Tests on propellers under static thrust conditions

Dynamometer tests of propellers under static thrust condition

A condensed-mass advection based model for the simulation of liquid polar stratospheric clouds

International audienceWe present a condensed-mass advection based model (MADVEC) designed to simulate the condensation/evaporation of liquid polar stratospheric cloud (PSC) particles. A (Eulerian-in-radius) discretization scheme is used, making the model suitable for use in global or mesoscale chemistry and transport models (CTMs). The mass advection equations are solved using an adaption of the weighted average flux (WAF) scheme. We validate the numerical scheme using an analytical solution for multicomponent aerosols. The physics of the model are tested using a test case designed by Meilinger et al. (1995). The results from this test corroborate the composition gradients across the size distribution under rapid cooling conditions that were reported in earlier studies.</p

3-D microphysical model studies of Arctic denitrification: comparison with observations

International audienceSimulations of Arctic denitrification using a 3-D chemistry-microphysics transport model are compared with observations for the winters 1994/95, 1996/97 and 1999/2000. The model of Denitrification by Lagrangian Particle Sedimentation (DLAPSE) couples the full chemical scheme of the 3-D chemical transport model, SLIMCAT, with a nitric acid trihydrate (NAT) growth and sedimentation scheme. We use observations from the Microwave Limb Sounder (MLS) and Improved Limb Atmospheric Sounder (ILAS) satellite instruments, the balloon-borne Michelsen Interferometer for Passive Atmospheric Sounding (MIPAS-B), and the in situ NOy instrument on-board the ER-2. As well as directly comparing model results with observations, we also assess the extent to which these observations are able to validate the modelling approach taken. For instance, in 1999/2000 the model captures the temporal development of denitrification observed by the ER-2 from late January into March. However, in this winter the vortex was already highly denitrified by late January so the observations do not provide a strong constraint on the modelled rate of denitrification. The model also reproduces the MLS observations of denitrification in early February 2000. In 1996/97 the model captures the timing and magnitude of denitrification as observed by ILAS, although the lack of observations north of ~67° N in the beginning of February make it difficult to constrain the actual timing of onset. The comparison for this winter does not support previous conclusions that denitrification must be caused by an ice-mediated process. In 1994/95 the model notably underestimates the magnitude of denitrification observed during a single balloon flight of the MIPAS-B instrument. Agreement between model and MLS HNO3 at 68 hPa in mid-February 1995 is significantly better. Sensitivity tests show that a 1.5 K overall decrease in vortex temperatures, or a factor 4 increase in assumed NAT nucleation rates, produce the best statistical fit to MLS observations. Both adjustments would be required to bring the model into agreement with the MIPAS-B observations. The agreement between the model and observations suggests that a NAT-only denitrification scheme (without ice), which was discounted by previous studies, must now be considered as one mechanism for the observed Arctic denitrification. The timing of onset and the rate of denitrification remain poorly constrained by the available observations

Structure of a potential therapeutic antibody bound to Interleukin-16 (IL-16): mechanistic insights and new therapeutic opportunities

Interleukin-16 (IL-16) is reported to be a chemoattractant cytokine and modulator of T-cell activation, and has been proposed as a ligand for the co-receptor CD4. The secreted active form of IL-16 has been detected at sites of TH1-mediated inflammation, such as those seen in autoimmune diseases, ischemic reperfusion injury (IRI), and tissue transplant rejection. Neutralization of IL-16 recruitment to its receptor, using an anti-IL16 antibody, has been shown to significantly attenuate inflammation and disease pathology in IRI, as well as in some autoimmune diseases. The 14.1 antibody is a monoclonal anti-IL-16 antibody, which when incubated with CD4+ cells is reported to cause a reduction in the TH1-type inflammatory response. Secreted IL-16 contains a characteristic PDZ domain. PDZ domains are typically characterized by a defined globular structure, along with a peptide-binding site located in a groove between the αB and βB structural elements and a highly conserved carboxylate-binding loop. In contrast to other reported PDZ domains, the solution structure previously reported for IL-16 reveals a tryptophan residue obscuring the recognition groove. We have solved the structure of the 14.1Fab fragment in complex with IL-16, revealing that binding of the antibody requires a conformational change in the IL-16 PDZ domain. This involves the rotation of the αB-helix, accompanied movement of the peptide groove obscuring tryptophan residue, and consequent opening up of the binding site for interaction. Our study reveals a surprising mechanism of action for the antibody and identifies new opportunities for the development of IL-16-targeted therapeutics, including small molecules that mimic the interaction of the antibody

High resolution global climate modelling; the UPSCALE project, a large simulation campaign

The UPSCALE (UK on PRACE: weather-resolving Simulations of Climate for globAL Environmental risk) project constructed and ran an ensemble of HadGEM3 (Hadley Centre Global Environment Model 3) atmosphere only global climate simulations over the period 1985–2011, at resolutions of N512 (25 km), N216 (60 km) and N96 (130 km) as used in current global weather forecasting, seasonal prediction and climate modelling respectively. Alongside these present climate simulations a parallel ensemble looking at extremes of future climate was run, using a timeslice methodology to consider conditions at the end of this century. These simulations were primarily performed using a 144 million core hour, single year grant of computing time from PRACE (the Partnership for Advanced Computing in Europe) in 2012, with additional resources supplied by the Natural Environment Research Council (NERC) and the Met Office. Almost 400 terabytes of simulation data were generated on the HERMIT supercomputer at the High Performance Computing Center Stuttgart (HLRS), and transferred to the JASMIN super-data cluster provided by the Science and Technology Facilities Council Centre for Data Archival (STFC CEDA) for analysis and storage. In this paper we describe the implementation of the project, present the technical challenges in terms of optimisation, data output, transfer and storage that such a project involves and include details of the model configuration and the composition of the UPSCALE data set. This data set is available for scientific analysis to allow assessment of the value of model resolution in both present and potential future climate conditions

A systematic genome-wide analysis of zebrafish protein-coding gene function

Since the publication of the human reference genome, the identities of specific genes associated with human diseases are being discovered at a rapid rate. A central problem is that the biological activity of these genes is often unclear. Detailed investigations in model vertebrate organisms, typically mice, have been essential for understanding the activities of many orthologues of these disease-associated genes. Although gene-targeting approaches1, 2, 3 and phenotype analysis have led to a detailed understanding of nearly 6,000 protein-coding genes3, 4, this number falls considerably short of the more than 22,000 mouse protein-coding genes5. Similarly, in zebrafish genetics, one-by-one gene studies using positional cloning6, insertional mutagenesis7, 8, 9, antisense morpholino oligonucleotides10, targeted re-sequencing11, 12, 13, and zinc finger and TAL endonucleases14, 15, 16, 17 have made substantial contributions to our understanding of the biological activity of vertebrate genes, but again the number of genes studied falls well short of the more than 26,000 zebrafish protein-coding genes18. Importantly, for both mice and zebrafish, none of these strategies are particularly suited to the rapid generation of knockouts in thousands of genes and the assessment of their biological activity. Here we describe an active project that aims to identify and phenotype the disruptive mutations in every zebrafish protein-coding gene, using a well-annotated zebrafish reference genome sequence18, 19, high-throughput sequencing and efficient chemical mutagenesis. So far we have identified potentially disruptive mutations in more than 38% of all known zebrafish protein-coding genes. We have developed a multi-allelic phenotyping scheme to efficiently assess the effects of each allele during embryogenesis and have analysed the phenotypic consequences of over 1,000 alleles. All mutant alleles and data are available to the community and our phenotyping scheme is adaptable to phenotypic analysis beyond embryogenesis

The inwardly rectifying K+ channel KIR7.1 controls uterine excitability throughout pregnancy

Abnormal uterine activity in pregnancy causes a range of important clinical disorders, including preterm birth, dysfunctional labour and post-partum haemorrhage. Uterine contractile patterns are controlled by the generation of complex electrical signals at the myometrial smooth muscle plasma membrane. To identify novel targets to treat conditions associated with uterine dysfunction, we undertook a genome-wide screen of potassium channels that are enriched in myometrial smooth muscle. Computational modelling identified Kir7.1 as potentially important in regulating uterine excitability during pregnancy. We demonstrate Kir7.1 current hyper-polarizes uterine myocytes and promotes quiescence during gestation. Labour is associated with a decline, but not loss, of Kir7.1 expression. Knockdown of Kir7.1 by lentiviral expression of miRNA was sufficient to increase uterine contractile force and duration significantly. Conversely, overexpression of Kir7.1 inhibited uterine contractility. Finally, we demonstrate that the Kir7.1 inhibitor VU590 as well as novel derivative compounds induces profound, long-lasting contractions in mouse and human myometrium; the activity of these inhibitors exceeds that of other uterotonic drugs. We conclude Kir7.1 regulates the transition from quiescence to contractions in the pregnant uterus and may be a target for therapies to control uterine contractility

Rubisco catalytic properties of wild and domesticated relatives provide scope for improving wheat photosynthesis

Rubisco is a major target for improving crop photosynthesis and yield, yet natural diversity in catalytic properties of this enzyme is poorly understood. Rubisco from 25 genotypes of the Triticeae tribe, including wild relatives of bread wheat (Triticum aestivum), were surveyed to identify superior enzymes for improving photosynthesis in this crop. In vitro Rubisco carboxylation velocity (V c), Michaelis–Menten constants for CO2 (K c) and O2 (K o) and specificity factor (S c/o) were measured at 25 and 35 °C. V c and K c correlated positively, while V c and S c/o were inversely related. Rubisco large subunit genes (rbcL) were sequenced, and predicted corresponding amino acid differences analysed in relation to the corresponding catalytic properties. The effect of replacing native wheat Rubisco with counterparts from closely related species was analysed by modelling the response of photosynthesis to varying CO2 concentrations. The model predicted that two Rubisco enzymes would increase photosynthetic performance at 25 °C while only one of these also increased photosynthesis at 35 °C. Thus, under otherwise identical conditions, catalytic variation in the Rubiscos analysed is predicted to improve photosynthetic rates at physiological CO2 concentrations. Naturally occurring Rubiscos with superior properties amongst the Triticeae tribe can be exploited to improve wheat photosynthesis and crop productivity

Subcellular discharge of a serine protease mediates release of invasive malaria parasites from host erythrocytes.

The most virulent form of malaria is caused by waves of replication of blood stages of the protozoan pathogen Plasmodium falciparum. The parasite divides within an intraerythrocytic parasitophorous vacuole until rupture of the vacuole and host-cell membranes releases merozoites that invade fresh erythrocytes to repeat the cycle. Despite the importance of merozoite egress for disease progression, none of the molecular factors involved are known. We report that, just prior to egress, an essential serine protease called PfSUB1 is discharged from previously unrecognized parasite organelles (termed exonemes) into the parasitophorous vacuole space. There, PfSUB1 mediates the proteolytic maturation of at least two essential members of another enzyme family called SERA. Pharmacological blockade of PfSUB1 inhibits egress and ablates the invasive capacity of released merozoites. Our findings reveal the presence in the malarial parasitophorous vacuole of a regulated, PfSUB1-mediated proteolytic processing event required for release of viable parasites from the host erythrocyte

The contributory role of autism symptomology in child pornography offending : why there is an urgent need for empirical research in this area

Purpose As recently highlighted by Creaby-Attwood and Allely (2017) it is crucial that the possible innate vulnerabilities that contributed to sexual offending behaviour in an individual with an autism spectrum disorder (ASD) are taken into consideration for the application of a diversion program to avoid the stigma of a criminal conviction or during sentencing for a non-custodial outcome. Specifically, in those defendants with a diagnosis of what used to be referred to as Asperger's Syndrome (AS) and now is recognised as an ASD and who are charged and convicted of a non-contact sexual offence, education and mental health intervention will best serve the interests of justice. Design/methodology/approach This paper focuses on one particular type of sexual offending behaviour, namely, possession of child pornography. A systematic PRISMA review was conducted. Findings The authors linked examples of child pornography in the research literature to the ASD symptomology and describe how the symptomology explains such behaviour as not reflecting actual sexual deviance. Originality/value Downloading and viewing of child pornography by individuals with ASD has received relatively little research outside the mental health field. This review is of particular importance to those in the criminal justice system who may not have much knowledge and understanding of ASD. It is suggested that diversion programmes and mental health courts should be set up for this particular population charged with this particular crime in mind so that the necessary treatment/intervention/support and care can be given to this particular group. Keywords: Autism Spectrum Disorder; Asperger’s syndrome; child pornography; child exploitative material; pretrial diversio