Non-invasive techniques for imaging in-vivo human corneal sub basal nerve mapping and migration rate in diabetic neuropathy

Purpose Corneal confocal microscopy (CCM) is a rapid non-invasive ophthalmic technique, which has been shown to diagnose and stratify the severity of diabetic neuropathy. Current morphometric techniques assess individual static images of the subbasal nerve plexus; this work explores the potential for non-invasive assessment of the wide-field morphology and dynamic changes of this plexus in vivo. Methods In this pilot study, laser scanning CCM was used to acquire maps (using a dynamic fixation target and semi-automated tiling software) of the central corneal sub-basal nerve plexus in 4 diabetic patients with and 6 without neuropathy and in 2 control subjects. Nerve migration was measured in an additional 7 diabetic patients with neuropathy, 4 without neuropathy and in 2 control subjects by repeating a modified version of the mapping procedure within 2-8 weeks, thus facilitating re-identification of distinctive nerve landmarks in the 2 montages. The rate of nerve movement was determined from these data and normalised to a weekly rate (µm/week), using customised software. Results Wide-field corneal nerve fibre length correlated significantly with the Neuropathy Disability Score (r = -0.58, p < 0.05), vibration perception (r = -0.66, p < 0.05) and peroneal conduction velocity (r = 0.67, p < 0.05). Central corneal nerve fibre length did not correlate with any of these measures of neuropathy (p > 0.05 for all). The rate of corneal nerve migration was 14.3 ± 1.1 µm/week in diabetic patients with neuropathy, 19.7 ± 13.3µm/week in diabetic patients without neuropathy, and 24.4 ± 9.8µm/week in control subjects; however, these differences were not significantly different (p = 0.543). Conclusions Our data demonstrate that it is possible to capture wide-field images of the corneal nerve plexus, and to quantify the rate of corneal nerve migration by repeating this procedure over a number of weeks. Further studies on larger sample sizes are required to determine the utility of this approach for the diagnosis and monitoring of diabetic neuropathy.

Elevated YKL40 is associated with advanced prostate cancer (PCa) and positively regulates invasion and migration of PCa cells

Chitinase 3-like 1 (CHI3L1 or YKL40) is a secreted glycoprotein highly expressed in tumours from patients with advanced stage cancers, including prostate cancer (PCa). The exact function of YKL40 is poorly understood, but it has been shown to play an important role in promoting tumour angiogenesis and metastasis. The therapeutic value and biological function of YKL40 are unknown in PCa. The objective of this study was to examine the expression and function of YKL40 in PCa. Gene expression analysis demonstrated that YKL40 was highly expressed in metastatic PCa cells when compared with less invasive and normal prostate epithelial cell lines. In addition, the expression was primarily limited to androgen receptor-positive cell lines. Evaluation of YKL40 tissue expression in PCa patients showed a progressive increase in patients with aggressive disease when compared with those with less aggressive cancers and normal controls. Treatment of LNCaP and C4-2B cells with androgens increased YKL40 expression, whereas treatment with an anti-androgen agent decreased the gene expression of YKL40 in androgen-sensitive LNCaP cells. Furthermore, knockdown of YKL40 significantly decreased invasion and migration of PCa cells, whereas overexpression rendered them more invasive and migratory, which was commensurate with an enhancement in the anchorage-independent growth of cells. To our knowledge, this study characterises the role of YKL40 for the first time in PCa. Together, these results suggest that YKL40 plays an important role in PCa progression and thus inhibition of YKL40 may be a potential therapeutic strategy for the treatment of PCa.

A random key genetic algorithm for live migration of multiple virtual machines in data centers

Live migration of multiple Virtual Machines (VMs) has become an integral management activity in data centers for power saving, load balancing and system maintenance. While state-of-the-art live migration techniques focus on the improvement of migration performance of an independent single VM, only a little has been investigated to the case of live migration of multiple interacting VMs. Live migration is mostly influenced by the network bandwidth and arbitrarily migrating a VM which has data inter-dependencies with other VMs may increase the bandwidth consumption and adversely affect the performances of subsequent migrations. In this paper, we propose a Random Key Genetic Algorithm (RKGA) that efficiently schedules the migration of a given set of VMs accounting both inter-VM dependency and data center communication network. The experimental results show that the RKGA can schedule the migration of multiple VMs with significantly shorter total migration time and total downtime compared to a heuristic algorithm.

Detoxification enzyme activities (CYP1A1 and GST) in the skin of humpback whales as a function of organochlorine burdens and migration status

The activities of glutathione-s-transferase (GST) and cytochrome P-450 1A1 (CYP1A1) enzymes were measured in freshly extracted epidermis of live-biopsied, migrating, southern hemisphere humpback whales (Megaptera novaeangliae). The two quantified enzyme activities did not correlate strongly with each other. Similarly, neither correlated strongly with any of the organochlorine compound groups previously measured in the superficial blubber of the sample biopsy core, likely reflecting the anticipated low levels of typical aryl-hydrocarbon receptor ligands. GST activity did not differ significantly between genders or between northward (early migration) or southward (late migration) migrating cohorts. Indeed, the inter-individual variability in GST measurements was relatively low. This observation raises the possibility that measured activities were basal activities and that GST function was inherently impacted by the fasting state of the sampled animals, as seen in other species. These results do not support the implementation of CYP1A1 or GST as effective biomarkers of organochlorine contaminant burdens in southern hemisphere populations of humpback whales as advocated for other cetacean species. Further investigation of GST activity in feeding versus fasting cohorts may, however, provide some insight into the fasting metabolism of these behaviourally adapted populations.

The glycosphingolipid P1 is an ovarian cancer-associated carbohydrate antigen involved in migration

Background The level of plasma-derived naturally circulating anti-glycan antibodies (AGA) to P1 trisaccharide has previously been shown to significantly discriminate between ovarian cancer patients and healthy women. Here we aim to identify the Ig class that causes this discrimination, to identify on cancer cells the corresponding P1 antigen recognised by circulating anti-P1 antibodies and to shed light into the possible function of this glycosphingolipid. Method An independent Australian cohort was assessed for the presence of anti-P1 IgG and IgM class antibodies using suspension array. Monoclonal and human derived anti-glycan antibodies were verified using three independent glycan-based immunoassays and flow cytometry-based inhibition assay. The P1 antigen was detected by LC-MS/MS and flow cytometry. FACS-sorted cell lines were studied on the cellular migration by colorimetric assay and real-time measurement using xCELLigence system. Results Here we show in a second independent cohort (n=155) that the discrimination of cancer patients is mediated by the IgM class of anti-P1 antibodies (P=0.0002). The presence of corresponding antigen P1 and structurally related epitopes in fresh tissue specimens and cultured cancer cells is demonstrated. We further link the antibody and antigen (P1) by showing that human naturally circulating and affinity-purified anti-P1 IgM isolated from patients ascites can bind to naturally expressed P1 on the cell surface of ovarian cancer cells. Cell-sorted IGROV1 was used to obtain two study subpopulations (P1-high, 66.1%; and P1-low, 33.3%) and observed that cells expressing high P1-levels migrate significantly faster than those with low P1-levels. Conclusions This is the first report showing that P1 antigen, known to be expressed on erythrocytes only, is also present on ovarian cancer cells. This suggests that P1 is a novel tumour-associated carbohydrate antigen recognised by the immune system in patients and may have a role in cell migration. The clinical value of our data may be both diagnostic and prognostic; patients with low anti-P1 IgM antibodies present with a more aggressive phenotype and earlier relapse.

The adhesion molecule L1 regulates transendothelial migration and trafficking of dendritic cells

The adhesion molecule L1, which is extensively characterized in the nervous system, is also expressed in dendritic cells (DCs), but its function there has remained elusive. To address this issue, we ablated L1 expression in DCs of conditional knockout mice. L1-deficient DCs were impaired in adhesion to and transmigration through monolayers of either lymphatic or blood vessel endothelial cells, implicating L1 in transendothelial migration of DCs. In agreement with these findings, L1 was expressed in cutaneous DCs that migrated to draining lymph nodes, and its ablation reduced DC trafficking in vivo. Within the skin, L1 was found in Langerhans cells but not in dermal DCs, and L1 deficiency impaired Langerhans cell migration. Under inflammatory conditions, L1 also became expressed in vascular endothelium and enhanced transmigration of DCs, likely through L1 homophilic interactions. Our results implicate L1 in the regulation of DC trafficking and shed light on novel mechanisms underlying transendothelial migration of DCs. These observations might offer novel therapeutic perspectives for the treatment of certain immunological disorders.

Ross River virus disease activity associated with naturally occurring non-tidal flood events in Australia : A systematic review

Ross River virus (RRV) disease is the most common and widespread mosquito-borne disease in Australia, resulting in considerable health and economic cost to communities. While naturally occurring non-tidal flood events may enhance mosquito abundance, little is known about the impact of such events on RRV transmission. This paper critically reviews the existing evidence for an association between naturally occurring non-tidal flood events and RRV transmission. A systematic literature search was conducted on RRV transmission related to flooding and inundation from rain and riverine overflow. Overall, the evidence to support a positive association between flooding and RRV outbreaks is largely circumstantial, with the literature mostly reporting only coincidental occurrence between the two. However, for the Murray River, river flow and height (surrogates of flooding) were positively and significantly associated with RRV transmission. The association between non-tidal flooding and RRV transmission has not been studied comprehensively. More frequent flood events arising from climate change may result in increased outbreaks of RRV disease. Understanding the link between flood events and RRV transmission is necessary if resources for mosquito spraying and public health warnings are to be utilized more effectively and efficiently.

Turbulence measurements in a shallow tidal estuary : analysis based on triple decomposition

In an estuary, mixing and dispersion are the result of the combination of large scale advection and small scale turbulence which are both complex to estimate. A field study was conducted in a small sub-tropical estuary in which high frequency (50 Hz) turbulent data were recorded continuously for about 48 hours. A triple decomposition technique was introduced to isolate the contributions of tides, resonance and turbulence in the flow field. A striking feature of the data set was the slow fluctuations which exhibited large amplitudes up to 50% the tidal amplitude under neap tide conditions. The triple decomposition technique allowed a characterisation of broader temporal scales of high frequency fluctuation data sampled during a number of full tidal cycles.

Leaving family behind: Understanding the irregular migration of unaccompanied asylum-seeking minors - A qualitative study

This qualitative study investigated the drivers and determinants of irregular maritime migration among 17 protection visa holders who arrived in Australia as unaccompanied asylum-seeking minors. Semi-structured interviews were also conducted with eight non-government service providers working with unaccompanied minors in the Greater Brisbane area.

Encouraging Empathy through Picture Books about Migration

Australia has become one of the most highly multilingual and multicultural societies in the world today with people descending from 270 ancestries, who speak more than 260 languages (Commonwealth of Australia, 2011). Immigration is something that children encounter in their daily lives either through personal experience or through witnessing the lives of migrants at school, in the community, or through popular media, including children’s literature. Schools are frequently the initial interface for individuals who resettle in Australia and they ‘play a significant role in establishing meaningful connections to Australian society and a sense of belonging in Australia’ (Uptin, Wright, & Harwood, 2013, p. 1). Children's literature about cultural and ethnic diversity explores the impacts of migration and related issues creating ‘imaginary realms’ (Dudek & Ommundsen, 2007). These fictional interpretations of the migrant experience or the experience of migration are supported by distinctive “real life” cultural experiences. Picture books furnish teachers and students with an accessible means to investigate these complex issues through sensitive discussions. This chapter investigates how picture books about migration help deepen children’s perceptive understanding of migrants’ plights, and thereby nurture tolerance and empathy.

Estimate of Lagrangian integral scales in shallow tidal water using high resolution GPS-tracked drifters

In estuaries and natural water channels, the estimate of velocity and dispersion coefficients is critical to the knowledge of scalar transport and mixing. This estimate is rarely available experimentally at sub-tidal time scale in shallow water channels where high frequency is required to capture its spatio-temporal variation. This study estimates Lagrangian integral scales and autocorrelation curves, which are key parameters for obtaining velocity fluctuations and dispersion coefficients, and their spatio-temporal variability from deployments of Lagrangian drifters sampled at 10 Hz for a 4-hour period. The power spectral densities of the velocities between 0.0001 and 0.8 Hz were well fitted with a slope of 5/3 predicted by Kolmogorov’s similarity hypothesis within the inertial subrange, and were similar to the Eulerian power spectral previously observed within the estuary. The result showed that large velocity fluctuations determine the magnitude of the integral time scale, TL. Overlapping of short segments improved the stability of the estimate of TL by taking advantage of the redundant data included in the autocorrelation function. The integral time scales were about 20 s and varied by up to a factor of 8. These results are essential inputs for spatial binning of velocities, Lagrangian stochastic modelling and single particle analysis of the tidal estuary.

A penalty-based genetic algorithm for the migration cost-aware virtual machine placement problem in cloud data centers

In the past few years, the virtual machine (VM) placement problem has been studied intensively and many algorithms for the VM placement problem have been proposed. However, those proposed VM placement algorithms have not been widely used in today's cloud data centers as they do not consider the migration cost from current VM placement to the new optimal VM placement. As a result, the gain from optimizing VM placement may be less than the loss of the migration cost from current VM placement to the new VM placement. To address this issue, this paper presents a penalty-based genetic algorithm (GA) for the VM placement problem that considers the migration cost in addition to the energy-consumption of the new VM placement and the total inter-VM traffic flow in the new VM placement. The GA has been implemented and evaluated by experiments, and the experimental results show that the GA outperforms two well known algorithms for the VM placement problem.

A Strength Pareto Evolutionary Algorithm for live migration of multiple interdependent virtual machines in data centers

Although live VM migration has been intensively studied, the problem of live migration of multiple interdependent VMs has hardly been investigated. The most important problem in the live migration of multiple interdependent VMs is how to schedule VM migrations as the schedule will directly affect the total migration time and the total downtime of those VMs. Aiming at minimizing both the total migration time and the total downtime simultaneously, this paper presents a Strength Pareto Evolutionary Algorithm 2 (SPEA2) for the multi-VM migration scheduling problem. The SPEA2 has been evaluated by experiments, and the experimental results show that the SPEA2 can generate a set of VM migration schedules with a shorter total migration time and a shorter total downtime than an existing genetic algorithm, namely Random Key Genetic Algorithm (RKGA). This paper also studies the scalability of the SPEA2.

Low-dose curcumin stimulates proliferation, migration and phagocytic activity of olfactory ensheathing cells

One of the promising strategies for neural repair therapies is the transplantation of olfactory ensheathing cells (OECs) which are the glial cells of the olfactory system. We evaluated the effects of curcumin on the behaviour of mouse OECs to determine if it could be of use to further enhance the therapeutic potential of OECs. Curcumin, a natural polyphenol compound found in the spice turmeric, is known for its anti-cancer properties at doses over 10 µM, and often at 50 µM, and it exerts its effects on cancer cells in part by activation of MAP kinases. In contrast, we found that low-dose curcumin (0.5 µM) applied to OECs strikingly modulated the dynamic morphology, increased the rate of migration by up to 4-fold, and promoted significant proliferation of the OECs. Most dramatically, low-dose curcumin stimulated a 10-fold increase in the phagocytic activity of OECs. All of these potently stimulated behavioural characteristics of OECs are favourable for neural repair therapies. Importantly, low-dose curcumin gave a transient activation of p38 kinases, which is in contrast to the high dose curcumin effects on cancer cells in which these MAP kinases tend to undergo prolonged activation. Low-dose curcumin mediated effects on OECs demonstrate cell-type specific stimulation of p38 and ERK kinases. These results constitute the first evidence that low-dose curcumin can modulate the behaviour of olfactory glia into a phenotype potentially more favourable for neural repair and thereby improve the therapeutic use of OECs for neural repair therapies