Interrogation of drug effects on the lipid composition of single cells and Drosophila brain using ToF-SIMS imaging

Lipids are essential for all living organisms on Earth. The most important function of lipids is that they act as the building blocks of cellular membranes. Lipids consist of polar head groups and non-polar tail groups and assemble into bilayer structures to create cell and organelle membranes. The plasma membrane of a cell provides a barrier which segregates cellular internal constituents from the external environment. In addition to acting as a barrier, membrane lipids are involved in many cellular processes including membrane trafficking, signal transduction, fission and fusion. Therefore, various conditions in the central nervous system involving lipid deficiencies can lead to function deficit. There are several drugs that induce the dysregulation of lipid metabolism linked to the impairment or enhancement of cognitive function. Hence, I have studied the lipid alterations in brain induced by drugs with regards to their effects on cognitive processes: cognitive impairing drugs (cocaine and zinc deficiency) and cognitive enhancing drugs (methylphenidate and fatty acids). Much work has been done to investigate the link between lipid metabolisms and these drugs. A powerful technique for lipid analysis is mass spectrometry imaging (MSI). MSI is a surface sensitive method which enables label-free detection of molecules in complex biological systems. In addition, MSI provides the relative composition as well as allows imaging of intact species with high spatial resolution in single experiments. One of the most common MSI techniques is time-of-flight secondary ion mass spectrometry (ToF-SIMS), which achieves high spatial resolution using a focused ion beam to eject and ionize molecules in the sample surface. Recently, gas cluster ion beams have been introduced to reduce the chemical damage during sampling of surfaces and to achieve enhancement of lipid signals. In our studies, ToF-SIMS has been applied to lipids in the membranes of cells and Drosophila melanogaster brain to get a better understanding about the effect of drugs in lipid mechanisms related to neuronal signal transmission. The papers included in this thesis describe the application of ToF-SIMS in biological samples to reveal the alterations of lipids after drug treatments. In paper I, the alterations in lipid distribution and composition induced by cocaine and methylphenidate, which cause the impairment and enhancement in cognitive performance respectively, were investigated. ToF-SIMS data were used to show that cocaine and methylphenidate have opposite effects on the relative levels of lipids in the central fly brain. To enhance our understanding about the lipid mechanisms, in paper II, I used stable deuterium-labeled omega-3 and -6 fatty acids as lipid precursors to analyze the synthesis and transportation of lipids into the plasma membrane of PC12 cells. The use of isotope-labeled fatty acids provided a tool to track the lipid turn-over as well as to measure their relative amounts. Paper III continued the work done in paper I, where experiments were performed to investigate the recovery of lipids after cocaine removal. In addition, the cognitive-enhancing drug, methylphenidate, was used to treat cocaine removal from flies to investigate the reversal of lipid changes in the brain caused by repeated-cocaine exposure. Zinc deficiency in the diet, which causes a decrease in cognitive function, was also studied in fly brain. ToF-SIMS data obtained reveal that the lipid types that change are similar to those when treated with cocaine as seen in paper IV.ToF-SIMS opens a new approach to visualize and relatively quantify phospholipids in biological tissues and cells. In the biological model systems studied here, cognition-affecting drugs show that alterations in the distribution and composition of specific lipids is altered differently based on whether the drug enhances versus diminishes cognition. These results provide new possible targets for lipid-modifying therapies to improve the cognitive decline in drug abuse and diseases

Spatial Patterns of Hand-Foot and Mouth Disease In Ho Chi Minh City, Vietnam

Background: Hand-Foot-and-Mouth Disease (HFMD) is most frequently caused by Enterovirus71 (EV-A71) or Coxsackie virus A16 (CV-A16), infants and young children are at greatest risk. Describing the spatial patterns of HFMD can help develop and better target interventions. The objective of this study is to identify spatial patterns of HFMD in the first 8-months of 2023 in Ho Chi Minh city, Vietnam. Methods: The global Moran’s I statistic, Moran’s I scatterplot and local Moran’s I statistic and Boxplot will be applied to study spatial patterns of HFMD. Spatial patterns including spatial clusters (high-high and low-low) and spatial outliers (low-high and high-low) will be identified for HFMD cases and HFMD infection rates. Results: three high-high spatial clusters were mainly distributed in districts in the western region of the city such as Binh Tan, Binh Chanh, and Tan Phu. These high-high spatial clusters belonged to districts having the highest rates of HFMD infections in the city with their corresponding rates of 289, 283 and 281 cases/100,000 inhabitants, respectively. On the other hand, two low-low spatial clusters were detected in Districts 1 and 5 in the city center with their HFMD infection rates of 190 and 209 cases/100,000 inhabitants, respectively. Conclusions : findings in this study support the usefulness of boxplots, local and global Moran's I statistics, and Moran's I scatterplots in the identification of spatial clusters and spatial outliers of HFM

Employment opportunities for Vietnamese American fisherfolk affected by the BP gulf oil spill in Louisiana

Thesis (M.C.P.)--Massachusetts Institute of Technology, Dept. of Urban Studies and Planning, 2011.Cataloged from PDF version of thesis.Includes bibliographical references (p. 63-65).This thesis explores potential employment opportunities in energy efficiency construction and aquaculture for Vietnamese American fisherfolk significantly impacted by the BP oil spill in Louisiana. First, the thesis explains the history of the Vietnamese American community in Louisiana and the affects of Hurricane Katrina as well as the BP oil spill on the community. This is done in order to build the case for the need to look for alternative employment for dislocated Vietnamese American fisherfolk. Second, it assesses the skills and job suitability for Vietnamese American dislocated fisherfolk. It then explores the potential growth of the energy efficiency construction and aquaculture industries in Louisiana. Finally, the thesis concludes with recommendations for how Vietnamese American fisherfolk can enter these industries and how Mary Queen of Vietnam Community Development Corporation can further explore future employment opportunities for dislocated Vietnamese American fisherfolk.by Mai T. Dang.M.C.P

Mass spectrometric imaging of plasma membrane lipid alteration correlated with amperometrically measured activity-dependent plasticity in exocytosis

The mechanism of synaptic plasticity and its link to memory formation are of interest, yet relatively obscure, especially the initial chemical change in the cell membrane following transmitter release. To understand the chemical mechanism of plasticity, we studied how repetitive stimuli regulate certain membrane lipid species to enhance exocytotic release using mass spectrometric imaging. We found that increasing high-curvature lipid species and decreasing low-curvature lipids in the cell membrane favor the formation of a longer-lasting exocytotic fusion pore, resulting in higher release fraction for individual exocytotic events. The lipid changes observed following repetitive stimuli are similar to those after exposure to the cognitive enhancing drug, methylphenidate, examined in a previous study, and offer an interesting point of view regarding the link between plasticity and memory and cognition

E-LEARNING AND TEACHING IN HO CHI MINH CITY UNIVERSITY OF TECHNOLOGY AND EDUCATION - INITIAL EVALUATION OF EFFECTIVENESS AND FEASIBILITY MODEL ON A LARGE SCALE

E-Learning and Teaching is a modern method of teaching and learning based on information technology. In particular, during the industrial revolution 4.0, information technology and digitization develop strongly and rapidly in all countries, which make the traditional teaching method lose the leading position in modern education. Because E-Learning and Teaching allows the maximum exploitation of its features and utility in online teaching and learning, reduces training costs, time and brings convenience for learners anytime and anywhere. Recognizing the importance of online teaching and learning trends in the industrial revolution 4.0, Ho Chi Minh City University of Technology and Education (HCMUTE) has applied and implemented the E-Learning and Teaching system on the basis of teaching management systems such as LMS/FHQLMS and Google Classroom. This article contributes to describing the current situation and difficulties in the implementation of E-Learning and Teaching, aiming to build an E-Learning and Teaching application on a large scale in HCMUTE in particular and Vietnam in general. Article visualizations

Binary-Continuous Sum-of-ratios Optimization: Discretization, Approximations, and Convex Reformulations

We study a class of non-convex sum-of-ratios programs which can be used for decision-making in prominent areas such as product assortment and price optimization, facility location, and security games. Such an optimization problem involves both continuous and binary decision variables and is known to be highly non-convex and intractable to solve. We explore a discretization approach to approximate the optimization problem and show that the approximate program can be reformulated as mixed-integer linear or second-order cone programs, which can be conveniently handled by an off-the-shelf solver (e.g., CPLEX or GUROBI). We further establish (mild) conditions under which solutions to the approximate problem converge to optimal solutions as the number of discretization points increases. We also provide approximation abounds for solutions obtained from the approximated problem. We show how our approach applies to product assortment and price optimization, maximum covering facility location, and Bayesian Stackelberg security games and provide experimental results to evaluate the efficiency of our approach

Étude du débalancement des acides gras dans les HDL et LDL chez les porteurs du polymorphisme de l’apolipoprotéine E Ɛ4

Résumé : L’apolipoprotéine E (apoE) joue un rôle important dans le transport des acides gras (AG) via les lipoprotéines. Cependant, il existe possiblement une perturbation dans l’homéostasie des AG au niveau des lipoprotéines chez les porteurs du génotype de l’apolipoprotéine E epsilon 4 (E4+). L’objectif de cette étude est de déterminer le profil en AG dans les lipoprotéines de hautes et de faibles densités (HDL et LDL) chez les E4+ et les non-porteurs (E4-), pendant une supplémentation en AG oméga-3 (n-3) de 28 jours. Matériels et Méthodes: 80 participants (34 hommes et 46 femmes) en santé, âgés entre 20-35 ans, ont consommé 1,6 g/jour d’AG n-3 sur une période de 28 jours. Des prélèvements sanguins à jeun ont été récoltés chaque semaine. Les lipoprotéines ont été séparées par ultracentrifugation sur gradient discontinu de sucrose. Les lipides totaux des particules de HDL et de LDL ont été analysés par chromatographie en phase gazeuse. Les génotypes de l’APOE (E4+ ou E4-) ont été déterminés par la méthode de polymorphisme de longueur des fragments de restriction (RFLP) et les données ont été analysées par logiciel SAS à l’aide d’une procédure MIXED. Résultats: Les caractéristiques anthropométriques et habitudes de vies ne variaient pas significativement entre les E4+ et E4-. Le ratio d’AG n-6/n–3 était environ 17% plus élevé chez les E4+ dans les LDL (P = 0.043) pendant la supplémentation. Ceci peut être attribuable au niveau plus élevé d’AG n-6, sans changement dans le niveau d’AG n-3 chez les E4+. Une interaction génotype × temps a été trouvée pour l’acide linoléique (LA) dans les HDL ainsi qu’un effet génotype pour les AG n-6 totaux dans les HDL et LDL (P ≤ 0.05). De plus, l’acide palmitique (PA) et palmitoléïque (PAL) est plus bas chez les E4+ comparativement aux E4-. Conclusion: Le débalancement de la distribution des AG dans les HDL et LDL chez les E4+ peut être causé par une altération de la spécificité de la β-oxydation des AG chez les E4+. Plus d’investigation doit être faite à cet égard afin de confirmer ces hypothèses