Data mining and visualization for anomaly detection and diagnosis in civil structures

Peer reviewed

Development of tumour imaging and therapy strategies utilising unengineered bacteria

The ability of systemically administered bacteria to target and replicate to high numbers within solid tumours is well established. Tumour localising bacteria can be exploited as biological vehicles for the delivery of nucleic acid, protein or therapeutic payloads to tumour sites and present researchers with a highly targeted and safe vehicle for tumour imaging and cancer therapy. This work aimed to utilise bacteria to activate imaging probes or prodrugs specifically within target tissue in order to facilitate the development of novel imaging and therapeutic strategies. The vast majority of existing bacterial-mediated cancer therapy strategies rely on the use of bacteria that have been genetically modified (GM) to express genes of interest. While these approaches have been shown to be effective in a preclinical setting, GM presents extra regulatory hurdles in a clinical context. Also, many strains of bacteria are not genetically tractably and hence cannot currently be engineered to express genes of interest. For this reason, the development of imaging and therapeutic systems that utilise unengineered bacteria for the activation of probes or drugs represents a significant improvement on the current gold standard. Endogenously expressed bacterial enzymes that are not found in mammalian cells can be used for the targeted activation of imaging probes or prodrugs whose activation is only achieved in the presence of these enzymes. Exploitation of the intrinsic enzymatic activity of bacteria allows the use of a wider range of bacteria and presents a more clinically relevant system than those that are currently in use. The nitroreductase (NTR) enzymes, found only in bacteria, represent one such option. Chapter 2 introduces the novel concept of utilising native bacterial NTRs for the targeted activation of the fluorophore CytoCy5S. Bacterial-mediated probe activation allowed for non-invasive fluorescence imaging of in vivo bacteria in models of infection and cancer. Chapter 3 extends the concept of using native bacterial enzymes to activate a novel luminescent, NTR activated probe. The use of luminescence based imaging improved the sensitivity of the system and provides researchers with a more accessible modality for preclinical imaging. It also represents an improvement over existing caged luciferin probe systems described to date. Chapter 4 focuses on the employment of endogenous bacterial enzymes for use in a therapeutic setting. Native bacterial enzymatic activity (including NTR enzymes) was shown to be capable of activating multiple prodrugs, in isolation and in combination, and eliciting therapeutic responses in murine models of cancer. Overall, the data presented in this thesis advance the fields of bacterial therapy and imaging and introduce novel strategies for disease diagnosis and treatment. These preclinical studies demonstrate potential for clinical translation in multiple fields of research and medicine.

Theranostic Fibers for Simultaneous Imaging and Drug Delivery

New methods for creating theranostic systems with simultaneous encapsulation of therapeutic, diagnostic, and targeting agents are much sought after. This work reports for the first time the use of coaxial electrospinning to prepare such systems in the form of core–shell fibers. Eudragit S100 was used to form the shell of the fibers, while the core comprised poly(ethylene oxide) loaded with the magnetic resonance contrast agent Gd(DTPA) (Gd(III) diethylenetriaminepentaacetate hydrate) and indomethacin as a model therapeutic agent. The fibers had linear cylindrical morphologies with clear core–shell structures, as demonstrated by electron microscopy. X-ray diffraction and differential scanning calorimetry proved that both indomethacin and Gd(DTPA) were present in the fibers in the amorphous physical form. This is thought to be a result of intermolecular interactions between the different components, the presence of which was suggested by infrared spectroscopy. In vitro dissolution tests indicated that the fibers could provide targeted release of the active ingredients through a combined mechanism of erosion and diffusion. The proton relaxivities for Gd(DTPA) released from the fibers into tris buffer increased (r1 = 4.79–9.75 s–1 mM–1; r2 = 7.98–14.22 s–1 mM–1) compared with fresh Gd(DTPA) (r1 = 4.13 s–1 mM–1 and r2 = 4.40 s–1 mM–1), which proved that electrospinning has not diminished the contrast properties of the complex. The new systems reported herein thus offer a new platform for delivering therapeutic and imaging agents simultaneously to the colon.

Acceleration and visualization of Dynamic Network Optimization

With the emerging prevalence of smart phones and 4G LTE networks, the demand for faster-better-cheaper mobile services anytime and anywhere is ever growing. The Dynamic Network Optimization (DNO) concept emerged as a solution that optimally and continuously tunes the network settings, in response to varying network conditions and subscriber needs. Yet, the DNO realization is still at infancy, largely hindered by the bottleneck of the lengthy optimization runtime. This paper presents the design and prototype of a novel cloud based parallel solution that further enhances the scalability of our prior work on various parallel solutions that accelerate network optimization algorithms. The solution aims to satisfy the high performance required by DNO, preliminarily on a sub-hourly basis. The paper subsequently visualizes a design and a full cycle of a DNO system. A set of potential solutions to large network and real-time DNO are also proposed. Overall, this work creates a breakthrough towards the realization of DNO.

Evaluating laser-driven Bremsstrahlung radiation sources for imaging and analysis of nuclear waste packages

A small scale sample nuclear waste package, consisting of a 28 mm diameter uranium penny encased in grout, was imaged by absorption contrast radiography using a single pulse exposure from an X-ray source driven by a high-power laser. The Vulcan laser was used to deliver a focused pulse of photons to a tantalum foil, in order to generate a bright burst of highly penetrating X-rays (with energy >500 keV), with a source size of <0.5 mm. BAS-TR and BAS-SR image plates were used for image capture, alongside a newly developed Thalium doped Caesium Iodide scintillator-based detector coupled to CCD chips. The uranium penny was clearly resolved to sub-mm accuracy over a 30 cm2 scan area from a single shot acquisition. In addition, neutron generation was demonstrated in situ with the X-ray beam, with a single shot, thus demonstrating the potential for multi-modal criticality testing of waste materials. This feasibility study successfully demonstrated non-destructive radiography of encapsulated, high density, nuclear material. With recent developments of high-power laser systems, to 10 Hz operation, a laser-driven multi-modal beamline for waste monitoring applications is envisioned.

Statistical modelling of the rheological and mucoadhesive properties of aqueous poly(methylvinylether-co-maleic acid) networks: Redefining biomedical applications and the relationship between viscoelasticity and mucoadhesion

Poly(methylvinylether-co-maleic acid) (PMVE/MA) is commonly used as a component of pharmaceutical platforms, principally to enhance interactions with biological substrates (mucoadhesion). However, the limited knowledge on the rheological properties of this polymer and their relationships with mucoadhesion has negated the biomedical use of this polymer as a mono-component platform. This study presents a comprehensive study of the rheological properties of aqueous PMVE/MA platforms and defines their relationships with mucoadhesion using multiple regression analysis. Using dilute solution viscometry the intrinsic viscosities of un-neutralised PMVE/MA and PMVE/MA neutralised using NaOH or TEA were 22.32 ± 0.89 dL g-1, 274.80 ± 1.94 dL g-1 and 416.49 ± 2.21 dL g-1 illustrating greater polymer chain expansion following neutralisation using Triethylamine (TEA). PMVE/MA platforms exhibited shear-thinning properties. Increasing polymer concentration increased the consistencies, zero shear rate (ZSR) viscosities (determined from flow rheometry), storage and loss moduli, dynamic viscosities (defined using oscillatory analysis) and mucoadhesive properties, yet decreased the loss tangents of the neutralised polymer platforms. TEA neutralised systems possessed significantly and substantially greater consistencies, ZSR and dynamic viscosities, storage and loss moduli, mucoadhesion and lower loss tangents than their NaOH counterparts. Multiple regression analysis enabled identification of the dominant role of polymer viscoelasticity on mucoadhesion (r > 0.98). The mucoadhesive properties of PMVE/MA platforms were considerable and were greater than those of other platforms that have successfully been shown to enhance in vivo retention when applied to the oral cavity, indicating a positive role for PMVE/MA mono-component platforms for pharmaceutical and biomedical applications.

Aged embankment imaging and assessment using surface waves

Rapid, non-intrusive surface wave surveys provide depth profiles from which ground models can be generated for use in earthwork condition assessment. Stiffness throughout earthworks controls the behaviour under static and dynamic loads, and characterising heterogeneity is of interest in relation to the stability of engineered backfill and life-cycle deterioration in aged utility and transportation infrastructure. Continuous surface wave methods were used to identify interfaces between fine- and coarse-grained fill in an end-tipped embankment along the Great Central Railway in Nottinghamshire, UK. Multichannel analysis of surface wave (MASW) methods were used to characterise subsurface voiding in a canal embankment along the Knottingley and Goole canal near Eggborough, Yorkshire. MASW methods are currently being used to study extreme weather impacts on the stability of a highplasticity clay embankment along the Gloucestershire–Warwickshire railway near Laverton. Optimal results were obtained using equipment capable of generating and detecting over wide frequency ranges.

Detector for imaging and dosimetry of laser-driven epithermal neutrons by alpha conversion

An epithermal neutron imager based on detecting alpha particles created via boron neutron capture mechanism is discussed. The diagnostic mainly consists of a mm thick Boron Nitride (BN) sheet (as an alpha converter) in contact with a non-borated cellulose nitride film (LR115 type-II) detector. While the BN absorbs the neutrons in the thermal and epithermal ranges, the fast neutrons register insignificantly on the detector due to their low neutron capture and recoil cross-sections. The use of solid-state nuclear track detectors (SSNTD), unlike image plates, micro-channel plates and scintillators, provide safeguard from the x-rays, gamma-rays and electrons. The diagnostic was tested on a proof-of-principle basis, in front of a laser driven source of moderated neutrons, which suggests the potential of using this diagnostic (BN+SSNTD) for dosimetry and imaging applications.

Cerebrotendinous xanthomatosis with bradyphrenia and psychiatric disorders: a case with 18F-FDG PET imaging and a literature review

Background and Objectives: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid-storage disease caused by mutations in the CYP27A1. The purpose of this study is to determine the clinical characteristics, neuroimaging and mutation detect in a family with CTX systematically. Methods: Collecting history materials and detecting the routine clinical biochemical tests and imaging examination, and for the first time taking the whole body positron emission tomography (PET)-CT examination for probed in the world to research abnormal metabolism activities in CTX. To observe the effect of treatment with chenodeoxycholic acid (CDCA) and stains before and after the intervention, using serum lipid level detection and neuropsychological evaluation. Genetic testing was carried out to screen the nine exons and exon-intron boundaries about 200-300bq of CYP27A1. Results: A 37-year-old woman with typical clinical characteristics of CTX. Magnetic resonance imaging (MRI) of brain showed bilateral lesions in the dentate nucleus of the cerebellum, then, PET images revealed multiple abnormal hypermetabolism areas at distal tendon, and multifocal areas of hypometabolism in bilateral sides of cerebellar hemispheres, the frontal lobe and temporal lobe. Histopathology reveals accumulation of xanthoma cells and dispersed lipid crystal clefts in xanthomas. In genetic analysis, it shown an insertion of cytosine (77-78insC) located in the first exon of CYP27A1 in the proband. Conclusions: We found that a Chinese patient presented a typical clinical feature of CTX along with clear correlation on both structural and functional imaging had a novel mutation in the CYP27A1 gene.

IVIS: Search and visualization on heterogeneous information networks

We build a system to support search and visualization on heterogeneous information networks. We first build our system on a specialized heterogeneous information network: DBLP. The system aims to facilitate people, especially computer science researchers, toward a better understanding and user experience about academic information networks. Then we extend our system to the Web. Our results are much more intuitive and knowledgeable than the simple top-k blue links from traditional search engines, and bring more meaningful structural results with correlated entities. We also investigate the ranking algorithm, and we show that the personalized PageRank and proposed Hetero-personalized PageRank outperform the TF-IDF ranking or mixture of TF-IDF and authority ranking. Our work opens several directions for future research.

A new technique to automatically quantify microstructures of fine grained carbonate mylonites: two-step etching combined with SEM imaging and image analysis

A two-step etching technique for fine-grained calcite mylonites using 0.37% hydrochloric and 0.1% acetic acid produces a topographic relief which reflects the grain boundary geometry. With this technique, calcite grain boundaries become more intensely dissolved than their grain interiors but second phase minerals like dolomite, quartz, feldspars, apatite, hematite and pyrite are not affected by the acid and therefore form topographic peaks. Based on digital backscatter electron images and element distribution maps acquired on a scanning electron microscope, the geometry of calcite and the second phase minerals can be automatically quantified using image analysis software. For research on fine-grained carbonate rocks (e.g. dolomite calcite mixtures), this low-cost approach is an attractive alternative to the generation of manual grain boundary maps based on photographs from ultra-thin sections or orientation contrast images.

Preoperative assessment of deep myometrial and cervical invasion in endometrial carcinoma: comparison of magnetic resonance imaging and histopathologic evaluation

This study aimed to evaluate the accuracy of magnetic resonance imaging (MRI) in the detection of deep myometrial invasion and cervical extension by endometrial carcinoma. This prospective study included 101 patients with histologically documented endometrial carcinoma, between July 1998 and April 2004. The findings of preoperative pelvic MRI were compared with histological diagnosis. From 101 cases studied by pelvic MRI, 43 were classified as deep myometrial invasion (50% of myometrium), where the pathological evaluation confirmed as having deep myometrial invasion. Cervical extension in the MRI study was found in 19 cases. Pathologic study found cervical extension and/or invasion in 31 cases including all cases identified by MRI. The accuracy, sensitivity and specificity of MRI were 95%, 89%, 100%, detecting deep myometrial invasion and 88%, 61%, 100%, detecting cervical invasion, respectively. The high accuracy achieved makes MRI an adequate method for determine the depth of myometrial and cervical invasion in endometrial carcinoma.

Probabilistic Imaging and Dynamic Modeling of Earthquake Source Processes

Investigation of large, destructive earthquakes is challenged by their infrequent occurrence and the remote nature of geophysical observations. This thesis sheds light on the source processes of large earthquakes from two perspectives: robust and quantitative observational constraints through Bayesian inference for earthquake source models, and physical insights on the interconnections of seismic and aseismic fault behavior from elastodynamic modeling of earthquake ruptures and aseismic processes.

To constrain the shallow deformation during megathrust events, we develop semi-analytical and numerical Bayesian approaches to explore the maximum resolution of the tsunami data, with a focus on incorporating the uncertainty in the forward modeling. These methodologies are then applied to invert for the coseismic seafloor displacement field in the 2011 Mw 9.0 Tohoku-Oki earthquake using near-field tsunami waveforms and for the coseismic fault slip models in the 2010 Mw 8.8 Maule earthquake with complementary tsunami and geodetic observations. From posterior estimates of model parameters and their uncertainties, we are able to quantitatively constrain the near-trench profiles of seafloor displacement and fault slip. Similar characteristic patterns emerge during both events, featuring the peak of uplift near the edge of the accretionary wedge with a decay toward the trench axis, with implications for fault failure and tsunamigenic mechanisms of megathrust earthquakes.

To understand the behavior of earthquakes at the base of the seismogenic zone on continental strike-slip faults, we simulate the interactions of dynamic earthquake rupture, aseismic slip, and heterogeneity in rate-and-state fault models coupled with shear heating. Our study explains the long-standing enigma of seismic quiescence on major fault segments known to have hosted large earthquakes by deeper penetration of large earthquakes below the seismogenic zone, where mature faults have well-localized creeping extensions. This conclusion is supported by the simulated relationship between seismicity and large earthquakes as well as by observations from recent large events. We also use the modeling to connect the geodetic observables of fault locking with the behavior of seismicity in numerical models, investigating how a combination of interseismic geodetic and seismological estimates could constrain the locked-creeping transition of faults and potentially their co- and post-seismic behavior.

Geospatial Data Indexing Analysis and Visualization via Web Services with Autonomic Resource Management

With the exponential growth of the usage of web-based map services, the web GIS application has become more and more popular. Spatial data index, search, analysis, visualization and the resource management of such services are becoming increasingly important to deliver user-desired Quality of Service. First, spatial indexing is typically time-consuming and is not available to end-users. To address this, we introduce TerraFly sksOpen, an open-sourced an Online Indexing and Querying System for Big Geospatial Data. Integrated with the TerraFly Geospatial database [1-9], sksOpen is an efficient indexing and query engine for processing Top-k Spatial Boolean Queries. Further, we provide ergonomic visualization of query results on interactive maps to facilitate the user’s data analysis. Second, due to the highly complex and dynamic nature of GIS systems, it is quite challenging for the end users to quickly understand and analyze the spatial data, and to efficiently share their own data and analysis results with others. Built on the TerraFly Geo spatial database, TerraFly GeoCloud is an extra layer running upon the TerraFly map and can efficiently support many different visualization functions and spatial data analysis models. Furthermore, users can create unique URLs to visualize and share the analysis results. TerraFly GeoCloud also enables the MapQL technology to customize map visualization using SQL-like statements [10]. Third, map systems often serve dynamic web workloads and involve multiple CPU and I/O intensive tiers, which make it challenging to meet the response time targets of map requests while using the resources efficiently. Virtualization facilitates the deployment of web map services and improves their resource utilization through encapsulation and consolidation. Autonomic resource management allows resources to be automatically provisioned to a map service and its internal tiers on demand. v-TerraFly are techniques to predict the demand of map workloads online and optimize resource allocations, considering both response time and data freshness as the QoS target. The proposed v-TerraFly system is prototyped on TerraFly, a production web map service, and evaluated using real TerraFly workloads. The results show that v-TerraFly can accurately predict the workload demands: 18.91% more accurate; and efficiently allocate resources to meet the QoS target: improves the QoS by 26.19% and saves resource usages by 20.83% compared to traditional peak load-based resource allocation.