Magnetic field design in a cylindrical high-permeability shield: The combination of simple building blocks and a genetic algorithm

Magnetically-sensitive experiments and newly-developed quantum technologies with integrated high-permeability magnetic shields require increasing control of their magnetic field environment and reductions in size, weight, power and cost. However, magnetic fields generated by active components are distorted by high-permeability magnetic shielding, particularly when they are close to the shield's surface. Here, we present an efficient design methodology for creating desired static magnetic field profiles by using discrete coils electromagnetically-coupled to a cylindrical passive magnetic shield. We utilize a modified Green's function solution that accounts for the interior boundary conditions on a closed finite-length high-permeability cylindrical magnetic shield, and determine simplified expressions when a cylindrical coil approaches the interior surface of the shield. We use an analytic formulation of simple discrete building blocks to provide a complete discrete coil basis to generate any physically-attainable magnetic field inside the shield. We then use a genetic algorithm to find optimized discrete coil structures composed of this basis. We use our methodology to generate an improved linear axial gradient field, $\mathrm{d}B_z/\mathrm{d}z$, and transverse bias field, $B_x$. These optimized structures increase, by a factor of seven and three compared to the standard configurations, the volume in which the desired and achieved fields agree within $1\%$ accuracy, respectively. This coil design method can be used to optimize active--passive magnetic field shaping systems that are compact and simple to manufacture, enabling accurate magnetic field control in spatially-confined experiments at low cost.Comment: The authors M. Packer and P. J. Hobson have contributed equally to this work. 24 pages, 16 figure

Valuation of livestock eco-agri-food systems: poultry, beef and dairy

As input for the TEEBAgriFood study, TEEB asked for a series of studies on livestock, rice, palm oil, inland fisheries and agro-forestry. This report deals with livestock production and aims to improve decision-making in livestock production policies, to enhance its viability, not just economically but also socially and environmentally. Livestock sector is important because they have high externalities and it is expected that livestock consumption will be 76% higher in 2050 compared to 2005 (Alexandratos and Bruisma, 2012) because of population growth, income growth, urbanization and preference shifts. This report aims to provide evidence that will help to identify policy options for the transition towards increased food security with sustainable livestock production systems, with particular emphasis on the role of smallholder farmers

Safety and efficacy of low-dose sirolimus in the PIK3CA-Related Overgrowth Spectrum

Purpose PIK3CA-related overgrowth spectrum (PROS) encompasses a range of debilitating conditions defined by asymmetric overgrowth caused by mosaic activating PIK3CA variants. PIK3CA encodes the p110α catalytic subunit of phosphatidylinositol-3-kinase (PI3K), a critical transducer of growth factor signaling. As mTOR mediates the growth-promoting actions of PI3K, we hypothesized that the mTOR inhibitor sirolimus would slow pathological overgrowth. Methods Thirty-nine participants with PROS and progressive overgrowth were enrolled into open-label studies across three centers, and results were pooled. For the primary outcome, tissue volumes at affected and unaffected sites were measured by dual energy X-ray absorptiometry during 26 weeks of untreated run-in and 26 weeks of sirolimus therapy. Results Thirty participants completed the study. Sirolimus led to a change in mean percentage total tissue volume of –7.2% (SD 16.0, p = 0.04) at affected sites, but not at unaffected sites (+1.7%, SD 11.5, p = 0.48) (n = 23 evaluable). Twenty-eight of 39 (72%) participants had ≥1 adverse event related to sirolimus of which 37% were grade 3 or 4 in severity and 7/39 (18%) participants were withdrawn consequently. Conclusion This study suggests that low-dose sirolimus can modestly reduce overgrowth, but cautions that the side-effect profile is significant, mandating individualized risk–benefit evaluations for sirolimus treatment in PROS

BPR1K653, a Novel Aurora Kinase Inhibitor, Exhibits Potent Anti-Proliferative Activity in MDR1 (P-gp170)-Mediated Multidrug-Resistant Cancer Cells

Over-expression of Aurora kinases promotes the tumorigenesis of cells. The aim of this study was to determine the preclinical profile of a novel pan-Aurora kinase inhibitor, BPR1K653, as a candidate for anti-cancer therapy. Since expression of the drug efflux pump, MDR1, reduces the effectiveness of various chemotherapeutic compounds in human cancers, this study also aimed to determine whether the potency of BPR1K653 could be affected by the expression of MDR1 in cancer cells.BPR1K653 specifically inhibited the activity of Aurora-A and Aurora-B kinase at low nano-molar concentrations in vitro. Anti-proliferative activity of BPR1K653 was evaluated in various human cancer cell lines. Results of the clonogenic assay showed that BPR1K653 was potent in targeting a variety of cancer cell lines regardless of the tissue origin, p53 status, or expression of MDR1. At the cellular level, BPR1K653 induced endo-replication and subsequent apoptosis in both MDR1-negative and MDR1-positive cancer cells. Importantly, it showed potent activity against the growth of xenograft tumors of the human cervical carcinoma KB and KB-derived MDR1-positive KB-VIN10 cells in nude mice. Finally, BPR1K653 also exhibited favorable pharmacokinetic properties in rats.BPR1K653 is a novel potent anti-cancer compound, and its potency is not affected by the expression of the multiple drug resistant protein, MDR1, in cancer cells. Therefore, BPR1K653 is a promising anti-cancer compound that has potential for the management of various malignancies, particularly for patients with MDR1-related drug resistance after prolonged chemotherapeutic treatments

An overview of using small punch testing for mechanical characterization of MCrAlY bond coats

Considerable work has been carried out on overlay bond coats in the past several decades because of its excellent oxidation resistance and good adhesion between the top coat and superalloy substrate in the thermal barrier coating systems. Previous studies mainly focus on oxidation and diffusion behavior of these coatings. However, the mechanical behavior and the dominant fracture and deformation mechanisms of the overlay bond coats at different temperatures are still under investigation. Direct comparison between individual studies has not yet been achieved due to the fragmentary data on deposition processes, microstructure and, more apparently, the difficulty in accurately measuring the mechanical properties of thin coatings. One of the miniaturized specimen testing methods, small punch testing, appears to have the potential to provide such mechanical property measurements for thin coatings. The purpose of this paper is to give an overview of using small punch testing to evaluate material properties and to summarize the available mechanical properties that include the ductile-to-brittle transition and creep of MCrAlY bond coat alloys, in an attempt to understand the mechanical behavior of MCrAlY coatings over a broad temperature range

Cell-based screen for altered nuclear phenotypes reveals senescence progression in polyploid cells after Aurora kinase B inhibition.

Cellular senescence is a widespread stress response and is widely considered to be an alternative cancer therapeutic goal. Unlike apoptosis, senescence is composed of a diverse set of subphenotypes, depending on which of its associated effector programs are engaged. Here we establish a simple and sensitive cell-based prosenescence screen with detailed validation assays. We characterize the screen using a focused tool compound kinase inhibitor library. We identify a series of compounds that induce different types of senescence, including a unique phenotype associated with irregularly shaped nuclei and the progressive accumulation of G1 tetraploidy in human diploid fibroblasts. Downstream analyses show that all of the compounds that induce tetraploid senescence inhibit Aurora kinase B (AURKB). AURKB is the catalytic component of the chromosome passenger complex, which is involved in correct chromosome alignment and segregation, the spindle assembly checkpoint, and cytokinesis. Although aberrant mitosis and senescence have been linked, a specific characterization of AURKB in the context of senescence is still required. This proof-of-principle study suggests that our protocol is capable of amplifying tetraploid senescence, which can be observed in only a small population of oncogenic RAS-induced senescence, and provides additional justification for AURKB as a cancer therapeutic target.This work was supported by the University of Cambridge, Cancer Research UK, Hutchison Whampoa; Cancer Research UK grants A6691 and A9892 (M.N., N.K., C.J.T., D.C.B., C.J.C., L.S.G, and M.S.); a fellowship from the Uehara Memorial Foundation (M.S.).This is the author accepted manuscript. The final version is available from the American Society for Cell Biology via http://dx.doi.org/10.1091/mbc.E15-01-000

Raising the Bar: Improving Methodological Rigour in Cognitive Alcohol Research

Background and Aims: A range of experimental paradigms claim to measure the cognitive processes underpinning alcohol use, suggesting that heightened attentional bias, greater approach tendencies and reduced cue-specific inhibitory control are important drivers of consumption. This paper identifies methodological shortcomings within this broad domain of research and exemplifies them in studies focused specifically on alcohol-related attentional bias. Argument and analysis: We highlight five main methodological issues: (i) the use of inappropriately matched control stimuli; (ii) opacity of stimulus selection and validation procedures; (iii) a credence in noisy measures; (iv) a reliance on unreliable tasks; and (v) variability in design and analysis. This is evidenced through a review of alcohol-related attentional bias (64 empirical articles, 68 tasks), which reveals the following: only 53% of tasks use appropriately matched control stimuli; as few as 38% report their stimulus selection and 19% their validation procedures; less than 28% used indices capable of disambiguating attentional processes; 22% assess reliability; and under 2% of studies were pre-registered. Conclusions: Well-matched and validated experimental stimuli, the development of reliable cognitive tasks and explicit assessment of their psychometric properties, and careful consideration of behavioural indices and their analysis will improve the methodological rigour of cognitive alcohol research. Open science principles can facilitate replication and reproducibility in alcohol research

A new species of Varanus (Anguimorpha: Varanidae) from the early Miocene of the Czech Republic, and its relationships and palaeoecology

Skeletal remains of a new early Miocene (Ottnangian, MN 4 mammal zone) monitor lizard, Varanus mokrensis sp. nov., are described from two karst fissures in the Mokrá-Western Quarry (1/2001 Turtle Joint; 2/2003 Reptile Joint), Czech Republic, providing the first documented example of a European varanid for which osteological data permit a well-supported assignment to the genus Varanus. The new species is morphologically similar to the Recent Indo-Asiatic varanids of the Varanus bengalensis group. It differs from all other Varanus species on the basis of a single autapomorphy and a combination of 11 characters. As a distinguishing feature of V. mokrensis, the parietal and squamosal processes of the postorbitofrontal form a narrowly acute angle. The teeth show distinct, smooth cutting edges along the mesial and distal margins of the apical portion of their crowns. This feature is not observed in most extant Asiatic Varanus species and may represent a plesiomorphic condition. The results of parsimony phylogenetic analyses, with and without character reweighting, reveal poor resolution within Varanus. A Bayesian analysis shows V. mokrensis to be closely related to extant representatives of the Indo-Asiatic Varanus clade, with close affinities to the V. bengalensis species group. The topology of the Bayesian tree supports the hypothesis that Miocene monitors from Mokrá are representatives of a lineage that is ancestral to the well-defined clade of extant African varanids, including the early Miocene V. rusingensis. In addition, our results support a Eurasian origin for the varanid clade. The extant African Varanus species probably originated in the late Oligocene. The radiation of African varanids probably occurred during the late Oligocene to early Miocene time interval. The occurrence of Varanus in the early Miocene of Mokrá-Western Quarry corresponds to the warm phase of the Miocene Climatic Optimum. Remains of a diverse aquatic and heliophobe amphibian fauna at the 2/2003 Reptile Joint site indicate more humid conditions than those at the 1/2001 Turtle Joint site