Thermoresponsive Microgels for Multicellular Spheroids Formation

Multicellular spheroids (MCS) are considered as the most promising three dimensional (3D) in-vitro model which will narrow down the gap between in-vitro two-dimensional culture and in-vivo animal models. They exhibit physiologically relevant cell-cell and cell-matrix interactions, and present similar gene expression, heterogeneity and structural complexity as in-vivo tissues. Multicellular spheroids have been attempted for drug screening and evaluation, mechanical studies on cancer cell invasion and migration, and regeneration medicine. However, fabrication of uniform-sized MCSs at a high throughput platform, and evaluation of MCSs for clinical relevance are two main challenges. In this thesis, thermally responsive microgels were employed as physical supports to culture multicellular spheroids from both tumor cells and stem cells, which are potentially applied in anti-cancer drug evaluation, tissue engineering and regeneration medicine. The thermally reversible poly (N-isopropylacrylamide-co-acrylic acid) (P(NIPAM-AA)) microgels were first employed to fabricate HeLa MCSs. This microgel approach restricted cell mobility at a lower initial cell density due to a large volume in the microgel networks, which resulted in uniform-sized spheroids formation compared to non-adhesive culture. Moreover, because of thermal reversibility of this microgel, spheroids were released from the physical supports via cooling down the system to room temperature. After demonstrating the formation of tumor spheroids in the microgel, HeLa cells were further encapsulated inside microgel-droplets generated from flow focusing microfluidics to obtain controllable uniform-sized spheroids. This approach combined the benefit of using thermal sensitive microgels as physical supports for MCS formation and droplet generation at a high throughput platform. Highly uniform-sized MCSs were obtained through this method. Importantly, the MCSs were easily released from the droplets by reducing the culture temperature to room temperature without using strong chemical or enzyme reagents. This approach may be used for generation of uniform-sized MCSs for drug screening and evaluation. The microenvironment generated from the microgel plays an important role in MCS formation. The key characteristics of the microenvironment, such as surface charge density, hydrophobicity, mechanical strength, and the microstructure of the microgels, were investigated by synthesizing a range of poly(N-isopropylacrylamide) (P(NIPAM)) based microgels, including P(NIPAM), P(NIPAM-co-methacrylic acid) (P(NIPAM-MAA)), P(NIPMAM-co-acrylic acid) (P(NIPAM-AA)), P(NIPAM-co-malic acid) (P(NIPAM-MA)) and P(NIPAM-co-itaconic acid)(P(NIPAM-IA)). It was found that the moderate negatively charged surface with high hydrophilicity P(NIPAM-IA) microgels was beneficial for cellular growth. The high or low charge density resulted in slow cell proliferation. The hydrophobicity of microgels had a negative impact on cell growth. The large pore size of the P(NIPAM-IA) networks also allowed cell migration which promoted MCSs formation. Different cell types (HEK 293, U87, HeLa and mesenchymal stem cells) have been demonstrated to successfully form MCSs within the P(NIPAM-IA) microgel. The thermal sensitive microgels were further applied to form stem cell MCSs. Human cardiac stem cells (hCSCs) were cultured in the P(NIPAM)) based microgel networks including P(NIPAM-co-dimethyl amino ethyl methacrylate) (P(NIPAM-DMAEMA)), P(NIPAM-IA), (P(NIPAM-co-2-hydroxyethyl methacrylate) (P(NIPAM-HEMA)), P(NIPAM-co-poly(ethylene glycol) methyl ether acrylate) (P(NIPAM-PEGA)). These microgels displayed different charges (cationic, anionic, and neutral) and different degrees of hydrophobicity. Through evaluation of hCSCs viability, proliferation and release of regenerative factors, P(NIPAM-IA) was identified as one of the best candidates for forming hCSCs spheroids because of its negatively charged surface with high hydrophilicity. The thermal reversibility of P(NIPAM-IA) renders it as injectable hydrogels. Initial results showed that injection of this microgel into mice did not elicit immune system responses, reduced myocardial apoptosis and promoted angiogenesis in the mice. In summary, we have fabricated MCSs in different types of thermal responsive microgels through either physical control of the uniform size by confining cells in the microgel-droplets generated from microfluidics or fine tune of the microenvironment for MCS formation. The P(NIPAM-IA) microgel with moderated anionic charge and high hydrophilicity was found to promote MCSs formation. This microgel did not elicit any immune response, which indicates the potential of using this microgel for future clinical studies.Thesis (Ph.D.) -- University of Adelaide, School of Chemical Engineering, 201

Unabridged phase diagram for single-phased FeSexTe1-x thin films

A complete phase diagram and its corresponding physical properties are essential prerequisites to understand the underlying mechanism of iron based superconductivity. For the structurally simplest 11 (FeSeTe) system, earlier attempts using bulk samples have not been able to do so due to the fabrication difficulties. Here, thin FeSexTe1-x films with the Se content covering the full range were fabricated by using pulsed laser deposition method. Crystal structure analysis shows that all films retain the tetragonal structure in room temperature. Significantly, the highest superconducting transition temperature (TC = 20 K) occurs in the newly discovered domain, 0.6 - 0.8. The single-phased superconducting dome for the full Se doping range is the first of its kind in iron chalcogenide superconductors. Our results present a new avenue to explore novel physics as well as to optimize superconductors

Electrospinning Synthesis and Photocatalytic Activity of Mesoporous TiO2 Nanofibers

Titanium dioxide (TiO2) nanofibers in the anatase structure were successfully prepared via electrospinning technique followed by calcination process. The morphologies, crystal structure, surface area, and the photocatalytic activity of resulting TiO2 nanofibers were characterized by field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), nitrogen sorption, and UV-vis spectroscopy. The results revealed that calcination temperature had greatly influenced the morphologies of TiO2 nanofibers, but no obvious effect was noticed on the crystal structure of TiO2 nanofibers. The photocatalytic properties of TiO2 nanofibers were evaluated by photocatalytic degradation of rhodamine B (RhB) in water under visible light irradiation. It was observed that TiO2 nanofibers obtained by calcination at 500°C for 3 hours exhibited the most excellent photocatalytic activity. We present a novel and simple method to fabricate TiO2 nanofibers with high-photocatalytic activity

Lightweight Neural Network with Knowledge Distillation for CSI Feedback

Deep learning (DL) has shown promise in enhancing channel state information (CSI) feedback. However, many studies indicate that better feedback performance often accompanies higher computational complexity. Pursuing better performance-complexity tradeoffs is crucial to facilitate practical deployment, especially on computation-limited devices, which may have to use lightweight autoencoder with unfavorable performance. To achieve this goal, this paper introduces knowledge distillation (KD) to achieve better tradeoffs, where knowledge from a complicated teacher autoencoder is transferred to a lightweight student autoencoder for performance improvement. Specifically, two methods are proposed for implementation. Firstly, an autoencoder KD-based method is introduced by training a student autoencoder to mimic the reconstructed CSI of a pretrained teacher autoencoder. Secondly, an encoder KD-based method is proposed to reduce training overhead by performing KD only on the student encoder. Additionally, a variant of encoder KD is introduced to protect user equipment and base station vendor intellectual property. Numerical simulations demonstrate that the proposed KD methods can significantly improve the student autoencoder's performance, while reducing the number of floating point operations and inference time to 3.05%-5.28% and 13.80%-14.76% of the teacher network, respectively. Furthermore, the variant encoder KD method effectively enhances the student autoencoder's generalization capability across different scenarios, environments, and bandwidths.Comment: 28 pages, 4 figure

Incipient fault diagnosis of rolling bearing using accumulative component kurtosis in SVD process

Rolling element bearing faults account for main causes of rotating machine failures. It is crucial to identify the incipient fault before the bearing steps into serious fault condition. The Hilbert envelope spectrum has been proved powerful and with high practical value to detect transient components in vibration signal but sensitive to noise. Based on the conventional singular value decomposition (SVD) theory, accumulative component kurtosis (ACK) is introduced to de-noising of vibration signal processing. The proposed ACK-SVD emphasizes the accumulative components (ACs) rather than the single singular component (SC) to select the effective SCs to recover signal. The superiority of the ACK-SVD over traditional SVD de-noising is verified by both simulated signals and actual vibration data from two rolling element bearing rigs. The results demonstrate the proposed method can efficiently identify the rolling element bearing faults, especially the early ones with strong background noise

The Efficacy and Safety of Chinese Herbal Decoction in Type 2 Diabetes: A 5-Year Retrospective Study

Background. The study was designed to assess the efficacy and safety of Chinese herbal decoction in treating outpatients with T2DM. Methods. All patients enrolled received decoction for at least 6 months. The primary outcome was the control rate of HbA1c and the change in HbA1c. FPG, 2hPG, HOMA-IR, and HOMA-β were also collected and evaluated. Results. The control rates after treatment at months 6, 12, 18, 24, 36, 48, and 60 were 45.07%, 52.78%, 47.22%, 45.83%, 50.00%, 57.14%, and 40.00%. Multiple linear regression showed the change of HbA1c has a significant relationship with the baseline HbA1c and duration of DM and BMI (p<0.05). Both FPG and 2hPG levels significantly decreased compared to the baseline (p<0.05). Chinese herbal decoction also improved islet cell function with decreased HOMA-IR and increased HOMA-β (p<0.05). 19 and 4 subjects deactivated the antidiabetes drugs or insulin, respectively, after taking decoction. One subject developed DKD and one developed DPN, and another subject showed abnormal liver function which was irrelevant to decoction treatment. Conclusions. Chinese herbal decoction significantly enhanced the hypoglycemic action and had certain effect on protecting islet cell function. As a candidate diabetes therapy, it may reduce the use of antidiabetes drugs and slow the progression to diabetes complications