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Department of ChemistryAlzheimer's disease (AD), which is one of the neurodegenerative diseases, is the most common form of dementia. The general symptoms associated with AD include memory loss, cognitive impairment, and loss of identity. Although much research has been conducted to elucidate the etiology of AD and develop a drug for curing the disease, it has been very challenging due to its complex nature. The accumulation of aggregated amyloid-?? (A??) peptides is observed as a pathological hallmark in the AD-affected brain. In addition, other pathological features [e.g., dyshomeostasis of metal ions and overproduction of reactive oxygen species (ROS) leading to oxidative stress] are also shown in the brain of AD. Moreover, it has been reported that these pathological elements, including A?? peptides, metal ions, and ROS could be interconnected with each other. For instance, redox-active metal ions can accelerate the rate of A?? aggregation and stabilize the toxic A?? aggregates, such as structured oligomers. Furthermore, redox-active metal ions are able to interact with A?? species forming metal-bound A?? (metal???A??) complexes that can generate ROS through Fenton-like reactions. Therefore, in order to effectively treat AD, it is necessary to elucidate an inter-relationship among multiple pathogenic factors. The studies presented in this thesis exhibit the development of chemical tools for targeting and regulating multiple pathogenic components found in the brain of AD. Chapter 1 describes a minimalistic redox-based design strategy for engineering compact molecules based on a simplest aromatic framework, benzene, with multi-reactivity against multiple pathological factors of AD. In Chapter 2, investigations of fluorescent probes for monitoring metal ions in biological systems are summarized. Collectively, our overall studies and findings, presented in this thesis, demonstrate the feasibility of establishing effective and efficient design strategies to target and regulate multiple factors found in AD in order to reveal their possible inter-related pathological network.clos

Small and Medium Amplitude Oscillatory Shear Rheology of Model Branched Polystyrene (PS) Melts

Linear and nonlinear rheological properties of model comb polystyrenes (PS) with loosely to densely grafted architectures were measured under small and medium amplitude oscillatory shear (SAOS and MAOS) flow. This comb PS set had the same length of backbone and branches but varied in the number of branches from 3 to 120 branches. Linear viscoelastic properties of the comb PS were compared with the hierarchical model predictions. The model underpredicted zero-shear viscosity and backbone plateau modulus of densely branched comb with 60 or 120 branches because the model does not include the effect of side chain crowding. First- and third-harmonic nonlinearities reflected the hierarchy in the relaxation motion of comb structures. Notably, the low-frequency plateau values of first-harmonic MAOS moduli scaled with M$^{-2}$$_{w}$ (total molecular weight), reflecting dynamic tube dilution (DTD) by relaxed branches. Relative intrinsic nonlinearity Q$_{0}$ exhibited the difference between comb and bottlebrush via no low-frequency Q$_{0}$ peak of bottlebrush corresponding to backbone relaxation, which is probably related to the stretched backbone conformation in bottlebrush

Development and characterization of stable cell lines constitutively expressing the porcine reproductive and respiratory syndrome virus nucleocapsid protein

Despite global efforts to control porcine reproductive and respiratory syndrome virus (PRRSV) infection, the virus continues to cause economic problems in the swine industry worldwide. In this study, we attempted to generate and characterize a panel of stable BHK cell lines that constitutively express the nucleocapsid (N) protein of type 1 or type 2 PRRSV. The established BHK cell lines were found to react well with N-specific antibodies as well as the hyperimmune serum of pigs raised against each genotype of PRRSV. Taken together, the data implicate a potential usefulness for the newly generated stable cell lines as a diagnostic reagent for PRRSV serology

cPlot: Contig-Plotting Visualization for the Analysis of Short-Read Nucleotide Sequence Alignments

Advances in the next-generation sequencing technology have led to a dramatic decrease in read-generation cost and an increase in read output. Reconstruction of short DNA sequence reads generated by next-generation sequencing requires a read alignment method that reconstructs a reference genome. In addition, it is essential to analyze the results of read alignments for a biologically meaningful inference. However, read alignment from vast amounts of genomic data from various organisms is challenging in that it involves repeated automatic and manual analysis steps. We, here, devised cPlot software for read alignment of nucleotide sequences, with automated read alignment and position analysis, which allows visual assessment of the analysis results by the user. cPlot compares sequence similarity of reads by performing multiple read alignments, with FASTA format files as the input. This application provides a web-based interface for the user for facile implementation, without the need for a dedicated computing environment. cPlot identifies the location and order of the sequencing reads by comparing the sequence to a genetically close reference sequence in a way that is effective for visualizing the assembly of short reads generated by NGS and rapid gene map construction

Immediate Effects of Mental Singing While Walking on Gait Disturbance in Hemiplegic Stroke Patients: A Feasibility Study

ObjectiveTo investigate the immediate therapeutic effects of mental singing while walking intervention on gait disturbances in hemiplegic stroke patients.MethodsEligible, post-stroke, hemiplegic patients were prospectively enrolled in this study. The inclusion criteria were a diagnosis of hemiplegia due to stroke, and ability to walk more than 10 m with or without gait aids. Each patient underwent structured music therapy sessions comprising 7 consecutive tasks, and were trained to sing in their mind (mental singing) while walking. Before, and after training sessions, gait ability was assessed using the 10-Meter Walk Test (10MWT), the Timed Up and Go test (TUG), gait velocity, cadence and stride length.ResultsTwenty patients were enrolled in the interventions. Following the mental singing while walking intervention, significant improvement was observed in the 10MWT (13.16±7.61 to 12.27±7.58; p=0.002) and the TUG test (19.36±15.37 to 18.42±16.43; p=0.006). Significant improvement was also seen in gait cadence (90.36±29.11 to 95.36±30.2; p<0.001), stride length (90.99±33.4 to 98.17±35.33; p<0.001) and velocity (0.66±0.45 to 0.71±0.47; p<0.002).ConclusionThese results indicate the possible effects of mental singing while walking on gait in patients diagnosed with hemiplegic stroke

Thermally conductive 2D filler orientation control in polymer using thermophoresis

To achieve efficient heat dissipation using polymer composites, it is important to optimize the heat conduction pathway. Therefore, manipulating the orientation of thermally conductive and anisotropic fillers in composites represents a judicious strategy. So far, external fields have been applied to align fillers within the matrix. However, these processes are energy-intensive and require stimuli-responsive fillers through surface modification, further complicating the process and deteriorating filler thermal conductivity. Herein, to these ends, a facile method for manufacturing composite with an orientation-controlled model anisotropic filler, hexagonal boron nitride (h-BN), was proposed by harnessing thermophoresis. Thermophoresis causes movement and/or rotation of solid particles in a fluid with a steady temperature gradient. A suspension of UV-curable monomer with well-dispersed h-BN was subjected to a temperature gradient, inducing filler rotation via thermophoresis. A subsequent photo-curing yielded a solid composite with the frozen h-BN aligned in a direction agreed with expected for thermophoresis, as indicated by the anisotropic thermal conductivity measurement and cross-sectional scanning electron microscopy (SEM) observation. Additionally, the theoretically estimated Peclet number, induced by thermophoresis, was higher than the experimentally determined value required to align suspended h-BN. To our best knowledge, the current study is the first experimental demonstration of controlling anisotropic filler orientation using thermophoresis

Morphological Evaluation of PP/PS Blends Filled with Different Types of Clays by Nonlinear Rheological Analysis

The effects of various Cloisite nanoparticulate clays with different hydrophobicities on (80/20) polypropylene/polystyrene (PP/PS) blends were investigated using their linear and nonlinear rheological properties. In descending order of hydrophobicity the four Cloisite clays examined were C20A > C10A > C30B > CNa+. Clays with a wetting coefficient ωa of between 1 and −1, that is C20A and C10A, located at PP/PS polymer interfaces and suppressed coalescence, while clays with a ωa of >1, that is C30B and CNa+, accumulated inside the PS droplets and increased viscosity ratios. As a result, C20A and C10A caused PS droplet size reductions while C30B and CNa+ did not change morphology of the PP/PS blend. Linear rheological properties as determined by SAOS (small amplitude oscillatory shear) test and nonlinear rheological properties determined by LAOS (large amplitude oscillatory shear) test revealed C20A and C10A increased mechanical properties of PP/PS blends. Rheological properties from SAOS and LAOS tests decreased in the same order as clay hydrophobicities at same concentration. The nonlinear–linear viscoelastic ratio (NLR is defined as normalized nonlinear viscoelastic properties/normalized linear viscoelastic properties) was used to quantify degrees of PS droplet dispersion and to determine the compatibilizing effects of the four clays on PP/PS blends. PP/PS blends filled with hydrophilic clays (C30B and CNa+) exhibited constant NLR values (NLR ≅ 1) with increasing clay concentration. However, NLR values of PP/PS blends containing C20A and C10A were much larger than 1 (NLR > 1) and increased with clay concentration, which concurred with reductions in droplet sizes. Interestingly, NLR values and droplet size changes exhibited inverse relationships with clay hydrophobicity. In addition, PS droplet sizes in PP/PS/C20A blends in the medium amplitude oscillatory shear (MAOS) flow region (Q0 zone) were observed to check NLR validation. It was found that droplet sizes did not change in the MAOS region where NLR values are calculated and that thus NLR values corresponded with droplet sizes. Finally, inverse composition (20/80) PP/PS/C20A blends were studied, and a good correlation was obtained between PP droplet sizes and NLR values

Relay detection of Zn 2+ and S 2??? by a quinoline-based fluorescent chemosensor in aqueous media and zebrafish

A new quinoline-based fluorescent chemosensor MDCQA was designed and synthesized for the relay sensing of Zn 2+ and S 2??? . MDCQA showed turn-on fluorescence toward Zn 2+ , and the resulting complex was able to detect S 2??? among the competitive anions by turn-off fluorescence. Detecting limits (0.06 ??M and 2.33 ??M) for zinc ion and sulfide were remarkably below WHO guidelines (76.0 ??M for zinc ion and 14.7 ??M for sulfide). In addition, sensor MDCQA successfully operated for imaging Zn 2+ in live zebrafish larvae and quantifying it in real water samples. The detecting properties and mechanisms of MDCQA toward zinc ion and sulfide were demonstrated by UV???vis and fluorescence spectroscopy, NMR titration, DFT calculations and ESI-Mass

A multiple target chemosensor for the sequential fluorescence detection of Zn2+ and S2- and the colorimetric detection of Fe3+/2+ in aqueous media and living cells

A novel multiple target sensor, (E)-5-((4-(diethylamino)-2-hydroxybenzyldene) amino)-1H-imidazole-4-carboxamide (DHIC), was synthesized for fluorescence detection of Zn2+ and S2- and colorimetric detection of Fe3+/2+ in aqueous media. DHIC can operate as a turn &quot;on-off&quot; sequential fluorescent sensor for Zn2+ and S2-. Detection limits (1.59 mu M and 8.03 mu M) for Zn2+ and S2- are below the WHO standards (76.0 mu M and 14.7 mu M). The DHIC-Zn2+ complex could be reversibly reused with ethylenediaminetetraacetic acid. Importantly, DHIC could image sequentially Zn2+ and S2- in living cells. Moreover, DHIC displayed a discriminatory color change from pale yellow to orange yellow to Fe3+/2+. The detection limit of DHIC for Fe3+/2+ (0.73 mu M and 1.11 mu M) is far below the EPA drinking water standard (5.37 mu M). The sensor DHIC could be applied to analyze Fe3+ in real samples