Developments and applications of the OPTIMADE API for materials discovery, design, and data exchange.

The Open Databases Integration for Materials Design (OPTIMADE) application programming interface (API) empowers users with holistic access to a growing federation of databases, enhancing the accessibility and discoverability of materials and chemical data. Since the first release of the OPTIMADE specification (v1.0), the API has undergone significant development, leading to the v1.2 release, and has underpinned multiple scientific studies. In this work, we highlight the latest features of the API format, accompanying software tools, and provide an update on the implementation of OPTIMADE in contributing materials databases. We end by providing several use cases that demonstrate the utility of the OPTIMADE API in materials research that continue to drive its ongoing development.

GPAW: An open Python package for electronic structure calculations.

We review the GPAW open-source Python package for electronic structure calculations. GPAW is based on the projector-augmented wave method and can solve the self-consistent density functional theory (DFT) equations using three different wave-function representations, namely real-space grids, plane waves, and numerical atomic orbitals. The three representations are complementary and mutually independent and can be connected by transformations via the real-space grid. This multi-basis feature renders GPAW highly versatile and unique among similar codes. By virtue of its modular structure, the GPAW code constitutes an ideal platform for the implementation of new features and methodologies. Moreover, it is well integrated with the Atomic Simulation Environment (ASE), providing a flexible and dynamic user interface. In addition to ground-state DFT calculations, GPAW supports many-body GW band structures, optical excitations from the Bethe-Salpeter Equation, variational calculations of excited states in molecules and solids via direct optimization, and real-time propagation of the Kohn-Sham equations within time-dependent DFT. A range of more advanced methods to describe magnetic excitations and non-collinear magnetism in solids are also now available. In addition, GPAW can calculate non-linear optical tensors of solids, charged crystal point defects, and much more. Recently, support for graphics processing unit (GPU) acceleration has been achieved with minor modifications to the GPAW code thanks to the CuPy library. We end the review with an outlook, describing some future plans for GPAW.

High-Throughput Search for Triplet Point Defects with Narrow Emission Lines in 2D Materials.

We employ a first-principles computational workflow to screen for optically accessible, high-spin point defects in wide band gap, two-dimensional (2D) crystals. Starting from an initial set of 5388 point defects, comprising both native and extrinsic, single and double defects in ten previously synthesized 2D host materials, we identify 596 defects with a triplet ground state. For these defects, we calculate the defect formation energy, hyperfine (HF) coupling, and zero-field splitting (ZFS) tensors. For 39 triplet transitions exhibiting particularly low Huang-Rhys factors, we calculate the full photoluminescence (PL) spectrum. Our approach reveals many spin defects with narrow PL line shapes and emission frequencies covering a broad spectral range. Most of the defects are hosted in hexagonal BN (hBN), which we ascribe to its high stiffness, but some are also found in MgI2, MoS2, MgBr2 and CaI2. As specific examples, we propose the defects vSMoS0 and NiSMoS0 in MoS2 as interesting candidates with potential applications to magnetic field sensors and quantum information technology.

Efficient first principles simulation of electron scattering factors for transmission electron microscopy.

Electron microscopy is a powerful tool for studying the properties of materials down to their atomic structure. In many cases, the quantitative interpretation of images requires simulations based on atomistic structure models. These typically use the independent atom approximation that neglects bonding effects, which may, however, be measurable and of physical interest. Since all electrons and the nuclear cores contribute to the scattering potential, simulations that go beyond this approximation have relied on computationally highly demanding all-electron calculations. Here, we describe a new method to generate ab initio electrostatic potentials when describing the core electrons by projector functions. Combined with an interface to quantitative image simulations, this implementation enables an easy and fast means to model electron scattering. We compare simulated transmission electron microscopy images and diffraction patterns to experimental data, showing an accuracy equivalent to earlier all-electron calculations at a much lower computational cost.

Interfacing CRYSTAL/AMBER to Optimize QM/MM Lennard⁻Jones Parameters for Water and to Study Solvation of TiO2 Nanoparticles.

Metal oxide nanoparticles (NPs) are regarded as good candidates for many technological applications, where their functional environment is often an aqueous solution. The correct description of metal oxide electronic structure is still a challenge for local and semilocal density functionals, whereas hybrid functional methods provide an improved description, and local atomic function-based codes such as CRYSTAL17 outperform plane wave codes when it comes to hybrid functional calculations. However, the computational cost of hybrids are still prohibitive for systems of real sizes, in a real environment. Therefore, we here present and critically assess the accuracy of our electrostatic embedding quantum mechanical/molecular mechanical (QM/MM) coupling between CRYSTAL17 and AMBER16, and demonstrate some of its capabilities via the case study of TiO2 NPs in water. First, we produced new Lennard⁻Jones (LJ) parameters that improve the accuracy of water⁻water interactions in the B3LYP/TIP3P coupling. We found that optimizing LJ parameters based on water tri- to deca-mer clusters provides a less overstructured QM/MM liquid water description than when fitting LJ parameters only based on the water dimer. Then, we applied our QM/MM coupling methodology to describe the interaction of a 1 nm wide multilayer of water surrounding a spherical TiO2 nanoparticle (NP). Optimizing the QM/MM water⁻water parameters was found to have little to no effect on the local NP properties, which provide insights into the range of influence that can be attributed to the LJ term in the QM/MM coupling. The effect of adding additional water in an MM fashion on the geometry optimized nanoparticle structure is small, but more evident effects are seen in its electronic properties. We also show that there is good transferability of existing QM/MM LJ parameters for organic molecules⁻water interactions to our QM/MM implementation, even though these parameters were obtained with a different QM code and QM/MM implementation, but with the same functional.

Cooperative targeting of melanoma heterogeneity with an AXL antibody-drug conjugate and BRAF/MEK inhibitors.

Intratumor heterogeneity is a key factor contributing to therapeutic failure and, hence, cancer lethality. Heterogeneous tumors show partial therapy responses, allowing for the emergence of drug-resistant clones that often express high levels of the receptor tyrosine kinase AXL. In melanoma, AXL-high cells are resistant to MAPK pathway inhibitors, whereas AXL-low cells are sensitive to these inhibitors, rationalizing a differential therapeutic approach. We developed an antibody-drug conjugate, AXL-107-MMAE, comprising a human AXL antibody linked to the microtubule-disrupting agent monomethyl auristatin E. We found that AXL-107-MMAE, as a single agent, displayed potent in vivo anti-tumor activity in patient-derived xenografts, including melanoma, lung, pancreas and cervical cancer. By eliminating distinct populations in heterogeneous melanoma cell pools, AXL-107-MMAE and MAPK pathway inhibitors cooperatively inhibited tumor growth. Furthermore, by inducing AXL transcription, BRAF/MEK inhibitors potentiated the efficacy of AXL-107-MMAE. These findings provide proof of concept for the premise that rationalized combinatorial targeting of distinct populations in heterogeneous tumors may improve therapeutic effect, and merit clinical validation of AXL-107-MMAE in both treatment-naive and drug-resistant cancers in mono- or combination therapy.

The atomic simulation environment-a Python library for working with atoms.

The atomic simulation environment (ASE) is a software package written in the Python programming language with the aim of setting up, steering, and analyzing atomistic simulations. In ASE, tasks are fully scripted in Python. The powerful syntax of Python combined with the NumPy array library make it possible to perform very complex simulation tasks. For example, a sequence of calculations may be performed with the use of a simple 'for-loop' construction. Calculations of energy, forces, stresses and other quantities are performed through interfaces to many external electronic structure codes or force fields using a uniform interface. On top of this calculator interface, ASE provides modules for performing many standard simulation tasks such as structure optimization, molecular dynamics, handling of constraints and performing nudged elastic band calculations.

Implementation of Constrained DFT for Computing Charge Transfer Rates within the Projector Augmented Wave Method.

Combining constrained density function theory (cDFT) with Marcus theory is an efficient and promising way to address charge transfer reactions. Here, we present a general and robust implementation of cDFT within the projector augmented wave (PAW) framework. PAW pseudopotentials offer a reliable frozen-core electron description across the whole periodic table, with good transferability, as well as facilitate the extraction of all-electron quantities. The present implementation is applicable to two different wave function representations, atomic-centered basis sets (LCAO) and the finite-difference (FD) approximation utilizing real-space grids. LCAO can be used for large systems, molecular dynamics, or quick initialization, while more accurate calculations are achieved with the FD basis. Furthermore, the calculations can be performed with flexible boundary conditions, ranging from isolated molecules to periodic systems in one-, two-, or three-dimensions. As such, this implementation is relevant for a wide variety of applications. We also present how to extract the electronic coupling element and reorganization energy from the resulting diabatic cDFT-PAW wave functions for the parametrization of Marcus theory. Here, the combined method is applied to important test cases where practical implementations of DFT fail due to the self-interaction error, such as the dissociation of the helium dimer cation, and it is compared to other established cDFT codes. Moreover, for charge localization in a diamine cation, where it was recently shown that the commonly used generalized gradient and hybrid functionals of DFT failed to produce the localized state, cDFT produces qualitatively and quantitatively accurate results when benchmarked against self-interaction corrected DFT and high-level CCSD(T) calculations at a fraction of the computational cost.

Association between sense of coherence in adolescence and social benefits later in life: a 12-year follow-up study.

OBJECTIVES: Local government concerns over expenditure on social and healthcare are growing. The aim of the present study was to explore the association between a weak 'sense of coherence' (SOC) in teens and their subsequent risk of receiving social and healthcare benefits during young adulthood, and to monitor how SOC developed during this period. DESIGN: Prospective cohort study. SETTING: North Denmark Region. PARTICIPANTS: 773 Pupils from seventh and eighth forms who answered a questionnaire in 1998. OUTCOME MEASURES: Different social benefits (from the Danish DREAM database embracing disbursed public social benefits). Change in SOC score from 1998 to 2010. RESULTS: 722 had answered seven items of the original SOC-13 questionnaire (denoted by SOC-7). Girls with a weak SOC-7 (the lowest 1st quartile) in 1998 had a significantly increased risk of receiving unemployment benefits (RR 1.3 (1.1 to 1.6)), social assistance (RR 1.8 (1.3 to 2.5)) and sickness benefits (RR 1.5 (1.2 to 2.0)) compared with girls with a strong SOC-7. For boys, only minor protective and non-significant differences were found. The SOC answers from 1998 and 2010 were compared (n=394). SOC increased significantly and mostly in girls. CONCLUSIONS: SOC-7 may serve as a predictor for social life event outcomes and hence facilitate an early identification and a selective approach to support teenage girls with a weak SOC. From adolescence to young adulthood, SOC-7 was of a relatively unstable nature.

Detecting reduced renal function in children: comparison of GFR-models and serum markers.

BACKGROUND: The aim of this study was to compare the ability of renal indicators [serum creatinine (SCr), cystatin C (SCysC)] and glomerular filtration rate (GFR)-models to discriminate normal and reduced renal function. As a single cut-off level will always lead to false classifications, we propose using two cut-off levels, dividing renal function into normal or reduced, with an intermediate "gray zone" of indeterminable results. METHODS: Glomerular filtration rate was measured by plasma clearance of (51)Cr-EDTA (13.7-147.4 mL/min/1.73 m(2)) in 119 children (age range 2.3-14.9 years). Reduced renal function was defined as a GFR of <82 mL/min/1.73 m(2). SCr, SCysC, age-normalized creatinine (SCr-ratio), and eight published GFR-models were compared for their ability to correctly classify renal function as normal or reduced. Cut-off levels were determined so as to give 99 % certainty outside the gray zone. RESULTS: The multivariable GFR-models by Schwartz et al. (J Am Soc Nephrol 2009; 20:629-637) and Zappitelli et al. (Am J Kidney Dis 2006; 48:221-230) and two models by Andersen et al. [Am J Kidney Dis 2012; 59(1):50-57: body cell mass (BCM)-model and Weight-model] performed significantly better than all other variables (P < 0.01), with the BCM-model performing the best (P < 0.05). The SCr-based Schwartz formula and SCr-ratio both performed better than SCr and SCysC. CONCLUSIONS: Among the 119 children enrolled in this study and the renal indicators tested, the BCM-model had the best diagnostic performance in terms of screening for normal or reduced renal function, and the SCr-ratio was a superior diagnostic tool to both SCr and SCysC.

Simplified methods for assessment of renal function as the ratio of glomerular filtration rate to extracellular fluid volume.

BACKGROUND: Instead of scaling glomerular filtration rate (GFR) to a body surface area of 1.73 m(2), it has been suggested to scale GFR to extracellular fluid volume (ECV). The ratio GFR/ECV has physiological meaning in that it indicates how often 'that which is to be regulated' (i.e. ECV) comes into contact with the 'regulator' (i.e. the kidneys). AIM: The aim of the present study was as follows: to analyse two published calculation methods for determining ECV and GFR/ECV; to develop a new simple and accurate formula for determining ECV; and to compare and evaluate these methods. MATERIALS AND METHODS: GFR was determined as (51)Cr-EDTA clearance. The study comprised 128 individuals (35 women, 66 men and 27 children) with a full (51)Cr-EDTA plasma concentration curve, determined from injection until 4-5 h p.i. Reference values for GFR and ECV were calculated from the full curve. One-pool approximations C/(1) and V(1) were calculated using only the final-slope curve. Four calculation methods were compared: simple one-pool values; GFR/ECV according to Peters and colleagues; ECV according to Brøchner-Mortensen (BM); and ECV according to a new method (JBM): y=2x-1, where x=Cl(1)/Cl and y=V(1)/ECV. RESULTS: The new JBM method is accurate and can be explained theoretically. BM has a slight bias for high renal function. The Peters method had bias in our data. GFR/ECV had better precision than ECV alone, especially for BM and JBM, which were within -4% to +7% of the reference values (95% limits of agreement in adults). CONCLUSION: GFR/ECV can be precisely determined, especially with the BM and JBM methods. Expressing GFR/ECV in unit %/h gives a simple interpretation. Normal ranges for GFR/ECV need to be established.

The minipig as nonrodent species in toxicology--where are we now?

Over the past 3 decades minipigs have moved from being an obscure alternative to dogs and nonhuman primates to being a standard animal model in regulatory toxicity studies. This article covers the use of minipigs as a model in the context of nonclinical drug safety and provides an overview of the minipig's developmental history and relates minipigs to other animal species commonly used in toxicology; and the minipig's translational power is supported by 43 case studies of marketed drug products covered. Special focus is given to criteria for selecting minipigs in nonclinical programs supporting the development of new medicines; the use of swine in the assessment of food additives, agrochemicals, and pesticides; as well as a regulatory perspective on the use of minipigs in Food and Drug Administration (FDA)-regulated products. This article presents the main points conveyed at a symposium held at the 2010 American College of Toxicology meeting in Baltimore, Maryland.

Social inequalities in childhood are predictors of unemployment in early adulthood.

INTRODUCTION: The aim of the present study was to establish if social inequalities in early childhood, particularly living in a socially and economically deprived neighbourhood, are predictive of later unemployment. MATERIAL AND METHODS: A cohort was established in 1987. It consists of 8-9 year-old children living in a socially deprived suburb who were followed in national registers for all categories of welfare benefits. The follow-up covered the period when participants were 21-27 years of age. A control group with the same age and gender distribution who were living in a neighbouring, relatively privileged middle class district were also followed for the purpose of comparison. RESULTS: The annual unemployment rate during the seven years of follow-up was significantly higher in the deprived neighbourhood group than in the middle class neighbourhood group, whereas long-term unemployment lasting more than two years did not differ significantly between the groups. Childhood background including a mother receiving social benefit was an independent factor associated with increased risk of later unemployment, whereas gender and single parenthood were not. CONCLUSION: The present findings suggest that socioeconomic disadvantage during childhood substantially increases the risk of unemployment in early adulthood, even during a follow-up period in the first decade of the 21st century when employment opportunities in Denmark were excellent. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

GFR prediction from cystatin C and creatinine in children: effect of including body cell mass.

BACKGROUND: Aiming to develop a more accurate cystatin C-based model for estimation of glomerular filtration rate (GFR) in children, we hypothesized that inclusion of body cell mass (BCM) would increase the accuracy of the GFR estimate in comparison to a well-established GFR reference method. STUDY DESIGN: Diagnostic test accuracy study. SETTINGS & PARTICIPANTS: 119 children (mean age, 8.8; range, 2.3-14.9 years) referred for GFR measurement by chromium 51 ethylenediaminetetraacetic acid ((51)Cr-EDTA) clearance (mean GFR, 98; range, 13.7-147.4 mL/min/1.73 m(2)). INDEX TEST: GFR estimations by the 2 prediction models resulting from theoretical considerations corroborated by forward stepwise variable selection: GFR (mL/min) = 0.542 × (BCM/SCysC)(0.40) × (height × BSA/SCr)(0.65) and GFR (mL/min) = 0.426 × (weight/SCysC)(0.39) × (height × BSA/SCr)(0.64), where SCysC is serum cystatin C level, BSA is body surface area, and SCr is serum creatinine level. The accuracy and precision of these models were compared with 7 previously published prediction models using random subsampling cross-validation. Local constants and coefficients were calculated for all models. Root mean square error, R(2), and percentage of predictions within ±10% and ±30% of the reference GFR were calculated for all models. Based on 1,000 runs of the cross-validation procedure, median values and 2.5th and 97.5th quantiles of the validation parameters were calculated. REFERENCE TEST: GFR measurement by (51)Cr-EDTA clearance. RESULTS: The BCM model predicted 98% within ±30% of reference GFR and 66% within ±10%, which was higher than for any other model. The weight model predicted 97.5% within ±30% of reference GFR and 62% within ±10%. The BCM model had the highest R(2) and the smallest root mean square error. LIMITATIONS: Included only 9 children with GFR <60 mL/min/1.73 m(2). Lack of independent validation cohort. CONCLUSIONS: The novel BCM model predicts GFR with higher accuracy than previously published models. The weight model is almost as accurate as the BCM model and allows for GFR estimation without knowledge of BCM. However, endogenous methods are still not sufficiently accurate to replace exogenous markers when GFR must be determined with high accuracy.

Dispersive and covalent interactions between graphene and metal surfaces from the random phase approximation.

We calculate the potential energy surfaces for graphene adsorbed on Cu(111), Ni(111), and Co(0001) using density functional theory and the random phase approximation (RPA). For these adsorption systems covalent and dispersive interactions are equally important and while commonly used approximations for exchange-correlation functionals give inadequate descriptions of either van der Waals or chemical bonds, RPA accounts accurately for both. It is found that the adsorption is a delicate competition between a weak chemisorption minimum close to the surface and a physisorption minimum further from the surface.

Ab initio van der waals interactions in simulations of water alter structure from mainly tetrahedral to high-density-like.

The structure of liquid water at ambient conditions is studied in ab initio molecular dynamics simulations in the NVE ensemble using van der Waals (vdW) density-functional theory, i.e., using the new exchange-correlation functionals optPBE-vdW and vdW-DF2, where the latter has softer nonlocal correlation terms. Inclusion of the more isotropic vdW interactions counteracts highly directional hydrogen bonds, which are enhanced by standard functionals. This brings about a softening of the microscopic structure of water, as seen from the broadening of angular distribution functions and, in particular, from the much lower and broader first peak in the oxygen-oxygen pair-correlation function (PCF) and loss of structure in the outer hydration shells. Inclusion of vdW interactions is shown to shift the balance of resulting structures from open tetrahedral to more close-packed. The resulting O-O PCF shows some resemblance with experiment for high-density water (Soper, A. K. and Ricci, M. A. Phys. Rev. Lett. 2000, 84, 2881), but not directly with experiment for ambient water. Considering the accuracy of the new functionals for interaction energies, we investigate whether the simulation protocol could cause the deviation. An O-O PCF consisting of a linear combination of 70% from vdW-DF2 and 30% from low-density liquid water, as extrapolated from experiments, reproduces near-quantitatively the experimental O-O PCF for ambient water. This suggests the possibility that the new functionals may be reliable and that instead larger-scale simulations in the NPT ensemble, where the density is allowed to fluctuate in accordance with proposals for supercooled water, could resolve the apparent discrepancy with the measured PCF.

Precision and within- and between-day variation of bioimpedance parameters in children aged 2-14 years.

BACKGROUND & AIMS: Bioimpedance spectroscopy (BIS) offers the possibility to perform rapid estimates of fluid distribution and body composition. Few studies, however, have addressed the precision and biological variation in a pediatric population. Our objectives were to evaluate precision, variation within- and between-days for the BIS-determined parameters total body fluid, extra-cellular fluid, intra-cellular fluid, body cell mass, fat-free mass, extra-cellular resistance, intra-cellular resistance and percentage body fat using a Xitron 4200. METHODS: All 133 children (81 boys, 52 girls; 2.4-14.9 years) had one series measured on day one (precision population). Forty-four children had a second series on day one (within-day sub-population). Thirty-two children had a series measured on the next day (between-day sub-population). Each measurement series consisted of three repeated measurements. A linear mixed model was used for statistical analysis. RESULTS: The precision was 0.3-0.8% in children ≥6 years and 0.5-2.4% in children <6 years with a statistically significant difference between the two age-groups (p<0.001). Within-day variation was 1.1-2.8% and between-day variation 2.4-5.7%. Total variation and reference change values are reported. CONCLUSION: The Xitron 4200 has a very good but age-dependent precision. The median value of three repeated measurements is recommended in order to avoid incorrect measurements.