CFD Modelling of Goaf Gas Migration to Improve the Control of Spontaneous Combustion in Longwalls

This paper provides an overview of computational fluid dynamics (CFD) modelling capability developed by CSIRO with the aim of improving the knowledge of flow migration dynamics within longwall goaf areas. The CFD models can be used to study the ingress of oxygen into the goaf in different ventilation scenarios and goaf drainage arrangements. This approach not only helps the design of effective gas control strategies but also the management of spontaneous combustion risk in the goaf. Innovative goaf inertisation strategies have been developed and implemented during longwall sealing operations. Work is continuing to develop general guidelines of proactive goaf inertisation strategies to suppress the development of spontaneous heating behind active longwall faces

Combining modern assessment methods to improve understanding of longwall geomechanics

Ongoing, collaborative research between CSIRO\u27s Exploration and Mining and Strata Control Technology has resulted in a better understanding of rock failure mechanisms around longwall extraction. Failure has occurred further ahead of the retreating face than predicted by conventional longwall geomechanics theory. In some cases significant failure has been detected several hundred metres ahead of the face position with demonstrated influences of minor geological discontinuities. Shear, rather than tensile failure has been the predominant failure mechanism in the environments monitored. Validating technologies of microseismic monitoring and new face monitoring techniques have assisted the development of predictive 2D computational modelling tools. The demonstrated 3D consequences of failure has assisted in the ongoing direction of the project to further investigate these effects

Current research into brain barriers and the delivery of therapeutics for neurological diseases: a report on CNS barrier congress London, UK, 2017.

This is a report on the CNS barrier congress held in London, UK, March 22-23rd 2017 and sponsored by Kisaco Research Ltd. The two 1-day sessions were chaired by John Greenwood and Margareta Hammarlund-Udenaes, respectively, and each session ended with a discussion led by the chair. Speakers consisted of invited academic researchers studying the brain barriers in relation to neurological diseases and industry researchers studying new methods to deliver therapeutics to treat neurological diseases. We include here brief reports from the speakers

Amelioration of systemic inflammation via the display of two different decoy protein receptors on extracellular vesicles

Extracellular vesicles (EVs) can be functionalized to display specific protein receptors on their surface. However, surface-display technology typically labels only a small fraction of the EV population. Here, we show that the joint display of two different therapeutically relevant protein receptors on EVs can be optimized by systematically screening EV-loading protein moieties. We used cytokine-binding domains derived from tumour necrosis factor receptor 1 (TNFR1) and interleukin-6 signal transducer (IL-6ST), which can act as decoy receptors for the pro-inflammatory cytokines tumour necrosis factor alpha (TNF-α) and IL-6, respectively. We found that the genetic engineering of EV-producing cells to express oligomerized exosomal sorting domains and the N-terminal fragment of syntenin (a cytosolic adaptor of the single transmembrane domain protein syndecan) increased the display efficiency and inhibitory activity of TNFR1 and IL-6ST and facilitated their joint display on EVs. In mouse models of systemic inflammation, neuroinflammation and intestinal inflammation, EVs displaying the cytokine decoys ameliorated the disease phenotypes with higher efficacy as compared with clinically approved biopharmaceutical agents targeting the TNF-α and IL-6 pathways.International Society for Advancement of Cytometry Marylou Ingram Scholar 2019-2023H2020 EXPERTSwedish foundation of Strategic Research (SSF-IRC; FormulaEx)ERC CoG (DELIVER)Swedish Medical Research CouncilAccepte

NPM1 directs PIDDosome-dependent caspase-2 activation in the nucleolus

The PIDDosome (PIDD–RAIDD–caspase-2 complex) is considered to be the primary signaling platform for caspase-2 activation in response to genotoxic stress. Yet studies of PIDD-deficient mice show that caspase-2 activation can proceed in the absence of PIDD. Here we show that DNA damage induces the assembly of at least two distinct activation platforms for caspase-2: a cytoplasmic platform that is RAIDD dependent but PIDD independent, and a nucleolar platform that requires both PIDD and RAIDD. Furthermore, the nucleolar phosphoprotein nucleophosmin (NPM1) acts as a scaffold for PIDD and is essential for PIDDosome assembly in the nucleolus after DNA damage. Inhibition of NPM1 impairs caspase-2 processing, apoptosis, and caspase-2–dependent inhibition of cell growth, demonstrating that the NPM1-dependent nucleolar PIDDosome is a key initiator of the caspase-2 activation cascade. Thus we have identified the nucleolus as a novel site for caspase-2 activation and function

Tumour brain: pre‐treatment cognitive and affective disorders caused by peripheral cancers

People that develop extracranial cancers often display co-morbid neurological disorders, such as anxiety, depression and cognitive impairment, even before commencement of chemotherapy. This suggests bidirectional crosstalk between non-CNS tumours and the brain, which can regulate peripheral tumour growth. However, the reciprocal neurological effects of tumour progression on brain homeostasis are not well understood. Here, we review brain regions involved in regulating peripheral tumour development and how they, in turn, are adversely affected by advancing tumour burden. Tumour-induced activation of the immune system, blood–brain barrier breakdown and chronic neuroinflammation can lead to circadian rhythm dysfunction, sleep disturbances, aberrant glucocorticoid production, decreased hippocampal neurogenesis and dysregulation of neural network activity, resulting in depression and memory impairments. Given that cancer-related cognitive impairment diminishes patient quality of life, reduces adherence to chemotherapy and worsens cancer prognosis, it is essential that more research is focused at understanding how peripheral tumours affect brain homeostasis

KDM1A microenvironment, its oncogenic potential, and therapeutic significance

The lysine-specific histone demethylase 1A (KDM1A) was the first demethylase to challenge the concept of the irreversible nature of methylation marks. KDM1A, containing a flavin adenine dinucleotide (FAD)-dependent amine oxidase domain, demethylates histone 3 lysine 4 and histone 3 lysine 9 (H3K4me1/2 and H3K9me1/2). It has emerged as an epigenetic developmental regulator and was shown to be involved in carcinogenesis. The functional diversity of KDM1A originates from its complex structure and interactions with transcription factors, promoters, enhancers, oncoproteins, and tumor-associated genes (tumor suppressors and activators). In this review, we discuss the microenvironment of KDM1A in cancer progression that enables this protein to activate or repress target gene expression, thus making it an important epigenetic modifier that regulates the growth and differentiation potential of cells. A detailed analysis of the mechanisms underlying the interactions between KDM1A and the associated complexes will help to improve our understanding of epigenetic regulation, which may enable the discovery of more effective anticancer drugs

CFD Modelling of Goaf Gas Migration to Improve the Control of Spontaneous Combustion in Longwalls

This paper provides an overview of computational fluid dynamics (CFD) modelling capability developed by CSIRO with the aim of improving the knowledge of flow migration dynamics within longwall goaf areas. The CFD models can be used to study the ingress of oxygen into the goaf in different ventilation scenarios and goaf drainage arrangements. This approach not only helps the design of effective gas control strategies but also the management of spontaneous combustion risk in the goaf. Innovative goaf inertisation strategies have been developed and implemented during longwall sealing operations. Work is continuing to develop general guidelines of proactive goaf inertisation strategies to suppress the development of spontaneous heating behind active longwall faces

Innovative CDF Modelling Ling to Improve Dust Control in Longwalls

Reducing dust exposure of operators on longwall faces remains a challenging issue for mine managements. Most of the Australian mines are adopting uni-di cutting method to reduce operators dust exposure levels. Even in this uni-di cutting mode, the dust roll-up towards the walkway area is very high in most cases and is resulting in high dust exposure levels for shearer and chock operators. With the support of ACARP, CSIRO has been undertaking several research projects (C12025, C13019 and C14036) based upon CFD modelling to improve the understanding of dust flow patterns around the longwall shearer and walkway under different operating conditions, and the study of a range of dust control options/concepts for reducing operators dust exposure levels. During these simulation studies, a shearer scrubber system has shown to be capable of significantly modifying the airflow patterns around the maingate cutting drum and reducing dust roll-up towards the walkway area

Development of Innovative Goaf Inertisation Practices to Improve Coal Mine Safety

In combination with detailed field studies and goaf gas characterisation, computational fluid dynamics (CFD) models have been used to develop optimum and effective strategies for inertisation during longwall sealing operations to achieve goaf inertisation within a few hours of panel seal-off operation. This study has combined detailed analysis of the performance of various inertisation field trials together with CFD modelling results of different inertisation operations in order to develop the optimum inertisation strategies. A number of parametric studies were conducted on the base case CFD models that had been calibrated and validated based on the information obtained from previous inertisation studies and goaf gas monitoring. These studies included changes in inert gas injection locations, inert gas flow rates, seam gradients, and different inertisation strategies to investigate their effect on goaf inertisation. Studies indicate that the strategy of inert gas injection through the MG seal was not as effective as the alternative strategy of inert gas injection at 200 m behind the face. Innovative inertisation strategies have been developed and subsequently implemented at an underground coal mine in Australia. Further investigations have been carried out in the development and demonstration of proactive inertisation strategies with the objective to suppress the occurrence of spontaneous heatings in active longwall faces, in particular under unexpected scenarios such as during slow retreat/face stoppage due to difficult geological conditions. Initial trials at two Australian longwall panels have demonstrated the great potential of this practice to contain the onset of heatings in the goaf