Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis

Systems-level identification and analysis of cellular circuits in the brain will require the development of whole-brain imaging with single-cell resolution. To this end, we performed comprehensive chemical screening to develop a whole-brain clearing and imaging method, termed CUBIC (clear, unobstructed brain imaging cocktails and computational analysis). CUBIC is a simple and efficient method involving the immersion of brain samples in chemical mixtures containing aminoalcohols, which enables rapid whole-brain imaging with single-photon excitation microscopy. CUBIC is applicable to multicolor imaging of fluorescent proteins or immunostained samples in adult brains and is scalable from a primate brain to subcellular structures. We also developed a whole-brain cell-nuclear counterstaining protocol and a computational image analysis pipeline that, together with CUBIC reagents, enable the visualization and quantification of neural activities induced by environmental stimulation. CUBIC enables time-course expression profiling of whole adult brains with single-cell resolution.

A framework for identification of similarities between multiple algorithms

This thesis in software engineering presents a novel automated framework to identify similar operations utilized by multiple algorithms for solving related computing problems. It provides a new effective solution to perform multi-application based algorithm analysis, employing fundamentally light-weight static analysis techniques compared to the state-of-art approaches. Significant performance improvements are achieved across the objective algorithms through enhancing the efficiency of the identified similar operations, targeting discrete application domains.

The O-specific polysaccharide structure and gene cluster of serotype O:12 of the Yersinia pseudotuberculosis complex, and the identification of a novel L-quinovose biosynthesis gene

A major virulence factor for Yersinia pseudotuberculosis is lipopolysaccharide, including O-polysaccharide (OPS). Currently, the OPS based serotyping scheme for Y. pseudotuberculosis includes 21 known O-serotypes, with genetic and structural data available for 17 of them. The completion of the OPS structures and genetics of this species will enable the visualization of relationships between O-serotypes and allow for analysis of the evolutionary processes within the species that give rise to new serotypes. Here we present the OPS structure and gene cluster of serotype O:12, thus adding one more to the set of completed serotypes, and show that this serotype is present in both Y. pseudotuberculosis and the newly identified Y. similis species. The O:12 structure is shown to include two rare sugars: 4-C[(R)-1-hydroxyethyl]-3,6-dideoxy-d-xylo-hexose (d-yersiniose) and 6-deoxy-l-glucopyranose (l-quinovose). We have identified a novel putative guanine diphosphate (GDP)-l-fucose 4-epimerase gene and propose a pathway for the synthesis of GDP-l-quinovose, which extends the known GDP-l-fucose pathway.

Improving the identification of fatigue-related crashes in the Australian Capital Territory

It has been well established nationally and internationally that fatigue-related driving is an important contributory factor in fatal and serious injury crashes. The purpose of this report was to survey a large, representative sample of residents living in both the NSW and ACT to ask about their experience of fatigue and their involvement in fatigue-related crashes and incidents. This will provide valuable data about the number and characteristics of fatigue-related crashes and incidents of ACT residents. Specifically this study assessed the prevalence of incidents of fatigue-related driving for residents of NSW and the ACT, the characteristics surrounding the incident, if the report would fit within the NSW, QLD, or ATSB proxy definition or if it would fall outside of the proxy definition...

A nationwide web-based automated system for early outbreak detection and rapid response in China

Timely reporting, effective analyses and rapid distribution of surveillance data can assist in detecting the aberration of disease occurrence and further facilitate a timely response. In China, a new nationwide web-based automated system for outbreak detection and rapid response was developed in 2008. The China Infectious Disease Automated-alert and Response System (CIDARS) was developed by the Chinese Center for Disease Control and Prevention based on the surveillance data from the existing electronic National Notifiable Infectious Diseases Reporting Information System (NIDRIS) started in 2004. NIDRIS greatly improved the timeliness and completeness of data reporting with real time reporting information via the Internet. CIDARS further facilitates the data analysis, aberration detection, signal dissemination, signal response and information communication needed by public health departments across the country. In CIDARS, three aberration detection methods are used to detect the unusual occurrence of 28 notifiable infectious diseases at the county level and to transmit that information either in real-time or on a daily basis. The Internet, computers and mobile phones are used to accomplish rapid signal generation and dissemination, timely reporting and reviewing of the signal response results. CIDARS has been used nationwide since 2008; all Centers for Disease Control and Prevention (CDC) in China at the county, prefecture, provincial and national levels are involved in the system. It assists with early outbreak detection at the local level and prompts reporting of unusual disease occurrences or potential outbreaks to CDCs throughout the country.

Four years on: Are the gazelles still running? A longitudinal study of firm performance after a period of rapid growth

This article examines variations in performance between fast-growth – the so-called gazelle – firms. Specifically, we investigate how the level of growth affects future profitability and how this relationship is moderated by firm strategy. Hypotheses are developed regarding the moderated growth–profitability relationship and are tested using longitudinal data from a sample of 964 Danish gazelle firms. We find a positive relationship between growth and profitability among gazelle firms. This relationship is moderated, however, by market strategy; it is stronger for firms pursuing a broad market strategy rather than a niche strategy. This study contributes to the current literature by providing a more nuanced view of the growth–profitability relationship and investigating the potential for the future performance of gazelle firms.

Nursing and medical perceptions of a hospital rapid response system: New process but same old game?

Perhaps no other patient safety intervention depends so acutely on effective interprofessional teamwork for patient survival than the hospital rapid response system (RRS). Yet little is known about nurse-physician relationships when rescuing at-risk patients. This study compared nursing and medical staff perceptions of a mature RRS at a large tertiary hospital. Findings indicate the RRS may be failing to address a hierarchical culture and systems-level barriers to early recognition and response to patient deterioration.

Microscopy for the detection, identification and quantification of malaria parasites on stained thick and thin blood films in research settings

Summary This manual was developed to guide a move towards common standards for undertaking and reporting research microscopy for malaria parasite detection, identification and quantification. It contains procedures based on agreed quality assurance standards for research malaria microscopy defined at a consultation of: TDR, the Special Programme for Research and Training in Tropical Diseases; the Worldwide Antimalarial Resistance Network (WWARN), United Kingdom; the Foundation for Innovative New Diagnostics (FIND), Switzerland; the Centers for Disease Control and Prevention (CDC), USA; the Kenya Medical Research Institute (KEMRI) and later expanded to include Amref Health Africa (Kenya); the Eijkman-Oxford Clinical Research Unit (EOCRU), Indonesia; Institut Pasteur du Cambodge (IPC); Institut de recherche pour le Développement (IRD), Senegal; the Global Good and Intellectual Ventures Laboratory (GG-IVL), USA; the Mahidol-Oxford Tropical Medicine Research Unit (MORU), Thailand; Queensland University of Technology (QUT), Australia, and the Shoklo Malaria Research Unit (SMRU), Thailand. These collaborating institutions commit to adhering to these standards in published research studies. It is hoped that they will form a solid basis for the wider adoption of standardized reference microscopy protocols for malaria research.

Identification of a BRCA1-mRNA splicing complex required for efficient DNA repair and maintenance of genomic stability

Mutations within BRCA1 predispose carriers to a high risk of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through the assembly of multiple protein complexes involved in DNA repair, cell-cycle arrest, and transcriptional regulation. Here, we report the identification of a DNA damage-induced BRCA1 protein complex containing BCLAF1 and other key components of the mRNA-splicing machinery. In response to DNA damage, this complex regulates pre-mRNA splicing of a number of genes involved in DNA damage signaling and repair, thereby promoting the stability of these transcripts/proteins. Further, we show that abrogation of this complex results in sensitivity to DNA damage, defective DNA repair, and genomic instability. Interestingly, mutations in a number of proteins found within this complex have been identified in numerous cancer types. These data suggest that regulation of splicing by the BRCA1-mRNA splicing complex plays an important role in the cellular response to DNA damage.

Modal parameters identification of heavy-haul railway RC bridges: Experience acquired

Traditionally, it is not easy to carry out tests to identify modal parameters from existing railway bridges because of the testing conditions and complicated nature of civil structures. A six year (2007-2012) research program was conducted to monitor a group of 25 railway bridges. One of the tasks was to devise guidelines for identifying their modal parameters. This paper presents the experience acquired from such identification. The modal analysis of four representative bridges of this group is reported, which include B5, B15, B20 and B58A, crossing the Carajás railway in northern Brazil using three different excitations sources: drop weight, free vibration after train passage, and ambient conditions. To extract the dynamic parameters from the recorded data, Stochastic Subspace Identification and Frequency Domain Decomposition methods were used. Finite-element models were constructed to facilitate the dynamic measurements. The results show good agreement between the measured and computed natural frequencies and mode shapes. The findings provide some guidelines on methods of excitation, record length of time, methods of modal analysis including the use of projected channel and harmonic detection, helping researchers and maintenance teams obtain good dynamic characteristics from measurement data.

Molecular recognition of 2,4,6-trinitrotoluene by 6-aminohexanethiol and surface-enhanced Raman scattering sensor

2,4,6-trinitrotoluene (TNT) is one of the most commonly used nitro aromatic explosives in landmine, military and mining industry. This article demonstrates rapid and selective identification of TNT by surface-enhanced Raman spectroscopy (SERS) using 6-aminohexanethiol (AHT) as a new recognition molecule. First, Meisenheimer complex formation between AHT and TNT is confirmed by the development of pink colour and appearance of new band around 500 nm in UV-visible spectrum. Solution Raman spectroscopy study also supported the AHT:TNT complex formation by demonstrating changes in the vibrational stretching of AHT molecule between 2800-3000 cm−1. For surface enhanced Raman spectroscopy analysis, a self-assembled monolayer (SAM) of AHT is formed over the gold nanostructure (AuNS) SERS substrate in order to selectively capture TNT onto the surface. Electrochemical desorption and X-ray photoelectron studies are performed over AHT SAM modified surface to examine the presence of free amine groups with appropriate orientation for complex formation. Further, AHT and butanethiol (BT) mixed monolayer system is explored to improve the AHT:TNT complex formation efficiency. Using a 9:1 AHT:BT mixed monolayer, a very low detection limit (LOD) of 100 fM TNT was realized. The new method delivers high selectivity towards TNT over 2,4 DNT and picric acid. Finally, real sample analysis is demonstrated by the extraction and SERS detection of 302 pM of TNT from spiked.

Reproducible and label-free biosensor for the selective extraction and rapid detection of proteins in biological fluids

Erythropoietin (EPO), a glycoprotein hormone of ∼34 kDa, is an important hematopoietic growth factor, mainly produced in the kidney and controls the number of red blood cells circulating in the blood stream. Sensitive and rapid recombinant human EPO (rHuEPO) detection tools that improve on the current laborious EPO detection techniques are in high demand for both clinical and sports industry. A sensitive aptamer-functionalized biosensor (aptasensor) has been developed by controlled growth of gold nanostructures (AuNS) over a gold substrate (pAu/AuNS). The aptasensor selectively binds to rHuEPO and, therefore, was used to extract and detect the drug from horse plasma by surface enhanced Raman spectroscopy (SERS). Due to the nanogap separation between the nanostructures, the high population and distribution of hot spots on the pAu/AuNS substrate surface, strong signal enhancement was acquired. By using wide area illumination (WAI) setting for the Raman detection, a low RSD of 4.92% over 150 SERS measurements was achieved. The significant reproducibility of the new biosensor addresses the serious problem of SERS signal inconsistency that hampers the use of the technique in the field. The WAI setting is compatible with handheld Raman devices. Therefore, the new aptasensor can be used for the selective extraction of rHuEPO from biological fluids and subsequently screened with handheld Raman spectrometer for SERS based in-field protein detection.

Engaging a multiple-track approach to building capacity for 21st Century engineering, opportunities and challenges for rapid curriculum renewal

‘Complexity’ is a term that is increasingly prevalent in conversations about building capacity for 21st Century professional engineers. Society is grappling with the urgent and challenging reality of accommodating seven billion people, meeting needs and innovating lifestyle improvements in ways that do not destroy atmospheric, biological and oceanic systems critical to life. Over the last two decades in particular, engineering educators have been active in attempting to build capacity amongst professionals to deliver ‘sustainable development’ in this rapidly changing global context. However curriculum literature clearly points to a lack of significant progress, with efforts best described as ad hoc and highly varied. Given the limited timeframes for action to curb environmental degradation proposed by scientists and intergovernmental agencies, the authors of this paper propose it is imperative that curriculum renewal towards education for sustainable development proceeds rapidly, systemically, and in a transformational manner. Within this context, the paper discusses the need to consider a multiple track approach to building capacity for 21st Century engineering, including priorities and timeframes for undergraduate and postgraduate curriculum renewal. The paper begins with a contextual discussion of the term complexity and how it relates to life in the 21st Century. The authors then present a whole of system approach for planning and implementing rapid curriculum renewal that addresses the critical roles of several generations of engineering professionals over the next three decades. The paper concludes with observations regarding engaging with this approach in the context of emerging accreditation requirements and existing curriculum renewal frameworks.

Mainstreaming EESD: Elements of rapid curriculum renewal

This keynote paper provides an overview of opportunities to rapidly renew curriculum to EESD, to meet the scale and pace of change required, in order to address the issues of our time – in time. The authors outline the key arguments of the six papers that will comprise the March 2009 special issue of the International Journal of Sustainability in Higher Education, on a proposed preliminary framework for rapid curriculum renewal to EESD. The authors invite conference delegates to provide feedback on these papers, and to consider how other concepts and methodologies presented at EESD08 might also be rapidly mainstreamed, to contribute to systemic integration of sustainability content throughout engineering education, in every engineering department.