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.

Proportionality : a valid alternative to correlation for relative data

Relative abundance data is common in the life sciences, but appreciation that it needs special analysis and interpretation is scarce. Correlation is popular as a statistical measure of pairwise association but should not be used on data that carry only relative information. Using timecourse yeast gene expression data, we show how correlation of relative abundances can lead to conclusions opposite to those drawn from absolute abundances, and that its value changes when different components are included in the analysis. Once all absolute information has been removed, only a subset of those associations will reliably endure in the remaining relative data, specifically, associations where pairs of values behave proportionally across observations. We propose a new statistic φ to describe the strength of proportionality between two variables and demonstrate how it can be straightforwardly used instead of correlation as the basis of familiar analyses and visualization methods.

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.

Spatial governance: The metalanguage of spatiotemporal information and its infrastructure

‘Spatial governance’ involves a large number of situations where knowledge of place and time is important in achieving acceptable organisational outcomes. This paper argues that spatial governance calls for information-intensive activity in three main areas. The first establishes ‘authority’ in a legal entity to decide issues regarding resources within a territorial jurisdiction. The second involves planning the future use of resources. It engages a language of design, purpose, modeling, visualization, expectations and risk. The third involves monitoring of outcomes to see if expectations are met; and whether changes to authority and planning regimes need to be made in the light of experience. This engages a language of observing, recording, accounting, auditing, statistical indicators and accountability. ‘Authority’, ‘planning’ and ‘monitoring’ regimes can be constructed using a relatively small number of elements, in much the same way that a large number of words with recognisable meanings can be created using a relatively few standardised letters of the alphabet. Words can combine in a similar process of combinatorial explosion to create any message that can be imagined. Similarly, combining authority, planning and monitoring regimes can create a metalanguage of ‘spatial governance’ to give purpose, meaning and value to any spatiotemporal information system that can be imagined, described, interpreted and understood.

Dynamics of gray matter loss in Alzheimer's disease

We detected and mapped a dynamically spreading wave of gray matter loss in the brains of patients with Alzheimer's disease (AD). The loss pattern was visualized in four dimensions as it spread over time from temporal and limbic cortices into frontal and occipital brain regions, sparing sensorimotor cortices. The shifting deficits were asymmetric (left hemisphere > right hemisphere) and correlated with progressively declining cognitive status (p < 0.0006). Novel brain mapping methods allowed us to visualize dynamic patterns of atrophy in 52 high-resolution magnetic resonance image scans of 12 patients with AD (age 68.4 ± 1.9 years) and 14 elderly matched controls (age 71.4 ± 0.9 years) scanned longitudinally (two scans; interscan interval 2.1 ± 0.4 years). A cortical pattern matching technique encoded changes in brain shape and tissue distribution across subjects and time. Cortical atrophy occurred in a well defined sequence as the disease progressed, mirroring the sequence of neurofibrillary tangle accumulation observed in cross sections at autopsy. Advancing deficits were visualized as dynamic maps that change over time. Frontal regions, spared early in the disease, showed pervasive deficits later (< 15% loss). The maps distinguished different phases of AD and differentiated AD from normal aging. Local gray matter loss rates (5.3 ± 2.3% per year in AD v 0.9 ± 0.9% per year in controls) were faster in the left hemisphere (p < 0.029) than the right. Transient barriers to disease progression appeared at limbic/frontal boundaries. This degenerative sequence, observed in vivo as it developed, provides the first quantitative, dynamic visualization of cortical atrophic rates in normal elderly populations and in those with dementia.

A 4D automatic simulation tool for construction resource planning: A case study

Purpose Traditional construction planning relies upon the critical path method (CPM) and bar charts. Both of these methods suffer from visualization and timing issues that could be addressed by 4D technology specifically geared to meet the needs of the construction industry. This paper proposed a new construction planning approach based on simulation by using a game engine. Design/methodology/approach A 4D automatic simulation tool was developed and a case study was carried out. The proposed tool was used to simulate and optimize the plans for the installation of a temporary platform for piling in a civil construction project in Hong Kong. The tool simulated the result of the construction process with three variables: 1) equipment, 2) site layout and 3) schedule. Through this, the construction team was able to repeatedly simulate a range of options. Findings The results indicate that the proposed approach can provide a user-friendly 4D simulation platform for the construction industry. The simulation can also identify the solution being sought by the construction team. The paper also identifies directions for further development of the 4D technology as an aid in construction planning and decision-making. Research limitations/implications The tests on the tool are limited to a single case study and further research is needed to test the use of game engines for construction planning in different construction projects to verify its effectiveness. Future research could also explore the use of alternative game engines and compare their performance and results. Originality/value The authors proposed the use of game engine to simulate the construction process based on resources, working space and construction schedule. The developed tool can be used by end-users without simulation experience.

Imagined Landscapes: Geovisualizing Australian Spatial Narratives

Imagined Landscapes teams geocritical analysis with digital visualization techniques to map and interrogate films, novels, and plays in which space and place figure prominently. Drawing upon A Cultural Atlas of Australia, a database-driven interactive digital map that can be used to identify patterns of representation in Australia’s cultural landscape, the book presents an integrated perspective on the translation of space across narrative forms and pioneers new ways of seeing and understanding landscape. It offers fresh insights on cultural topography and spatial history by examining the technical and conceptual challenges of georeferencing fictional and fictionalized places in narratives. Among the items discussed are Wake in Fright, a novel by Kenneth Cook, adapted iconically to the screen and recently onto the stage; the Australian North as a mythic space; spatial and temporal narrative shifts in retellings of the story of Alexander Pearce, a convict who gained notoriety for resorting to cannibalism after escaping from a remote Tasmanian penal colony; travel narratives and road movies set in Western Australia; and the challenges and spatial politics of mapping spaces for which there are no coordinates.

Thinking like Disney: Supporting the Disney method using ambient feedback based on group performance

The Disney method is a collaborative creativity technique that uses three roles - dreamer, realist and critic - to facilitate the consideration of different perspectives on a topic. Especially for novices it is important to obtain guidance in applying this method. One way is providing groups with a trained moderator. However, feedback about the group’s behavior might interrupt the flow of the idea finding process. We built and evaluated a system that provides ambient feedback to a group about the distribution of their statements among the three roles. Our preliminary field study indicates that groups supported by the system contribute more and roles are used in a more balanced way while the visualization does not disrupt the group work.

Single molecule microscopy in 3D cell cultures and tissues

From the onset of the first microscopic visualization of single fluorescent molecules in living cells at the beginning of this century, to the present, almost routine application of single molecule microscopy, the method has well-proven its ability to contribute unmatched detailed insight into the heterogeneous and dynamic molecular world life is composed of. Except for investigations on bacteria and yeast, almost the entire story of success is based on studies on adherent mammalian 2D cell cultures. However, despite this continuous progress, the technique was not able to keep pace with the move of the cell biology community to adapt 3D cell culture models for basic research, regenerative medicine, or drug development and screening. In this review, we will summarize the progress, which only recently allowed for the application of single molecule microscopy to 3D cell systems and give an overview of the technical advances that led to it. While initially posing a challenge, we finally conclude that relevant 3D cell models will become an integral part of the on-going success of single molecule microscopy.

FlexAnalytics: A flexible data analytics framework for big data applications with I/O performance improvement

Increasingly larger scale applications are generating an unprecedented amount of data. However, the increasing gap between computation and I/O capacity on High End Computing machines makes a severe bottleneck for data analysis. Instead of moving data from its source to the output storage, in-situ analytics processes output data while simulations are running. However, in-situ data analysis incurs much more computing resource contentions with simulations. Such contentions severely damage the performance of simulation on HPE. Since different data processing strategies have different impact on performance and cost, there is a consequent need for flexibility in the location of data analytics. In this paper, we explore and analyze several potential data-analytics placement strategies along the I/O path. To find out the best strategy to reduce data movement in given situation, we propose a flexible data analytics (FlexAnalytics) framework in this paper. Based on this framework, a FlexAnalytics prototype system is developed for analytics placement. FlexAnalytics system enhances the scalability and flexibility of current I/O stack on HEC platforms and is useful for data pre-processing, runtime data analysis and visualization, as well as for large-scale data transfer. Two use cases – scientific data compression and remote visualization – have been applied in the study to verify the performance of FlexAnalytics. Experimental results demonstrate that FlexAnalytics framework increases data transition bandwidth and improves the application end-to-end transfer performance.

On the effect of Reynolds number for flow past three side-by-side square cylinders for unequal gap spacings

Flow patterns and aerodynamic characteristics behind three side-by-side square cylinders has been found depending upon the unequal gap spacing (g1 = s1/d and g2 = s2/d) between the three cylinders and the Reynolds number (Re) using the Lattice Boltzmann method. The effect of Reynolds numbers on the flow behind three cylinders are numerically studied for 75 ≤ Re ≤ 175 and chosen unequal gap spacings such as (g1, g2) = (1.5, 1), (3, 4) and (7, 6). We also investigate the effect of g2 while keeping g1 fixed for Re = 150. It is found that a Reynolds number have a strong effect on the flow at small unequal gap spacing (g1, g2) = (1.5, 1.0). It is also found that the secondary cylinder interaction frequency significantly contributes for unequal gap spacing for all chosen Reynolds numbers. It is observed that at intermediate unequal gap spacing (g1, g2) = (3, 4) the primary vortex shedding frequency plays a major role and the effect of secondary cylinder interaction frequencies almost disappear. Some vortices merge near the exit and as a result small modulation found in drag and lift coefficients. This means that with the increase in the Reynolds numbers and unequal gap spacing shows weakens wakes interaction between the cylinders. At large unequal gap spacing (g1, g2) = (7, 6) the flow is fully periodic and no small modulation found in drag and lift coefficients signals. It is found that the jet flows for unequal gap spacing strongly influenced the wake interaction by varying the Reynolds number. These unequal gap spacing separate wake patterns for different Reynolds numbers: flip-flopping, in-phase and anti-phase modulation synchronized, in-phase and anti-phase synchronized. It is also observed that in case of equal gap spacing between the cylinders the effect of gap spacing is stronger than the Reynolds number. On the other hand, in case of unequal gap spacing between the cylinders the wake patterns strongly depends on both unequal gap spacing and Reynolds number. The vorticity contour visualization, time history analysis of drag and lift coefficients, power spectrum analysis of lift coefficient and force statistics are systematically discussed for all chosen unequal gap spacings and Reynolds numbers to fully understand this valuable and practical problem.

Detection of anuran calling activity in long field recordings for bio-acoustic monitoring

This paper presents a system to analyze long field recordings with low signal-to-noise ratio (SNR) for bio-acoustic monitoring. A method based on spectral peak track, Shannon entropy, harmonic structure and oscillation structure is proposed to automatically detect anuran (frog) calling activity. Gaussian mixture model (GMM) is introduced for modelling those features. Four anuran species widespread in Queensland, Australia, are selected to evaluate the proposed system. A visualization method based on extracted indices is employed for detection of anuran calling activity which achieves high accuracy.

Complex crystallization dynamics in amorphous germanium observed with dynamic transmission electron microscopy

Crystallization of amorphous germanium (a-Ge) by laser or electron beam heating is a remarkably complex process that involves several distinct modes of crystal growth and the development of intricate microstructural patterns on the nanosecond to ten microsecond time scales. Here we use dynamic transmission electron microscopy (DTEM) to study the fast, complex crystallization dynamics with 10 nm spatial and 15 ns temporal resolution. We have obtained time-resolved real-space images of nanosecond laser-induced crystallization in a-Ge with unprecedentedly high spatial resolution. Direct visualization of the crystallization front allows for time-resolved snapshots of the initiation and roughening of the dendrites on submicrosecond time scales. This growth is followed by a rapid transition to a ledgelike growth mechanism that produces a layered microstructure on a time scale of several microseconds. This study provides insights into the mechanisms governing this complex crystallization process and is a dramatic demonstration of the power of DTEM for studying time-dependent material processes far from equilibrium.

Towards collaborative modeling of business processes on large interactive touch display walls

Analyzing and redesigning business processes is a complex task, which requires the collaboration of multiple actors. Current approaches focus on workshops where process stakeholders together with modeling experts create a graphical visualization of a process in a model. Within these workshops, stakeholders are mostly limited to verbal contributions, which are integrated into a process model by a modeling expert using traditional input devices. This limitation negatively affects the collaboration outcome and also the perception of the collaboration itself. In order to overcome this problem we created CubeBPM – a system that allows groups of actors to interact with process models through a touch based interface on a large interactive touch display wall. Using this system for collaborative modeling, we expect to provide a more effective collaboration environment thus improving modeling performance and collaboration.

Dashboards in performance management: The foundations and research opportunities for their effective use

When designed effectively dashboards are expected to reduce information overload and improve performance management. Hence, interest in dashboards has increased recently,which is also evident from the proliferation of dashboard solution providers in the market. Despite dashboards popularity, little is known about the extent of their effectiveness in organizations. Dashboards draw from multiple disciplines but ultimately use visualization to communicate important information to stakeholders. Thus,a better understanding of visualization can improve the design and use of dashboards. This paper reviews the foundations and roles of dashboards in performance management and proposes a framework for future research, which can enhance dashboard design and perceived usefulness depending on the fit between the features of the dashboard and the characteristics of the users.