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Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.
AFM-based nanoelectrical modes have numerous
applications in fields ranging from semiconductors
to biology. The data produced have traditionally
been in the form of a 2D map, generated in contact
mode, with a single electrical data point per
XY location. Electrical ramps
or spectra would be generated at a few, carefully
selected locations. This article discusses a new
approach to nanoelectrical imaging that creates an
electrical data cube and a correlated nanomechanical
data cube while operating at normal imaging speeds.
This approach avoids contact mode imaging, thus
extending electrical measurements to soft and
fragile samples and improving measurement
consistency. Moreover, this is a general approach
that is applicable to most nanoelectrical modes and
From a 45ks Chandra observation of V42G Oph we have obtained high-resolution X-ray spectra at moderate signal-to-noise, and a, good quality, uninterrupted lightcurve. The spectra are reasonably fit with a cooling flow model, similar to EX Hya and U Gem. Our analysis of the Chandra and additional X-ray/optical lightcurves reveals a persistent modulation at 4.2 hr from 1988 to 2003, likely the white dwarf spin period indicating an intermediate polar nature for V426 Oph.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
The Taipan galaxy survey (hereafter simply ‘Taipan’) is a multi-object spectroscopic survey starting in 2017 that will cover 2π steradians over the southern sky (δ ≲ 10°, |b| ≳ 10°), and obtain optical spectra for about two million galaxies out to z < 0.4. Taipan will use the newly refurbished 1.2-m UK Schmidt Telescope at Siding Spring Observatory with the new TAIPAN instrument, which includes an innovative ‘Starbugs’ positioning system capable of rapidly and simultaneously deploying up to 150 spectroscopic fibres (and up to 300 with a proposed upgrade) over the 6° diameter focal plane, and a purpose-built spectrograph operating in the range from 370 to 870 nm with resolving power R ≳ 2000. The main scientific goals of Taipan are (i) to measure the distance scale of the Universe (primarily governed by the local expansion rate, H0) to 1% precision, and the growth rate of structure to 5%; (ii) to make the most extensive map yet constructed of the total mass distribution and motions in the local Universe, using peculiar velocities based on improved Fundamental Plane distances, which will enable sensitive tests of gravitational physics; and (iii) to deliver a legacy sample of low-redshift galaxies as a unique laboratory for studying galaxy evolution as a function of dark matter halo and stellar mass and environment. The final survey, which will be completed within 5 yrs, will consist of a complete magnitude-limited sample (i ⩽ 17) of about 1.2 × 106 galaxies supplemented by an extension to higher redshifts and fainter magnitudes (i ⩽ 18.1) of a luminous red galaxy sample of about 0.8 × 106 galaxies. Observations and data processing will be carried out remotely and in a fully automated way, using a purpose-built automated ‘virtual observer’ software and an automated data reduction pipeline. The Taipan survey is deliberately designed to maximise its legacy value by complementing and enhancing current and planned surveys of the southern sky at wavelengths from the optical to the radio; it will become the primary redshift and optical spectroscopic reference catalogue for the local extragalactic Universe in the southern sky for the coming decade.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
Functional magnetic resonance imaging (fMRI) of multiple neural networks during the brain's ‘resting state’ could facilitate biomarker development in patients with Huntington's disease (HD) and may provide new insights into the relationship between neural dysfunction and clinical symptoms. To date, however, very few studies have examined the functional integrity of multiple resting state networks (RSNs) in manifest HD, and even less is known about whether concomitant brain atrophy affects neural activity in patients.
Using MRI, we investigated brain structure and RSN function in patients with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data a group-independent component analysis identified spatiotemporally distinct patterns of motor and prefrontal RSNs of interest. We used voxel-based morphometry to assess regional brain atrophy, and ‘biological parametric mapping’ analyses to investigate the impact of atrophy on neural activity.
Compared with controls, patients showed connectivity changes within distinct neural systems including lateral prefrontal, supplementary motor, thalamic, cingulate, temporal and parietal regions. In patients, supplementary motor area and cingulate cortex connectivity indices were associated with measures of motor function, whereas lateral prefrontal connectivity was associated with cognition.
This study provides evidence for aberrant connectivity of RSNs associated with motor function and cognition in early manifest HD when controlling for brain atrophy. This suggests clinically relevant changes of RSN activity in the presence of HD-associated cortical and subcortical structural abnormalities.
Major depressive disorder (MDD) is characterized by alterations in brain function that are identifiable also during the brain's ‘resting state’. One functional network that is disrupted in this disorder is the default mode network (DMN), a set of large-scale connected brain regions that oscillate with low-frequency fluctuations and are more active during rest relative to a goal-directed task. Recent studies support the idea that the DMN is not a unitary system, but rather is composed of smaller and distinct functional subsystems that interact with each other. The functional relevance of these subsystems in depression, however, is unclear.
Here, we investigated the functional connectivity of distinct DMN subsystems and their interplay in depression using resting-state functional magnetic resonance imaging.
We show that patients with MDD exhibit increased within-network connectivity in posterior, ventral and core DMN subsystems along with reduced interplay from the anterior to the ventral DMN subsystems.
These data suggest that MDD is characterized by alterations of subsystems within the DMN as well as of their interactions. Our findings highlight a critical role of DMN circuitry in the pathophysiology of MDD, thus suggesting these subsystems as potential therapeutic targets.
Depressive symptoms are prominent psychopathological features of Huntington's disease (HD), making a negative impact on social functioning and well-being.
We compared the frequencies of a history of depression, previous suicide attempts and current subthreshold depression between 61 early-stage HD participants and 40 matched controls. The HD group was then split based on the overall HD group's median Hospital Anxiety and Depression Scale-depression score into a group of 30 non-depressed participants (mean 0.8, s.d. = 0.7) and a group of 31 participants with subthreshold depressive symptoms (mean 7.3, s.d. = 3.5) to explore the neuroanatomy underlying subthreshold depressive symptoms in HD using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI).
Frequencies of history of depression, previous suicide attempts or current subthreshold depressive symptoms were higher in HD than in controls. The severity of current depressive symptoms was also higher in HD, but not associated with the severity of HD motor signs or disease burden. Compared with the non-depressed HD group DTI revealed lower fractional anisotropy (FA) values in the frontal cortex, anterior cingulate cortex, insula and cerebellum of the HD group with subthreshold depressive symptoms. In contrast, VBM measures were similar in both HD groups. A history of depression, the severity of HD motor signs or disease burden did not correlate with FA values of these regions.
Current subthreshold depressive symptoms in early HD are associated with microstructural changes – without concomitant brain volume loss – in brain regions known to be involved in major depressive disorder, but not those typically associated with HD pathology.
We propcoe a novel technique to convert polymer films into useful inorganic films by ion beam irradiation. Along the track of an ion the polymer is dissociated into smaller fragments. volatile fragments diffuse through the film and escape. Any element which is not removed in the form of volatile species is subsequently enriched with respect to the other elements. We demonstrate this effect in a polymer poly(dimethylsilylene-co-methylphenylsilylene), which initially has a C:Si ratio of 45:1. Upon irradiation with 2 MeV Ar+ ions at a dose of 1015 ions/cm2 the C:Si ratio changes to 3.4:1 as verified by Rutherford backscattering spectrometry. We believe that the effect of the ion beam irradiation is to produce more Si-C bonds at the expeme of the C-H and Si-Si bonds, with ≲10% of the original hydrogen being present in the film at high doses. The loss of the H atoms is further confirmed by a nuclear reaction technique. The IR spectra of the film as a function of the irradiation dose shows a progressive loss of fine molecular features with significant increase of the refractive index. The IR spectrum at the high doses appears to be due to a mixture of various Si and C bonds. However, the irradiated films are very hard and scratch resistant (knoop value ≳1300) suggesting an increase in the number of silicon carbide bonds
The energies of the Σ = 5, 13, and 17 (001) coincidentsite lattice (CSL) twist boundaries in Al containing small amounts of Zn solutes have been calculated using an iterative energy minimization technique in conjunction with interatomic potentials derived entirely from first principles. By determining both the energies of substitution in the bulk and in different sites in the boundary, the site selectivity for Zn segregation at the grain boundary has been investigated. In the lattice plane immediately near the grain boundary, Zn solutes were found to prefer the lower-symmetry non-coincidence sites while, in the next plane, substitution in the coincidence sites is preferred. The effect of Zn-Zn interactions has also been considered for small solute concentrations. It is found that the magnitude of the Zn-Zn interaction energy is remarkably insensitive to the particular sites occupied by the Zn atoms as well as the detailed geometry of the interface.
It is demonstrated that the most important geometrical parameter governing the identification of “special” interfaces is the interplanar spacing of the lattice planes parallel to the interfacial plane and not, as often assumed, the inverse density of coincident-site lattice points, Σ. A simple geometrical selection rule for the identification of “special” or “favored” boundaries is formulated on the basis of the interplanar lattice constant.
The properties encompassed by the family of complex metal oxides span the spectrum from superconductors to insulating ferroelectrics. Included in this family are the new colossal magnetoresistive perovskites with potential applications in advanced high density magnetic data storage devices based on single or multilayer thin films units of these materials fabricated by vapor phase deposition (PVD) methods. The realization of this potential requires solving basic thin film materials problems requiring understanding and controlling the growth of these materials. Toward this end, we have grown La0.7Ca0.3MnO3 and La0.7Sr0.3MnO3 on LaAlO3 single crystal substrates by pulsed laser and RF sputter deposition at temperatures from 500° C to 900° C and annealed at over 900° C for about 10 hours. The evolution of the microstructure of these films was studied by scanning probe microscopies and transmission electron microscopy (TEM).
The results of SPM characterization showed that at the lower end of the growth temperature range, the as-grown films were polygranular with grain size increasing with temperature. The 500° C as-grown films appeared to be amorphous while the 750° C film grains were layered with terrace steps often one unit cell high. In contrast, films grown at 900° C consisted of coalesced islands with some 3-D surface crystals. After annealing, all films had coalesced into very large extended layered islands. The change in microstructure was reflected in a decreased resistivity of coalesced films over their unannealed granular precursors. Previous reported work on the growth of La0.84 Sr0.16MnO3 and La0.8Sr0 2CoO3 grown demonstrated the sensitivity of the microstructure to substrate and deposition conditions. Films grown on an “accidental” vicinal surface grew by a step flow mechanism.
The macroscopic properties of many materials are controlled by the structure and chemistry at grain boundaries. A basic understanding of the structure-property relationship requires a technique which probes both composition and chemical bonding on an atomic scale. High-resolution Z-contrast imaging in the scanning transmission electron microscope (STEM) forms an incoherent image in which changes in atomic structure and composition across an interface can be interpreted directly without the need for preconceived atomic structure models (1). Since the Z-contrast image is formed by electrons scattered through high angles, parallel detection electron energy loss spectroscopy (PEELS) can be used simultaneously to provide complementary chemical information on an atomic scale (2). The fine structure in the PEEL spectra can be used to investigate the local electronic structure and the nature of the bonding across the interface (3). In this paper we use the complimentary techniques of high resolution Zcontrast imaging and PEELS to investigate the atomic structure and chemistry of a 25° symmetric tilt boundary in a bicrystal of the electroceramic SrTiO3.
Thin films of the orthorhombic perovskite GdAlO3 were grown on R-plane sapphire single crystals. Two different film growth methods were used, viz. (i) a chemical reaction of a Gd-O plasma with the sapphire crystals, and (ii) the reactive radio frequency (r.f.) sputtering of a GdAlO3 target. Subsequently, YBa2Cu3O7-δ (YBCO) films were deposited onto the GdAlO3 buffer by pulsed laser deposition (PLD). The GdAlO3 and YBCO films were investigated by Xray diffraction pole figure analysis and transmission electron microscopy (TEM), including highresolution transmission electron microscopy of cross sections. Independent of the deposition method the GdAlO3 films grew according to the nearly equivalent orientation relationships The GdAlO3 grains are additionally tilted by angles up to ± 3° around the sapphire [11.1] axis. On top of these buffer layers the YBCO films grew with c-orientation and with an in-plane rotation of 45°. YBCO films of 200 nm thickness on GdAlO3 buffer layers with a thickness of 10 to 20 nm showed a Tc > 87 K and a jc(77 K) > 3×106 A/cm2.
Epitaxial single layer (001) SrTiO3 films and an epitaxial Yba2Cu3O7-x/SrTiO3 multilayer were dc and rf sputtered on (110)rhombohedral LaAIO3 substrates. The microstructure of the films was characterised using transmission electron microscopy. The single layer SrTiO3 films exhibited different columnar morphologies. The column boundaries were due to the lattice mismatch between film and substrate. The boundaries were associated with interfacial dislocations at the film/substrate interface, where the dislocations relaxed the strain in the a, b plane. The columns consisted of individual subgrains. These subgrains were misoriented with respect to each other, with different in-plane orientations and different tilts of the (001) planes. The subgrain boundaries were antiphase or tilt boundaries.
The individual layers of the Yba2Cu3O7-x/SrTiO3 multilayer were relatively uniform. A distortion of the SrTiO3 unit cell of 0.9% in the ‘001’ direction and a Sr/Ti ratio of 0.62±0.04 was observed, both in correspondence with the single layer SrTiO3 films. Areas with different tilt of the (001)-planes were also present, within each individual SrTiO3 layer.
Studies performed by our group on orientation-microstructure-property relationships of Pb(ZrxTil1-x)O3 (PZT) / metal or metal-oxide layered heterostructure are reviewed. The work discussed is related to the synthesis and characterization of ferroelectric PZT and conductive Pt, RuO2, and Lao.5Sr0.5CoO3 layers and their integration into heterostructure capacitors suitable for non-volatile memories. The main objective of our research was to determine the influence of deposition techniques and their related parameters and layer processing on the orientation, microstructure, and properties of PZT-based capacitors, with the goal of controlling electrical properties such as polarization fatigue, retention, and imprint effects, in order to produce commercial non-volatile ferroelectric memories. The work discussed relates to the synthesis of films by ion beam sputter-deposition (IBSD), and pulsed laser ablation deposition (PLAD), where the heterostructures are grown in-situ without exposing the interfaces to uncontrollable atmospheric conditions. Comparisons are presented between orientation and microstructural characteristics and properties of PZT heterostructure capacitors produced by IBSD and PLAD and those synthesized by the sol-gel technique. The work reviewed indicates that substrate and template layers (at the ferroelectric/bottom electrode interface) and/or bottom electrode material type contribute to the control of orientation and/or microstructure, and properties of PZT-based capacitors.
Thin films (∼1000 Å) of LaxCa1−xMnOδ (x=0.67) were deposited onto LaA1O3 (100) substrates at of 600 and 700°C. Varying the oxygen deposition pressure between 15 and 400 mTorr systematically changed the oxygen concentrations in the as deposited films. Asdeposited films exhibited an orthorhombic structure with an oxygen pressure dependent lattice parameter. The films were highly oriented as characterized by narrow x-ray ω-scans (FWHM ≤ 0.16 −0.70°). At low pressures, the films were preferentially (202) oriented while at high pressures deposited films had a (040) preferred orientation. A 900°C anneal in flowing oxygen for a film deposited at low oxygen pressures resulted in a decrease in the lattice parameter (associated with an increase in δ) and a change in the preferred orientation from (202) to (040). The resistivity as a function of temperature (R(T)) showed a significant variation as a function of growth conditions. At 600°C, the peak in the resistivity curve (Tm) varied between 73 and 93 K for P(O2) = 15 to 400 mTorr, while at 700°C, Tm was ∼150 K. For films deposited at 600°C, the resistivity was reduced by a factor of 103 for H = 9T and Tm was shifted to 150 K. The activation energy associated with the semiconducting phase was approximately the same for all as-deposited films (∼100 meV).