Influence of primary and secondary air supply on gaseous emissions from a small-scale staged solid biomass fuel combustor

The emissions from traditional biomass combustion systems for cooking and heating are, globally, the main cause for premature mortality as a result of air pollution. A staged combustion process that separates the thermochemical conversion of the solid fuel and the combustion of the released products offers potential to reduce harmful emissions for solid fuel combustion and could, therefore, help mitigate the issue. In the present study, the fundamental combustion behavior of a small-scale staged combustor was investigated, with a focus on an independent systematic analysis of relevant parameters. Natural and forced draft conditions as well as a combination of both were tested. The relative location of primary to secondary air was also varied. When lighting the fuel, higher air flows lead to faster ignition and lower emissions. A steady-state combustion phase is achieved when gasification products are burned with secondary air, which occurs mainly while the solid fuel is being pyrolyzed. After the steady-state phase, char remains as the solid pyrolysis product. Gasification of the remaining char was found to release great amounts of CO, which are emitted from the combustor, in the case of natural draft secondary air (SA). With higher air flows of forced SA, an exceptionally high nominal combustion efficiency [NCE = XCO2/(XCO + XCO2)] can be achieved in the steady-state phase. Forced SA flows cause a longer duration of the steady-state phase from the combustion of raw biomass gasification products into the combustion of char gasification products. This extension leads to a significant reduction of emissions of incomplete combustion. Additionally, smaller distances between the SA inlet and the fuel stack caused lower emissions of incomplete combustion. The combination of forced draft primary air and natural draft SA presented worse combustor performance than under natural draft conditions.Thomas Kirch, Cristian H. Birzer, Philip J. van Eyk, and Paul R. Medwel

RNA pathogenesis via Toll-like receptor-activated inflammation in expanded repeat neurodegenerative diseases

Previously, we hypothesized that an RNA-based pathogenic pathway has a causal role in the dominantly inherited unstable expanded repeat neurodegenerative diseases. In support of this hypothesis we, and others, have characterized rCAG.rCUG100 repeat double-strand RNA (dsRNA) as a previously unidentified agent capable of causing pathogenesis in a Drosophila model of neurodegenerative disease. Dicer, Toll, and autophagy pathways have distinct roles in this Drosophila dsRNA pathology. Dicer dependence is accompanied by cleavage of rCAG.rCUG100 repeat dsRNA down to r(CAG)7 21-mers. Among the “molecular hallmarks” of this pathway that have been identified in Drosophila, some [i.e., r(CAG)7 and elevated tumor necrosis factor] correlate with observations in affected people (e.g., Huntington’s disease and amyotrophic lateral sclerosis) or in related animal models (i.e., autophagy). The Toll pathway is activated in the presence of repeat-containing dsRNA and toxicity is also dependent on this pathway. How might the endogenously expressed dsRNA mediate Toll-dependent toxicity in neuronal cells? Endogenous RNAs are normally shielded from Toll pathway activation as part of the mechanism to distinguish “self” from “non-self” RNAs. This typically involves post-transcriptional modification of the RNA. Therefore, it is likely that rCAG.rCUG100 repeat dsRNA has a characteristic property that interferes with or evades this normal mechanism of shielding. We predict that repeat expansion leads to an alteration in RNA structure and/or form that perturbs RNA modification, causing the unshielded repeat RNA (in the form of its Dicer-cleaved products) to be recognized by Toll-like receptors (TLRs), with consequent activation of the Toll pathway leading to loss of cell function and then ultimately cell death. We hypothesize that the proximal cause of expanded repeat neurodegenerative diseases is the TLR recognition (and resultant innate inflammatory response) of repeat RNA as “non-self” due to their paucity of “self” modification.Robert I. Richards, Saumya E. Samaraweera, Clare L. van Eyk, Louise V. O’Keefe and Catherine M. Sute

Influences of fuel bed depth and air supply on small-scale batch-fed reverse downdraft biomass conversion

The producer gas composition and the thermochemical conversion process of a small-scale reverse downdraft reactor has been investigated under ten operating conditions with different fuel bed depths and air supply rates. The operating principle of this research reactor is a batch-fed reverse downdraft process, using wood pellets as the solid biomass fuel. The oxygen-limited regime, where the fuel consumption increases nearly linearly with the air supply, has been identified, and four flow rates over the range of this regime have been investigated. The fuel bed depth was varied between one and four reactor diameters (1D (100 mm)–4D (400 mm)). The results demonstrate that increasing the primary air mass flux leads to both greater fuel consumption and higher temperatures as well as heating rates in the reaction front. Greater air supply rates and the resulting higher temperatures lead to a substantial increase in fuel conversion into permanent gases, rather than tars or char, and a rise in the cold gas efficiency (CGE) from 33% to 73%, from the lowest to highest air flow rate at a 4D fuel bed depth. However, the temporal producer gas heating value is similar in all configurations. With increasing depth, it is evident that H₂ production is promoted by the char layer downstream of the reaction front and that a certain layer thickness is necessary to achieve the potential near steady-state product flow at a specific flow rate. Interestingly, a greater fuel bed depth enhances the hydrogen conversion rate to permanent gases by more than 20% and the CGE from 48% to 53%, while the fuel consumption and temperature profiles remain similar. A general trend of increasing performance was identified at the 3D and 4D depths, when compared with the 1D and 2D fuel bed depths. The produced char exhibits a high fixed and elemental carbon content. Therefore, the conversion efficiency of this process can be increased both through increasing the fuel bed depth and, even more, through adjusting the air supply, promoting the yield of permanent gases and the conversion of produced tars.Thomas Kirch, Paul R. Medwell, Cristian H. Birzer and Philip J. van Ey

To what extent can the activities of the South Australian Health in All Policies initiative be linked to population health outcomes using a program theory-based evaluation?

BACKGROUND: This paper reports on a five-year study using a theory-based program logic evaluation, and supporting survey and interview data to examine the extent to which the activites of the South Australian Health in All Policies initiative can be linked to population health outcomes. METHODS: Mixed-methods data were collected between 2012 and 2016 in South Australia (144 semi-structured key informant interviews; two electronic surveys of public servants in 2013 (n = 435) and 2015 (n = 483); analysis of state government policy documents; and construction of a program logic model to shape assessment of the feasibility of attribution to population health outcomes). RESULTS: Multiple actions on social determinants of health in a range of state government sectors were reported and most could be linked through a program logic model to making some contribution to future population health outcomes. Context strongly influences implementation; not all initiatives will be successful and experimentation is vital. Successful initiatives included HiAP influencing the urban planning department to be more concerned with the health impacts of planning decisions, and encouraging the environment department to be concerned with the health impacts of its work. CONCLUSIONS: The theory-based program logic suggests that SA HiAP facilitated improved population health through working with multiple government departments. Public servants came to appreciate how their sectors impact on health. Program logic is a mechanism to evaluate complex public health interventions in a way that takes account of political and economic contexts. SA HiAP was mainly successful in avoiding lifestyle drift in strategy. The initiative encouraged a range of state government departments to tackle conditions of daily living. The broader underpinning factors dictating the distribution of power, money and resources were not addressed by HiAP. This reflects HiAP's use of a consensus model which was driven by (rather than drove) state priorities and sought 'win-win' strategies

Perturbation of the Akt/Gsk3-beta signalling pathway is common to Drosophila expressing expanded untranslated CAG, CUG and AUUCU repeat RNAs

Recent evidence supports a role for RNA as a common pathogenic agent in both the ‘polyglutamine’ and ‘untranslated’ dominant expanded repeat disorders. One feature of all repeat sequences currently associated with disease is their predicted ability to form a hairpin secondary structure at the RNA level. In order to investigate mechanisms by which hairpin-forming repeat RNAs could induce neurodegeneration, we have looked for alterations in gene transcript levels as hallmarks of the cellular response to toxic hairpin repeat RNAs. Three disease-associated repeat sequences—CAG, CUG and AUUCU—were specifically expressed in the neurons of Drosophila and resultant common transcriptional changes assessed by microarray analyses. Transcripts that encode several components of the Akt/Gsk3-β signalling pathway were altered as a consequence of expression of these repeat RNAs, indicating that this pathway is a component of the neuronal response to these pathogenic RNAs and may represent an important common therapeutic target in this class of diseases.Clare L. van Eyk, Louise V. O'Keefe, Kynan T. Lawlor, Saumya E. Samaraweera, Catherine J. McLeod, Gareth R. Price, Deon J. Venter and Robert I. Richard

Analysis of 182 cerebral palsy transcriptomes points to dysregulation of trophic signalling pathways and overlap with autism

Cerebral palsy (CP) is the most common motor disability of childhood. It is characterised by permanent, non-progressive but not unchanging problems with movement, posture and motor function, with a highly heterogeneous clinical spectrum and frequent neurodevelopmental comorbidities. The aetiology of CP is poorly understood, despite recent reports of a genetic contribution in some cases. Here we demonstrate transcriptional dysregulation of trophic signalling pathways in patient-derived cell lines from an unselected cohort of 182 CP-affected individuals using both differential expression analysis and weighted gene co-expression network analysis (WGCNA). We also show that genes differentially expressed in CP, as well as network modules significantly correlated with CP status, are enriched for genes associated with ASD. Combining transcriptome and whole exome sequencing (WES) data for this CP cohort likely resolves an additional 5% of cases separated to the 14% we have previously reported as resolved by WES. Collectively, these results support a convergent molecular abnormality in CP and ASD.Clare L. van Eyk, Mark A. Corbett, Alison Gardner, Bregje W. van Bon, Jessica L. Broadbent, Kelly Harper, Alastair H. MacLennan and Jozef Gec

Methionine Adenosyltransferase α1 Is Targeted to the Mitochondrial Matrix and Interacts with Cytochrome P450 2E1 to Lower Its Expression

Methionine adenosyltransferase α1 (MATα1, encoded by MAT1A) is responsible for hepatic biosynthesis of S‐adenosyl methionine, the principal methyl donor. MATα1 also act as a transcriptional cofactor by interacting and influencing the activity of several transcription factors. Mat1a knockout (KO) mice have increased levels of cytochrome P450 2E1 (CYP2E1), but the underlying mechanisms are unknown. The aims of the current study were to identify binding partners of MATα1 and elucidate how MATα1 regulates CYP2E1 expression. We identified binding partners of MATα1 by coimmunoprecipitation (co‐IP) and mass spectrometry. Interacting proteins were confirmed using co‐IP using recombinant proteins, liver lysates, and mitochondria. Alcoholic liver disease (ALD) samples were used to confirm relevance of our findings. We found that MATα1 negatively regulates CYP2E1 at mRNA and protein levels, with the latter being the dominant mechanism. MATα1 interacts with many proteins but with a predominance of mitochondrial proteins including CYP2E1. We found that MATα1 is present in the mitochondrial matrix of hepatocytes using immunogold electron microscopy. Mat1a KO hepatocytes had reduced mitochondrial membrane potential and higher mitochondrial reactive oxygen species, both of which were normalized when MAT1A was overexpressed. In addition, KO hepatocytes were sensitized to ethanol and tumor necrosis factor α–induced mitochondrial dysfunction. Interaction of MATα1 with CYP2E1 was direct, and this facilitated CYP2E1 methylation at R379, leading to its degradation through the proteasomal pathway. Mat1a KO livers have a reduced methylated/total CYP2E1 ratio. MATα1’s influence on mitochondrial function is largely mediated by its effect on CYP2E1 expression. Patients with ALD have reduced MATα1 levels and a decrease in methylated/total CYP2E1 ratio. Conclusion: Our findings highlight a critical role of MATα1 in regulating mitochondrial function by suppressing CYP2E1 expression at multiple levels

Integrating Clinical Phenotype With Multiomics Analyses of Human Cardiac Tissue Unveils Divergent Metabolic Remodeling in Genotype-Positive and Genotype-Negative Patients With Hypertrophic Cardiomyopathy

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is caused by sarcomere gene mutations (genotype-positive HCM) in ≈50% of patients and occurs in the absence of mutations (genotype-negative HCM) in the other half of patients. We explored how alterations in the metabolomic and lipidomic landscape are involved in cardiac remodeling in both patient groups. METHODS: We performed proteomics, metabolomics, and lipidomics on myectomy samples (genotype-positive N=19; genotype-negative N=22; and genotype unknown N=6) from clinically well-phenotyped patients with HCM and on cardiac tissue samples from sex- and age-matched and body mass index-matched nonfailing donors (N=20). These data sets were integrated to comprehensively map changes in lipid-handling and energy metabolism pathways. By linking metabolomic and lipidomic data to variability in clinical data, we explored patient group-specific associations between cardiac and metabolic remodeling. RESULTS:HCM myectomy samples exhibited (1) increased glucose and glycogen metabolism, (2) downregulation of fatty acid oxidation, and (3) reduced ceramide formation and lipid storage. In genotype-negative patients, septal hypertrophy and diastolic dysfunction correlated with lowering of acylcarnitines, redox metabolites, amino acids, pentose phosphate pathway intermediates, purines, and pyrimidines. In contrast, redox metabolites, amino acids, pentose phosphate pathway intermediates, purines, and pyrimidines were positively associated with septal hypertrophy and diastolic impairment in genotype-positive patients. CONCLUSIONS: We provide novel insights into both general and genotype-specific metabolic changes in HCM. Distinct metabolic alterations underlie cardiac disease progression in genotype-negative and genotype-positive patients with HCM.</p

Identifying Patients at High Risk of a Cardiovascular Event in the Near Future Current Status and Future Directions: Report of a National Heart, Lung, and Blood Institute Working Group

The National Heart, Lung, and Blood Institute convened a working group to provide basic and clinical research recommendations to the National Heart, Lung, and Blood Institute on the development of an integrated approach for identifying those individuals who are at high risk for a cardiovascular event such as acute coronary syndromes (ACS) or sudden cardiac death in the “near term.” The working group members defined near-term as occurring within 1 year of the time of assessment. The participants reviewed current clinical cardiology practices for risk assessment and state-of-the-science techniques in several areas, including biomarkers, proteomics, genetics, psychosocial factors, imaging, coagulation, and vascular and myocardial susceptibility. This report presents highlights of these reviews and a summary of suggested research directions

Ubiquitous Expression of CUG or CAG Trinucleotide Repeat RNA Causes Common Morphological Defects in a Drosophila Model of RNA-Mediated Pathology

Expanded DNA repeat sequences are known to cause over 20 diseases, including Huntington’s disease, several types of spinocerebellar ataxia and myotonic dystrophy type 1 and 2. A shared genetic basis, and overlapping clinical features for some of these diseases, indicate that common pathways may contribute to pathology. Multiple mechanisms, mediated by both expanded homopolymeric proteins and expanded repeat RNA, have been identified by the use of model systems, that may account for shared pathology. The use of such animal models enables identification of distinct pathways and their ‘molecular hallmarks’ that can be used to determine the contribution of each pathway in human pathology. Here we characterise a tergite disruption phenotype in adult flies, caused by ubiquitous expression of either untranslated CUG or CAG expanded repeat RNA. Using the tergite phenotype as a quantitative trait we define a new genetic system in which to examine ‘hairpin’ repeat RNA-mediated cellular perturbation. Further experiments use this system to examine whether pathways involving Muscleblind sequestration or Dicer processing, which have been shown to mediate repeat RNA-mediated pathology in other model systems, contribute to cellular perturbation in this model