Chronic obstructive pulmonary disease: Longitudinal hyperpolarized (3)He MR imaging

PURPOSE: To quantitatively evaluate a small pilot group of ex-smokers with chronic obstructive pulmonary disease (COPD) and healthy volunteers during approximately 2 years by using hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging. MATERIALS AND METHODS: All subjects provided written informed consent to the study protocol, which was approved by the local research ethics board and Health Canada and was compliant with the Personal Information Protection and Electronic Documents Act and HIPAA. Hyperpolarized (3)He MR imaging, hydrogen 1 MR imaging, spirometry, and plethysmography were performed in 15 ex-smokers with COPD and five healthy volunteers (with the same mean age and age range) at baseline and 26 months +/- 2 (standard deviation) later. Apparent diffusion coefficients (ADCs) derived from (3)He MR imaging were calculated from diffusion-weighted (3)He MR images, and (3)He ventilation defect volume (VDV) and ventilation defect percentage (VDP) were generated after manual segmentation of (3)He MR spin-density images. RESULTS: For subjects with COPD, significant increases in (3)He MR imaging-derived VDV (P = .03), VDP (P = .006), and ADC (P = .02) were detected, whereas there was no significant change in forced expiratory volume in 1 second (FEV(1)) (P = .97). For healthy never-smokers, there was no significant change in imaging or pulmonary function measurements at follow-up. There was a significant correlation between changes in FEV(1) and changes in VDV (r = -0.70, P = .02) and VDP (r = -0.70, P = .03). CONCLUSION: For this small pilot group of ex-smokers with COPD, (3)He MR imaging-derived VDV, VDP, and ADC measurements worsened significantly, but there was no significant change in FEV(1), suggesting increased sensitivity of hyperpolarized (3)He MR imaging for depicting COPD changes during short time periods

A single crystal study of CPO-27 and UTSA-74 for nitric oxide storage and release

Funding: UK EPSRC EP/K005499/1, EP/K503162, and EP/L017008/1).Single crystal CPO-27-Mg, -Zn and its structural isomer UTSA-74 have been prepared through use of acid modulators; salicylic acid and benzoic acid, respectively. Salicylic acid directed the synthesis of CPO-27-Mg/Zn whereas benzoic acid the synthesis of UTSA-74. Through “in-house” SCXRD, DMF was seen to bind to the Zn2+ and water to the Mg2+ metal sites in CPO-27-M. Although the synthesis conditions were analogous for UTSA-74, DMF is too large to bind due to the proximity of the binding sites. A dissolution–recrystallisation transformation was examined from UTSA-74 to CPO-27-Zn. The release of nitric oxide was measured for each material.PostprintPeer reviewe

Hyperpolarized 3He and 129Xe magnetic resonance imaging apparent diffusion coefficients: physiological relevance in older never- and ex-smokers

Noble gas pulmonary magnetic resonance imaging (MRI) is transitioning away from (3)He to (129)Xe gas, but the physiological/clinical relevance of (129)Xe apparent diffusion coefficient (ADC) parenchyma measurements is not well understood. Therefore, our objective was to generate (129)Xe MRI ADC for comparison with (3)He ADC and with well-established measurements of alveolar structure and function in older never-smokers and ex-smokers with chronic obstructive pulmonary disease (COPD). In four never-smokers and 10 COPD ex-smokers, (3)He (b = 1.6 sec/cm(2)) and (129)Xe (b = 12, 20, and 30 sec/cm(2)) ADC, computed tomography (CT) density-threshold measurements, and the diffusing capacity for carbon monoxide (DLCO) were measured. To understand regional differences, the anterior-posterior (APG) and superior-inferior (∆SI) ADC differences were evaluated. Compared to never-smokers, COPD ex-smokers showed greater (3)He ADC (P = 0.006), (129)Xe ADCb12 (P = 0.006), and ADCb20 (P = 0.006), but not for ADCb30 (P \u3e 0.05). Never-smokers and COPD ex-smokers had significantly different APG for (3)He ADC (P = 0.02), (129)Xe ADCb12 (P = 0.006), and ADCb20 (P = 0.01), but not for ADCb30 (P \u3e 0.05). ∆SI for never- and ex-smokers was significantly different for (3)He ADC (P = 0.046), but not for (129)Xe ADC (P \u3e 0.05). There were strong correlations for DLCO with (3)He ADC and (129)Xe ADCb12 (both r = -0.95, P \u3c 0.05); in a multivariate model (129)Xe ADCb12 was the only significant predictor of DLCO (P = 0.049). For COPD ex-smokers, CT relative are

Inhibition of caveolar uptake, SV40 infection, and β1-integrin signaling by a nonnatural glycosphingolipid stereoisomer

Caveolar endocytosis is an important mechanism for the uptake of certain pathogens and toxins and also plays a role in the internalization of some plasma membrane (PM) lipids and proteins. However, the regulation of caveolar endocytosis is not well understood. We previously demonstrated that caveolar endocytosis and β1-integrin signaling are stimulated by exogenous glycosphingolipids (GSLs). In this study, we show that a synthetic GSL with nonnatural stereochemistry, β-d-lactosyl-N-octanoyl-l-threo-sphingosine, (1) selectively inhibits caveolar endocytosis and SV40 virus infection, (2) blocks the clustering of lipids and proteins into GSLs and cholesterol-enriched microdomains (rafts) at the PM, and (3) inhibits β1-integrin activation and downstream signaling. Finally, we show that small interfering RNA knockdown of β1 integrin in human skin fibroblasts blocks caveolar endocytosis and the stimulation of signaling by a GSL with natural stereochemistry. These experiments identify a new compound that can interfere with biological processes by inhibiting microdomain formation and also identify β1 integrin as a potential mediator of signaling by GSLs

Hyperpolarized 3He and 129Xe MR imaging in healthy volunteers and patients with chronic obstructive pulmonary disease

PURPOSE: To quantitatively compare hyperpolarized helium 3 (3He) and xenon 129 (129Xe) magnetic resonance (MR) images obtained within 5 minutes in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD) and to evaluate the correlations between 3He and 129Xe MR imaging measurements and those from spirometry and plethysmography. MATERIALS AND METHODS: This study was approved by an ethics board and compliant with HIPAA. Written informed consent was obtained from all subjects. Eight healthy volunteers and 10 patients with COPD underwent MR imaging, spirometry, and plethysmography. Ventilation defect percentages (VDPs) at 3He and 129Xe imaging were obtained by using semiautomated segmentation. Apparent diffusion coefficients (ADCs) were calculated from 3He (b=1.6 sec/cm2) and 129Xe (b=12 sec/cm2) diffusion-weighted images. VDPs at hyperpolarized 3He and 129Xe imaging were compared with a two-tailed Wilcoxon signed rank test and analysis of variance; Pearson correlation coefficients were used to evaluate the relationships among measurements. RESULTS: 129Xe VDP was significantly greater than 3He VDP for patients with COPD (P CONCLUSION: In patients with COPD, the VDP obtained with hyperpolarized 29Xe MR imaging was significantly greater than that with 3He MR imaging, suggesting incomplete or delayed filling of lung regions that may be related to the different properties of 129Xe gas and physiologic and/or anatomic abnormalities in COPD

Transcending Scale Dependence in Identifying Habitat with Resource Selection Functions

Multi-scale resource selection modeling is used to identify factors that limit species distributions across scales of space and time. This multi-scale nature of habitat suitability complicates the translation of inferences to single, spatial depictions of habitat required for conservation of species. We estimated resource selection functions (RSFs) across three scales for a threatened ungulate, woodland caribou (Rangifer tarandus caribou), with two objectives: (1) to infer the relative effects of two forms of anthropogenic disturbance (forestry and linear features) on woodland caribou distributions at multiple scales and (2) to estimate scale-integrated resource selection functions (SRSFs) that synthesize results across scales for management-oriented habitat suitability mapping. We found a previously undocumented scale-specific switch in woodland caribou response to two forms of anthropogenic disturbance. Caribou avoided forestry cut-blocks at broad scales according to first-and second-order RSFs and avoided linear features at fine scales according to third-order RSFs, corroborating predictions developed according to predator-mediated effects of each disturbance type. Additionally, a single SRSF validated as well as each of three single-scale RSFs when estimating habitat suitability across three different spatial scales of prediction. We demonstrate that a single SRSF can be applied to predict relative habitat suitability at both local and landscape scales in support of critical habitat identification and species recovery

In situ solid-state NMR and XRD studies of the ADOR process and the unusual structure of zeolite IPC-6

R.E.M. and M.N. thank the Royal Society and the E.P.S.R.C. (Grants EP/L014475/1, EP/K025112/1 and EP/K005499/1) for funding work in this area. R.E.M. and J.Č. acknowledge the Czech Science Foundation for the project P106/12/G015 and OP VVV "Excellent Research Teams", project No. CZ.02.1.01/0.0/0.0/15_003/0000417 - CUCAM. S.E.A. would like to thank the ERC (EU FP7 Consolidator Grant 614290 “EXONMR”) and the Royal Society and Wolfson Foundation for a merit award. The UK 850 MHz solid-state NMR Facility used in this research was funded by EPSRC and BBSRC (contract reference PR140003), as well as the University of Warwick including via part funding through Birmingham Science City Advanced Materials Projects 1 and 2 supported by Advantage West Midlands (AWM) and the European Regional Development Fund (ERDF). W.A.S. and D.S.W. acknowledge the Research Council of Norway and NOTUR are acknowledged for providing the computer time at the Norwegian supercomputer facilities (under the project number NN2875k).The assembly–disassembly–organization–reassembly (ADOR) mechanism is a recent method for preparing inorganic framework materials and, in particular, zeolites. This flexible approach has enabled the synthesis of isoreticular families of zeolites with unprecedented continuous control over porosity, and the design and preparation of materials that would have been difficult—or even impossible—to obtain using traditional hydrothermal techniques. Applying the ADOR process to a parent zeolite with the UTL framework topology, for example, has led to six previously unknown zeolites (named IPC-n, where n = 2, 4, 6, 7, 9 and 10). To realize the full potential of the ADOR method, however, a further understanding of the complex mechanism at play is needed. Here, we probe the disassembly, organization and reassembly steps of the ADOR process through a combination of in situ solid-state NMR spectroscopy and powder X-ray diffraction experiments. We further use the insight gained to explain the formation of the unusual structure of zeolite IPC-6.PostprintPeer reviewe

The relative emission from chromospheres and coronae: Dependence on spectral type and age

Extreme-ultraviolet and X-ray emission from stellar coronae drives mass loss from exoplanet atmospheres, and ultraviolet emission from stellar chromospheres drives photochemistry in exoplanet atmospheres. Comparisons of the spectral energy distributions of host stars are, therefore, essential for understanding the evolution and habitability of exoplanets. The large number of stars observed with the MUSCLES, Mega-MUSCLES, and other recent Hubble Space Telescope observing programs has provided for the first time a large sample (79 stars) of reconstructed Lyα fluxes that we compare with X-ray fluxes to identify significant patterns in the relative emission from these two atmospheric regions as a function of stellar age and effective temperature. We find that as stars age on the main sequence, the emissions from their chromospheres and coronae follow a pattern in response to the amount of magnetic heating in these atmospheric layers. A single trend-line slope describes the pattern of X-ray versus Lyα emission for G and K dwarfs, but the different trend lines for M dwarf stars show that the Lyα fluxes of M stars are significantly smaller than those of warmer stars with the same X-ray flux. The X-ray and Lyα luminosities divided by the stellar bolometric luminosities show different patterns depending on stellar age. The L (Lyα)/L(bol) ratios increase smoothly to cooler stars of all ages, but the L(X)/L(bol) ratios show different trends. For older stars, the increase in coronal emission with decreasing Teff is much steeper than that of chromospheric emission. We suggest a fundamental link between atmospheric properties and trend lines relating coronal and chromospheric heating.Fil: Linsky, Jeffrey L.. State University of Colorado at Boulder; Estados UnidosFil: Wood, Brian E.. Spece Sciences División. Naval Research Laboratory; Estados UnidosFil: Youngblood, Allison. State University of Colorado at Boulder; Estados UnidosFil: Brown, Alexander. State University of Colorado at Boulder; Estados UnidosFil: Froning, Cynthia S.. University of Texas at Austin; Estados UnidosFil: France, Kevin. State University of Colorado at Boulder; Estados UnidosFil: Buccino, Andrea Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Cranmer, Steven R.. State University of Colorado at Boulder; Estados UnidosFil: Mauas, Pablo Jacobo David. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Miguel, Yamila. Leiden Observatory; Países BajosFil: Sebastian Pineda, J.. State University of Colorado at Boulder; Estados UnidosFil: Rugheimer, Sarah. University of Oxford; Reino UnidoFil: Vieytes, Mariela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Wheatley, Peter J.. University of Warwick; Reino UnidoFil: Wilson, David J.. University of Texas at Austin; Estados Unido

ZANATLIJE U SPLITU POČETKOM XVIII STOLJEĆA

The authors would like to acknowledge the financial support from the EPSRC industrial CASE award (grant EP/N50936X/1).Here we demonstrate the synthesis and structural characterisation of a novel copper MOF: STAM-NMe2, developed using the linker 5-dimethylamino isophthalic acid. The material is a member of the STAM series of MOFs, with a Kagome lattice structure and contains two types of pore system. The structure was investigated using single crystal X-ray diffraction, variable temperature powder X-ray diffraction was used to determine the thermal stability of the MOF, and nitrogen BET adsorption was employed to determine the porosity of the material.PostprintPeer reviewe