Function value-based multi-objective optimisation of reheating furnace operations using Hooke-Jeeves algorithm

Improved thermal efficiency in energy-intensive metal-reheating furnaces has attracted much attention recently in efforts to reduce both fuel consumption, and CO2 emissions. Thermal efficiency of these furnaces has improved in recent years (through the installation of regenerative or recuperative burners), and improved refractory insulation. However, further improvements can still be achieved through setting up reference values for the optimal set-point temperatures of the furnaces. Having a reasonable expression of objective function is of particular importance in such optimisation. This paper presents a function value-based multi-objective optimisation where the objective functions, which address such concerns as discharge temperature, temperature uniformity, and specific fuel consumption, are dependent on each other. Hooke-Jeeves direct search algorithm (HJDSA) was used to minimise the objective functions under a series of production rates. The optimised set-point temperatures were further used to construct an artificial neural network (ANN) of set-point temperature in each control zone. The constructed artificial neural networks have the potential to be incorporated into a more advanced control solution to update the set-point temperatures when the reheating furnace encounters a production rate change. The results suggest that the optimised set-point temperatures can highly improve heating accuracy, which is less than 1 °C from the desired discharge temperature

Influence of moisture absorption on electrical properties and charge dynamics of polyethylene silica-based nanocomposites

The use of nanocomposites as dielectric materials is expected to lead to improved electrical performance. However, recent research has shown that moisture absorption can cause a deterioration in the electrical performance of nanocomposites. Although it is generally accepted that hydroxyl groups attached to nanoparticle surfaces are the main cause of moisture absorption, the impact of this absorption on the electrical properties of nanocomposites is still not fully understood. In this paper, a series of measurements, including thermogravimetric analysis, DC breakdown, surface potential decay and space charge, are conducted with the aim of determining the impact of moisture absorption on the electrical properties of polyethylene/silica nanocomposites. The results show that the loading ratio of nanosilica and the humidity of the conditioning environment determine the amount of absorbed moisture. According to the Zhuravlev model, the main contribution to the deterioration in electrical properties of nanocomposites comes from the large amount of moisture absorbed in multilayer form. It is found that the loading ratio of nanosilica is the most significant factor in reducing DC breakdown strength

A multi-jurisdictional outbreak of Salmonella Typhimurium infections linked to backyard poultry—Australia, 2020

Zoonotic salmonellosis can occur either through direct contact with an infected animal or through indirect contact, such as exposure to an infected animal's contaminated environment. Between May and August 2020, a multi-jurisdictional outbreak of Salmonella Typhimurium (STm) infection due to zoonotic transmission was investigated in Australia. In total, 38 outbreak cases of STm with a median age of 5 years were reported. Epidemiological investigation showed contact with live poultry to be a common risk factor with most cases recently purchasing one-week old chicks from produce/pet stores. Traceback investigation of cases identified 25 product/pet stores of which 18 were linked to a single poultry breeder farm. On farm environmental sampling identified the same STm genotype as identified in cases. Whole genome sequencing of both environmental and human outbreak isolates found them to be highly related by phylogenetic analysis. This investigation describes the first documented widespread zoonotic salmonellosis outbreak in Australia attributed to backyard poultry exposure and identified potential risk factors and prevention and control measures for future outbreaks. Prevention of future outbreaks will require an integrated One Health approach involving the poultry industry, produce/pet store owners, animal healthcare providers, public health and veterinary health agencies and the public

S100 Calcium Binding Protein Family Members Associate With Poor Patient Outcome and Response to Proteasome Inhibition in Multiple Myeloma

Despite several new therapeutic options, multiple myeloma (MM) patients experience multiple relapses and inevitably become refractory to treatment. Insights into drug resistance mechanisms may lead to the development of novel treatment strategies. The S100 family is comprised of 21 calcium binding protein members with 17 S100 genes located in the 1q21 region, which is commonly amplified in MM. Dysregulated expression of S100 family members is associated with tumor initiation, progression and inflammation. However, the relationship between the S100 family and MM pathogenesis and drug response is unknown. In this study, the roles of S100 members were systematically studied at the copy number, transcriptional and protein level with patients’ survival and drug response. Copy number analysis revealed a predominant pattern of gains occurring in S100 genes clustering in the 1q21 locus. In general, gains of genes encoding S100 family members associated with worse patient survival. However, S100 gene copy number and S100 gene expression did not necessarily correlate, and high expression of S100A4 associated with poor patient survival. Furthermore, integrated analysis of S100 gene expression and ex vivo drug sensitivity data showed significant negative correlation between expression of S100 family members (S100A8, S100A9, and S100A12) and sensitivity to some drugs used in current MM treatment, including proteasome inhibitors (bortezomib, carfilzomib, and ixazomib) and histone deacetylase inhibitor panobinostat. Combined proteomic and pharmacological data exhibited significant negative association of S100 members (S100A4, S100A8, and S100A9) with proteasome inhibitors and panobinostat. Clinically, the higher expression of S100A4 and S100A10 were significantly linked to shorter progression free survival in patients receiving carfilzomib-based therapy. The results indicate an association and highlight the potential functional importance of S100 members on chromosome 1q21 in the development of MM and resistance to established myeloma drugs, including proteasome inhibitors.Peer reviewe

Predictive value of cell-surface markers in infections in critically ill patients: protocol for an observational study (ImmuNe FailurE in Critical Therapy (INFECT) Study).

INTRODUCTION: Critically ill patients are at high risk of nosocomial infections, with between 20% and 40% of patients admitted to the intensive care unit (ICU) acquiring infections. These infections result in increased antibiotic use, and are associated with morbidity and mortality. Although critical illness is classically associated with hyperinflammation, the high rates of nosocomial infection argue for an importance of effect of impaired immunity. Our group recently demonstrated that a combination of 3 measures of immune cell function (namely neutrophil CD88, monocyte HLA-DR and % regulatory T cells) identified a patient population with a 2.4-5-fold greater risk for susceptibility to nosocomial infections. METHODS AND ANALYSIS: This is a prospective, observational study to determine whether previously identified markers of susceptibility to nosocomial infection can be validated in a multicentre population, as well as testing several novel markers which may improve the risk of nosocomial infection prediction. Blood samples from critically ill patients (those admitted to the ICU for at least 48 hours and requiring mechanical ventilation alone or support of 2 or more organ systems) are taken and undergo whole blood staining for a range of immune cell surface markers. These samples undergo analysis on a standardised flow cytometry platform. Patients are followed up to determine whether they develop nosocomial infection. Infections need to meet strict prespecified criteria based on international guidelines; where these criteria are not met, an adjudication panel of experienced intensivists is asked to rule on the presence of infection. Secondary outcomes will be death from severe infection (sepsis) and change in organ failure. ETHICS AND DISSEMINATION: Ethical approval including the involvement of adults lacking capacity has been obtained from respective English and Scottish Ethics Committees. Results will be disseminated through presentations at scientific meetings and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02186522; Pre-results.Innovate UK (formerly Technology Strategy Board) (Grant ID: 15457-108136), Becton Dickinson bioscience, NHS Lothian via the Edinburgh Health Services Research Unit, National Institute of Academic AnaesthesiaThis is the final version of the article. It first appeared from BMJ Publishing Group via http://dx.doi.org/10.1136/bmjopen-2016-01132

Modelling and simulation of steel reheating processes under oxy-fuel combustion conditions – Technical and environmental perspectives

This paper investigates the impact of flameless oxy-fuel combustion on the thermal performance of a pilot-scale steel reheating furnace. A comprehensive mathematical model, based on the zone method of radiation analysis, was developed, which takes into account the non-grey behaviour of the furnace atmosphere under oxy-fuel combustion conditions. The model was subsequently used to simulate the temperature profile of an instrumented slab used in the experiment. The results showed that the predicted slab temperature profile along the furnace is in good agreement with measurement. However the model over predicted the absolute slab temperatures due to the influence of formation of oxide scales on the slab surface, which was not taken into account in the current model. When compared to air-fuel combustion simulation, the results of oxy-fuel combustion also indicated a marked improvement in the furnace specific fuel consumption (approximately 16%). This was mainly due to the enhanced radiative properties of the furnace atmosphere and reduced exhaust energy losses as the result of less dilution effect from nitrogen. This resulted in reduction in the overall heating time by approximately 14 min. Furthermore, if the economics of carbon capture is taken into consideration, theoretically, the energy consumption per kilogram of CO2 captured can be reduced from 3.5 to 4.2 MJ kg−1 to 0.96 MJ kg−1. In conclusion, the current studies support the view that oxy-fuel combustion retrofitting to reheating furnaces is a promising option, both from a technical and from an environmental point of view

Piperidinols that show anti-tubercular activity as inhibitors of arylamine N-acetyltransferase: an essential enzyme for mycobacterial survival inside macrophages

Latent M. tuberculosis infection presents one of the major obstacles in the global eradication of tuberculosis (TB). Cholesterol plays a critical role in the persistence of M. tuberculosis within the macrophage during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids. Arylamine N-acetyltransferase (NAT) is encoded within a gene cluster that is involved in the cholesterol sterol-ring degradation and is essential for intracellular survival. The ability of the NAT from M. tuberculosis (TBNAT) to utilise propionyl-CoA links it to the cholesterol-catabolism pathway. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. TBNAT has been investigated as a potential target for TB therapies. From a previous high-throughput screen, 3-benzoyl-4-phenyl-1-methylpiperidinol was identified as a selective inhibitor of prokaryotic NAT that exhibited antimycobacterial activity. The compound resulted in time-dependent irreversible inhibition of the NAT activity when tested against NAT from M. marinum (MMNAT). To further evaluate the antimycobacterial activity and the NAT inhibition of this compound, four piperidinol analogues were tested. All five compounds exert potent antimycobacterial activity against M. tuberculosis with MIC values of 2.3-16.9 µM. Treatment of the MMNAT enzyme with this set of inhibitors resulted in an irreversible time-dependent inhibition of NAT activity. Here we investigate the mechanism of NAT inhibition by studying protein-ligand interactions using mass spectrometry in combination with enzyme analysis and structure determination. We propose a covalent mechanism of NAT inhibition that involves the formation of a reactive intermediate and selective cysteine residue modification. These piperidinols present a unique class of antimycobacterial compounds that have a novel mode of action different from known anti-tubercular drugs

Age-dependent maintenance of motor control and corticostriatal innervation by death receptor 3

Death receptor 3 is a proinflammatory member of the immunomodulatory tumor necrosis factor receptor superfamily, which has been implicated in several inflammatory diseases such as arthritis and inflammatory bowel disease. Intriguingly however, constitutive DR3 expression has been detected in the brains of mice, rats, and humans, although its neurological function remains unknown. By mapping the normal brain expression pattern of DR3, we found that DR3 is expressed specifically by cells of the neuron lineage in a developmentally regulated and region-specific pattern. Behavioral studies on DR3-deficient (DR3(ko)) mice showed that constitutive neuronal DR3 expression was required for stable motor control function in the aging adult. DR3(ko) mice progressively developed behavioral defects characterized by altered gait, dyskinesia, and hyperactivity, which were associated with elevated dopamine and lower serotonin levels in the striatum. Importantly, retrograde tracing showed that absence of DR3 expression led to the loss of corticostriatal innervation without significant neuronal loss in aged DR3(ko) mice. These studies indicate that DR3 plays a key nonredundant role in the retention of normal motor control function during aging in mice and implicate DR3 in progressive neurological disease

Association of ACTN3 R577X but not ACE I/D gene variants with elite rugby union player status and playing position

We aimed to quantify the ACE I/D and ACTN3 R577X (rs1815739) genetic variants in elite rugby athletes (rugby union and league), compare genotype frequencies to controls and between playing positions. The rugby athlete cohort consisted of 507 Caucasian men, including 431 rugby union athletes that for some analyses were divided into backs and forwards and into specific positional groups: front five, back row, half backs, centers and back three. Controls were 710 Caucasian men and women. Real-time PCR of genomic DNA was used to determine genotypes using TaqMan probes and groups were compared using Chi-square and odds ratio (OR) statistics. Correction of p-values for multiple comparisons was according to Benjamini-Hochberg. There was no difference in ACE I/D genotype between groups. ACTN3 XX genotype tended to be underrepresented in rugby union backs (15.7%) compared to forwards (24.8%; P=0.06). Interestingly, the 69 back three players (wings and full backs) in rugby union included only six XX genotype individuals (8.7%), with the R allele more common in the back three (68.8%) than controls (58.0%; χ2=6.672, P=0.04; OR=1.60) and forwards (47.5%; χ2=11.768, P=0.01; OR=2.00). Association of ACTN3 R577X with playing position in elite rugby union athletes suggests inherited fatigue resistance is more prevalent in forwards while inherited sprint ability is more prevalent in backs, especially wings and full backs. These results also demonstrate the advantage of focusing genetic studies on a large cohort within a single sport, especially when intra-sport positional differences exist, instead of combining several sports with varied demands and athlete characteristics

Lipoprotein signatures of cholesteryl ester transfer protein and HMG-CoA reductase inhibition

Cholesteryl ester transfer protein (CETP) inhibition reduces vascular event risk, but confusion surrounds its effects on low-density lipoprotein (LDL) cholesterol. Here, we clarify associations of genetic inhibition of CETP on detailed lipoprotein measures and compare those to genetic inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). We used an allele associated with lower CETP expression (rs247617) to mimic CETP inhibition and an allele associated with lower HMGCR expression (rs12916) to mimic the well-known effects of statins for comparison. The study consists of 65,427 participants of European ancestries with detailed lipoprotein subclass profiling from nuclear magnetic resonance spectroscopy. Genetic associations were scaled to 10% reduction in relative risk of coronary heart disease (CHD). We also examined observational associations of the lipoprotein subclass measures with risk of incident CHD in 3 population-based cohorts totalling 616 incident cases and 13,564 controls during 8-year follow-up. Genetic inhibition of CETP and HMGCR resulted in near-identical associations with LDL cholesterol concentration estimated by the Friedewald equation. Inhibition of HMGCR had relatively consistent associations on lower cholesterol concentrations across all apolipoprotein B-containing lipoproteins. In contrast, the associations of the inhibition of CETP were stronger on lower remnant and very-low-density lipoprotein (VLDL) cholesterol, but there were no associations on cholesterol concentrations in LDL defined by particle size (diameter 18-26 nm) (-0.02 SD LDL defined by particle size; 95% CI: -0.10 to 0.05 for CETP versus -0.24 SD, 95% CI -0.30 to -0.18 for HMGCR). Inhibition of CETP was strongly associated with lower proportion of triglycerides in all high-density lipoprotein (HDL) particles. In observational analyses, a higher triglyceride composition within HDL subclasses was associated with higher risk of CHD, independently of total cholesterol and triglycerides (strongest hazard ratio per 1 SD higher triglyceride composition in very large HDL 1.35; 95% CI: 1.18-1.54). In conclusion, CETP inhibition does not appear to affect size-specific LDL cholesterol but is likely to lower CHD risk by lowering concentrations of other atherogenic, apolipoprotein B-containing lipoproteins (such as remnant and VLDLs). Inhibition of CETP also lowers triglyceride composition in HDL particles, a phenomenon reflecting combined effects of circulating HDL, triglycerides, and apolipoprotein B-containing particles and is associated with a lower CHD risk in observational analyses. Our results reveal that conventional composite lipid assays may mask heterogeneous effects of emerging lipid-altering therapies.Peer reviewe