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Simple Summary: With recent progress in radiation therapy, patients with bone metastases can be treated curatively, provided precise delineation of metastatic lesions is adequately identified. Tumor segmentation is a highly active area of research, but only limited studies have been on bone metastasis. This review aims to investigate methods for differentiating benign from malignant bone lesions and characterizing malignant bone lesions specifically in the context of bone metastases. While computer vision techniques have opened new opportunities for quantifying cancer growth with minimal expert supervision, fully automatic segmentation algorithms still require improvement. This is partly due to limited contrast between tumors and surrounding tissue and the lack of a widely agreed upon "gold standard" for defining these boundaries. Additionally, many studies do not provide evidence that their proposed methods are suitable for use in clinical practice. Purpose: To investigate the segmentation approaches for bone metastases in differentiating benign from malignant bone lesions and characterizing malignant bone lesions. Method: The literature search was conducted in Scopus, PubMed, IEEE and MedLine, and Web of Science electronic databases following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A total of 77 original articles, 24 review articles, and 1 comparison paper published between January 2010 and March 2022 were included in the review. Results: The results showed that most studies used neural network-based approaches (58.44%) and CT-based imaging (50.65%) out of 77 original articles. However, the review highlights the lack of a gold standard for tumor boundaries and the need for manual correction of the segmentation output, which largely explains the absence of clinical translation studies. Moreover, only 19 studies (24.67%) specifically mentioned the feasibility of their proposed methods for use in clinical practice. Conclusion: Development of tumor segmentation techniques that combine anatomical information and metabolic activities is encouraging despite not having an optimal tumor segmentation method for all applications or can compensate for all the difficulties built into data limitations. [ABSTRACT FROM AUTHOR]

Background: Imaging data contains a substantial amount of information which can be difficult to evaluate by eye. With the expansion of high throughput microscopy methodologies producing increasingly large datasets, automated and objective analysis of the resulting images is essential to effectively extract biological information from this data. CellProfiler is a free, open source image analysis program which enables researchers to generate modular pipelines with which to process microscopy images into interpretable measurements. Results: Herein we describe CellProfiler 4, a new version of this software with expanded functionality. Based on user feedback, we have made several user interface refinements to improve the usability of the software. We introduced new modules to expand the capabilities of the software. We also evaluated performance and made targeted optimizations to reduce the time and cost associated with running common large-scale analysis pipelines. Conclusions: CellProfiler 4 provides significantly improved performance in complex workflows compared to previous versions. This release will ensure that researchers will have continued access to CellProfiler's powerful computational tools in the coming years. [ABSTRACT FROM AUTHOR]

Summary Image-based experiments can yield many thousands of individual measurements describing each object of interest, such as cells in microscopy screens. CellProfiler Analyst is a free, open-source software package designed for the exploration of quantitative image-derived data and the training of machine learning classifiers with an intuitive user interface. We have now released CellProfiler Analyst 3.0, which in addition to enhanced performance adds support for neural network classifiers, identifying rare object subsets, and direct transfer of objects of interest from visualization tools into the Classifier tool for use as training data. This release also increases interoperability with the recently released CellProfiler 4, making it easier for users to detect and measure particular classes of objects in their analyses. Availability CellProfiler Analyst binaries for Windows and MacOS are freely available for download at https://cellprofileranalyst.org/. Source code is implemented in Python 3 and is available at https://github.com/CellProfiler/CellProfiler-Analyst/. A sample dataset is available at https://cellprofileranalyst.org/examples , based on images freely available from the Broad Bioimage Benchmark Collection. [ABSTRACT FROM AUTHOR]

We describe new open source software called QuantiFish for rapid quantitation of fluorescent foci in zebrafish larvae, to support infection research in this animal model. QuantiFish extends the conventional measurements of bacterial load and number of bacterial foci to include measures for dissemination of infection. These are represented by the proportions of bacteria between foci and their spatial distribution. We showcase these measures by comparison of intravenous and hindbrain routes of Mycobacterium marinum infection, which are indistinguishable by measurement of bacterial load and not consistently differentiated by the number of bacterial foci. The intravenous route showed dose dependent dissemination of infection, reflected by increased spatial dispersion of bacteria and lower proportions of bacteria distributed across many foci. In contrast, hindbrain infection resulted in localised disease, limited to a smaller area and higher proportions of bacteria distributed across fewer foci. The application of QuantiFish may extend beyond models of infection, to study other pathologies such as metastatic cancer. [ABSTRACT FROM AUTHOR]

Measuring dispersal in rare sessile benthic species is important in the development of conservation measures such as MPA networks. However, efforts to understand dispersal dynamics for many species of conservation concern are hampered by a lack of fundamental life-history information. Here we present the first description of larvae of the fan mussel, Atrina fragilis , and examine key life-history traits that affect dispersal. Larval identification was accomplished using complementary molecular and morphologic techniques. Atrina- specific primers were designed by aligning Atrina COI sequences available in GenBank. As none of these were from UK specimens, primers were designed in the most conserved regions found across A. fragilis and its closest relative A. chautardi. A monthly time-series of zooplankton samples (2014–2015) suggests that A. fragilis follows the same pattern in spawning observed for other pinnids at temperate latitudes, with peak spawning in summer and winter. Average shell growth was estimated to be 6 μm d–1 based on presumed daily growth lines on larval shells. Measurements of the larval shell visible through the juvenile shell indicate a length of up to 770 μm at settlement. Using presumed daily growth lines, this translates into a pelagic larval duration of around 4 months. [ABSTRACT FROM AUTHOR]

Drug resistance is a challenge in anticancer therapy. In many cases, cancers can be resistant to the drug prior to exposure, that is, possess intrinsic drug resistance. However, we lack target-independent methods to anticipate resistance in cancer cell lines or characterize intrinsic drug resistance without a priori knowledge of its cause. We hypothesized that cell morphology could provide an unbiased readout of drug resistance. To test this hypothesis, we used HCT116 cells, a mismatch repair-deficient cancer cell line, to isolate clones that were resistant or sensitive to bortezomib, a well-characterized proteasome inhibitor and anticancer drug to which many cancer cells possess intrinsic resistance. We then expanded these clones and measured high-dimensional single-cell morphology profiles using Cell Painting, a high-content microscopy assay. Our imagingand computation-based profiling pipeline identified morphological features that differed between resistant and sensitive cells. We used these features to generate a morphological signature of bortezomib resistance. We then employed this morphological signature to analyze a set of HCT116 clones (five resistant and five sensitive) that had not been included in the signature training dataset, and correctly predicted sensitivity to bortezomib in seven cases, in the absence of drug treatment. This signature predicted bortezomib resistance better than resistance to other drugs targeting the ubiquitin-proteasome system, indicating specificity for mechanisms of resistance to bortezomib. Our results establish a proof-of-concept framework for the unbiased analysis of drug resistance using high-content microscopy of cancer cells, in the absence of drug treatment. [ABSTRACT FROM AUTHOR]

Aim Given the paucity of data on the distribution of habitats and species for most marine species, particularly those that are rare and in need of protection, there is a need to model species distributions. Using the fan mussel, Atrina fragilis (Pennant 1777), as our case species, the aim of the study was to predict new areas of occurrence for A. fragilis, estimate the extent of potentially suitable areas, determine the proportion of these areas that are included in the recently designated nature conservation MPAs off the west of Scotland and identify possible environmental drivers in the distribution of A. fragilis. Location West coast of Scotland, UK. Methods Using a point process framework, we modelled presence-only data, including historic records. A quadrat survey employing digital still photography was conducted in areas of high and low suitability to verify the model, and subsequently, a targeted survey was undertaken in areas predicted as highly suitable by the models using towed video cameras. Results Five environmental variables were of prime importance in explaining the distribution of A. fragilis. The results from the verification survey support model performance. Atrina fragilis was found in 80% of the targeted transects undertaken. Approximately 14% of the total area predicted as suitable for A. fragilis occurred within recently designated marine protected areas ( MPAs) indicating considerable potential for recolonization given suitable protection. Main conclusions The verified model suggests that limited presence-only and historical records of rare species can perform well within a SDM framework allowing the identification of further suitable areas. The prominence of bathymetric ruggedness in the models is unexpected, given the understood ecological niche for A. fragilis and pinnids in general, but is consistent with the fact that seabed topography can offer protection from fishing pressure. These results will inform restoration objectives of the MPA network. [ABSTRACT FROM AUTHOR]

The modeling and measurement of the biodynamic response of the seated human body has recently been an active research topic, with major applications to ergonomics and automotive suspension control system technologies. This paper presents a holistic literature survey of topics including the latest research in the area of vibration signal processing and modeling of the biodynamic response of the seated human to vibrations. This paper reviews recent sensing systems that are reported to measure the motion of the seated body. The data processing techniques that are currently accepted are surveyed and these include impedance, transmissibility measures, frequency response function estimation, and model development. A review of applications of biodynamic response analysis and modeling to seating vibration isolation technologies and vibration monitoring systems is presented within this paper. This survey paper provides a discussion on the direction that the future research in this field will aim toward based on the trends in the recent research and the introduction and application of new technologies. [ABSTRACT FROM PUBLISHER]

Stirling et al. use two-photon excitation, confocal spectral microscopy and a novel ex vivo whole spinal cord model to assess the microglial response to spinal cord injury in real-time. Stimulation of microglia with a synthetic toll-like receptor 2 agonist, Pam2CSK4, modulated the microglial response and reduced white matter injury.Improving neurological outcome after spinal cord injury is a major clinical challenge because axons, once severed, do not regenerate but ‘dieback’ from the lesion site. Although microglia, the immunocompetent cells of the brain and spinal cord respond rapidly to spinal cord injury, their role in subsequent injury or repair remains unclear. To assess the role of microglia in spinal cord white matter injury we used time-lapse two-photon and spectral confocal imaging of green fluorescent protein-labelled microglia, yellow fluorescent protein-labelled axons, and Nile Red-labelled myelin of living murine spinal cord and revealed dynamic changes in white matter elements after laser-induced spinal cord injury in real time. Importantly, our model of acute axonal injury closely mimics the axonopathy described in well-characterized clinically relevant models of spinal cord injury including contusive-, compressive- and transection-based models. Time-lapse recordings revealed that microglia were associated with some acute pathophysiological changes in axons and myelin acutely after laser-induced spinal cord injury. These pathophysiological changes included myelin and axonal spheroid formation, spectral shifts in Nile Red emission spectra in axonal endbulbs detected with spectral microscopy, and ‘bystander’ degeneration of axons that survived the initial injury, but then succumbed to secondary degeneration. Surprisingly, modulation of microglial-mediated release of neurotoxic molecules failed to protect axons and myelin. In contrast, sterile stimulation of microglia with the specific toll-like receptor 2 agonist Pam2CSK4 robustly increased the microglial response to ablation, reduced secondary degeneration of central myelinated fibres, and induced an alternative (mixed M1:M2) microglial activation profile. Conversely, Tlr2 knock out: Thy1 yellow fluorescent protein double transgenic mice experienced greater axonal dieback than littermate controls. Thus, promoting an alternative microglial response through Pam2CSK4 treatment is neuroprotective acutely following laser-induced spinal cord injury. Therefore, anti-inflammatory treatments that target microglial activation may be counterintuitive after spinal cord injury. [ABSTRACT FROM AUTHOR]

Background: One of the major obstacles to the exploitation of genetic variation in human medicine, veterinary medicine, and animal breeding is the difficulty in defining haplotypes in unrelated individuals. Results: We have developed a Multiplex Double Amplification Refractory Mutation System combined with Solid Phase PCR on Fluorescently labelled beads. The process is inherently amenable to automation. It provides a high degree of internal Quality Control, as each PCR product is represented in duplicate on the bead array, and each SNP is tested against multiple partners. This technique can resolve very complex genotypes into their constituent haplotypes; it defined all the alleles at 60 SNP in exon 2 of the ovine DRB1 MHC locus in a sample of 109 rams. These 60 SNP formed 33 DRB1 exon 2 alleles; two of which had not been previously identified; although both of them have been independently confirmed. Conclusion: This technique has the same resolution as allele specific sequencing. Sequencing has the advantage of identifying novel polymorphic sites but where all SNP sites have been identified this novel procedure can resolve all alleles and haplotypes and identify novel combinations of polymorphisms. This method is similar in price to direct sequencing and provides a low cost system for direct haplotyping of extended DNA sequences. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) induces a robust inflammatory response and the extravasation of leukocytes into the injured tissue. To further knowledge of the functions of neuroinflammation in SCI in mice, we depleted the early arriving neutrophils using an anti-Ly6G/Gr-1 antibody. Complete blood counts revealed that neutrophils increased~3-fold over uninjured controls and peaked at 6 -12 h after injury, and that anti-Ly6G/Gr-1 treatment reduced circulating neutrophils by>90% at these time points. Intravital and spinning disk confocal microscopy of the exposed posterior vein and postcapillary venules showed a significant reduction in rolling and adhering neutrophils in vivo after anti-Ly6G/Gr-1 treatment; this was accompanied by a parallel reduction in neutrophil numbers within the injured spinal cord at 24 and 48 h as determined by flow cytometry. The evolution of astrocyte reactivity, a wound healing response, was reduced in anti-Ly6G/Gr-1-treated mice, which also had less spared white matter and axonal preservation compared with isotype controls. These histological outcomes may be caused by alterations of growth factors and chemokines important in promoting wound healing. Importantly, anti-Ly6G/Gr-1 treatment worsened behavioral outcome as determined using the Basso Mouse Scale and subscores. Although the spectrum of cells affected by anti-Ly6G/Gr-1 antibody treatment cannot be fully ascertained at this point, the correspondence of neutrophil depletion and worsened recovery suggests that neutrophils promote recovery after SCI through wound healing and protective events that limit lesion propagation. [ABSTRACT FROM AUTHOR]

Abstract-Harmonic monitoring has become an important tool for harmonic management in distribution system. A comprehensive harmonic monitoring program has been designed and implemented on a typical electrical medium-voltage distribution system in Australia. The monitoring program involved measurements of the three-phase harmonic currents and voltages from the residential, commercial, and industrial load sectors. Data over a three year period have been downloaded and available for analysis. The large amount of acquired data makes it difficult to identify operational events that significantly impact the harmonics generated on the system. More sophisticated analysis methods are required to automatically determine which part of the measurement data are of importance. Based on this information, a closer inspection of smaller data sets can then be carried out to determine the reasons for its detection. In this paper, we classify the measurement data using unsupervised learning based on clustering techniques using the minimum message length technique, which can provide the engineers with a rapid, visually oriented method of evaluating the underlying operational information contained within the clusters. Supervised learning is then used to describe the generated clusters and to predict the occurrences of unusual clusters in future measurement data. [ABSTRACT FROM AUTHOR]

Minocycline has been demonstrated to be neuroprotective after spinal cord injury (SCI). However, the cellular consequences of minocydine treatment on the secondary injury response are poorly understood. We examined the ability of minocycline to reduce oligodendrocyte apoptosis, microglial/macrophage activation, corticospinal tract (CST) dieback, and lesion size and to improve functional outcome after SCI. Adult rats were subjected to a C7-C8 dorsal column transection, and the presence of apoptotic oligodendrocytes was assessed within the ascending sensory tract (AST) and descending CST in segments (3-7 mm) both proximal and distal to the injury site. Surprisingly, the numbers of dying oligodendrocytes in the proximal and distal segments were comparable, suggesting more than the lack of axon- cell body contiguity played a role in their demise. Minocycline or vehicle control was injected into the intraperitoneal cavity 30 min and 8 hr after SCI and thereafter twice daffy for 2 d. We report a reduction of apoptotic oligodendrocytes and microglia within both proximal and distal segments of the AST after minocycline treatment, using immunostaining for active caspase-3 and Hoechst 33258 staining in combination with cell-specific markers. Activated microglial/macrophage density was reduced remote to the lesion as well as at the lesion site. Both CST dieback and lesion size were diminished after minocycline treatment. Footprint analysis revealed improved functional outcome after minocycline treatment. Thus, minocycline ameliorates multiple secondary events after SCI, rendering this clinically used drug an attractive candidate for SCI treatment trials. [ABSTRACT FROM AUTHOR]

1. The methane mono-oxygenase from Methylosinus trichosporium OB3b was soluble. The only suitable electron donor was NAD(P)H, neither sodium L-ascorbate nor electrons derived from the oxidation of methanol could substitute for NAD(P)H. Evidence is presented for the existence of an NAD+-linked formaldehyde dehydrogenase. 2. Monooxygenase activity was not inhibited by a range of potential inhibitors including potassium cyanide, amytal, carbon monoxide or various metal-chelating agents, although 8-hydroxy-quinoline and ethyne were effective in this respect. 3. Although the enzyme preparations were unstable on storage, the crude extract could be resolved into two components by ion-exchange chromatography. Activity could be restored to one of the components on addition of purified components from Methylococcus capsulatus (Bath). 4. Cross-reactivity of mono-oxygenase components and other similarities between the enzymes from M. trichosporium and M. capsulatus are discussed. The properties of the M. trichosporium methane mono-oxygenase reported here are contrasted with the properties of the same enzyme reported by others. [ABSTRACT FROM AUTHOR]

Ryanodine receptors (RyRs) mediate calcium release from calcium stores and have been implicated in axonal degeneration. Here, we use an intravital imaging approach to determine axonal fate after spinal cord injury (SCI) in real-time and assess the efficacy of ryanodine receptor inhibition as a potential therapeutic approach to prevent intra-axonal calcium-mediated axonal degeneration. Adult 6-8 week old Thy1YFP transgenic mice that express YFP in axons, as well as triple transgenic Avil-Cre:Ai9:Ai95 mice that express the genetically-encoded calcium indicator GCaMP6f in tdTomato positive axons, were used to visualize axons and calcium changes in axons, respectively. Mice received a mild SCI at the T12 level of the spinal cord. Ryanodine, a RyR antagonist, was given at a concentration of 50 μM intrathecally within 15 min of SCI or delayed 3 h after injury and compared with vehicle-treated mice. RyR inhibition within 15 min of SCI significantly reduced axonal spheroid formation from 1 h to 24 h after SCI and increased axonal survival compared with vehicle controls. Delayed ryanodine treatment increased axonal survival and reduced intra-axonal calcium levels at 24 h after SCI but had no effect on axonal spheroid formation. Together, our results support a role for RyR in secondary axonal degeneration. [ABSTRACT FROM AUTHOR]

Cryptococcus neoformans is an opportunistic human pathogen, which causes serious disease in immunocompromised hosts. Infection with this pathogen is particularly relevant in HIV+ patients, where it leads to around 200,000 deaths per annum. A key feature of cryptococcal pathogenesis is the ability of the fungus to survive and replicate within the phagosome of macrophages, as well as its ability to be expelled from host cells via a novel non-lytic mechanism known as vomocytosis. Here we show that cryptococcal vomocytosis from macrophages is strongly enhanced by viral coinfection, without altering phagocytosis or intracellular proliferation of the fungus. This effect occurs with distinct, unrelated human viral pathogens and is recapitulated when macrophages are stimulated with the anti-viral cytokines interferon alpha or beta (IFNα or IFNβ). Importantly, the effect is abrogated when type-I interferon signalling is blocked, thus underscoring the importance of type-I interferons in this phenomenon. Lastly, our data help resolve previous, contradictory animal studies on the impact of type I interferons on cryptococcal pathogenesis and suggest that secondary viral stimuli may alter patterns of cryptococcal dissemination in the host. Author summary: Infectious diseases are typically studied in isolation, but in real life people often encounter multiple infections simultaneously. Here we investigate how the innate immune response to the fatal fungus Cryptococcus neoformans is influenced by viral coinfection. Whilst virally-infected macrophages retain a normal capacity to engulf and kill Cryptococci, they demonstrate a dramatically enhanced propensity to expel them through vomocytosis. Activation of vomocytosis is driven by type-I interferons, generic 'antiviral' molecules, which signal back to the infected macrophage, triggering expulsion of the fungus. We propose that this hitherto unobserved phenomenon represents a 'reprioritisation' pathway for innate immune cells, by which they can alter the frequency with which they expel one pathogen depending on the level of threat from a secondary infection. [ABSTRACT FROM AUTHOR]

The vagus nerve is comprised primarily of non-myelinated sensory neurons whose cell bodies are located in the nodose ganglion (NG). The vagus has widespread projections that supply most visceral organs, including the bladder. Due to its non-spinal route, the vagus nerve itself is not directly damaged from spinal cord injury (SCI). Because most viscera, including bladder, are dually innervated by spinal and vagal sensory neurons, an impact of SCI on the sensory component of vagal circuitry may contribute to post-SCI visceral pathologies. To determine if SCI, in male Wistar rats, might impact neurochemical characteristics of NG neurons, immunohistochemical assessments were performed for P2X3 receptor expression, IB4 binding, and Substance-P expression, three known injury-responsive markers in sensory neuronal subpopulations. In addition to examining the overall population of NG neurons, those innervating the urinary bladder also were assessed separately. All three of the molecular markers were represented in the NG from non-injured animals, with the majority of the neurons binding IB4. In the chronically injured rats, there was a significant increase in the number of NG neurons expressing P2X3 and a significant decrease in the number binding IB4 compared to non-injured animals, a finding that held true also for the bladder-innervating population. Overall, these results indicate that vagal afferents, including those innervating the bladder, display neurochemical plasticity post-SCI that may have implications for visceral homeostatic mechanisms and nociceptive signaling. [ABSTRACT FROM AUTHOR]

The blue skate (Dipturus batis) has a patchy distribution across the North‐East Atlantic Ocean, largely restricted to occidental seas around the British Isles following fisheries‐induced population declines and extirpations. The viability of remnant populations remains uncertain and could be impacted by continued fishing and by‐catch pressure, and the projected impacts of climate change. We genotyped 503 samples of D. batis, obtained opportunistically from the widest available geographic range, across 6 350 single nucleotide polymorphisms (SNPs) using a reduced‐representation sequencing approach. Genotypes were used to assess the species' contemporary population structure, estimate effective population sizes and identify putative signals of selection in relation to environmental variables using a seascape genomics approach. We identified genetic discontinuities between inshore (British Isles) and offshore (Rockall and Faroe Island) populations, with differentiation most pronounced across the deep waters of the Rockall Trough. Effective population sizes were largest in the Celtic Sea and Rockall, but low enough to be of potential conservation concern among Scottish and Faroese sites. Among the 21 candidate SNPs under positive selection was one significantly correlated with environmental variables predicted to be affected by climate change, including bottom temperature, salinity and pH. The paucity of well‐annotated elasmobranch genomes precluded us from identifying a putative function for this SNP. Nevertheless, our findings suggest that climate change could inflict a strong selective force upon remnant populations of D. batis, further constraining its already‐restricted habitat. Furthermore, the results provide fundamental insights on the distribution, behaviour and evolutionary biology of D. batis in the North‐East Atlantic that will be useful for the establishment of conservation actions for this and other critically endangered elasmobranchs. [ABSTRACT FROM AUTHOR]

Vulnerable marine ecosystems (VMEs) are particularly susceptible to bottom-fishing activity as they are easily disturbed and slow to recover. A data-driven approach was developed to provide management options for the protection of VMEs under the European Union "deep-sea access regulations." A total of two options within two scenarios were developed. The first scenario defined VME closure areas without consideration of fishing activity. Option 1 proposed closures for the protection of VME habitats and likely habitat, while Option 2 also included areas where four types of VME geophysical elements were present. The second scenario additionally considered fishing. This scenario used VME biomass—fishing intensity relationships to identify a threshold where effort of mobile bottom-contact gears was low and unlikely to have caused significant adverse impacts. Achieving a high level of VME protection requires the creation of many closures (> 100), made up of many small (∼50 km2) and fewer larger closures (> 1000 km2). The greatest protection of VMEs will affect approximately 9% of the mobile fleet fishing effort, while closure scenarios that avoid highly fished areas reduce this to around 4–6%. The framework allows managers to choose the level of risk-aversion they wish to apply in protecting VMEs by comparing alternative strategies. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To examine the effects of acute insulin-induced hypoglycemia on inflammation, endothelial dysfunction, and platelet activation in adults with and without type I diabetes. RESEARCH DESIGN AND METHODS-- We studied 16 nondiabetic adults and 16 subjects with type 1 diabetes during euglycemia (blood glucose 4.5 mmol/l) and hypoglycemia (blood glucose 2.5 mmol/l). Markers of inflammation, thrombosis, and endothelial dysfunction (soluble P-selectin, interleukin-6, von Willebrand factor [vWF], tissue plasminogen activator [tPA], high-sensitivity C-reactive protein [hsCRP], and soluble CD40 ligand [sCD40L]) were measured; platelet-monocyte aggregation and CD40 expression on monocytes were determined using flow cytometry. RESULTS-- In nondiabetic participants, platelet activation occurred after hypoglycemia, with increments in platelet-monocyte aggregation and P-selectin (P ≤ 0.02). Inflammation was triggered with CD40 expression increasing maximally at 24 h (3.13 ± 2.3% vs. 2.06 ± 1.0%) after hypoglycemia (P = 0.009). Both sCD40L and hsCRP (P = 0.02) increased with a nonsignificant rise in vWF and tPA, indicating a possible endothelial effect. A reduction in sCD40L, tPA, and P-selectin occurred during euglycemia (P = 0.03, P ≤ 0.006, and P = 0.006, respectively). In type 1 diabetes, both CD40 expression (5.54 ± 4.4% vs. 3.65 ± 1.8%; P = 0.006) and plasma sCD40L concentrations increased during hypoglycemia (peak 3.41 ± 3.2 vs. 2.85 ± 2.8 ng/ml; P = 0.03). Platelet-monocyte aggregation also increased significantly at 24 h after hypoglycemia (P = 0.03). A decline in vWF. and P-selectin occurred during euglycemia (P ≤ 0.04). CONCLUSIONS -- Acute hypoglycemia may provoke upregulation and release of vasoactive substances in adults with and without type I diabetes. This may be a putative mechanism for hypoglycemia-induced vascular injury. [ABSTRACT FROM AUTHOR]

Monocytes and macrophages provide key targets for the action of novel anti-inflammatory therapeutics targeted at inhibition of PDE4 cAMP-specific phosphodiesterases. PDE4 enzymes provide the dominant cAMP phosphodiesterase activity in U937 human monocytic cells. Differentiation of U937 monocytic cells to a macrophage-like phenotype causes a marked reduction in total cellular PDE4 activity. Monocytic U937 cells express the long PDE4A4, PDE4D5 and PDE4D3 isoforms plus the short PDE4B2 isoform. Differentiation of U937 cells to a macrophage-like phenotype causes a marked downregulation of PDE4D3 and PDE4D5, elicits a marked upregulation of PDE4B2 and induces the novel PDE4A10 long isoform. Comparable patterns are found in human peripheral blood monocytes and macrophages differentiated from them. Immunopurification of PDE4 subfamilies identifies long PDE4D isoforms as providing the major PDE4 activity in U937 monocytic cells. In U937 macrophage-like cells, the activity of the short PDE4B2 isoform predominates. No indication of either the expression or induction of PDE4C was evident. Activation of ERK exerts an inhibitory effect on total PDE4 activity in monocytic U937 cells, where the activity of long PDE4 isoforms predominates. The effect of ERK activation is switched to one of overall stimulation of total PDE4 activity in macrophage U937 cells, where the activity of the short PDE4B2 isoform predominates.10 The profound differentiation-induced changes in PDE4 isoform profile identified here suggests that the development of inhibitors specific for particular PDE4 isoforms may allow for selective effects on monocytes and macrophages to be achieved. [ABSTRACT FROM AUTHOR]

SUMMARY: Comparison of pectenotoxin (PTX) profiles between the toxic dinoflagellate Dinophysis acuta and scallops Pecten novaezelandiae collected at Wedge Point, Queen Charlotte Sound, New Zealand was carried out by liquid chromatography–mass spectrometry (LC-MS) with turbo-ionspray ionization. Although the major PTX homolog in D. acuta was pectenotoxin-2 (PTX2), the scallops contained pectenotoxin-2 seco acid (PTX2SA) as the predominant toxin. Pectenotoxin-2 isolated from D. acuta was rapidly converted to PTX2SA and its epimer 7-epi-pectenotoxin-2 seco acid (7-epi-PTX2SA) in the scallop extracts. These results indicate that PTX2SA and 7-epi-PTX2SA arose from the conversion of PTX2 by scallop tissue. The results indicate that New Zealand scallops have an ability to reduce the cytotoxicity of PTX2 by conversion to PTX2SA. [ABSTRACT FROM AUTHOR]

Secondary axonal loss contributes to the persistent functional disability following trauma. Consequently, preserving axons following spinal cord injury (SCI) is a major therapeutic goal to improve neurological outcome; however, the complex molecular mechanisms that mediate secondary axonal degeneration remain unclear. We previously showed that IP 3 R-mediated Ca2+ release contributes to axonal dieback and axonal loss following an ex vivo laser-induced SCI. Nevertheless, targeting IP 3 R in a clinically relevant in vivo model of SCI and determining its contribution to secondary axonal degeneration has yet to be explored. Here we used intravital two-photon excitation microscopy to assess the role of IP 3 R in secondary axonal degeneration in real-time after a contusive-SCI in vivo. To visualize Ca2+ changes specifically in spinal axons over time, adult 6–8 week-old triple transgenic Avil -Cre:Ai9:Ai95 (sensory neuron-specific expression of tdTomato and the genetic calcium indicator GCaMP6f) mice were subjected to a mild (30 kdyn) T12 contusive-SCI and received delayed treatment with the IP 3 R blocker 2-APB (100 μM, intrathecal delivery at 3, and 24 h following injury) or vehicle control. To determine the IP 3 R subtype involved, we knocked-down IP 3 R3 using capped phosphodiester oligonucleotides. Delayed treatment with 2-APB significantly reduced axonal spheroids, increased axonal survival, and reduced intra-axonal Ca2+ accumulation within dorsal column axons at 24 h following SCI in vivo. Additionally, knockdown of IP 3 R3 yielded increased axon survival 24 h post-SCI. These results suggest that IP 3 R-mediated Ca2+ release contributes to secondary axonal degeneration in vivo following SCI. • Intravital imaging following contusive SCI reveals changes in spinal axons in real-time. • IP3R contribute to secondary axonal degeneration. • Delayed application of the IP3R antagonist, 2-APB increased axonal survival. • Delayed application of 2-APB reduced axonal spheroid formation. • Knockdown of IP3R subtype 3 increased axonal survival. [ABSTRACT FROM AUTHOR]

HIV-1 must replicate in cells that are equipped to defend themselves from infection through intracellular innate immune systems. HIV-1 evades innate immune sensing through encapsidated DNA synthesis and encodes accessory genes that antagonize specific antiviral effectors. Here, we show that both particle associated, and expressed HIV-1 Vpr, antagonize the stimulatory effect of a variety of pathogen associated molecular patterns by inhibiting IRF3 and NF-κB nuclear transport. Phosphorylation of IRF3 at S396, but not S386, was also inhibited. We propose that, rather than promoting HIV-1 nuclear import, Vpr interacts with karyopherins to disturb their import of IRF3 and NF-κB to promote replication in macrophages. Concordantly, we demonstrate Vpr-dependent rescue of HIV-1 replication in human macrophages from inhibition by cGAMP, the product of activated cGAS. We propose a model that unifies Vpr manipulation of nuclear import and inhibition of innate immune activation to promote HIV-1 replication and transmission. [ABSTRACT FROM AUTHOR]

Small molecules targeting the cereblon-containing E3 ubiquitin ligase including thalidomide, lenalidomide, and pomalidomide modulate turnover of downstream client proteins and demonstrate pre-clinical and clinical anti-myeloma activity. Different drugs that engage with cereblon hold the potential of unique phenotypic effects, and we therefore studied the novel protein homeostatic modulator (PHM™) BTX306 with a unique thiophene-fused scaffold bearing a substituted phenylurea and glutarimide. This agent much more potently reduced human-derived myeloma cell line viability, with median inhibitory concentrations in the single nanomolar range versus micromolar values for lenalidomide or pomalidomide, and more potently activated caspases 3/8/9. While lenalidomide and pomalidomide induced greater degradation of Ikaros and Aiolos in myeloma cells, BTX306 more potently reduced levels of GSPT1, eRF1, CK1α, MCL-1, and c-MYC. Suppression of cereblon or overexpression of Aiolos or Ikaros induced relative resistance to BTX306, and this agent did not impact viability of murine hematopoietic cells in an in vivo model, demonstrating its specificity for human cereblon. Interestingly, BTX306 did show some reduced activity in lenalidomide-resistant cell line models but nonetheless retained its nanomolar potency in vitro, overcame bortezomib resistance, and was equipotent against otherwise isogenic cell line models with either wild-type or knockout TP53. Finally, BTX306 demonstrated strong activity against primary CD138-positive plasma cells, showed enhanced anti-proliferative activity in combination with bortezomib and dexamethasone, and was effective in an in vivo systemic model of multiple myeloma. Taken together, the data support further translational studies of BTX306 and its derivatives to the clinic for patients with relapsed and/or refractory myeloma. Key messages: BTX306 has a unique thiophene-fused scaffold bearing phenylurea and glutarimide. BTX306 is more potent against myeloma cells than lenalidomide or pomalidomide. BTX306 overcomes myeloma cell resistance to lenalidomide or bortezomib in vitro. BTX306 is active against primary myeloma cells, and shows efficacy in vivo. [ABSTRACT FROM AUTHOR]

Axonal degeneration plays a key role in the pathogenesis of numerous neurological disorders including spinal cord injury. After the irreversible destruction of the white matter elements during the primary (mechanical) injury, spared axons and their supporting glial cells begin to breakdown causing an expansion of the lesion site. Here we mechanistically link external sources of calcium entry through axoplasmic reticulum calcium store depletion that contributes to secondary axonal degeneration through a process called store-operated calcium entry. There is increasing evidence suggesting that store-operated calcium entry impairment is responsible for numerous disorders. Nevertheless, its role following spinal cord injury remains poorly understood. We hypothesize that store-operated calcium entry mediates secondary white matter degeneration after spinal cord injury. We used our previously published model of laser-induced spinal cord injury to focally transect mid cervical dorsal column axons from live 6–8-week-old heterozygous CNPaseGFP/+: Thy1 YFP+ double transgenic murine spinal cord preparations (five treated, eight controls) and documented the dynamic changes in axons over time using two-photon excitation microscopy. We report that 1 hour delayed treatment with YM-58483, a potent inhibitor of store-operated calcium entry, significantly decreased intra-axonal calcium accumulation, axonal dieback both proximal and distal to the lesion site, reduced secondary axonal "bystander" damage acutely after injury, and promoted greater oligodendrocyte survival compared to controls. We also targeted store-operated calcium entry following a clinically relevant contusion spinal cord injury model in vivo. Adult, 6–8-week-old Advillin-Cre: Ai9 mice were subjected to a mild 30 kdyn contusion and imaged to observe secondary axonal degeneration in live animals. We found that delayed treatment with YM-58483 increased axonal survival and reduced axonal spheroid formation compared to controls (n = 5 mice per group). These findings suggest that blocking store-operated calcium entry acutely is neuroprotective and introduces a novel target to prevent pathological calcium entry following spinal cord injury using a clinically relevant model. • Live imaging of a laser-induced SCI model reveals changes in spinal axons in real-time. • Delayed SOCE inhibition reduces axonal dieback and axonal degeneration post-LiSCI. • Delayed SOCE inhibition reduces Ca2+ concentrations in degenerating axons post-LiSCI. • Delayed SOCE inhibition increases axonal survival post contusive-SCI in vivo. [ABSTRACT FROM AUTHOR]

The glucocorticoid receptor (GR) is a major drug target in inflammatory disease. However, chronic glucocorticoid (GC) treatment leads to disordered energy metabolism, including increased weight gain, adiposity, and hepatosteatosis - all programs modulated by the circadian clock. We demonstrated that while antiinflammatory GC actions were maintained irrespective of dosing time, the liver was significantly more GC sensitive during the day. Temporal segregation of GC action was underpinned by a physical interaction of GR with the circadian transcription factor REVERBa and co-binding with liver-specific hepatocyte nuclear transcription factors (HNFs) on chromatin. REVERBa promoted efficient GR recruitment to chromatin during the day, acting in part by maintaining histone acetylation, with REVERBa-dependent GC responses providing segregation of carbohydrate and lipid metabolism. Importantly, deletion of Reverba inverted circadian liver GC sensitivity and protected mice from hepatosteatosis induced by chronic GC administration. Our results reveal a mechanism by which the circadian clock acts through REVERBa in liver on elements bound by HNF4A/HNF6 to direct GR action on energy metabolism. [ABSTRACT FROM AUTHOR]

• Driver cognitive fatigue patterns also reflect in postural behaviour. • Body posture variations of alert drivers are minimal in long monotonous freeways. • In pre-fatigue state, driver's yawning behaviour has trivial sternum variations. • Fatigued posture has frequent occurrences of nodding and shaking of the head. • Driver's postural variations are validated against brain signals technique. Driver cognitive fatigue can significantly affect driving and may lead to fatal accidents. In this regard, automatic detection of underload driver cognitive fatigue based on upper body posture dynamics is studied in this paper, where a semi-supervised approach is developed to identify the cognitive fatigue patterns of driver posture. Initially, an unsupervised Gaussian Mixture Model (GMM) clustering is applied to the acceleration data representing the driver's head, neck, and sternum obtained in a simulated driving through a motion capture suit. This provides the optimum clusters of the most-similar and correlated time-series data of driver upper posture. Then, an automatic labelling algorithm is developed that mines the maximal value and the standard deviation of each GMM cluster and assigns a symbol according to the discrepancy in postural behaviour. Finally, novel machine learning supervised classifiers, including Gaussian Support Vector Machines, and Bootstrap-Aggregating based Ensemble Classifiers, are trained on the GMM-labelled upper body posture dataset, as real-time algorithms, to detect the driver fatigue. The proposed method was validated against cognitive fatigue measured through a neurophysiological method based on an electroencephalogram. The results show that the proposed semi-supervised approach outperforms the existing state-of-art systems in accurately detecting the cognitive fatigue patterns. It successfully recognizes different driving postures with accuracies of 93% and 90% for two test subjects. The shortcomings of the proposed work and directions for potential expansion of current work are discussed. [ABSTRACT FROM AUTHOR]

The laboratory plays an important role in teaching engineering skills. An Electrical Engineering department at an Australian University implemented a reform to monitor and improve student satisfaction with the teaching laboratories. A Laboratory Manager was employed to oversee the quality of 27 courses containing instructional laboratories. Student satisfaction surveys were carried out on all relevant laboratories every year, and the data were used for continuous improvement. This paper will investigate the reforms that were implemented and outline a number of the improvements made. It also examines the program's overall impact on: 1) overall satisfaction; 2) laboratory notes; 3) learning experiences; 4) computer facilities; 5) engineering equipment; and 6) condition of the laboratory. Student satisfaction with the laboratories increased by 32% between 2007 and 2013. The results show that the laboratory notes (activity and clarity) and the quality of the equipment used are among the most influential factors on student satisfaction. In particular, it is important to have notes or resources that explain in some detail how to use and troubleshoot equipment and software used in the laboratory. [ABSTRACT FROM AUTHOR]

This paper describes in detail a successful training program developed for sessional (part-time or nonpermanent) laboratory demonstrators employed in the Electrical Engineering Department of an Australian university. Such demonstrators play an important role in teaching practical concepts and skills in engineering. The success of the program relies on a centralized approach coordinated by a carefully selected Laboratory Manager responsible for the recruitment, allocation, training, and development of sessional teachers, and for assessing student satisfaction with them. The paper examines the overall impact of the program on these teachers': 1) introducing laboratory material; 2) preparation; 3) communication; 4) interest in student learning; 5) ability to respond to questions; and 6) overall effectiveness. Sessional teacher satisfaction with the training program is also examined, and the data were used to inform the program's further development. The results show that the training program successfully improved the demonstrators' teaching skills and thus led to greater satisfaction and hence learning experience of both students and demonstrators. [ABSTRACT FROM AUTHOR]

Nanotechnology plays an increasingly important role in the biomedical arena. In particular, magnetic nanoparticles (mNPs) have become important tools in molecular diagnostics, in vivo imaging and improved treatment of disease, with the ultimate aim of producing a more theranostic approach. Due to their small sizes, the nanoparticles can cross most of the biological barriers such as the blood vessels and the blood brain barrier, thus providing ubiquitous access to most tissues. In all biomedical applications maximum nanoparticle uptake into cells is required. Two promising methods employed to this end include functionalization of mNPs with cell-penetrating peptides to promote efficient translocation of cargo into the cell and the use of external magnetic fields for enhanced delivery. This study aimed to compare the effect of both penetratin and a static magnetic field with regards to the cellular uptake of 200 nm magnetic NPs and determine the route of uptake by both methods. Results demonstrated that both techniques increased particle uptake, with penetratin proving more cell specific. Clathrinmedicated endocytosis appeared to be responsible for uptake as shown via PCR and western blot, with Pitstop 2 (known to selectively block clathrin formation) blocking particle uptake.Interestingly, it was further shown that a magnetic field was able to reverse or overcome the blocking, suggesting an alternative route of uptake. [ABSTRACT FROM AUTHOR]

Abstract: This study investigates the effect of multiple sources using STS across a Time-Hopping-PPM Modulation that is over an UWB Saleh-Valenzuela channel with each source using two transmit antennas. We model and analyze this system, showing that the presence of such MAI results in a significant degradation in BER performance. Simulation results show that for strong signal strength of interfering MAI signals degradation in BER performance is observed for the cases where we have five and 10 distinct MAI sources present when using Walsh-Hadamard thirty two chip spreading sequences. Using simulation, we investigate the use of other sets of orthogonal spreading sequences with improved cross correlation properties and find that for some sequences a significant improvement is seen compared to Walsh-Hadamard sequences when they are similarly misaligned. We show that MAI degrades the BER performance of such systems and that selection of improved cross correlation spreading code sequence sets improves BER. [Copyright &y& Elsevier]

Objective: To examine the effects of acute insulin-induced hypoglycemia on inflammation, endothelial dysfunction, and platelet activation in adults with and without type 1 diabetes.Research Design and Methods: We studied 16 nondiabetic adults and 16 subjects with type 1 diabetes during euglycemia (blood glucose 4.5 mmol/l) and hypoglycemia (blood glucose 2.5 mmol/l). Markers of inflammation, thrombosis, and endothelial dysfunction (soluble P-selectin, interleukin-6, von Willebrand factor [vWF], tissue plasminogen activator [tPA], high-sensitivity C-reactive protein [hsCRP], and soluble CD40 ligand [sCD40L]) were measured; platelet-monocyte aggregation and CD40 expression on monocytes were determined using flow cytometry.Results: In nondiabetic participants, platelet activation occurred after hypoglycemia, with increments in platelet-monocyte aggregation and P-selectin (P Conclusions: Acute hypoglycemia may provoke upregulation and release of vasoactive substances in adults with and without type 1 diabetes. This may be a putative mechanism for hypoglycemia-induced vascular injury. [ABSTRACT FROM AUTHOR]

Lenalidomide (Revlimid®; CC-5013) and pomalidomide (CC-4047) are IMiDs® proprietary drugs having immunomodulatory properties that have both shown activity in cancer clinical trials; lenalidomide is approved in the United States for a subset of MDS patients and for treatment of patients with multiple myeloma when used in combination with dexamethasone. These drugs exhibit a range of interesting clinical properties, including anti-angiogenic, anti-proliferative, and pro-erythropoietic activities although exact cellular target(s) remain unclear. Also, anti-inflammatory effects on LPS-stimulated monocytes (TNF-α is decreased) and costimulatory effects on anti-CD3 stimulated T cells, (enhanced T cell proliferation and proinflammatory cytokine production) are observed These drugs also cause augmentation of NK-cell cytotoxic activity against tumour-cell targets. Having shown that pomalidomide confers T cell-dependant adjuvant-like protection in a preclinical whole tumour-cell vaccine-model, we now show that lenalidomide and pomalidomide strongly inhibit T-regulatory cell proliferation and suppressor-function. Both drugs inhibit IL-2-mediated generation of FOXP3 positive CTLA-4 positive CD25high CD4+ T regulatory cells from PBMCs by upto 50%. Furthermore, suppressor function of pre-treated T regulatory cells against autologous responder-cells is abolished or markedly inhibited without drug related cytotoxicity. Also, Balb/C mice exhibit 25% reduction of lymph-node T regulatory cells after pomalidomide treatment. Inhibition of T regulatory cell function was not due to changes in TGF-β or IL-10 production but was associated with decreased T regulatory cell FOXP3 expression. In conclusion, our data provide one explanation for adjuvant properties of lenalidomide and pomalidomide and suggest that they may help overcome an important barrier to tumour-specific immunity in cancer patients. [ABSTRACT FROM AUTHOR]

Background: Ocular melanoma is the leading intraocular malignancy. There is no effective treatment for metastatic ocular melanoma. We sought a treatment targeting the tumor microenvironment as well as the tumor cells. Methods: Migration of HUVEC cells, the ability of HUVEC cells to form tubes, and proliferative capacity of a human ocular melanoma cell line were tested in the presence of lenalidomide and sorafenib alone and in combination. The compounds were also tested in a rat aortic ring assay and were tested in a highly aggressive human ocular melanoma xenograft model. Results: Lenalidomide and Sorafenib inhibit HUVEC ability to migrate and form tubes and when used in combination the inhibition is increased. The agents alone and in combination inhibit outgrowth in the rat aortic ring model. The combination of the agents improved the inhibition over either single agent. In a xenograft model, combination therapy inhibited tumor growth over inhibition by single agent alone in a significant fashion (p < 0.004: lenalidomide and p < 0.0035: sorafenib). Furthermore, spontaneous lung metastasis development was completely inhibited in the combination treated animals. Sixty percent of vehicle treated animals developed lung metastases compared to 50% of lenalidomide treated animals, and 33% of sorafenib treated animals. Conclusion: Lenalidomide and sorafenib are effective at targeting endothelial cells, inhibiting growth of ocular melanoma cells and can inhibit growth of tumors in a xenograft model as well as inhibit development of metastases. Combining these agents works in an additive to synergistic way to inhibit the growth of tumors and development of metastases. [ABSTRACT FROM AUTHOR]

Reliable quantitative evaluation of molecular pathways is critical for both drug discovery and treatment monitoring. We have modified the CAM assay to quantitatively measure vascular density, endothelial proliferation, and changes in protein expression in response to anti-angiogenic and pro-angiogenic agents. This improved CAM assay can correlate changes in vascular density with changes seen on a molecular level. We expect that these described modifications will result in a single in vivo assay system, which will improve the ability to investigate molecular mechanisms underlying the angiogenic response. [ABSTRACT FROM AUTHOR]

Leprosy is a chronic infection of the skin and nerves caused by Mycobacterium leprae. Erythema nodosum leprosum (ENL) is a reactive state in lepromatous leprosy. Thalidomide has been used to treat ENL since the 1960s. One of its mechanisms of action is anti-inflammatory through selective inhibition of the pro-inflammatory cytokine TNF-α produced by monocytes. [Copyright &y& Elsevier]

• Limited deep-sea exploration still hinders assessments of its environmental status. • We applied the Nested Environmental status Assessment Tool to deep EU waters. • 24 indicators were selected, helping implement MSFD in the EU's deep sea. • NEAT results were in reasonable agreement with expert judgement and literature. The deep sea is the largest biome on Earth but the least explored. Our knowledge of it comes from scattered sources spanning different spatial and temporal scales. Implementation of marine policies like the European Union's Marine Strategy Framework Directive (MSFD) and support for Blue Growth in the deep sea are therefore hindered by lack of data. Integrated assessments of environmental status require tools to work with different and disaggregated datasets (e.g. density of deep-sea habitat-forming species, body-size distribution of commercial fishes, intensity of bottom trawling) across spatial and temporal scales. A feasibility study was conducted as part of the four-year ATLAS project to assess the effectiveness of the open-access Nested Environmental status Assessment Tool (NEAT) to assess deep-sea environmental status. We worked at nine selected study areas in the North Atlantic focusing on five MSFD descriptors (D1-Biodiversity, D3-Commercial fish and shellfish, D4-Food webs, D6-Seafloor integrity, D10-Marine litter). The objectives of the present study were to i) explore and propose indicators that could be used in the assessment of deep-sea environmental status, ii) evaluate the performance of NEAT in the deep sea, and iii) identify challenges and opportunities for the assessment of deep-sea status. Based on data availability, data quality and expert judgement, in total 24 indicators (one for D1, one for D3, seven for D4, 13 for D6, two for D10) were used in the assessment of the nine study areas, their habitats and ecosystem components. NEAT analyses revealed differences among the study areas for their environmental status ranging from "poor" to "high". Overall, the NEAT results were in moderate to complete agreement with expert judgement, previous assessments, scientific literature on human-pressure gradients and expected management outcomes. We suggest that the assessment of deep-sea environmental status should take place at habitat and ecosystem level (rather than at species level) and at relatively large spatial scales, in comparison to shallow-water areas. Limited knowledge across space (e.g. distribution of habitat-forming species) and the scarcity of long-term data sets limit our knowledge about natural variability and human impacts in the deep sea preventing a more systematic assessment of habitat and ecosystem components in the deep sea. However, stronger cross-sectoral collaborations, the use of novel technologies and open data-sharing platforms will be critical for establishing environmental baseline indicator values in the deep sea that will contribute to the science base supporting the implementation of marine policies and stimulating Blue Growth. [ABSTRACT FROM AUTHOR]