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Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
The longstanding association between the major histocompatibility complex (MHC) locus and schizophrenia (SZ) risk has recently been accounted for, partially, by structural variation at the complement component 4 (C4) gene. This structural variation generates varying levels of C4 RNA expression, and genetic information from the MHC region can now be used to predict C4 RNA expression in the brain. Increased predicted C4A RNA expression is associated with the risk of SZ, and C4 is reported to influence synaptic pruning in animal models.
Based on our previous studies associating MHC SZ risk variants with poorer memory performance, we tested whether increased predicted C4A RNA expression was associated with reduced memory function in a large (n = 1238) dataset of psychosis cases and healthy participants, and with altered task-dependent cortical activation in a subset of these samples.
We observed that increased predicted C4A RNA expression predicted poorer performance on measures of memory recall (p = 0.016, corrected). Furthermore, in healthy participants, we found that increased predicted C4A RNA expression was associated with a pattern of reduced cortical activity in middle temporal cortex during a measure of visual processing (p < 0.05, corrected).
These data suggest that the effects of C4 on cognition were observable at both a cortical and behavioural level, and may represent one mechanism by which illness risk is mediated. As such, deficits in learning and memory may represent a therapeutic target for new molecular developments aimed at altering C4’s developmental role.
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.
Functional neurological disorders (FNDs), also known as conversion disorder, are unexplained neurological symptoms unrelated to a neurological cause. The disorder is common, yet poorly understood. The symptoms are experienced as involuntary but have similarities to voluntary processes. Here we studied intention awareness in FND.
A total of 26 FND patients and 25 healthy volunteers participated in this functional magnetic resonance study using Libet's clock.
FND is characterized by delayed awareness of the intention to move relative to the movement itself. The reporting of intention was more precise, suggesting that these findings are reliable and unrelated to non-specific attentional deficits. That these findings were more prominent with aberrant positive functional movement symptoms rather than negative symptoms may be relevant to impairments in timing for an inhibitory veto process. Attention towards intention relative to movement was associated with lower right inferior parietal cortex activity in FND, a region early in the processing of intention. During rest, aberrant functional connectivity was observed with the right inferior parietal cortex and other motor intention regions.
The results converge with observations of low inferior parietal activity comparing involuntary with voluntary movement in FND, emphasizing core deficiencies in intention. Heightened precision of this impaired intention is consistent with Bayesian theories of impaired top-down priors that might influence the sense of involuntariness. A primary impairment in voluntary motor intention at an early processing stage might explain clinical observations of slowed effortful voluntary movement, heightened self-directed attention and underlie functional movements. These findings further suggest novel therapeutic targets.
In general, observationally derived wind compositions of WR stars are in reasonable agreement with predictions from stellar evolution models for massive stars. However, Barlow et al. (1988) identified a major discrepancy for neon in γ2 Vel (WC8+O) using ground-based observations. The advent of the ESA Infrared Space Observatory (ISO) has allowed the study of neon in many more WC stars, using mid-IR fine structure lines ([Ne II] 12.81 μm, [NeIII] 15.55μm and [NEV] 14.32 μm). Willis et al. (1998) used ISO-SWS observations of WR 146 (WC5+O) to derive a neon abundance that was within the range expected theoretically. Here we undertake a study of WR 90 (HD 156385), the only (apparently) single WC7 star in our Galaxy, using ISO-SWS spectroscopy. The only spectroscopic neon feature in the mid-IR of WR 90 is [Ne III] 15.55 μm, in addition to numerous C IV and He II transitions (see Figure 1).
A K-band (18-25 GHz) reflected-wave ruby maser (Moore and Clauss 1979) has been borrowed from the National Radio Astronomy Observatory for radio astronomy use on the NASA 64-m antenna of the Deep Space Network at the Tidbinbilla Tracking Station, near Canberra. The purpose of the installation is to provide additional sensitive spectral line, continuum, and VLBI capabilities in the southern hemisphere. Previous measurements at 22.3 GHz (λ = 13.5 mm) determined that the Tidbinbilla 64-m antenna has a peak aperture efficiency of ˜22%, a well-behaved beam shape and consistent pointing (Fourikis and Jauncey 1979). Before installing the maser on the antenna a cooled (circulator) switch was added to provide a beam-switching capability, and a spectral line receiver following the maser was incorporated. The system was assembled and tested at JPL in late 1980 and installed at Tidbinbilla early in 1981. We give here a brief description and present some of the first line observations made in February and March 1981. Extensive line and continuum observations are planned with the present system and a program is under way to determine the telescope pointing characteristics.
We have recently shown how capture-recapture models can be used in conjunction with stratigraphic range data to estimate taxonomic extinction rates and taxonomic diversity. Here we present a new method that can be used to estimate taxonomic turnover (defined here as the proportion of taxa extant at time i, that originated in the interval i – 1 to i). We used these methods in conjunction with stratigraphic range data for families in five phyla of Paleozoic marine invertebrates. We estimated fossil encounter probabilities, extinction rates, diversity, and turnover and used these estimates to test hypotheses about variation among phyla and geologic series. Encounter probabilities varied among taxa and showed evidence of a decrease over time for the geologic series examined. The number of families varied substantially among the five phyla and showed some evidence of an increase over the series examined. There was no evidence of variation in extinction probabilities among the phyla. Although there was evidence of temporal variation in extinction probabilities within phyla, there was no evidence of a linear decrease in extinction probabilities over time, as has been reported by others. We did find evidence of high extinction probabilities for the two intervals that had been identified by others as periods of mass extinction. We found no evidence of variation in turnover among the five phyla. There was evidence of temporal variation in turnover, with greater turnover occurring in the older series.
The present study explores the burning of microscale porous silicon channels with sodium perchlorate. These on-chip porous silicon energetics were embedded in crystalline silicon, and therefore surrounded on three sides by an efficient thermal conductor. For slow burning systems, this presents complications as heat loss to the crystalline silicon substrate can result in inconsistent burning or flame extinction. We investigated <100 μm wide porous silicon strips, sparsely filled with sodium perchlorate (NaClO4), to probe the limits of on-chip combustion. Four different etch times were attempted to decrease the dimensions of the porous silicon strips. The smallest size achieved was 12 x 64 µm, and despite the small dimensions, demonstrated the same flame speed as the larger porous silicon strips of 6-7 m/s. We predict that unreacted porous silicon acts as a thermal insulator to aid combustion for slow burning porous silicon channels, and SEM images provide evidence to support this. We also investigated the small scale combustion of a rapidly burning sample (∼1200 m/s). Despite the rapid flame speed, the propagation followed a designed, winding flame path. The use of these small scale porous silicon samples could significantly reduce the energetic material footprint for future microscale applications.
We present the first quantitative assessment of combustion dynamics of on-chip porous silicon (PS) energetic material using sulfur and nitrate-based oxidizers with potential for improved moisture stability and/or minimized environmental impact compared to sodium perchlorate (NaClO4). Material properties of the PS films were characterized using gas adsorption porosimetry, and profilometry to calculate specific surface area, porosity and etch depth. The PS/sulfur energetic composite was formed using three pore loading techniques, where the combustion speeds ranged from 2.9 – 290 m/s. The nitrate-based oxidizers were solution-deposited using different compatible solvents, and depending on the metal-nitrate yielded combustion speeds of 3.1 – 21 m/s. Additionally, the combustion enthalpies from bomb calorimetry experiments are reported for the alternative PS/oxidizer systems in both nitrogen and oxygen environments.
Iron oxides resulting from the corrosion of large quantities of steel that are planned to be installed throughout a deep geological disposal facility (GDF) are expected to be one of the key surfaces of interest for controlling radionuclide behaviour under disposal conditions. Over the lengthy timescales associated with a GDF, the system is expected to become anoxic so that reduced Fe(II) phases will dominate. Batch experiments have therefore been completed in order to investigate how a model reduced Fe-oxide surface (wüstite, Fe1–xO) alters as a function of exposure to aqueous solutions with compositions representative of conditions expected within a GDF. Additional experiments were performed to constrain the effect that highly alkaline solutions (up to pH 13) have on the adsorption behaviour of the uranyl (UO22+) ion onto the surfaces of both wüstite and portlandite [Ca(OH)2; representative of the expected cementitious phases]. Surface co-ordination chemistry and speciation were determined by ex situ X-ray absorption spectroscopy measurements (both X-ray absorption near-edge structure analysis (XANES) and extended X-ray absorption fine structure analysis (EXAFS)). Diffraction, elemental analysis and XANES showed that the bulk solid composition and Fe oxidation state remained relatively unaltered over the time frame of these experiments (120 h), although under alkaline conditions possible surface hydroxylation is observed, due presumably to the formation of surface hydroxyl complexes. The surface morphology, however, is altered significantly with a large degree of roughening and an observed decrease in the average particle size. Reduction of U(VI) to U(IV) occurs during adsorption in almost all cases and this is interpreted to indicate that wüstite may be an effective reductant of U during surface adsorption. This work also shows that increasing the carbonate concentration in reactant solutions dramatically decreases the adsorption coefficients for U on both wüstite and portlandite, consistent with U speciation and surface reactivity determined in other studies. Finally, the EXAFS results include new details about exactly how U bonds to this metal oxide surface.
We performed a study to determine rates of reinfection in three groups followed for 2 years after successful treatment: American Indian/Alaska Native (AI/AN) persons living in urban (group 1) and rural (group 2) communities, and urban Alaska non-Native persons (group 3). We enrolled adults diagnosed with H. pylori infection based on a positive urea breath test (13C-UBT). After successful treatment was documented at 2 months, we tested each patient by 13C-UBT at 4, 6, 12 and 24 months. At each visit, participants were asked about medication use, illnesses and risk factors for reinfection. We followed 229 persons for 2 years or until they became reinfected. H. pylori reinfection occurred in 36 persons; cumulative reinfection rates were 14·5%, 22·1%, and 12·0% for groups 1, 2, and 3, respectively. Study participants who became reinfected were more likely to have peptic ulcer disease (P = 0·02), low education level (P = 0·04), or have a higher proportion of household members infected with H. pylori compared to participants who did not become reinfected (P = 0·03). Among all three groups, reinfection occurred at rates higher than those reported for other US populations (<5% at 2 years); rural AI/AN individuals appear to be at highest risk for reinfection.
Polarimetry of the far infrared emission from magnetically-aligned interstellar grains is one of the best ways of studying the magnetic field at the Galactic center. We describe the HAWC+ instrument, under development for flight on SOFIA starting in 2015, which will provide a major advance in capability for these critically important measurements.
We present experimental results supporting physics-based ejecta model development, where our main assumption is that ejecta form as a special limiting case of a Richtmyer–Meshkov (RM) instability at a metal–vacuum interface. From this assumption, we test established theory of unstable spike and bubble growth rates, rates that link to the wavelength and amplitudes of surface perturbations. We evaluate the rate theory through novel application of modern laser Doppler velocimetry (LDV) techniques, where we coincidentally measure bubble and spike velocities from explosively shocked solid and liquid metals with a single LDV probe. We also explore the relationship of ejecta formation from a solid material to the plastic flow stress it experiences at high-strain rates () and high strains (700 %) as the fundamental link to the onset of ejecta formation. Our experimental observations allow us to approximate the strength of Cu at high strains and strain rates, revealing a unique diagnostic method for use at these extreme conditions.
Evidence has accumulated over the past twenty years to suggest that the deep-sea environment is not as constant as was at one time thought, but exhibits temporal variations related to the seasonally in the overlying surface waters. Recent results from deep-moored sediment traps suggest that this coupling is mediated through the sedimentation of organic material, while observations in the Porcupine Seabight indicate that in this region, at least, there is a major and rapid seasonal deposition of aggregated phytodetritus to the sea-floor at slope and abyssal depths.
This paper summarises the results of the Porcupine Seabight studies over the past five years or so, using time-lapse sea-bed photography and microscopic, microbiological and chemical analyses of samples of phytodetritus and of the underlying sediment. The data are to some extent equivocal, but they suggest that the seasonal deposition is a regular and dramatic phenomenon and that the material undergoes relatively little degradation during its passage through the water column. The mechanisms leading to the aggregation of the phytodetritus have not been identified, and it is not yet known whether the phenomenon is geographically widespread nor whether it is of significance to the deep-living mid-water and benthic communities.
A micro (∼1 cm3) dynamic heat engine, capable of producing electrical power from lowgrade heat sources, utilizes a micro-machined diaphragm with a piezoelectric element as a The electromechanical coupling of a piezoelectric diaphragm under large initial stresses and/or large deflections – in the membrane limit – is described here. A simple model is derived for electromechanical transduction of a pressurized piezoelectric membrane and an experiment is described to measure it. Electromechanical coupling initially increases as the square of the center-point deflection as the residual stress is overcome. In the limit of large pressures, the electromechanical coupling approaches a limit that is predicted by the model.
The lifetime of non-compliant eutectic solder joints was improved by an order magnitude by rapid quenching. The quenching produces a fine equiaxed superplastic grain structure which lowers the stresses in the solder joints for the fatigue cycle strain range. Similarly, compliant J Bend and Gull wing joints, which last thousands of cycles, operate at lower stresses where superplastic deformation predominates.