Human preadipocyte proliferation and differentiation

Obesity represents a major health, social and economic burden to many developing and Westernized communities, with the prevalence increasing at a rate exceeding almost all other medical conditions. Despite major recent advances in our understanding of adipose tissue metabolism and dynamics, we still have limited insight into the regulation of adipose tissue mass in humans. Any significant increase in adipose tissue mass requires proliferation and differentiation of precursor cells (preadipocytes) present in the stromo-vascular compartment of adipose tissue. These processes are very complex and an increasing number of growth factors and hormones have been shown to modulate the expression of genes involved in preadipocyte proliferation and differentiation. A number of transcription factors, including the C/EBP family and PP ARy, have been identified as integral to adipose tissue development and preadipocyte differentiation. Together PP ARy and C/EBPa regulate important events in the activation and maintenance of the terminally differentiated phenotype. The ability of PP ARy to increase transcription through its DNA recognition site is dependent on the binding of ligands. This suggests that an endogenous PP ARy ligand may be an important regulator of adipogenesis. Adipose tissue functions as both the major site of energy storage in the body and as an endocrine organ synthesizing and secreting a number of important molecules involved in regulation of energy balance. For optimum functioning therefore, adipose tissue requires extensive vascularization and previous studies have shown that growth of adipose tissue is preceded by development of a microvascular network. This suggests that paracrine interactions between constituent cells in adipose tissue may be involved in both new capillary formation and fat cell growth. To address this hypothesis the work in this project was aimed at (a) further development of a method for inducing preadipocyte differentiation in subcultured human cells; (b) establishing a method for simultaneous isolation and separate culture of both preadipocytes and microvascular endothelial cells from the same adipose tissue biopsies; (c) to determine, using conditioned medium and co-culture techniques, if endothelial cell-derived factors influence the proliferation and/or differentiation of human preadipocytes; and (d) commence characterization of factors that may be responsible for any observed paracrine effects on aspects of human adipogenesis. Major findings of these studies were as follows: (A) Inclusion of either linoleic acid (a long-chain fatty acid reported to be a naturally occurring ligand for PP ARy) or Rosiglitazone (a member of the thiazolidinedione class of insulin-sensitizing drugs and a synthetic PPARy ligand) in differentiation medium had markedly different effects on preadipocyte differentiation. These studies showed that human preadipocytes have the potential to accumulate triacylglycerol irrespective of their stage of biochemical differentiation, and that thiazolidinediones and fatty acids may exert their adipogenic and lipogenic effects via different biochemical pathways. It was concluded that Rosiglitazone is a more potent inducer of human preadipocyte differentiation than linoleic acid. (B) A method for isolation and culture of both endothelial cells and preadipocytes from the same adipose tissue biopsy was developed. Adipose-derived microvascular endothelial cells were found to produce factor/s, which enhance both proliferation and differentiation of human preadipocytes. (C) The adipogenic effects of microvascular endothelial cells can be mimicked by exposure of preadipocytes to members of the Fibroblast Growth Factor family, specifically ~-ECGF and FGF-1. (D) Co-culture of human preadipocytes with endothelial cells or exposure of preadipocytes to either ~-ECGF or FGF-1 were found to 'prime' human preadipocytes, during their proliferative phase of growth, for thiazolidinedione-induced differentiation. (E) FGF -1 was not found to be acting as a ligand for PP ARy in this system. Findings from this project represent a significant step forward in our understanding of factors involved in growth of human adipose tissue and may lead to the development of therapeutic strategies aimed at modifying the process. Such strategies would have potential clinical utility in the treatment of obesity and obesity related disorders such as Type II Diabetes.

Translation of addictions science into practice

Recent advances in the understanding of the genetic, neurochemical, behavioral and cultural underpinnings of addiction have led to rapid advances in the understanding of addiction as a disease. In fact, advances in basic science and the development of new pharmacological and behavioral therapies associated with them are appearing faster than can be assimilated not only by clinical researchers but practitioners and policy makers as well. Translation of science-based addictions knowledge into improved prevention, assessment and treatment, and communication of these changes to researchers and practitioners are significant challenges to the field. The general aim of this book is to summarize current and potential linkages between advances in addiction science and innovations in clinical practice. Whilst this book is primarily focused on translation, it also encompasses some scientific advances that are relevant to dissemination, and the book is itself a tool for disseminating innovative thinking. The goal is to generate interest in application opportunities from both recent research and theoretical advances.

Secure tracking for critical applications : communications, GPS and future Galileo services

Tracking/remote monitoring systems using GNSS are a proven method to enhance the safety and security of personnel and vehicles carrying precious or hazardous cargo. While GNSS tracking appears to mitigate some of these threats, if not adequately secured, it can be a double-edged sword allowing adversaries to obtain sensitive shipment and vehicle position data to better coordinate their attacks, and to provide a false sense of security to monitoring centers. Tracking systems must be designed with the ability to perform route-compliance and thwart attacks ranging from low-level attacks such as the cutting of antenna cables to medium and high-level attacks involving radio jamming and signal / data-level simulation, especially where the goods transported have a potentially high value to terrorists. This paper discusses the use of GNSS in critical tracking applications, addressing the mitigation of GNSS security issues, augmentation systems and communication systems in order to provide highly robust and survivable tracking systems.

Wavelet based approaches and high resolution methods for complex process models

Many industrial processes and systems can be modelled mathematically by a set of Partial Differential Equations (PDEs). Finding a solution to such a PDF model is essential for system design, simulation, and process control purpose. However, major difficulties appear when solving PDEs with singularity. Traditional numerical methods, such as finite difference, finite element, and polynomial based orthogonal collocation, not only have limitations to fully capture the process dynamics but also demand enormous computation power due to the large number of elements or mesh points for accommodation of sharp variations. To tackle this challenging problem, wavelet based approaches and high resolution methods have been recently developed with successful applications to a fixedbed adsorption column model. Our investigation has shown that recent advances in wavelet based approaches and high resolution methods have the potential to be adopted for solving more complicated dynamic system models. This chapter will highlight the successful applications of these new methods in solving complex models of simulated-moving-bed (SMB) chromatographic processes. A SMB process is a distributed parameter system and can be mathematically described by a set of partial/ordinary differential equations and algebraic equations. These equations are highly coupled; experience wave propagations with steep front, and require significant numerical effort to solve. To demonstrate the numerical computing power of the wavelet based approaches and high resolution methods, a single column chromatographic process modelled by a Transport-Dispersive-Equilibrium linear model is investigated first. Numerical solutions from the upwind-1 finite difference, wavelet-collocation, and high resolution methods are evaluated by quantitative comparisons with the analytical solution for a range of Peclet numbers. After that, the advantages of the wavelet based approaches and high resolution methods are further demonstrated through applications to a dynamic SMB model for an enantiomers separation process. This research has revealed that for a PDE system with a low Peclet number, all existing numerical methods work well, but the upwind finite difference method consumes the most time for the same degree of accuracy of the numerical solution. The high resolution method provides an accurate numerical solution for a PDE system with a medium Peclet number. The wavelet collocation method is capable of catching up steep changes in the solution, and thus can be used for solving PDE models with high singularity. For the complex SMB system models under consideration, both the wavelet based approaches and high resolution methods are good candidates in terms of computation demand and prediction accuracy on the steep front. The high resolution methods have shown better stability in achieving steady state in the specific case studied in this Chapter.

Optimization problems for controlled mechanical systems : bridging the gap between theory and application

Mechanical control systems have become a part of our everyday life. Systems such as automobiles, robot manipulators, mobile robots, satellites, buildings with active vibration controllers and air conditioning systems, make life easier and safer, as well as help us explore the world we live in and exploit it’s available resources. In this chapter, we examine a specific example of a mechanical control system; the Autonomous Underwater Vehicle (AUV). Our contribution to the advancement of AUV research is in the area of guidance and control. We present innovative techniques to design and implement control strategies that consider the optimization of time and/or energy consumption. Recent advances in robotics, control theory, portable energy sources and automation increase our ability to create more intelligent robots, and allows us to conduct more explorations by use of autonomous vehicles. This facilitates access to higher risk areas, longer time underwater, and more efficient exploration as compared to human occupied vehicles. The use of underwater vehicles is expanding in every area of ocean science. Such vehicles are used by oceanographers, archaeologists, geologists, ocean engineers, and many others. These vehicles are designed to be agile, versatile and robust, and thus, their usage has gone from novelty to necessity for any ocean expedition.

A geometric approach to trajectory design for an autonomous underwater vehicle : surveying the bulbous bow of a ship

In this paper, we present a control strategy design technique for an autonomous underwater vehicle based on solutions to the motion planning problem derived from differential geometric methods. The motion planning problem is motivated by the practical application of surveying the hull of a ship for implications of harbor and port security. In recent years, engineers and researchers have been collaborating on automating ship hull inspections by employing autonomous vehicles. Despite the progresses made, human intervention is still necessary at this stage. To increase the functionality of these autonomous systems, we focus on developing model-based control strategies for the survey missions around challenging regions, such as the bulbous bow region of a ship. Recent advances in differential geometry have given rise to the field of geometric control theory. This has proven to be an effective framework for control strategy design for mechanical systems, and has recently been extended to applications for underwater vehicles. Advantages of geometric control theory include the exploitation of symmetries and nonlinearities inherent to the system. Here, we examine the posed inspection problem from a path planning viewpoint, applying recently developed techniques from the field of differential geometric control theory to design the control strategies that steer the vehicle along the prescribed path. Three potential scenarios for surveying a ship?s bulbous bow region are motivated for path planning applications. For each scenario, we compute the control strategy and implement it onto a test-bed vehicle. Experimental results are analyzed and compared with theoretical predictions.

Semi-supervised intelligent surveillance system for secure environments

This paper proposes a semi-supervised intelligent visual surveillance system to exploit the information from multi-camera networks for the monitoring of people and vehicles. Modules are proposed to perform critical surveillance tasks including: the management and calibration of cameras within a multi-camera network; tracking of objects across multiple views; recognition of people utilising biometrics and in particular soft-biometrics; the monitoring of crowds; and activity recognition. Recent advances in these computer vision modules and capability gaps in surveillance technology are also highlighted.

Secure data aggregation in wireless sensor networks

A Wireless Sensor Network (WSN) is a set of sensors that are integrated with a physical environment. These sensors are small in size, and capable of sensing physical phenomena and processing them. They communicate in a multihop manner, due to a short radio range, to form an Ad Hoc network capable of reporting network activities to a data collection sink. Recent advances in WSNs have led to several new promising applications, including habitat monitoring, military target tracking, natural disaster relief, and health monitoring. The current version of sensor node, such as MICA2, uses a 16 bit, 8 MHz Texas Instruments MSP430 micro-controller with only 10 KB RAM, 128 KB program space, 512 KB external ash memory to store measurement data, and is powered by two AA batteries. Due to these unique specifications and a lack of tamper-resistant hardware, devising security protocols for WSNs is complex. Previous studies show that data transmission consumes much more energy than computation. Data aggregation can greatly help to reduce this consumption by eliminating redundant data. However, aggregators are under the threat of various types of attacks. Among them, node compromise is usually considered as one of the most challenging for the security of WSNs. In a node compromise attack, an adversary physically tampers with a node in order to extract the cryptographic secrets. This attack can be very harmful depending on the security architecture of the network. For example, when an aggregator node is compromised, it is easy for the adversary to change the aggregation result and inject false data into the WSN. The contributions of this thesis to the area of secure data aggregation are manifold. We firstly define the security for data aggregation in WSNs. In contrast with existing secure data aggregation definitions, the proposed definition covers the unique characteristics that WSNs have. Secondly, we analyze the relationship between security services and adversarial models considered in existing secure data aggregation in order to provide a general framework of required security services. Thirdly, we analyze existing cryptographic-based and reputationbased secure data aggregation schemes. This analysis covers security services provided by these schemes and their robustness against attacks. Fourthly, we propose a robust reputationbased secure data aggregation scheme for WSNs. This scheme minimizes the use of heavy cryptographic mechanisms. The security advantages provided by this scheme are realized by integrating aggregation functionalities with: (i) a reputation system, (ii) an estimation theory, and (iii) a change detection mechanism. We have shown that this addition helps defend against most of the security attacks discussed in this thesis, including the On-Off attack. Finally, we propose a secure key management scheme in order to distribute essential pairwise and group keys among the sensor nodes. The design idea of the proposed scheme is the combination between Lamport's reverse hash chain as well as the usual hash chain to provide both past and future key secrecy. The proposal avoids the delivery of the whole value of a new group key for group key update; instead only the half of the value is transmitted from the network manager to the sensor nodes. This way, the compromise of a pairwise key alone does not lead to the compromise of the group key. The new pairwise key in our scheme is determined by Diffie-Hellman based key agreement.

A forensic investigation of single human hair fibres using FTIR-ATR spectroscopy and chemometrics

Human hair fibres are ubiquitous in nature and are found frequently at crime scenes often as a result of exchange between the perpetrator, victim and/or the surroundings according to Locard's Principle. Therefore, hair fibre evidence can provide important information for crime investigation. For human hair evidence, the current forensic methods of analysis rely on comparisons of either hair morphology by microscopic examination or nuclear and mitochondrial DNA analyses. Unfortunately in some instances the utilisation of microscopy and DNA analyses are difficult and often not feasible. This dissertation is arguably the first comprehensive investigation aimed to compare, classify and identify the single human scalp hair fibres with the aid of FTIR-ATR spectroscopy in a forensic context. Spectra were collected from the hair of 66 subjects of Asian, Caucasian and African (i.e. African-type). The fibres ranged from untreated to variously mildly and heavily cosmetically treated hairs. The collected spectra reflected the physical and chemical nature of a hair from the near-surface particularly, the cuticle layer. In total, 550 spectra were acquired and processed to construct a relatively large database. To assist with the interpretation of the complex spectra from various types of human hair, Derivative Spectroscopy and Chemometric methods such as Principal Component Analysis (PCA), Fuzzy Clustering (FC) and Multi-Criteria Decision Making (MCDM) program; Preference Ranking Organisation Method for Enrichment Evaluation (PROMETHEE) and Geometrical Analysis for Interactive Aid (GAIA); were utilised. FTIR-ATR spectroscopy had two important advantages over to previous methods: (i) sample throughput and spectral collection were significantly improved (no physical flattening or microscope manipulations), and (ii) given the recent advances in FTIR-ATR instrument portability, there is real potential to transfer this work.s findings seamlessly to on-field applications. The "raw" spectra, spectral subtractions and second derivative spectra were compared to demonstrate the subtle differences in human hair. SEM images were used as corroborative evidence to demonstrate the surface topography of hair. It indicated that the condition of the cuticle surface could be of three types: untreated, mildly treated and treated hair. Extensive studies of potential spectral band regions responsible for matching and discrimination of various types of hair samples suggested the 1690-1500 cm^-1 IR spectral region was to be preferred in comparison with the commonly used 1750-800 cm^-1. The principal reason was the presence of the highly variable spectral profiles of cystine oxidation products (1200-1000 cm^-1), which contributed significantly to spectral scatter and hence, poor hair sample matching. In the preferred 1690-1500 cm^-1 region, conformational changes in the keratin protein attributed to the α-helical to β-sheet transitions in the Amide I and Amide II vibrations and played a significant role in matching and discrimination of the spectra and hence, the hair fibre samples. For gender comparison, the Amide II band is significant for differentiation. The results illustrated that the male hair spectra exhibit a more intense β-sheet vibration in the Amide II band at approximately 1511 cm^-1 whilst the female hair spectra displayed more intense α-helical vibration at 1520-1515cm^-1. In terms of chemical composition, female hair spectra exhibit greater intensity of the amino acid tryptophan (1554 cm^-1), aspartic and glutamic acid (1577 cm^-1). It was also observed that for the separation of samples based on racial differences, untreated Caucasian hair was discriminated from Asian hair as a result of having higher levels of the amino acid cystine and cysteic acid. However, when mildly or chemically treated, Asian and Caucasian hair fibres are similar, whereas African-type hair fibres are different. In terms of the investigation's novel contribution to the field of forensic science, it has allowed for the development of a novel, multifaceted, methodical protocol where previously none had existed. The protocol is a systematic method to rapidly investigate unknown or questioned single human hair FTIR-ATR spectra from different genders and racial origin, including fibres of different cosmetic treatments. Unknown or questioned spectra are first separated on the basis of chemical treatment i.e. untreated, mildly treated or chemically treated, genders, and racial origin i.e. Asian, Caucasian and African-type. The methodology has the potential to complement the current forensic analysis methods of fibre evidence (i.e. Microscopy and DNA), providing information on the morphological, genetic and structural levels.

Mesoporous bioactive glasses as drug delivery and bone tissue regeneration platforms

The use of mesoporous bioactive glasses (MBG) for drug delivery and bone tissue regeneration has grown significantly over the past 5 years. In this review, we highlight the recent advances made in the preparation of MBG particles, spheres, fibers and scaffolds. The advantages of MBG for drug delivery and bone scaffold applications are related to this material’s well-ordered mesopore channel structure, superior bioactivity, and the application for the delivery of both hydrophilic and hydrophobic drugs. A brief forward-looking perspective on the potential clinical applications of MBG in regenerative medicine is also discussed.

Epithelial—mesenchymal and mesenchymal—epithelial transitions in carcinoma progression

Like a set of bookends, cellular, molecular, and genetic changes of the beginnings of life mirror those of one of the most common cause of death—metastatic cancer. Epithelial to mesenchymal transition (EMT) is an important change in cell phenotype which allows the escape of epithelial cells from the structural constraints imposed by tissue architecture, and was first recognized by Elizabeth Hay in the early to mid 1980's to be a central process in early embryonic morphogenesis. Reversals of these changes, termed mesenchymal to epithelial transitions (METs), also occur and are important in tissue construction in normal development. Over the last decade, evidence has mounted for EMT as the means through which solid tissue epithelial cancers invade and metastasize. However, demonstrating this potentially rapid and transient process in vivo has proven difficult and data connecting the relevance of this process to tumor progression is still somewhat limited and controversial. Evidence for an important role of MET in the development of clinically overt metastases is starting to accumulate, and model systems have been developed. This review details recent advances in the knowledge of EMT as it occurs in breast development and carcinoma and prostate cancer progression, and highlights the role that MET plays in cancer metastasis. Finally, perspectives from a clinical and translational viewpoint are discussed

TOPSIG : Topology Preserving Document Signatures

Performance comparisons between File Signatures and Inverted Files for text retrieval have previously shown several significant shortcomings of file signatures relative to inverted files. The inverted file approach underpins most state-of-the-art search engine algorithms, such as Language and Probabilistic models. It has been widely accepted that traditional file signatures are inferior alternatives to inverted files. This paper describes TopSig, a new approach to the construction of file signatures. Many advances in semantic hashing and dimensionality reduction have been made in recent times, but these were not so far linked to general purpose, signature file based, search engines. This paper introduces a different signature file approach that builds upon and extends these recent advances. We are able to demonstrate significant improvements in the performance of signature file based indexing and retrieval, performance that is comparable to that of state of the art inverted file based systems, including Language models and BM25. These findings suggest that file signatures offer a viable alternative to inverted files in suitable settings and positions the file signatures model in the class of Vector Space retrieval models.

Possible genetic predisposition to lymphedema after breast cancer

Background: Known risk factors for secondary lymphedema only partially explain who develops lymphedema following cancer, suggesting that inherited genetic susceptibility may influence risk. Moreover, identification of molecular signatures could facilitate lymphedema risk prediction prior to surgery or lead to effective drug therapies for prevention or treatment. Recent advances in the molecular biology underlying development of the lymphatic system and related congenital disorders implicate a number of potential candidate genes to explore in relation to secondary lymphedema. Methods and Results: We undertook a nested case-control study, with participants who had developed lymphedema after surgical intervention within the first 18 months of their breast cancer diagnosis serving as cases (n=22) and those without lymphedema serving as controls (n=98), identified from a prospective, population-based, cohort study in Queensland, Australia. TagSNPs that covered all known genetic variation in the genes SOX18, VEGFC, VEGFD, VEGFR2, VEGFR3, RORC, FOXC2, LYVE1, ADM and PROX1 were selected for genotyping. Multiple SNPs within three receptor genes, VEGFR2, VEGFR3 and RORC, were associated with lymphedema defined by statistical significance (p<0.05) or extreme risk estimates (OR<0.5 or >2.0). Conclusions: These provocative, albeit preliminary, findings regarding possible genetic predisposition to secondary lymphedema following breast cancer treatment warrant further attention for potential replication using larger datasets.

Design and implementation of wideband baluns for Archimedean spiral antennas

The demand for high-speed data services for portable device has become a driving force for development of advanced broadband access technologies. Despite recent advances in broadband wireless technologies, there remain a number of critical issues to be resolved. One of the major concerns is the implementation of compact antennas that can operate in a wide frequency band. Spiral antenna has been used extensively for broadband applications due to its planar structure, wide bandwidth characteristics and circular polarisation. However, the practical implementation of spiral antennas is challenged by its high input characteristic impedance, relatively low gain and the need for balanced feeding structures. Further development of wideband balanced feeding structures for spiral antennas with matching impedance capabilities remain a need. This thesis proposes three wideband feeding systems for spiral antennas which are compatible with wideband array antenna geometries. First, a novel tapered geometry is proposed for a symmetric coplanar waveguide (CPW) to coplanar strip line (CPS) wideband balun. This balun can achieve the unbalanced to balanced transformation while matching the high input impedance of the antenna to a reference impedance of 50 . The discontinuity between CPW and CPS is accommodated by using a radial stub and bond wires. The bandwidth of the balun is improved by appropriately tapering the CPW line instead of using a stepped impedance transformer. Next, the tapered design is applied to an asymmetric CPW to propose a novel asymmetric CPW to CPS wideband balun. The use of asymmetric CPW does away with the discontinuities between CPW and CPS without having to use a radial stub or bond wires. Finally, a tapered microstrip line to parallel striplines balun is proposed. The balun consists of two sections. One section is the parallel striplines which are connected to the antenna, with the impedance of balanced line equal to the antenna input impedance. The other section consists of a microstrip line where the width of the ground plane is gradually reduced to eventually resemble a parallel stripline. The taper accomplishes the mode and impedance transformation. This balun has significantly improved bandwidth characteristics. Characteristics of proposed feeding structures are measured in a back-to-back configuration and compared to simulated results. The simulated and measured results show the tapered microstrip to parallel striplines balun to have more than three octaves of bandwidth. The tapered microstrip line to parallel striplines balun is integrated with a single Archimedean spiral antenna and with an array of spiral antennas. The performance of the integrated structures is simulated with the aid of electromagnetic simulation software, and results are compared to measurements. The back-to-back microstrip to parallel strip balun has a return loss of better than 10 dB over a wide bandwidth from 1.75 to 15 GHz. The performance of the microstrip to parallel strip balun was validated with the spiral antennas. The results show the balun to be an effective mean of feeding network with a low profile and wide bandwidth (2.5 to 15 GHz) for balanced spiral antennas.

The perceived importance of mall retail categories and its effect on likelihood of purchase during a recession

Recessions impact the retail sector and as such research into consumer decision making during such times is imperative. In response to this, our study takes an innovative approach to examining how the perceived importance of retail store categories in a shopping mall influences the relationship between consumers' shopping attitudes and likelihood of purchasing in those categories during a recession. The overall findings show the importance of a product category to a consumer, which is often overlooked, has a strong explanatory influence on consumer purchase intentions for that specific retail store categories in a shopping mall under recession conditions. Findings also show that for consumers’ who have altered their shopping behaviour the perceived importance of a retail store category fully mediates the relationship for: Majors, Leisure, Food Catered and Mini Majors categories, and partial mediation for Apparel. Importance has no mediating effect for: Food Retail, General Retail, Mobile Phone Services, Home wares, and Retail Services. Our study makes a key contribution to the retail management literature with the findings suggesting that redefining and articulating the importance of the value offering for specific retail store categories can help reduce the impact of changes in consumers' recessionary shopping intentions across the mall tenant mix. Such actions can then help preserve the image of the shopping mall in the minds of the consumers when the economic recovery begins.