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

Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis

Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD–abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions

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

A Cu2O-CuSCN Nanocomposite as a Hole-Transport Material of Perovskite Solar Cells for Enhanced Carrier Transport and Suppressed Interfacial Degradation

Interfacial degradation in perovskite solar cells is a critical issue affecting long-term stability for future commercialization. In particular, a perovskite and an organic hole-transport layer (HTL) react easily when the device is exposed to extreme operating conditions (heat, light, and air). To prevent degradation, an inorganic CuSCN HTL has emerged as an alternative, yet the interfacial reactivity is still not clearly elucidated. Herein, Cu2O and CuSCN are coutilized to form an efficient and stable HTL. While uniform film formation using Cu2O is difficult despite its high mobility, a Cu2O-CuSCN nanocomposite can be excellently synthesized as an effective HTL, exhibiting a power conversion efficiency (PCE) of 19.2% and sustaining its PCE over 90% for 720 h under extreme conditions (85 degrees C/85% of relative humidity, encapsulated). A chemical distribution analysis by secondary-ion mass spectroscopy (SIMS) suggests that a Cu2O nanoparticle layer protects the interface between the perovskite and CuSCN. The optoelectronic properties of the nanocomposite HTL and the improved solar cell performance are correlated with the recombination rate, electronic trap distribution in the band gap, and charge extraction efficiencies.N

Mechanochemical synthesis and electrochemical behavior of Na3FeF6 in sodium and lithium batteries

We report Na3FeF6 as a novel cathode material for sodium and lithium batteries. The material is synthesized through a mechanochemical process by reacting precursors (NaF and FeF3) in a ball mill under argon flow. These syntheses are environmentally friendly and safe because the entire processes do not require any hazardous gasses or high temperatures. XRD spectra confirm that the synthesized material has a well-defined crystal structure and can be indexed to a monoclinic crystal structure under the P2(1)/C space group. Thermal analyses up to 500 degrees C confirm the stability of the crystal structure and safety of this material. Electrochemical results indicate that Na3FeF6 is electrochemically active in both Na and Li cells while undergoing conversion reactions and exhibiting decent reversible capacities of larger than 100 and 200 mAh g(-1) at room temperature, respectively. (C) 2012 Elsevier B.V. All rights reserved.

Improved electrochemical performance of LiNi0.6Co0.2Mn0.2O2 cathode material synthesized by citric acid assisted sol-gel method for lithium ion batteries

A citric acid assisted sol-gel method is employed for synthesizing LiNi0.6Co0.2Mn0.2O2 for use as a cathode material in lithium-ion batteries. The effects of heat-treatment temperature and oxygen atmosphere on the structural and electrochemical properties of LiNi0.6Co0.2Mn0.2O2 are investigated, in order to determine optimal conditions for the synthesis of LiNi0.6Co0.2Mn0.2O2 via the citric acid assisted sol-gel method. In particular, the presence of oxygen in the atmosphere effectively leads to a decrease in the degree of cation mixing and the formation of LiOH and Li2CO3 on the surface of LiNi0.6Co0.2Mn0.2O2. Furthermore, heat-treatment in an oxygen atmosphere improves the uniformity of oxidation state of Ni ions between the surface and bulk. LiNi0.6Co0.2Mn0.2O2 synthesized by heat-treatment at 850 degrees C under an oxygen atmosphere shows a discharge capacity of 174 mA h g(-1) and 89% capacity retention after 100 cycles. In addition, it shows high rate capability (i.e., 41% capacity retention at 10 C), which is an improved rate performance over a previous report. The results of this study should provide useful information for the synthesis of Ni-rich layered oxides for lithium ion batteries. (C) 2016 Elsevier B.V. All rights reserved.

Sol-gel synthesis of aliovalent vanadium-doped LiNi0.5Mn1.5O4 cathodes with excellent performance at high temperatures

Extraordinary performance at elevated temperature is achieved for high-voltage spinel-phase LiNi0.5Mn1.5O4 cathodes prepared using an adipic-acid-assisted sol–gel technique and doped with vanadium. V-substitution in the Li sites (Wykoff position 8a) is confirmed by V K-edge X-ray absorption spectroscopy and Rietveld refinement (Li0.995V0.005Ni0.5Mn1.5O4). V-doped LiNi0.5Mn1.5O4 delivered a reversible capacity of approximately 130 and 142 mAh g−1 at ambient and elevated temperature conditions, respectively. Furthermore, the Li0.995V0.005Ni0.5Mn1.5O4 phase rendered approximately 94 % and 84 % of initial capacity compared to approximately 85 % and 3 % for the LiNi0.5Mn1.5O4 phase after 100 cycles in ambient and elevated temperature conditions, respectively. The enhancements are mainly because of the suppression of Mn dissolution and unwanted side reaction with electrolyte counterpart, and to the increase in conductivity, improving the electrochemical profiles for the V-doped phase

New Iron-Based Mixed-Polyanion Cathodes for Lithium and Sodium Rechargeable Batteries: Combined First Principles Calculations and Experimental Study

New iron-based mixed-polyanion compounds LixNa4-xFe3(PO4)(2)(P2O7) (x = 0-3) were synthesized, and their crystal structures were determined. The new compounds contained three-dimensional (3D)-sodium/lithium paths supported by P2O7 pillars in the crystal. First principles calculations identified the complex 3D paths with their activation barriers and revealed them as fast ionic conductors. The reversible electrode operation was found in both Li and Na cells with capacities of one-electron reaction per Fe atom, 140 and 129 mAh g(-1), respectively. The redox potential of each phase was similar to 3.4 V (vs Li) for the Li-ion cell and similar to 3.2 V (vs Na) for the Na-ion cell. The properties of high power, small volume change, and high thermal stability were also recognized, presenting this new compound as a potential competitor to other iron-based electrodes such as Li2FeP2O7, Li2FePO4F, and LiFePO4