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Various nanostructured sensor designs currently aim to achieve or claim single molecular detection by a reduction of the active sensor size. However, a reduction of the sensor size has the negative effect of reducing the capture probability considering the diffusion-based analyte transport commonly used. Here we introduce and apply a localized programmable electrodynamic precipitation concept as an alternative to diffusion. The process provides higher collection rates of airborne species and detection at lower concentration. As an example, we compare an identical nanostructured surfaced-enhanced Raman spectroscopy sensor with and without localized delivery and find that the sensitivity and detection time is improved by at least two orders of magnitudes. Localized collection in an active-matrix array-like fashion is also tested, yielding hybrid molecular arrays on a single chip over a broad range of molecular weights, including small benzenethiol (110.18 Da) and 4-fluorobenzenethiol (128.17 Da), or large macromolecules such as anti-mouse IgG (~150 kDa). Effective collection of molecules on a small sensing area is not possible based on diffusion alone and the employment of a directed force is required. The authors report a localized electrodynamic precipitation concept to collect, spot and detect airborne species in an active-matrix array-like fashion.

Material and optical analyses of three InGaN/GaN quantum-well (QW) samples with different Si-doping conditions were conducted. Quantum-dot (QD) structures were observed in samples of Si doping either in barriers or wells. The calibrated-radiative lifetimes in both Si-doped samples showed the consistent trend of the formation of 0-D structure upon Si doping. In optical characterization, the barrier-doped sample showed a blueshift of the photoluminescence (PL) peak, enhancement of integrated PL intensity, reduction of Stokes shift (SS), decrease of carrier-activation energy, and shortening of PL decay time. Except the insignificant PL peak shift, the well-doped sample showed similar trends, although they are not as prominent as the barrier-doped sample. Such results mainly originated from the reduction of the quantum-confined Stark effect (QCSE) within the clusters. Contrary to the interpretation in the past, the major mechanism for QCSE reduction is due to strain relaxation, instead of carrier screening, in conjunction with the formation of QD structures. Such a conclusion is supported by the result of smaller changes of optical behavior in the well-doped sample, in which carrier screening is expected to be more significant. In this sample, besides strain relaxation, enhanced carrier localization (CL) might represent another important mechanism for photon-emission improvement. 21 refs.

This thesis focuses on nanomanufacturing processes for the heterogeneous integration of nanomaterials and molecules. We demonstrate and discovered a novel gas phase method to control material flux at specific points on a surface which is based on the interplay of high mobility gas ions and lower mobility nanoparticles and molecules in the presence of a patterned substrate. The thesis is divided into two parts describing applications of the discovered process for the localized deposition of (A) metallic and semiconducting particles producing functional nanostructured deposits including multimaterial sensor arrays and nanostructured electrodes for photovoltaic applications and, (B) molecules for gas sensor application demonstrating improved collection efficiencies and sensitivity over previously methods. Section (A) begins with the description of an arc discharge based method to produce a flux of charged nanoparticles (<5nm particles Au, Ag, Pt, W, TiO2 , ZnO and Ge) which are characterized using various methods. It then describes a process to locally deposit the charged particles into extended two and three dimensional metallic and semiconducting nanostructured deposits. The thesis describes the use externally-biased electrodes to achieve an electronic shutter to turn ON/OFF the deposition in selected domains. Subsequently it explores and describes the use of patterned dielectrics whereby the patterned dielectrics are charged to define arrays of electrodynamic lenses. Incorporation of these lensing structures was found to enable nanostructured deposits with sub 100nm lateral resolution. The utility of the discovered processes are demonstrated in two areas. For the first application, semiconducting nanomaterial are sequentially deposited on the same substrate to fabricate a multi-material/multi-functional sensor array on a single substrate in a single deposition process. The process eliminates critical alignment and masking steps and has a higher material efficiency when compared with traditional vapor deposition methods. In the second application, we demonstrate the fabrication of 3D nanostructured electrodes for photovoltaic application. The second application adjusts the material flux in selected domains to identify nanostructures and device metrics in a combinatorial way. Section (B) applies the process to the localized collection of airborne molecules. The goal was to determine if the process can be scaled to particles with molecular dimensions. This turned out to be the case. As an application we demonstrate enhanced collection efficiencies of molecular species in gas sensor applications. The research recognizes that various nanostructured sensor designs currently aim to achieve or claim single molecular detection by a reduction of the active sensor size. However, a reduction of the sensor size has the negative effect of reducing the capture probability considering the diffusion based analyte transport commonly used. Specifically, we applied the discovered localized programmable electrodynamic precipitation concept to collect, spot, and detect airborne species in an active-matrix array-like fashion. The method is tested using surface enhanced Raman spectroscopy (SERS). The process can produce hybrid molecular arrays on a single chip over a broad range of molecular weights including small molecules or large macromolecules. From a gas sensor system point of view it was possible to improved collection efficiencies and sensitivity over previously method.

Mesenchymal stem cell (MSC)-based therapies may aid in the repair of articular cartilage defects. The purpose of this study was to investigate the effects of intraarticular injection of allogeneic MSCs in an in vivo anterior cruciate ligament transection (ACLT) model of osteoarthritis in rabbits. Allogeneic bone marrow-derived MSCs were isolated and cultured under hypoxia (1% O2). After 8 weeks following ACLT, MSCs suspended in hyaluronic acid (HA) were injected into the knees, and the contralateral knees were injected with HA alone. Additional controls consisted of a sham operation group as well as an untreated osteoarthritis group. The tissues were analyzed by macroscopic examination as well as histologic and immunohistochemical methods at 6 and 12 weeks post-transplantation. At 6 and 12 weeks, the joint surface showed less cartilage loss and surface abrasion after MSC injection as compared to the tissues receiving HA injection alone. Significantly better histological scores and cartilage content were observed with the MSC transplantation. Furthermore, engraftment of allogenic MSCs were evident in surface cartilage. Thus, injection of the allogeneic MSCs reduced the progression of osteoarthritis in vivo.

The aberrant regulation of phosphatidylinositide 3-kinases (PI3-K)/Akt, AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (m-TOR) signaling pathways in cancer has prompted significant interest in the suppression of these pathways to treat cancer. Caffeic acid (CA) has been reported to possess important anti-inflammatory actions. However, the molecular mechanisms by which CA derivatives including caffeic acid phenethyl ester (CAPE) and caffeic acid phenylpropyl ester (CAPPE), exert inhibitory effects on the proliferation of human colorectal cancer (CRC) cells have yet to be elucidated. CAPE and CAPPE were evaluated for their ability to modulate these signaling pathways and suppress the proliferation of CRC cells both in vitro and in vivo. Anti-cancer effects of these CA derivatives were measured by using proliferation assays, cell cycle analysis, western blotting assay, reporter gene assay and immunohistochemical (IHC) staining assays both in vitro and in vivo. This study demonstrates that CAPE and CAPPE exhibit a dose-dependent inhibition of proliferation and survival of CRC cells through the induction of G0/G1 cell cycle arrest and augmentation of apoptotic pathways. Consumption of CAPE and CAPPE significantly inhibited the growth of colorectal tumors in a mouse xenograft model. The mechanisms of action included a modulation of PI3-K/Akt, AMPK and m-TOR signaling cascades both in vitro and in vivo. In conclusion, the results demonstrate novel anti-cancer mechanisms of CA derivatives against the growth of human CRC cells. CA derivatives are potent anti-cancer agents that augment AMPK activation and promote apoptosis in human CRC cells. The structure of CA derivatives can be used for the rational design of novel inhibitors that target human CRC cells.

The treatment of human colorectal cancer (CRC) cells through suppressing the abnormal survival signaling pathways has recently become a significant area of focus. In this study, our results demonstrated that decyl caffeic acid (DC), one of the novel caffeic acid derivatives, remarkedly suppressed the growth of CRC cells both in vitro and in vivo. The inhibitory effects of DC on CRC cells were investigated in an in vitro cell model and in vivo using a xenograft mouse model. CRC cells were treated with DC at various dosages (0, 10, 20 and 40 μM), and cell survival, the apoptotic index and the autophagy level were measured using an MTT assay and flow cytometry analysis, respectively. The signaling cascades in CRC were examined by Western blot assay. The anti-cancer effects of DC on tumor growth were examined by using CRC HCT-116 cells implanted in an animal model. Our results indicated that DC differentially suppressed the growth of CRC HT-29 and HCT-116 cells through an enhancement of cell-cycle arrest at the S phase. DC inhibited the expression of cell-cycle regulators, which include cyclin E and cyclin A proteins. The molecular mechanisms of action were correlated to the blockade of the STAT3 and Akt signaling cascades. Strikingly, a high dosage of DC prompted a self-protection action through inducing cell-dependent autophagy in HCT-116 cells. Suppression of autophagy induced cell death in the treatment of DC in HCT-116 cells. DC seemed to inhibit cell proliferation of CRC differentially, and the therapeutic advantage appeared to be autophagy dependent. Moreover, consumption of DC blocked the tumor growth of colorectal adenocarcinoma in an experimental animal model. In conclusion, our results suggested that DC could act as a therapeutic agent through the significant suppression of tumor growth of human CRC cells.

Left ventricular dysfunction is a known risk factor for morbidity and mortality in hemodialysis patients. The prognostic value of left ventricular global longitudinal strain (LV GLS) among those with preserved left ventricular ejection fraction (LVEF) remains uncertain. Subjects with end-stage renal disease initiated hemodialysis at Taipei Veteran General Hospital between 2015 and 2018 were registered. All participants received annually echocardiographic studies thereafter. Left ventricular end-systolic volume (LVESV), end-diastolic volume (LVEDV) and internal diameter in systole (LVIDs), LVEF, and LV GLS were measured. A LV GLS of > – 15.9% was defined as reduced LV GLS. Clinical outcomes of mortality and hospitalization for heart failure (HHF) were followed. A total of 319 patients with preserved LVEF (66.3 ± 15.1 years, 48.6% men) were recruited in the study. Subjects with reduced LV GLS had more coronary artery disease (CAD), higher LVESV and LVIDs, but were similar in age, gender, co-morbidities, biochemistries and other echocardiographic parameters as the counterpart. Both CAD [(odds ratio (OR) and 95% confidence intervals (CIs): 1.669, 1.023–2.724], and LVESV (OR per-1 mL and 95% CIs: 1.073, 1.004–1.146) were independent determinants of reduced LV GLS. Kaplan-Meier analysis indicated that patients with reduced LV GLS had a significantly lower event-free survival rate compared to those with preserved GLS. The multivariate Cox regression analysis further demonstrated LV GLS as a significant predictor of adverse clinical events (hazard ratio per-1% and 95% CIs: 1.055, 1.002–1.110) after accounting for age, gender, and diabetes. Among the hemodialysis patients with preserved LVEF, LV GLS but not the conventional left ventricular functional indices were associated with long-term mortality and HHF. CAD could be a modifiable risk factor among the subjects with reduced LV GLS.

Screening for oral potentially malignant disorders (OPMDs) with dysplasia in high-risk groups is suggested in countries with a high prevalence of the disorders. This study aimed to compare the accuracy of diagnoses of OPMDs with dysplasia made by a primary examiner (general dental clinician) and a specialist (oral and maxillofacial surgeon) using the current Taiwanese Nationwide Oral Mucosal Screening Program (TNOMSP). A total of 134 high-risk participants were enrolled for oral mucosal screening via the TNOMSP. A primary examiner and a specialist examined each participant. Mucosal biopsies were obtained and subjected to histopathological analysis. The OPMD most frequently diagnosed by the primary examiner was thin homogeneous leukoplakia (48/134; 35.8%), and in 39/134 participants (29.1%) the diagnosis was uncertain, but abnormalities were suggested. The OPMDs most frequently diagnosed by the specialist were erythroleukoplakia (23/134; 17.2%) and thin homogeneous leukoplakia (21/134; 15.7%), and 51/134 participants (38.1%) were diagnosed with other diseases. Via histopathology, 70/134 participants (52.3%) were diagnosed with dysplasia, and 58/134 (43.3%) were diagnosed with benign conditions. The specialist’s diagnoses exhibited a higher specificity, positive predictive value, and accuracy than the primary examiners. A specialist using the current TNOMSP for high-risk participants diagnosed OPMDs with dysplasia more accurately than a primary examiner. Early diagnosis of high-risk OPMDs is crucial in countries with a high prevalence of the disorders. Proficient examination via the current TNOMSP by trained clinician is effective for the management of OPMDs with dysplasia.

People with hearing impairments often face increased risks related to traffic accidents due to their reduced ability to perceive surrounding sounds. Given the cost and usage limitations of traditional hearing aids and cochlear implants, this study aims to develop a sound alert assistance system (SAAS) to enhance situational awareness and improve travel safety for people with hearing impairments. We proposed the VAS-Compass Net (Vehicle Alert Sound–Compass Net), which integrates three lightweight convolutional neural networks: EfficientNet-lite0, MobileNetV3-Small, and GhostNet. Through employing a fuzzy ranking ensemble technique, our proposed model can identify different categories of vehicle alert sounds and directions of sound sources on an edge computing device. The experimental dataset consisted of images derived from the sounds of approaching police cars, ambulances, fire trucks, and car horns from various directions. The audio signals were converted into spectrogram images and Mel-frequency cepstral coefficient images, and they were fused into a complete image using image stitching techniques. We successfully deployed our proposed model on a Raspberry Pi 5 microcomputer, paired with a customized smartwatch to realize an SAAS. Our experimental results demonstrated that VAS-Compass Net achieved an accuracy of 84.38% based on server-based computing and an accuracy of 83.01% based on edge computing. Our proposed SAAS has the potential to significantly enhance the situational awareness, alertness, and safety of people with hearing impairments on the road.

Background: Human endothelial progenitor cells (hEPCs), originating from hemangioblasts in bone marrow (BM), migrate into the blood circulation, differentiate into endothelial cells, and could act as an alternative tool for tissue regeneration. In addition, trimethylamine-N-oxide (TMAO), one of the gut microbiota metabolites, has been identified as an atherosclerosis risk factor. However, the deleterious effects of TMAO on the neovascularization of hEPCs have not been studied yet. Results: Our results demonstrated that TMAO dose-dependently impaired human stem cell factor (SCF)-mediated neovascularization in hEPCs. The action of TMAO was through the inactivation of Akt/endothelial nitric oxide synthase (eNOS), MAPK/ERK signaling pathways, and an upregulation of microRNA (miR)-221. Docosahexaenoic acid (DHA) could effectively inhibit the cellular miR-221 level and induce the phosphorylation level of Akt/eNOS, MAPK/ERK signaling molecules, and neovascularization in hEPCs. DHA enhanced cellular amounts of reduced form glutathione (GSH) through an increased expression of the gamma-glutamylcysteine synthetase (γ-GCS) protein. Conclusions: TMAO could significantly inhibit SCF-mediated neovascularization, in part in association with an upregulation of miR-221 level, inactivation of Akt/eNOS and MAPK/ERK cascades, suppression of γ-GCS protein, and decreased levels of GSH and GSH/GSSG ratio. Furthermore, the DHA could alleviate the detrimental effects of TMAO and induce neovasculogenesis through suppression of miR-221 level, activation of Akt/eNOS and MAPK/ERK signaling cascades, increased expression of γ-GCS protein, and increment of cellular GSH level and GSH/GSSG ratio in hEPCs.