Influence of Br−^{-}/S2−^{2-} site-exchange on Li diffusion mechanism in Li6_6PS5_5Br -- a computational study

We investigate the influence of Br$^-$/S$^{2-}$ site-exchange on lithium diffusion in the agyrodite-type solid electrolyte Li$_6$PS$_5$Br by ab-initio molecular dynamics simulations. Based on the calculated trajectories a new mechanism for the internal lithium reorganization within the Li-cages around the $4d$ sites is identified. This reorganization mechanism is highly concerted and cannot be described by one single rotation axis only. Simulations with Br$^-$/S$^{2-}$ defects reveal that Li$^._i$ interstitials are the dominant mobile charge carriers, which originate from Frenkel pairs. These are formed because Br$^._\text{S}$ defects on the $4d$ sites cause the transfer of one or even two Li$^._i$ to the neighboring 12 cages. The lithium interstitials then carry out intercage jumps via interstitial and interstitialcy mechanisms. With that, one single Br$^._\text{S}$ defect enables Li diffusion over an extended spatial area explaining why low degrees of site-exchange are sufficient to trigger superionic conduction. The vacant sites of the Frenkel pairs, namely V$'_\text{Li}$, are mostly immobile and bound to the Br$^._\text{S}$ defect. To a lesser degree also S$'_\text{Br}$ defects induce disturbances in the lithium distribution and act as sinks for lithium interstitials restricting the Li$^._i$ motion to the vicinity of the S$'_\text{Br}$ defect

Effect of Particle Size and Pressure on the Transport Properties of the Fast Ion Conductor t‐Li₇SiPS₈

All‐solid‐state batteries promise higher energy and power densities as well as increased safety compared to lithium‐ion batteries by using non‐flammable solid electrolytes and metallic lithium as the anode. Ensuring permanent and close contact between the components and individual particles is crucial for long‐term operation of a solid‐state cell. This study investigates the particle size dependent compression mechanics and ionic conductivity of the mechanically soft thiophosphate solid electrolyte tetragonal Li₇SiPS₈ (t‐LiSiPS) under pressure. The effect of stack and pelletizing pressure is demonstrated as a powerful tool to influence the microstructure and, hence, ionic conductivity of t‐LiSiPS. Heckel analysis for granular powder compression reveals distinct pressure regimes, which differently impact the Li ion conductivity. The pelletizing process is simulated using the discrete element method followed by finite volume analysis to disentangle the effects of pressure‐dependent microstructure evolution from atomistic activation volume effects. Furthermore, it is found that the relative density of a tablet is a weaker descriptor for the sample's impedance compared to the particle size distribution. The multiscale experimental and theoretical study thus captures both atomistic and microstructural effects of pressure on the ionic conductivity, thus emphasizing the importance of microstructure, particle size distribution and pressure control in solid electrolytes

Heat Shock Proteins and Amateur Chaperones in Amyloid-Beta Accumulation and Clearance in Alzheimer’s Disease

The pathologic lesions of Alzheimer’s disease (AD) are characterized by accumulation of protein aggregates consisting of intracellular or extracellular misfolded proteins. The amyloid-β (Aβ) protein accumulates extracellularly in senile plaques and cerebral amyloid angiopathy, whereas the hyperphosphorylated tau protein accumulates intracellularly as neurofibrillary tangles. “Professional chaperones”, such as the heat shock protein family, have a function in the prevention of protein misfolding and subsequent aggregation. “Amateur” chaperones, such as apolipoproteins and heparan sulfate proteoglycans, bind amyloidogenic proteins and may affect their aggregation process. Professional and amateur chaperones not only colocalize with the pathological lesions of AD, but may also be involved in conformational changes of Aβ, and in the clearance of Aβ from the brain via phagocytosis or active transport across the blood–brain barrier. Thus, both professional and amateur chaperones may be involved in the aggregation, accumulation, persistence, and clearance of Aβ and tau and in other Aβ-associated reactions such as inflammation associated with AD lesions, and may, therefore, serve as potential targets for therapeutic intervention

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images

Neuroimaging measurements derived from magnetic resonance imaging provide important information required for detecting changes related to the progression of mild cognitive impairment (MCI). Cortical features and changes play a crucial role in revealing unique anatomical patterns of brain regions, and further differentiate MCI patients from normal states. Four cortical features, namely, gray matter volume, cortical thickness, surface area, and mean curvature, were explored for discriminative analysis among three groups including the stable MCI (sMCI), the converted MCI (cMCI), and the normal control (NC) groups. In this study, 158 subjects (72 NC, 46 sMCI, and 40 cMCI) were selected from the Alzheimer's Disease Neuroimaging Initiative. A sparse-constrained regression model based on the l2-1-norm was introduced to reduce the feature dimensionality and retrieve essential features for the discrimination of the three groups by using a support vector machine (SVM). An optimized strategy of feature addition based on the weight of each feature was adopted for the SVM classifier in order to achieve the best classification performance. The baseline cortical features combined with the longitudinal measurements for 2 years of follow-up data yielded prominent classification results. In particular, the cortical thickness produced a classification with 98.84% accuracy, 97.5% sensitivity, and 100% specificity for the sMCI–cMCI comparison; 92.37% accuracy, 84.78% sensitivity, and 97.22% specificity for the cMCI–NC comparison; and 93.75% accuracy, 92.5% sensitivity, and 94.44% specificity for the sMCI–NC comparison. The best performances obtained by the SVM classifier using the essential features were 5–40% more than those using all of the retained features. The feasibility of the cortical features for the recognition of anatomical patterns was certified; thus, the proposed method has the potential to improve the clinical diagnosis of sub-types of MCI and predict the risk of its conversion to Alzheimer's disease

Quantitative 18F-AV1451 Brain Tau PET Imaging in Cognitively Normal Older Adults, Mild Cognitive Impairment, and Alzheimer's Disease Patients

Recent developments of tau Positron Emission Tomography (PET) allows assessment of regional neurofibrillary tangles (NFTs) deposition in human brain. Among the tau PET molecular probes, 18F-AV1451 is characterized by high selectivity for pathologic tau aggregates over amyloid plaques, limited non-specific binding in white and gray matter, and confined off-target binding. The objectives of the study are (1) to quantitatively characterize regional brain tau deposition measured by 18F-AV1451 PET in cognitively normal older adults (CN), mild cognitive impairment (MCI), and AD participants; (2) to evaluate the correlations between cerebrospinal fluid (CSF) biomarkers or Mini-Mental State Examination (MMSE) and 18F-AV1451 PET standardized uptake value ratio (SUVR); and (3) to evaluate the partial volume effects on 18F-AV1451 brain uptake.Methods: The study included total 115 participants (CN = 49, MCI = 58, and AD = 8) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed 18F-AV1451 PET images, structural MRIs, and demographic and clinical assessments were downloaded from the ADNI database. A reblurred Van Cittertiteration method was used for voxelwise partial volume correction (PVC) on PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. The parametric images of 18F-AV1451 SUVR relative to cerebellum were calculated. The ROI SUVR measurements from PVC and non-PVC SUVR images were compared. The correlation between ROI 18F-AV1451 SUVR and the measurements of MMSE, CSF total tau (t-tau), and phosphorylated tau (p-tau) were also assessed.Results:18F-AV1451 prominently specific binding was found in the amygdala, entorhinal cortex, parahippocampus, fusiform, posterior cingulate, temporal, parietal, and frontal brain regions. Most regional SUVRs showed significantly higher uptake of 18F-AV1451 in AD than MCI and CN participants. SUVRs of small regions like amygdala, entorhinal cortex and parahippocampus were statistically improved by PVC in all groups (p < 0.01). Although there was an increasing tendency of 18F-AV-1451 SUVRs in MCI group compared with CN group, no significant difference of 18F-AV1451 deposition was found between CN and MCI brains with or without PVC (p > 0.05). Declined MMSE score was observed with increasing 18F-AV1451 binding in amygdala, entorhinal cortex, parahippocampus, and fusiform. CSF p-tau was positively correlated with 18F-AV1451 deposition. PVC improved the results of 18F-AV-1451 tau deposition and correlation studies in small brain regions.Conclusion: The typical deposition of 18F-AV1451 tau PET imaging in AD brain was found in amygdala, entorhinal cortex, fusiform and parahippocampus, and these regions were strongly associated with cognitive impairment and CSF biomarkers. Although more deposition was observed in MCI group, the 18F-AV-1451 PET imaging could not differentiate the MCI patients from CN population. More tau deposition related to decreased MMSE score and increased level of CSF p-tau, especially in ROIs of amygdala, entorhinal cortex and parahippocampus. PVC did improve the results of tau deposition and correlation studies in small brain regions and suggest to be routinely used in 18F-AV1451 tau PET quantification

Ab-initio calculations of structure and properties of lithium thiophosphates (V2)

Batteries, and in particular lithium ion batteries, are widely used energy storage and supply systems. Recently, the conventional lithium ion battery that uses a liquid electrolyte is under revision due to safety issues. As an alternative, liquid electrolytes can be substituted with solid electrolytes. A potential class of solid electrolytes are lithium thiophosphates of the xLi2:(100-x)P_2S_5 system. These materials are usually prepared as glasses or glassceramics. Depending on the preparation method, a glass-ceramic can have improved or reduced transport properties compared to its mother glasses. The reason for this that either highly or poorly ion conductive crystalline phases can be formed. In the 67Li_2:33P_2S_5 (Li_4P_2S_7) glass system, the formation of the crystalline Li_4P_2S_6 phase results in a severe loss of ionic conductivity. In a previous investigation, we analyzed the defect thermodynamics and migration barriers of bulk Li_4P_2S_6 in detail by applying Density Functional Theory calculations and explained that its low ionic conductivity is mainly due to high defect formation energies. Furthermore, thermodynamic considerations and explicit interface models indicated the instability against metallic lithium. In the present wotk, in order to obtain a deeper understanding of lithium thiophosphates we wanted to model glass-ceramics. Therefore, we first focussed on the glassy part. After analyzing the crystalline model structure c-Li_4P_2S_7, we prepared glass-models by a meltquenching protocol. By melting at high temperatures and applying a slow quenching rate, energetically reasonable glass models were obtained. However, their structures differ considerably from what is reported by experimental findings: alongside the usually reported P_2S_7^4-,PS_4^3- and P_2S_6^4- structural motifs (“usual units”) we found a variety of different units (“unusual units”). Idealized glass models with increased relative stabilty compared to the melt-quenched model could be generated. But also for the idealized glass models, the structural motifs vary from the ideal usual units in the sense that the usual units are crosslinked via S-S bonds. This is in line with a simple charge argument. By comparing the transport properties of all glass models it was found that their ionic conductivities at room temperature are very similiar. The averaged diffusion coefficients show an excellent linearity in the Arrhenius plot. Using the averaged data, an ionic conductivity of 1.43 x 10^-2 S/cm was calculated. This value is two to three orders of magnitude larger than what is reported from experiments. From stacking fault and grain boundary models of Li_4P_2S_6 we concluded that these planar defects can enhance the ionic conductivity of Li4P2S6. But the effect is minor and compared to the glassy matrix Li_4P_2S_6 can still be regarded as a non-conductive phase. Finally, our modelling of glass-ceramic interfaces showed the preference of the (001)-orientation of the Li_4P_2S_6 over the (100)-orientation. Both orientation seem to be stable. For the (001)-orientation, glass and crystal are separated by an accumulation layer of lithium ions. For the (100)-orientation, lithium ions of Li4P2S6 close to the interface leave their initial site and migrate into the interface. At the same time, they leave behind a vacant site

Properties of Sulfide Solid Electrolytes Studied by Electronic Structure Calculations

Rechargeable all-solid-state batteries (ASSBs) are traded as next-generation power sources for mobile applications, because they are believed to provide increased energy densities, higher power densities and improved cyclability compared to conventional Li-ion batteries (LIBs).[1] Moreover, the replacement of flammable liquid organic electrolytes, used in LIBs, with non-flammable solid electrolytes (SEs) might eliminate safety issues and enables new battery designs.[2] In this regard, sulfide SEs are promising candidates because they show ionic conductivities of up to ≈10 mS/cm at room temperature and convince with favorably soft mechanical properties that enable an easy integration into the battery.[3-5] Their disadvantage, however, is a lack of electrochemical stability against most electrode materials.[3,6,7] Despite the huge effort to study sulfide SEs, however, many of the related processes, such as exact diffusion mechanisms or interface degradation reactions, have not been understood in detail. Such an understanding could offer new optimization strategies, and we have therefore used atomistically resolved density functional theory (DFT) calculations and ab-initio molecular dynamics (AIMD) simulation over the past years to investigate selected sulfide SEs. A detailed introduction into the topic is given in Chapter 1 and a literature review for the materials of interest in Chapter 2 will lay out the specific research questions tackled in this work. The applied methods and theoretical background are explained in Chapter 3 and lay the foundation for the following chapters. In Chapter 4 we will discuss the litium thiophosphate (LiPS) system that comprises multiple crystalline phases such as Li3PS4, Li7P3S11 and Li4P2S6. Structurally, the situation is further complicated by the coexistence of glass phases exhibiting an amorphous structure.[8] Hence, most sulfide SEs are actually glass-ceramics whose properties are determined by the types and amounts of the underlying phases. We strongly focus on glass phases as their structure is difficult to analyze by experiments. To this end, we generated structure models for LiPS glasses at various compositions by applying a computational melt-quenching approach and compare the stability, structure and Li+ transport properties of crystalline and glassy phases. We find that all glasses are metastable and exhibit similar Li+ diffusion coefficients despite the fact that they are comprised of different basic structural units (PS4^3-, P2S7^4-, P2S6^4-). Furthermore, the occurrence of unusual structural units is observed and the association of structural units via cross-linking S-S bonds is derived as compensation mechanism in case of local Li deficiency. Finally, the interfacial stability against Li metal and internal interfaces are investigated. In this regard, the usage of defect formation energies as descriptors to judge the stability of interfaces is discussed. Next, the quaternary, argyrodite-type system Li6PS5Br is analyzed in Chapter 5. The key question concerns the experimentally observed Br-/S2- site-exchange among its 4a and 4d sites, that can be controlled via the synthesis procedure without altering the composition:[9,10] How does the Br-/S2- site-exchange influence the structure and properties of the material? We will show that the ordered structure is the most stable configuration and that the lattice constants show a minimum at 50% site-exchange. The main part discusses the Li+ transport properties and how the introduction of Br-/S2- site-exchange enables the transition from local to long-range Li+ diffusion. Moreover, we were able to identify the underlying diffusion mechanism and show that especially the Br- ions on S2- sites facilitate the generation of Li+ Frenkel pairs with mobile Li+ interstitials. Finally, we have a closer look on the Li+ substructure and analyze how the Br-/S2- site-exchange interacts with the Li+ transport properties of symmetrical tilt and twist grain boundaries. In Chapter 6 we will deal with the recently developed Li7SiPS8, which was found to crystallize in an orthorhombic phase (ortho-Li7SiPS8) with rather poor Li+ transport properties and a more promising tetragonal phase (tetra-Li7SiPS8).[11] As not much is known about the material we examined several of its properties, also in light of the Si/P disorder that is observed experimentally. We show that ortho-Li7SiPS8 is the more stable phase and experimental trend of poor transport properties is confirmed. Tetra-Li7SiPS8 is the much better conductor owing to its fast diffusion along the c axis. The Si/P distribution was found to have a negligible influence on the transport properties, and a compression of the material leads to decreased diffusion coefficients. Finally, the interfacial instability of tetra-Li7SiPS8 against Li metal was probed by means of explicit interface calculations. At long last, we will conclude this work in Chapter 7 and present open questions and promising directions for future studies