Giant Negative Thermal Expansion Induced by the Synergistic Effects of Ferroelectrostriction and Spin-Crossover in PbTiO3-Based Perovskites

The discovery of unusual negative thermal expansion (NTE) provides the opportunity to control the common but much desired property of thermal expansion, which is valuable not only in scientific interests but also in practical applications. However, most of the available NTE materials are limited to a narrow temperature range, and the NTE effect is generally weakened by means of various modifications. Here, we report an enhanced NTE effect that occurs over a wide temperature range (\alpha V = -5.24 * 10-5 {\deg}C^-1, 25-575 {\deg} C), and this NTE effect is accompanied by an abnormal enhanced tetragonality, a large spontaneous polarization, and a G-type antiferromagnetic ordering in the present perovskite-type ferroelectric of (1-x)PbTiO3-xBiCoO3. Specifically, for the composition of 0.5PbTiO3-0.5BiCoO3, an extensive volumetric contraction of ~4.8 % has been observed near the Curie temperature of 700 {\deg}C, which represents the highest level in PbTiO3-based ferroelectrics. According to our experimental and theoretical results, the giant NTE originates from a synergistic effect of the ferroelectrostriction and spin-crossover of cobalt on the crystal lattice. The actual NTE mechanism is contrasted with previous functional NTE materials, in which the NTE is simply coupled with one ordering such as electronic, magnetic, or ferroelectric ordering. The present study sheds light on the understanding of NTE mechanisms and it attests that NTE could be simultaneouslycoupled with different orderings, which will pave a new way toward the design of large NTE materials.Comment: 30 page

PO-0954 Click! Engaging Children In Research About Their Lives: Experiences Of Using Photo-elicitation From England, Australia And New Zealand

Background and aims. Engaging children in research about their lives is an essential component of providing excellent health care services. Utilising participatory, visual/arts-based approaches such as photo-elicitation (PE) can extend opportunities for children to reflect on and talk about their lives. This paper aims to explore the use of, benefits and issues associated with using PE with children. Methods. PE is a participatory, qualitative method that does not rely on high levels of verbal or written literacy and which creates equitable conditions for children’s engagement in research. Within a broad brief, children are asked to take topic-related photos. Apart from safety/privacy related guidance about where it might not be appropriate to take photographs, the children are free to take any image that has meaning to them. The children then select the images they wish to discuss and the researcher literally has to ‘follow’ the children’s data and adopt a flexible approach to the conversational interview. Results. Reflecting on our experience with PE we note how the quality of discussion is enhanced and intriguing and unexpected insights into children’s lives are revealed. What children choose to photograph or omit can create interesting tensions; these and other lessons will be shared along with exemplar photographs and stories. Conclusions. Although PE provides considerable opportunities and benefits, it is challenging research to be part of and requires skilled researchers to ensure children are safe during research engagement and that the data provides a robust depth of insight into their lives

Cholesterol metabolism is a potential therapeutic target in Duchenne muscular dystrophy

Background: Duchenne muscular dystrophy (DMD) is a lethal muscle disease detected in approximately 1:5000 male births. DMD is caused by mutations in the DMD gene, encoding a critical protein that links the cytoskeleton and the extracellular matrix in skeletal and cardiac muscles. The primary consequence of the disrupted link between the extracellular matrix and the myofibre actin cytoskeleton is thought to involve sarcolemma destabilization, perturbation of Ca homeostasis, activation of proteases, mitochondrial damage, and tissue degeneration. A recently emphasized secondary aspect of the dystrophic process is a progressive metabolic change of the dystrophic tissue; however, the mechanism and nature of the metabolic dysregulation are yet poorly understood. In this study, we characterized a molecular mechanism of metabolic perturbation in DMD. Methods: We sequenced plasma miRNA in a DMD cohort, comprising 54 DMD patients treated or not by glucocorticoid, compared with 27 healthy controls, in three groups of the ages of 4–8, 8–12, and 12–20 years. We developed an original approach for the biological interpretation of miRNA dysregulation and produced a novel hypothesis concerning metabolic perturbation in DMD. We used the mdx mouse model for DMD for the investigation of this hypothesis. Results: We identified 96 dysregulated miRNAs (adjusted P-value <0.1), of which 74 were up-regulated and 22 were down-regulated in DMD. We confirmed the dysregulation in DMD of Dystro-miRs, Cardio-miRs, and a large number of the DLK1-DIO3 miRNAs. We also identified numerous dysregulated miRNAs yet unreported in DMD. Bioinformatics analysis of both target and host genes for dysregulated miRNAs predicted that lipid metabolism might be a critical metabolic perturbation in DMD. Investigation of skeletal muscles of the mdx mouse uncovered dysregulation of transcription factors of cholesterol and fatty acid metabolism (SREBP-1 and SREBP-2), perturbation of the mevalonate pathway, and the accumulation of cholesterol in the dystrophic muscles. Elevated cholesterol level was also found in muscle biopsies of DMD patients. Treatment of mdx mice with Simvastatin, a cholesterol-reducing agent, normalized these perturbations and partially restored the dystrophic parameters. Conclusions: This investigation supports that cholesterol metabolism and the mevalonate pathway are potential therapeutic targets in DMD. 2

A sensitivity analysis of the New Zealand standard model of foot and mouth disease

Summary Disease simulation models can be a valuable tool for planning a response to exotic disease incursions, as they provide a fast, low-cost mechanism for identifying the likely outcomes of a range of outbreak scenarios and disease control strategies. To use these tools effectively and with confidence, decisionmakers must understand the simplifications and framing assumptions that underlie a model&apos;s structure. Sensitivity analysis, the analytical process of identifying which input variables are the key drivers of the model&apos;s output, is a crucial process in developing this understanding. This paper describes the application of a sampling-based sensitivity analysis to the New Zealand standard model (NZSM). This model is a parameter set developed for the InterSpread Plus model platform to allow the exploration of different outbreak scenarios for an epidemic of foot and mouth disease in New Zealand. Based on 200 iterations of the NZSM, run for a simulation period of 60 days, settings related to farm-to-saleyard movements and the detection of disease during the active surveillance phase of the epidemic had the greatest influence on the predicted number of infected premises. A small number of counter-intuitive findings indicated areas of model design, implementation and/or parameterisation that should be investigated further. A potentially useful result from this work would be information to aid the grouping or elimination of non-influential model settings. This would go some way towards reducing the overall complexity of the NZSM, while still allowing it to remain fit for purpose

Reflection of barotropic vortices from a step-like topography

The motion of a barotropic vortex on a b-plane approaching a meridional, step-like topography is studied by means of laboratory experiments and numerical simulations. In the experimental arrangement, the north-south direction is defined by a uniform weakly sloping bottom in order to simulate the b-effect. The numerical simulations are performed by using a finite-differences code, which solves the barotropic non-divergent equation. Initially, the vortices are created at the eastern side of the step. Thus cyclonic (anticyclonic) vortices drift northwestward (southwestward) on the b-plane and eventually interact with the step. The study is focused on cases where v0DHD0, with v0 the initial vortex peak vorticity and DH the step height, defined positive for a step-down and negative for a step-up topography. In both situations (cyclones approaching a step-down and anticyclones approaching a step-up), the vortices are stopped from crossing the step. This dramatic effect on the vortex trajectory is due to the entrainment of fluid from the other side of the step. Due to potential vorticity conservation, these entrained fluid columns acquire oppositely signed vorticity (relative to the vortex) as they experience depth variations, and form together with the original vortex a dipolar structure that moves away from the step. This effect is referred to as “vortex reflection”. The reflection effect is enhanced either by increasing the Rossby number or by decreasing the step height. In cases where v0DHE0, cyclonic (anticyclonic) vortices are able to cross a step-up (down)

Equipamento de baixo custo para extração em fase sólida em amostras aquosas de grande volume utilizando pressão positiva de N

Extraction/concentration is a crucial step for the analysis of organic compounds at trace level concentrations and dispersed in complex matrices. Solid-phase extraction (SPE) is one of the techniques used for this purpose. In this work, a low cost apparatus for SPE was developed that uses nitrogen under positive pressure and ensures the maintenance of the sample flow, while also allows the simultaneous extraction of different samples without cross-contamination and sample contact with plastic materials. For the system set up, easily accessible materials were used such as hypodermic needles, stainless steel tubes, rubber stoppers, and 3-way valves from serum delivery apparatus

Futibatinib, an irreversible FGFR1-4 inhibitor, in patients with advanced solid tumors harboring FGF/FGFR aberrations: a phase I dose-expansion study

Futibatinib, a highly selective, irreversible FGFR1-4 inhibitor, was evaluated in a large multihistology phase I dose-expansion trial that enrolled 197 patients with advanced solid tumors. Futibatinib demonstrated an objective response rate (ORR) of 13.7%, with responses in a broad spectrum of tumors (cholangiocarcinoma and gastric, urothelial, central nervous system, head and neck, and breast cancer) bearing both known and previously uncharacterized FGFR1-3 aberrations. The greatest activity was observed in FGFR2 fusion/rearrangement-positive intrahepatic cholangiocarcinoma (ORR, 25.4%). Some patients with acquired resistance to a prior FGFR inhibitor also experienced responses with futibatinib. Futibatinib demonstrated a manageable safety profile. The most common treatment-emergent adverse events were hyperphosphatemia (81.2%), diarrhea (33.5%), and nausea (30.4%). These results formed the basis for ongoing futibatinib phase II/III trials and demonstrate the potential of genomically selected early-phase trials to help identify molecular subsets likely to benefit from targeted therapy