice compared with wild-type mice. The mAPP−/− mice crossed to an APP/PS1 transgenic mouse line demonstrated reduced microgliosis and cytokine levels and improved memory compared with wild-type mice despite robust fibrillar Aβ plaque deposition. These data define a novel function for microglial APP in regulating their ability to acquire a proinflammatory phenotype during disease. SIGNIFICANCE STATEMENT A hallmark of Alzheimer\u27s disease (AD) brains is the accumulation of amyloid β (Aβ) peptide within plaques robustly invested with reactive microglia. This supports the notion that Aβ stimulation of microglial activation is one source of brain inflammatory changes during disease. Aβ is a cleavage product of the ubiquitously expressed amyloid precursor protein (APP) and is able to self-associate into a wide variety of differently sized and structurally distinct multimers. In this study, we demonstrate both in vitro and in vivo that nonfibrillar, oligomeric forms of Aβ are able to interact with the parent APP protein to stimulate microglial activation. This provides a mechanism by which metabolism of APP results in possible autocrine or paracrine Aβ production to drive the microgliosis associated with AD brains

    Evaluating Data Assimilation Algorithms

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    Data assimilation leads naturally to a Bayesian formulation in which the posterior probability distribution of the system state, given the observations, plays a central conceptual role. The aim of this paper is to use this Bayesian posterior probability distribution as a gold standard against which to evaluate various commonly used data assimilation algorithms. A key aspect of geophysical data assimilation is the high dimensionality and low predictability of the computational model. With this in mind, yet with the goal of allowing an explicit and accurate computation of the posterior distribution, we study the 2D Navier-Stokes equations in a periodic geometry. We compute the posterior probability distribution by state-of-the-art statistical sampling techniques. The commonly used algorithms that we evaluate against this accurate gold standard, as quantified by comparing the relative error in reproducing its moments, are 4DVAR and a variety of sequential filtering approximations based on 3DVAR and on extended and ensemble Kalman filters. The primary conclusions are that: (i) with appropriate parameter choices, approximate filters can perform well in reproducing the mean of the desired probability distribution; (ii) however they typically perform poorly when attempting to reproduce the covariance; (iii) this poor performance is compounded by the need to modify the covariance, in order to induce stability. Thus, whilst filters can be a useful tool in predicting mean behavior, they should be viewed with caution as predictors of uncertainty. These conclusions are intrinsic to the algorithms and will not change if the model complexity is increased, for example by employing a smaller viscosity, or by using a detailed NWP model

    Determination of freedom-from-rabies for small Indian mongoose populations in the United States Virgin Islands, 2019–2020

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    Mongooses, a nonnative species, are a known reservoir of rabies virus in the Caribbean region. A cross-sectional study of mongooses at 41 field sites on the US Virgin Islands of St. Croix, St. John, and St. Thomas captured 312 mongooses (32% capture rate). We determined the absence of rabies virus by antigen testing and rabies virus exposure by antibody testing in mongoose populations on all three islands. USVI is the first Caribbean state to determine freedom-from-rabies for its mongoose populations with a scientifically-led robust cross-sectional study. Ongoing surveillance activities will determine if other domestic and wildlife populations in USVI are rabies-free

    Full-length structural model of RET3 and SEC21 in COPI: identification of binding sites on the appendage for accessory protein recruitment motifs

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    COPI, a 600 kD heptameric complex (consisting of subunits α, β, γ, δ, ε, ζ, and β′) “coatomer,” assembles non-clathrin-coated vesicles and is responsible for intra-Golgi and Golgi-to-ER protein trafficking. Here, we report the three-dimensional structures of the entire sequences of yeast Sec21 (γ-COPI mammalian ortholog), yeast Ret3 (ζ-COPI mammalian ortholog), and the results of successive molecular dynamics investigations of the subunits and assembly based on a protein–protein docking experiment. The three-dimensional structures of the subunits in their complexes indicate the residues of the two subunits that impact on assembly, the conformations of Ret3 and Sec21, and their binding orientations in the complexed state. The structure of the appendage domain of Sec21, with its two subdomains—the platform and the β-sandwich, was investigated to explore its capacity to bind to accessory protein recruitment motifs. Our study shows that a binding site on the platform is capable of binding the Eps15 DPF and epsin DPW2 peptides, whereas the second site on the platform and the site on the β-sandwich subdomain were found to selectively bind to the amphiphysin FXDXF and epsin DPW1 peptides, respectively. Identifying the regions of both the platform and sandwich subdomains involved in binding each peptide motif clarifies the mechanism through which the appendage domain of Sec21 engages with the accessory proteins during the trafficking process of non-clathrin-coated vesicles

    Performance of the CMS Cathode Strip Chambers with Cosmic Rays

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    The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns
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