523 research outputs found

    Spectral aerosol extinction (SpEx): a new instrument for in situ ambient aerosol extinction measurements across the UV/visible wavelength range

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    We introduce a new instrument for the measurement of in situ ambient aerosol extinction over the 300– 700 nm wavelength range, the spectral aerosol extinction (SpEx) instrument. This measurement capability is envisioned to complement existing in situ instrumentation, allowing for simultaneous measurement of the evolution of aerosol optical, chemical, and physical characteristics in the ambient environment. In this work, a detailed description of the instrument is provided along with characterization tests performed in the laboratory. Measured spectra of NO2 and polystyrene latex spheres (PSLs) agreed well with theoretical calculations. Good agreement was also found with simultaneous aerosol extinction measurements at 450, 530, and 630 nm using CAPS PMex instruments in a series of 22 tests including nonabsorbing compounds, dusts, soot, and black and brown carbon analogs. SpEx measurements are expected to help identify the presence of ambient brown carbon due to its 300 nm lower wavelength limit compared to measurements limited to longer UV and visible wavelengths. Extinction spectra obtained with SpEx contain more information than can be conveyed by a simple power law fit (typically represented by Ångström exponents). Planned future improvements aim to lower detection limits and ruggedize the instrument for mobile operation

    circRNAs expressed in human peripheral blood are associated with human aging phenotypes, cellular senescence and mouse lifespan.

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    Circular RNAs (circRNAs) are an emerging class of non-coding RNA molecules that are thought to regulate gene expression and human disease. Despite the observation that circRNAs are known to accumulate in older organisms and have been reported in cellular senescence, their role in aging remains relatively unexplored. Here, we have assessed circRNA expression in aging human blood and followed up age-associated circRNA in relation to human aging phenotypes, mammalian longevity as measured by mouse median strain lifespan and cellular senescence in four different primary human cell types. We found that circRNAs circDEF6, circEP300, circFOXO3 and circFNDC3B demonstrate associations with parental longevity or hand grip strength in 306 subjects from the InCHIANTI study of aging, and furthermore, circFOXO3 and circEP300 also demonstrate differential expression in one or more human senescent cell types. Finally, four circRNAs tested showed evidence of conservation in mouse. Expression levels of one of these, circPlekhm1, was nominally associated with lifespan. These data suggest that circRNA may represent a novel class of regulatory RNA involved in the determination of aging phenotypes, which may show future promise as both biomarkers and future therapeutic targets for age-related disease

    Targeting the alternative oxidase (AOX) for human health and food security, a pharmaceutical and agrochemical target or a rescue mechanism?

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    Some of the most threatening human diseases are due to a blockage of the mitochondrial electron transport chain (ETC). In a variety of plants, fungi, and prokaryotes, there is a naturally evolved mechanism for such threats to viability, namely a bypassing of the blocked portion of the ETC by alternative enzymes of the respiratory chain. One such enzyme is the alternative oxidase (AOX). When AOX is expressed, it enables its host to survive life-threatening conditions or, as in parasites, to evade host defenses. In vertebrates, this mechanism has been lost during evolution. However, we and others have shown that transfer of AOX into the genome of the fruit fly and mouse results in a catalytically engaged AOX. This implies that not only is the AOX a promising target for combating human or agricultural pathogens but also a novel approach to elucidate disease mechanisms or, in several cases, potentially a therapeutic cure for human diseases. In this review, we highlight the varying functions of AOX in their natural hosts and upon xenotopic expression, and discuss the resulting need to develop species-specific AOX inhibitors.publishedVersionPeer reviewe

    Mapping the Operation of the Miniature Combustion Aerosol Standard (Mini-CAST) Soot Generator

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    The Jing Ltd. miniature combustion aerosol standard (Mini- CAST) soot generator is a portable, commercially available burner that is widely used for laboratory measurements of soot processes. While many studies have used the Mini-CAST to generate soot with known size, concentration, and organic carbon fraction under a single or few conditions, there has been no systematic study of the burner operation over a wide range of operating conditions. Here, we present a comprehensive characterization of the microphysical, chemical, morphological, and hygroscopic properties of Mini- CAST soot over the full range of oxidation air and mixing N2 flow rates. Very fuel-rich and fuel-lean flame conditions are found to produce organic-dominated soot with mode diameters of 10–60 nm, and the highest particle number concentrations are produced under fuel-rich conditions. The lowest organic fraction and largest diameter soot (70–130 nm) occur under slightly fuel-lean conditions. Moving from fuel-rich to fuel-lean conditions also increases the O:C ratio of the soot coatings from ~0.05 to ~0.25, which causes a small fraction of the particles to act as cloud condensation nuclei near the Kelvin limit (κ ~ 0–10−3). Comparison of these property ranges to those reported in the literature for aircraft and diesel engine soots indicates that the Mini-CAST soot is similar to real-world primary soot particles, which lends itself to a variety of process-based soot studies. The trends in soot properties uncovered here will guide selection of burner operating conditions to achieve optimum soot properties that are most relevant to such studies

    KDM4B is a master regulator of the estrogen receptor signalling cascade

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    The importance of the estrogen receptor (ER) in breast cancer (BCa) development makes it a prominent target for therapy. Current treatments, however, have limited effectiveness, and hence the definition of new therapeutic targets is vital. The ER is a member of the nuclear hormone receptor superfamily of transcription factors that requires co-regulator proteins for complete regulation. Emerging evidence has implicated a small number of histone methyltransferase (HMT) and histone demethylase (HDM) enzymes as regulators of ER signalling, including the histone H3 lysine 9 tri-/di-methyl HDM enzyme KDM4B. Two recent independent reports have demonstrated that KDM4B is required for ER-mediated transcription and depletion of the enzyme attenuates BCa growth in vitro and in vivo. Here we show that KDM4B has an overarching regulatory role in the ER signalling cascade by controlling expression of the ER and FOXA1 genes, two critical components for maintenance of the estrogen-dependent phenotype. KDM4B interacts with the transcription factor GATA-3 in BCa cell lines and directly co-activates GATA-3 activity in reporter-based experiments. Moreover, we reveal that KDM4B recruitment and demethylation of repressive H3K9me3 marks within upstream regulatory regions of the ER gene permits binding of GATA-3 to drive receptor expression. Ultimately, our findings confirm the importance of KDM4B within the ER signalling cascade and as a potential therapeutic target for BCa treatment

    Advances in the Projective Dynamics Method: A Procedure of Discretizing the Space applied to Markovian Processes

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    AbstractThe projection of a continuous space process to a discrete space process via the transition rates between neighboring bins allows us to relate a master equation to a solution of a stochastic differential equation. The presented method is formulated in its general form for the first time and tested with the Brownian Diffusion process of noninteracting particles with white noise in simple one-dimensional potentials. The comparison of the first passage time obtained with Projective Dynamics, Brownian motion simulations and analytical solutions show the accuracy of this method as well as a wide independence of the particular choice of the binning process

    Normal modes of the Indian elephant bell

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    Copyright 2012 Acoustical Society of America. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the Acoustical Society of America. The following article appeared in Journal of the Acoustical Society of America, 2012, 131 (3), pp. 2288 - 2294 and may be found at http://dx.doi.org/10.1121/1.3681924The geometrical structure of the Indian elephant bell is presented and the requirements on its normal modes from group representation theory are described. These are in good agreement with the results of a finite-element model (FEM) for a specific 16-tine case. The spectrum consists of a sequence of families of modes lying on saturation curves, completely different from those of conventional bells. Physical explanations for the occurrence of these families are presented in terms of the tines behaving as a closed loop of coupled cantilevers with constraints from the dome. Each family is found to consist of modes in one of two specific sequences of symmetry types. Experimental measurements of the modes of this same 16-tine bell, using electronic speckle patterninterferometry (ESPI), have been made and are compared with the FEM predictions. Although the interpretation of the interferograms is difficult in all but the simpler cases, agreement in terms of frequencies is surprisingly good for the first few family sequences. The ESPI study also showed up numerous harmonics and subharmonics of true normal modes, showing the system to be rather non-linear and making comparisons with the FEM results tricky

    Comparison of the kinetic parameters of alternative oxidases from Trypanosoma brucei and Arabidopsis thaliana-a tale of two cavities

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    The alternative oxidase (AOX) is widespread in plants, fungi, and some protozoa. While the general structure of the AOX remains consistent, its overall activity, sources of kinetic activation and their sensitivity to inhibitors varies between species. In this study, the recombinant Trypanosoma brucei AOX (rTAO) and Arabidopsis thaliana AOX1A (rAtAOX1A) were expressed in the Escherichia coli ΔhemA mutant FN102, and the kinetic parameters of purified AOXs were compared. Results showed that rTAO possessed the highest V max and K m for quinol-1, while much lower V max and K m were observed in the rAtAOX1A. The catalytic efficiency (k cat/K m) of rTAO was higher than that of rAtAOX1A. The rTAO also displayed a higher oxygen affinity compared to rAtAOX1A. It should be noted that rAtAOX1a was sensitive to α-keto acids while rTAO was not. Nevertheless, only pyruvate and glyoxylate can fully activate Arabidopsis AOX. In addition, rTAO and rAtAOX1A showed different sensitivity to AOX inhibitors, with ascofuranone (AF) being the best inhibitor against rTAO, while colletochlorin B (CB) appeared to be the most effective inhibitor against rAtAOX1A. Octylgallate (OG) and salicylhydroxamic acid (SHAM) are less effective than the other inhibitors against protist and plant AOX. A Caver analysis indicated that the rTAO and rAtAOX1A differ with respect to the mixture of polar residues lining the hydrophobic cavity, which may account for the observed difference in kinetic and inhibitor sensitivities. The data obtained in this study are not only beneficial for our understanding of the variation in the kinetics of AOX within protozoa and plants but also contribute to the guidance for the future development of phytopathogenic fungicides

    Hard loss of stability in Painlev\'e-2 equation

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    A special asymptotic solution of the Painlev\'e-2 equation with small parameter is studied. This solution has a critical point tt_* corresponding to a bifurcation phenomenon. When t<tt<t_* the constructed solution varies slowly and when t>tt>t_* the solution oscillates very fast. We investigate the transitional layer in detail and obtain a smooth asymptotic solution, using a sequence of scaling and matching procedures
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