VictorJuiz/thesis huggingface dataset:
Microfluidics for particle manipulation: new simulation techniques for novel devices and applications
Keywords: diagnostic device
particle separation
microfluidics
magnetic separation
two-phase flow
surface marker point
Dean flow

This thesis focuses on fundamental aspects of microfluidic systems and applies relevant findings to innovative designs for advanced particle manipulation applications.
Computational Fluid Dynamics (CFD) is adopted for fluid modeling, based on the Finite Volume method. The accuracy of the solutions obtained is confirmed by grid sensitivity analysis and by comparisons with experimental work. Curved microchannel features and the induced Dean flow are studied through a parametric space exploration and simulations. The Lagrange-Euler coupling method – Surface Marker Point methodology – is applied to simulate large-size particles (of comparable size to the channel). Through this simulation approach, all the forces on such particles are directly derived through solving the governing equations and the influence of these particles on the flow is considered in a fully coupled manner. A new approach – the Frozen Flow & Flow Correction Coefficient method – is developed, making trans-relaxation-time simulations possible and improving computational efficiency significantly, for 3D simulations of arbitrary shape and size microparticles in complicated microfluidic channels. Detailed comparisons between simulation results and experiments involving particle sedimentation and particle equilibrium position have been conducted for methodology validation.
Mechanisms of hydrodynamic particle manipulation are then studied, including hydrodynamic focusing and separation. It is found that the Tubular Pinch effect, Dean flow and the Radial Pressure Gradient effect interact to yield two distinct particle separation mechanisms. For advanced applications, particle focusing, non-magnetic and magnetic separation for neutrally buoyant particles are proposed, based on newly gained insight on the above-mentioned mechanisms. Appropriate channel designs have been proposed both for particle focusing and size-based particle separation, while the vertical-magnetic-Dean separation scheme is highlighted for magnetic separation.
Finally, a new integrated system is proposed, that combines the above novel designs into a device-like ensemble. It promises to offer functionality for biomaterial separation and detection, including different types of cells, antigens and biomarkers.
A system-level approach to single-molecule live-cell fluorescence microscopy
Keywords: single-molecule
fluorescence
optics
colocalisation

In this work a system-level approach was taken to the single-molecule fluorescence microscopy of living cells. This primarily involved the unification of relevant information within appropriately structured artefacts that were used to inform and enhance experimentation.
Initially the diversity of emerging single-molecule techniques was reviewed and presented with a novel article structure to suit the purpose of designing an experiment (Harriman and Leake 2011). Techniques were grouped by the type of information they could access, rather than the standard organisation centred on the techniques themselves.
A bespoke microscope was conceived and built with reference to knowledge and tools from the fields of Architecture and Systems-Engineering. The microscope layout would enable multiple experiment types through independent control of multiple illumination beams. A technique was developed enabling the prescription of evanescent field penetration depth for each incident beam.
The various empirical and theoretical results that are used to understand and modify a microscopy experiment were integrated into an internally consistent simulation model (Harriman and Leake. 2013). This was used to inform the selection of experimental components and parameters and ultimately acquire higher data quality as measured by functions such as signal-to-noise ratio (SNR).
The combined experimental system of microscope and simulation model was applied in two live-cell investigations. In Escherichia coli, the spatial distribution of membrane bound proteins was investigated and a novel technique was applied to the analysis of colocalisation. Results indicate that NADH dehydrogenase and ATP synthase follow uncorrelated trajectories. This supports the hypothesis of spatial decoupling of molecules that energise the membrane and molecules that use membrane energy.
In human carcinoma cells, the mechanism of ligand-receptor binding was investigated. Data was collected prior to and periodically after the addition of ligands, and fluorescence images were acquired of both ligands and receptors. Analyses based on single particle tracking are currently being carried out by a collaborator to extract information on stoichiometry and dynamics at the single-molecule level.
Models for adaptive feeding and population dynamics in plankton
Keywords: population dynamics
dynamical systems in biology
Filippov systems
bifurcations of limit cycles and periodic orbits
planktonic protozoa-algae dynamics
Lotka-Volterra interaction

Traditionally, differential-equation models for population dynamics have considered organisms as "fixed" entities in terms of their behaviour and characteristics. However, there have been many observations of adaptivity in organisms, both at the level of behaviour and as an evolutionary change of traits, in response to the environmental conditions. Taking such adaptiveness into account alters the qualitative dynamics of traditional models and is an important factor to be included, for example, when developing reliable model predictions under changing environmental conditions. In this thesis, we consider piecewise-smooth and smooth dynamical systems to represent adaptive change in a 1 predator-2 prey system.
First, we derive a novel piecewise-smooth dynamical system for a predator switching between its preferred and alternative prey type in response to prey abundance. We consider a linear ecological trade-off and discover a novel bifurcation as we change the slope of the trade-off. Second, we reformulate the piecewise-smooth system as two novel 1 predator-2 prey smooth dynamical systems. As opposed to the piecewise-smooth system that includes a discontinuity in the vector fields and assumes that a predator switches its feeding strategy instantaneously, we relax this assumption in these systems and consider continuous change in a predator trait.
We use plankton as our reference organism because they serve as an important model system. We compare the model simulations with data from Lake Constance on the German-Swiss-Austrian border and suggest possible mechanistic explanations for cycles in plankton concentrations in spring.
Engineering antibodies to study and improve immunomagnetic isolation of tumour cells
Keywords: 4D5
magnetic bead
tumour cell
BT474
immunomagnetic
microbiology
flow cytometry
protein engineering
9E10
clamping
Herceptin
HER2
cell isolation
circulating tumour cell
periplasmic expression
Fab
streptavidin
cell sorting
antibodies
myc peptide
biotinylation
cancer
cholesterol

Cell separation based on antibody-targeted magnetic beads has been widely used in a number of applications in immunology, microbiology, oncology and more recently, in the isolation of circulating tumour cells (CTCs) in cancer patients. Although other cell separation techniques such as size based cell filtration and Fluorescence Activated Cell Sorting have also been in popular use, immunomagnetic cell isolation possesses the advantages of high throughput, good specificity and reduced cell stress. However, certain fundamental features of the cell-bead interface are still unknown.
In this study, some of the key features of the cell-bead synapse were investigated in an effort to improve the efficiency of immunomagnetic cell isolation and reduce its dependence on high expressing cell surface markers. A clinically relevant antibody fragment (Fab) against tyrosine kinase receptor HER2 was applied to study the immunomagnetic isolation of HER2 expressing cancer cells. First, the minimum number of target proteins required on a cell for it to be isolated was determined. Second, the importance of the primary antibody affinity was investigated, using a series of Fab mutants with known kinetics and it was shown that despite starting with sub-nanomolar affinity, improving Fab affinity increased cell isolation. Third, the influence of the connection between the primary antibody and the bead was studied by comparing Fab bridged to the magnetic bead via a secondary antibody, Protein L or streptavidin; the high affinity biotin-streptavidin linkage increased isolation sensitivity by an order of magnitude. Fourth, the effect of manipulating cytoskeletal polymerization and cell membrane fluidity using small molecules was tested; cholesterol depletion decreased isolation and cholesterol loading increased cell isolation. The insights from these observations were then applied to isolate a panel of cell lines expressing a wide range of surface HER2. While the standard approach isolated less than 10% of low HER2 expressing cancer cells from spiked rabbit and human blood, our enhanced approach with the optimized cholesterol level, antibody affinity and antibody-bead linkage could specifically isolate more than 80% of such cells. The final part of this work focussed on developing an antibody clamp that could physically restrict the antigen within its binding site on the Fab and prevent antigen dissociation, using the HER2-Fab complex and the anti-myc peptide antibody 9E10.
Work from this thesis provides useful insights into the molecular and cellular parameters guiding immunomagnetic cell isolation and can be used to extend the range of target receptors and biomarkers for tumour cell isolation and other types of cell separation, thereby enhancing the power and capacity of this approach.
Controlled synthesis and properties of layered double hydroxides
Keywords: DIFFaX
reverse micelle/microemulsion
LDH

The aims of this thesis are concerned with the synthesis of layered double hydroxide nanoparticles with controlled morphology and particle size distribution and an investigation of their physical properties. An introduction of layer double hydroxide chemistry, especially existing synthetic approaches, is reviewed in Chapter 1. Structural investigations, characterisation techniques, the properties and the applications of LDHs are discussed consecutively.
The first successful synthesis of lithium aluminium nanorods using the hydrothermal treatment of a gibbsite precursor with a rod-like morphology is described in Chapter 2. The rod morphology is depicted using electron microscopy and confirmed by comparing refined X-ray diffraction patterns to a standard sample.
Chapter 3 describes the application of reverse microemulsion method to prepare Co-Al and Ni-Al LDH nanoplatelets. The LDH particle sizes can be effectively controlled, and the structures of the nanoplatelets are investigated. The magnetic properties of the LDH nanoplatelets are dependent on the size of the nanoplatelets.
A novel single component microemulsion system for the synthesis of LDHs is developed in Chapter 4. Mg-Al LDH nanoplatelets were successfully synthesised with precise particle size control. The factors affecting the formation of the microemulsions and the mechanism of the synthesis are discussed.
Chapter 5 focuses on the applications of the novel single component microemulsion methods to prepare a range of LDHs with different metal combinations including Co-Al, Ni-Al, Zn-Al, Li-Al, Ca-Al, and Ni-Fe. This method proves very effective at controlling the particle sizes. The magnetic properties of the LDHs containing paramagnetic transition metal centres have been studied in detail.
In Chapter 6, the DIFFaX program has been used to simulate the XRD patterns of layered structures. The factors influencing the XRD patterns in these materials have been systematically investigated including the effects of particle size, stacking faults, and disorder. The XRD patterns of materials described in previous chapters are simulated using the latest DIFFaX+ code in order to estimate the particle sizes and stacking sequences.
The characterising techniques and the experimental details are listed in Chapter 7.
Segmentation and sizing of breast cancer masses with ultrasound elasticity imaging
Keywords: medical image analysis
ultrasound
breast cancer
elasticity imaging

Uncertainty in the sizing of breast cancer masses is a major issue in breast screening programs, as there is a tendency to severely underestimate the sizing of malignant masses, especially with ultrasound imaging as part of the standard triple assessment. Due to this issue about 20% of all surgically treated women have to undergo a second resection, therefore the aim of this thesis is to address this issue by developing novel image analysis methods. Ultrasound elasticity imaging has been proven to have a better ability to differentiate soft tissues compared to standard B-mode. Thus a novel segmentation algorithm is presented, employing elasticity imaging to improve the sizing of malignant breast masses in ultrasound. The main contributions of this work are the introduction of a novel filtering technique to significantly improve the quality of the B-mode image, the development of a segmentation algorithm and their application to an ongoing clinical trial. Due to the limitations of the employed ultrasound device, the development of a method to improve the contrast and signal to noise ratio of B-mode images was required. Thus, an autoregressive model based filter on the radio-frequency signal is presented which is able to reduce the misclassification error on a phantom by up to 90% compared to the employed device, achieving similar results to a state-of-the art ultrasound system. By combining the output of this filter with elasticity data into a region based segmentation framework, a computationally highly efficient segmentation algorithm using Graph-cuts is presented. This method is shown to successfully and reliably segment objects on which previous highly cited methods have failed. Employing this method on 18 cases from a clinical trial, it is shown that the mean absolute error is reduced by 2 mm, and the bias of the B-Mode sizing to underestimate the size was overcome. Furthermore, the ability to detect widespread DCIS is demonstrated.
The invention of the new culture movement in 1919
Keywords: Chinese newspapers
1919
baihua
May Fourth Movement
Chinese history
New Culture Movement
Republican Period

The expression ‘New Culture Movement’ was born in summer 1919, in the intersections of academic debate, political activism, media coverage and intellectual marketing strategies. I have traced the emergence of the phrase and the discourses around it, using sources like journals, newspapers, student essays, advertisements and conference protocols.
The New Culture Movement was a buzzword, deployed by practically-minded but lesser-known intellectuals to promote agendas they had held long before its invention. Many notions we associate with the Movement until today already surrounded it in 1919: for example, that it was connected to the political protests of ‘May Fourth,’ and driven by star intellectuals such as Hu Shi and Chen Duxiu. But closer scrutiny reveals that the New Culture Movement and its network of associations were a construct, an amalgam of newspaper stories and intellectual marketing ploys: the connection to May Fourth was created by newspapers; the intellectuals at the periphery drew upon Hu Shi’s and Chen Duxiu’s prestige to add glamour to their own agendas. Nevertheless, the New Culture Movement shaped China’s 20th century. As only some agendas could credibly be sold as the Movement, it catalysed the plethora of competing agendas that had emerged since the 19th century to tackle the challenges of a changed world order.
The New Culture Movement later became a founding myth of ‘Modern China’ and was regarded as the obvious result of global trends towards ‘modernisation,’ which visionary intellectuals recognised. But more recent literature has decentred the Movement, noted a longer history of its ideas and the careerism of its participants. I drive this point further by showing that, at the Movement’s very core, were practically-minded business and marketing strategies, deployed by numerous, lesser-known actors. It was in this way that the course for 20th-century China and one of its founding myths was set.
Clash of organisational cultures?  A comparative analysis of American and British approaches to the coordination of defence, diplomacy and development in stability operations, 2001-2010
Keywords: post-conflict reconstruction
civil-military relations
state-building

This thesis examines the challenge of coordinating civilian and military efforts within a so-called ‘whole-of-government’ approach to stability operations. The empirical analysis focuses on British and American attempts to implement an integrated civilian-military strategy in Afghanistan and Iraq between 2001 and 2010. Unlike many existing analyses, the thesis consciously avoids jumping to the search for solutions to fix the problem of coordination and instead offers a nuanced explanation of why it arises in the first instance. Empirical data was gathered through personal interviews with a wide range of civilian and military practitioners between 2007 and 2011. Together with the in-depth study of official documents released by, and on, the defence, diplomatic and development components of the British and American governments, they provide the basis for a fine-grained analysis of obstacles to interagency coordination.
The thesis offers a framework for analysis that is grounded in organisation theory and distinguishes between material, bureaucratic and cultural dimensions of obstacles to interagency coordination. It identifies organisational cultures as a crucial force behind government agencies’ reluctance to participate and invest in an integrated approach. The empirical chapters cover interagency dynamics within the government bureaucracy and in operations on the ground, including the role of specialised coordination units and Provincial Reconstruction Teams in the pursuit of coordination. The thesis concludes that stabilisation remains an inherently contested endeavour for all organisations involved and that the roles and expectations implied by contemporary templates for coordination clash with prevailing organisational identities and self-perceptions. These findings caution against the procedural and technocratic approach to interagency coordination that permeates the existing literature on the subject and many proposals for reform. While the thesis examines a specific empirical context, its conclusions have broader implications for civilian-military coordination and the quest for an integrated approach to security in the twenty-first century.
Vital sign monitoring and data fusion for paediatric triage
Keywords: Photoplethysmogram
Novelty Detection
Vital Signs
Breathing Rate
Pulse Oximeter
Respiratory Rate
Paediatric Triage
Physiological Monitoring

Accurate assessment of a child’s health is critical for appropriate allocation of medical resources and timely delivery of healthcare in both primary care (GP consultations) and secondary care (ED consultations). Serious illnesses such as meningitis and pneumonia account for 20% of deaths in childhood and require early recognition and treatment in order to maximize the chances of survival of affected children. Due to time constraints, poorly defined normal ranges, difficulty in achieving accurate readings and the difficulties faced by clinicians in interpreting combinations of vital signs, vital signs are rarely measured in primary care and their utility is limited in emergency departments.
This thesis aims to develop a monitoring and data fusion system, to be used in both primary care and emergency department settings during the initial assessment of children suspected of having a serious infection. The proposed system relies on the photoplethysmogram (PPG) which is routinely recorded in different clinical settings with a pulse oximeter using a small finger probe. The most difficult vital sign to measure accurately is respiratory rate which has been found to be predictive of serious infection. An automated method is developed to estimate the respiratory rate from the PPG waveform using both the amplitude modulation caused by changes in thoracic pressure during the respiratory cycle and the phenomenon of respiratory sinus arrhythmia, the heart rate variability associated with respiration. The performance of such automated methods deteriorates when monitoring children as a result of frequent motion artefact. A method is developed that automatically identifies high-quality PPG segments mitigating the effects of motion on the estimation of respiratory rate.
In the final part of the thesis, the four vital signs (heart rate, temperature, oxygen saturation and respiratory rate) are combined using a probabilistic framework to provide a novelty score for ranking various diagnostic groups, and predicting the severity of infection in two independent data sets from two different clinical settings.
Multi-agent exploration of unknown areas
Keywords: multi-agent systems
exploration
robotics

This work focuses on the autonomous exploration of unknown areas by a swarm of mobile robots, referred to as agents. When an emergency happens within a building, it is dangerous to send human responders to search the area for hazards and victims. This motivates the need for autonomous agents that are able to coordinate with each other to explore the area as fast as possible. We investigate this problem from an algorithmic, rather than a robotics point of view, and thus abstract away from practical problems, such as obstacle detection and navigation over rough terrain. Our focus is on distributed algorithms that can cope with the following challenges: the topology of the area is typically unknown, communication between agents is intermittent and unreliable, and agents are not aware of their location in indoor environments. In order to address these challenges, we adopt the stigmergy approach, that is, we assume that the area is instrumented with small inexpensive sensors (called tags) and agents coordinate indirectly with each other by reading and updating the state of local tags. We propose three novel distributed algorithms that allow agents to explore unknown areas by coordinating indirectly through a tag-instrumented environment. In addition, we propose two mechanisms for discovering evacuation routes from critical points in the area to emergency exits. Agents are able to combine the tasks of area exploration and evacuation route discovery in a seamless manner. We study the proposed algorithms analytically, and evaluate them empirically in a custom-built simulation environment in a variety of scenarios. We then build a real testbed of agents and tags, and investigate practical mechanisms that allow agents to detect and localise nearby tags, and navigate toward them. Using the real testbed, we derive realistic models of detection, localisation and navigation errors, and investigate how they impact the performance of the proposed exploration algorithms. Finally, we design fault-tolerant exploration algorithms that are robust to these errors and evaluate them extensively in a simulation environment.