Probabilistic design of a molybdenum-base alloy using a neural network

An artificial intelligence tool is exploited to discover and characterize a new molybdenum-base alloy that is the most likely to simultaneously satisfy targets of cost, phase stability, precipitate content, yield stress, and hardness. Experimental testing demonstrates that the proposed alloy fulfills the computational predictions, and furthermore the physical properties exceed those of other commercially available Mo-base alloys for forging-die applications.The authors acknowledge the financial support of Rolls-Royce plc, EPSRC under EP/H022309/1 and EP/H500375/1, the Royal Society, and Gonville & Caius College

On the entropic stabilisation of an Al<inf>0.5</inf>CrFeCoNiCu high entropy alloy

The extent to which configurational entropy can stabilise a single solid solution in an Al0.5CrFeCoNiCu high entropy alloy has been assessed through characteristion of samples following casting and heat treatment at 1000 C. At temperatures between 1000 C and the onset of melting, the alloy was shown to be within a two phase field and these phases were stable following prolonged exposure at elevated temperature. X-ray and transmission electron diffraction indicated that both constituent phases had an fcc structure. Therefore, these phases share a Gibbs energy curve that must contain two local minima at the solidus temperature, rather than the single minimum required for a continuous solid solution. These observations indicate that there is no temperature at which this material is in a stable, solid state single phase field and that therefore, the configurational complexity is insufficient to stabilise a solid solution phase against enthalpic effects.EPSRC/Rolls-Royce Strategic partnership for funding (NGJ, AB and HJS under EP/H500375/1, JWA and BDC under EP/H022309/1).This is the final published manuscript distributed under a Creative Commons Attribution License 2.0 UK. This article can also be viewed on the publisher's website at: http://www.sciencedirect.com/science/article/pii/S0966979514001848

Design of a nickel-base superalloy using a neural network

A new computational tool has been developed to model, discover, and optimize new alloys that simultaneously satisfy up to eleven physical criteria. An artificial neural network is trained from pre-existing materials data that enables the prediction of individual material properties both as a function of composition and heat treatment routine, which allows it to optimize the material properties to search for the material with properties most likely to exceed a target criteria. We design a new polycrystalline nickel-base superalloy with the optimal combination of cost, density, gamma' phase content and solvus, phase stability, fatigue life, yield stress, ultimate tensile strength, stress rupture, oxidation resistance, and tensile elongation. Experimental data demonstrates that the proposed alloy fulfills the computational predictions, possessing multiple physical properties, particularly oxidation resistance and yield stress, that exceed existing commercially available alloys

Magnetism, X-rays and accretion rates in WD 1145+017 and other polluted white dwarf systems

This paper reports circular spectropolarimetry and X-ray observations of several polluted white dwarfs including WD 1145+017, with the aim to constrain the behaviour of disc material and instantaneous accretion rates in these evolved planetary systems. Two stars with previously observed Zeeman splitting, WD 0322–019 and WD 2105–820, are detected above 5σ and Bz > 1 kG, while WD 1145+017, WD 1929+011, and WD 2326+049 yield (null) detections below this minimum level of confidence. For these latter three stars, high-resolution spectra and atmospheric modelling are used to obtain limits on magnetic field strengths via the absence of Zeeman splitting, finding B∗ < 20 kG based on data with resolving power R ≈ 40 000. An analytical framework is presented for bulk Earth composition material falling on to the magnetic polar regions of white dwarfs, where X-rays and cyclotron radiation may contribute to accretion luminosity. This analysis is applied to X-ray data for WD 1145+017, WD 1729+371, and WD 2326+049, and the upper bound count rates are modelled with spectra for a range of plasma kT = 1–10 keV in both the magnetic and non-magnetic accretion regimes. The results for all three stars are consistent with a typical dusty white dwarf in a steady state at 108–109 g s−1. In particular, the non-magnetic limits for WD 1145+017 are found to be well below previous estimates of up to 1012 g s−1, and likely below 1010 g s−1, thus suggesting the star-disc system may be average in its evolutionary state, and only special in viewing geometry

Microcavity controlled coupling of excitonic qubits

Controlled non-local energy and coherence transfer enables light harvesting in photosynthesis and non-local logical operations in quantum computing. The most relevant mechanism of coherent coupling of distant qubits is coupling via the electromagnetic field. Here, we demonstrate the controlled coherent coupling of spatially separated excitonic qubits via the photon mode of a solid state microresonator. This is revealed by two-dimensional spectroscopy of the sample's coherent response, a sensitive and selective probe of the coherent coupling. The experimental results are quantitatively described by a rigorous theory of the cavity mediated coupling within a cluster of quantum dots excitons. Having demonstrated this mechanism, it can be used in extended coupling channels - sculptured, for instance, in photonic crystal cavities - to enable a long-range, non-local wiring up of individual emitters in solids

Can the Cancer-related Fatigue Case-definition Criteria Be Applied to Chronic Medical Illness? A Comparison between Breast Cancer and Systemic Sclerosis

OBJECTIVE: Fatigue is a crucial determinant of quality of life across rheumatic diseases, but the lack of agreed-upon standards for identifying clinically significant fatigue hinders research and clinical management. Case definition criteria for cancer-related fatigue were proposed for inclusion in the International Classification of Diseases. The objective was to evaluate whether the cancer-related fatigue case definition performed equivalently in women with breast cancer and systemic sclerosis (SSc) and could be used to identify patients with chronic illness-related fatigue. METHODS: The cancer-related fatigue interview (case definition criteria met if ≥ 5 of 9 fatigue-related symptoms present with functional impairment) was completed by 291 women with SSc and 278 women successfully treated for breast cancer. Differential item functioning was assessed with the multiple indicator multiple cause model. RESULTS: Items 3 (concentration) and 10 (short-term memory) were endorsed significantly less often by women with SSc compared with cancer, controlling for responses on other items. Omitting these 2 items from the case definition and requiring 4 out of the 7 remaining symptoms resulted in a similar overall prevalence of cancer-related fatigue in the cancer sample compared with the original criteria (37.4% vs 37.8%, respectively), with 97.5% of patients diagnosed identically with both definitions. Prevalence of chronic illness-related fatigue was 36.1% in SSc using 4 of 7 symptoms. CONCLUSION: The cancer-related fatigue criteria can be used equivalently to identify patients with chronic illness-related fatigue when 2 cognitive fatigue symptoms are omitted. Harmonized definitions and measurement of clinically significant fatigue will advance research and clinical management of fatigue in rheumatic diseases and other conditions

Using item response theory to explore the psychometric properties of extended matching questions examination in undergraduate medical education

BACKGROUND: As assessment has been shown to direct learning, it is critical that the examinations developed to test clinical competence in medical undergraduates are valid and reliable. The use of extended matching questions (EMQ) has been advocated to overcome some of the criticisms of using multiple-choice questions to test factual and applied knowledge. METHODS: We analysed the results from the Extended Matching Questions Examination taken by 4th year undergraduate medical students in the academic year 2001 to 2002. Rasch analysis was used to examine whether the set of questions used in the examination mapped on to a unidimensional scale, the degree of difficulty of questions within and between the various medical and surgical specialties and the pattern of responses within individual questions to assess the impact of the distractor options. RESULTS: Analysis of a subset of items and of the full examination demonstrated internal construct validity and the absence of bias on the majority of questions. Three main patterns of response selection were identified. CONCLUSION: Modern psychometric methods based upon the work of Rasch provide a useful approach to the calibration and analysis of EMQ undergraduate medical assessments. The approach allows for a formal test of the unidimensionality of the questions and thus the validity of the summed score. Given the metric calibration which follows fit to the model, it also allows for the establishment of items banks to facilitate continuity and equity in exam standards

Targeting BTK for the treatment of FLT3-ITD mutated acute myeloid leukemia

Approximately 20% of patients with acute myeloid leukaemia (AML) have a mutation in FMS-like-tyrosine-kinase-3 (FLT3). FLT3 is a trans-membrane receptor with a tyrosine kinase domain which, when activated, initiates a cascade of phosphorylated proteins including the SRC family of kinases. Recently our group and others have shown that pharmacologic inhibition and genetic knockdown of Bruton's tyrosine kinase (BTK) blocks AML blast proliferation, leukaemic cell adhesion to bone marrow stromal cells as well as migration of AML blasts. The anti-proliferative effects of BTK inhibition in human AML are mediated via inhibition of downstream NF-κB pro-survival signalling however the upstream drivers of BTK activation in human AML have yet to be fully characterised. Here we place the FLT3-ITD upstream of BTK in AML and show that the BTK inhibitor ibrutinib inhibits the survival and proliferation of FLT3-ITD primary AML blasts and AML cell lines. Furthermore ibrutinib inhibits the activation of downstream kinases including MAPK, AKT and STAT5. In addition we show that BTK RNAi inhibits proliferation of FLT3-ITD AML cells. Finally we report that ibrutinib reverses the cyto-protective role of BMSC on FLT3-ITD AML survival. These results argue for the evaluation of ibrutinib in patients with FLT3-ITD mutated AML

Effects of bed net use, female size, and plant abundance on the first meal choice (blood vs sugar) of the malaria mosquito Anopheles gambiae

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to determine whether the sugar-or-blood meal choice of <it>Anopheles gambiae </it>females one day after emergence is influenced by blood-host presence and accessibility, nectariferous plant abundance, and female size. This tested the hypothesis that the initial meal of female <it>An. gambiae </it>is sugar, even when a blood host is available throughout the night, and, if not, whether the use of a bed net diverts mosquitoes to sugar sources.</p> <p>Methods</p> <p>Females and males <1-day post-emergence were released in a mesocosm. Overnight they had access to either one or six <it>Senna didymobotrya </it>plants. Simultaneously they had access to a human blood host, either for 8 h or for only 30 min at dusk and dawn (the remainder of the night being excluded by an untreated bed net). In a third situation, the blood host was not present. All mosquitoes were collected in the morning. Their wing lengths, an indicator of pre-meal energetic state, were measured, and their meal choice was determined by the presence of midgut blood and of fructose.</p> <p>Results</p> <p>Female sugar feeding after emergence was facultative. When a blood host was accessible for 8 h per night, 92% contained blood, and only 3.7% contained sugar. Even with the use of a bed net, 78% managed to obtain a blood meal during the 30 min of accessibility at dusk or dawn, but 14% of females were now fructose-positive. In the absence of a blood host, and when either one or six plants were available, a total of 21.7% and 23.6% of females and 30.8% and 43.5% of males contained fructose, respectively. Feeding on both sugar and blood was more likely with bed net use and with greater plant abundance. Further, mosquitoes that fed on both resources were more often small and had taken a sugar meal earlier than the blood meal. The abundance of sugar hosts also affected the probability of sugar feeding by males and the amount of fructose obtained by both males and females.</p> <p>Conclusion</p> <p>Even in an abundance of potential sugar sources, female <it>An. gambiae </it>appear to prefer a nearby human source of blood. However, the decision to take sugar was more likely if energy reserves were low. Results probably would differ if sugar hosts were more attractive or yielded larger sugar meals. The diversion of energetically deprived mosquitoes to sugar sources suggests a possible synergy between bed nets and sugar-based control methods.</p

Chemical combinations elucidate pathway interactions and regulation relevant to Hepatitis C replication

SREBP-2, oxidosqualene cyclase (OSC) or lanosterol demethylase were identified as novel sterol pathway-associated targets that, when probed with chemical agents, can inhibit hepatitis C virus (HCV) replication.Using a combination chemical genetics approach, combinations of chemicals targeting sterol pathway enzymes downstream of and including OSC or protein geranylgeranyl transferase I (PGGT) produce robust and selective synergistic inhibition of HCV replication. Inhibition of enzymes upstream of OSC elicit proviral responses that are dominant to the effects of inhibiting all downstream targets.Inhibition of the sterol pathway without inhibition of regulatory feedback mechanisms ultimately results in an increase in HCV replication because of a compensatory upregulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) expression. Increases in HMGCR expression without inhibition of HMGCR enzymatic activity ultimately stimulate HCV replication through increasing the cellular pool of geranylgeranyl pyrophosphate (GGPP).Chemical inhibitors that ultimately prevent SREBP-2 activation, inhibit PGGT or encourage the production of polar sterols have great potential as HCV therapeutics if associated toxicities can be reduced