Using CFD to improve the design of a circulating water channel

Computational Fluid Dynamics (CFD) has been used as a design tool to investigate means of improving flow uniformity in the working section of a circulating water channel. The CFD model was based on a 1/10th scale wind-tunnel model of the circulating water channel at the Australian Maritime Hydrodynamics Research Centre (AMHRC). The CFD analysis was compared with experimental results obtained from the wind-tunnel model to validate the use of the CFD model. Three changes to the design were investigated; alteration of turning vane angle, increased resistance coefficient of a honeycomb screen and addition of trailing edge extensions to the turning vanes. The turning vane angle changes resulted in little improvement in flow uniformity. Increasing the resistance coefficient of the honeycomb screen resulted in improved uniformity, but at the expense of increased pressure loss. The addition of trailing edge extensions to the turning vanes resulted in the most significant improvements in flow uniformity. These results will be useful in selecting improvements to the circulating water channel

Histidine Residues at the Active Site of the Pasteurella multocida Toxin

We have investigated histidine residues near the active site of the mitogenic Pasteurella multocida toxin. Mutation of H1202 or H1228 had little effect, while the effect of mutation on H1223 depended on the amino acid substituted. Mutation of H1205 caused complete loss of activity, indicating its importance in PMT activity

The SERL Observatory Dataset: Longitudinal Smart Meter Electricity and Gas Data, Survey, EPC and Climate Data for over 13,000 Households in Great Britain

The Smart Energy Research Lab (SERL) Observatory dataset described here comprises half-hourly and daily electricity and gas data, SERL survey data, Energy Performance Certificate (EPC) input data and 24 local hourly climate reanalysis variables from the European Centre for Medium-Range Weather Forecasts (ECMWF) for over 13,000 households in Great Britain (GB). Participants were recruited in September 2019, September 2020 and January 2021 and their smart meter data are collected from up to one year prior to sign up. Data collection will continue until at least August 2022, and longer if funding allows. Survey data relating to the dwelling, appliances, household demographics and attitudes were collected at sign up. Data are linked at the household level and UK-based academic researchers can apply for access within a secure virtual environment for research projects in the public interest. This is a data descriptor paper describing how the data were collected, the variables available and the representativeness of the sample compared to national estimates. It is intended to be a guide for researchers working with or considering using the SERL Observatory dataset, or simply looking to learn more about it

The over-prediction of energy use by EPCs in Great Britain: A comparison of EPC-modelled and metered primary energy use intensity

This analysis compares the difference between the Energy Performance Certificate (EPC)-modelled and smart-meter measured annual energy use on a like-for-like basis in 1,374 gas-heated British households from the Smart Energy Research Lab (SERL) Observatory. EPCs and metered energy use were converted to primary energy use intensity (PEUI) to provide a comparison of the same quantity for the first time. We show that EPCs predict significantly more energy use than metered in homes in Great Britain. EPC bands A and B show no statistically significant difference, but all other bands show a significant gap which increases as EPC rating worsens. The PEUI gap widens from −26 kWh/yr/m2 (−8%) for band C to −276 kWh/y/m2 (−48%) for bands F and G. Unlike previous research, we show that the difference persists in homes matching the EPC-model assumptions regarding occupancy, thermostat set-point and whole-home heating; suggesting that occupant behaviour is unlikely to fully explain the discrepancy. EPCs are a core tool in the residential energy sector, and the gap between EPC-modelled and metered energy use could have a significant impact on policy, research, and industry. Future research should investigate disaggregated components of energy use, the underlying thermal model, and assumptions regarding building characteristics

Three patients with homozygous familial hypercholesterolemia: Genomic sequencing and kindred analysis.

BackgroundHomozygous Familial Hypercholesterolemia (HoFH) is an inherited recessive condition associated with extremely high levels of low-density lipoprotein (LDL) cholesterol in affected individuals. It is usually caused by homozygous or compound heterozygous functional mutations in the LDL receptor (LDLR). A number of mutations causing FH have been reported in literature and such genetic heterogeneity presents great challenges for disease diagnosis.ObjectiveWe aim to determine the likely genetic defects responsible for three cases of pediatric HoFH in two kindreds.MethodsWe applied whole exome sequencing (WES) on the two probands to determine the likely functional variants among candidate FH genes. We additionally applied 10x Genomics (10xG) Linked-Reads whole genome sequencing (WGS) on one of the kindreds to identify potentially deleterious structural variants (SVs) underlying HoFH. A PCR-based screening assay was also established to detect the LDLR structural variant in a cohort of 641 patients with elevated LDL.ResultsIn the Caucasian kindred, the FH homozygosity can be attributed to two compound heterozygous LDLR damaging variants, an exon 12 p.G592E missense mutation and a novel 3kb exon 1 deletion. By analyzing the 10xG phased data, we ascertained that this deletion allele was most likely to have originated from a Russian ancestor. In the Mexican kindred, the strikingly elevated LDL cholesterol level can be attributed to a homozygous frameshift LDLR variant p.E113fs.ConclusionsWhile the application of WES can provide a cost-effective way of identifying the genetic causes of FH, it often lacks sensitivity for detecting structural variants. Our finding of the LDLR exon 1 deletion highlights the broader utility of Linked-Read WGS in detecting SVs in the clinical setting, especially when HoFH patients remain undiagnosed after WES

The lipoprotein lipase gene in combined hyperlipidemia: evidence of a protective allele depletion

BACKGROUND: Lipoprotein Lipase (LPL), a key enzyme in lipid metabolism, catalyzes the hydrolysis of triglycerides (TG) from TG-rich lipoproteins, and serves a bridging function that enhances the cellular uptake of lipoproteins. Abnormalities in LPL function are associated with pathophysiological conditions, including familial combined hyperlipidemia (FCH). Whereas two LPL susceptibility alleles were found to co-segregate in a few FCH kindred, a role for common, protective alleles remains unexplored. The LPL Ser447Stop (S447X) allele is associated with anti-atherogenic lipid profiles and a modest reduction in risk for coronary disease. We hypothesize that significant depletion of the 447X allele exists in combined hyperlipidemia cases versus controls. A case-control design was employed. The polymorphism was assessed by restriction assay in 212 cases and 161 controls. Genotypic, allelic, and phenotypic associations were examined. RESULTS: We found evidence of significant allelic (447X(control): 0.130 vs. 447X(case): 0.031, χ(2 )= 29.085; 1df; p < 0.001) and genotypic association (SS: 0.745 vs. 0.939, and SX+XX: 0.255 vs. 0.061) in controls and cases, respectively (χ(2 )= 26.09; 1df; p < 0.001). In cases, depletion of the 447X allele is associated with a significant elevation in very-low-density lipoprotein cholesterol (VLDL-C, p = 0.045). Consonant with previous studies of this polymorphism, regression models predict that carriers of the 447X allele displayed significantly lower TG, low-density lipoprotein cholesterol (LDL-C) and TG/high-density lipoprotein cholesterol (HDL-C) ratio. CONCLUSION: These findings suggest a role for the S447X polymorphism in combined hyperlipidemia and demonstrate the importance of evaluating both susceptibility and protective genetic risk factors

Diurnal Variation in repeated sprint performance cannot be offset when rectal and muscle temperatures are at optimal levels (38.5 C)

The present study investigated whether increasing morning rectal temperatures (Trec) to evening levels, or increasing morning and evening Trec to an “optimal” level (38.5°C), resulting in increased muscle temperatures (Tm), would offset diurnal variation in repeated sprint (RS) performance in a causal manner. Twelve trained males underwent five sessions [age (mean ± SD) 21.0 ± 2.3 years, maximal oxygen consumption (V̇O2max) 60.0 ± 4.4 mL.kg–1 min–1, height 1.79 ± 0.06 m, body mass 78.2 ± 11.8 kg]. These included control morning (M, 07:30 h) and evening (E, 17:30 h) sessions (5-min warm-up), and three further sessions consisting of a warm-up morning trial (ME, in 39–40°C water) until Trec reached evening levels; two “optimal” trials in the morning and evening (M38.5 and E38.5, in 39–40°C water) respectively, until Trec reached 38.5°C. All sessions included 3 × 3-s task-specific warm-up sprints, thereafter 10 × 3-s RS with 30-s recoveries were performed a non-motorised treadmill. Trec and Tm measurements were taken at the start of the protocol and following the warm-up periods. Values for Trec and Tm at rest were higher in the evening compared to morning values (0.48°C and 0.69°C, p < 0.0005). RS performance was lower (7.8–8.3%) in the M for distance covered (DC; p = 0.002), average power (AP; p = 0.029) and average velocity (AV; p = 0.002). Increasing Trec in the morning to evening values or optimal values (38.5°C) did not increase RS performance to evening levels (p = 1.000). However, increasing Trec in the evening to “optimal” level through a passive warm-up significantly reduced DC (p = 0.008), AP (p < 0.0005) and AV (p = 0.007) to values found in the M condition (6.0–6.9%). Diurnal variation in Trec and Tm is not wholly accountable for time-of-day oscillations in RS performance on a non-motorised treadmill; the exact mechanism(s) for a causal link between central temperature and human performance are still unclear and require more research

Diurnal differences in human muscle isometric force and rate of force development in vivo are associated with differential phosphorylation of sarcomeric M-band proteins.

The maximum force of skeletal muscle exhibits circadian variation that is associated with time-of-day differences in athletic performance. We investigated whether the diurnal difference in force is associated with the post-translational state of muscle proteins. Twenty physically active men (mean ± SD; age 26.0 ± 4.4 y, height 177.3 ± 6.8 cm, body mass 75.1 ± 8.2.8 kg) completed 5 familiarisation sessions where-in they practiced all maximal efforts. Thereafter they performed experimental sessions, in the morning (08:00 h) and evening (17:00 h), counterbalanced in order of administration and separated by at least 72 h. Rectal, skin, muscle temperatures and ratings of perceived effort measurements where made after the subjects had reclined for 30 min (rest) and after the 5-min cycle ergometry warm-ups and prior to the measurement of knee extensor maximal voluntary isometric contraction (MVIC; including twitch-interpolation) and peak rate of force development (RFD). Data handling: 10 subjects from the cohort of 20 volunteered for muscle biopsy procedures, hence only their data is reported for temperature, MVIC and RFD to align with proteomic analyses. Samples of vastus lateralis were collected immediately after exercise and were analysed by ‘top-down’ and ‘bottom-up’ proteomic methods. Rectal and muscle temperatures were higher at rest in the evening (mean difference of 0.51°C and 0.69°C; p<0.05) than in the morning. MVIC force in the evening was significantly greater than in the morning (mean difference of 67 N, 9.3%; p<0.05), similarly peak RFD (mean difference of 1080 N/s, 15.3%; p<0.05) was improved in the evening. 2D gel analysis encompassed 122 proteoforms and discovered 6 statistically significant (p<0.05; false discovery rate [FDR] = 10%) diurnal differences. Phosphopeptide analysis identified 1,693 phosphopeptides and detected 140 phosphopeptides from 104 proteins that were more phosphorylated (p<0.05, FDR=22%) in the morning vs. evening. Myomesin 2, muscle creatine kinase and the C-terminus of titin, exhibited the most robust (FDR<10%) diurnal differences. In summary, the effects of time of day where seen in measures of rectal and muscle temperature and muscle performance. Exercise in the morning, compared to the evening, coincided with greater phosphorylation of M-band-associated proteins in human muscle. These protein modifications may alter M-band structure and disrupt force transmission, thus potentially explaining the lower force output in the morning