137 research outputs found
The Mass Spectrometry-based Lipidomics to Study the Response of Various Organs in Mice after Naphthalene exposure
No full text萘，為最常見的多環芳香烴類化合物，是一種普遍存在樟腦丸和石油產物中的環境污染物。過去，以核磁共振 (NMR) 為基礎的代謝體學研究結果顯示，小鼠經萘暴露後，一些親水性和疏水性代謝產物會受到其幹擾並產生影響。然而，核磁共振的低解析度限制了脂質等疏水性代謝物的結構辨識能力。因此，本研究開發以液相層析串聯質譜法 (LC-MS/MS) 為基礎的脂質體學方法平臺，並應用於分析萘暴露對不同器官脂質體造成的改變。為了探討在萘處理後不同器官中的脂質物種變化，以及對萘毒性可能之角色，我們開發了一套二維 (2D)液相層析系統，以提高脂質物種的分析。本研究所研發結合親水性交互作用（hydrophilic interaction liquid chromatography，HILIC）暨逆相之二維液相層析系統 (2D HILIC-RPLC) 可針對從生物檢體中所萃取出的神經醯胺(ceramide) 和磷脂醯膽鹼脂質 (phosphorylcholine-containing lipid) 做全面性的研究分析。本系統於第一階段利用Silica HILIC 層析管柱將脂質依種類進行分離，之後利用ACQUITY BEH C18 層析管柱針對同類脂質做進一步的分離。與傳統一維液相層析串聯質譜系統相比，本次開發之二維液相層析串聯質譜系統顯著降低基質效應，並且其偵測極限相對降低了二至三倍。我們證明本研究所建立的方法具有高精確度與再現性，統計結果顯示三個添加濃度之相對標準偏差小於百分之二十。新開發的系統可有效地應用在經過萘處理後實驗小鼠中的肺臟，肝臟與腎臟脂質體的分析。從化學計量學分析顯示，在小鼠中的肺臟和肝臟中磷脂醯膽鹼和神經醯胺量均有顯著改變，而腎臟只有磷脂醯膽鹼有變化。本研究結合以液相層析串聯質譜為基礎的脂質體學與以核磁共振為基礎的代謝體學方法平台分析萘在不同器官引發的變化。總結，小鼠暴露萘48 小時後,代謝體結果呈現，受傷的器官進行修復，在這個時間點脂質的變化與細胞膜修復機制有關。Naphthalene, a polycyclic aromatic hydrocarbon, a ubiquitous environmental pollutant present in mothballs and petroleum products, has the capability of causing illness in human. Previously, nuclear magnetic resonance (NMR)-based metabolomics revealed that several hydrophilic and hydrophobic metabolites were perturbed in mice after naphthalene treatments. However, low NMR resolution limited the identification of the hydrophobic metabolites including lipid. Therefore, in this study, liquid chromatography-tandem mass spectrometry- (LC-MS/MS) based focus lipidomics was applied to profile lipid species changes in various organs after naphthalene treatment. In order to profile the lipid species changes in various organs after naphthalene treatment, two-dimensional (2D) LC system has been developed to enhance the profiling of lipid species. Concisely, a 2D hydrophilic interaction liquid chromatography (HILIC) and reverse-phase (RP) liquid chromatography (LC) system coupled with triple-quadrupole mass spectrometry (MS) was developed to comprehensively profile ceramides and phosphorylcholine containing lipids in extracted biological samples. Developed 2D HILIC-RPLC system used a silica HILIC column operated in the first dimension to distinguish the lipid classes and a BEH C18 column operated in the second dimension to separate the lipid species of the same class. The regression linearity of each lipid was satisfactory in both systems; however,the absolute matrix effect factor was reduced in 2D LC-MS/MS system. Limits of detection of 2D LC-MS/MS system were 2-3-fold lower compared toone-dimensional (1D) RPLC-MS/MS. To summarize, developed method was proven to be accurate and producible, as relative standard deviations remained smaller than 20% at three spiked levels.The efficiency of this newly developed system was applied to profile lipidome in the lung, liver and kidney of mice after naphthalene treatment to understand the mechanisms of naphthalene induced toxicities. Chemometric analysis revealed that phosphorylcholine-containing lipids and ceramides were significantly altered in the lung and liver, whereas, only phosphatidylcholines (PCs) was observed in kidney. Elevated number of unsaturated bonds and fatty acyl chains in both ceramide and PCs were deemed to reduce cellular membrane rigidity and facilitating the trafficking of recovery elements into the cell for rejuvenation. Coupling the MS-based focus lipidomics and NMR-based metabolomics enabled the characterization of naphthalene-induced changes in various organs. As conclusion, 48 h after naphthalene treatment, the injured organs underwent rejuvenation and the lipids changes at this time points majorly responsible for the cellular rejuvenations.Table of Contents
摘要 I
Abstract II
Thesis overview IV
Table of Contents VI
List of Figure VIII
List of Tables XI
Chapter 1 1
Introduction 1
1.1 Naphthalene introduction 1
1.2 Naphthalene: Mode of action 2
1.3 Experimental study on naphthalene 3
1.4 Naphthalene metabolisms and detoxification. 7
1.4 Metabolomics 9
1.5. Lipids and focus lipidomics 9
1.6 Sphingolipid: Ceramide and ceramide-1-phosphate. 16
1.7 Phosphorylcholine-containing lipid: Diacyl-phosphatidylcholine, plasmenylcholine, plasmanylcholine and sphingomyelin 17
1.8 Lipidomics practices 20
1.9 Lipidomic Coupling of LC system to MS 26
1.10 Purpose of this study. 27
1.11 References 28
Chapter 2 36
Two-dimensional LC-MS/MS to enhance ceramides and phosphorylcholine-containing lipids profiling 36
2.1 Introduction 36
2.2 Material and method 39
2.3 Results and discussion 54
2.4 Summary 59
2.5 References 60
Chapter 3 62
MS-based Lipidomics: Various Organ Responses Following Naphthalene Intervention 62
3.1 Introduction 62
3.2 Materials and methods 63
3.3 Results 68
3.4. Discussion 78
3.5 Summary of the toxicological effects of naphthalene 88
3.6 References 91
3.7 Supplementary information 96
Chapter 4 116
Conclusions 116
Chapter 5 117
Future work 117
Appendix 12
NMR- and MS-based metabolomics: various organ responses following naphthalene intervention
No full textNaphthalene, a polycyclic aromatic hydrocarbon, is a ubiquitous environmental pollutant capable of causing illness. In this study, we deconvoluted the metabolites related to naphthalene intervention in various organs by using nuclear magnetic resonance (NMR) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Male ICR mice were intraperitoneally dosed with olive oil (vehicle), and a low dose and a high dose (100 and 200 mg kg(-1) body wt, respectively) of naphthalene. After 48 h, the lungs, liver, and kidneys were collected for analysing the metabolic responses. The metabolites were extracted and non-targeted profiled using NMR. Low NMR resolution limited the identification of the hydrophobic metabolites. Therefore, LC-MS/MS-based focus lipidomics was applied to profile phosphorylcholine-containing lipids and sphingolipids. Chemometric analysis revealed that succinate and lactate were significantly increased in the lungs, suggesting that energy metabolisms and antioxidation were increased following naphthalene treatment. In the liver, anti-oxidative stress-related metabolites increased, enabling the oxidative stress during naphthalene biotransformation and detoxification to be overcome. The elevation of glutathione protected kidneys from reactive-naphthalene-metabolite-induced injury. Significant alteration of hydrophobic metabolites (membrane constituents) revealed lung and liver were the target organs of naphthalene treatment. MS data demonstrated that phosphatidylcholine (PC) and ceramide species were significantly altered in the lungs and liver, whereas only PC was observed in the kidneys. Elevated numbers of unsaturated bonds and fatty acyl chains in both ceramides and PCs were determined to reduce cellular membrane rigidity and facilitating the trafficking of recovery elements into the cell for rejuvenation. To conclude, the complementary results of NMR-and MS-based metabolomics enabled the characterization of naphthalene-induced changes in various organs
DESA : a design method that reduces system complexity
No full textThis research deals with a fonnal design method called "Design Equations for
Systems Analysis", or DESA. This method reduces system complexity, and has been
demonstrated to effectively reduce the complexity of human-machine systems. It also
increases the usability of products. The author summarized two other design methods
that reduce system complexity - Axiomatic Design (AD) and Design Structure Matrix
(DSM) - and explained their differences from DESA. A case study was then
presented to demonstrate the ability ofAD and DSM to complement each other. Since
DESA builds on AD, it can complement DSM similarly. The author revised the
framework that DESA utilizes. A tenninology was established to define the technical
tenns in DESA. DESA was then employed to design an inspection method that
evaluates usability. It was also employed to reduce the complexity of an objectoriented
software system. These two applications of DESA are presented as case
studies. These two case studies respectively demonstrate that DESA designs for
usability and effectively reduces the complexity of object-oriented software systems.MASTER OF ENGINEERING (MAE
University as stimulus to promote intention to separate food waste: a study on the Chinese female residential students
No full textAbstractOverwhelming food waste impacted society and the environment. One of the initiatives to mitigate this problem is to separate the food waste and utilise it for alternative purposes. However, few studies have examined universities’ role in separating female residential students’ food waste, even though universities contribute to food waste generation. Therefore, this study investigates the university’s role on this matter. Through purposive sampling, 339 responses from female residential students were gathered and analysed using the Partial-Least-Square-Structure Equation Modelling (PLS-SEM) and Importance-Performance Map Analysis (IPMA) techniques. The results revealed that the university environment (UE) and university policy regulation (UPR) influenced female residential students’ attitudes (ATT) toward food waste separation. In contrast, UPR and ATT significantly influenced the students’ food waste separation intention (FWSI). The mediation analysis also showed the significance of the UE and UPR, which could indirectly affect the students’ FWSI through ATT. Furthermore, the Importance-Performance Map Analysis (IPMA) showed that the improvement effort should be more focused on ATT as the current performance is low. Thus, the importance of the university-related factors was provided in this study. The finding is expected to bring theoretical and practical advantages
New Representations for via Reciprocity Theorems
No full textTwo new representations for Ramanujan’s function σ(q) are obtained. The proof of the first one uses the three-variable reciprocity theorem due to Soon-Yi Kang and a transformation due to R.P. Agarwal while that of the second uses the four-variable reciprocity theorem due to George Andrews and a generalization of a recent transformation of Andrews, Schultz, Yee, and the second author. The advantage of these representations is that they involve free complex parameters—one in the first representation, and two in the second. In the course of obtaining these results, we arrive at one- and two-variable generalizations of σ(q)
Use of Nuclear Magnetic Resonance-Based Metabolomics to Characterize the Biochemical Effects of Naphthalene on Various Organs of Tolerant Mice
No full textNaphthalene, the most common polycyclic aromatic hydrocarbon, causes airway epithelium injury in mice. Repeated exposure of mice to naphthalene induces airway epithelia that are resistant to further injury. Previous studies revealed that alterations in bioactivation enzymes and increased levels of gamma-glutamylcysteine synthase in the bronchioles protect tolerant mice from naphthalene and its reactive metabolites. In our current study, tolerance was induced in male ICR mice using a total of 7 daily intraperitoneal injections of naphthalene (200 mg/kg). Both naphthalene-tolerant and non-tolerantmice were challenged with a dose of 300 mg/kg naphthalene on day 8 to investigate metabolite differences. The lungs, liver, and kidneys were collected for histopathology 24 h after the challenge dose. Bronchial alveolar lavage fluid (BALF) and both hydrophilic and hydrophobic extracts from each organ were analyzed using nuclear magnetic resonance (NMR)-based metabolomics. The histological results showed no observable injuries to the airway epithelium of naphthalene-tolerant mice when compared with the control. In contrast, airway injuries were observed in mice given a single challenge dose (injury mice). The metabolomics analysis revealed that the energy metabolism in the lungs of tolerant and injury mice was significantly perturbed. However, antioxidant metabolites, such as glutathione and succinate, were significantly increased in the lungs of tolerant mice, suggesting a role for these compounds in the protection of organs from naphthalene-induced electrophilic metabolites and free radicals. Damage to the airway cellular membrane, as shown by histopathological results and increased acetone in the BALF and perturbation of hydrophobic lung extracts, including cholesterol, phosphorylcholine-containing lipids, and fatty acyl chains, were observed in injury mice. Consistent with our histopathological results, fewer metabolic effects were observed in the liver and kidney of mice after naphthalene treatments. In conclusion, NMR-based metabolomics reveals possible mechanisms of naphthalene tolerance and naphthalene-induced toxicity in the respiratory system of mice
Pilot scale single chamber up-flow membrane-less microbial fuel cell for wastewater treatment and electricity generation
No full textThe presence, enjoyment, mood experience, attitude and preference towards exergames scale in children with mild intellectual disability
No full textPurpose: The purpose of this study was to examine the factor structure and cross-cultural validity of the self-report questionnaire of Ho, Lwin, Sng & Yee (2017) in a sample of Greek primary school students with mild intellectual disability (ID) using VR exergames. The questionnaire consisted of five scales, namely self-presence, mood experience, game enjoyment, attitude toward exergames and preference for future gameplay. Methods: Participants were 103 primary school students with mild ID aged 9–12 years old (males = 52.4%, females = 47.6%). Confirmatory Factor Analysis was undertaken through structural equation modelling to determine factorial validity. Convergent validity and internal consistency were calculated by considering the average variance extracted and the composite reliability respectively, while discriminant validity was estimated by maximum shared squared variance. Results: Results indicated that the model was a good fit for the data as soon as seven items were dropped from the scale because of presenting poor consistency. Instrument was shown to have good internal consistency, appropriate convergent and discriminant validity. Conclusion: Evidence was found in support of the psychometric integrity of the Ho, Lwin, Sng & Yee (2017) questionnaire when implemented to children with mild ID. © 2021, The Author(s), under exclusive licence to Springer-Verlag Italia S.r.l., part of Springer Nature
Imidazolium grafted cellulose nanocrystals for ion exchange applications
No full textAn imidazolium salt was grafted to cellulose nanocrystals (also called nanowhiskers) using copper(I) catalysed azide-alkyne cycloaddition and the bromide anion was successfully exchanged for bistriflimide and an anionic dye, providing the opportunity to synthesize a wide variety of ion exchange systems or catalysts using cellulose nanocrystals as a support medium.sponsorship: SE and WT thank the Engineering and Physical Sciences Research Council (EPSRC) for funding this research through the DICE project (EP/D501229/1), The University of Nottingham XPS service and The University of Leeds Elemental Analysis service for their respective analyses, Soon Yee Liew for AFM image acquisition and Neal Fairley, author of CasaXPS, for help with the software. (Engineering and Physical Sciences Research Council (EPSRC)|EP/D501229/1, EPSRC|EP/D501229/1)status: Publishe
Development of tourism policies case study : Singapore.
No full textAn analysis of tourism policies in Singapore from 1980 to 200
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