Progress in Flaps Down Flight Reynolds Number Testing Techniques at the NTF

A series of NASA/Boeing cooperative low speed wind tunnel tests was conducted in the National Transonic Facility (NTF) between 2003 and 2004 using a semi-span high lift model representative of the 777-200 aircraft. The objective of this work was to develop the capability to acquire high quality, low speed (flaps down) wind tunnel data at up to flight Reynolds numbers in a facility originally optimized for high speed full span models. In the course of testing, a number of facility and procedural improvements were identified and implemented. The impact of these improvements on key testing metrics data quality, productivity, and so forth - was significant, and is discussed here, together with the relevance of these metrics as applied to cryogenic wind tunnel testing in general. Details of the improvements at the NTF are discussed in AIAA-2006-0508 (Recent Improvements in Semi-span Testing at the National Transonic Facility). The development work at the NTF culminated with validation testing of a 787-8 semi-span model at full flight Reynolds number in the first quarter of 2006

Institutional management of credit derivatives

The credit derivatives market has grown dramatically in the last three years and with that growth has come new opportunities for financial institutions to take advantage of this market. In this paper, we explore these market developments and lay a conceptual framework for the strategic management of credit derivatives by banking institutions. We argue that the development of the market now means that banks need to choose a strategic path for their credit derivative operations, and more specifically whether they will use the instruments simply as a tool for portfolio management, or participate in the market as a market-maker. The study of credit risk has gained rapidly in importance in recent years, mainly due to the emergence of the credit derivative market. Most of the research and analysis has been focused on the pricing of credit risk and or credit derivatives, while little attention has been given in the academic literature to the structural implications of the developing credit derivative market. Furthermore, even less attention has been paid to the managerial issues that arise with the development of this still relatively new market that has the potential to radically change the allocation, pricing, regulation and management of credit risk. In this paper we attempt to start a dialogue on the management issues of credit derivatives and to lay a conceptual framework for studying the issues. The central conclusion is that a banking institution needs to determine the depth and extent of its operations and more fundamentally determine whether as an institution it will be utilizing the credit derivatives market as an end-user for credit management or as a market maker intending to make a profit from trading and servicing clients. Section one gives a brief overview of credit derivatives. The second section describes the features of this market as it concerns banking as an industry, while section three discusses some of the managerial implications. The fourth and final section concludes and provides some directions for further research and analysis

Response of Degarelix treatment in human prostate cancer monitored by HR-MAS 1H NMR spectroscopy.

INTRODUCTION: The androgen receptor (AR) is the master regulator of prostate cancer cell metabolism. Degarelix is a novel gonadotrophin-releasing hormone blocker, used to decrease serum androgen levels in order to treat advanced human prostate cancer. Little is known of the rapid metabolic response of the human prostate cancer tissue samples to the decreased androgen levels. OBJECTIVES: To investigate the metabolic responses in benign and cancerous tissue samples from patients after treatment with Degarelix by using HRMAS 1H NMR spectroscopy. METHODS: Using non-destructive HR-MAS 1H NMR spectroscopy we analysed the metabolic changes induced by decreased AR signalling in human prostate cancer tissue samples. Absolute concentrations of the metabolites alanine, lactate, glutamine, glutamate, citrate, choline compounds [t-choline = choline + phosphocholine (PC) + glycerophosphocholine (GPC)], creatine compounds [t-creatine = creatine (Cr) + phosphocreatine (PCr)], taurine, myo-inositol and polyamines were measured in benign prostate tissue samples (n = 10), in prostate cancer specimens from untreated patients (n = 7) and prostate cancer specimens from patients treated with Degarelix (n = 6). RESULTS: Lactate, alanine and t-choline concentrations were significantly elevated in high-grade prostate cancer samples when compared to benign samples in untreated patients. Decreased androgen levels resulted in significant decreases of lactate and t-choline concentrations in human prostate cancer biopsies. CONCLUSIONS: The reduced concentrations of lactate and t-choline metabolites due to Degarelix could in principle be monitored by in vivo 1H MRS, which suggests that it would be possible to monitor the effects of physical or chemical castration in patients by that non-invasive method.We acknowledge the support of The University of Cambridge, Cancer Research UK (C14303/A17197) and Hutchison Whampoa Limited. The Human Research Tissue Bank is supported by the NIHR Cambridge Biomedical Research Centre.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s11306-016-1055-0

Ex-vivo HRMAS of adult brain tumours: metabolite quantification and assignment of tumour biomarkers

Background: High-resolution magic angle spinning (HRMAS) NMR spectroscopy allows detailed metabolic analysis of whole biopsy samples for investigating tumour biology and tumour classification. Accurate biochemical assignment of small molecule metabolites that are “NMR visible” will improve our interpretation of HRMAS data and the translation of NMR tumour biomarkers to in-vivo studies. Results: 1D and 2D 1H HRMAS NMR was used to determine that 29 small molecule metabolites, along with 8 macromolecule signals, account for the majority of the HRMAS spectrum of the main types of brain tumour(astrocytoma grade II, grade III gliomas, glioblastomas, metastases, meningiomas and also lymphomas). Differences in concentration of 20 of these metabolites were statistically significant between these brain tumour types. During the course of an extended 2D data acquisition the HRMAS technique itself affects sample analysis: glycine, glutathione and glycerophosphocholine all showed small concentration changes; analysis of the sample after HRMAS indicated structural damage that may affect subsequent histopathological analysis. Conclusions: A number of small molecule metabolites have been identified as potential biomarkers of tumour type that may enable development of more selective in-vivo 1H NMR acquisition methods for diagnosis and prognosis of brain tumours

Implementing within‐cross genomic prediction to reduce oat breeding costs

A barrier to the adoption of genomic prediction in small breeding programs is the initial cost of genotyping material. Although decreasing, marker costs are usually higher than field trial costs. In this study we demonstrate the utility of stratifying a narrow‐base biparental oat population genotyped with a modest number of markers to employ genomic prediction at early and later generations. We also show that early generation genotyping data can reduce the number of lines for later phenotyping based on selections of siblings to progress. Using sets of small families selected at an early generation could enable the use of genomic prediction for adaptation to multiple target environments at an early stage in the breeding program. In addition, we demonstrate that mixed marker data can be effectively integrated to combine cheap dominant marker data (including legacy data) with more expensive but higher density codominant marker data in order to make within generation and between lineage predictions based on genotypic information. Taken together, our results indicate that small programs can test and initiate genomic predictions using sets of stratified, narrow‐base populations and incorporating low density legacy genotyping data. This can then be scaled to include higher density markers and a broadened population base

Experiences of in-patient mental health services: systematic review

Background In-patients in crisis report poor experiences of mental healthcare not conducive to recovery. Concerns include coercion by staff, fear of assault from other patients, lack of therapeutic opportunities and limited support. There is little high-quality evidence on what is important to patients to inform recovery-focused care.Aims To conduct a systematic review of published literature, identifying key themes for improving experiences of in-patient mental healthcare.Method A systematic search of online databases (MEDLINE, PsycINFO and CINAHL) for primary research published between January 2000 and January 2016. All study designs from all countries were eligible. A qualitative analysis was undertaken and study quality was appraised. A patient and public reference group contributed to the review.Results Studies (72) from 16 countries found four dimensions were consistently related to significantly influencing in-patients' experiences of crisis and recovery-focused care: the importance of high-quality relationships; averting negative experiences of coercion; a healthy, safe and enabling physical and social environment; and authentic experiences of patient-centred care. Critical elements for patients were trust, respect, safe wards, information and explanation about clinical decisions, therapeutic activities, and family inclusion in care.Conclusions A number of experiences hinder recovery-focused care and must be addressed with the involvement of staff to provide high-quality in-patient services. Future evaluations of service quality and development of practice guidance should embed these four dimensions.Declaration of interest K.B. is editor of British Journal of Psychiatry and leads a national programme (Synergi Collaborative Centre) on patient experiences driving change in services and inequalities

Gas Condensation in the Galactic Halo

Using adaptive mesh refinement (AMR) hydrodynamic simulations of vertically stratified hot halo gas, we examine the conditions under which clouds can form and condense out of the hot halo medium to potentially fuel star formation in the gaseous disk. We find that halo clouds do not develop from linear isobaric perturbations. This is a regime where the cooling time is longer than the Brunt-Vaisala time, confirming previous linear analysis. We extend the analysis into the nonlinear regime by considering mildly or strongly nonlinear perturbations with overdensities up to 100, also varying the initial height, the cloud size, and the metallicity of the gas. Here, the result depends on the ratio of cooling time to the time required to accelerate the cloud to the sound speed (similar to the dynamical time). If the ratio exceeds a critical value near unity, the cloud is accelerated without further cooling and gets disrupted by Kelvin-Helmholtz and/or Rayleigh-Taylor instabilities. If it is less than the critical value, the cloud cools and condenses before disruption. Accreting gas with overdensities of 10-20 is expected to be marginally unstable; the cooling fraction will depend on the metallicity, the size of the incoming cloud, and the distance to the galaxy. Locally enhanced overdensities within cold streams have a higher likelihood of cooling out. Our results have implications on the evolution of clouds seeded by cold accretion that are barely resolved in current cosmological hydrodynamic simulations and absorption line systems detected in galaxy halos.Comment: 13 pages, 8 figures, submitted to Ap

The impact of maturing food safety culture and a pathway to economic gain

Research into the connection between organizational effectiveness and culture has been documented since the early nineteen nineties. A connection between economic performance and organizational culture has been established directly linking strong cultural drivers to economic performance in both the finance and retail sectors. This research proposes a similar association between food safety culture, the measures of maturity and cost of poor quality. Through data collected at five multi-national food companies, this association is explored, and an improved food safety maturity model suggested. The authors also propose a dynamic model of food safety culture, segmenting it into 4 building blocks: I. Organizational effectiveness, II. Organizational culture norms, III. Working group learned and shared assumptions, and behaviours, and IV. Individual intent and behaviours; and discuss the crucial role of actions between building blocks as part of the pathway to realizing economic gain

Tapping diversity lost in transformations—in vitro amplification of ligation reactions

Molecular evolution is a powerful means of engineering proteins. It usually requires the generation of a large recombinant DNA library of variants for cloning into a phage or plasmid vector, and the transformation of a host organism for expression and screening of the variant proteins. However, library size is often limited by the low yields of circular DNA and the poor transformation efficiencies of linear DNA. Here we have overcome this limitation by amplification of recombinant circular DNA molecules directly from ligation reactions. The amplification by bacteriophage Phi29 polymerase increased the number of transformants; thus from a nanogram-scale ligation of DNA fragments comprising two sub-libraries of variant antibody domains, we succeeded in amplifying a highly diverse and large combinatorial phage antibody library (>10(9) transformants in Escherichia coli and 10(5)-fold more transformants than without amplification). From the amplified library, but not from the smaller un-amplified library, we could isolate several antibody fragments against a target antigen. It appears that amplification of ligations with Phi29 polymerase can help recover clones and molecular diversity otherwise lost in the transformation step. A further feature of the method is the option of using PCR-amplified vectors for ligations

A causal role for TRESK loss of function in migraine mechanisms

The two-pore potassium channel, TRESK has been implicated in nociception and pain disorders. We have for the first time investigated TRESK function in human nociceptive neurons using induced pluripotent stem cell-based models. Nociceptors from migraine patients with the F139WfsX2 mutation show loss of functional TRESK at the membrane, with a corresponding significant increase in neuronal excitability. Furthermore, using CRISPR-Cas9 engineering to correct the F139WfsX2 mutation, we show a reversal of the heightened neuronal excitability, linking the phenotype to the mutation. In contrast we find no change in excitability in induced pluripotent stem cell derived nociceptors with the C110R mutation and preserved TRESK current; thereby confirming that only the frameshift mutation is associated with loss of function and a migraine relevant cellular phenotype. We then demonstrate the importance of TRESK to pain states by showing that the TRESK activator, cloxyquin, can reduce the spontaneous firing of nociceptors in an in vitro human pain model. Using the chronic nitroglycerine rodent migraine model, we demonstrate that mice lacking TRESK develop exaggerated nitroglycerine-induced mechanical and thermal hyperalgesia, and furthermore, show that cloxyquin conversely is able to prevent sensitization. Collectively, our findings provide evidence for a role of TRESK in migraine pathogenesis and its suitability as a therapeutic target