Density functional theory describes matter at the quantum level, but all popular approximations suffer from systematic errors that arise from the violation of mathematical properties of the exact ...functional. We overcame this fundamental limitation by training a neural network on molecular data and on fictitious systems with fractional charge and spin. The resulting functional, DM21 (DeepMind 21), correctly describes typical examples of artificial charge delocalization and strong correlation and performs better than traditional functionals on thorough benchmarks for main-group atoms and molecules. DM21 accurately models complex systems such as hydrogen chains, charged DNA base pairs, and diradical transition states. More crucially for the field, because our methodology relies on data and constraints, which are continually improving, it represents a viable pathway toward the exact universal functional.
Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults and continues to portend poor survival, despite multimodal treatment using surgery and chemoradiotherapy. The addition ...of tumour-treating fields (TTFields)-an approach in which alternating electrical fields exert biophysical force on charged and polarisable molecules known as dipoles-to standard therapy, has been shown to extend survival for patients with newly diagnosed GBM, recurrent GBM and mesothelioma, leading to the clinical approval of this approach by the FDA. TTFields represent a non-invasive anticancer modality consisting of low-intensity (1-3 V/cm), intermediate-frequency (100-300 kHz), alternating electric fields delivered via cutaneous transducer arrays configured to provide optimal tumour-site coverage. Although TTFields were initially demonstrated to inhibit cancer cell proliferation by interfering with mitotic apparatus, it is becoming increasingly clear that TTFields show a broad mechanism of action by disrupting a multitude of biological processes, including DNA repair, cell permeability and immunological responses, to elicit therapeutic effects. This review describes advances in our current understanding of the mechanisms by which TTFields mediate anticancer effects. Additionally, we summarise the landscape of TTFields clinical trials across various cancers and consider how emerging preclinical data might inform future clinical applications for TTFields.
Summary Background Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial ...resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae. Methods The mcr-1 gene in E coli strain SHP45 was identified by whole plasmid sequencing and subcloning. MCR-1 mechanistic studies were done with sequence comparisons, homology modelling, and electrospray ionisation mass spectrometry. The prevalence of mcr-1 was investigated in E coli and Klebsiella pneumoniae strains collected from five provinces between April, 2011, and November, 2014. The ability of MCR-1 to confer polymyxin resistance in vivo was examined in a murine thigh model. Findings Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10−1 to 10−3 cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa . In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011–14, and 16 (1%) of 1322 samples from inpatients with infection. Interpretation The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria. Funding Ministry of Science and Technology of China, National Natural Science Foundation of China.
We report the development of a python-based auxiliary-field quantum Monte Carlo (AFQMC) program, ipie, with preliminary timing benchmarks and new AFQMC results on the isomerization of Cu2O22+. We ...demonstrate how implementations for both central and graphical processing units (CPUs and GPUs) are achieved in ipie. We show an interface of ipie with PySCF as well as a straightforward template for adding new estimators to ipie. Our timing benchmarks against other C++ codes, QMCPACK and Dice, suggest that ipie is faster or similarly performing for all chemical systems considered on both CPUs and GPUs. Our results on Cu2O22+ using selected configuration interaction trials show that it is possible to converge the ph-AFQMC isomerization energy between bis(μ-oxo) and μ-η2:η2 peroxo configurations to the exact known results for small basis sets with 105–106 determinants. We also report the isomerization energy with a quadruple-zeta basis set with an estimated error less than a kcal/mol, which involved 52 electrons and 290 orbitals with 106 determinants in the trial wave function. These results highlight the utility of ph-AFQMC and ipie for systems with modest strong correlation and large-scale dynamic correlation.
Summary Background In 2005, with the goal of reducing the numbers of maternal and neonatal deaths, the Government of India launched Janani Suraksha Yojana (JSY), a conditional cash transfer scheme, ...to incentivise women to give birth in a health facility. We independently assessed the effect of JSY on intervention coverage and health outcomes. Methods We used data from the nationwide district-level household surveys done in 2002–04 and 2007–09 to assess receipt of financial assistance from JSY as a function of socioeconomic and demographic characteristics; and used three analytical approaches (matching, with-versus-without comparison, and differences in differences) to assess the effect of JSY on antenatal care, in-facility births, and perinatal, neonatal, and maternal deaths. Findings Implementation of JSY in 2007–08 was highly variable by state—from less than 5% to 44% of women giving birth receiving cash payments from JSY. The poorest and least educated women did not always have the highest odds of receiving JSY payments. JSY had a significant effect on increasing antenatal care and in-facility births. In the matching analysis, JSY payment was associated with a reduction of 3·7 (95% CI 2·2–5·2) perinatal deaths per 1000 pregnancies and 2·3 (0·9–3·7) neonatal deaths per 1000 livebirths. In the with-versus-without comparison, the reductions were 4·1 (2·5–5·7) perinatal deaths per 1000 pregnancies and 2·4 (0·7–4·1) neonatal deaths per 1000 livebirths. Interpretation The findings of this assessment are encouraging, but they also emphasise the need for improved targeting of the poorest women and attention to quality of obstetric care in health facilities. Continued independent monitoring and evaluations are important to measure the effect of JSY as financial and political commitment to the programme intensifies. Funding Bill & Melinda Gates Foundation.
•Defines the general issue of Emerging Infectious Diseases in the context of landscape planning.•Proposes a “global urban ecosystem” (GUE) conceptual framework to best understand how pandemics ...occur.•Outlines pandemic HIV/AIDS and pandemic influenza as the result of the global urban ecosystem.
This paper considers the role of landscape planning and design in the context of a growing need for research and policy recommendations associated with Emerging Infectious Diseases (EIDs), of which COVID-19 is the most recent. Beginning with a definition of EIDs and their origins within the context of landscape planning, the paper then argues that planning and design scholars and practitioners should begin by seeing the importance of a “global urban ecosystem” (GUE) comprised of rapidly transforming metropolitan and regional “patches” connected through “corridors” of relatively unregulated global transportation and mobility networks. It then revisits the history of the two prior global pandemics of HIV/AIDS and pandemic influenza to establish the importance of a landscape planning perspective at the intersection of wildlife, livestock, and globally connected human communities. The essay concludes by arguing that this GUE concept can facilitate creative planning and design by adapting concepts established in other patch and corridor networks like urban transit systems to the ongoing risk of future pandemic EIDs.
The established model-free methods for the processing of two-electron dipolar spectroscopy data DEER (double electron-electron resonance), PELDOR (pulsed electron double resonance), DQ-EPR ...(double-quantum electron paramagnetic resonance), RIDME (relaxation-induced dipolar modulation enhancement), etc. use regularized fitting. In this communication, we describe an attempt to process DEER data using artificial neural networks trained on large databases of simulated data. Accuracy and reliability of neural network outputs from real experimental data were found to be unexpectedly high. The networks are also able to reject exchange interactions and to return a measure of uncertainty in the resulting distance distributions. This paper describes the design of the training databases, discusses the training process, and rationalizes the observed performance. Neural networks produced in this work are incorporated as options into Spinach and DeerAnalysis packages.
Deep neural networks have been very successful as highly accurate wave function Ansätze for variational Monte Carlo calculations of molecular ground states. We present an extension of one such ...Ansatz, FermiNet, to calculations of the ground states of periodic Hamiltonians, and study the homogeneous electron gas. FermiNet calculations of the ground-state energies of small electron gas systems are in excellent agreement with previous initiator full configuration interaction quantum Monte Carlo and diffusion Monte Carlo calculations. We investigate the spin-polarized homogeneous electron gas and demonstrate that the same neural network architecture is capable of accurately representing both the delocalized Fermi liquid state and the localized Wigner crystal state. The network converges on the translationally invariant ground state at high density and spontaneously breaks the symmetry to produce the crystalline ground state at low density, despite being given no a priori knowledge that a phase transition exists.
The straightforward non-covalent functionalization and solubilization of hexagonal boron nitride nanosheets (BNNSs) has been achieved by reacting either polythiophene or polyvinylpyrrolidone polymers ...with exfoliated BNNSs. The BNNSs apparently form strong
π
–
π
stacking interactions with the polymers to yield stable derivatized nanosheets with modified properties. A number of polythiophene polymers functionalized with carboxylic acid groups that are connected to the thiophene subunit by varying numbers of CH
2
-hydrocarbon linker units have also been tethered to the exfoliated BNNSs. These BNNS–polythiophene–(CH
2
)
n
–COOH structures have been further coordinated to pre-formed TiO
2
nanoparticles to form more complex BNNS–polythiophene–(CH
2
)
n
–COO–TiO
2
hybrid nanomaterials through covalent binding between the TiO
2
nanoparticle surface and the carboxylic acid functional group of the BNNS–polythiophene unit. These novel structures have been characterized by SEM, TEM, FTIR, UV–Vis, and other spectroscopic data.
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