5,738 research outputs found

    Graduate Catalog of Studies, 2023-2024

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    Modeling and MR-thermometry for adaptive hyperthermia in cervical Cancer

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    Determinants of embryonic and foetal growth

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    The main aims of this thesis were:1. To investigate whether there are associations between determinants related to the living environment (in particular neighbourhood deprivation and air pollution) and embryonic growth, foetal growth and pregnancy outcomes;2. To assess the associations between maternal cardiometabolic determinants in pregnancy (lipid status and the presence of hypertensive disorders of pregnancy)and embryonic growth, foetal growth and childhood outcomes;3. To investigate the impact of neighbourhood deprivation on the effectiveness ofthe mHealth “Smarter Pregnancy” program, aimed at improving nutrition and lifestyle behaviours;<br/

    Graduate Catalog of Studies, 2023-2024

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    Natural and Technological Hazards in Urban Areas

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    Natural hazard events and technological accidents are separate causes of environmental impacts. Natural hazards are physical phenomena active in geological times, whereas technological hazards result from actions or facilities created by humans. In our time, combined natural and man-made hazards have been induced. Overpopulation and urban development in areas prone to natural hazards increase the impact of natural disasters worldwide. Additionally, urban areas are frequently characterized by intense industrial activity and rapid, poorly planned growth that threatens the environment and degrades the quality of life. Therefore, proper urban planning is crucial to minimize fatalities and reduce the environmental and economic impacts that accompany both natural and technological hazardous events

    LIPIcs, Volume 251, ITCS 2023, Complete Volume

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    LIPIcs, Volume 251, ITCS 2023, Complete Volum

    Effects of municipal smoke-free ordinances on secondhand smoke exposure in the Republic of Korea

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    ObjectiveTo reduce premature deaths due to secondhand smoke (SHS) exposure among non-smokers, the Republic of Korea (ROK) adopted changes to the National Health Promotion Act, which allowed local governments to enact municipal ordinances to strengthen their authority to designate smoke-free areas and levy penalty fines. In this study, we examined national trends in SHS exposure after the introduction of these municipal ordinances at the city level in 2010.MethodsWe used interrupted time series analysis to assess whether the trends of SHS exposure in the workplace and at home, and the primary cigarette smoking rate changed following the policy adjustment in the national legislation in ROK. Population-standardized data for selected variables were retrieved from a nationally representative survey dataset and used to study the policy action’s effectiveness.ResultsFollowing the change in the legislation, SHS exposure in the workplace reversed course from an increasing (18% per year) trend prior to the introduction of these smoke-free ordinances to a decreasing (−10% per year) trend after adoption and enforcement of these laws (β2 = 0.18, p-value = 0.07; β3 = −0.10, p-value = 0.02). SHS exposure at home (β2 = 0.10, p-value = 0.09; β3 = −0.03, p-value = 0.14) and the primary cigarette smoking rate (β2 = 0.03, p-value = 0.10; β3 = 0.008, p-value = 0.15) showed no significant changes in the sampled period. Although analyses stratified by sex showed that the allowance of municipal ordinances resulted in reduced SHS exposure in the workplace for both males and females, they did not affect the primary cigarette smoking rate as much, especially among females.ConclusionStrengthening the role of local governments by giving them the authority to enact and enforce penalties on SHS exposure violation helped ROK to reduce SHS exposure in the workplace. However, smoking behaviors and related activities seemed to shift to less restrictive areas such as on the streets and in apartment hallways, negating some of the effects due to these ordinances. Future studies should investigate how smoke-free policies beyond public places can further reduce the SHS exposure in ROK

    Synthesis of multifunctional glyco-pseudodendrimers and glyco-dendrimers and their investigation as anti-Alzheimer agents

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    As the world population is aging, the cases of Alzheimer’s Disease (AD) are increasing. AD is a disorder of the brain which is characterized by the aggregation of amyloid beta (Aβ) plaques. This leads to the death of numerous brain cells thus affecting the cognitive and motor functions of the individual. Till date, no cure for the disease is available. Aβ are peptides with 40/42 amino acid residues but, their exact mechanism(s) of action in AD is under debate. Having different amino acid residues makes them susceptible to form hydrogen bonds. Dendrimers with sugar units are often referred to as glycopolymers and have been shown to have potential anti-amyloidogenic activity. However, they also have drawbacks, the synthesis involves multiple tedious steps, and dendrimers themselves offer only a limited number of functional units. Pseudodendrimers are another class of branched polymers based on hyperbranched polymers. Unlike the dendrimers, they are easy to synthesize with a dense shell of functional units on the surface. One of the main goals in this dissertation is the synthesis and characterization of pseudodendrimers and dendrimers based on 2,2-bis(hydroxymethyl)-propionic acid (bis-MPA), an aliphatic polyester scaffold, as it offers biocompatibility and easy degradability. Furthermore, they are decorated with mannose units on the surface using a ‘click’ reaction forming glyco-pseudodendrimers and glyco-dendrimers. A detailed characterization of their structures and physical properties was undertaken using techniques such as size exclusion chromatography, asymmetric flow field flow fractionation (AF4), and dynamic light scattering. The second main focus of this work has been to investigate the interaction of synthesized glyco-pseudodendrimers and glyco-dendrimers with Aβ 40 peptides. For this task, five different concentrations of the synthesized glycopolymers were tested with Aβ 40 using the Thioflavin T assay. The results of the synthesized polymers which produced the best results of showing maximum anti-aggregation behavior against Aβ 40 were confirmed with circular dichroism spectroscopy. AF4 was also used to investigate Aβ 40-glycopolymer aggregates, which has never been done before and constitutes the highlight of this dissertation. Atomic force microscopy was used to image Aβ 40-glycopseudodenrimer aggregates. A basic but important step in the development of drug delivery platforms is to evaluate the toxicity of the drugs synthesized. In this work, preliminary studies of the cytotoxicity of glyco-pseudodendrimers were performed in two different cell lines. Thus, this study comprises a preliminary investigation of the anti-amyloidogenic activity of glyco-pseudodendrimers synthesized on an aliphatic polyester backbone.:Abstract List of Tables List of Figures Abbreviations 1 Introduction 1.1 Objectives of the work 1.2 Thesis overview 2 Fundamentals and Literature 2.1 Alzheimer’s Disease and its impact 2.1.1 Neurological diagnosis of AD 2.1.2 Histopathology of AD 2.1.3 Amyloid precursor protein (APP) and its role in AD 2.2. Amyloid Beta (Aβ) peptide 2.2.1 Aβ peptide 2.2.2. Location and function 2.2.3 Amyloid hypothesis 2.2.4 The mechanism of Aβ aggregation 2.2.5 Amyloid fibrils 2.2.6 Toxicity of Aβ 2.3 Research methods to study Aβ aggregates 2.3.1 Models to study the mode of action of aggregates 2.3.2 Endogenous Aβ aggregates and synthetic aggregates 2.3.3 Strategies to alter aggregation of amyloids 2.4 Treatment and therapeutics 2.4.1 Current therapeutics 2.4.2 Current therapeutic research 2.4.2.1 Reduction of Aβ production 2.4.2.2 Reduction of Aβ plaque accumulation 2.4.2.2.1 Anti-amyloid aggregation agents 2.4.2.2.2 Metals 2.4.2.2.3 Immunotherapy 2.4.2.2.4 Dendrimers as potential anti-amyloidogenic agent 2.6 Dendrimers 2.6.1 Definition 2.6.2 Structure Table of Contents 2.6.3 Synthesis 2.6.4 Properties 2.7 Pseudodendrimers - a sub-class of hyperbranched polymer 2.7.1 Definition 2.7.2 Structure 2.7.3 Synthesis 3 Analytical Techniques 3.1 Size Exclusion Chromatography Coupled to Light Scattering (SEC-MALS) 3.2 Asymmetric Flow Field Flow Fractionation (AF4) 3.3 Dynamic Light Scattering 3.4 Molecular Dynamics Simulation 3.5 Nuclear Magnetic Resonance Spectroscopy 3.6 Thioflavin T fluorescence 3.6.1 Kinetic analysis 3.7 Circular Dichroism Spectroscopy 3.8 Atomic Force Microscopy 3.9 Cytotoxic assay 3.9.1 MTT assay 3.9.2 Determining the level of reactive oxygen species 3.9.3 Changes in mitochondrial transmembrane potential 3.9.4 Flow cytometric detection of phosphatidyl serine exposure 4 Experimental Details and Methodology 4.1 Details of chemicals/components used 4.1.1 Other materials 4.1.2 Peptide preparation 4.1.3 Buffer preparation 4.1.4 Fibril growth conditions 4.2 Synthesis and characterization of polymers 4.2.1 Synthesis and characterization of pseudodendrimers and dendrimers 4.2.1.1 Synthesis of hyperbranched polymer (1) 4.2.1.2 Synthesis of protected monomer 4.2.1.2.1 bis-MPA acetonide (2) 4.2.1.2.2 bis-MPA-acetonide anhydride (3) 4.2.1.3 Synthesis of protected pseudodendrimers (4, 6 and 8) and protected dendrimers (10, 12, and 14) 4.2.1.4 Deprotection of pseudodendrimers (5,7, and 9) and dendrimers (11,13 and 15) 4.2.2 Synthesis of glyco-pseudodendrimers and glyco-dendrimers 4.2.2.1 Pentynoic anhydride (16) 4.2.2.2 Synthesis of pentinate modified pseudodendrimers (17, 18 and 19) and dendrimers (20, 21 and 22) 4.2.2.3 3-Azido-1-propanol (23) 4.2.2.4 Mannose propyl azide tetraacetate (24) Table of Contents 4.2.2.5 Mannosepropylazide (25) 4.2.2.6 Glyco-pseudodendrimers (Gl-P) (26, 27 and 28) and glyco- dendrimers (Gl-D) (29, 30 and 31) 4.3 Analytical techniques and their general details 4.3.1 SEC-MALS - Instrumentation, software and analysis 4.3.2 AF4 - Instrumentation, software and analysis 4.3.2.1 Sample preparation 4.3.2.2 Method development for analysis of Gl-P and Gl-D 4.3.2.3 Method development for analysis of Aβ 40 and its interaction with Gl-P and Gl-D 4.3.3 Batch DLS - Instrumentation, software and analysis 4.3.3.1 Sample preparation 4.3.4 Theoretical calculations and molecular dynamics simulations 4.3.4.1 Ab-initio calculations 4.3.4.2 Modelling of the polymer structures 4.3.4.2.1 Pseudodendrimers 4.3.4.2.2 Dendrimers 4.3.4.2.3 Modification of the polymers with special end groups 4.3.4.2.4 Preparing of the THF solvent box 4.3.4.2.5 Solvation of the polymer structures 4.3.4.3 Molecular dynamics simulations 4.3.4.3.1 Evaluation of the simulation trajectories 4.4 Investigation of interaction of Gl-P and Gl-D with amyloid beta (Aβ 40) 4.4.1 ThT Assay - Instrumentation and software 4.4.1.1 Sample preparation 4.4.1.2 Kinetics based on ThT assay- software and data analysis 4.4.2 CD spectroscopy - Instrumentation and software 4.4.2.1 Sample preparation 4.4.3 AFM - Instrumentation and software 4.4.3.1 Substrate and sample preparation 4.4.3.2 Height determination and counting procedures 4.4.3.3 Topography and diameter 4.5 Cytotoxicity 4.5.1 Zeta potential 4.5.2 Cell culturing 4.5.3 Sample preparation 4.5.4 MTT assay 4.5.5 Changes in mitochondrial transmembrane potential (JC-1 method) 4.5.6 Flow cytometric detection of phosphatidyl serine exposure (Annexin V and PI method) 5 Results and Discussion 5.1 Synthesis and characterization of glyco-pseudodendrimers and glyco- dendrimers 5.1.1 Synthesis and characterization of hyperbranched polyester Table of Contents 5.1.2 Synthesis and characterization of pseudodendrimers P-G1-OH, P-G2-OH and P-G3-OH 5.1.3 Synthesis and characterization of dendrimers D-G4-OH, D-G5-OH and D-G6-OH 5.1.4 Synthesis and characterization of Gl-P and Gl-D 5.1.4.1 Molecular size determination of Gl-P and Gl-D using SEC 5.1.4.2 Particle size determination using batch DLS 5.1.4.3 Apparent densities 5.1.4.4 Molecular size determination of Gl-P and Gl-D using AF4 ..... 5.1.5 Molecular dynamics simulation 5.2 Investigation of interaction of Gl-P and Gl-D with amyloid beta (Aβ 40) ...... 5.2.1 ThT Assay 5.2.1.1 Kinetics based on ThT assay 5.2.2 CD spectroscopy 5.2.3 Time dependent AF4 5.3.2.1 Separation of Aβ 40 by AF4 5.3.2.2 Aβ 40 amyloid aggregation in the presence of Gl-P and Gl-D 5.2.4 AFM 5.2.4.1 Height 5.2.4.2 Topography and diameter 5.2.4.3 Length 5.2.4.4 Morphology 5.2.5 Cytotoxicity 5.2.5.1 MTT assay 5.2.5.2 Changes in mitochondrial transmembrane potential 5.2.5.3 Flow cytometric detection of phosphatidyl serine exposure 6 Conclusions and Outlook 7 Bibliography Appendix Acknowledgement

    Deep Learning Paradigms for Existing and Imminent Lung Diseases Detection: A Review

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    Diagnosis of lung diseases like asthma, chronic obstructive pulmonary disease, tuberculosis, cancer, etc., by clinicians rely on images taken through various means like X-ray and MRI. Deep Learning (DL) paradigm has magnified growth in the medical image field in current years. With the advancement of DL, lung diseases in medical images can be efficiently identified and classified. For example, DL can detect lung cancer with an accuracy of 99.49% in supervised models and 95.3% in unsupervised models. The deep learning models can extract unattended features that can be effortlessly combined into the DL network architecture for better medical image examination of one or two lung diseases. In this review article, effective techniques are reviewed under the elementary DL models, viz. supervised, semi-supervised, and unsupervised Learning to represent the growth of DL in lung disease detection with lesser human intervention. Recent techniques are added to understand the paradigm shift and future research prospects. All three techniques used Computed Tomography (C.T.) images datasets till 2019, but after the pandemic period, chest radiographs (X-rays) datasets are more commonly used. X-rays help in the economically early detection of lung diseases that will save lives by providing early treatment. Each DL model focuses on identifying a few features of lung diseases. Researchers can explore the DL to automate the detection of more lung diseases through a standard system using datasets of X-ray images. Unsupervised DL has been extended from detection to prediction of lung diseases, which is a critical milestone to seek out the odds of lung sickness before it happens. Researchers can work on more prediction models identifying the severity stages of multiple lung diseases to reduce mortality rates and the associated cost. The review article aims to help researchers explore Deep Learning systems that can efficiently identify and predict lung diseases at enhanced accuracy

    Large‐scale mass movements recorded in the sediments of Lake Hallstatt (Austria)–evidence for recurrent natural hazards at a UNESCO World Heritage site

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    The Bronze to Iron Age underground salt mining complex of Hallstatt (Austria) is widely recognised for its cultural importance and wealth of archaeological artefacts. However, while the daily life in the salt mines is archaeologically well documented and environmental effects of the mining activity have been investigated recently, the impact of natural hazards on the prehistoric mining community is still poorly understood. For instance, while it is well established that the prehistoric underground mines have repeatedly been destroyed by large-scale mass movements, only little is known about the characteristics and extent of these events as well as about mass-movement recurrence during more recent times. To shed light on past mass-movement activity in the vicinity of the Hallstatt salt mines, we investigated sediment cores from adjacent Lake Hallstatt. Within the regular lake sediments we identified three large-scale event deposits, which are interpreted to originate from spontaneous or seismically induced mass movements in the mid-19th and late 9th century ce and the mid-4th century bce. While the age of the latter event is in good agreement with the abandonment of the famous Iron Age cemetery at Hallstatt, the younger events indicate that large-scale mass movements also occurred repeatedly during the Common Era
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