Immunosedation: a consideration for sepsis

In a recent issue of Critical Care, Qiao and colleagues showed in a rat model of sepsis that dexmedetomidine and midazolam suppress the generation of pro-inflammatory mediators but the effects vary between agents. While dexmedetomidine limited apoptosis to a greater extent than midazolam, both agents significantly reduced short-term mortality compared with saline. This study, in addition to those by others, suggests there are disparate immunomodulating effects between sedatives. Clinical studies are warranted to investigate whether these effects impact outcomes of septic patients. Perhaps one day the choice of sedative in septic patients will not be based solely on sedative properties but rather immunosedative profiles

Measurements of Far-UV Emission from Elliptical Galaxies at z=0.375

The ``UV upturn'' is a sharp rise in spectra of elliptical galaxies shortward of rest-frame 2500 A. It is a ubiquitous phenomenon in nearby giant elliptical galaxies, and is thought to arise primarily from low-mass evolved stars on the extreme horizontal branch and beyond. Models suggest that the UV upturn is a very strong function of age for these old stellar populations, increasing as the galaxy gets older. In some models the change in UV/optical flux ratio is a factor of 25 over timescales of less than 3 Gyr. To test the predictions for rapid evolution of the UV upturn, we have observed a sample of normal elliptical galaxies in the z=0.375 cluster Abell 370 with the Faint Object Camera aboard the Hubble Space Telescope. A combination of two long-pass filters was used to isolate wavelengths shortward of rest-frame 2700 A, providing a measurement of the UV upturn at a lookback time of approximately 4 Gyr. Surprisingly, the four elliptical galaxies observed show a range of UV upturn strength that is similar to that seen in nearby elliptical galaxies, with an equivalent 1550-V color ranging from 2.9-3.4 mag. Our result is inconsistent with some models for the UV upturn; other models are consistent only for a high redshift of formation (z_f >= 4).Comment: 4 pages, Latex. 1 figure. To appear in ApJL. Uses emulateapj.sty and apjfonts.sty. Revision includes minor ApJ edits & fixes typo

Programmable RNA editing with endogenous ADAR enzymes – a feasible option for the treatment of inherited retinal disease?

RNA editing holds great promise for the therapeutic correction of pathogenic, single nucleotide variants (SNV) in the human transcriptome since it does not risk creating permanent off-targets edits in the genome and has the potential for innovative delivery options. Adenine deaminases acting on RNA (ADAR) enzymes catalyse the most widespread form of posttranscriptional RNA editing in humans and their ability to hydrolytically deaminate adenosine to inosine in double stranded RNA (dsRNA) has been harnessed to change pathogenic single nucleotide variants (SNVs) in the human genome on a transcriptional level. Until now, the most promising target editing rates have been achieved by exogenous delivery of the catalytically active ADAR deaminase domain (ADARDD) fused to an RNA binding protein. While it has been shown that endogenous ADARs can be recruited to a defined target site with the sole help of an ADAR-recruiting guide RNA, thus freeing up packaging space, decreasing the chance of an immune response against a foreign protein, and decreasing transcriptome-wide off-target effects, this approach has been limited by a low editing efficiency. Through the recent development of novel circular ADAR-recruiting guide RNAs as well as the optimisation of ADAR-recruiting antisense oligonucleotides, RNA editing with endogenous ADAR is now showing promising target editing efficiency in vitro and in vivo. A target editing efficiency comparable to RNA editing with exogenous ADAR was shown both in wild-type and disease mouse models as well as in wild-type non-human primates (NHP) immediately following and up to 6 weeks after application. With these encouraging results, RNA editing with endogenous ADAR has the potential to present an attractive option for the treatment of inherited retinal diseases (IRDs), a field where gene replacement therapy has been established as safe and efficacious, but where an unmet need still exists for genes that exceed the packaging capacity of an adeno associated virus (AAV) or are expressed in more than one retinal isoform. This review aims to give an overview of the recent developments in the field of RNA editing with endogenous ADAR and assess its applicability for the field of treatment of IRD

Active chiral plasmonics: flexoelectric control of nanoscale chirality

The ability to electrically control the optical properties of metamaterials is an essential capability required for technological innovation. The creation of dynamic electrically tuneable metamaterials in the visible and near IR region are important for a range of imaging and fibre optic technologies. However current approaches require complex nanofabrication processes which are incompatible for low cost device production. Here, we report a novel simple approach for electrical control of optical properties which utilises a flexoelectric dielectric element to electromechanically manipulate the form factor of a chiral nanostructure. By altering the dimensions of the chiral nanostructure, we allow the polarisation properties of light to be electrically controlled. The flexoelectric element is part of a composite metafilm that is templated on to a nanostructured polymer substrate. Since the flexoelectric element does not require in situ high temperature annealing it can be readily combined with polymer‐based substrates produced by high throughput methods. This is not the case for piezoelectric elements, routinely used in microelectromechanical (MEM) devices which require high temperature processing. Consequently, combining amorphous flexoelectric dielectric and low‐cost polymer‐based materials provides a route to the high throughput production of electrically responsive disposable metadevices

Investigating the medium range order in amorphous Ta₂O₅ coatings

Ion-beam sputtered amorphous heavy metal oxides, such as Ta2O5, are widely used as the high refractive index layer of highly reflective dielectric coatings. Such coatings are used in the ground based Laser Interferometer Gravitational-wave Observatory (LIGO), in which mechanical loss, directly related to Brownian thermal noise, from the coatings forms an important limit to the sensitivity of the LIGO detector. It has previously been shown that heat-treatment and TiO2 doping of amorphous Ta2O5 coatings causes significant changes to the levels of mechanical loss measured and is thought to result from changes in the atomic structure. This work aims to find ways to reduce the levels of mechanical loss in the coatings by understanding the atomic structure properties that are responsible for it, and thus helping to increase the LIGO detector sensitivity. Using a combination of Reduced Density Functions (RDFs) from electron diffraction and Fluctuation Electron Microscopy (FEM), we probe the medium range order (in the 2-3 nm range) of these amorphous coatings

Order within disorder: the atomic structure of ion-beam sputtered amorphous tantala (a-Ta2O5)

Amorphous tantala (a-Ta2O5) is a technologically important material often used in high-performance coatings. Understanding this material at the atomic level provides a way to further improve performance. This work details extended X-ray absorption fine structure measurements of a-Ta2O5 coatings, where high-quality experimental data and theoretical fits have allowed a detailed interpretation of the nearest-neighbor distributions. It was found that the tantalum atom is surrounded by four shells of atoms in sequence; oxygen, tantalum, oxygen, and tantalum. A discussion is also included on how these models can be interpreted within the context of published crystalline Ta 2O5 and other a-T2O5 studies

Fast pixelated detectors in scanning transmission electron microscopy. Part II: post acquisition data processing, visualisation, and structural characterisation

Fast pixelated detectors incorporating direct electron detection (DED) technology are increasingly being regarded as universal detectors for scanning transmission electron microscopy (STEM), capable of imaging under multiple modes of operation. However, several issues remain around the post acquisition processing and visualisation of the often very large multidimensional STEM datasets produced by them. We discuss these issues and present open source software libraries to enable efficient processing and visualisation of such datasets. Throughout, we provide examples of the analysis methodologies presented, utilising data from a 256×256 pixel Medipix3 hybrid DED detector, with a particular focus on the STEM characterisation of the structural properties of materials. These include the techniques of virtual detector imaging; higher order Laue zone analysis; nanobeam electron diffraction; and scanning precession electron diffraction. In the latter, we demonstrate nanoscale lattice parameter mapping with a fractional precision ≤6×10−4 (0.06%)

Age and Abundance Discrimination in Old Stellar Populations Using Mid-Ultraviolet Colors

The restframe mid-ultraviolet spectral region (2000-3200 A) is important in analyzing the stellar populations of the "red envelope" systems observed at high redshifts. Here, we explore the usefulness of the mid-UV for determining ages and abundances of old populations. A mid-UV to optical/IR wavelength baseline provides good separation of population components because the main sequence turnoff dominates the integrated light between 2500 and 4000 A. We find a six magnitude difference in the mid-UV continuum level over the metallicity range -1.5 < log Z/Z_o < +0.5 and a comparable difference (per unit log t) for ages in the range 4-16 Gyr. Logarithmic derivatives of mid-UV colors with respect to age or metal abundance are 3-10 times larger than for the UBV region. Most of the spectral information on old populations therefore resides below 4000 A. We investigate the capability of UBV and mid-UV broad-band colors to separately determine age and abundance, taking into account precision in the color measurements. We find that the mid-UV improves resolution in (log t,log Z) space by about a factor of 3 for a given observational precision. Contamination by hot horizontal branch phases can seriously affect mid-UV spectra, reaching over 80% in some cases. However, this is straightforward to remove as long as far-UV measurements are available. Finally, we show that a 4 Gyr, solar abundance model based on empirical spectra provides an excellent fit to the mid-UV spectrum of the E galaxy M32. This indicates that the poorer results obtained from theoretical spectra arise from limitations of the synthesis models for individual stars. [Condensed]Comment: 38 pages, 8 figures. Accepted by ApJ. Full resolution figures available at: http://www.astro.virginia.edu/~rwo/miduv-fullresfigs.ps.g