Vortex shedding from tapered, triangular plates: taper and aspect ratio effects

Further experiments on features of the vortex shedding from tapered flat plates normal to an airstream are described. The work extends that of Castro and Rogers (2002) and concentrates on the study of the effects of varying the spanwise aspect ratio for a fixed shape plate, by appropriate adjustment of end-plates, and of the nature of the shedding as the degree of taper becomes very large, so that the body is more like a triangular plate—e.g. an isosceles triangle—than a slightly tapered plate. With the taper ratio TR defined as the ratio of plate length to average cross-stream width, the paper concentrates on the range 0.58<TR<60. Reynolds numbers, based on the average plate width, exceed 104. It is confirmed that for a small enough taper ratio the geometrical three-dimensionality is sufficiently strong that all signs of periodic vortex shedding cease. For all other cases, however, the flow at different locations along the span can vary substantially, depending on taper. There appear to be at least four different regimes, each appropriate for a different range of taper ratio. These various regimes are described

Understanding land administration systems

This is a preprint of a paper from 14th PCGIAP Meeting (International Seminar on Land Administration Trends & Issues in Asia & The Pacific Region), 19-20 August 2008. http://www.csdila.unimelb.edu.au/projects/PCGIAPLASeminar/index.html.19-20 August 200

Using the Delphi Technique to Determine Which Outcomes to Measure in Clinical Trials: Recommendations for the Future Based on a Systematic Review of Existing Studies

Ian Sinha and colleagues advise that when using the Delphi process to develop core outcome sets for clinical trials, patients and clinicians be involved, researchers and facilitators avoid imposing their views on participants, and attrition of participants be minimized

Planning a method for covariate adjustment in individually randomised trials: a practical guide

Background: It has long been advised to account for baseline covariates in the analysis of confirmatory randomised trials, with the main statistical justifications being that this increases power and, when a randomisation scheme balanced covariates, permits a valid estimate of experimental error. There are various methods available to account for covariates but it is not clear how to choose among them. // Methods: Taking the perspective of writing a statistical analysis plan, we consider how to choose between the three most promising broad approaches: direct adjustment, standardisation and inverse-probability-of-treatment weighting. // Results: The three approaches are similar in being asymptotically efficient, in losing efficiency with mis-specified covariate functions and in handling designed balance. If a marginal estimand is targeted (for example, a risk difference or survival difference), then direct adjustment should be avoided because it involves fitting non-standard models that are subject to convergence issues. Convergence is most likely with IPTW. Robust standard errors used by IPTW are anti-conservative at small sample sizes. All approaches can use similar methods to handle missing covariate data. With missing outcome data, each method has its own way to estimate a treatment effect in the all-randomised population. We illustrate some issues in a reanalysis of GetTested, a randomised trial designed to assess the effectiveness of an electonic sexually transmitted infection testing and results service. // Conclusions: No single approach is always best: the choice will depend on the trial context. We encourage trialists to consider all three methods more routinely

The Synaptic Vesicle SNARE Neuronal Synaptobrevin Promotes Endolysosomal Degradations and Prevents Neurodegeneration

Soluble NSF attachment protein receptors (SNAREs) are the core proteins in membrane fusion. The neuron-specific synaptic v-SNARE n-syb (neuronal Synaptobrevin) plays a key role during synaptic vesicle exocytosis. In this paper, we report that loss of n-syb caused slow neurodegeneration independent of its role in neurotransmitter release in adult Drosophila melanogaster photoreceptor neurons. In addition to synaptic vesicles, n-Syb localized to endosomal vesicles. Loss of n-syb lead to endosomal accumulations, transmembrane protein degradation defects, and a secondary increase in autophagy. Our evidence suggests a primary defect of impaired delivery of vesicles that contain degradation proteins, including the acidification-activated Cathepsin proteases and the neuron-specific proton pump and V0 adenosine triphosphatase component V100. Overexpressing V100 partially rescued n-syb–dependent degeneration through an acidification-independent endosomal sorting mechanism. Collectively, these findings reveal a role for n-Syb in a neuron-specific sort-and-degrade mechanism that protects neurons from degeneration. Our findings further shed light on which intraneuronal compartments exhibit increased or decreased neurotoxicity

Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. The mechanisms underlying injury and age-dependent susceptibility have been unknown, and lack of a diagnostic marker heralding brain injury has impeded intervention efforts. Using a mouse model of GA-I, we show that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance (1H NMR) spectroscopy as a diagnostic marker. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings provide what we believe are new monitoring and treatment strategies that may translate for use in human GA-I

MARCH6 and TRC8 facilitate the quality control of cytosolic and tail-anchored proteins.

Misfolded or damaged proteins are typically targeted for destruction by proteasome-mediated degradation, but the mammalian ubiquitin machinery involved is incompletely understood. Here, using forward genetic screens in human cells, we find that the proteasome-mediated degradation of the soluble misfolded reporter, mCherry-CL1, involves two ER-resident E3 ligases, MARCH6 and TRC8. mCherry-CL1 degradation is routed via the ER membrane and dependent on the hydrophobicity of the substrate, with complete stabilisation only observed in double knockout MARCH6/TRC8 cells. To identify a more physiological correlate, we used quantitative mass spectrometry and found that TRC8 and MARCH6 depletion altered the turnover of the tail-anchored protein heme oxygenase-1 (HO-1). These E3 ligases associate with the intramembrane cleaving signal peptide peptidase (SPP) and facilitate the degradation of HO-1 following intramembrane proteolysis. Our results highlight how ER-resident ligases may target the same substrates, but work independently of each other, to optimise the protein quality control of selected soluble and tail-anchored proteins

16-O-methylcafestol is present in ground roast Arabica coffees: Implications for authenticity testing

High-field and low-field proton NMR spectroscopy were used to analyse lipophilic extracts from ground roast coffees. Using a sample preparation method that produced concentrated extracts, a small marker peak at 3.16 ppm was observed in 30 Arabica coffees of assured origin. This signal has previously been believed absent from Arabicas, and has been used as a marker for detecting adulteration with robusta. Via 2D 600 MHz NMR and LC-MS, 16-O-methylcafestol and 16-O-methylkahweol were detected for the first time in Arabica roast coffee and shown to be responsible for the marker peak. Using low-field NMR, robusta in Arabica could be detected at levels of the order of 1-2% w/w. A surveillance study of retail purchased "100% Arabica" coffees found that 6 out of 60 samples displayed the 3.16 ppm marker signal to a degree commensurate with adulteration at levels of 3-30% w/w