Prognostic model for predicting Alzheimer's disease conversion using functional connectome manifolds.

BACKGROUND: Early detection of Alzheimer's disease (AD) is essential for timely management and consideration of therapeutic options; therefore, detecting the risk of conversion from mild cognitive impairment (MCI) to AD is crucial during neurodegenerative progression. Existing neuroimaging studies have mostly focused on group differences between individuals with MCI (or AD) and cognitively normal (CN), discarding the temporal information of conversion time. Here, we aimed to develop a prognostic model for AD conversion using functional connectivity (FC) and Cox regression suitable for conversion event modeling. METHODS: We developed a prognostic model using a large-scale Alzheimer's Disease Neuroimaging Initiative dataset, and it was validated using external data obtained from the Open Access Series of Imaging Studies. We considered individuals who were initially CN or had MCI but progressed to AD and those with MCI with no progression to AD during the five-year follow-up period. As the exact conversion time to AD is unknown, we inferred this information using imputation approaches. We generated cortex-wide principal FC gradients using manifold learning techniques and computed subcortical-weighted manifold degrees from baseline functional magnetic resonance imaging data. A penalized Cox regression model with an elastic net penalty was adopted to define a risk score predicting the risk of conversion to AD, using FC gradients and clinical factors as regressors. RESULTS: Our prognostic model predicted the conversion risk and confirmed the role of imaging-derived manifolds in the conversion risk. The brain regions that largely contributed to predicting AD conversion were the heteromodal association and visual cortices, as well as the caudate and hippocampus. Our risk score based on Cox regression was consistent with the expected disease trajectories and correlated with positron emission tomography tracer uptake and symptom severity, reinforcing its clinical usefulness. Our findings were validated using an independent dataset. The cross-sectional application of our model showed a higher risk for AD than that for MCI, which correlated with symptom severity scores in the validation dataset. CONCLUSION: We proposed a prognostic model predicting the risk of conversion to AD. The associated risk score may provide insights for early intervention in individuals at risk of AD conversion.

Integrating Multimodal Neuroimaging and Genetics: A Structurally-Linked Sparse Canonical Correlation Analysis Approach.

Neuroimaging genetics represents a multivariate approach aimed at elucidating the intricate relationships between high-dimensional genetic variations and neuroimaging data. Predominantly, existing methodologies revolve around Sparse Canonical Correlation Analysis (SCCA), a framework we expand to 1) encompass multiple imaging modalities and 2) promote the simultaneous identification of structurally linked features across imaging modalities. The structurally linked brain regions were assessed using diffusion tensor imaging, which quantifies the presence of neuronal fibers, thereby grounding our approach in biologically well-founded prior knowledge within the SCCA model. In our proposed structurally linked SCCA framework, we leverage T1-weighted MRI and functional MRI (fMRI) time series data to delineate both the structural and functional characteristics of the brain. Genetic variations, specifically single nucleotide polymorphisms (SNPs), are also incorporated as a genetic modality. Validation of our methodology was conducted using a simulated dataset and large-scale normative data from the Human Connectome Project (HCP). Our approach demonstrated superior performance compared to existing methods on simulated data and revealed interpretable gene-imaging associations in the real dataset. Thus, our methodology lays the groundwork for elucidating the genetic underpinnings of brain structure and function, thereby providing novel insights into the field of neuroscience. Our code is available at https://github.com/mungegg.

Progressive Control of Rashba State on Topological Dirac Semimetal KZnBi.

Rashba states have been actively revisited as a platform for advanced applications such as spintronics and topological quantum computation. Yet, access to the Rashba state is restricted to the specific material sets, and the methodology to control the Rashba state is not established. Here, we report the Rashba states on the (001) surface of KZnBi, a 3D Dirac semimetal. Using angle-resolved photoemission spectroscopy and first-principles calculations, we investigated the evolution of Rashba states under different surface conditions controlled by alkali metal deposition. We observed that restoring surface ordering enables a Rashba state, which is absent in freshly cleaved surfaces. Interestingly, we were able to modify the dispersion of the Rashba state from an ordinary parabolic dispersion to a linearly dispersing Dirac-like state by additional alkali-metal deposition. Our findings provide a methodology for engineering the properties of Rashba states for advanced applications and redefine topological systems as generic hosts of Rashba states.

Coupling Between Electrons and Charge Density Wave Fluctuation and its Possible Role in Superconductivity.

In most charge density wave (CDW) systems of different material classes, ranging from traditional correlated systems in low-dimension to recent topological systems with Kagome lattice, superconductivity emerges when the system is driven toward the quantum critical point (QCP) of CDW via external parameters of doping and pressure. Despite this rather universal trend, the essential hinge between CDW and superconductivity has not been established yet. Here, the evidence of coupling between electron and CDW fluctuation is reported, based on a temperature- and intercalation-dependent kink in the angle-resolved photoemission spectra of 2H-PdxTaSe2. Kinks are observed only when the system is in the CDW phase, regardless of whether a long- or short-range order is established. Notably, the coupling strength is enhanced upon long-range CDW suppression, albeit the coupling energy scale is reduced. Interestingly, the estimation of the superconducting critical temperature by incorporating the observed coupling characteristics into McMillan's equation yields results closely resembling the known values of the superconducting dome. The results thus highlight a compelling possibility that this new coupling mediates Cooper pairs, which provides new insights into the competing relationship not only for CDW but also for other competing orders.

Effects of Antisolvent Treatment on Copper(I) Thiocyanate Hole Transport Layer in n-i-p Perovskite Solar Cells.

Copper(I) thiocyanate (CuSCN) is considered an efficient HTL of low cost and with high stability in perovskite solar cells (PSCs). However, the diethyl sulfide solvent used for CuSCN preparation is known to cause damage to the underlying perovskite layer in n-i-p PSCs. Antisolvent treatment of CuSCN during spin-coating can effectively minimize interfacial interactions. However, the effects of antisolvent treatment are not sufficiently understood. In this study, the effects of five different antisolvents were investigated. Scanning electron microscopy and X-ray diffraction analyses showed that the antisolvent treatment improved the crystallinity of the CuSCN layer on the perovskite layer and reduced damage to the perovskite layer. However, X-ray and ultraviolet photoelectron spectroscopy analyses showed that antisolvent treatment did not affect the chemical bonds or electronic structures of CuSCN. As a result, the power conversion efficiency of the PSCs was increased from 14.72% for untreated CuSCN to 15.86% for ethyl-acetate-treated CuSCN.

Multimodal analysis of disease onset in Alzheimer's disease using Connectome, Molecular, and genetics data.

Alzheimer's disease (AD) and its related age at onset (AAO) are highly heterogeneous, due to the inherent complexity of the disease. They are affected by multiple factors, such as neuroimaging and genetic predisposition. Multimodal integration of various data types is necessary; however, it has been nontrivial due to the high dimensionality of each modality. We aimed to identify multimodal biomarkers of AAO in AD using an extended version of sparse canonical correlation analysis, in which we integrated two imaging modalities, functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), and genetic data in the form of single-nucleotide polymorphisms (SNPs) obtained from the Alzheimer's disease neuroimaging initiative database. These three modalities cover low-to-high-level complementary information and offer multiscale insights into the AAO. We identified multivariate markers of AAO in AD using fMRI, PET, and SNP. Furthermore, the markers identified were largely consistent with those reported in the existing literature. In particular, our serial mediation analysis suggests that genetic variants influence the AAO in AD by indirectly affecting brain connectivity by mediation of amyloid-beta protein accumulation, supporting a plausible path in existing research. Our approach provides comprehensive biomarkers related to AAO in AD and offers novel multimodal insights into AD.

Topological Fermi-arc surface state covered by floating electrons on a two-dimensional electride.

Two-dimensional electrides can acquire topologically non-trivial phases due to intriguing interplay between the cationic atomic layers and anionic electron layers. However, experimental evidence of topological surface states has yet to be verified. Here, via angle-resolved photoemission spectroscopy (ARPES) and scanning tunnelling microscopy (STM), we probe the magnetic Weyl states of the ferromagnetic electride [Gd2C]2+·2e-. In particular, the presence of Weyl cones and Fermi-arc states is demonstrated through photon energy-dependent ARPES measurements, agreeing with theoretical band structure calculations. Notably, the STM measurements reveal that the Fermi-arc states exist underneath a floating quantum electron liquid on the top Gd layer, forming double-stacked surface states in a heterostructure. Our work thus not only unveils the non-trivial topology of the [Gd2C]2+·2e- electride but also realizes a surface heterostructure that can host phenomena distinct from the bulk.

Programmable Retention Characteristics in MoS2-Based Atomristors for Neuromorphic and Reservoir Computing Systems.

In this study, we investigate the coexistence of short- and long-term memory effects owing to the programmable retention characteristics of a two-dimensional Au/MoS2/Au atomristor device and determine the impact of these effects on synaptic properties. This device is constructed using bilayer MoS2 in a crossbar structure. The presence of both short- and long-term memory characteristics is proposed by using a filament model within the bilayer transition-metal dichalcogenide. Short- and long-term properties are validated based on programmable multilevel retention tests. Moreover, we confirm various synaptic characteristics of the device, demonstrating its potential use as a synaptic device in a neuromorphic system. Excitatory postsynaptic current, paired-pulse facilitation, spike-rate-dependent plasticity, and spike-number-dependent plasticity synaptic applications are implemented by operating the device at a low-conductance level. Furthermore, long-term potentiation and depression exhibit symmetrical properties at high-conductance levels. Synaptic learning and forgetting characteristics are emulated using programmable retention properties and composite synaptic plasticity. The learning process of artificial neural networks is used to achieve high pattern recognition accuracy, thereby demonstrating the suitability of the use of the device in a neuromorphic system. Finally, the device is used as a physical reservoir with time-dependent inputs to realize reservoir computing by using short-term memory properties. Our study reveals that the proposed device can be applied in artificial intelligence-based computing applications by utilizing its programmable retention properties.

Origin of Distinct Insulating Domains in the Layered Charge Density Wave Material 1T-TaS2.

Vertical charge order shapes the electronic properties in layered charge density wave (CDW) materials. Various stacking orders inevitably create nanoscale domains with distinct electronic structures inaccessible to bulk probes. Here, the stacking characteristics of bulk 1T-TaS2 are analyzed using scanning tunneling spectroscopy (STS) and density functional theory (DFT) calculations. It is observed that Mott-insulating domains undergo a transition to band-insulating domains restoring vertical dimerization of the CDWs. Furthermore, STS measurements covering a wide terrace reveal two distinct band insulating domains differentiated by band edge broadening. These DFT calculations reveal that the Mott insulating layers preferably reside on the subsurface, forming broader band edges in the neighboring band insulating layers. Ultimately, buried Mott insulating layers believed to harbor the quantum spin liquid phase are identified. These results resolve persistent issues regarding vertical charge order in 1T-TaS2, providing a new perspective for investigating emergent quantum phenomena in layered CDW materials.

In vitro and in vivo antiviral effects of CLEVir-X against porcine reproductive and respiratory syndrome virus.

The aim of this study was to investigate the in vitro and in vivo antiviral effects of CLEVir-X, against porcine reproductive and respiratory syndrome virus (PRRSV). CLEVir-X is a nucleoside analogue and a dialdehyde form of xanthosine. CLEVir-X demonstrated antiviral action during the in vitro portion of this experiment with its inosine monophosphate dehydrogenase (IMPDH) inhibition against PRRSV. The anti-PRRSV effect of CLEVir-X was recovered through supplementation with guanosine. This suggests that PRRSV replication may be regulated through IMPDH and its guanosine biosynthetic pathway. CLEVir-X treatment in cultures resulted in mutation frequency increase of up to 7.8-fold within the viral genomes (e.g. ORF6) compared to their parallel, untreated cultures. The incorporation of CLEVir-X into the viral genome causes lethal mutagenesis and subsequent decrease in specific infectivity. During the in vivo antiviral experiment, 21-day-old pigs began oral administration of 5 mL of phosphate buffered saline containing CLEVir-X (with purity of 68 % and dosage of 40 mg/kg body weight). This treatment was provided twice daily at 9:00AM and 5:00PM for 14 days. Pigs were simultaneously intranasally inoculated with PRRSV at the beginning of CLEVir-X treatment (21 days of age). Several beneficial effects from the oral administration of CLEVir-X were observed including reduction of body temperature, alleviation of respiratory clinical signs, decreased PRRSV load in both blood and lung tissues, and mitigation of lung interstitial pneumonia lesions. The results of the present study demonstrated that CLEVir-X has mutagenic and nonmutagenic modes of antiviral action against PRRSV based on both in vitro and in vivo antiviral experiments.

Cardioprotection via mitochondrial transplantation supports fatty acid metabolism in ischemia-reperfusion injured rat heart.

In addition to cellular damage, ischemia-reperfusion (IR) injury induces substantial damage to the mitochondria and endoplasmic reticulum. In this study, we sought to determine whether impaired mitochondrial function owing to IR could be restored by transplanting mitochondria into the heart under ex vivo IR states. Additionally, we aimed to provide preliminary results to inform therapeutic options for ischemic heart disease (IHD). Healthy mitochondria isolated from autologous gluteus maximus muscle were transplanted into the hearts of Sprague-Dawley rats damaged by IR using the Langendorff system, and the heart rate and oxygen consumption capacity of the mitochondria were measured to confirm whether heart function was restored. In addition, relative expression levels were measured to identify the genes related to IR injury. Mitochondrial oxygen consumption capacity was found to be lower in the IR group than in the group that underwent mitochondrial transplantation after IR injury (p < 0.05), and the control group showed a tendency toward increased oxygen consumption capacity compared with the IR group. Among the genes related to fatty acid metabolism, Cpt1b (p < 0.05) and Fads1 (p < 0.01) showed significant expression in the following order: IR group, IR + transplantation group, and control group. These results suggest that mitochondrial transplantation protects the heart from IR damage and may be feasible as a therapeutic option for IHD.

The North Equatorial Current and rapid intensification of super typhoons.

Super Typhoon Mangkhut, which traversed the North Equatorial Current (NEC; 8-17 °N) in the western North Pacific in 2018, was the most intense Category-5 tropical cyclone (TC) with the longest duration in history-3.5 days. Here we show that the combination of two factors-high ocean heat content (OHC) and increased stratification - makes the NEC region the most favored area for a rapid intensification (RI) of super typhoons, instead of the Eddy Rich Zone (17-25 °N), which was considered the most relevant for RI occurrence. The high OHC results from a northward deepening thermocline in geostrophic balance with the westward-flowing NEC. The stratification is derived from precipitation associated with the Inter-Tropical Convergence Zone in the summer peak typhoon season. These factors, which are increasingly significant over the past four decades, impede the TC-induced sea surface cooling, thus enhancing RI of TCs and simultaneously maintaining super typhoons over the NEC region.

Biomechanical analysis for different mandibular total distalization methods with clear aligners: A finite element study.

Objective: : The purpose of this finite element method (FEM) study was to analyze the biomechanical differences and tooth displacement patterns according to the traction direction, methods, and sites for total distalization of the mandibular dentition using clear aligner treatment (CAT). Methods: : A finite element analysis was performed on four FEM models using different traction methods (via a precision cut hook or button) and traction sites (mandibular canine or first premolar). A distalization force of 1.5 N was applied to the traction site by changing the direction from -30 to +30° to the occlusal plane. The initial tooth displacement and von Mises stress on the clear aligners were analyzed. Results: : All CAT-based total distalization groups showed an overall trend of clockwise or counterclockwise rotation of the occlusal plane as the force direction varied. Mesiodistal tipping of individual teeth was more prominent than that of bodily movements. The initial displacement pattern of the mandibular teeth was more predominant based on the traction site than on the traction method. The elastic deformation of clear aligners is attributed to unintentional lingual tipping or extrusion of the mandibular anterior teeth. Conclusions: : The initial tooth displacement can vary according to different distalization strategies for CAT-based total distalization. Discreet application and biomechanical understanding of traction sites and directions are necessary for appropriate mandibular total distalization.

Converting the Bulk Transition Metal Dichalcogenides Crystal into Stacked Monolayers via Ethylenediamine Intercalation.

We report the synthesis of ethylenediamine-intercalated NbSe2 and Li-ethylenediamine-intercalated MoSe2 single crystals with increased interlayer distances and their electronic structures measured by means of angle-resolved photoemission spectroscopy (ARPES). X-ray diffraction patterns and transmission electron microscopy images confirm the successful intercalation and an increase in the interlayer distance. ARPES measurement reveals that intercalated NbSe2 shows an electronic structure almost identical to that of monolayer NbSe2. Intercalated MoSe2 also returns the characteristic feature of the monolayer electronic structure, a direct band gap, which generates sizable photoluminescence even in the bulk form. Our results demonstrate that the properties and phenomena of the monolayer transition metal dichalcogenides can be achieved with large-scale bulk samples by blocking the interlayer interaction through intercalation.

Maxillary basal arch forms in operated adult patients with cleft lip and palate using root apices: A pilot study.

OBJECTIVES: The purpose was to identify the maxillary basal arch forms utilizing the root apices and compare the maxillary basal arch form of groups with cleft lip and palate (CLP) and normal group. MATERIALS AND METHODS: This study included 30 patients (21.8 ± 3.5 years old) with unilateral CLP (ULCP group) and 30 patients (20.9 ± 2.2 years old) with bilateral CLP (BCLP group). The normal group consisted of 30 non-cleft patients (21.2 ± 2.3 years old) with normal occlusion. Three-dimensional (3D) Cartesian coordinates of the root apices of each tooth were determined using cone-beam computed tomography. The 3D coordinates were projected onto the palatal plane to create the 2D coordinates. Thereafter, the basal arch forms were constructed by the Procrustes superimposition. Finally, For the basal arch form comparisons among groups, the inter-root widths were measured. RESULTS: Both CLP groups had a narrower inter-root width than the normal group. The BCLP group had significantly narrower premolar and molar widths than the UCLP group (P < .05). Especially, the inter-first molar width of the UCLP and BCLP groups was 3.7 ± 0.7 (P < .001) and 6.6 ± 0.8 (P < .001) mm smaller than that of the normal group, respectively. CONCLUSIONS: We used the root apices to identify the basal arch forms. The basal arch form of patients with CLP was narrower than that of the normal group. The basal arch form of patients with BCLP was narrower than that of patients with UCLP. Our findings may help clinicians better comprehend basal arch forms in patients with CLP and transverse discrepancies.

Artificial Synapse Emulated by Indium Tin Oxide/SiN/TaN Resistive Switching Device for Neuromorphic System.

In this paper, we fabricate an ITO/SiN/TaN memristor device and analyze its electrical characteristics for a neuromorphic system. The device structure and chemical properties are investigated using transmission electron microscopy and X-ray photoelectron spectroscopy. Uniform bipolar switching is achieved through DC sweep under a compliance current of 5 mA. Also, the analog reset phenomenon is observed by modulating the reset voltage for long-term memory. Additionally, short-term memory characteristics are obtained by controlling the strength of the pulse response. Finally, bio-inspired synaptic characteristics are emulated using Hebbian learning rules such as spike-rate-dependent plasticity (SRDP) and spike-timing-dependent plasticity (STDP). As a result, we believe that the coexistence of short-term and long-term memories in the ITO/SiN/TaN device can provide flexibility in device design in future neuromorphic applications.

Improved Uniformity of TaOx-Based Resistive Switching Memory Device by Inserting Thin SiO2 Layer for Neuromorphic System.

RRAM devices operating based on the creation of conductive filaments via the migration of oxygen vacancies are widely studied as promising candidates for next-generation memory devices due to their superior memory characteristics. However, the issues of variation in the resistance state and operating voltage remain key issues that must be addressed. In this study, we propose a TaOx/SiO2 bilayer device, where the inserted SiO2 layer localizes the conductive path, improving uniformity during cycle-to-cycle endurance and retention. Transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) confirm the device structure and chemical properties. In addition, various electric pulses are used to investigate the neuromorphic system properties of the device, revealing its good potential for future memory device applications.

Double-Forming Mechanism of TaOx-Based Resistive Memory Device and Its Synaptic Applications.

The bipolar resistive switching properties of Pt/TaOx/InOx/ITO-resistive random-access memory devices under DC and pulse measurement conditions are explored in this work. Transmission electron microscopy and X-ray photoelectron spectroscopy were used to confirm the structure and chemical compositions of the devices. A unique two-step forming process referred to as the double-forming phenomenon and self-compliance characteristics are demonstrated under a DC sweep. A model based on oxygen vacancy migration is proposed to explain its conduction mechanism. Varying reset voltages and compliance currents were applied to evaluate multilevel cell characteristics. Furthermore, pulses were applied to the devices to demonstrate the neuromorphic system's application via testing potentiation, depression, spike-timing-dependent plasticity, and spike-rate-dependent plasticity.

Synaptic plasticity and non-volatile memory characteristics in TiN-nanocrystal-embedded 3D vertical memristor-based synapses for neuromorphic systems.

Although vertical configurations for high-density storage require challenging process steps, such as etching high aspect ratios and atomic layer deposition (ALD), they are more affordable with a relatively simple lithography process and have been employed in many studies. Herein, the potential of memristors with CMOS-compatible 3D vertical stacked structures of Pt/Ti/HfOx/TiN-NCs/HfOx/TiN is examined for use in neuromorphic systems. The electrical characteristics (including I-V properties, retention, and endurance) were investigated for both planar single cells and vertical resistive random-access memory (VRRAM) cells at each layer, demonstrating their outstanding non-volatile memory capabilities. In addition, various synaptic functions (including potentiation and depression) under different pulse schemes, excitatory postsynaptic current (EPSC), and spike-timing-dependent plasticity (STDP) were investigated. In pattern recognition simulations, an improved recognition rate was achieved by the linearly changing conductance, which was enhanced by the incremental pulse scheme. The achieved results demonstrated the feasibility of employing VRRAM with TiN nanocrystals in neuromorphic systems that resemble the human brain.