Novel Marmoset (Callithrix jacchus) Model of Human Herpesvirus 6A and 6B Infections: Immunologic, Virologic and Radiologic Characterization

Human Herpesvirus 6 (HHV-6) is a ubiquitous virus with an estimated seroprevalence of 95% in the adult population. HHV-6 is associated with several neurologic disorders, including multiple sclerosis, an inflammatory demyelinating disease affecting the CNS. Animal models of HHV-6 infection would help clarify its role in human disease but have been slow to develop because rodents lack CD46, the receptor for cellular entry. Therefore, we investigated the effects of HHV-6 infections in a non-human primate, the common marmoset Callithrix jacchus. We inoculated a total of 12 marmosets with HHV-6A and HHV-6B intravenously and HHV-6A intranasally. Animals were monitored for 25 weeks post-inoculation clinically, immunologically and by MRI. Marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms and generated virus-specific antibody responses, while those inoculated intravenously with HHV-6B were asymptomatic and generated comparatively lower antibody responses. Viral DNA was detected at a low frequency in paraffin-embedded CNS tissue of a subset of marmosets inoculated with HHV-6A and HHV-6B intravenously. When different routes of HHV-6A inoculation were compared, intravenous inoculation resulted in virus-specific antibody responses and infrequent detection of viral DNA in the periphery, while intranasal inoculation resulted in negligible virus-specific antibody responses and frequent detection of viral DNA in the periphery. Moreover, marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms, while marmosets inoculated with HHV-6A intranasally were asymptomatic. We demonstrate that a marmoset model of HHV-6 infection can serve to further define the contribution of this ubiquitous virus to human neurologic disorders

Nematic liquid crystal alignment on chemical patterns

Patterned Self-Assembled Monolayers (SAMs) promoting both homeotropic and planar degenerate alignment of 6CB and 9CB in their nematic phase, were created using microcontact printing of functionalised organothiols on gold films. The effects of a range of different pattern geometries and sizes were investigated, including stripes, circles and checkerboards. EvanescentWave Ellipsometry was used to study the orientation of the liquid crystal (LC) on these patterned surfaces during the isotropic-nematic phase transition. Pretransitional growth of a homeotropic layer was observed on 1 ¹m homeotropic aligning stripes, followed by a homeotropic mono-domain state prior to the bulk phase transition. Accompanying Monte-Carlo simulations of LCs aligned on nano-patterned surfaces were also performed. These simulations also showed the presence of the homeotropic mono-domain state prior to the transition.</p

Large Coherence Area Thin-Film Photonic Stop-Band Lasers

We demonstrate that the shift of the stop band position with increasing oblique angle in periodic structures results in a wide transverse exponential field distribution corresponding to strong angular confinement of the radiation. The beam expansion follows an effective diffusive equation depending only upon the spectral mode width. In the presence of gain, the beam cross section is limited only by the size of the gain area. As an example of an active periodic photonic medium, we calculate and measure laser emission from a dye-doped cholesteric liquid crystal film

Determination of the director profile in a nematic cell from guided wave data: an inverse problem

Copyright © 2007 IOP Publishing Ltd and Deutsche Physikalische Gesellschaft. This is the published version of an article published in New Journal of Physics Vol. 9, article 166. DOI: 10.1088/1367-2630/9/6/166We consider an inverse problem: the estimation of the nematic director profile from experimental fully leaky guided mode data. This inverse problem is ill-posed in that small changes in the data may lead to large changes in the estimates of the director profile. The continuum equations for a nematic are exploited to stabilize the problem. We use experimental data drawn from a study of the dynamics of a hybrid-aligned nematic cell as an example

A uniform asteroseismic analysis of 22 solar-type stars observed by Kepler

Asteroseismology with the Kepler space telescope is providing not only an improved characterization of exoplanets and their host stars, but also a new window on stellar structure and evolution for the large sample of solar-type stars in the field. We perform a uniform analysis of 22 of the brightest asteroseismic targets with the highest signal-to-noise ratio observed for 1 month each during the first year of the mission, and we quantify the precision and relative accuracy of asteroseismic determinations of the stellar radius, mass, and age that are possible using various methods. We present the properties of each star in the sample derived from an automated analysis of the individual oscillation frequencies and other observational constraints using the Asteroseismic Modeling Portal (AMP), and we compare them to the results of model-grid-based methods that fit the global oscillation properties. We find that fitting the individual frequencies typically yields asteroseismic radii and masses to \sim1% precision, and ages to \sim2.5% precision (respectively 2, 5, and 8 times better than fitting the global oscillation properties). The absolute level of agreement between the results from different approaches is also encouraging, with model-grid-based methods yielding slightly smaller estimates of the radius and mass and slightly older values for the stellar age relative to AMP, which computes a large number of dedicated models for each star. The sample of targets for which this type of analysis is possible will grow as longer data sets are obtained during the remainder of the mission.Comment: 13 pages, 5 figures in the main text, 22 figures in Appendix. Accepted for publication in Ap

Loss of the sphingolipid desaturase DEGS1 causes hypomyelinating leukodystrophy.

Sphingolipid imbalance is the culprit in a variety of neurological diseases, some affecting the myelin sheath. We have used whole-exome sequencing in patients with undetermined leukoencephalopathies to uncover the endoplasmic reticulum lipid desaturase DEGS1 as the causative gene in 19 patients from 13 unrelated families. Shared features among the cases include severe motor arrest, early nystagmus, dystonia, spasticity, and profound failure to thrive. MRI showed hypomyelination, thinning of the corpus callosum, and progressive thalamic and cerebellar atrophy, suggesting a critical role of DEGS1 in myelin development and maintenance. This enzyme converts dihydroceramide (DhCer) into ceramide (Cer) in the final step of the de novo biosynthesis pathway. We detected a marked increase of the substrate DhCer and DhCer/Cer ratios in patients' fibroblasts and muscle. Further, we used a knockdown approach for disease modeling in Danio rerio, followed by a preclinical test with the first-line treatment for multiple sclerosis, fingolimod (FTY720, Gilenya). The enzymatic inhibition of Cer synthase by fingolimod, 1 step prior to DEGS1 in the pathway, reduced the critical DhCer/Cer imbalance and the severe locomotor disability, increasing the number of myelinating oligodendrocytes in a zebrafish model. These proof-of-concept results pave the way to clinical translation

Precise Transit And Radial-Velocity Characterization Of A Resonant Pair: The Warm Jupiter TOI-216c And Eccentric Warm Neptune TOI-216b

TOI-216 hosts a pair of warm, large exoplanets discovered by the TESS mission. These planets were found to be in or near the 2:1 resonance, and both of them exhibit transit timing variations (TTVs). Precise characterization of the planets\u27 masses and radii, orbital properties, and resonant behavior can test theories for the origins of planets orbiting close to their stars. Previous characterization of the system using the first six sectors of TESS data suffered from a degeneracy between planet mass and orbital eccentricity. Radial-velocity measurements using HARPS, FEROS, and the Planet Finder Spectrograph break that degeneracy, and an expanded TTV baseline from TESS and an ongoing ground-based transit observing campaign increase the precision of the mass and eccentricity measurements. We determine that TOI-216c is a warm Jupiter, TOI-216b is an eccentric warm Neptune, and that they librate in 2:1 resonance with a moderate libration amplitude of ${60}_{-2}^{+2}$deg, a small but significant free eccentricity of ${0.0222}_{-0.0003}^{+0.0005}$for TOI-216b, and a small but significant mutual inclination of 1fdg2–3fdg9 (95% confidence interval). The libration amplitude, free eccentricity, and mutual inclination imply a disturbance of TOI-216b before or after resonance capture, perhaps by an undetected third planet

TOI-199 b: A well-characterized 100-day transiting warm giant planet with TTVs seen from Antarctica

We present the spectroscopic confirmation and precise mass measurement of the warm giant planet TOI-199 b. This planet was first identified in TESS photometry and confirmed using ground-based photometry from ASTEP in Antarctica including a full 6.5$\,$h long transit, PEST, Hazelwood, and LCO; space photometry from NEOSSat; and radial velocities (RVs) from FEROS, HARPS, CORALIE, and CHIRON. Orbiting a late G-type star, TOI-199\,b has a $\mathrm{104.854_{-0.002}^{+0.001} \, d}$ period, a mass of $\mathrm{0.17\pm0.02 \, M_J}$, and a radius of $\mathrm{0.810\pm0.005 \, R_J}$. It is the first warm exo-Saturn with a precisely determined mass and radius. The TESS and ASTEP transits show strong transit timing variations, pointing to the existence of a second planet in the system. The joint analysis of the RVs and TTVs provides a unique solution for the non-transiting companion TOI-199 c, which has a period of $\mathrm{273.69_{-0.22}^{+0.26} \, d}$ and an estimated mass of $\mathrm{0.28_{-0.01}^{+0.02} \, M_J}$. This period places it within the conservative Habitable Zone.Comment: 33 pages, 23 figures. Accepted for publication in A

TIC 168789840: A Sextuply Eclipsing Sextuple Star System

We report the discovery of a sextuply eclipsing sextuple star system from TESS data, TIC 168789840, also known as TYC 7037-89-1, the first known sextuple system consisting of three eclipsing binaries. The target was observed in Sectors 4 and 5 during Cycle 1, with lightcurves extracted from TESS Full Frame Image data. It was also previously observed by the WASP survey and ASAS-SN. The system consists of three gravitationally bound eclipsing binaries in a hierarchical structure of an inner quadruple system with an outer binary subsystem. Follow-up observations from several different observatories were conducted as a means of determining additional parameters. The system was resolved by speckle interferometry with a 0farcs42 separation between the inner quadruple and outer binary, inferring an estimated outer period of ~2 kyr. It was determined that the fainter of the two resolved components is an 8.217 day eclipsing binary, which orbits the inner quadruple that contains two eclipsing binaries with periods of 1.570 days and 1.306 days. Markov Chain Monte Carlo (MCMC) analysis of the stellar parameters has shown that the three binaries of TIC 168789840 are triplets, as each binary is quite similar to the others in terms of mass, radius, and Teff. As a consequence of its rare composition, structure, and orientation, this object can provide important new insight into the formation, dynamics, and evolution of multiple star systems. Future observations could reveal if the intermediate and outer orbital planes are all aligned with the planes of the three inner eclipsing binaries