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At least 397 records · Page 22

Diagnosis and prognosis of Alzheimer's disease using brain morphometry and white matter connectomes

Accurate, reliable prediction of risk for Alzheimer's disease (AD) is essential for early, disease-modifying therapeutics. Multimodal MRI, such as structural and diffusion MRI, is likely to contain complementary information of neurodegenerative processes in AD. Here we tested the utility of the multimodal MRI (T1-weighted structure and diffusion MRI), combined with high-throughput brain phenotyping—morphometry and structural connectomics—and machine learning, as a diagnostic tool for AD. We used, firstly, a clinical cohort at a dementia clinic (National Health Insurance Service-Ilsan Hospital [NHIS-IH]; N = 211; 110 AD, 64 mild cognitive impairment [MCI], and 37 cognitively normal with subjective memory complaints [SMC]) to test the diagnostic models; and, secondly, Alzheimer's Disease Neuroimaging Initiative (ADNI)-2 to test the generalizability. Our machine learning models trained on the morphometric and connectome estimates (number of features = 34,646) showed optimal classification accuracy (AD/SMC: 97% accuracy, MCI/SMC: 83% accuracy; AD/MCI: 97% accuracy) in NHIS-IH cohort, outperforming a benchmark model (FLAIR-based white matter hyperintensity volumes). In ADNI-2 data, the combined connectome and morphometry model showed similar or superior accuracies (AD/HC: 96%; MCI/HC: 70%; AD/MCI: 75% accuracy) compared with the CSF biomarker model (t-tau, p-tau, and Amyloid β, and ratios). In predicting MCI to AD progression in a smaller cohort of ADNI-2 (n = 60), the morphometry model showed similar performance with 69% accuracy compared with CSF biomarker model with 70% accuracy. Our comparisons of the classifiers trained on structural MRI, diffusion MRI, FLAIR, and CSF biomarkers showed the promising utility of the white matter structural connectomes in classifying AD and MCI in addition to the widely used structural MRI-based morphometry, when combined with machine learning.

60 APPLIED LIFE SCIENCES↗

ERα inhibited myocardin-induced differentiation in uterine fibroids

Uterine fibroids, also known as uterine leiomyomas, are a benign tumor of the human uterus and the commonest estrogen-dependent benign tumor found in women. Myocardin is an important transcriptional regulator in smooth and cardiac muscle development. The role of myocardin and its relationship with ERα in uterine fibroids have barely been addressed. We noticed that the expression of myocardin was markedly reduced in human uterine fibroid tissue compared with corresponding normal or adjacent myometrium tissue. Here we reported that myocardin induced the transcription and expression of differentiation markers SM22α and alpha smooth muscle actin (α-SMA) in rat primary uterine smooth muscle cells (USMCs) and this effect was inhibited by ERα. Notably, we showed that, ERα induced expression of proliferation markers PCNA and ki-67 in rat primary USMCs. We also found ERα interacted with myocardin and formed complex to bind to CArG box and inhibit the SM22α promoter activity. Furthermore, ERα inhibited the transcription and expression of myocardin, and reduced the levels of transcription and expression of downstream target SM22α, a SMC differentiation marker. Our data thus provided important and novel insights into how ERα and myocardin interact to control the cell differentiation and proliferation of USMCs. Thus, it may provide potential therapeutic target for uterine fibroids.

60 APPLIED LIFE SCIENCES↗

Porous Silicon Gradient Refractive Index Micro-Optics

We see the emergence and growth of transformation optics over the past decade has revitalized interest in how a gradient refractive index (GRIN) can be used to control light propagation. Two-dimensional demonstrations with lithographically defined silicon (Si) have displayed the power of GRIN optics and also represent a promising opportunity for integrating compact optical elements within Si photonic integrated circuits. Here, we demonstrate the fabrication of three-dimensional Si-based GRIN micro-optics through the shape-defined formation of porous Si (PSi). Conventional microfabrication creates Si square microcolumns (SMCs) that can be electrochemically etched into PSi elements with nanoscale porosity along the shape-defined etching pathway, which imparts the geometry with structural birefringence. Free-space characterization of the transmitted intensity distribution through a homogeneously etched PSi SMC exhibits polarization splitting behavior resembling that of dielectric metasurfaces that require considerably more laborious fabrication. Coupled birefringence/GRIN effects are studied by way of PSi SMCs etched with a linear (increasing from edge to center) GRIN profile. The transmitted intensity distribution shows polarization-selective focusing behavior with one polarization focused to a diffraction-limited spot and the orthogonal polarization focused into two laterally displaced foci. Optical thickness-based analysis readily predicts the experimentally observed phenomena, which strongly match finite-element electromagnetic simulations.

36 MATERIALS SCIENCE↗

A Combined Global and Local Approach to Elucidate Spatial Organization of the Mycobacterial ParB-parS Partition Assembly

Combining diverse sets of data at global (size, shape) and local (residue) scales is an emerging trend for elucidating the organization and function of the cellular assemblies. We used such a strategy, combining data from X-ray and neutron scattering with H/D-contrast variation and X-ray footprinting with mass spectrometry, to elucidate the spatial organization of the ParB-parS assembly from Mycobacterium tuberculosis. The ParB-parS participates in plasmid and chromosome segregation and condensation in predivisional bacterial cells. ParB polymerizes around the parS centromere(s) to form a higher-order assembly that serves to recruit cyto-skeletal ParA ATPases and SMC proteins for chromosome segregation. A hybrid model of the ParB-parS was built by combining and correlating computational models with experiment-derived information about size, shape, position of the symmetry axis within the shape, internal topology, DNA-protein interface, exposed surface patches, and prior knowledge. This first view of the ParB-parS leads us to propose how ParB spread on the chromosome to form a larger assembly.

59 BASIC BIOLOGICAL SCIENCES↗

Heliconical smectic phases formed by achiral molecules

Chiral symmetry breaking in soft matter is a hot topic of current research. Recently, such a phenomenon was found in a fluidic phase showing orientational order of molecules - the nematic phase; although built of achiral molecules, the phase can exhibit structural chirality - average molecular direction follows a short-pitch helix. Here in this paper, we report a series of achiral asymmetric dimers with an odd number of atoms in the spacer, which form twisted structures in nematic as well as in lamellar phases. The tight pitch heliconical nematic (N TB) phase and heliconical tilted smectic C (SmC TB ) phase are formed. The formation of a variety of helical structures is accompanied by a gradual freezing of molecular rotation. In the lowest temperature smectic phase, HexI, the twist is expressed through the formation of hierarchical structure: nanoscale helices and mesoscopic helical filaments. The short-pitch helical structure in the smectic phases is confirmed by resonant X-ray measurements.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Large-scale genomic analyses with machine learning uncover predictive patterns associated with fungal phytopathogenic lifestyles and traits

Abstract Invasive plant pathogenic fungi have a global impact, with devastating economic and environmental effects on crops and forests. Biosurveillance, a critical component of threat mitigation, requires risk prediction based on fungal lifestyles and traits. Recent studies have revealed distinct genomic patterns associated with specific groups of plant pathogenic fungi. We sought to establish whether these phytopathogenic genomic patterns hold across diverse taxonomic and ecological groups from the Ascomycota and Basidiomycota, and furthermore, if those patterns can be used in a predictive capacity for biosurveillance. Using a supervised machine learning approach that integrates phylogenetic and genomic data, we analyzed 387 fungal genomes to test a proof-of-concept for the use of genomic signatures in predicting fungal phytopathogenic lifestyles and traits during biosurveillance activities. Our machine learning feature sets were derived from genome annotation data of carbohydrate-active enzymes (CAZymes), peptidases, secondary metabolite clusters (SMCs), transporters, and transcription factors. We found that machine learning could successfully predict fungal lifestyles and traits across taxonomic groups, with the best predictive performance coming from feature sets comprising CAZyme, peptidase, and SMC data. While phylogeny was an important component in most predictions, the inclusion of genomic data improved prediction performance for every lifestyle and trait tested. Plant pathogenicity was one of the best-predicted traits, showing the promise of predictive genomics for biosurveillance applications. Furthermore, our machine learning approach revealed expansions in the number of genes from specific CAZyme and peptidase families in the genomes of plant pathogens compared to non-phytopathogenic genomes (saprotrophs, endo- and ectomycorrhizal fungi). Such genomic feature profiles give insight into the evolution of fungal phytopathogenicity and could be useful to predict the risks of unknown fungi in future biosurveillance activities.

59 BASIC BIOLOGICAL SCIENCES↗

A ubiquitin-like domain is required for stabilizing the N-terminal ATPase module of human SMCHD1

Variants in the gene SMCHD1, which encodes an epigenetic repressor, have been linked to both congenital arhinia and a late-onset form of muscular dystrophy called facioscapulohumeral muscular dystrophy type 2 (FSHD2). This suggests that SMCHD1 has a diversity of functions in both developmental time and space. The C-terminal end of SMCHD1 contains an SMC-hinge domain which mediates homodimerization and chromatin association, whereas the molecular architecture of the N-terminal region, which harbors the GHKL-ATPase domain, is not well understood. We present the crystal structure of the human SMCHD1 N-terminal ATPase module bound to ATP as a functional dimer. The dimer is stabilized by a novel N-terminal ubiquitin-like fold and by a downstream transducer domain. While disease variants map to what appear to be critical interdomain/intermolecular interfaces, only the FSHD2-specific mutant constructs we tested consistently abolish ATPase activity and/or dimerization. These data suggest that the full functional profile of SMCHD1 has yet to be determined.

59 BASIC BIOLOGICAL SCIENCES↗

Y-shaped tricatenar azobenzenes – functional liquid crystals with synclinic–anticlinic transitions and spontaneous helix formation

A series of achiral tricatenar rod-like molecules with a 3,5-disubstitution pattern at one end and a single alkyl chain at the other end of a rod-like azobenzene derived core is reported. Depending on temperature and alkyl chain length, these Y-shaped compounds self-assemble into different types of liquid crystalline (LC) phases, ranging from non-tilted and synclinic tilted hexatic, via non-tilted and anticlinic tilted smectic and bicontinuous cubic LC phases, to a spontaneous mirror symmetry broken isotropic liquid (Iso 1 [*]) or a related achiral liquid network phase (Iso 1 ). An additional tilted, but uniaxial smectic phase was observed at the transition between anticlinic and synclinic tilt correlation and was investigated by soft resonant X-ray scattering with respect to possible helix formation. This work provides a new concept for the design of technological interesting azobenzene based LC materials with anticlinic tilted smectic C phases (SmC a ) and with azobenzene units organized in the long range or short range helical network structures of bicontinuous cubic and chiral isotropic liquid phases, respectively. Core fluorination removes all lamellar phases, leaving only the cubic phase over wide temperature ranges, even at ambient temperature.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

APSIDAL MOTIONS OF 27 BINARY SYSTEMS IN THE SMALL MAGELLANIC CLOUD

We present the periods of apsidal motion for 27 early-type eclipsing binaries with high eccentricity located in the Small Magellanic Cloud. New times of minima were derived from the light curves constructed by the MACHO, Optical Gravitational Lensing Experiment (OGLE)-II, and OGLE-III survey data. The eclipse timing diagrams of the binary systems were analyzed using those timings and the elements of apsidal motions were obtained in detail for the first time. The apsidal motion periods of all systems were estimated by detailed analysis of both eclipse timings and light curves; a strong correlation value between both methods is shown. We confirm that OGLE-SMC-ECL-2194 shows the shortest known apsidal motion period of 7.1 yr in a detached system with main sequence stars. Nineteen systems show intermediate apsidal motion periods between 10 and 100 yr, and seven systems exhibit long apsidal periods of more than 100 yr.

79 ASTRONOMY AND ASTROPHYSICS↗

SPECTRAL VARIATIONS OF Of?p OBLIQUE MAGNETIC ROTATOR CANDIDATES IN THE MAGELLANIC CLOUDS

Optical spectroscopic monitoring has been conducted of two O stars in the SMC and one in the LMC, the spectral characteristics of which place them in the Of?p category, which has been established in the Galaxy to consist of oblique magnetic rotators. All of these Magellanic stars show systematic spectral variations typical of the Of?p class, further strengthening their magnetic candidacy to the point of virtual certainty. The spectral variations are related to photometric variations derived from Optical Gravitational Lensing Experiment data by Nazé et al. in a parallel study, which yields rotational periods for two of them. Now circular spectropolarimetry is required to measure their fields, and ultraviolet spectroscopy to further characterize their low-metallicity, magnetically confined winds, in support of hydrodynamical analyses.

79 ASTRONOMY AND ASTROPHYSICS↗

ANALYSIS OF TWO SMALL MAGELLANIC CLOUD H II REGIONS CONSIDERING THERMAL INHOMOGENEITIES: IMPLICATIONS FOR THE DETERMINATIONS OF EXTRAGALACTIC CHEMICAL ABUNDANCES

We present long-slit spectrophotometry considering the presence of thermal inhomogeneities (t{sup 2}) of two H II regions in the Small Magellanic Cloud (SMC): NGC 456 and NGC 460. Physical conditions and chemical abundances were determined for three positions in NGC 456 and one position in NGC 460, first under the assumption of uniform temperature and then allowing for the possibility of thermal inhomogeneities. We determined t{sup 2} values based on three different methods: (1) by comparing the temperature derived using oxygen forbidden lines with the temperature derived using helium recombination lines (RLs), (2) by comparing the abundances derived from oxygen forbidden lines with those derived from oxygen RLs, and (3) by comparing the abundances derived from ultraviolet carbon forbidden lines with those derived from optical carbon RLs. The first two methods averaged t{sup 2} = 0.067 {+-} 0.013 for NGC 456 and t{sup 2} = 0.036 {+-} 0.027 for NGC 460. These values of t{sup 2} imply that when gaseous abundances are determined with collisionally excited lines they are underestimated by a factor of nearly two. From these objects and others in the literature, we find that in order to account for thermal inhomogeneities and dust depletion, the O/H ratio in low-metallicity H II regions should be corrected by 0.25-0.45 dex depending on the thermal structure of the nebula or by 0.35 dex if such information is not available.

79 ASTRONOMY AND ASTROPHYSICS↗

THE PROPERTIES OF THE 2175 A EXTINCTION FEATURE DISCOVERED IN GRB AFTERGLOWS

The unequivocal, spectroscopic detection of the 2175 A bump in extinction curves outside the Local Group is rare. To date, the properties of the bump have been examined in only two gamma-ray burst (GRB) afterglows (GRB 070802 and GRB 080607). In this work, we analyze in detail the detections of the 2175 Angstrom-Sign extinction bump in the optical spectra of two further GRB afterglows: GRB 080605 and 080805. We gather all available optical/near-infrared photometric, spectroscopic, and X-ray data to construct multi-epoch spectral energy distributions (SEDs) for both GRB afterglows. We fit the SEDs with the Fitzpatrick and Massa model with a single or broken power law. We also fit a sample of 38 GRB afterglows, known to prefer a Small Magellanic Cloud (SMC)-type extinction curve, with the same model. We find that the SEDs of GRB 080605 and GRB 080805 at two epochs are fit well with a single power law with a derived extinction of A{sub V} = 0.52{sup +0.13}{sub -0.16} and 0.50{sup +0.13}{sub -0.10}, and 2.1{sup +0.7}{sub -0.6} and 1.5 {+-} 0.2, respectively. While the slope of the extinction curve of GRB 080805 is not well constrained, the extinction curve of GRB 080605 has an unusual very steep far-UV rise together with the 2175 A bump. Such an extinction curve has previously been found in only a small handful of sightlines in the Milky Way. One possible explanation of such an extinction curve may be dust arising from two different regions with two separate grain populations, however we cannot distinguish the origin of the curve. We finally compare the four 2175 A bump sightlines to the larger GRB afterglow sample and to Local Group sightlines. We find that while the width and central positions of the bumps are consistent with what is observed in the Local Group, the relative strength of the detected bump (A{sub bump}) for GRB afterglows is weaker for a given A{sub V} than for almost any Local Group sightline. Such dilution of the bump strength may offer tentative support to a dual dust-population scenario.

79 ASTRONOMY AND ASTROPHYSICS↗

ON THE EXCITATION AND FORMATION OF CIRCUMSTELLAR FULLERENES

We compare and analyze the Spitzer mid-infrared spectrum of three fullerene-rich planetary nebulae in the Milky Way and the Magellanic Clouds: Tc1, SMP SMC 16, and SMP LMC 56. The three planetary nebulae share many spectroscopic similarities. The strongest circumstellar emission bands correspond to the infrared active vibrational modes of the fullerene species C{sub 60} and little or no emission is present from polycyclic aromatic hydrocarbons. The strengths of the fullerene bands in the three planetary nebulae are very similar, while the ratios of the [Ne III]15.5 {mu}m/[Ne II]12.8 {mu}m fine structure lines, an indicator of the strength of the radiation field, are markedly different. This raises questions about their excitation mechanism and we compare the fullerene emission to fluorescent and thermal models. In addition, the spectra show other interesting and common features, most notably in the 6-9 {mu}m region, where a broad plateau with substructure dominates the emission. These features have previously been associated with mixtures of aromatic/aliphatic hydrocarbon solids. We hypothesize on the origin of this band, which is likely related to the fullerene formation mechanism, and compare it with modeled hydrogenated amorphous carbon that present emission in this region.

79 ASTRONOMY AND ASTROPHYSICS↗

A REST-FRAME OPTICAL VIEW ON z {approx} 4 GALAXIES. I. COLOR AND AGE DISTRIBUTIONS FROM DEEP IRAC PHOTOMETRY OF THE IUDF10 AND GOODS SURVEYS

We present a study of rest-frame UV-to-optical color distributions for z {approx} 4 galaxies based on the combination of deep HST/ACS+WFC3/IR data with Spitzer/IRAC imaging. In particular, we use new, ultra-deep data from the IRAC Ultradeep Field program (IUDF10), together with previous, public IRAC data over the GOODS fields. Our sample contains a total of {approx}2600 galaxies selected as B-dropout Lyman-break Galaxies in the HUDF and its deep parallel field HUDF09-2, as well as GOODS-North/South. This sample is used to investigate the UV continuum slopes {beta} and Balmer break colors (J{sub 125} - [4.5]) as a function of rest-frame optical luminosity (using [4.5] to avoid optical emission lines). We find that galaxies at M{sub z} < -21.5 (roughly corresponding to L{sup *}{sub z{approx}4}) are significantly redder than their lower luminosity counterparts. The UV continuum slopes and the J{sub 125} - [4.5] colors are well correlated, indicating that the dust reddening at these redshifts is better described by an SMC-like extinction curve, rather than the typically assumed Calzetti reddening. After dust correction, we find that the galaxy population shows mean stellar population ages in the range 10{sup 8.5} to 10{sup 9} yr, with a dispersion of {approx}0.5 dex, and only weak trends as a function of luminosity. Only a small fraction of galaxies shows Balmer break colors consistent with extremely young ages, younger than 100 Myr. Under the assumption of smooth star-formation histories, this fraction is 12%-19% for galaxies at M{sub z} < -19.75. Our results are consistent with a gradual build-up of stars and dust in galaxies at z > 4 with only a small fraction of stars being formed in short, intense bursts of star-formation.

79 ASTRONOMY AND ASTROPHYSICS↗

La Silla quest RR Lyrae star survey: Region I

A search for RR Lyrae stars (RRLSs) in ∼840 deg{sup 2} of the sky in right ascension 150°-210° and declination –10° to + 10° yielded 1013 type ab and 359 type c RRLS. This sample is used to study the density profile of the Galactic halo, halo substructures, and the Oosterhoff type of the halo over distances (d {sub ☉}) from ∼5 to ∼80 kpc. The halo is flattened toward the Galactic plane, and its density profile steepens in slope at galactocentric distances greater than ∼25 kpc. The RRLS in the stellar stream from the Sagittarius dwarf spheroidal (dSph) galaxy match well the model of Law and Majewski for the stars that were stripped 1.3-3.2 Gyr ago, but not for the ones stripped 3.2-5.0 Gyr ago. Over densities are found at the locations of the Virgo Overdensity and the Virgo Stellar Stream. Within 1° of 1220-1, which Jerjen et al. identify as a halo substructure at d {sub ☉} ∼ 24 kpc, there are four RRLS that are possibly members. Away from substructures, the RRLS are a mixture of Oosterhoff types I and II, but mostly OoI (∼73%). The accretion of galaxies resembling in RRLS content the most massive Milky Way satellites (LMC, SMC, For, Sgr) may explain this preponderance of OoI. Six new RRLS and three new anomalous Cepheids were found in the Sextans dSph galaxy.

79 ASTRONOMY AND ASTROPHYSICS↗

OGLE-ing the Magellanic system: stellar populations in the Magellanic Bridge

We report the discovery of a young stellar bridge that forms a continuous connection between the Magellanic Clouds. This finding is based on number density maps for stellar populations found in data gathered by OGLE-IV that fully cover over 270 deg{sup 2} of the sky in the Magellanic Bridge area. This is the most extensive optical survey of this region to date. We find that the young population is present mainly in the western half of the MBR, which, together with the newly discovered young population in the eastern Bridge, form a continuous stream of stars connecting both galaxies along δ ∼ –73.5 deg. The young population distribution is clumped, with one of the major densities close to the SMC and the other fairly isolated and located approximately mid-way between the Clouds, which we call the OGLE island. These overdensities are well matched by H I surface density contours, although the newly found young population in the eastern Bridge is offset by ∼2 deg north from the highest H I density contour. We observe a continuity of red clump stars between the Magellanic Clouds which represent an intermediate-age population. Red clump stars are present mainly in the southern and central parts of the Magellanic Bridge, below its gaseous part, and their presence is reflected by a strong deviation from the radial density profiles of the two galaxies. This may indicate either a tidal stream of stars, or that the stellar halos of the two galaxies overlap. On the other hand, we do not observe such an overlap within an intermediate-age population represented by the top of the red giant branch and the asymptotic giant branch stars. We also see only minor mixing of the old populations of the Clouds in the southern part of the Bridge, represented by the lowest part of the red giant branch.

79 ASTRONOMY AND ASTROPHYSICS↗

THE NATURE OF DAMPED LYMAN-α AND Mg II ABSORBERS EXPLORED THROUGH THEIR DUST CONTENTS

We estimate the abundance of dust in damped Lyman-α absorbers (DLAs) by statistically measuring the excess reddening they induce on their background quasars. We detect systematic reddening behind DLAs consistent with the SMC-type reddening curve and inconsistent with the Milky Way type. We find that the derived dust-to-gas ratio is, on average, inversely proportional to the column density of neutral hydrogen, implying that the amount of dust is constant, regardless of the column density of hydrogen. It means that the average metallicity is inversely proportional to the column density of hydrogen, unless the average dust-to-metal ratio varies with the hydrogen column density. This indicates that the prime origin of metals seen in DLAs is not by in situ star formation, with which Z∼N{sub H} {sub I}{sup +0.4} is expected from the empirical star formation law, contrary to our observation. We interpret the metals observed in absorbers to be deposited dominantly from nearby galaxies by galactic winds ubiquitous in intergalactic space. When extrapolating the relation between dust-to-gas ratio and H I column density to lower column density, we find a value that is consistent with what is observed for Mg II absorbers.

79 ASTRONOMY AND ASTROPHYSICS↗