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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’.
Parkinson's disease (PD) is characterized by proteinaceous aggregates named Lewy Bodies and Lewy Neurites containing α-synuclein fibrils. The underlying aggregation mechanism of this protein is dominated by a secondary process at mildly acidic pH, as in endosomes and other organelles. This effect manifests as a strong acceleration of the aggregation in the presence of seeds and a weak dependence of the aggregation rate on monomer concentration. The molecular mechanism underlying this process could be nucleation of monomers on fibril surfaces or fibril fragmentation. Here, we aim to distinguish between these mechanisms. The nature of the secondary processes was investigated using differential sedimentation analysis, trap and seed experiments, quartz crystal microbalance experiments and super-resolution microscopy. The results identify secondary nucleation of monomers on the fibril surface as the dominant secondary process leading to rapid generation of new aggregates, while no significant contribution from fragmentation was found. The newly generated oligomeric species quickly elongate to further serve as templates for secondary nucleation and this may have important implications in the spreading of PD.
At the centre of the Parkes 64—m radio telescope a region of diameter 17 m has recently been resurfaced to improve its efficiency at high frequencies. The first measurements using this section have been made at 22 GHz, in observations of both continuum sources and water tfapour masers. For these observations the receiver front-end used a mixer cooled in liquid nitrogen, followed by a 5 GHz cryogenic parametric amplifier as a second stage. The option of switching against an offset horn was available and the total system
noise temperature was ∽ 750 K.
The results of 1959-1960 radar measurements of the distance of the Moon are given. The method of reduction of the data is described The possible effects of lunar topography and errors of other origins are discussed, as well as the effects of different constants such as the radii of the Earth and of the Moon.
A study was conducted on a GA(W)-1 wing in order to investigate the effect of testing inverted wings in ground effect at low Reynolds numbers. The wing was tested at a range of ground clearances and Reynolds numbers and results showed that the wing’s performance was dependent on both these parameters. Surface flow-visualisation and numerical simulation results highlighted the existence of a laminar separation bubble on the wing’s suction surface. The results also indicated that both the bubble’s length and the onset of separation were sensitive to ground clearance and Reynolds number. Attempts were made to minimise the wing’s Reynolds number dependency by using transition strips on the suction surface. The transition strip results highlighted the influence that a laminar separation bubble has on the overall performance of the wing and how its presence alters the force enhancement and reduction mechanisms on an inverted wing in ground effect.
An experimental study incorporating the use of the Background-Oriented Schlieren (BOS) technique was performed to measure the density field of a rectangular supersonic jet. This technique is easier to set up than conventional schlieren since the optical alignment involving the various mirrors, lenses and knife-edge is replaced by a background pattern and a single digital camera. The acquired images which contain information of density gradients in the flow are solved as a Poisson equation and further processed using deconvolution and tomographic algorithms to generate a 3D domain which contains information about the actual density. 2D slices can then be extracted to quantitatively visualise the density along any required planes. The results from supersonic axisymmetric jets are used for validation of the code; these show excellent agreement with pre-validated CFD data. The results for a rectangular supersonic jet are then obtained. These show good agreement with the CFD data, in terms of shock-cell spacing and overall structure of the jet. The technique has proved useful for investigating axis-switching, a phenomenon generally associated with non-axisymmetric jets.
This paper presents an experimental investigation of the evolution of the leading-edge vortex and spanwise flow generated by an insect-like flapping-wing at a Reynolds number relevant to flapping-wing micro air vehicles (FMAVs) (Re = ~15,000). Experiments were accomplished with a first-of-its-kind flapping-wing apparatus. Dense pseudo-volumetric particle image velocimetry (PIV) measurements from 18% – 117% span were taken at 12 azimuthal positions throughout a flapping half cycle. Results revealed the formation of a primary leading-edge vortex (LEV) which saw an increase in size and spanwise flow (towards the tip) through its core as the wing swept from rest to the mid-stroke position where signs of vortex breakdown were observed. Beyond mid-stroke, spanwise flow decreased and the tip vortex grew in size and exhibited a reversal in its axial direction. At the end of the flapping half cycle, the primary LEV was still present over the wing surface, suggesting that the LEV remains attached to the wing throughout the entire flapping half cycle.
In a cross-sectional study, data from records of cattle slaughtered over a 1-year period at a large abattoir in South West England were analysed using an ordered category response model to investigate the inter-relationships between age, sex and breed on development of the permanent anterior (PA) teeth. Using the model, transition points at which there was a 50% probability of membership of each category of paired PA teeth were identified. Data from ∼60 000 animals were initially analysed for age and sex effect. The age transition was found to be ∼23 months moving from zero to two teeth; 30 months for two to four teeth; 37 months for four to six teeth and 42 months for six to eight teeth. Males were found to develop, on average, ∼22 days earlier than females across all stages. A reduced data set of ∼23 000 animals registered as pure-bred only was used to compare breed and type interactions and to investigate sex effects within the sub-categories. Breeds were grouped into dairy and beef-type and beef breeds split into native and continental. It was found that dairy-types moved through the transition points earlier than beef-types across all stages (interval varying between ∼8 and 12 weeks) and that collectively, native beef breeds moved through the transition points by up to 3 weeks earlier than the continental beef breeds. Interestingly, in contrast to beef animals, dairy females matured before dairy males. However, the magnitude of the difference between dairy females and males diminished at the later stages of development. Differences were found between breeds. Across the first three stages, Ayrshires and Guernseys developed between 3 and 6 weeks later than Friesian/Holsteins and Simmental, Limousin and Blonde Aquitaine 6 and 8 weeks later than Aberdeen Angus. Herefords, Charolais and South Devon developed later but by a smaller interval and Red Devon and Galloway showed the largest individual effect with transition delayed by 8 to 12 weeks.
In this paper, flow control effectiveness of a passive device in relation to open cavity flowfield is investigated computationally and compared with experimental work. Specifically the modification in the cavity flowfield due to the presence of a spoiler is studied in details to explain the physics behind the flow control effects. A combination of 2D and 3D flow visualisation tools are used to understand the flow behaviour inside the cavity and the quantitative analysis of the unsteady pressure fluctuations is also performed to assess the unsteady effects. Flow simulations with a turbulence model based on a hybrid RANS/LES (commonly known as Detached-Eddy Simulation (DES)) are used in this study. The time-mean flow visualisation clearly showed the presence of three dimensional effects inside the empty cavity whereas the 3D effects were found to diminish in the presence of a spoiler. In the unsteady flow analysis, near-field acoustic spectra were computed for empty cavity as well as cavity-with-spoiler cases. Study of unsteady pressure spectra for the cavity-with-spoiler case was found to record the complete suppression of the dominant tones in the presence of the spoiler. The analysis has indicated that the main reason behind this suppression is due to the inability of faintly energised vortical structures (faintly energised as a result of the extraction of turbulent kinetic energy by the spoiler) to maintain the unsteady flapping of the separated shear layer.
In this paper, the results of computational studies on the unsteady flow features in three-dimensional empty cavities and cavities with a representative store are presented. Flow simulations with a turbulence model based on a hybrid method, which behaves as a standard Reynolds-averaged Navier-Stokes (RANS) model within the attached boundary layer and as a Large-Eddy Simulation LES sub-grid scale model in the rest of the flow (commonly known as Detached-Eddy Simulation (DES)) are used in this study. The time-mean flow study showed the presence of three-dimensional effects inside the cavities. The mean flowfield visualisation also clearly showed the presence of a pair of ‘tornado-like’ vortices in the upstream half of the cavity which merge to a single, large recirculation further downstream. Visualisation for the cavity-with-store case revealed that the mean flowfield was effectively divided into two halves with significant reduction of the spanwise flow across the cavity width. In the unsteady flow study, near-field acoustic spectra were computed for the empty cavity and cavity-with-store cases. Study of unsteady pressure spectra for the cavity-with-store case found the presence of many peaks and the corresponding mode frequencies were found to agree well with the Rossiter modes. The blockage effect of store and strut on the spanwise flow is thought to have reduced the interaction, and subsequent non-linear coupling, between the Rossiter modes. This may be the reason for the co-existence of multiple modes without the coupling among them.
Experts have proposed removing obsessive–compulsive disorder (OCD) from the anxiety disorders section and grouping it with putatively related conditions in DSM-5. The current study uses co-morbidity and familiality data to inform these issues.
Case family data from the OCD Collaborative Genetics Study (382 OCD-affected probands and 974 of their first-degree relatives) were compared with control family data from the Johns Hopkins OCD Family Study (73 non-OCD-affected probands and 233 of their first-degree relatives).
Anxiety disorders (especially agoraphobia and generalized anxiety disorder), cluster C personality disorders (especially obsessive–compulsive and avoidant), tic disorders, somatoform disorders (hypochondriasis and body dysmorphic disorder), grooming disorders (especially trichotillomania and pathological skin picking) and mood disorders (especially unipolar depressive disorders) were more common in case than control probands; however, the prevalences of eating disorders (anorexia and bulimia nervosa), other impulse-control disorders (pathological gambling, pyromania, kleptomania) and substance dependence (alcohol or drug) did not differ between the groups. The same general pattern was evident in relatives of case versus control probands. Results in relatives did not differ markedly when adjusted for demographic variables and proband diagnosis of the same disorder, though the strength of associations was lower when adjusted for OCD in relatives. Nevertheless, several anxiety, depressive and putative OCD-related conditions remained significantly more common in case than control relatives when adjusting for all of these variables simultaneously.
On the basis of co-morbidity and familiality, OCD appears related both to anxiety disorders and to some conditions currently classified in other sections of DSM-IV.
Phase contrast techniques in the transmission electron microscope are used to measure directly the electrostatic potentials at θ = 24°  symmetrical tilt grain boundaries in both undoped and Nb-doped SrTiO3 bicrystals. The boundaries are all found to have significantly lower scattering potentials than the surrounding bulk material. The depths and the shapes of the potential wells at the boundaries are discussed in the light of both theoretical models of the grain boundary chemistry of pure and doped strontium titanate and other experimental data that we have acquired on these boundaries from high resolution transmission electron microscopy, diffuse dark field imaging, energy dispersive X-ray spectroscopy and electron energy loss spectroscopy.
The aerodynamics of insect-like flapping are dominated by the production of a large, stable, and lift-enhancing leading-edge vortex (LEV) above the wing. In this paper the phenomenology behind the LEV is explored, the reasons for its stability are investigated, and the effects on the LEV of changing Reynolds number or angle-of-attack are studied. A predominantly-computational method has been used, validated against both existing and new experimental data. It is concluded that the LEV is stable over the entire range of Reynolds numbers investigated here and that changes in angle-of-attack do not affect the LEV’s stability. The primary motivation of the current work is to ascertain whether insect-like flapping can be successfully ‘scaled up’ to produce a flapping-wing micro air vehicle (FMAV) and the results presented here suggest that this should be the case.
The interaction of multiple jets with the ground is of great importance for the design and operation of short take-off, vertical landing aircraft. The fountain upwash flow, generated by the impingement of two axisymmetric, compressible, turbulent jets onto a ground plane was studied using laser-based particle image velocimetry and laser Doppler velocimetry. Measurements were made with nozzle pressure ratios of between 1·05 and 4, nozzle height-to-diameter ratios of between 2·4 and 8·4, nozzle splay angles of between ±15 degrees and a nozzle spacing-to-diameter ratio of seven. The effect of varying these parameters on the fountain velocity decay, spreading rate and momentum flux ratio are discussed. Mean fountain upwash velocity profiles were found to be self-similar for all test conditions. A distinct frequency of fountain oscillation was identified but only at a nozzle height of 4·4 diameters.
Obsessive–compulsive disorder (OCD) is probably an etiologically heterogeneous condition. Many patients manifest other psychiatric syndromes. This study investigated the relationship between OCD and co-morbid conditions to identify subtypes.
Seven hundred and six individuals with OCD were assessed in the OCD Collaborative Genetics Study (OCGS). Multi-level latent class analysis was conducted based on the presence of eight co-morbid psychiatric conditions [generalized anxiety disorder (GAD), major depression, panic disorder (PD), separation anxiety disorder (SAD), tics, mania, somatization disorders (Som) and grooming disorders (GrD)]. The relationship of the derived classes to specific clinical characteristics was investigated.
Two and three classes of OCD syndromes emerge from the analyses. The two-class solution describes lesser and greater co-morbidity classes and the more descriptive three-class solution is characterized by: (1) an OCD simplex class, in which major depressive disorder (MDD) is the most frequent additional disorder; (2) an OCD co-morbid tic-related class, in which tics are prominent and affective syndromes are considerably rarer; and (3) an OCD co-morbid affective-related class in which PD and affective syndromes are highly represented. The OCD co-morbid tic-related class is predominantly male and characterized by high conscientiousness. The OCD co-morbid affective-related class is predominantly female, has a young age at onset, obsessive–compulsive personality disorder (OCPD) features, high scores on the ‘taboo’ factor of OCD symptoms, and low conscientiousness.
OCD can be classified into three classes based on co-morbidity. Membership within a class is differentially associated with other clinical characteristics. These classes, if replicated, should have important implications for research and clinical endeavors.
In the present chapter we study the equilibrium and quasistatic response of a thin bar composed of a material modeled by the stress–strain curve shown in Figure 2.2 of the preceding chapter. There is an extensive experimental literature devoted to tensile loading and unloading of bars made of materials that are capable of undergoing displacive phase transitions; often the materials studied are technologically important shape-memory alloys such as nickel–titanium. For a small sample of this literature, the reader might consult the papers of Krishnan and Brown , Nakanishi , Shaw and Kyriakides , and Lin et al. , as well as the references cited there. The loading in such experiments is slow, in the sense that inertia is insignificant. The objective is typically the determination of the relation between the applied stress and the overall elongation of the bar, though in some studies, such as that of Shaw and Kyriakides , local strain and temperature measurements are made as well. The stress–elongation relation that is observed in such experiments exhibits hysteresis, the phase transition being the primary mechanism responsible for such dissipative behavior. For a given material, the size and other qualitative features of the hysteresis loops depend on the loading rate and the temperature at which the test takes place. In the model to be discussed in this chapter, thermal effects are omitted; they will be accounted for in later chapters.