Studies of the Tumor-Vasculature Interface : Role of TGF-beta 1-induced Epithelial to Mesenchymal Transition

Tumor metastasis is a complex multistep process. Among key steps that occur during metastatic spread are acquisition of tumor cell motility, intravasation of tumor cells into blood or lymphatic vessels and extravasation of tumor cells at distal sites. However, the precise mechanisms that govern these metastatic steps remain elusive. This thesis aimed to bridge the fields of tumor and vascular biology to provide new insights into the metastatic process. Results are presented indicating a role of the cytokine transforming growth factor beta (TGF-β) in activating breast cancer cells for dissemination through the lymphatic system through re-activation of a latent development process termed epithelial to mesenchymal transition (EMT). Furthermore, essential roles of the coxsackie-and adenovirus receptor (CAR) for lymph vessel development, and the sphingosine-1-phosphate receptor (S1PR1) for blood vessel stabilization are presented. We expect the findings to have impact on our understanding of the interface between tumor and vascular biology and to influence future strategies to target cancer metastasis. In paper I, we present data identifying an essential role of CAR for normal development of lymphatic vessels in the mouse. We show that genetic deletion of the CAR gene (Cxadr) from E12.5 during mouse development leads to subcutaneous edema, hemorrhage and embryonic death. The lymphatic vessels in CAR-deficient mice were dilated and structurally abnormal with the presence of gaps and holes at lymphatic endothelial cell-cell junctions. In addition, blood-filled lymphatics were observed in CAR-deficient mice suggesting an incomplete separation between the blood and lymphatic vascular systems. The data demonstrate that CAR plays a crucial role in the development of lymphatic vasculature in mice through formation of lymphatic endothelial cell-cell junctions. In paper II, we demonstrate that S1PR1 plays critical role in suppressing angiogenesis and promoting vascular stability during mouse development. S1PR1 signaling promotes cell-cell adhesion and prevents sprouting angiogenesis whereas S1PR1-deficiency leads to hypersprouting angiogenesis. These data suggest that S1PR1 signaling might protect developing blood vessels from abnormal angiogenic signals through promotion of vascular stability. In paper III, we show that TGF-β-induced EMT promotes chemotactic migration of tumor cells through the lymphatic system by mediating crosstalk between tumor cells and lymphatic endothelial cells through the chemokine receptor 7 (CCR7) and its chemokine ligand, CCL21. Reversal of EMT process through p38 MAPK inhibition inhibited tumor cell invasion in vitro and migration towards the lymphatics in vivo suggesting that p38 MAPK inhibition may be a useful therapeutic approach to inhibit tumor cell dissemination through the lymphatic system. In paper IV, we describe development of a novel co-culture system to study tumor cell migration and interaction with lymphatic endothelial cells within a 3-dimensional matrix component. This assay allows manipulation of tumor properties or matrix components and can be used as a platform to screen for pharmacological agents which inhibit tumor-endothelial interactions

Modeling, Simulation And Design Of Membrane Based Palm Oil Mill Effluent (POME) Treatment Plant From Pilot Plant Studies [QK495.P17 C549 2007 f rb].

Tanpa rawatan, pembuangan kumbahan kilang kelapa sawit (POME) ke persekitaran mengakibatkan masalah pencemaran yang serius dan rawatan POME berasaskan membran telah dicadangkan sebagai salah satu penyelesaiannya. If untreated, the discharge of Palm Oil Mill Effluent (POME) into the environment leads to serious pollution problems and the membrane based POME treatment process has been suggested as a solution

Experimentation of Abrasion Erosion at High Temperature for Concentrated Solar Power Systems

Concentrated solar power (CSP) is an alternative and sustainable way to produce energy. Studies have shown that running these plants at high temperatures above 700°C can increase the thermal efficiency in heat transfer. Molten salt is usually used as the heat transfer medium but cannot be used due to its low maximum temperature and high freezing point. Running these plants at high temperature brings up the concern of erosion and oxidation. Abrasion erosion occurs through the interaction of particles and material. The goal of this research is to understand material degradation due to abrasion erosion to understand the durability of using solid particles as the heat transfer medium. Previous research has been done but not at the high temperature and low velocity to simulate these conditions. An apparatus was built to test the interaction of particles and materials at 800°C, periodically measuring the mass of each specimen and running a total of around 700 hours. Analysis for the specimen included calculating abrasion wear, surface profilometry, and cross-sectional scanning electron microscope imaging. Analysis for the particles included reflectance and particle size analysis. It was found temperature had the greatest effect on abrasion wear. For a test with silica quartz Wedload 430 particles and stainless steel 326H specimen, abrasion wear at 800°C and 25°C was -2.9281 mg/cm2 and -0.1956 mg/cm2, respectively. There was no erosion of particles based on their circularity before and after testing

Development Of An Intelligent System For River Water Quality Classification Based On Algae Composition

Throughout the years, many researches have been conducted on the potential applications of Artificial Intelligence (AI) in the biological monitoring of river quality. This project will provide an overview regarding the feasibility of the application of neural networks for direct classification of river water quality based on algae composition. A brief introduction to neural networks and the suitability of neural network for use in river water quality determination will be investigated. In this project, several neural networks will be developed and their performance are compared to yield the most suitable network that will be used to model the classification system for determination of river water quality based on algae composition. Among the types of neural network that will be developed are Multilayer Perceptron network (MLP), Radial Basis Function (RBF) network and Hybrid Multilayer Perceptron (HMLP) network. This study proves that the HMLP network trained using the MRPE algorithm achieves the best performance as compared to the MLP and RBF network. The HMLP network produces 90% accuracy. In this study, an intelligent system is developed for the classification of river water quality using the HMLP network. The proposed system provides several advantages in terms of its applicability, high accuracy, user-friendliness and as well as yields faster results compared to conventional system

STUDY ON FEAR OF COVID-19 AMONG DIFFERENT GENDER IN MALAYSIA AND ITS IMPACT ON PSYCHOLOGICAL DISTRESS

The main objective of this research is to investigate the significant gender difference on the level of COVID- 19 fear and the significance relationship between fear of COVID-19 and psychological distress. A total of 270 samples population consisting of 135 males and 135 females were included in the research study. All the participants are Malaysians who stayed in Malaysia during the COVID-19 pandemic and over the age of 18. The research design was quantitative research where data were obtained from the google form. This study used the fear of COVID-19 scale (FCV-19S) to measure participants’ fear toward COVID- 19 and the Kessler psychological distress scale (K10) was used to measure psychological distress of an individual. Independent- samples T- test and Pearson correlation were used to test the research hypothesis. According to the findings, it shows there is no significant gender difference on the level of COVID-19 fear whereas according to the Pearson correlation result, it shows there is a significance relationship between the fear of COVID-19 and psychological distress. The research finding can help to increase Malaysian's awareness regarding the COVID-19 fear and thus, it also can help to enhance their mental health during the COVID-19 pandemic

INTEGRATED ECOLOGICAL PLANNING IN SINGAPORE: NEOTIEWPIA ECO-VILLAGE IN BUSTLING METROPOLITAN

ABSTRACT :The Neotiewpia Eco-Village is located within the Lim Chu Kang district at the north of Singapore. The Eco-Village only comprised of 3.5 sq km. Meanwhile the area was dominated by farms, chalets and Sungei Buloh Wetland Reserve. In 2006, National University of Singapore, School of Design and Environment (SDE), MSc. Environmental Management and Nature Society of Singapore initiated an ecological planning exercise within the Neotiewpia site to reduce the environmental impact from the development while providing Eco-friendly Tourism and R&D activities that feasible in the site. We did participate in the exercise and we tried explaining the ecological process, the limitation and potential development for integrated ecological planning framework in Developing Countries like Indonesia, Brazil, etc with high ecological-values ecosystems. The Vision of Neotiewpia was “A Model Eco-Village that Respects its Natural Heritage, Builds Strong Community Links and Promotes Economic Development on Nature’s Premises." And Neotiewpia was successfully planned and designed with integrated ecological planning approach. It embraced the land evaluation and impact assessment. Further the plan was found feasible by the Singapore Government by earmarking the Lim Chu Kang and Kranji for Agri-tainment development in 2008 (although partially implemented). The Neotiewpia or Lim Chu Kang area was found thriving with Green-Economy and Agro-Tourism. This integrated ecological planning could be translated to other areas in Developing Countries with agriculture potential and facing development pressures such as Neotiewpia. This concept would give alternate Green-Solution to the current economic crisis

Optimisation of extraction and sludge dewatering efficiencies of bio-flocculants extracted from Abelmoschus esculentus (okra)

The production of natural biopolymers as flocculants for water treatment is highly desirable due to their inherent low toxicity and low environmental footprint. In this study, bio-flocculants were extracted from Hibiscus/Abelmoschus esculentus (okra) by using a water extraction method, and the extract yield and its performance in sludge dewatering were evaluated. Single factor experimental design was employed to obtain the optimum conditions for extraction temperature (25–90 °C), time (0.25–5 h), solvent loading (0.5–5 w/w) and agitation speed (0–225 rpm). Results showed that extraction yield was affected non-linearly by all experimental variables, whilst the sludge dewatering ability was only influenced by the temperature of the extraction process. The optimum extraction conditions were obtained at 70 °C, 2 h, solvent loading of 2.5 w/w and agitation at 200 rpm. Under the optimal conditions, the extract yield was 2.38%, which is comparable to the extraction of other polysaccharides (0.69–3.66%). The bio-flocculants displayed >98% removal of suspended solids and 68% water recovery during sludge dewatering, and were shown to be comparable with commercial polyacrylamide flocculants. This work shows that bio-flocculants could offer a feasible alternative to synthetic flocculants for water treatment and sludge dewatering applications, and can be extracted using only water as a solvent, minimising the environmental footprint of the extraction process

Determination of total antioxidant activity in three types of local vegetables shoots and the cytotoxic effect of their ethanolic extracts against different cancer cell lines.

Antioxidants play an important role in inhibiting and scavenging radicals, thus providing protection to humans against infections and degenerative diseases. Literature shows that the antioxidant activity is high on herbal and vegetable plants. Realizing the fact, this research was carried out to determine total antioxidant activity and the potential anticancer properties in three types of selected local vegetable shoots such as Diplazium esculentum (paku shoot), Manihot utillissima (tapioca shoot) and Sauropous androgynus (cekur manis). The research was also done to determine the effect of boiling, on total antioxidant activity whereby samples of fresh shoots are compared with samples of boiled shoots. In every case, antioxidant activity is compared to alpha-tocopherol and two methods of extraction used are the organic and the aqueous methods. Besides that, two research methods used were the ferric thiocyanate (FTC) and thiobarbituric acid (TBA) with absorbance of 500nm and 532nm respectively. Oneway ANOVA test at P D. esculentum (fresh) > S.androgynus (fresh) > M.utilissima (boiled) > D. esculentum (boiled) > S.androgynus (boiled). It also was found that S.androgynus shoots ethanolic extract was able to inhibit the viability of the breast cancer cell lines, MDA-MB-231 with the IC50 value of 53.33 μg/ml. However, S.androgynus shoots and D. esculentum shoots ethanolic extracts did not inhibit the viability of MDA-MB-231 cell line. While, the tapioca shoot ethanolic extract was able to inhibit the viability of MCF-7 cell line with the IC50 value of 52.49 μg/ml. S.androgynus shoots and D.esculentum shoots ethanolic extracts did not give an IC50 value against the MCF-7 cell line. S.androgynus, tapioca and D.esculentum shoots ethanolic extracts did not show cytotoxic effect against the Caco-2 and HepG2. There was no IC50-value from any sample against Chang Liver cell line. In conclusion, the antioxidant activity of both fresh and boiled samples were higher than alpha-tocopherol, although fresh vegetable shoots were found to be higher in antioxidant activity compared to boiled shoots. This study also suggested that S.androgynus shoots and tapioca shoots have potential as an anticancer agent against certain breast tumours

Integrating new assessment strategies into mathematics classrooms: an exploratory study in Singapore primary and secondary schools

Educational researchers and practitioners have in recent years paid mounting attention to the importance of new assessment (or the so-called alternative assessment) strategies in Mathematics instruction to better reflect the new desired educational goals and shifted values in education. However, research is wanting in this area, particularly in Singapore's educational setting. This project seeks to investigate the influence of using new assessment strategies in Mathematics teaching and learning on students' achievements, in both the cognitive and affective domains, in our local school settings. A quasi-experimental study with about 15-20 teachers at primary and lower secondary levels will be carried out to assess the impact of using a variety of strategies (e.g., projects, journal writing, oral presentation, performance tasks, student self-assessment, classroom observation and interview, etc.) for three school semesters on students' learning. The project will also look into issues concerning how to use new assessment strategies effectively in classrooms in local schools. For this purpose, data will be collected from classroom observation, interviews with teachers and students, and questionnaire surveys. It is hoped that the project will provide research-based evidence and practical suggestions for promoting the effective use of alternative assessment in Singapore Mathematics classrooms. <br/