Effect of varying internal geometry on the static performance of rectangular thrust-reverser ports

An investigation has been conducted to evaluate the effects of several geometric parameters on the internal performance of rectangular thrust-reverser ports for nonaxisymmetric nozzles. Internal geometry was varied with a test apparatus which simulated a forward-flight nozzle with a single, fully deployed reverser port. The test apparatus was designed to simulate thrust reversal (conceptually) either in the convergent section of the nozzle or in the constant-area duct just upstream of the nozzle. The main geometric parameters investigated were port angle, port corner radius, port location, and internal flow blocker angle. For all reverser port geometries, the port opening had an aspect ratio (throat width to throat height) of 6.1 and had a constant passage area from the geometric port throat to the exit. Reverser-port internal performance and thrust-vector angles computed from force-balance measurements are presented

Basins of attraction in nonsmooth models of gear rattle

This paper is concerned with the computation of the basins of attraction of a simple one degree-of-freedom backlash oscillator using cell-to-cell mapping techniques. This analysis is motivated by the modeling of order vibration in geared systems. We consider both a piecewise-linear stiffness model and a simpler infinite stiffness impacting limit. The basins reveal rich and delicate dynamics, and we analyze some of the transitions in the system's behavior in terms of smooth and discontinuity-induced bifurcations. The stretching and folding of phase space are illustrated via computations of the grazing curve, and its preimages, and manifold computations of basin boundaries using DsTool (Dynamical Systems Toolkit)

The role of the exit in the initial screening of investment opportunities: The case of business angel syndicate gatekeepers

The exit process has been largely ignored in business angel research.. The practitioner community identifies the difficulty in achieving exits as the most pressing problem for investors. This has been attributed to the failure of investors to adopt an exit-centric approach to investing. The validity of this claim is examined via a study of the investment approach of 21 ‘gatekeepers’ (managers) of angel groups in Scotland and Northern Ireland. Most gatekeepers say that they do consider the exit when they invest. However, this is contradicted by a verbal protocol analysis which indicates that the exit is not a significant consideration in their initial screening process. The small number of exits achieved by the groups is consistent with the general lack of an exit-centric approach to investing. Only three groups exhibit evidence of a strong exit-centric approach to investing. The lack of exits may have a negative impact on the level of future angel investment activity

Opinion Piece: The case for establishing a minimal medication alternative for psychosis and schizophrenia

The development of severe mental health conditions is strongly linked to our environments, particularly experiences of trauma and adversity. However treatments for severe mental health conditions are often primarily biomedical, centred around medication. For people diagnosed with schizophrenia or psychosis, this is antipsychotic medication. Although antipsychotics have been found to reduce symptoms and risk of relapse, some patients derive little benefit from these drugs, and they can lead to severe adverse effects. Subsequently, a high proportion of people do not want to take antipsychotics and request an alternative. Yet in the UK and in many countries there are currently no guidelines for stopping antipsychotics or formal treatment alternatives, despite such alternatives being available in some countries. For example, in Norway and Vermont (USA), in response to pressure from service user organisations, governments have mandated the establishment of “minimal medication” services. We examine whether everyone with a psychotic condition needs long-term antipsychotic treatment and evidence for alternative models of care. We recommend that healthcare providers should be encouraged to develop a psychosocial treatment package for people with psychosis or schizophrenia that provides a realistic possibility of minimising antipsychotic exposure

The effect of throat contouring on two-dimensional converging-diverging nozzles at static conditions

An experiment was conducted at static conditions to determine the internal performance effects of nozzle throat contouring, the result of increasing the circular-arc throat radius. Five nonaxisymmetric converging-diverging nozzles were tested at nozzle pressure ratios up to 9.0. Data are presented as internal thrust ratios, discharge coefficients, and static-pressure distributions. Comparisons of internal performance data for the five nozzles show that throat contouring increases the value of discharge coefficient but has no significant effect on internal thrust ratio except in cases of internal flow separation. To illustrate the use of the two dimensional converging-diverging (2-D C-D) nozzle data base, a two dimensional inviscid theory was applied to the five configurations. The generally good agreement of data with theoretical results indicates that two-dimensional inviscid theory can be successfully applied to the prediction of 2-D C-D nozzle internal flow

Predicting clinical diagnosis in Huntington's disease: An imaging polymarker

Objective Huntington's disease (HD) gene carriers can be identified before clinical diagnosis; however, statistical models for predicting when overt motor symptoms will manifest are too imprecise to be useful at the level of the individual. Perfecting this prediction is integral to the search for disease modifying therapies. This study aimed to identify an imaging marker capable of reliably predicting real‐life clinical diagnosis in HD. Method A multivariate machine learning approach was applied to resting‐state and structural magnetic resonance imaging scans from 19 premanifest HD gene carriers (preHD, 8 of whom developed clinical disease in the 5 years postscanning) and 21 healthy controls. A classification model was developed using cross‐group comparisons between preHD and controls, and within the preHD group in relation to “estimated” and “actual” proximity to disease onset. Imaging measures were modeled individually, and combined, and permutation modeling robustly tested classification accuracy. Results Classification performance for preHDs versus controls was greatest when all measures were combined. The resulting polymarker predicted converters with high accuracy, including those who were not expected to manifest in that time scale based on the currently adopted statistical models. Interpretation We propose that a holistic multivariate machine learning treatment of brain abnormalities in the premanifest phase can be used to accurately identify those patients within 5 years of developing motor features of HD, with implications for prognostication and preclinical trials

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

Narrative exposure therapy for survivors of human trafficking: feasibility randomised controlled trial

BACKGROUND: Human trafficking is a grave human rights violation and a major public health concern. Survivors present with high rates of mental health problems including post-traumatic stress disorder (PTSD). Studies of effective treatments for PTSD in survivors of human trafficking are lacking. Narrative exposure therapy (NET) is an effective PTSD treatment for multiple, prolonged and complex trauma, but its efficacy has not been rigorously tested in survivors of human trafficking. AIMS: To test the feasibility and acceptability of a randomised controlled trial (RCT) offering NET as a treatment for PTSD in trafficking survivors with a history of multiple traumatic events, as well as providing preliminary evidence regarding its efficacy (trial registration: ISRCTN95136302). METHOD: A single-blind RCT compared NET with a wait-list control in survivors of trafficking with PTSD (n = 25). In the NET arm of the study, participants attended a mean of 17 sessions. RESULTS: NET was well tolerated by participants. There were significant reductions in PTSD, depression and anxiety symptoms post-treatment in the NET group but no significant change in the wait-list group. CONCLUSIONS: The results indicate that NET is a promising and acceptable treatment for trafficking survivors. Psychological therapy in an RCT design can be safely delivered to this vulnerable group, although modifications are required to ensure their holistic needs are properly addressed

The Impact of Non-Equipartition on Cosmological Parameter Estimation from Sunyaev-Zel'dovich Surveys

The collisionless accretion shock at the outer boundary of a galaxy cluster should primarily heat the ions instead of electrons since they carry most of the kinetic energy of the infalling gas. Near the accretion shock, the density of the intracluster medium is very low and the Coulomb collisional timescale is longer than the accretion timescale. Electrons and ions may not achieve equipartition in these regions. Numerical simulations have shown that the Sunyaev-Zel'dovich observables (e.g., the integrated Comptonization parameter Y) for relaxed clusters can be biased by a few percent. The Y-mass relation can be biased if non-equipartition effects are not properly taken into account. Using a set of hydrodynamical simulations, we have calculated three potential systematic biases in the Y-mass relations introduced by non-equipartition effects during the cross-calibration or self-calibration when using the galaxy cluster abundance technique to constraint cosmological parameters. We then use a semi-analytic technique to estimate the non-equipartition effects on the distribution functions of Y (Y functions) determined from the extended Press-Schechter theory. Depending on the calibration method, we find that non-equipartition effects can induce systematic biases on the Y functions, and the values of the cosmological parameters Omega_8, sigma_8, and the dark energy equation of state parameter w can be biased by a few percent. In particular, non-equipartition effects can introduce an apparent evolution in w of a few percent in all of the systematic cases we considered. Techniques are suggested to take into account the non-equipartition effect empirically when using the cluster abundance technique to study precision cosmology. We conclude that systematic uncertainties in the Y-mass relation of even a few percent can introduce a comparable level of biases in cosmological parameter measurements.Comment: 10 pages, 3 figures, accepted for publication in the Astrophysical Journal, abstract abridged slightly. Typos corrected in version