Analysis of Sequence Divergence in Mammalian ABCGs Predicts a Structural Network of Residues That Underlies Functional Divergence

The five members of the mammalian G subfamily of ATP-binding cassette transporters differ greatly in their substrate specificity. Four members of the subfamily are important in lipid transport and the wide substrate specificity of one of the members, ABCG2, is of significance due to its role in multidrug resistance. To explore the origin of substrate selectivity in members 1, 2, 4, 5 and 8 of this subfamily, we have analysed the differences in conservation between members in a multiple sequence alignment of ABCG sequences from mammals. Mapping sets of residues with similar patterns of conservation onto the resolved 3D structure of ABCG2 reveals possible explanations for differences in function, via a connected network of residues from the cytoplasmic to transmembrane domains. In ABCG2, this network of residues may confer extra conformational flexibility, enabling it to transport a wider array of substrates.     

Operational optimization of a building-level integrated energy system considering additional potential benefits of energy storage

As a key component of an integrated energy system (IES), energy storage can effectively alleviate the problem of the times between energy production and consumption. Exploiting the benefits of energy storage can improve the competitiveness of multi-energy systems. This paper proposes a method for day-ahead operation optimization of a building-level integrated energy system (BIES) considering additional potential benefits of energy storage. Based on the characteristics of peak-shaving and valley-filling of energy storage, and further consideration of the changes in the system’s load and real-time electricity price, a model of additional potential benefits of energy storage is developed. Aiming at the lowest total operating cost, a bi-level optimal operational model for day-ahead operation of BIES is developed. A case analysis of different dispatch strategies verifies that the addition of the proposed battery scheduling strategy improves economic operation. The results demonstrate that the model can exploit energy storage’s potential, further optimize the power output of BIES and reduce the economic cost.     

Coagulation Signaling through PAR1 as a Therapeutic Target in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with a 5-year survival rate of less than 10% following diagnosis. The aggressive and invasive properties of pancreatic cancer tumors coupled with poor diagnostic options contribute to the high mortality rate since most patients present with late-stage disease. Accordingly, PDAC is linked to the highest rate of cancer-associated venous thromboembolic disease of all solid tumor malignancies. However, in addition to promoting clot formation, recent studies suggest that the coagulation system in PDAC mediates a reciprocal relationship, whereby coagulation proteases and receptors promote PDAC tumor progression and dissemination. Here, upregulation of tissue factor (TF) by tumor cells can drive local generation of the central coagulation protease thrombin that promotes cell signaling activity through protease-activated receptors (PARs) expressed by both tumor cells and multiple stromal cell subsets. Moreover, the TF-thrombin-PAR1 signaling axis appears to be a major mechanism of cancer progression in general and PDAC in particular. Here, we summarize the current literature regarding the role of PAR1 in PDAC and review possibilities for pharmacologically targeting PAR1 as a PDAC therapeutic approach.     

Plasma Metabolomics Analysis of Polyvinyl Chloride Workers Identifies Altered Processes and Candidate Biomarkers for Hepatic Hemangiosarcoma and Its Development

Background: High-level occupational vinyl chloride (VC) exposures have been associated with hepatic hemangiosarcoma, which typically develops following a long latency period. Although VC is genotoxic, a more comprehensive mode of action has not been determined and diagnostic biomarkers have not been established. The purpose of this study is to address these knowledge gaps through plasma metabolomics. Methods: Plasma samples from polyvinyl chloride polymerization workers who developed hemangiosarcoma (cases, n = 15) and VC exposure-matched controls (n = 17) underwent metabolomic analysis. Random forest and bioinformatic analyses were performed. Results: Cases and controls had similar demographics and routine liver biochemistries. Mass spectroscopy identified 606 known metabolites. Random forest analysis had an 82% predictive accuracy for group classification. 60 metabolites were significantly increased and 44 were decreased vs. controls. Taurocholate, bradykinin and fibrin degradation product 2 were up-regulated by greater than 80-fold. The naturally occurring anti-angiogenic phenol, 4-hydroxybenzyl alcohol, was down-regulated 5-fold. Top affected ontologies involved: (i) metabolism of bile acids, taurine, cholesterol, fatty acids and amino acids; (ii) inflammation and oxidative stress; and (iii) nicotinic cholinergic signaling. Conclusions: The plasma metabolome was differentially regulated in polyvinyl chloride workers who developed hepatic hemangiosarcoma. Ontologies potentially involved in hemangiosarcoma pathogenesis and candidate biomarkers were identified.     

A comparative study of comminution in rotary and vibratory ball mills

A comparative study of the comminution in rotary and vibratory ball mills using sodium chloride is presented. The many advantages of vibratory over rotary ball milling are outlined and it is shown experimentally that the rate and extent of grinding is higher for the vibratory ball mill. It is further shown that fine particles re-aggregate in the rotary ball mill and ‘cake’ irreversibly. This phenomenon, exclusive to the rotary ball mill, is explained in terms of consolidation and high stress relaxation of the crystals occurring during prolonged grinding.     

Preparation and characterization of surfactant‐free stimuli‐sensitive microgel dispersions

A surfactant‐free method to produce responsive polymer microgels is introduced. As an example, poly(methacrylic acid) hydrogels with varying crosslinking density have been synthesized in bulk and then chopped using a high shear mechanical cutter to form microgel particles dispersed in water. The mechanical cutting technique enables the concentration and particle size distribution of the microgel suspensions to be easily controlled, therefore making the rheology of the suspensions tuneable. The particle size distribution of the dispersions, characterized using light scattering, was dependent on the speed and duration of mechanical cutting. The particle size distribution also depended on the degree of crosslinking of the hydrogel. The higher the crosslinking density, the lower the average mean diameter of the resulting microgel particles. The lower the crosslinking density of the hydrogel, the larger the difference between the maximum and minimum particle size. The time to complete swelling of the particles upon change in pH was measured to be up to 45 s, depending on the particle size. The rheology of the resulting suspensions as a function of pH was investigated. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 104: 1912–1919, 2007     

Property-composition relationships for diesel and kerosene fuels

A range of 18 diesel fuels and 21 kerosene fuels from mainly Australian petroleum and synthetic fuel sources, including coal, shale and peat, was investigated. Compositional details were defined as the weight per cent abundances of n-alkanes, branched plus cyclic saturates, single-ring aromatics, doublering aromatics and polynuclear aromatics, using both h.p.l.c. and ¹³C n.m.r. techniques. Relationships between fuel composition and a range of fuel properties were sought. Simple linear relationships between property values and compositional data were used. Explicit correlative expressions were derived using multiple linear regression analysis, with the coefficient of multiple determination, R², indicating the quality of the fit between observed and calculated property values. In most cases good correlations were achieved. For diesels the properties investigated, with R² values in parentheses, were: inverse specific gravity (0.99); ¹³C n.m.r. aromaticity (0.99); ¹H n.m.r. aromaticity (0.88); cetane index (0.97); aniline point (0.96); diesel index (0.98); and FIA-measured aromatics content (0.77). For kerosenes the properties, with R² values in parentheses, were: ¹³C n.m.r. aromaticity (0.98); ¹H n.m.r. aromaticity (0.97); smoke point (0.88); and FIA-measured aromatics content (0.94). The results are shown to be of value in assessing the potential and limitations of hydrotreating as a process for upgrading synfuels.     

Dewatering behaviour of water treatment sludges associated with contaminated site remediation in Antarctica

Sludge reduction and dewatering is an important aspect of water and waste water treatment. This is especially true in the case of Australia's Antarctic contaminated site remediation program, where the reduction in volume of wastes to be returned to Australia can lead to significant transport and handling cost savings. The dewatering characterisation of water treatment sludges from an Antarctic contaminated site was conducted using a theory of suspension dewatering developed by Buscall, Landman and White. This theory uses fundamental material properties of compressibility and permeability to determine the diffusivity of a suspension. Diffusivity is a useful property that can be used to directly compare the dewaterability of various sludges. In this investigation, several water treatment sludges were collected and characterised in the field to determine the impact of temperature and additives on compressibility, permeability and diffusivity. The Antarctic sludges were found to be less compressible and less permeable than materials such as mineral suspensions and alum water treatment sludges. Compressibility was found to decrease with the addition of powdered coagulation aids such as bentonite and chitosan.     

The ageing Australian firefighter: an argument for age-based recruitment and fitness standards for urban fire services

Currently, there is no enforcement of physical standards within Australian fire services post-recruitment, possibly leading to inappropriate fitness and body composition. This study evaluated the impacts of ageing on physical standards of Australian firefighters. Seventy-three firefighters from three different 10-year age groups [25–34 years (n = 27), 35–44 years (n = 27), 45–54 years (n = 19)] volunteered for physical testing using dual-energy X-ray analysis and existing fitness tests used for recruitment by an Australian fire service. Older (45–54 years) participants demonstrated significantly poorer physical standards compared with younger participants including cardiovascular fitness (p < 0.05), strength (p = 0.001) and simulated operational power testing tasks (p < 0.001). Age-related body composition changes were also observed independent of body mass index. Minimum recruitment standards and fitness programs need to account for age-related declines in physical capabilities to ensure that the minimum standard is maintained regardless of age.

Practitioner Summary: Using dual-energy X-ray analysis and established fitness testing protocols, this study aimed to gain an appreciation of the current standards of body composition and fitness of Australian firefighters and the effects of ageing on their physical abilities post-recruitment. The study demonstrated a significant decline in physical standards due to age.