Chromatin modifications involved in the DNA damage response to double strand breaks

In eukaryotes, genomic DNA is tightly compacted into a protein-DNA complex known as chromatin. This dense structure presents a barrier to DNA-dependent processes including transcription, replication and DNA repair. The repressive structure of chromatin is overcome by ATP-dependent chromatin remodelling complexes and chromatin-modifying enzymes. There is now ample evidence that DNA double-strand breaks (DSBs) elicit various histone modifications (such as acetylation, deacetylation, and phosphorylation) that function combinatorially to control the dynamic structure of the chromatin microenvironment. The role of these mechanisms during transcription and replication has been well studied, while the research into their impact on regulation of DNA damage response is rapidly gaining momentum. How chromatin structure is remodeled in response to DNA damage and how such alterations influence DSB repair are currently significant questions. This review will summarise the major chromatin modifications and chromatin remodelling complexes implicated in the DNA damage response to DSBs.

Static and dynamic performance of lightweight hybrid composite floor plate system

In the modern built environment, building construction and demolition consume a large amount of energy and emits greenhouse gasses due to widely used conventional construction materials such as reinforced and composite concrete. These materials consume high amount of natural resources and possess high embodied energy. More energy is required to recycle or reuse such materials at the cessation of use. Therefore, it is very important to use recyclable or reusable new materials in building construction in order to conserve natural resources and reduce the energy and emissions associated with conventional materials. Advancements in materials technology have resulted in the introduction of new composite and hybrid materials in infrastructure construction as alternatives to the conventional materials. This research project has developed a lightweight and prefabricatable Hybrid Composite Floor Plate System (HCFPS) as an alternative to conventional floor system, with desirable properties, easy to construct, economical, demountable, recyclable and reusable. Component materials of HCFPS include a central Polyurethane (PU) core, outer layers of Glass-fiber Reinforced Cement (GRC) and steel laminates at tensile regions. This research work explored the structural adequacy and performance characteristics of hybridised GRC, PU and steel laminate for the development of HCFPS. Performance characteristics of HCFPS were investigated using Finite Element (FE) method simulations supported by experimental testing. Parametric studies were conducted to develop the HCFPS to satisfy static performance using sectional configurations, spans, loading and material properties as the parameters. Dynamic response of HCFPS floors was investigated by conducting parametric studies using material properties, walking frequency and damping as the parameters. Research findings show that HCFPS can be used in office and residential buildings to provide acceptable static and dynamic performance. Design guidelines were developed for this new floor system. HCFPS is easy to construct and economical compared to conventional floor systems as it is lightweight and prefabricatable floor system. This floor system can also be demounted and reused or recycled at the cessation of use due to its component materials.

A hybrid association rule mining approach for characterizing network traffic behaviour

Understanding network traffic behaviour is crucial for managing and securing computer networks. One important technique is to mine frequent patterns or association rules from analysed traffic data. On the one hand, association rule mining usually generates a huge number of patterns and rules, many of them meaningless or user-unwanted; on the other hand, association rule mining can miss some necessary knowledge if it does not consider the hierarchy relationships in the network traffic data. Aiming to address such issues, this paper proposes a hybrid association rule mining method for characterizing network traffic behaviour. Rather than frequent patterns, the proposed method generates non-similar closed frequent patterns from network traffic data, which can significantly reduce the number of patterns. This method also proposes to derive new attributes from the original data to discover novel knowledge according to hierarchy relationships in network traffic data and user interests. Experiments performed on real network traffic data show that the proposed method is promising and can be used in real applications. Copyright2013 John Wiley & Sons, Ltd.

Design, modelling and measurement of hybrid powerplant for unmanned aerial vehicles (UAVs)

The success or effectiveness for any aircraft design is a function of many trade-offs. Over the last 100 years of aircraft design these trade-offs have been optimized and dominant aircraft design philosophies have emerged. Pilotless aircraft (or uninhabited airborne systems, UAS) present new challenges in the optimization of their configuration. Recent developments in battery and motor technology have seen an upsurge in the utility and performance of electric powered aircraft. Thus, the opportunity to explore hybrid-electric aircraft powerplant configurations is compelling. This thesis considers the design of such a configuration from an overall propulsive, and energy efficiency perspective. A prototype system was constructed using a representative small UAS internal combustion engine (10cc methanol two-stroke) and a 600W brushless Direct current (BLDC) motor. These components were chosen to be representative of those that would be found on typical small UAS. The system was tested on a dynamometer in a wind-tunnel and the results show an improvement in overall propulsive efficiency of 17% when compared to a non-hybrid powerplant. In this case, the improvement results from the utilization of a larger propeller that the hybrid solution allows, which shows that general efficiency improvements are possible using hybrid configurations for aircraft propulsion. Additionally this approach provides new improvements in operational and mission flexibility (such as the provision of self-starting) which are outlined in the thesis. Specifically, the opportunity to use the windmilling propeller for energy regeneration was explored. It was found (in the prototype configuration) that significant power (60W) is recoverable in a steep dive, and although the efficiency of regeneration is low, the capability can allow several options for improved mission viability. The thesis concludes with the general statement that a hybrid powerplant improves the overall mission effectiveness and propulsive efficiency of small UAS.

A hybrid genetic algorithm for the minimum interconnection cut problem

In the real world there are many problems in network of networks (NoNs) that can be abstracted to a so-called minimum interconnection cut problem, which is fundamentally different from those classical minimum cut problems in graph theory. Thus, it is desirable to propose an efficient and effective algorithm for the minimum interconnection cut problem. In this paper we formulate the problem in graph theory, transform it into a multi-objective and multi-constraint combinatorial optimization problem, and propose a hybrid genetic algorithm (HGA) for the problem. The HGA is a penalty-based genetic algorithm (GA) that incorporates an effective heuristic procedure to locally optimize the individuals in the population of the GA. The HGA has been implemented and evaluated by experiments. Experimental results have shown that the HGA is effective and efficient.

Hybrid placemaking in the library : designing digital technology to enhance users’ on-site experience

This paper presents research findings and design strategies that illustrate how digital technology can be applied as a tool for hybrid placemaking in ways that would not be possible in purely digital or physical space. Digital technology has revolutionised the way people learn and gather new information. This trend has challenged the role of the library as a physical place, as well as the interplay of digital and physical aspects of the library. The paper provides an overview of how the penetration of digital technology into everyday life has affected the library as a place, both as designed by place makers, and, as perceived by library users. It then identifies a gap in current library research about the use of digital technology as a tool for placemaking, and reports results from a study of Gelatine – a custom built user check-in system that displays real-time user information on a set of public screens. Gelatine and its evaluation at The Edge, at State Library of Queensland illustrates how combining affordances of social, spatial and digital space can improve the connected learning experience among on-site visitors. Future design strategies involving gamifying the user experience in libraries are described based on Gelatine’s infrastructure. The presented design ideas and concepts are relevant for managers and designers of libraries as well as other informal, social learning environments.

Hybrid place : blurring the edge between the digital and physical layers of urban environments

The purpose of this paper is to investigate the edge condition between the digital layers and the physical layers of the city and how tangible expressions of the interrelationships between them to create and define new experiences of place, creating hybrid place. To date there has been discussion and investigation into understanding the importance of place, similarly into defining hybrid space. This paper explores principles of place and space to question how they can be applied into defining and proposing the notion of hybrid place in urban environments. The integration of media spaces into architecture provide infrastructure for the development of hybrid place. The physical boundaries of urban spaces become blurred through the integration of media such as computer technologies connecting the physical environment with the digital. Literature and case studies that reflect the current trends of use of technology by people in space and place within urban environments are examined.

Comparison of genomic DNA extraction techniques from whole blood samples : a time, cost and quality evaluation study

Genomic DNA obtained from patient whole blood samples is a key element for genomic research. Advantages and disadvantages, in terms of time-efficiency, cost-effectiveness and laboratory requirements, of procedures available to isolate nucleic acids need to be considered before choosing any particular method. These characteristics have not been fully evaluated for some laboratory techniques, such as the salting out method for DNA extraction, which has been excluded from comparison in different studies published to date. We compared three different protocols (a traditional salting out method, a modified salting out method and a commercially available kit method) to determine the most cost-effective and time-efficient method to extract DNA. We extracted genomic DNA from whole blood samples obtained from breast cancer patient volunteers and compared the results of the product obtained in terms of quantity (concentration of DNA extracted and DNA obtained per ml of blood used) and quality (260/280 ratio and polymerase chain reaction product amplification) of the obtained yield. On average, all three methods showed no statistically significant differences between the final result, but when we accounted for time and cost derived for each method, they showed very significant differences. The modified salting out method resulted in a seven- and twofold reduction in cost compared to the commercial kit and traditional salting out method, respectively and reduced time from 3 days to 1 hour compared to the traditional salting out method. This highlights a modified salting out method as a suitable choice to be used in laboratories and research centres, particularly when dealing with a large number of samples.

A genetic analysis of serotonergic biosynthetic and metabolic enzymes in migraine using a DNA pooling approach

Migraine is a common debilitating primary headache disorder with significant mental, physical and social health implications. The brain neurotransmitter 5-hydroxytryptamine (5-HT; serotonin) is involved in nociceptive pathways and has been implicated in the pathophysiology of migraine. With few genetic studies investigating biosynthetic and metabolic enzymes governing the rate of 5-HT activity and their relationship to migraine, it was the objective of this study to assess genetic variants within the human tryptophan hydroxylase (TPH), amino acid decarboxylase (AADC) and monoamine oxidase A (MAOA) genes in migraine susceptibility. This objective was undertaken using a high-throughput DNA pooling experimental design, which proved to be a very accurate, sensitive and specific method of estimating allele frequencies for single nucleotide polymorphism, insertion deletion and variable number tandem repeat loci. Application of DNA pooling to a wide array of genetic loci provides greater scope in the assessment of population-based genetic association study designs. Despite the application of this high-throughput genotyping method, negative results from the two-stage DNA pooling design used to screen loci within the TPH, AADC and MAOA genes did not support their role in migraine susceptibility.

Molecular cytogenetic analysis of basal cell carcinoma DNA using comparative genomic hybridization

In an attempt to define genomic copy number changes associated with the development of basal cell carcinoma, we investigated 15 sporadic tumors by comparative genomic hybridization. With the incorporation of tissue microdissection and degenerate oligonucleotide primed-polymerase chain reaction we were able to isolate, and then universally amplify, DNA from the tumor type. This combined approach allows the investigation of chromosomal imbalances within a histologically distinct region of tissue. Using comparative genomic hybridization we have observed novel and recurrent chromosomal gains at 6p (47%), 6q (20%), 9p (20%), 7 (13%), and X (13%). In addition comparative genomic hybridization revealed regional loss on 9q in 33% of tested tumors encompassing 9q22.3 to which the putative tumor suppressor gene, Patched, has been mapped. The deletion of Patched has been indicated in the development of hereditary and sporadic basal cell carcinomas. The identification of these recurrent genetic aberrations suggests that basal cell carcinomas may not be as genetically stable as previously thought. Further investigation of these regions may lead to the identification of other genes responsible for basal cell carcinoma formation.

The embodied hybrid space : designing social and digital interventions to facilitate connected learning in coworking spaces

This thesis developed and evaluated strategies for social and ubiquitous computing designs that can enhance connected learning and networking opportunities for users in coworking spaces. Based on a social and a technical design intervention deployed at the State Library of Queensland, the research findings illustrate the potential of combining social, spatial and digital affordances in order to nourish peer-to-peer learning, creativity, inspiration, and innovation. The study proposes a hybrid notion of placemaking as a new way of thinking about the design of coworking and interactive learning spaces.

Regional chromosomal assignment of human renin gene to 1q12→qter and use in linkage studies in Charcot-Marie-Tooth disease

The gene for renin, previously mapped to human chromosome 1, was further localized to 1q12 → qter using human-mouse somatic cell hybrid DNAs. The renin DNA probe used (λ HR5) could detect a HindIII restriction fragment length polymorphism. When used in studies of 12 informative families, no linkage could be found between the renin and Charcot-Marie-Tooth disease. Furthermore, an association of any renin allele with hypertension was not apparent.

Isolation and use of chromosome 1 probes for linkage studies on Charcot-Marie-Tooth disease

Nine probes were isolated from a human chromosome 1 enriched library and mapped to regions of chromosome 1 using somatic cell hybrid lines. One clone, LR67, which mapped 1q12→q23 detected a BglI RFLP. This probe, as well as 4 other known chromosome 1 markers, α-spectrin, Factor XIIIB, DR10 and DR78, were used for linkage studies in 15 Charcot-Marie-Tooth disease (CMT1) families. Close linking of CMT1 to any of the 5 markers was not indicated. Total lod scores excluded linkage of CMT1 to LR67 and to DR10 at 5 cM or less, to DR78 and 10 cM or less, α-spectrin at 15 cM or less and Factor XIIIB at 20 cM or less. Possible linkage, however, was shown between LR67 and CMT1 at a distance of 30 cM. Also linkage at a distance of 5 cM was detected between this probe and α-spectrin.