Distinguishing between mechanisms of cell aggregation using pair-correlation functions

Many cell types form clumps or aggregates when cultured in vitro through a variety of mechanisms including rapid cell proliferation, chemotaxis, or direct cell-to-cell contact. In this paper we develop an agent-based model to explore the formation of aggregates in cultures where cells are initially distributed uniformly, at random, on a two-dimensional substrate. Our model includes unbiased random cell motion, together with two mechanisms which can produce cell aggregates: (i) rapid cell proliferation, and (ii) a biased cell motility mechanism where cells can sense other cells within a finite range, and will tend to move towards areas with higher numbers of cells. We then introduce a pair-correlation function which allows us to quantify aspects of the spatial patterns produced by our agent-based model. In particular, these pair-correlation functions are able to detect differences between domains populated uniformly at random (i.e. at the exclusion complete spatial randomness (ECSR) state) and those where the proliferation and biased motion rules have been employed - even when such differences are not obvious to the naked eye. The pair-correlation function can also detect the emergence of a characteristic inter-aggregate distance which occurs when the biased motion mechanism is dominant, and is not observed when cell proliferation is the main mechanism of aggregate formation. This suggests that applying the pair-correlation function to experimental images of cell aggregates may provide information about the mechanism associated with observed aggregates. As a proof of concept, we perform such analysis for images of cancer cell aggregates, which are known to be associated with rapid proliferation. The results of our analysis are consistent with the predictions of the proliferation-based simulations, which supports the potential usefulness of pair correlation functions for providing insight into the mechanisms of aggregate formation.

Context-specific stressors, work-related social support and work-family conflict : a mediation study

Understanding the antecedents of work-family conflict is important as it allows organisations to effectively engage in work design for professional employees. This study examines the impact of sources of social support as antecedents of work-family conflict. The hypotheses were tests using Partial Least Squares modelling on a sample of 366 professional employees. The path model showed that context-specific stressors impacted positively on job demand, which led to higher levels of work-family conflict. Contrary to our expectation, non-work related social support did not have any statistical relationship with job demand and work-family conflict. In addition, individuals experiencing high job demands were found to obtain more social support from both work and non-work-related sources. Individuals with more work-related social support were less likely to have less work-family conflict. Surprisingly, non-work social support sources had no statistically significant relationship with work-family conflict.

Species-specific homing mechanisms of human prostate cancer metastasis in tissue engineered bone

The development of effective therapeutic strategies against prostate cancer bone metastases has been impeded by the lack of adequate animal models that are able to recapitulate the biology of the disease in humans. Bioengineered approaches allow researchers to create sophisticated experimentally and physiologically relevant in vivo models to study interactions between cancer cells and their microenvironment under reproducible conditions. The aim of this study was to engineer a morphologically and functionally intact humanized organ bone which can serve as a homing site for human prostate cancer cells. Transplantation of biodegradable tubular composite scaffolds seeded with human mesenchymal progenitor cells and loaded with rhBMP-7 resulted in the development of a chimeric bone construct including a large number of human mesenchymal cells which were shown to be metabolically active and capable of producing extracellular matrix components. Micro-CT analysis demonstrated that the newly formed ossicle recapitulated the morphological features of a physiological organ bone with a trabecular network surrounded by a cortex-like outer structure. This microenvironment was supportive of the lodgement and maintenance of murine haematopoietic cell clusters, thus mimicking a functional organ bone. Bioluminescence imaging demonstrated that luciferase-transduced human PC3 cells reproducibly homed to the humanized tissue engineered bone constructs, proliferated, and developed macro-metastases. This model allows the analysis of interactions between human prostate cancer cells and a functional humanized bone organ within an immuno-incompetent murine host. The system can serve as a reproducible platform to study effects of therapeutics against prostate cancer bone metastases within a humanized microenvironment.

GNSS ambiguity resolution with controllable failure rate for long baseline network RTK

Many large-scale GNSS CORS networks have been deployed around the world to support various commercial and scientific applications. To make use of these networks for real-time kinematic positioning services, one of the major challenges is the ambiguity resolution (AR) over long inter-station baselines in the presence of considerable atmosphere biases. Usually, the widelane ambiguities are fixed first, followed by the procedure of determination of the narrowlane ambiguity integers based on the ionosphere-free model in which the widelane integers are introduced as known quantities. This paper seeks to improve the AR performance over long baseline through efficient procedures for improved float solutions and ambiguity fixing. The contribution is threefold: (1) instead of using the ionosphere-free measurements, the absolute and/or relative ionospheric constraints are introduced in the ionosphere-constrained model to enhance the model strength, thus resulting in the better float solutions; (2) the realistic widelane ambiguity precision is estimated by capturing the multipath effects due to the observation complexity, leading to improvement of reliability of widelane AR; (3) for the narrowlane AR, the partial AR for a subset of ambiguities selected according to the successively increased elevation is applied. For fixing the scalar ambiguity, an error probability controllable rounding method is proposed. The established ionosphere-constrained model can be efficiently solved based on the sequential Kalman filter. It can be either reduced to some special models simply by adjusting the variances of ionospheric constraints, or extended with more parameters and constraints. The presented methodology is tested over seven baselines of around 100 km from USA CORS network. The results show that the new widelane AR scheme can obtain the 99.4 % successful fixing rate with 0.6 % failure rate; while the new rounding method of narrowlane AR can obtain the fix rate of 89 % with failure rate of 0.8 %. In summary, the AR reliability can be efficiently improved with rigorous controllable probability of incorrectly fixed ambiguities.

A Satellite Selection Algorithm for Achieving High Reliability of Ambiguity Resolution with GPS and Beidou Constellations

Reliability of carrier phase ambiguity resolution (AR) of an integer least-squares (ILS) problem depends on ambiguity success rate (ASR), which in practice can be well approximated by the success probability of integer bootstrapping solutions. With the current GPS constellation, sufficiently high ASR of geometry-based model can only be achievable at certain percentage of time. As a result, high reliability of AR cannot be assured by the single constellation. In the event of dual constellations system (DCS), for example, GPS and Beidou, which provide more satellites in view, users can expect significant performance benefits such as AR reliability and high precision positioning solutions. Simply using all the satellites in view for AR and positioning is a straightforward solution, but does not necessarily lead to high reliability as it is hoped. The paper presents an alternative approach that selects a subset of the visible satellites to achieve a higher reliability performance of the AR solutions in a multi-GNSS environment, instead of using all the satellites. Traditionally, satellite selection algorithms are mostly based on the position dilution of precision (PDOP) in order to meet accuracy requirements. In this contribution, some reliability criteria are introduced for GNSS satellite selection, and a novel satellite selection algorithm for reliable ambiguity resolution (SARA) is developed. The SARA algorithm allows receivers to select a subset of satellites for achieving high ASR such as above 0.99. Numerical results from a simulated dual constellation cases show that with the SARA procedure, the percentages of ASR values in excess of 0.99 and the percentages of ratio-test values passing the threshold 3 are both higher than those directly using all satellites in view, particularly in the case of dual-constellation, the percentages of ASRs (>0.99) and ratio-test values (>3) could be as high as 98.0 and 98.5 % respectively, compared to 18.1 and 25.0 % without satellite selection process. It is also worth noting that the implementation of SARA is simple and the computation time is low, which can be applied in most real-time data processing applications.

What further benefit, if any, might Australia get from the ALI-III Transnational Insolvency: Global Principles for Cooperation in International Insolvency Cases?

In 2006, the American Law Institute (ALI) and the International Insolvency Institute (III) established a Transnational Insolvency Project and appointed Professor Ian Fletcher (United Kingdom) and Professor Bob Wessels (Netherlands) as Joint Reporters. The objective was to investigate whether the essential provisions of the ALI Principles of Cooperation among the NAFTA Countries (ALI-NAFTA Principles) and the annexed Guidelines Applicable to Court-to-Court Communication in Cross-border Cases (ALI-NAFTA Guidelines) may, with certain necessary modifications, be acceptable for use by jurisdictions across the world. In 2012, Professor Fletcher and Professor Wessels presented the report Transnational Insolvency: Global Principles for Cooperation in International Insolvency Cases (“ALI-III Report”) to the Annual Meetings of the American Law Institute and the International Insolvency Institute. In 2013, the Australian Academy of Law (AAL) provided support to the authors to undertake research on the possible benefits for Australia of courts and insolvency administrators of referring to the ALI-III Report when addressing international insolvency cases. This AAL project was at the request of the Council of Chief Justices of Australia and New Zealand. This research Report compares the Global Principles for Cooperation in International Insolvency Cases with the Cross-border Insolvency Act 2008 and the UNCITRAL Model Law as it has been adopted and has force of law in Australia. Further, it examines the Global Guidelines for Court-to-Court Communications in International Insolvency Cases in light of Australian cross-border insolvency and procedural law. Finally, it makes brief reference to and commentary on the Global Rules on Conflict–of-Laws Matters in International Insolvency Cases annexed to the ALI-III Report from the perspective of Australian choice of law rules.

The development of an effective and efficient dispute resolution processes for strata scheme disputes in peninsular Malaysia

Dispute resolution in strata schemes in Peninsular Malaysia should focus on more than just "settlement." The quality of the outcome, its sustainability and its relevance in supporting the basic principles of a good neighbourhood and self-governance in a strata scheme are also fundamental. Based on the comprehensive law movement, this thesis develops a theoretical framework for strata scheme disputes within the parameters of therapeutic jurisprudence, preventive law, alternative dispute resolution (ADR) and problem-solving courts. The therapeutic orientation of this model offers approaches that promote positive communication between disputing parties, preserve neighbour relations and optimise people's psychological and emotional well-being.

EdU, a new thymidine analogue for labelling proliferating cells in the nervous system

The standard method of labelling proliferating cells uses the thymidine analogue, bromodeoxyuridine (BrdU), which incorporates into the DNA during S-phase of the cell cycle. A disadvantage of this method is that the immunochemical processing requires pre-treatment of the cells and tissue with heat or acid to reveal the antigen. This pre-treatment reduces reliability of the method and degrades the specimen, reducing the ability for multiple immuno-fluorescence labelling at high resolution. We report here the utility of a novel thymidine analogue, ethynyl deoxyuridine (EdU), detected with a fluorescent azide via the “click” chemistry reaction (the Huisgen 1,3-dipolar cycloaddition reaction of an organic azide to a terminal acetylene). The detection of EdU requires no heat or acid treatment and the incorporated EdU is covalently conjugated to fluorescent probe. The reaction is quick and compatible with fluorescence immunochemistry and other fluorescent probes. We show here that EdU is non-toxic in vitro and in vivo and can be used in place of BrdU to label cells during neurogenesis and the progeny identified at least 30 days later. The fluorescent labelling of EdU, markedly improves the detection of proliferating cells and allows concurrent high resolution fluorescence immunochemistry.

Interactions between organizational culture, trustworthiness, and mechanisms for inter-project knowledge sharing

This research used a multiple-case study approach to empirically investigate the complex relationship between factors influencing inter-project knowledge sharing—trustworthiness, organizational culture, and knowledge-sharing mechanisms. Adopting a competing values framework, we found evidence of patterns existing between the type of culture, on the project management unit level, and project managers’ perceptions of valuing trustworthy behaviors and the way they share knowledge, on the individual level. We also found evidence for mutually reinforcing the effect of trust and clan culture, which shape tacit knowledge-sharing behaviors.

Understanding the abnormal brain activity in epilepsy as a potential predictor of the onset of an epileptic seizure

The Brain Research Institute (BRI) uses various types of indirect measurements, including EEG and fMRI, to understand and assess brain activity and function. As well as the recovery of generic information about brain function, research also focuses on the utilisation of such data and understanding to study the initiation, dynamics, spread and suppression of epileptic seizures. To assist with the future focussing of this aspect of their research, the BRI asked the MISG 2010 participants to examine how the available EEG and fMRI data and current knowledge about epilepsy should be analysed and interpreted to yield an enhanced understanding about brain activity occurring before, at commencement of, during, and after a seizure. Though the deliberations of the study group were wide ranging in terms of the related matters considered and discussed, considerable progress was made with the following three aspects. (1) The science behind brain activity investigations depends crucially on the quality of the analysis and interpretation of, as well as the recovery of information from, EEG and fMRI measurements. A number of specific methodologies were discussed and formalised, including independent component analysis, principal component analysis, profile monitoring and change point analysis (hidden Markov modelling, time series analysis, discontinuity identification). (2) Even though EEG measurements accurately and very sensitively record the onset of an epileptic event or seizure, they are, from the perspective of understanding the internal initiation and localisation, of limited utility. They only record neuronal activity in the cortical (surface layer) neurons of the brain, which is a direct reflection of the type of electrical activity they have been designed to record. 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Conflicting notions of risk : the chasm of conflict between institutions and the public

The trust and credibility gap between institutional regulators and the public is based on fundamental social and cultural differences related to power and authority. It is also associated with the 'distance' of a bureaucracies from those whom they serve. The nature of public concern about risk may be investigated by considering specific cognitive decision making 'rules' such as 'familiarity' of a hazard or 'voluntariness' of exposure. A more complete appreciation of the 'how' and 'why' of public response to danger from industrial hazards can be gained by appreciating these 'rules' within the broader context of mis-communication between 'elite' regulators and a highly diverse public. If the results of risk assessments are expressed in technical terms alone, it is unlikely that any real communication will occur. Further, if issues related to the 'remote' nature of much institutional decision making are not addressed, closure of the 'gap' may be difficult to bring about.

Exploration of mechanisms underlying the strain-rate-dependent mechanical property of single chondrocytes

Based on the characterization by Atomic Force Microscopy (AFM), we report that the mechanical property of single chondrocytes has dependency on the strain-rates. By comparing the mechanical deformation responses and the Young’s moduli of living and fixed chondrocytes at four different strain-rates, we explore the deformation mechanisms underlying this dependency property. We found that the strain-rate-dependent mechanical property of living cells is governed by both of the cellular cytoskeleton (CSK) and the intracellular fluid when the fixed chondrocytes is mainly governed by their intracellular fluid which is called the consolidation-dependent deformation behavior. Finally, we report that the porohyperelastic (PHE) constitutive material model which can capture the consolidation-dependent behavior of both living and fixed chondrocytes is a potential candidature to study living cell biomechanics.

Designing and evaluating an online role play in conflict management

Purpose This paper aims to identify, through a literature review, key issues regarding how online role plays can be designed and to apply them when designing a role play on conflict management. Design/methodology/approach By drawing on the key issues identified in the literature review, a role play on conflict management was designed and evaluated. Data were collected by developing a survey that focused on perceived learning, participation and satisfaction. Findings Overall, a majority of the students felt that they learned and participated in the role play. The most positive finding was that the students were satisfied with their role play experience. Research limitations/implications Researchers are urged to further develop the dimensions and measures of online role play success. The measures that were developed for evaluating perceived learning, participation and satisfaction with role plays can be further developed and tested. It is suggested that the effects on learning need to be further explored. Practical implications It is suggested that teachers take the identified key issues of online role play design into account. An important challenge seems to be to encourage students to reflect and do additional reading and research in relation with online role plays. Originality/value Online collaboration is commonly argued as beneficial from an e-learning perspective. However, a challenge for research and practice is to learn how collaborative e-learning activities may be developed. This paper contributes by focusing on how online role plays can be designed and evaluated.

Mechanisms of glycerol dehydration

Dehydration of neutral and protonated glycerol was investigated using quantum mechanical calculations (CBS-QB3). Calculations on neutral glycerol show that there is a high barrier for simple 1,2-dehydration, E-a = 70.9 kcal mol(-1), which is lowered to 65.2 kcal mol(-1) for pericyclic 1,3-dehydration. In contrast, the barriers for dehydration of protonated glycerol are much lower. Dehydration mechanisms involving hydride transfer, pinacol rearrangement, or substitution reactions have barriers between 20 and 25 kcal mol(-1). Loss of water from glycerol via substitution results in either oxirane or oxetane intermediates, which can interconvert over a low barrier. Subsequent decomposition of these intermediates proceeds via either a second dehydration step or loss of formaldehyde. The computed mechanisms for decomposition of protonated glycerol are supported by the gas-phase fragmentation of protonated glycerol observed using a triple-quadrupole mass spectrometer.