230 research outputs found
Advanced Photodetectors for Hyperspectroscopy and Other Applications
Hyperspectroscopy is a new method of surface image taking, providing
simultaneously high position and spectral resolutions which allow one to make
some conclusions about chemical compositions of the surfaces. We are now
studying applications of the hyperspctroscopic technique to be used for
medicine. This may allow one to develop early diagnostics of some illnesses, as
for example, skin cancer. For image taking advanced MCPs are currently used,
sensitive in the spectral interval of 450-850 nm. One of the aims of this work
is to extend the hyperspectrocpic method to the UV region of spectra: 185-280
nm. For this we have developed and successfully tested innovative 1D and 2D UV
sealed photosensitive gaseous detectors with resistive electrodes. These
detectors are superior MCPs due to the very low rate of noise pulses and thus
due to the high signal to noise ratio. Other important features of these
detectors are that they have excellent position resolutions - 30 micron in
digital form, are vibration stable and are spark protected. The first results
from the application of these detectors for spectroscopy, hyperspectroscopy and
the flame detection are presented.Comment: Presented at the IEEE Nuclear Science Syposium, Puerto Rico, October
200
The first applications of novel gaseous detectors for UV visualization
We have demonstrated experimentally that recently developed gaseous detectors combined with solid or gaseous photo-cathodes have exceptionally low noise and high quantum efficiency for UV photons while being solar blind. For this reason they can be used for the detection of weak UV sources in daylight conditions. These detectors are extremely robust, can operate in poor gas conditions and are cheap. We present the first results of their applications to hyper-spectroscopy and flame detection in daylight conditions
Inactivation of Ppp1r15a minimises weight gain and insulin resistance during caloric excess in female mice.
Phosphorylation of the translation initiation factor eIF2α within the mediobasal hypothalamus is known to suppress food intake, but the role of the eIF2α phosphatases in regulating body weight is poorly understood. Mice deficient in active PPP1R15A, a stress-inducible eIF2α phosphatase, are healthy and more resistant to endoplasmic reticulum stress than wild type controls. We report that when female Ppp1r15a mutant mice are fed a high fat diet they gain less weight than wild type littermates owing to reduced food intake. This results in healthy leaner Ppp1r15a mutant animals with reduced hepatic steatosis and improved insulin sensitivity, albeit with a possible modest defect in insulin secretion. By contrast, no weight differences are observed between wild type and Ppp1r15a deficient mice fed a standard diet. We conclude that female mice lacking the C-terminal PP1-binding domain of PPP1R15A show reduced dietary intake and preserved glucose tolerance. Our data indicate that this results in reduced weight gain and protection from diet-induced obesity.The work was also supported by Diabetes UK and the MRC [G1002610]. VP held an Arthur and Sadie Pethybridge PhD Studentship from Diabetes UK. The CIMR microscopy core facility is supported by a Wellcome Trust Strategic Award [100140] and a Wellcome Trust equipment grant [093026]
Evolution of Linear Absorption and Nonlinear Optical Properties in V-Shaped Ruthenium(II)-Based Chromophores
In this article, we describe a series of complexes with electron-rich cis-{Ru^(II)(NH_3)_4}^(2+) centers coordinated to two pyridyl ligands bearing N-methyl/arylpyridinium electron-acceptor groups. These V-shaped dipolar species are new, extended members of a class of chromophores first reported by us (Coe, B. J. et al. J. Am. Chem. Soc. 2005, 127, 4845−4859). They have been isolated as their PF_6− salts and characterized by using various techniques including ^1H NMR and electronic absorption spectroscopies and cyclic voltammetry. Reversible Ru^(III/II) waves show that the new complexes are potentially redox-switchable chromophores. Single crystal X-ray structures have been obtained for four complex salts; three of these crystallize noncentrosymmetrically, but with the individual molecular dipoles aligned largely antiparallel. Very large molecular first hyperpolarizabilities β have been determined by using hyper-Rayleigh scattering (HRS) with an 800 nm laser and also via Stark (electroabsorption) spectroscopic studies on the intense, visible d → π^* metal-to-ligand charge-transfer (MLCT) and π → π^* intraligand charge-transfer (ILCT) bands. The latter measurements afford total nonresonant β_0 responses as high as ca. 600 × 10^(−30) esu. These pseudo-C_(2v) chromophores show two substantial components of the β tensor, β_(zzz) and β_(zyy), although the relative significance of these varies with the physical method applied. According to HRS, β_(zzz) dominates in all cases, whereas the Stark analyses indicate that β_(zyy) is dominant in the shorter chromophores, but β_(zzz) and β_(zyy) are similar for the extended species. In contrast, finite field calculations predict that β_(zyy) is always the major component. Time-dependent density functional theory calculations predict increasing ILCT character for the nominally MLCT transitions and accompanying blue-shifts of the visible absorptions, as the ligand π-systems are extended. Such unusual behavior has also been observed with related 1D complexes (Coe, B. J. et al. J. Am. Chem. Soc. 2004, 126, 3880−3891)
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SREBP1-induced fatty acid synthesis depletes macrophages antioxidant defences to promote their alternative activation
Macrophages exhibit a spectrum of activation states ranging from classical to alternative activation1. Alternatively, activated macrophages are involved in diverse pathophysiological processes such as confining tissue parasites2, improving insulin sensitivity3 or promoting an immune tolerant microenvironment that facilitates tumour growth and metastasis4. Recently, the role of metabolism regulating macrophage function has come into focus as both the classical and alternative activation programmes require specific regulated metabolic reprogramming5. While most of the studies regarding immunometabolism have focussed on the catabolic pathways activated to provide energy, little is known about the anabolic pathways mediating macrophage alternative activation. In this study, we show that the anabolic transcription factor sterol regulatory element binding protein 1 (SREBP1) is activated in response to the canonical Th2 cytokine interleukin 4 (IL-4) to trigger the de novo lipogenesis (DNL) programme, as a necessary step for macrophage alternative activation. Mechanistically, DNL consumes NADPH, partitioning it away from cellular antioxidant defences and raising ROS levels. ROS serves as a second messenger, signalling sufficient DNL, and promoting macrophage alternative activation. The pathophysiological relevance of this mechanism is validated by showing that SREBP1/DNL is essential for macrophage alternative activation in vivo in a helminth infection model.This work was supported by the British Heart Foundation (RG/18/7/33636), the MRC (MC_UU_00014/2) and the FP7 MITIN (223450). K.P. was a recipient of a fellowship from the Wellcome Trust. A.N.J.M. and E.J. are supported by the Wellcome Trust (100963/Z/13/Z) and the MRC (U105178805). J.L. is a recipient fellowship of the British Heart Foundation. A.D. was a Marie-Curie Early-Stage Researcher supported by the European Union’s Horizon 2020 research and innovation programme (675585 Marie-Curie ITN ‘SymBioSys’) to J.S.-R. A.K. is supported by the Wellcome Trust (106260/Z/14/Z) and an ERC award (648889). P.F. is supported by the Science Foundation Ireland (10/IN.1/B3004). The IMS Genomics and Transcriptomics and Histology cores (B.M.-A., B.Y.H.L. and M.K.M.) are funded by the UK MRC Metabolic Disease Unit (MRC_MC_UU_12012/5) and a Wellcome Trust Strategic Award (100574/Z/12/Z). The Disease Model Core is part of the MRC Metabolic Diseases Unit (MRC_MC_UU_12012/5) and Wellcome Trust Strategic Award (100574/Z/12/Z)
Investigation of the local environment of Eu3+ in a silicophosphate glass using site-selective spectroscopy and Molecular Dynamics simulations
Silicophosphate glasses (SiO2-P2O5) doped with Eu3+ ions were synthesized by the sol-gel process. Optical properties of these glasses were investigated by means of emission spectra and lifetime measurements. The Fluorescence Line Narrowing (FLN) technique was also used to explore the local structure around the Eu3+ ions in this host and to understand the role of phosphate as a codopant. As it is the case for aluminum, the ability of phosphate to avoid the rare earth clustering was investigated, and the role of this codopant in modifying the local order around the rare earth ion was evidenced. The analysis of the FLN spectra and lifetime measurements is consistent with this interpretation. Molecular Dynamics simulations were performed to evaluate and confirm these structural features. Two classes of europium sites were distinguished in agreement with the experimental characterization
Lipodystrophy-Linked LMNA p.R482W Mutation Induces Clinical Early Atherosclerosis and In Vitro Endothelial Dysfunction
Objective—Some mutations in LMNA, encoding A-type lamins, are responsible for Dunnigan-type-familial partial lipodystrophy (FPLD2), with altered fat distribution and metabolism. The high prevalence of early and severe cardiovascular outcomes in these patients suggests that, in addition to metabolic risk factors, FPLD2-associated LMNA mutations could have a direct role on the vascular wall cells.
Approach and Results—We analyzed the cardiovascular phenotype of 19 FPLD2 patients aged >30 years with LMNA p.R482 heterozygous substitutions, and the effects of p.R482W-prelamin-A overexpression in human coronary artery endothelial cells. In 68% of FPLD2 patients, early atherosclerosis was attested by clinical cardiovascular events, occurring before the age of 45 in most cases. In transduced endothelial cells, exogenous wild-type-prelamin-A was correctly processed and localized, whereas p.R482W-prelamin-A accumulated abnormally at the nuclear envelope. Patients’ fibroblasts also showed a predominant nuclear envelope distribution with a decreased rate of prelamin-A maturation. Only p.R482W-prelamin-A induced endothelial dysfunction, with decreased production of NO, increased endothelial adhesion of peripheral blood mononuclear cells, and cellular senescence. p.R482W-prelamin-A also induced oxidative stress, DNA damages, and inflammation. These alterations were prevented by treatment of endothelial cells with pravastatin, which inhibits prelamin-A farnesylation, or with antioxidants. In addition, pravastatin allowed the correct relocalization of p.R482W-prelamin-A within the endothelial cell nucleus. These data suggest that farnesylated p.R482W-prelamin-A accumulation at the nuclear envelope is a toxic event, leading to cellular oxidative stress and endothelial dysfunction.
Conclusions—LMNA p.R482 mutations, responsible for FPLD2, exert a direct proatherogenic effect in endothelial cells, which could contribute to patients’ early atherosclerosis
Electrode Polarization Effects in Broadband Dielectric Spectroscopy
In the present work, we provide broadband dielectric spectra showing strong
electrode polarization effects for various materials, belonging to very
different material classes. This includes both ionic and electronic conductors
as, e.g., salt solutions, ionic liquids, human blood, and
colossal-dielectric-constant materials. These data are intended to provide a
broad data base enabling a critical test of the validity of phenomenological
and microscopic models for electrode polarization. In the present work, the
results are analyzed using a simple phenomenological equivalent-circuit
description, involving a distributed parallel RC circuit element for the
modeling of the weakly conducting regions close to the electrodes. Excellent
fits of the experimental data are achieved in this way, demonstrating the
universal applicability of this approach. In the investigated ionically
conducting materials, we find the universal appearance of a second dispersion
region due to electrode polarization, which is only revealed if measuring down
to sufficiently low frequencies. This indicates the presence of a second
charge-transport process in ionic conductors with blocking electrodes.Comment: 9 pages, 6 figures, experimental data are provided in electronic form
(see "Data Conservancy"
Colossal dielectric constants in transition-metal oxides
Many transition-metal oxides show very large ("colossal") magnitudes of the
dielectric constant and thus have immense potential for applications in modern
microelectronics and for the development of new capacitance-based
energy-storage devices. In the present work, we thoroughly discuss the
mechanisms that can lead to colossal values of the dielectric constant,
especially emphasising effects generated by external and internal interfaces,
including electronic phase separation. In addition, we provide a detailed
overview and discussion of the dielectric properties of CaCu3Ti4O12 and related
systems, which is today's most investigated material with colossal dielectric
constant. Also a variety of further transition-metal oxides with large
dielectric constants are treated in detail, among them the system La2-xSrxNiO4
where electronic phase separation may play a role in the generation of a
colossal dielectric constant.Comment: 31 pages, 18 figures, submitted to Eur. Phys. J. for publication in
the Special Topics volume "Cooperative Phenomena in Solids: Metal-Insulator
Transitions and Ordering of Microscopic Degrees of Freedom
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