A critical examination of compound stability predictions from machine-learned formation energies

Machine learning has emerged as a novel tool for the efficient prediction of material properties, and claims have been made that machine-learned models for the formation energy of compounds can approach the accuracy of Density Functional Theory (DFT). The models tested in this work include five recently published compositional models, a baseline model using stoichiometry alone, and a structural model. By testing seven machine learning models for formation energy on stability predictions using the Materials Project database of DFT calculations for 85,014 unique chemical compositions, we show that while formation energies can indeed be predicted well, all compositional models perform poorly on predicting the stability of compounds, making them considerably less useful than DFT for the discovery and design of new solids. Most critically, in sparse chemical spaces where few stoichiometries have stable compounds, only the structural model is capable of efficiently detecting which materials are stable. The nonincremental improvement of structural models compared with compositional models is noteworthy and encourages the use of structural models for materials discovery, with the constraint that for any new composition, the ground-state structure is not known a priori. This work demonstrates that accurate predictions of formation energy do not imply accurate predictions of stability, emphasizing the importance of assessing model performance on stability predictions, for which we provide a set of publicly available tests

Interoception, Contemplative Practice, and Health

AcceptedArticleCopyright: © 2015 Farb, Daubenmier, Price, Gard, Kerr, Dunn, KLein, Paulus and Mehling.This Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permission.Interoception can be broadly defined as the sense of signals originating within the body. As such, interoception is critical for our sense of embodiment, motivation and well-being. And yet, despite its importance, interoception remains poorly understood within modern science. This paper reviews interdisciplinary perspectives on interoception, with the goal of presenting a unified perspective from diverse fields such as neuroscience, clinical practice, and contemplative studies. It is hoped that this integrative effort will advance our understanding of how interoception determines well-being, and identify the central challenges to such understanding. To this end, we introduce an expanded taxonomy of interoceptive processes, arguing that many of these processes can be understood through an emerging predictive coding model for mind-body integration. The model, which describes the tension between expected and felt body sensation, parallels contemplative theories, and implicates interoception in a variety of affective and psychosomatic disorders. We conclude that maladaptive construal of bodily sensations may lie at the heart of many contemporary maladies, and that contemplative practices may attenuate these interpretative biases, restoring a person’s sense of presence and agency in the world

Using Whole Genome Sequences to Investigate Adenovirus Outbreaks in a Hematopoietic Stem Cell Transplant Unit

A recent surge in human mastadenovirus (HAdV) cases, including five deaths, amongst a haematopoietic stem cell transplant population led us to use whole genome sequencing (WGS) to investigate. We compared sequences from 37 patients collected over a 20-month period with sequences from GenBank and our own database of HAdVs. Maximum likelihood trees and pairwise differences were used to evaluate genotypic relationships, paired with the epidemiological data from routine infection prevention and control (IPC) records and hospital activity data. During this time period, two formal outbreaks had been declared by IPC, while WGS detected nine monophyletic clusters, seven were corroborated by epidemiological evidence and by comparison of single-nucleotide polymorphisms. One of the formal outbreaks was confirmed, and the other was not. Of the five HAdV-associated deaths, three were unlinked and the remaining two considered the source of transmission. Mixed infection was frequent (10%), providing a sentinel source of recombination and superinfection. Immunosuppressed patients harboring a high rate of HAdV positivity require comprehensive surveillance. As a consequence of these findings, HAdV WGS is being incorporated routinely into clinical practice to influence IPC policy contemporaneously

Chaste: an open source C++ library for computational physiology and biology

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials

Correction: CD93 is expressed on chronic myeloid leukemia stem cells and identifies a quiescent population which persists after tyrosine kinase inhibitor therapy

Correction to: Leukemia https://doi.org/10.1038/s41375-019-0684-

Statistical analysis plan for the ‘Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage’ (TICH-2) trial

Rationale Aside from blood pressure lowering, treatment options for intracerebral haemorrhage remain limited and a proportion of patients will undergo early haematoma expansion with resultant significant morbidity and mortality. Tranexamic acid (TXA), an anti-fibrinolytic drug, has been shown to significantly reduce mortality in patients, who are bleeding following trauma, when given rapidly. TICH-2 is testing whether TXA is effective at improving outcome in spontaneous intracerebral haemorrhage (SICH). Methods and design TICH-2 is a pragmatic, phase III, prospective, double-blind, randomised placebo-controlled trial. Two thousand adult (aged ≥ 18 years) patients with an acute SICH, within 8 h of stroke onset, will be randomised to receive TXA or the placebo control. The primary outcome is ordinal shift of modified Rankin Scale score at day 90. Analyses will be performed using intention-to-treat. Results This paper and its attached appendices describe the statistical analysis plan (SAP) for the trial and were developed and published prior to database lock and unblinding to treatment allocation. The SAP includes details of analyses to be undertaken and unpopulated tables which will be reported in the primary and key secondary publications. The database will be locked in early 2018, ready for publication of the results later in the same year. Discussion The SAP details the analyses that will be done to avoid bias arising from prior knowledge of the study findings. The trial will determine whether TXA can improve outcome after SICH, which currently has no definitive therapy. Trial registration ISRCTN registry, ID: ISRCTN93732214. Registered on 17 January 2013

Protracted timescales of lower crustal growth at the fast-spreading East Pacific Rise

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Geoscience 5 (2012): 275-278, doi:10.1038/ngeo1378.Formation of the oceanic crust at mid-ocean ridges is a fundamental component of plate tectonics. A majority of the crust at many ridges is composed of plutonic rocks that form by crystallization of mantle-derived magmas within the crust. Recent application of U/Pb dating to samples from in-situ oceanic crust has begun to provide exciting new insight into the timing, duration and distribution of magmatism during formation of the plutonic crust1-4. Previous studies have focused on samples from slow-spreading ridges, however, the time scales and processes of crustal growth are expected to vary with plate spreading rate. Here we present the first high-precision dates from plutonic crust formed at the fast-spreading East Pacific Rise (EPR). Individual zircon minerals yielded dates from 1.420–1.271 million years ago, with uncertainties of ± 0.006–0.081 million years. Within individual samples, zircons record a range of dates of up to ~0.124 million years, consistent with protracted crystallization or assimilation of older zircons from adjacent rocks. The variability in dates is comparable to data from the Vema lithospheric section on the Mid-Atlantic Ridge (MAR)3, suggesting that time scales of magmatic processes in the lower crust may be similar at slow- and fast-spreading ridges.This research was partially funded by NSF grant OCE-0727914 (SAB), a Cardiff University International Collaboration Award (CJL) and NERC grant NE/C509023/1 (CJM).2012-07-2

Regulation of p14ARF expression by miR-24: a potential mechanism compromising the p53 response during retinoblastoma development

<p>Abstract</p> <p>Background</p> <p>Most human cancers show inactivation of both pRB- and p53-pathways. While retinoblastomas are initiated by loss of the <it>RB1 </it>tumor suppressor gene, <it>TP53 </it>mutations have not been found. High expression of the p53-antagonist MDM2 in human retinoblastomas may compromise p53 tumor surveillance so that <it>TP53 </it>mutations are not selected for in retinoblastoma tumorigenesis. We previously showed that p14^ARFprotein, which activates p53 by inhibiting MDM2, is low in retinoblastomas despite high mRNA expression.</p> <p>Methods</p> <p>In human fetal retinas, adult retinas, and retinoblastoma cells, we determined endogenous <it>p14^ARF</it>mRNA, ARF protein, and miR-24 expression, while integrity of p53 signalling in WERI-Rb1 cells was tested using an adenovirus vector expressing p14^ARF. To study p14^ARFbiogenesis, retinoblastoma cells were treated with the proteasome inhibitor, MG132, and siRNA against miR-24.</p> <p>Results</p> <p>In human retinoblastoma cell lines, <it>p14^ARF</it>mRNA was disproportionally high relative to the level of p14^ARFprotein expression, suggesting a perturbation of p14^ARFregulation. When p14^ARFwas over-expressed by an adenovirus vector, expression of p53 and downstream targets increased and cell growth was inhibited indicating an intact p14^ARF-p53 axis. To investigate the discrepancy between <it>p14^ARF</it>mRNA and protein in retinoblastoma, we examined p14^ARFbiogenesis. The proteasome inhibitor, MG132, did not cause p14^ARFaccumulation, although p14^ARFnormally is degraded by proteasomes. miR-24, a microRNA that represses p14^ARFexpression, is expressed in retinoblastoma cell lines and correlates with lower protein expression when compared to other cell lines with high <it>p14^ARF</it>mRNA. Transient over-expression of siRNA against miR-24 led to elevated p14^ARFprotein in retinoblastoma cells.</p> <p>Conclusions</p> <p>In retinoblastoma cells where high levels of <it>p14^ARF</it>mRNA are not accompanied by high p14^ARFprotein, we found a correlation between miR-24 expression and low p14^ARFprotein. p14^ARFprotein levels were restored without change in mRNA abundance upon miR-24 inhibition suggesting that miR-24 could functionally repress expression, effectively blocking p53 tumor surveillance. During retinal tumorigenesis, miR-24 may intrinsically compromise the p53 response to <it>RB1 </it>loss.</p