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International audience; Understanding the generation and evolution of defects induced in matter by ion irradiation is of fundamental importance to estimate the degradation of functional properties of materials. Computational approaches used in different communities, from space radiation effects to nuclear energy experiments, are based on a number of approximations that, among others, traditionally neglect the coupling between electronic and ionic degrees of freedom in the description of displacements. In this work, we study collision cascades in GaAs, including the electronic stopping power for self-projectiles in different directions obtained via real-time time-dependent density functional theory in molecular dynamics simulations of collision cascades, using the recent electron-phonon model and the previously developed two-temperature model. We show that the former can be well applied to describe the effects of electronic stopping in molecular dynamics simulations of collision cascades in a multielement semiconductor and that the number of defects is considerably affected by electronic stopping effects. The results are also discussed in the wider context of the commonly used nonionizing energy loss model to estimate degradation of materials by cumulative displacements.

Neurodegenerative disorders are associated with different pathologies that often co-occur but cannot be measured specifically with in vivo methods.Thirty-three brain hemispheres from donors with an Alzheimer's disease (AD) spectrum diagnosis underwent T2-weighted magnetic resonance imaging (MRI). Gray matter thickness was paired with histopathology from the closest anatomic region in the contralateral hemisphere.Partial Spearman correlation of phosphorylated tau and cortical thickness with TAR DNA-binding protein 43 (TDP-43) and α-synuclein scores, age, sex, and postmortem interval as covariates showed significant relationships in entorhinal and primary visual cortices, temporal pole, and insular and posterior cingulate gyri. Linear models including Braak stages, TDP-43 and α-synuclein scores, age, sex, and postmortem interval showed significant correlation between Braak stage and thickness in the parahippocampal gyrus, entorhinal cortex, and Broadman area 35.We demonstrated an association of measures of AD pathology with tissue loss in several AD regions despite a limited range of pathology in these cases.Neurodegenerative disorders are associated with co-occurring pathologies that cannot be measured specifically with in vivo methods. Identification of the topographic patterns of these pathologies in structural magnetic resonance imaging (MRI) may provide probabilistic biomarkers. We demonstrated the correlation of the specific patterns of tissue loss from ex vivo brain MRI with underlying pathologies detected in postmortem brain hemispheres in patients with Alzheimer's disease (AD) spectrum disorders. The results provide insight into the interpretation of in vivo structural MRI studies in patients with AD spectrum disorders.

A recently proposed theoretical framework for the description of electronic quantum friction for constant-velocity nuclear projectiles traversing periodic crystals is here implemented using a local basis representation. The theory requires a change of reference frame to that of the projectile, and a basis set transformation for the target basis functions to a gliding basis is presented, which is time-periodic but does not displace in space with respect to the projectile, allowing a local-basis Floquet impurity-scattering formalism to be used. It is illustrated for a one-dimensional single-band tight-binding model, as the simplest paradigmatic example, displaying the qualitative behaviour of the formalism. The time-dependent non-orthogonality of the gliding basis requires care in the proper (simplest) definition of a local projectile perturbation. The Fermi level is tilted with a slope given by the projectile velocity, which complicates integration over occupied states. It is solved by a recurrent application of the Lippmann-Schwinger equation, in analogy with previous non-equilibrium treatment of electron ballistic transport. Aiming towards a first-principles mean-field-like implementation, the final result is the time-periodic particle density in the region around the projectile, describing the stroboscopically stationary perturbation cloud around the projectile, out of which other quantities can be obtained, such as the electronic stopping power.

The amygdaloid complex (AC) is involved in very relevant cognitive and emotional pathways, and exhibit changes in aging and in some neurological and psychiatric disorders. The quantitative estimators of AC could be useful to understand the impact of amygdaloid pathology in these processes, both globally and for each nucleus in particular, and their neurons. The present study analyzes morphometric and stereological estimators in the whole AC and its three main nuclei (lateral (La), basal (Ba) and accessory basal (AB) in six Macaca fascicularis monkeys. All the brains were fixed and sectioned in the coronal plane; Nissl stained sections were used for estimation of size and form parameters in both, the AC, and the La, Ba, and AB nuclei separately. The study includes stereological estimates of the volume and surface area of the AC; also, volume of the neurons in the amygdaloid nuclei was estimated using the point-sampled intercepts method. Our results show that the AB nucleus is smaller than both the La and Ba nuclei in both morphometric and stereological estimators. Brain hemispheric side had not significant influence on any of quantitative estimates. The neuron volume was higher in the AB nucleus relative to LA and Ba of the nuclei. These data describe some quantitative parameters of the amygdaloid complex and their main nuclei that could help us to detect small changes in neurodegenerative and other pathological processes. This article is protected by copyright. All rights reserved.

The computational study of DNA and its interaction with ligands is a highly relevant area of research, with significant consequences for developing new therapeutic strategies. However, the computational description of such large and complex systems requires considering interactions of different types simultaneously in a balanced way, such as non-covalent weak interactions (namely hydrogen bonds and stacking), metal–ligand interactions, polarisation and charge transfer effects. All these considerations imply a real challenge for computational chemistry. The possibility of studying large biological systems using quantum methods for the entire system requires significant computational resources, with improvements in parallelisation and optimisation of theoretical strategies. Computational methods, such as Linear-Scaling Density Functional Theory (LS-DFT) and DLPNO-CCSD(T), may allow performing ab initio quantum mechanics calculations, including the electronic structure for large biological systems, in a reasonable computing time. In this work, we study the interaction of small molecules and cations with DNA (both duplex DNA and G-quadruplexes), comparing different computational methods: a LS-DFT method at the LMKLL/DZDP level of theory, semi-empirical methods (PM6-DH2 and PM7), mixed QM/MM, and DLPNO-CCSD(T). Our goal is to demonstrate the adequacy of LS-DFT to treat the different types of interactions present in DNA-dependent systems. We show that LMKLL/DZDP using SIESTA can yield very accurate geometries and energetics in all the different systems considered in this work: duplex DNA (dDNA), phenanthroline intercalating dDNA, G-quadruplexes, and metal-G-tetrads considering alkaline metals of different sizes. As far as we know, this is the first time that full G-quadruplex geometry optimisations have been carried out using a DFT method thanks to its linear-scaling capabilities. Moreover, we show that LS-DFT provides high-quality structures, and some semi-empirical Hamiltonians can also yield suitable geometries. However, DLPNO-CCSD(T) and LS-DFT are the only methods that accurately describe interaction energies for all the systems considered in our study., This research was financially supported by Diputación Foral de Gipuzkoa through the Gipuzkoa Fellows Program to A. G. This research was also financially supported by the Fundação para a Ciência e a Tecnologia (FCT) by means of Projects PTDC/QUI-QFI/29236/2017, UIDB/04046/2020, and UIDP/04046/2020 and by the Spanish Ministry of Economy, Industry and Competitiveness under the Maria de Maeztu Units of Excellence Program/MDM-2016-0618). A. G. is thankful to ARAID – Fundación Agencia Aragonesa para la Investigación y el Desarrollo for current funding in the frame of ARAID researchers. The authors also thank for technical and human support provided by IZO-SGI (SGIker) of UPV/EHU and European funding (ERDF and ESF). Financial support comes also from Eusko Jaurlaritza (Basque Government) through the project IT1254-19 and IT1584-22, from Spanish MICINN through Grant No. PID2019-107338RB-C61/AEI/10.13039/501100011033, and grant PGC2018-099321-B-100 from the Ministry of Science, Innovation and Universities through the Office of Science Research (MINECO/FEDER). Pseudopotentials and Numerical Atomic Orbitals Basis Dataset for SIESTA were provided by Simune Atomistics S. L. (www.simuneatomistics.com). S. E. thanks the Ministry of Higher Education and Scientific Research of Tunisia for the funding of intership carried out in Portugal and Spain. I. O. D. L. is also very grateful to CICnanoGUNE BRTA for his PhD grant.

The phenomenological theory for the polar instability giving rise to a two-dimensional electron gas at perovskite interfaces is hereby extended to include the coupling to perovskite tilts. A Landau theory for homogeneous tilts is first explored, setting the scene for the further, more realistic Landau-Ginzburg theory describing varying tilt amplitudes across a thin film. The theory is also generalized to account for the response to an applied electric field normal to the interface, which allows a finer control on phase transitions. The conventionally described physics of a single metal-insulator transition is substantially enriched by the coupling, the model describing various scenarios with one or two transitions, possibly continuous or discontinuous. First-principles calculations permit the estimation of the parameters defining the model, which have been calculated for the interface between lanthanum aluminate and strontium titanate., Comment: Accepted version

The electronic stopping power ($S_e$) of water vapor (H$_2$O), hydrogen (H$_2$) and oxygen (O$_2$) gases for protons in a broad range of energies, centered in the Bragg peak, was calculated using real-time time-dependent density functional theory (rt-TDDFT) simulations with Gaussian basis sets. This was done for a kinetic energy of incident protons ($E_k$) ranging from 1.56 keV/amu to 1.6 MeV/amu. $S_e$ was calculated as the average over geometrically pre-sampled short ion trajectories. The average $S_e(E_k)$ values were found to rapidly converge with 25-30 pre-sampled, 2 nm-long ion trajectories. The rt-TDDFT $S_e(E_k)$ curves were compared to experimental and SRIM data, and used to validate the Bragg's Additivity Rule (BAR). Discrepancies were analyzed in terms of basis set effects and omitted nuclear stopping at low energies. At variance with SRIM, we found that BAR is applicable to our rt-TDDFT simulations of $\mathrm{2H_2+O_2}$ $\mathrm{\rightarrow 2H_2O}$ without scaling for $E_k>40$ keV/amu. The hydrogen and oxygen Core and Bond (CAB) contributions to electronic stopping were calculated and found to be slightly smaller than SRIM values as a result of a red-shift in our rt-TDDFT $S_e(E_k)$ curves and a re-distribution of weights due to some bond contributions being neglected in SRIM., 15 pages 5 figures, 1 table

Tau neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimer’s disease (AD). To elucidate patterns of structural change in the MTL specifically associated with tau pathology, we compared high-resolution ex vivo MRI scans of human postmortem MTL specimens with histology-based pathological assessments of the MTL. MTL specimens were obtained from twenty-nine brain donors, including patients with AD, other dementias, and individuals with no known history of neurological disease. Ex vivo MRI scans were combined using a customized groupwise diffeomorphic registration approach to construct a 3D probabilistic atlas that captures the anatomical variability of the MTL. Using serial histology imaging in eleven specimens, we labelled the MTL subregions in the atlas based on cytoarchitecture. Leveraging the atlas and neuropathological ratings of tau and TAR DNA-binding protein 43 (TDP-43) pathology severity, morphometric analysis was performed to correlate regional MTL thickness with the severity of tau pathology, after correcting for age and TDP-43 pathology. We found significant correlations between tau pathology and thickness in the entorhinal cortex (ERC) and stratum radiatum lacunosum moleculare (SRLM). When focusing on cases with low levels of TDP-43 pathology, we found strong associations between tau pathology and thickness in the ERC, SRLM and the subiculum/cornu ammonis 1 (CA1) subfields of the hippocampus, consistent with early Braak stages. Supplementary Information The online version contains supplementary material available at 10.1186/s40478-021-01275-7.

The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-β and α-synuclein pathology were rated on a scale of 0 (absent)—3 (severe) in the hippocampus and entorhinal cortex (ERC) of 58 individuals with and without neurodegenerative diseases (median age 75.0 years, 60.3% male). Thickness measurements in ERC, Brodmann Area (BA) 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare (SRLM) were derived from 0.2 × 0.2 × 0.2 mm3 post-mortem MRI scans of excised MTL specimens from the contralateral hemisphere using a semi-automated approach. Spearman’s rank correlations were performed between neurodegenerative pathologies and thickness, correcting for age, sex and hemisphere, including all four proteinopathies in the model. We found significant associations of (1) TDP-43 with thickness in all subregions (r = − 0.27 to r = − 0.46), and (2) tau with BA35 (r = − 0.31) and SRLM thickness (r = − 0.33). In amyloid-β and TDP-43 negative cases, we found strong significant associations of tau with ERC (r = − 0.40), BA35 (r = − 0.55), subiculum (r = − 0.42) and CA1 thickness (r = − 0.47). This unique dataset shows widespread MTL atrophy in relation to TDP-43 pathology and atrophy in regions affected early in Braak stageing and tau pathology. Moreover, the strong association of tau with thickness in early Braak regions in the absence of amyloid-β suggests a role of Primary Age-Related Tauopathy in neurodegeneration. Supplementary Information The online version contains supplementary material available at 10.1186/s40478-021-01225-3.

Cosmic Rays, in particular the high charge and high energy (HZE) particles and eventual secondary low energy protons, are high Linear Energy Transfer (LET) radiation, i.e. they transfer a high amount of energy to the target per unit path length travelled in the target itself, leaving behind a dense track of ionization and atomic excitations. Understanding the radiation physics and the biology induced by the impact of high LET radiation is of importance for different fields of research, such as radiation therapy with charged particles, space radiation protection of astronauts and of human explorers on Mars and eventually also survival of any bacterial, plant cell on other planetary/small bodies. While data for low LET radiation such as X-ray have been studied in the survivors of the atomic-bombs, medical patients and nuclear reactor workers, for high LET radiation there is no relevant collection of human data for risk estimates, and experiments with nuclei created at accelerators are necessary.At present we still do not have an understanding of how the radiation interaction with a single nanometric target (units of DNA), the so-called track structure [1], should decide the fate of the irradiated cell. Monte Carlo (MC) track structure codes essentially work only with the physics given by impact cross sections on the sole water, there is no real consideration of the electronic/chemical characteristics of the hosted biomolecule [2]. Limitations given by such an approach have been highlighted [3], but on the positive side a massive effort is being done to follow the different steps of radiation effects up to biological damage [4].In this contribution we would like to highlight how a chain of models from different communities could be of help to study the radiation effects on biomolecules. In particular, we will present how ab-initio (parameter-free) approaches from the chemical-physics community can be used to derive in detail the energy loss of the impacting ions/secondary electrons on water and small biological units [5,6], either following in real time the ion or based on perturbative theories for low energy electrons, and how the derived quantity can be given as input to Monte Carlo track structure codes, extending their capabilities to different relevant targets. Given the physical limitations and high costs of irradiation experiments, such calculations offer an efficient approach that can boost the understanding of radiation physics and consolidate existing MC track structure codes.This work is initiated in the context of the EU H2020 project ESC2RAD, Grant 776410.[1] H. Nikjoo, S. Uehara, W.E. Wilson, et al, International Journal of Radiation Biology 73, 355 (1998)[2] H. Palmans, H Rabus, A L Belchior, et al, Br. J. Radiol. 88, 20140392 (2015)[3] H. Rabus and H. Nettelback, Radiation Measurements 46, 1522 (2011)[4] M. Karamitros, S. Luan, M.A. Bernal, et al, Journal of Computational Physics 274, 841 (2014)[5] B. Gu, B. Cunningham D. Munoz-Santiburcio, F. Da Pieve, E. Artacho and J. Kohanoff, J. Chem. Phys. 153, 034113 (2020)[6] N. Koval, J. Kohanoff, E. Artacho et al, in preparation

Tau protein neurofibrillary tangles (NFT) are closely linked to neuronal/synaptic loss and cognitive decline in Alzheimer's disease (AD) and related dementias. Our knowledge of the pattern of NFT progression in the human brain, critical to the development of imaging biomarkers and interpretation of in vivo imaging studies in AD, is based on conventional 2D histology studies that only sample the brain sparsely. To address this limitation, ex vivo MRI and dense serial histological imaging in 18 human medial temporal lobe (MTL) specimens were used to construct 3D quantitative maps of NFT burden in the MTL at individual and group levels. These maps reveal significant variation in NFT burden along the anterior-posterior axis. While early NFT pathology is thought to be confined to the transentorhinal region, we find similar levels of NFT burden in this region and other MTL subregions, including amygdala, temporopolar cortex, and subiculum/CA1.

Tau protein neurofibrillary tangles are closely linked to neuronal/synaptic loss and cognitive decline in Alzheimer’s disease and related dementias. Our knowledge of the pattern of neurofibrillary tangle progression in the human brain, critical to the development of imaging biomarkers and interpretation of in vivo imaging studies in Alzheimer’s disease, is based on conventional two-dimensional histology studies that only sample the brain sparsely. To address this limitation, ex vivo MRI and dense serial histological imaging in 18 human medial temporal lobe specimens (age 75.3 ± 11.4 years, range 45 to 93) were used to construct three-dimensional quantitative maps of neurofibrillary tangle burden in the medial temporal lobe at individual and group levels. Group-level maps were obtained in the space of an in vivo brain template, and neurofibrillary tangles were measured in specific anatomical regions defined in this template. Three-dimensional maps of neurofibrillary tangle burden revealed significant variation along the anterior-posterior axis. While early neurofibrillary tangle pathology is thought to be confined to the transentorhinal region, we found similar levels of burden in this region and other medial temporal lobe subregions, including amygdala, temporopolar cortex, and subiculum/cornu ammonis 1 hippocampal subfields. Overall, the three-dimensional maps of neurofibrillary tangle burden presented here provide more complete information about the distribution of this neurodegenerative pathology in the region of the cortex where it first emerges in Alzheimer’s disease, and may help inform the field about the patterns of pathology spread, as well as support development and validation of neuroimaging biomarkers.

This article is part of the JCP Special Topic on Electronic Structure Software., A review of the present status, recent enhancements, and applicability of the SIESTA program is presented. Since its debut in the mid-1990s, SIESTA’s flexibility, efficiency, and free distribution have given advanced materials simulation capabilities to many groups worldwide. The core methodological scheme of SIESTA combines finite-support pseudo-atomic orbitals as basis sets, norm-conserving pseudopotentials, and a realspace grid for the representation of charge density and potentials and the computation of their associated matrix elements. Here, we describe the more recent implementations on top of that core scheme, which include full spin–orbit interaction, non-repeated and multiple-contact ballistic electron transport, density functional theory (DFT)+U and hybrid functionals, time-dependent DFT, novel reduced-scaling solvers, density-functional perturbation theory, efficient van der Waals non-local density functionals, and enhanced molecular-dynamics options. In addition, a substantial effort has been made in enhancing interoperability and interfacing with other codes and utilities, such as WANNIER90 and the second-principles modeling it can be used for, an AiiDA plugin for workflow automatization, interface to Lua for steering SIESTA runs, and various post-processing utilities. SIESTA has also been engaged in the Electronic Structure Library effort from its inception, which has allowed the sharing of various low-level libraries, as well as data standards and support for them, particularly the PSeudopotential Markup Language definition and library for transferable pseudopotentials, and the interface to the ELectronic Structure Infrastructure library of solvers. Code sharing is made easier by the new open-source licensing model of the program. This review also presents examples of application of the capabilities of the code, as well as a view of on-going and future developments., Siesta development was historically supported by different Spanish National Plan projects (Project Nos. MEC-DGES-PB95-0202, MCyT-BFM2000-1312, MEC-BFM2003-03372, FIS2006-12117, FIS2009-12721, FIS2012-37549, FIS2015-64886-P, and RTC-2016-5681-7), the latter one together with Simune Atomistics Ltd. We are thankful for financial support from the Spanish Ministry of Science, Innovation and Universities through Grant No. PGC2018-096955-B. We acknowledge the Severo Ochoa Center of Excellence Program [Grant Nos. SEV-2015-0496 (ICMAB) and SEV-2017-0706 (ICN2)], the GenCat (Grant No. 2017SGR1506), and the European Union MaX Center of Excellence (EU-H2020 Grant No. 824143). P.G.-F. acknowledges support from Ramón y Cajal (Grant No. RyC-2013-12515). J.I.C. acknowledges Grant No. RTI2018-097895-B-C41. R.C. acknowledges the European Union’s Horizon 2020 Research and Innovation Program under Marie Skłodoswka-Curie Grant Agreement No. 665919. D.S.P, P.K., and P.B. acknowledge Grant No. MAT2016-78293-C6, FET-Open No. 863098, and UPV-EHU Grant No. IT1246-19. V. W. Yu was supported by a MolSSI Fellowship (U.S. NSF Award No. 1547580), and V.B. and V.W.Y. were supported by the ELSI Development by the NSF (Award No. 1450280).

Known force terms arising in the Ehrenfest dynamics of quantum electrons and classical nuclei, due to a moving basis set for the former, can be understood in terms of the curvature of the manifold hosting the quantum states of the electronic subsystem. Namely, the velocity-dependent terms appearing in the Ehrenfest forces on the nuclei acquire a geometrical meaning in terms of the intrinsic curvature of the manifold, while Pulay terms relate to its extrinsic curvature., Comment: 4 pages, no figures, as accepted in SciPost Physics

Neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimer’s Disease (AD). In this work, we investigate the relationship between MTL morphometry features derived from high-resolution ex vivo imaging and histology-based measures of NFT pathology using a topological unfolding framework applied to a dataset of 18 human postmortem MTL specimens. The MTL has a complex 3D topography and exhibits a high degree of inter-subject variability in cortical folding patterns which poses a significant challenge for volumetric registration methods typically used during MRI template construction. By unfolding the MTL cortex, the proposed framework explicitly accounts for the sheet-like geometry of the MTL cortex and provides a two-dimensional reference coordinate space which can be used to implicitly register cortical folding patterns across specimens based on distance along the cortex despite large anatomical variability. Leveraging this framework in a subset of 15 specimens, we characterize the associations between NFTs and morphological features such as cortical thickness and surface curvature and identify regions in the MTL where patterns of atrophy are strongly correlated with NFT pathology.

This book collects the lectures presented in the first COST TUMIEE Training School held in Greece in 2019, supplemented with specific applications that illustrate how the multi-scale approach is implemented in specific cases of interest. The book is intended both as a reference in the field and as a textbook for people becoming interested or entering the field. The first part focuses on experimental methods, the second on theoretical approaches, and the third on cases of interest.

The numerical integration of the Schr\"odinger equation by discretization of time is explored for the curved manifolds arising from finite representations based on evolving basis states. In particular, the unitarity of the evolution is assessed, in the sense of the conservation of mutual scalar products in a set of evolving states, and with them the conservation of orthonormality and particle number. Although the adequately represented equation is known to give rise to unitary evolution in spite of curvature, discretized integrators easily break that conservation, thereby deteriorating their stability. The Crank Nicolson algorithm, which offers unitary evolution in Euclidian spaces independent of time-step size $\mathrm{d}t$, can be generalised to curved manifolds in different ways. Here we compare a previously proposed algorithm that is unitary by construction, albeit integrating the wrong equation, with a faithful generalisation of the algorithm, which is, however, not strictly unitary for finite $\mathrm{d}t$., Comment: 12 pages, 5 figures. Accepted in Phys. Rev. Research