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We proposed two deep neural network based methods to accelerate the estimation of microstructural features of crossing fascicles in the white matter. Both methods focus on the acceleration of a multi-dictionary matching problem, which is at the heart of Microstructure Fingerprinting, an extension of Magnetic Resonance Fingerprinting to diffusion MRI. The first acceleration method uses efficient sparse optimization and a dedicated feed-forward neural network to circumvent the inherent combinatorial complexity of the fingerprinting estimation. The second acceleration method relies on a feed-forward neural network that uses a spherical harmonics representation of the DW-MRI signal as input. The first method exhibits a high interpretability while the second method achieves a greater speedup factor. The accuracy of the results and the speedup factors of several orders of magnitude obtained on in vivo brain data suggest the potential of our methods for a fast quantitative estimation of microstructural features in complex white matter configurations.
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The femoral head is one of the most commonly used bones for allografts and biomechanical studies. However, there are few reports on the trabecular bone microarchitectural parameters of freshly harvested trabecular bones. To our knowledge, this is the first study to characterize the microstructure of femoral heads tested immediately after surgery and compare it with the microstructure obtained with conventional freezing. This study aims to investigate whether freezing at -80 °C for 6 weeks affects the trabecular microstructure of freshly harvested bone tissue. This study was divided into two groups: one with freshly harvested human femoral heads and the other with the same human femoral heads frozen at -80 °C for 6 weeks. Each femoral head was scanned using an X-ray microcomputed tomography scanner (µCT) to obtain the microarchitectural parameters, including the bone volume fraction (BV/TV), the mean trabecular thickness (Tb.th), the trabecular separation (Tb.sp), the degree of anisotropy (DA), and the connectivity density (Conn.D). There was no statistically significant difference between the fresh and the frozen groups for any of the parameters measured. This study shows that freezing at -80 °C for 6 weeks does not alter bone microstructure compared with freshly harvested femoral heads tested immediately after surgery.
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Tumor organoids and tumors-on-chips can be built by placing patient-derived cells within an extracellular matrix (ECM) for personalized medicine. The ECM influences the tumor response, and understanding the ECM-tumor relationship is important before translating tumor-on-chips into clinics. In this work, we tuned the physical and structural characteristics of ECM in a bioprinted soft-tissue sarcoma microtissue. We formed 3D spheroids at a controlled size and encapsulated them into our gelatin methacryloyl (GelMA)-based bioink to make perfusable hydrogel-based microfluidic chips. We then demonstrated the scalability and customization flexibility of our hydrogel-based chip via engineering tools. A multiscale physical and structural data analysis suggested a relationship between cell invasion response and bioink characteristics. Tumor cell invasive behavior and focal adhesion properties were observed in response to varying polymer network densities of the GelMA-based bioink. Immunostaining assays and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) helped assess the bioactivity of the microtissue and measure the cell invasion. The RT-qPCR results showed higher expressions of HIF-1α, CD44, and MMP2 genes in a lower polymer density, highlighting the correlation between bioink structural porosity, ECM stiffness, and tumor spheroid response. In conclusion, this work is the first step in modeling STS tumor invasiveness in hydrogel-based microfluidic chips, and our tunable bioink may help reduce the variability of current tumor-on-chips. STATEMENT OF SIGNIFICANCE: We optimized an engineering protocol for making tumor spheroids at a controlled size, embedding spheroids into a gelatin-based matrix, and constructing a perfusable microfluidic device. A higher tumor invasion was observed in a low-stiffness matrix than a high-stiffness matrix. The physical characterizations revealed how the stiffness is controlled by the density of polymer chain networks and porosity. The biological assays revealed how the structural properties of the gelatin matrix and hypoxia in tumor progression impact cell invasion. The cell spheroids' responses underscore the importance of replicating physical and structural properties to mimic tumor response. This work can contribute to personalized medicine by making more effective, tailored cancer models.
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Egg yolk production processed after separating egg white is a common method to shorten cycle, but its taste quality will change even the vitelline membrane is intact. This might be related to the slight non-destructive deformation causing redistribution and fusion of protein-lipid assemblies within the egg yolk spheres. We investigated the mechanism of the change in thermal gel properties under slight deformation. The results of microscopic structural morphology revealed that the whole boiled egg yolk (WEY) underwent a transition in protein-lipid assembly morphology within yolk spheres, which changed from local aggregation to disordered fusion in shaken boiled egg yolks (SEYs). The spectroscopic and physicochemical properties analysis demonstrated that the redistribution of protein-lipid assemblies gave rise to marked changes in water migration, texture properties, molecular interactions, and oral sensation simulation of egg yolk thermal gels. This is benefit to guide the regulation of the taste quality egg yolk products in industry.
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The Irish Sea and the Baltic Sea are nowadays still the two most Cs-137 contaminated Seas worldwide. However, the origins of this contaminations are completely different. While the Baltic Sea was unintentionally contaminated due to global fallout after the accident in the Chernobyl nuclear powerplant in 1986, the Irish sea was intentionally used for low level liquid radioactive waste discharges from the Sellafield nuclear reprocessing facility (called Windscale until 1981) between the 1950s and 1990s. Nowadays, more than 30 years later, it is still possible to detect these contaminations in fish, water and sediments of both seas. Since fish are an important part of the human diet, monitoring Cs-137 levels in fish is essential for assessing the potential radiation exposure to humans. In 2019 and 2020 two surveys were dedicated to study the current levels of radioactive contamination in fish species from both Seas. During both surveys, fish samples were collected and analysed by gamma spectrometry later on. The results show that the average Cs-137 activity in benthic, demersal and pelagic fish species from the Baltic Sea are 2.7, 4.6 and 4.2, respectively, times higher than the corresponding values of the Irish Sea. Based on this and two other comparisons, it is concluded that the Baltic Sea is the most contaminated with Cs-137.
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Hard to cook is a textural defect that affects the nutritional quality of beans stored under adverse temperature and humidity conditions. This defect is related to intrinsic characteristics such as seed coat thickness, composition and microstructure. The aim of the present study was to evaluate the chemical and microstructural characteristics of common bean (Phaseolus vulgaris L.) during 270 days of post-harvest storage at 30 °C and 70% relative humidity. Microstructural analysis revealed alteration of the cotyledon cell wall and seed coat affecting seed viability and restricting seedling emergence. The seed coat thickness contraction from 105.79 µm to 97.35 µm (270 days). Changes are related with the protein bodies migration from cotyledons to seed coat. An increase in neutral detergent fiber and the presence of CaOx crystals were observed, which confer rigidity to the seed coat and affect water diffusion after 150 days causing permeability changes that contributed to seed hardening.
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PURPOSE: Parkinson's disease (PD) involves pathological alterations that include cortical impairments at levels of region and network. However, its microstructural abnormalities remain to be further elucidated via an appropriate diffusion neuroimaging approach. This study aimed to comprehensively demonstrate the microstructural patterns of PD as mapped by diffusion kurtosis imaging (DKI). METHODS: The microstructure of grey matter in both the PD group and the matched healthy control group was quantified by a DKI metric (mean kurtosis). The intergroup difference and classification performance of global microstructural complexity were analyzed in a voxelwise manner and via a machine learning approach, respectively. The patterns of information flows were explored in terms of structural connectivity, network covariance and modular connectivity. RESULTS: Patients with PD exhibited global microstructural impairments that served as an efficient diagnostic indicator. Disrupted structural connections between the striatum and cortices as well as between the thalamus and cortices were widely distributed in the PD group. Aberrant covariance of the striatocortical circuitry and thalamocortical circuitry was observed in patients with PD, who also showed disrupted modular connectivity within the striatum and thalamus as well as across structures of the cortex, striatum and thalamus. CONCLUSION: These findings verified the potential clinical application of DKI for the exploration of microstructural patterns in PD, contributing complementary imaging features that offer a deeper insight into the neurodegenerative process.
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Concrete durability is greatly influenced by the transport rate of aggressive chemicals. Moisture diffusion plays a key role in the long-term performance of cementitious materials, as it facilitates the entry of aggressive chemicals into concrete. The pore size distribution plays a critical role in determining moisture diffusivity. However, the characteristics of the concrete pore structure have not been included comprehensively in the material models so far. In this paper, a theoretical model was developed to obtain the pore size volume fractions for each diffusion mechanism including Molecular, Knudsen and Surface diffusions. An effective moisture diffusivity in concrete was then obtained using the weighted average based on the diffusion mechanisms and pore size volume fractions. The model's validity was demonstrated by comparing model predictions with available experimental data. The findings of this study provide valuable insights into the behavior of the concrete pore structure and its impact on moisture diffusivity.
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The physicochemical properties of Nemipterus virgatus surimi gel were investigated, with tremella powder (TP) at concentrations ranging from 0 to 0.5% (w/w) combined with continuous microwave heating (CMH) using water-bath heating (WBH) as control. Results showed that TP addition (0.1%-0.3%, w/w) could significantly enhance the water holding capacity and reduce whiteness and cooking loss, attributed to the changed lateral relaxation time of water distribution. Notably, at 0.3% TP and 80 °C, the gel strength significantly increased by 96.84%, and the hardness, chewiness, and adhesiveness improved, but the quality of surimi decreased above 0.3% TP. The gel network structure was influenced by protein secondary structure composition, especially for increasing ß-sheet in Raman spectra, thus promoting the gel microstructure density and uniform protein distribution. These findings offer insights for enhancing surimi gel quality and broadening tremella application in product processing.
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Low flexural strength and toughness have posed enduring challenges to cementitious materials. As the main hydration product of cement, calcium silicate hydrate (C-S-H) plays important roles in the mechanical performance of cementitious materials while exhibiting random microstructures with pores and defects, which hinder mechanical enhancement. Inspired by the "brick-and-mortar" microstructure of natural nacre, this paper presents a method combining freeze casting, freeze-drying, in situ polymerization, and hot pressing to fabricate C-S-H nacre with high flexural strength, high toughness, and lightweight. Poly(acrylamide-co-acrylic acid) was used to disperse C-S-H and toughen C-S-H building blocks, which function as "bricks", while poly(methyl methacrylate) was impregnated as "mortar". The flexural strength, toughness, and density of C-S-H nacre reached 124 MPa, 5173 kJ/m3, and 0.98 g/cm3, respectively. The flexural strength and toughness of the C-S-H nacre are 18 and 1230 times higher than those of cement paste, respectively, with a 60% reduction in density, outperforming existing cementitious materials and natural nacre. This research establishes the relationship between material composition, fabrication process, microstructure, and mechanical performance, facilitating the design of high-performance C-S-H-based and cement-based composites for scalable engineering applications.
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In the present study, non-conventional and green technology (ultrasonication) was utilized to recover bioactive compounds from the small, medium and large sized defatted date seed powder (DDSP) particles. Bioactive compounds recovered from DDSP and the remaining fiber-rich residue were incorporated as functional ingredient in the biscuit dough to enhance the functionality and the quality characteristics of the dough and biscuit. The polyphenolic extract and 2.5 %, 5 % and 7.5 % substitution levels of fiber-rich extraction residue were incorporated in formulations followed by investigating the effect on rheological, physical and microstructural properties of dough and biscuit. Loss and storage moduli, G'' and G', respectively, of dough increased with decreasing particle size and increasing substitution level while tan δ decreased with increasing substitution level of fiber-rich extraction residue. The smallest particles at 7.5 % substitution level resulted in the lowest creep strain value in dough. Hardness of the dough and biscuit increased with decreasing particle size and increasing substitution level of the residue. The 7.5 % substitution level of the smallest particle size resulted in the darkest dough and biscuit. Spread ratio and diameter of the biscuit decreased with increasing substitution level of the residue. The smallest diameter of 50.61 mm and spread ratio of 8.36 was observed in the biscuits substituted with the largest particle size with 7.5 % substitution level. Microstructural images of dough and biscuit revealed that the continuity of the gluten network was disrupted by the incorporation of the fiber-rich extraction residue. This study provided valuable insights into extracting bioactive components from date by-products using green ultrasonication technique and utilizing such compounds to improve functional attributes of bakery products, as a sustainable approach for valorizing date by-products.
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The primary objective of this study is to investigate the microstructural, mechanical, and wear behaviour of AZ31/TiC surface composites fabricated through friction stir processing (FSP). TiC particles are reinforced onto the surface of AZ31 magnesium alloy to enhance its mechanical properties for demanding industrial applications. The FSP technique is employed to achieve a uniform dispersion of TiC particles and grain refinement in the surface composite. Microstructural characterization, mechanical testing (hardness and tensile strength), and wear behaviour evaluation under different operating conditions are performed. Response surface methodology (RSM) is utilized to optimize the wear rate by considering the effects of process parameters. The results reveal a significant improvement in hardness (41.3%) and tensile strength (39.1%) of the FSP-TiC composite compared to the base alloy, attributed to the refined grain structure (6-10 µm) and uniform distribution of TiC particles. The proposed regression model accurately predicts the wear rate, with a confirmation test validating an error percentage within ± 4%. Worn surface analysis elucidates the wear mechanisms, such as shallow grooves, delamination, and oxide layer formation, influenced by the applied load, sliding distance, and sliding velocity. The enhanced mechanical properties and wear resistance are attributed to the synergistic effects of grain refinement, particle-accelerated nucleation, the barrier effect of TiC particles, and improved interfacial bonding achieved through FSP. The optimized FSP-TiC composites exhibit potential for applications in industries demanding high strength, hardness, and wear resistance.
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Comprehensive studies on the freeze-thaw (F-T) damage mechanism in siliceous slates are lacking. In this study, we investigated the evolutionary characteristics of F-T damage in siliceous slates. To this end, scanning electron microscopy, X-ray diffraction, X-ray fluorescence, and uniaxial compression tests were used to analyze the microstructure, phase composition, porosity, and macroscopic mechanical parameters of siliceous slate with varying initial water content during F-T cycles. The results revealed several insights. (1) The microstructure of siliceous slate undergoes significant change with respect to increasing water content and number of F-T cycles. The rock surface changed from smooth to rough, and the arrangement of the mineral particles changed from tight to loose. (2) More than 80 % of the contents of siliceous slate comprise oxygen, aluminum, silicon, potassium, and iron. In particular, siliceous slate comprises muscovite, quartz, clinochlore, and kaolinite. Both the clinochlore and kaolinite are unstable clay minerals. As clay minerals exhibit strong water absorption and expansion characteristics, kaolinite undergoes strong hydration reactions. Compared to rock samples without F-T cycles in the dry state, the clay mineral content of siliceous slate decreased by nearly 50 %, from 28.8 % to 15.5 %, after 30 F-T cycles in the saturated state. (3) The mechanical parameters of siliceous slates with varying water content decreased exponentially with the number of F-T cycles, while their porosity exhibited a positive correlation with the number of F-T cycles. The degree of deterioration in both increased with increasing water content. Both the number of F-T cycles and the initial water content were observed to wield a significant effect on the deterioration of siliceous slates. (4) The evolution curve of F-T load damage in siliceous slate exhibited characteristics of transitioning from gentle to concave and then to a convex stage of growth. Our results are expected to provide theoretical guidance for the evaluation and prevention of F-T disasters in cold regions.
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Capacitors are essential components in modern electrical systems, functioning primarily to store electrical charges and regulate current flow. Capacitive sensors, developed in the 20th century, have become crucial in various applications, including touchscreens and smart devices, due to their ability to detect both metallic and non-metallic objects with high sensitivity and low energy consumption. The advancement of microelectromechanical systems (MEMS) and nanotechnology has significantly enhanced the capabilities of capacitive sensors, leading to unprecedented sensitivity, dynamic range, and cost-effectiveness. These sensors are integral to modern devices, enabling precise measurements of proximity, pressure, strain, and other parameters. This review provides a comprehensive overview of the development, fabrication, and integration of micro and nanostructured capacitive sensors. In terms of an electric field, the working and detection principles are discussed with analytical equations and our numerical results. The focus extends to novel fabrication methods using advanced materials to enhance sensitivities for various parameters, such as proximity, force, pressure, strain, temperature, humidity, and liquid sensing. Their applications are demonstrated in wearable devices, human-machine interfaces, biomedical sensing, health monitoring, robotics control, industrial monitoring, and molecular detection. By consolidating existing research, this review offers insights into the advancements and future directions of capacitive sensor technology.
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Neuroanatomical changes to the cortex during adolescence have been well documented using MRI, revealing ongoing cortical thinning and volume loss with age. However, the underlying cellular mechanisms remain elusive with conventional neuroimaging. Recent advances in MRI hardware and new biophysical models of tissue informed by diffusion MRI data hold promise for identifying the cellular changes driving these morphological observations. This study used ultra-strong gradient MRI to obtain high-resolution, in vivo estimates of cortical neurite and soma microstructure in sample of typically developing children and adolescents. Cortical neurite signal fraction, attributed to neuronal and glial processes, increased with age (mean R2 fneurite=.53, p<3.3e-11, 11.91% increase over age), while apparent soma radius decreased (mean R2 Rsoma=.48, p<4.4e-10, 1% decrease over age) across domain-specific networks. To complement these findings, developmental patterns of cortical gene expression in two independent post-mortem databases were analysed. This revealed increased expression of genes expressed in oligodendrocytes, and excitatory neurons, alongside a relative decrease in expression of genes expressed in astrocyte, microglia and endothelial cell-types. Age-related genes were significantly enriched in cortical oligodendrocytes, oligodendrocyte progenitors and Layer 5-6 neurons (pFDR<.001) and prominently expressed in adolescence and young adulthood. The spatial and temporal alignment of oligodendrocyte cell-type gene expression with neurite and soma microstructural changes suggest that ongoing cortical myelination processes contribute to adolescent cortical development. These findings highlight the role of intra-cortical myelination in cortical maturation during adolescence and into adulthood.
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The human brain undergoes age-related microstructural alterations across the lifespan. Soma and Neurite Density Imaging (SANDI), a novel biophysical model of diffusion MRI, provides estimates of cell body (soma) radius and density, and neurite density in gray matter. The goal of this cross-sectional study was to assess the sensitivity of high-gradient diffusion MRI toward age-related alterations in cortical microstructure across the adult lifespan using SANDI. Seventy-two cognitively unimpaired healthy subjects (ages 19-85 years; 40 females) were scanned on the 3T Connectome MRI scanner with a maximum gradient strength of 300mT/m using a multi-shell diffusion MRI protocol incorporating 8 b-values and diffusion time of 19 ms. Intra-soma signal fraction obtained from SANDI model-fitting to the data was strongly correlated with age in all major cortical lobes (r = -0.69 to -0.60, FDR-p < 0.001). Intra-soma signal fraction (r = 0.48-0.63, FDR-p < 0.001) and soma radius (r = 0.28-0.40, FDR-p < 0.04) were significantly correlated with cortical volume in the prefrontal cortex, frontal, parietal, and temporal lobes. The strength of the relationship between SANDI metrics and age was greater than or comparable to the relationship between cortical volume and age across the cortical regions, particularly in the occipital lobe and anterior cingulate gyrus. In contrast to the SANDI metrics, all associations between diffusion tensor imaging (DTI) and diffusion kurtosis imaging metrics and age were low to moderate. These results suggest that high-gradient diffusion MRI may be more sensitive to underlying substrates of neurodegeneration in the aging brain than DTI and traditional macroscopic measures of neurodegeneration such as cortical volume and thickness.
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Edible films are effective alternatives to plastic packaging, however, the hydrophilicity of edible films based on protein and polysaccharide limits the application. Therefore, we fabricated a water-stable hybrid film with a linear-spherical interpenetrating molecular topology network using egg white (EW), chitosan (CS), and pectin. Meanwhile, the nisin-tannin acid self-assembly complex nanoparticles were employed as a multifunctional cross-linker, antibacterial and antioxidant agent to improve the performance of films. The FTIR, XRD, and SEM analysis revealed that the conformation and crystalline structure rearrangement of chitosan induced by the alkaline environment provided by egg white enhanced the network structure of films, effectively avoided the addition of modifying reagents. The proposed hybrid films exhibited excellent properties, with EW/TNPCS3 showing the best overall performance. The water contact angle (WCA) increased to 105.27 ± 1.62°, and its dissolution and swelling rates were significantly lower than pure egg white and pure chitosan films. Moreover, tannin-nisin (TN) nanoparticles endowed the films with excellent antimicrobial activity against the common Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. Thus, the prepared blending films have great application potential in food preservation, especially to maintain stable performance in high humidity environment.
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Background: The ligamentum flavum (LF) degeneration is a critical factor in spinal stenosis, leading to nerve compression and pain. Even with new treatment options becoming available, it is vital to have a better understanding of LF degeneration to ensure the effectiveness of these treatments. Objective: This study aimed to provide insight into LF degeneration by examining the connections between various aspects of LF degeneration, including histology, microstructure, chemical composition, and biomechanics. Method: We analyzed 30 LF samples from 27 patients with lumbar vertebrae, employing magnetic resonance imaging (MRI) to link lumbar disc degeneration grades with fibrosis levels in the tissue. X-ray diffraction (XRD) analysis assessed microstructural alterations in the LF matrix component due to degeneration progression. Instrumented nanoindentation combined with Raman spectroscopy explored the spatial microbiomechanical and biochemical characteristics of the LF's ventral and dorsal regions. Results: Our outcomes revealed a clear association between the severity of LF fibrosis grades and increasing LF thickness. XRD analysis showed a rise in crystalline components and hydroxyapatite molecules with progressing degeneration. Raman spectroscopy detected changes in the ratio of phosphate, proteoglycan, and proline/hydroxyproline over the amide I band, indicating alterations in the extracellular matrix composition. Biomechanical testing demonstrated that LF tissue becomes stiffer and less extensible with increasing fibrosis. Discussion: Notably, the micro-spatial assessment revealed the dorsal side of the LF experiencing more significant mechanical stress, alongside more pronounced biochemical and biomechanical changes compared to the ventral side. Degeneration of the LF involves complex processes that affect tissue histology, chemical composition, and biomechanics. It is crucial to fully understand these changes to develop new and effective treatments for spinal stenosis. These findings can improve diagnostic accuracy, identify potential biomarkers and treatment targets, guide personalized treatment strategies, advance tissue engineering approaches, help make informed clinical decisions, and educate patients about LF degeneration.
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Background: During the course of adulthood and aging, white matter (WM) structure and organization are characterized by slow degradation processes such as demyelination and shrinkage. An acceleration of such aging processes has been linked to the development of a range of diseases. Thus, an accurate description of healthy brain maturation, particularly in terms of WM features, is fundamental to the understanding of aging. Methods: We used longitudinal diffusion magnetic resonance imaging to provide an overview of WM changes at different spatial and temporal scales in the UK Biobank (UKB) (n = 2678; agescan 1 = 62.38 ± 7.23 years; agescan 2 = 64.81 ± 7.1 years). To examine the genetic overlap between WM structure and common clinical conditions, we tested the associations between WM structure and polygenic risk scores for the most common neurodegenerative disorder, Alzheimer's disease, and common psychiatric disorders (unipolar and bipolar depression, anxiety, obsessive-compulsive disorder, autism, schizophrenia, attention-deficit/hyperactivity disorder) in longitudinal (n = 2329) and cross-sectional (n = 31,056) UKB validation data. Results: Our findings indicate spatially distributed WM changes across the brain, as well as distributed associations of polygenic risk scores with WM. Importantly, brain longitudinal changes reflected genetic risk for disorder development better than the utilized cross-sectional measures, with regional differences giving more specific insights into gene-brain change associations than global averages. Conclusions: We extend recent findings by providing a detailed overview of WM microstructure degeneration on different spatial levels, helping to understand fundamental brain aging processes. Further longitudinal research is warranted to examine aging-related gene-brain associations.
In their study, Korbmacher et al. benchmark healthy aging processes in the brain's white matter. Findings of degrading white matter at higher ages were consistent with recent cross-sectional and longitudinal findings, particularly outlining changes in ventricle-near and cerebellar white matter. Degenerative processes were also found to accelerate at a higher age. Finally, the polygenic risk to develop psychiatric and neurodegenerative disorders was weakly associated with the white matter change in the otherwise healthily aging participants.
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The exploration of deformation behaviors within titanium and its alloys across a spectrum of temperatures, in particular at the low temperature range, is imperative for the development of strong and tough titanium alloys. This study has been meticulously devised with an emphasis on the deformed microstructure and mechanical property of pure titanium at temperatures of 77â¯K, 180â¯K, 240â¯K, and 298â¯K. Tensile results indicate a concurrent enhancement in both strength and ductility, as well as the work hardening capacity, as the deformation temperature decreases. Quantitative analysis demonstrated such superior mechanical properties and hardening capacity are attributed to the high twin density and the predominant twin variations converting from {11-22} twins to {10-12} twins at low temperatures. Therefore, the present study potentially offers insights into the understanding and development of titanium alloys by facilitating the strategic manipulation of temperature-mediated twin activity.