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In recent, Botulinum Neurotoxin A1 (BoNT/A1) has been suggested as a potential anticancer agent due to neuronal innervation in tumor cells. Although potential BoNT/A1’s mechanism of action for the tumor suppression has been gradually revealed so far, there were no reports to figure out the exposure-response relationships because of the difficulty of its quantitation in the biological matrix. The main objectives of this study were to measure the anticancer effect of BoNT/A1 using a syngeneic mouse model transplanted with melanoma cells (B16-F10) and developed a kinetic-pharmacodynamic (K-PD) model for quantitative exposure-response evaluation. To overcome the lack of exposure information, the K-PD model was implemented by the virtual pharmacokinetic compartment link to the pharmacodynamic compartment of Simeoni’s tumor growth inhibition model and evaluated using curve-fitting for the tumor growth-time profile after intratumoral injection of BoNT/A1. The final K-PD model was adequately explained for a pattern of tumor growth depending on represented exposure parameters and simulation studies were conducted to determine the optimal dose under various scenarios considering dose strength and frequency. The optimal dose range and regimen of ≥13.8 units kg−1 once a week or once every 3 days was predicted using the final model in B16-F10 syngeneic model and it was demonstrated with an extra in-vivo experiment. In conclusion, the K-PD model of BoNT/A1 was well developed to optimize the dosing regimen for evaluation of anticancer effect and this approach could be expandable to figure out quantitative interpretation of BoNT/A1’s efficacy in various xenograft and/or syngeneic models.

The three-dimensional culture models have been developed to promote better simulation of in vivo conditions of cellular interactions and phenotypic expressions. Since each cell line behaves differently and not all aggregate three-dimensionally, the objectives of this study were to standardize the conditions for cultivation spheroids produced from the human non-smal-cell lung cancer cell line NCI-H460, and evaluate the effects of cisplatin in this model. We investigated the best cell density for the formation of spheroids and their growth time in culture conditions. For this, spheroids were treated with different concentrations of cisplatin. The analysis was performed by measuring the diameter of the spheroids before treatment and measured 48 h after treatment and then every 3 days. The standard cell density conditions obtained was 10 x 104 cells. Spheroids were collected from the 7th day and isolated in a non-adherent matrix well (covered with 2% agar and culture medium), remaining viable until the 17th day. From the 8th day of isolated culture, the cisplatin promoted a reduction in the growth of spheroids dependent on the concentration used. Thus, it was concluded that it was possible to standardize the effective methodology for the formation and maintenance of spheroids from this cell line, as well as cisplatin inhibited the growth of the spheroids, suggesting its cytotoxic effect also cultures in three-dimensional model.

В работе исследована возможность улучшения качества гетероэпитаксиальных структур Ge / Si с буферным слоем. Показано, что при использовании подготовительного слоя, состоящего из наноостровков, зарощенных низкотемпературным буферным слоем, возможно проявление так называемого эффекта аннигиляции дислокаций несоответствия в объеме буферного слоя Buf, что значительно улучшает приборное качество получаемых структур. Представлена зависимость морфологии поверхности слоя чистого Ge на буфере от времени роста наноостровков в интерфейсе Si / Buf . Выявлены оптимальные технологические параметры роста наноостровков для получения слоя Ge с минимальной значением шероховатости. Наилучших результатов удалось достичь при времени осаждения наноостровков 2 мин. При этом была достигнута минимальное значение шероховатости поверхности, равное 78 нм. Показано, что при дальнейшем увеличении размеров наноостровков, процесс аннигиляции дефектов замедляется, и рост низкотемпературного буферного слоя сменяется трехмерным островковым ростом, что увеличивает перепады рельефа поверхности выращиваемого слоя. The possibility of improving the quality of Ge / Si heteroepitaxial structures with a buffer layer is investigated. It is shown that when using a preparatory layer consisting of nanostructures overgrown with a low-temperature buffer layer, it is possible to manifest the so-called effect of annihilation of the misfit dislocations in the bulk of the buffer layer Buf , which significantly improves the quality of the resulting structures. The dependence of the morphology of the surface of the pure Ge layer on the buffer on the growth time of nanostructures in the Si / Buf interface is presented. The optimal technological parameters of the growth of nanostructures for obtaining a Ge layer with a minimum roughness value are revealed. The best results were achieved when the deposition time of nanostructures was 2 min. At the same time, the minimum surface roughness value of 78 nm was achieved. It is shown that with a further increase in the size of the nanostructures, the process of annihilation of defects slows down, and the growth of the low-temperature buffer layer is replaced by a three-dimensional island growth, which increases the differences in the relief of the surface of the grown layer.

Abstract Ecotoxicity assessments based on bacteria as model organisms is widely used for routine toxicity screening because it has advantages of time-saving, high sensitivity, cost-effectiveness, and less ethical responsibility. Determination of ecotoxicity effect via bacterial growth can avoid the restriction of model bacteria selection and unique equipment requirement, but traditional viable cell count methods are relatively labor- and time-intensive. The Start Growth Method (SGT) is a high-throughput and time-conserving method to determine the amount of viable bacterial cells. However, its usability and stability for ecotoxicity assessment are rarely studied. This study confirmed its applicability in terms of bacterial types (gram-positive and gram-negative), growth phases (middle exponential and early stationary phases), and simultaneous existence of dead cells (adjustment by flow cytometry). Our results verified that the stability of establishing SGT correlation is independent of the bacterial type and dead-cell portion. Moreover, we only observed the effect of growth phases on the slope value of established SGT correlation in Shewanella oneidensis, which suggests that preparing inoculum for the SGT method should be consistent in keeping its stability. Our results also elucidate that the SGT values and the live cell percentages meet the non-linear exponential correlation with high correlation coefficients from 0.97 to 0.99 for all the examined bacteria. The non-linear exponential correlation facilitates the application of the SGT method on the ecotoxicity assessment. Finally, applying the exponential SGT correlation to evaluate the ecotoxicity effect of copper ions on E. coli was experimentally validated. The SGT-based method would require about 6 to 7 hours to finish the assessment and obtained an estimated EC50 at 2.27 ± 0.04 mM. This study demonstrates that the exponential SGT correlation can be a high-throughput, time-conversing, and wide-applicable method for bacterial ecotoxicity assessment.

This study aims to obtain the optimum dose of manure for red dragon fruit plant growth on Andosol, optimum K fertilizer dose for red dragon fruit plant growth on Andosol, and the interaction of manure and K fertilizer for red dragon fruit plant growth on Andosol. This research was conducted from August 2018 to November 2018 at the Horticulture Seed Center, Kepahiang Regency, Bengkulu Province. This study used a completely randomized design (CRD) consisting of two factors with three replications. The first factor is cow manure, which is 0 g/polybag, 20 g/polybag, 40 g/ polybag, and 60 g/polybag. The second factor is K fertilizer, which is 0 g/polybag, 1.38 g/polybag, 2.76 g/polybag, and 5.52 g/polybag. The results showed that the application of cow manure with a dose of 60 g/polybag resulted in the best shoot growth time and shoot fresh weight

A new model of axially symmetric concentrated vortex generation was developed herein. In this work, the solution of a nonlinear equation for internal gravity waves in an unstable stratified atmosphere was obtained and analysed in the framework of ideal hydrodynamics. The related expressions for the velocities in the inner and outer regions of the vortex were described by Bessel functions and modified zeroth-order Bessel functions. The proposed new nonlinear analytical model allows the study of the structure and dynamics of vortices in the radial region. The formation of jets (i.e., structures elongated in the vertical direction with finite components of the poloidal (radial and vertical) velocities that grow exponentially in time in an unstable stratified atmosphere) was also analysed. The characteristic growth time was determined by the inverse growth rate of instability. It is shown that a seed vertical vorticity component may be responsible for the formation of vortices with a finite azimuthal velocity.

Gallium oxide (Ga2O3) thin films of various thicknesses were grown on sapphire (0001) substrates by metal organic chemical vapor deposition (MOCVD) using trimethylgallium (TMGa), high purity deionized water, and silane (SiH4) as gallium, oxygen, and silicon precursors, respectively. N2 was used as carrier gas. Hall measurements revealed that films grown with a lower VI/III ratio had a dominant p-type conduction with room temperature mobilities up to 7 cm2/Vs and carrier concentrations up to ~1020 cm−3 for thinner layers. High resolution transmission electron microscopy suggested that the layers were mainly κ phase. Microstrip field-effect transistors (FETs) were fabricated using 2D p-type Ga2O3:Si, channels. They achieved a maximum drain current of 2.19 mA and an on/off ratio as high as ~108. A phenomenological model for the p-type conduction was also presented. As the first demonstration of a p-type Ga2O3, this work represents a significant advance which is state of the art, which would allow the fabrication of p-n junction based devices which could be smaller/thinner and bring both cost (more devices/wafer and less growth time) and operating speed (due to miniaturization) advantages. Moreover, the first scaling down to 2D device channels opens the prospect of faster devices and improved heat evacuation.

The properties of H2S gas sensing were investigated using a ZnO nanostructure prepared with AZO (zinc oxide with aluminium) and Al surfaces which were developed on a MEMS (Micro Electromechanical System) device. Hydrothermal synthesis was implemented for the deposition of the ZnO nanostructure. To find the optimal conditions for H2S gas sensing, different ZnO growth times and different temperatures were considered and tested, and the results were analysed. At 250 °C and 90 min growth time, a ZnO sensor prepared with AZO and 40 nm Al recorded an 8.5% H2S gas-sensing response at a 200 ppb gas concentration and a 14% sensing response at a gas concentration of 1000 ppb. The dominant sensing response provided the optimal conditions for the ZnO sensor, which were 250 °C temperature and 90 min growth time. Gas sensor selectivity was tested with five different gases (CO, SO2, NO2, NH3 and H2S) and the sensor showed great selectivity towards H2S gas.

<p>Microelectrode arrays (MEAs) have been shown as a successful approach for neuroscientists to monitor the signal communication within the neuronal networks for understanding the functionality of the nervous system. However, using conventional planar MEAs is shown to be incapable of precise signal recording from neuronal networks at single-cell resolution due to low signal-to-ratio (SNR). This thesis looks at developing an electronic platform that comprises of zinc oxide nanowires (ZnO-NWs) on MEAs as a future device to record action potential (AP) signals with high SNR from human neuronal networks at single-cell resolution. Specifically, I studied the controlled growth of ZnO nanowires with various morphologies at exact locations across the substrate. I then investigated the biocompatibility of ZnO nanowires with different morphology and geometry for interaction with human NTera2.D1 (hNT) neurons. Finally, I examined the electrical characteristics of MEAs that were integrated with ZnO nanowires and metal encapsulated ZnO nanowires in comparison to the planar MEAs.  The hydrothermal growth of ZnO nanowires is thoroughly investigated as a technique to allow synthesis of the nanowires at a low temperature (95°C) with a low cost and high scalability that can also be applied on flexible substrates. The morphology of the ZnO nanowires was varied (diameters of 20–300 nm, lengths of 0.15–6.2 µm, aspect ratios of 6–95 and densities of 10–285 NWs/µm²) by controlling the critical growth parameters such as the precursor concentration (2.5–150 mM), growth time (1–20 h) and additive polyethylenimine (PEI) concentration (0–8 mM). The diameter and length of the ZnO nanowires were increased by increasing the precursor concentration and growth time. Using the standard precursor concentration of 25 mM, growth times of up to 4 h were found effective for the active growth of the nanowires due to the consumption of the precursor ions and precipitation of ZnO. The addition of 6 mM PEI to the growth solution was shown to mediate the growth solution, allowing the extension of the nanowire growth to 20 h or longer. The PEI molecules were also attached to the lateral faces of the nanowires that confined their lateral growth and promoted their axial growth (enhanced aspect ratio from 12 ± 3 to 67 ± 21).  Standard photolithography techniques were also introduced to selectively grow ZnO nanowires on exact locations across the substrates. The role of the ZnO seed layer geometry, seed layer area and gap, on the growth of ZnO nanowires was also investigated. Despite using the constant growth parameters (25 mM of precursor concentration with 4 h of growth time) changing the seed line widths (4 µm–1 mm) and the gap between the seed lines (2 µm–800 µm) resulted in the morphology of the nanowires to vary across the same substrate (diameters of 50–240 nm, lengths of 1.2–4.6 µm, aspect ratios of 9–34 and densities of 28–120 NWs/µm²). The seed area ratio of 50% was determined as a threshold to influence the nanowire morphology, where decreasing the seed area ratio below 50% (by increasing the adjacent gap or decreasing the seed layer area) increased the growth rate of the nanowires.  The biocompatibility of ZnO nanowires with human hNT neurons was investigated in this work for the first time. The adhesion and growth of hNT neurons on the arrays of ZnO nanowire florets were determined to be influenced by both geometry and morphology of the nanowires. The growth of the hNT neurons was promoted by 30% compared to the control Si/SiO₂ substrate surface when ZnO nanowires with lengths shorter than 500 nm and densities higher than 350 NWs/µm² were grown. The hNT neurons on all nanowires were also demonstrated to be functionally viable as they responded to the glutamate stimulation.  ZnO nanowires were shown to improve the electrical properties of the MEAs by reducing the electrochemical impedance due to the increased 3D surface area. The ZnO nanowires that were grown with 50 mM of precursor concentration for 4 h of growth time lowered the impedance from 835 ± 40 kΩ of planar Cr/Au MEAs to 540 ± 20 kΩ at a frequency of 1 kHz. In contrast, the ZnO nanowires that were grown with PEI for 35 h showed that despite the increased surface area by a factor of 45× the impedance was found to be quite high, 2.25 ± 0.2 MΩ at 1 kHz of frequency. The adsorption of PEI molecules to the lateral surfaces of the nanowires was thought to behave as a passivation layer that could have restricted the charge transfer characteristics of the ZnO-NW MEAs.  Encapsulation of the pristine ZnO nanowires that were grown with standard precursor concentration of 25 mM for 4 h of growth time with different metallic layers (Cr/Au, Ti and Pt) further improved the electrical characteristics of the MEAs. The ZnO nanowires that were encapsulated with a 10 nm thin layer of Ti and Pt achieved the lowest electrochemical impedance of 400 ± 25 kΩ at 1 kHz in this work. The robustness of the Ti encapsulated ZnO nanowires were also improved in comparison to the PEI ZnO nanowires. The improved electrochemical characteristics and mechanical stability of the MEAs integrated with metal encapsulated ZnO nanowires have shown a great promise for improving the SNR of recording signals from neuronal cells for long term measurements.  This work concludes that both pristine ZnO nanowire MEAs and metal encapsulated ZnO nanowire MEAs will be capable of recording AP signals from human neuronal networks at single-cell resolution. However, further optimisation and extensions of the work are required to record AP signals from human neuronal cells.</p>

<p>Microelectrode arrays (MEAs) have been shown as a successful approach for neuroscientists to monitor the signal communication within the neuronal networks for understanding the functionality of the nervous system. However, using conventional planar MEAs is shown to be incapable of precise signal recording from neuronal networks at single-cell resolution due to low signal-to-ratio (SNR). This thesis looks at developing an electronic platform that comprises of zinc oxide nanowires (ZnO-NWs) on MEAs as a future device to record action potential (AP) signals with high SNR from human neuronal networks at single-cell resolution. Specifically, I studied the controlled growth of ZnO nanowires with various morphologies at exact locations across the substrate. I then investigated the biocompatibility of ZnO nanowires with different morphology and geometry for interaction with human NTera2.D1 (hNT) neurons. Finally, I examined the electrical characteristics of MEAs that were integrated with ZnO nanowires and metal encapsulated ZnO nanowires in comparison to the planar MEAs.  The hydrothermal growth of ZnO nanowires is thoroughly investigated as a technique to allow synthesis of the nanowires at a low temperature (95°C) with a low cost and high scalability that can also be applied on flexible substrates. The morphology of the ZnO nanowires was varied (diameters of 20–300 nm, lengths of 0.15–6.2 µm, aspect ratios of 6–95 and densities of 10–285 NWs/µm²) by controlling the critical growth parameters such as the precursor concentration (2.5–150 mM), growth time (1–20 h) and additive polyethylenimine (PEI) concentration (0–8 mM). The diameter and length of the ZnO nanowires were increased by increasing the precursor concentration and growth time. Using the standard precursor concentration of 25 mM, growth times of up to 4 h were found effective for the active growth of the nanowires due to the consumption of the precursor ions and precipitation of ZnO. The addition of 6 mM PEI to the growth solution was shown to mediate the growth solution, allowing the extension of the nanowire growth to 20 h or longer. The PEI molecules were also attached to the lateral faces of the nanowires that confined their lateral growth and promoted their axial growth (enhanced aspect ratio from 12 ± 3 to 67 ± 21).  Standard photolithography techniques were also introduced to selectively grow ZnO nanowires on exact locations across the substrates. The role of the ZnO seed layer geometry, seed layer area and gap, on the growth of ZnO nanowires was also investigated. Despite using the constant growth parameters (25 mM of precursor concentration with 4 h of growth time) changing the seed line widths (4 µm–1 mm) and the gap between the seed lines (2 µm–800 µm) resulted in the morphology of the nanowires to vary across the same substrate (diameters of 50–240 nm, lengths of 1.2–4.6 µm, aspect ratios of 9–34 and densities of 28–120 NWs/µm²). The seed area ratio of 50% was determined as a threshold to influence the nanowire morphology, where decreasing the seed area ratio below 50% (by increasing the adjacent gap or decreasing the seed layer area) increased the growth rate of the nanowires.  The biocompatibility of ZnO nanowires with human hNT neurons was investigated in this work for the first time. The adhesion and growth of hNT neurons on the arrays of ZnO nanowire florets were determined to be influenced by both geometry and morphology of the nanowires. The growth of the hNT neurons was promoted by 30% compared to the control Si/SiO₂ substrate surface when ZnO nanowires with lengths shorter than 500 nm and densities higher than 350 NWs/µm² were grown. The hNT neurons on all nanowires were also demonstrated to be functionally viable as they responded to the glutamate stimulation.  ZnO nanowires were shown to improve the electrical properties of the MEAs by reducing the electrochemical impedance due to the increased 3D surface area. The ZnO nanowires that were grown with 50 mM of precursor concentration for 4 h of growth time lowered the impedance from 835 ± 40 kΩ of planar Cr/Au MEAs to 540 ± 20 kΩ at a frequency of 1 kHz. In contrast, the ZnO nanowires that were grown with PEI for 35 h showed that despite the increased surface area by a factor of 45× the impedance was found to be quite high, 2.25 ± 0.2 MΩ at 1 kHz of frequency. The adsorption of PEI molecules to the lateral surfaces of the nanowires was thought to behave as a passivation layer that could have restricted the charge transfer characteristics of the ZnO-NW MEAs.  Encapsulation of the pristine ZnO nanowires that were grown with standard precursor concentration of 25 mM for 4 h of growth time with different metallic layers (Cr/Au, Ti and Pt) further improved the electrical characteristics of the MEAs. The ZnO nanowires that were encapsulated with a 10 nm thin layer of Ti and Pt achieved the lowest electrochemical impedance of 400 ± 25 kΩ at 1 kHz in this work. The robustness of the Ti encapsulated ZnO nanowires were also improved in comparison to the PEI ZnO nanowires. The improved electrochemical characteristics and mechanical stability of the MEAs integrated with metal encapsulated ZnO nanowires have shown a great promise for improving the SNR of recording signals from neuronal cells for long term measurements.  This work concludes that both pristine ZnO nanowire MEAs and metal encapsulated ZnO nanowire MEAs will be capable of recording AP signals from human neuronal networks at single-cell resolution. However, further optimisation and extensions of the work are required to record AP signals from human neuronal cells.</p>