Vibrational properties of phonons in random binary alloys: An augmented space recursive technique in the k-representation

We present here an augmented space recursive technique in the k-representation which include diagonal, off-diagonal and the environmental disorder explicitly : an analytic, translationally invariant, multiple scattering theory for phonons in random binary alloys.We propose the augmented space recursion (ASR) as a computationally fast and accurate technique which will incorporate configuration fluctuations over a large local environment. We apply the formalism to $Ni_{55}Pd_{45}$, Ni_{88}Cr_12} and $Ni_{50}Pt_{50}$ alloys which is not a random choice. Numerical results on spectral functions, coherent structure factors, dispersion curves and disordered induced FWHM's are presented. Finally the results are compared with the recent itinerant coherent potential approximation (ICPA) and also with experiments.Comment: 20 pages, LaTeX, 23 figure

Conserving biodiversity in production landscapes

Alternative land uses make different contributions to the conservation of biodiversity and have different implementation and management costs. Conservation planning analyses to date have generally assumed that land is either protected or unprotected and that the unprotected portion does not contribute to conservation goals. We develop and apply a new planning approach that explicitly accounts for the contribution of a diverse range of land uses to achieving conservation goals. Using East Kalimantan (Indonesian Borneo) as a case study, we prioritize investments in alternative conservation strategies and account for the relative contribution of land uses ranging from production forest to well-managed protected areas. We employ data on the distribution of mammals and assign species-specific conservation targets to achieve equitable protection by accounting for life history characteristics and home range sizes. The relative sensitivity of each species to forest degradation determines the contribution of each land use to achieving targets. We compare the cost effectiveness of our approach to a plan that considers only the contribution of protected areas to biodiversity conservation, and to a plan that assumes that the cost of conservation is represented by only the opportunity costs of conservation to the timber industry. Our preliminary results will require further development and substantial stakeholder engagement prior to implementation; nonetheless we reveal that, by accounting for the contribution of unprotected land, we can obtain more refined estimates of the costs of conservation. Using traditional planning approaches would overestimate the cost of achieving the conservation targets by an order of magnitude. Our approach reveals not only where to invest, but which strategies to invest in, in order to effectively and efficiently conserve biodiversity. Copyright ESA. All rights reserved

Elastic and anelastic relaxation behaviour of perovskite multiferroics II: PbZr0.53_{0.53}Ti0.47_{0.47}O3_3 (PZT)–PbFe0.5_{0.5}Ta0.5_{0.5}O3_3 (PFT)

Elastic and anelastic properties of ceramic samples of multiferroic perovskites with nominal compositions across the binary join PbZr$_{0.53}$Ti$_{0.47}$O$_3$–PbFe$_{0.5}$Ta$_{0.5}$O$_3$ (PZT–PFT) have been assembled to create a binary phase diagram and to address the role of strain relaxation associated with their phase transitions. Structural relationships are similar to those observed previously for PbZr$_{0.53}$Ti$_{0.47}$O$_3$–PbFe$_{0.5}$Nb$_{0.5}$O$_3$ (PZT–PFN), but the magnitude of the tetragonal shear strain associated with the ferroelectric order parameter appears to be much smaller. This leads to relaxor character for the development of ferroelectric properties in the end member PbFe$_{0.5}$Ta$_{0.5}$O$_3$. As for PZT–PFN, there appear to be two discrete instabilities rather than simply a reorientation of the electric dipole in the transition sequence cubic–tetragonal–monoclinic, and the second transition has characteristics typical of an improper ferroelastic. At intermediate compositions, the ferroelastic microstructure has strain heterogeneities on a mesoscopic length scale and, probably, also on a microscopic scale. This results in a wide anelastic freezing interval for strain-related defects rather than the freezing of discrete twin walls that would occur in a conventional ferroelastic material. In PFT, however, the acoustic loss behaviour more nearly resembles that due to freezing of conventional ferroelastic twin walls. Precursor softening of the shear modulus in both PFT and PFN does not fit with a Vogel–Fulcher description, but in PFT there is a temperature interval where the softening conforms to a power law suggestive of the role of fluctuations of the order parameter with dispersion along one branch of the Brillouin zone. Magnetic ordering appears to be coupled only weakly with a volume strain and not with shear strain but, as with multiferroic PZT–PFN perovskites, takes place within crystals which have significant strain heterogeneities on different length scales.RUS facilities in Cambridge were established with funding from the Natural Environment Research Council (Grants NE/B505738/1, NE/F017081/1). The present work was supported by Grant No. EP/ I036079/1 from the Engineering and Physical Sciences Research Council. We thank Dr. Sam Crossley for his assistance with dielectric analysis and the use of his software to run those measurements. JAS gratefully acknowledges the hospitality of the Max Planck Institute for Chemical Physics of Solids. The Nanopaleomagnetism lab has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007– 2013)/ERC Grant Agreement 320750. SED and HS acknowledge support from the Winton Programme for the physics of sustainability. HS also acknowledges support from the Funai Foundation for Information Technology and the British Council Japan Association. Part of the work was carried out at the University of Puerto Rico, supported by the DOEEBSCoR project DEG02-ER46526

IMAGES-III: The evolution of the Near-Infrared Tully-Fisher relation over the last 6 Gyr

Using the multi-integral field spectrograph GIRAFFE at VLT, we have derived the K-band Tully-Fisher relation (TFR) at z~0.6 for a representative sample of 65 galaxies with emission lines. We confirm that the scatter in the z~0.6 TFR is caused by galaxies with anomalous kinematics, and find a positive and strong correlation between the complexity of the kinematics and the scatter that they contribute to the TFR. Considering only relaxed-rotating disks, the scatter, and possibly also the slope of the TFR, do not appear to evolve with z. We detect an evolution of the K-band TFR zero point between z~0.6 and z=0, which, if interpreted as an evolution of the K-band luminosity of rotating disks, would imply that a brightening of 0.66+/-0.14 mag occurs between z~0.6 and z=0. Any disagreement with the results of Flores et al. (2006) are attributed to both an improvement of the local TFR and the more detailed accurate measurement of the rotation velocities in the distant sample. Most of the uncertainty can be explained by the relatively coarse spatial-resolution of the kinematical data. Because most rotating disks at z~0.6 are unlikely to experience further merging events, one may assume that their rotational velocity does not evolve dramatically. If true, our result implies that rotating disks observed at z~0.6 are rapidly transforming their gas into stars, to be able to double their stellar masses and be observed on the TFR at z=0. The rotating disks observed are indeed emission-line galaxies that are either starbursts or LIRGs, which implies that they are forming stars at a high rate. Thus, a significant fraction of the rotating disks are forming the bulk of their stars within 6 to 8 Gyr, in good agreement with former studies of the evolution of the M-Z relation.Comment: 17 pages, 11 figures, accepted for publication in A&A. v2 taking into account comments from language edito

Anti-tumour necrosis factor therapy for early-stage Dupuytren's disease (RIDD): a phase 2b, randomised, double-blind, placebo-controlled trial

Background Dupuytren's disease is a common fibrotic condition that causes the fingers to flex irreversibly into the palm. Treatments for late-stage disease all have limitations, and there is no approved treatment for early-stage disease. We identified tumour necrosis factor as a therapeutic target in Dupuytren's disease, and in a dose ranging trial found 40 mg adalimumab in 0·4 mL to be most efficacious. Here we aimed to assess the effects of intranodular injection of adalimumab in early-stage disease. Methods In this phase 2b, randomised, double-blind, placebo-controlled trial adults with early-stage Dupuytren's disease and an established clinically distinct nodule with a clear history of progression in the preceding 6 months were recruited from two clinical centres in the UK and were randomly assigned 1:1 to receive four injections of adalimumab or saline every 3 months. Participants and assessors were masked. The primary outcome was nodule hardness measured with a durometer at 12 months. Data were analysed by linear mixed effects regression models in the intention-to-treat population with multiple imputation for missing primary outcome data. The trial is registered at the ISRCTN registry, ISRCTN 27786905 and is complete. Findings Between Feb 17, 2017, and Jan 11, 2019, 284 participants were screened in the UK and 140 were enrolled. 47 (34%) participants were female and 93 (66%) were male. Mean age of participants was 59·7 years (SD 10·0). Primary outcome data were available from 113 participants. Nodule hardness was lower (−4·6 AU [95% CI −7·1 to −2·2], p=0·0002) in the adalimumab compared with the saline group at 12 months. There were no related serious adverse events; the most common adverse events were minor injection site reactions. Interpretation Intranodular injections of adalimumab in participants with early-stage Dupuytren's disease resulted in softening and reduction in size of the nodules. Longer follow-up would be required to assess the effect of tumour necrosis factor inhibition on disease progression, extension deficit and hand function. Funding Health Innovation Challenge Fund (Wellcome Trust, Department of Health) and 180 Life Sciences

Use of structure-activity landscape index curves and curve integrals to evaluate the performance of multiple machine learning prediction models

<p>Abstract</p> <p>Background</p> <p>Standard approaches to address the performance of predictive models that used common statistical measurements for the entire data set provide an overview of the average performance of the models across the entire predictive space, but give little insight into applicability of the model across the prediction space. Guha and Van Drie recently proposed the use of structure-activity landscape index (SALI) curves via the SALI curve integral (SCI) as a means to map the predictive power of computational models within the predictive space. This approach evaluates model performance by assessing the accuracy of pairwise predictions, comparing compound pairs in a manner similar to that done by medicinal chemists.</p> <p>Results</p> <p>The SALI approach was used to evaluate the performance of continuous prediction models for MDR1-MDCK <it>in vitro </it>efflux potential. Efflux models were built with ADMET Predictor neural net, support vector machine, kernel partial least squares, and multiple linear regression engines, as well as SIMCA-P+ partial least squares, and random forest from Pipeline Pilot as implemented by AstraZeneca, using molecular descriptors from <it>SimulationsPlus </it>and AstraZeneca.</p> <p>Conclusion</p> <p>The results indicate that the choice of training sets used to build the prediction models is of great importance in the resulting model quality and that the SCI values calculated for these models were very similar to their Kendall τ values, leading to our suggestion of an approach to use this SALI/SCI paradigm to evaluate predictive model performance that will allow more informed decisions regarding model utility. The use of SALI graphs and curves provides an additional level of quality assessment for predictive models.</p

Cardiosphere-derived cells suppress allogeneic lymphocytes by production of PGE2 acting via the EP4 receptor

derived cells (CDCs) are a cardiac progenitor cell population, which have been shown to possess cardiac regenerative properties and can improve heart function in a variety of cardiac diseases. Studies in large animal models have predominantly focussed on using autologous cells for safety, however allogeneic cell banks would allow for a practical, cost-effective and efficient use in a clinical setting. The aim of this work was to determine the immunomodulatory status of these cells using CDCs and lymphocytes from 5 dogs. CDCs expressed MHC I but not MHC II molecules and in mixed lymphocyte reactions demonstrated a lack of lymphocyte proliferation in response to MHC-mismatched CDCs. Furthermore, MHC-mismatched CDCs suppressed lymphocyte proliferation and activation in response to Concanavalin A. Transwell experiments demonstrated that this was predominantly due to direct cell-cell contact in addition to soluble mediators whereby CDCs produced high levels of PGE2 under inflammatory conditions. This led to down-regulation of CD25 expression on lymphocytes via the EP4 receptor. Blocking prostaglandin synthesis restored both, proliferation and activation (measured via CD25 expression) of stimulated lymphocytes. We demonstrated for the first time in a large animal model that CDCs inhibit proliferation in allo-reactive lymphocytes and have potent immunosuppressive activity mediated via PGE2

Antarctic last interglacial isotope peak in response to sea ice retreat not ice-sheet collapse

Several studies have suggested that sea-level rise during the last interglacial implies retreat of the West Antarctic Ice Sheet (WAIS). The prevalent hypothesis is that the retreat coincided with the peak Antarctic temperature and stable water isotope values from 128,000 years ago (128 ka); very early in the last interglacial. Here, by analysing climate model simulations of last interglacial WAIS loss featuring water isotopes, we show instead that the isotopic response to WAIS loss is in opposition to the isotopic evidence at 128 ka. Instead, a reduction in winter sea ice area of 65±7% fully explains the 128 ka ice core evidence. Our finding of a marked retreat of the sea ice at 128 ka demonstrates the sensitivity of Antarctic sea ice extent to climate warming

Elastic and anelastic relaxation behaviour of perovskite multiferroics I: PbZr0.53Ti0.47O3(PZT)-PbFe0.5Nb0.5O3(PNF)

Perovskites in the ternary system PbTiO3 (PT)–PbZrO3 (PZ)–Pb(Fe0.5Nb0.5)O3 (PFN) have attracted close interest because they can display simultaneous ferroelectric, magnetic and ferroelastic properties. Those with the most sensitive response to external fields are likely to have compositions near the morphotropic phase boundary (MPB) which lies close to the binary join Pb(Zr0.53Ti0.47)O3 (PZT)–PFN. In the present study, the strength and dynamics of strain coupling behaviour which accompanies the development of ferroelectricity and (anti)ferromagnetism in ceramic PZT–PFN samples have been investigated by resonant ultrasound spectroscopy. Elastic softening ahead of the cubic–tetragonal transition does not fit with models based on dispersion of the soft mode or relaxor characteristics but is attributed, instead, to coupling between acoustic modes and a central peak mode from correlated relaxations and/or microstructure dynamics. Softening of the shear modulus through the transition by up to ~50 % fits with the expected pattern for linear/quadratic strain/order parameter coupling at an improper ferroelastic transition and close to tricritical evolution for the order parameter. Superattenuation of acoustic resonances in a temperature interval of ~100 K below the transition point is indicative of mobile ferroelastic twin walls. By way of contrast, the first-order tetragonal–monoclinic transition involves only a small change in the shear modulus and is not accompanied by significant changes in acoustic dissipation. The dominant feature of the elastic and anelastic properties at low temperatures is a concave-up variation of the shear modulus and relatively high loss down to the lowest temperature, which appears to be the signature of materials with substantial local strain heterogeneity and a spectrum of strain relaxation times. No evidence of magnetoelastic coupling has been found, in spite of the samples displaying ferromagnetism below ~550 K and possible spin glass ordering below ~50 K. For the important multiferroic perovskite ceramics with compositions close to the MPB of ternary PT-PZ-PFN, there must be some focus in future on the role of strain heterogeneity