Alzheimer disease classification using KPCA,LDA, and multi‐kernel learning SVM

Early diagnosis of Alzheimer disease (AD) and mild cognitive impairment (MCI) is always useful. Preventive measures might have an impact on reducing AD risk factors. Structural magnetic resonance (MR) imaging, one of the vital sensitive biomarkers for cerebral atrophy in the brain, is used to extract volumetric feature by FreeSurfer and the CIVET toolbox. All of the structural magnetic resonance imaging (s‐MRI) data that we used were downloaded from the Alzheimer's disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu) of imaging data. This novel approach is applied for the diagnosis of AD and MCI from healthy controls (HCs) combining extracted features with the MMSE (mini‐mental state examination) scores, applying a two sample t‐test to select a subset of features. The subset of features is fed to kernel principal component analysis (KPCA) module to project data onto the reduced principal component coefficients at higher dimensional kernel space to increase the linear separability. Then, the kernel PCA coefficients are projected into the more efficient linear discriminant space using linear discriminant analysis. A multi‐kernel learning support vector machine (SVM) is used on newly projected data for stratification of AD and MCI from HCs. Using this approach, we obtain 93.85% classification accuracy when detecting AD from HCs for segmented volumetric features (using FreeSurfer) with high sensitivity and specificity. When distinguishing MCI from HCs and AD using volumetric features after subcortical segmentation, the detection rate reaches 86.54% and 75.12%, respectively.     

Small Extracellular Vesicles Derived from Human Chorionic MSCs as Modern Perspective towards Cell-Free Therapy

Mesenchymal stem cells (MSCs) are of great interest to scientists due to their application in cell therapy of many diseases, as well as regenerative medicine and tissue engineering. Recently, there has been growing evidence surrounding the research based on extracellular vesicles (EVs), especially small EVs (sEVs)/exosomes derived from MSCs. EVs/exosomes can be secreted by almost all cell types and various types of EVs show multiple functions. In addition, MSCs-derived exosomes have similar characteristics and biological activities to MSCs and their therapeutic applications are considered as a safe strategy in cell-free therapy. The aim of this study was the characterization of MSCs isolated from the chorion (CHo-MSCs) of human full-term placenta, as well as the isolation and analysis of small EVs obtained from these cells. Accordingly, in this study, the ability of small EVs’ uptake is indicated by synovial fibroblasts, osteoblasts and periosteum-derived MSCs. Improvement in the understanding of the structure, characteristics, mechanism of action and potential application of MSCs-derived small EVs can provide new insight into improved therapeutic strategies.     

Influence of Hypoxia on Radiosensitization of Cancer Cells by 5-Bromo-2′-deoxyuridine

Radiotherapy is a crucial cancer treatment, but its outcome is still far from satisfactory. One of the reasons that cancer cells show resistance to ionizing radiation is hypoxia, defined as a low level of oxygenation, which is typical for solid tumors. In the hypoxic environment, cancer cells are 2–3 times more resistant to ionizing radiation than normoxic cells. To overcome this important impediment, radiosensitizers should be introduced to cancer therapy. When modified with an electrophilic substituent, nucleosides may undergo efficient dissociative electron attachment (DEA) that leaves behind nucleoside radicals, which, in secondary reactions, are able to induce DNA damage, leading to cancer cell death. We report the radiosensitizing effect of one of the best-known DEA-type radiosensitizers—5-bromo-2′-deoxyuridine (BrdU)—on breast (MCF-7) and prostate (PC3) cancer cells under both normoxia and hypoxia. MCF-7 and PC3 cells were treated with BrdU to investigate the effect of hypoxia on cell proliferation, incorporation into DNA and radiosensitivity. While the oxygen concentration did not significantly affect the efficiency of BrdU incorporation into DNA or the proliferation of tumor cells, the radiosensitizing effect of BrdU on hypoxic cells was more evident than on normoxic cells. Further mechanistic studies performed with the use of flow cytometry showed that under hypoxia, BrdU increased the level of histone H2A.X phosphorylation after X-ray exposure to a greater extent than under normal oxygenation conditions. These results confirm that the formation of double-strand breaks in hypoxic BrdU-treated cancer cells is more efficient. In addition, by performing stationary radiolysis of BrdU solution in the presence of an ^●OH radical scavenger, we compared the degree of its electron-induced degradation under aerobic and anaerobic conditions. It was determined that radiodegradation under anaerobic conditions was almost twice as high as that under aerobic conditions.     

E-Cadherin-dependent growth suppression is mediated by the cyclin-dependent kinase inhibitor p27(KIP1)

Recent studies have demonstrated the importance of E-cadherin, a homophilic cell-cell adhesion molecule, in contact inhibition of growth of normal epithelial cells. Many tumor cells also maintain strong intercellular adhesion, and are growth-inhibited by cell- cell contact, especially when grown in three-dimensional culture. To determine if E-cadherin could mediate contact-dependent growth inhibition of nonadherent EMT/6 mouse mammary carcinoma cells that lack E-cadherin, we transfected these cells with an exogenous E-cadherin expression vector. E-cadherin expression in EMT/6 cells resulted in tighter adhesion of multicellular spheroids and a reduced proliferative fraction in three-dimensional culture. In addition to increased cell-cell adhesion, E-cadherin expression also resulted in dephosphorylation of the retinoblastoma protein, an increase in the level of the cyclin-dependent kinase inhibitor p27(kip1) and a late reduction in cyclin D1 protein. Tightly adherent spheroids also showed increased levels of p27 bound to the cyclin E-cdk2 complex, and a reduction in cyclin E-cdk2 activity. Exposure to E-cadherin-neutralizing antibodies in three-dimensional culture simultaneously prevented adhesion and stimulated proliferation of E-cadherin transfectants as well as a panel of human colon, breast, and lung carcinoma cell lines that express functional E-cadherin. To test the importance of p27 in E-cadherin-dependent growth inhibition, we engineered E-cadherin-positive cells to express inducible p27. By forcing expression of p27 levels similar to those observed in aggregated cells, the stimulatory effect of E-cadherin-neutralizing antibodies on proliferation could be inhibited. This study demonstrates that E-cadherin, classically described as an invasion suppressor, is also a major growth suppressor, and its ability to inhibit proliferation involves upregulation of the cyclin-dependent kinase inhibitor p27.     

Xyloneside A: A New Glycosylated Incisterol Derivative from Xylaria sp. FB

Xylaria species are prolific natural product producers. Here, we report the characterization of a new glycosylated incisterol derivative, called xyloneside A ( 1 ) and two known lignans ( 2 and 3 ) from the ascomycetous Xylaria sp. FB. The structure of xyloneside A ( 1 ) was determined by 1D and 2D NMR spectroscopy, high-resolution electrospray ionization mass spectrometry and electronic circular dichroism measurements. Xyloneside A is composed of a 1,2,3,4,5,10,19- heptanorergosterane skeleton and a β-D-mannopyranose moiety. This is the first report of an incisterol derivative from an Ascomycete. The biological effects of the isolated metabolites on cytotoxicity, autophagy, cell-migration, and angiogenesis were evaluated.     

Preparation and properties of a MnCo2O4 for ceramic interconnect of solid oxide fuel cell via glycine nitrate process

MnCo₂O₄ powder was prepared by a wet chemistry method using metal nitrates and glycine in an aqueous solution. The phase stability, sintering behavior, thermal expansion and electrical conductivity were examined to characterize powder suitability as an interconnect material in solid oxide fuel cells (SOFCs). X-ray diffraction indicated that the MnCo₂O₄ spinel synthesized by the glycine nitrate process was stable until 1100 °C and it was possible to obtain a fully densified single phase spinel. On the other hand, the MnCo₂O₄ synthesized by a solid state reaction decomposed into a cubic spinel and CoO after being sintered at 1100 °C. This might be associated with the reduction of Co³⁺ in the octahedral site of the cubic spinel phase. MnCo₂O₄ showed a thermal expansion coefficient comparable to that of other SOFCs components, as well as good electrical conductivity. Therefore, MnCo₂O₄ is a potential candidate for the ceramic interconnects in SOFCs, provided the phase instability under reducing environments can be improved.     

Topology optimization of a PCB substrate considering mechanical constraints and heat conductivity

A material mixing method was suggested to obtain an optimal topology for a multiple material structure with multiple thermal criteria, based on Evolutionary Structural Optimization (ESO). To examine the validity of the method, it was applied to a printed circuit board (PCB) substrate. The overall efficiency of material usage in a PCB substrate was measured in terms of the combination of thermal stress and heat flux density by using a combination strategy with weighting factors. A Pareto optimal topology solution having multiple thermal criteria was obtained. The effects of weighting factors for multiple thermal criteria as well as mechanical boundary conditions on optimal topologies were investigated. It was found that as the weighting factor for heat flux density becomes larger, the sizes of holes at the center portion become larger in order to dissipate thermal energy much more efficiently. It was also found that as the magnitudes of the heat conduction are getting larger, a similar tendency of the optimal topologies is obtained to the above. The thermal stress on the clamped four sides is larger than that on the two sides clamped. It is verified that the suggested material mixing method works very well for topology optimization of a PCB substrate for various mechanical boundary conditions with multiple thermal criteria.     

Study on the periodic flows in a rectangular container under a background rotation

We present numerical and experimental results of the periodic flows inside a rectangular container under a background rotation. In numerical computation, a parallel-computation technique with MPI is implemented. Flow visualization and PIV measurement are also performed to obtain velocity fields at the free surface. Through a series of numerical and experimental works, we aim to clarify the fundamental reasons of discrepancy between the two-dimensional computation and the experimental measurement, which was detected in the previous study for the same flow model. Specifically, we check if the various assumptions prerequisite for the validity of the classical Ekman pumping law are satisfied for periodic flows under a background rotation.