Influence of polymorphisms of the human glutathione transferases and cytochrome P450 2E1 enzyme on the metabolism and toxicity of ethylene oxide and acrylonitrile

A cohort of 59 persons with industrial handling of low levels of acrylonitrile is being studied as part of a medical surveillance programme. Previously, an extended haemoglobin adduct monitoring (N-(cyanoethyl)valine and N-(hydroxyethyl)-valine) was performed regarding the glutathione transferases hGSTM1 and hGSTT1 polymorphisms but no influence of hGSTM1 or hGSTT1 polymorphisms on specific adduct levels was found. A compilation of case reports of human accidental poisonings had pointed to significant individual differences in human acrylonitrile metabolism and toxicity. Therefore, a re-evaluation of the industrial cohort included known polymorphisms of the glutathione transferases hGSTM3 and hGSTP1 as well as of the cytochrome P450 CYP2E1. A detailed statistical analysis revealed that exposed carriers of the allelic variants of hGSTP1, hGSTP1*B/hGSTP1*C, characterized by a single nucleotide polymorphism at nucleotide 313 which results in a change from Ile to Val at codon 104, had higher levels of the acrylonitrile-specific haemoglobin adduct N-(cyanoethyl)valine compared to the carriers of the codon 113 alleles hGSTP1*A and hGSTP1*D. The single nucleotide polymorphism at codon 113 of hGSTP1 (hGSTP1*A/hGSTP1*B versus hGSTP1*C/hGSTP1*D) did not show an effect, and also no influence was seen on specific haemoglobin adduct levels of the polymorphisms of hGSTM3 or CYP2E1. The data, therefore, point to a possible influence of a human enzyme polymorphism of the GSTP1 gene at codon 104 on the detoxication of acrylonitrile which calls for experimental toxicological investigation. The study also confirmed the impact of GSTT1 polymorphism on background N-(hydroxyethyl)-valine adduct levels in haemoglobin which are caused by endogenous ethylene oxide.

Detoxification enzyme activities (CYP1A1 and GST) in the skin of humpback whales as a function of organochlorine burdens and migration status

The activities of glutathione-s-transferase (GST) and cytochrome P-450 1A1 (CYP1A1) enzymes were measured in freshly extracted epidermis of live-biopsied, migrating, southern hemisphere humpback whales (Megaptera novaeangliae). The two quantified enzyme activities did not correlate strongly with each other. Similarly, neither correlated strongly with any of the organochlorine compound groups previously measured in the superficial blubber of the sample biopsy core, likely reflecting the anticipated low levels of typical aryl-hydrocarbon receptor ligands. GST activity did not differ significantly between genders or between northward (early migration) or southward (late migration) migrating cohorts. Indeed, the inter-individual variability in GST measurements was relatively low. This observation raises the possibility that measured activities were basal activities and that GST function was inherently impacted by the fasting state of the sampled animals, as seen in other species. These results do not support the implementation of CYP1A1 or GST as effective biomarkers of organochlorine contaminant burdens in southern hemisphere populations of humpback whales as advocated for other cetacean species. Further investigation of GST activity in feeding versus fasting cohorts may, however, provide some insight into the fasting metabolism of these behaviourally adapted populations.

Anomaly detection in online social networks : using data-mining techniques and fuzzy logic

This research is a step forward in improving the accuracy of detecting anomaly in a data graph representing connectivity between people in an online social network. The proposed hybrid methods are based on fuzzy machine learning techniques utilising different types of structural input features. The methods are presented within a multi-layered framework which provides the full requirements needed for finding anomalies in data graphs generated from online social networks, including data modelling and analysis, labelling, and evaluation.

Fuzzy logic to evaluate driving maneuvers: An integrated approach to improve training

Driver training is one of the interventions aimed at mitigating the number of crashes that involve novice drivers. Our failure to understand what is really important for learners, in terms of risky driving, is one of the many drawbacks restraining us to build better training programs. Currently, there is a need to develop and evaluate Advanced Driving Assistance Systems that could comprehensively assess driving competencies. The aim of this paper is to present a novel Intelligent Driver Training System (IDTS) that analyses crash risks for a given driving situation, providing avenues for improvement and personalisation of driver training programs. The analysis takes into account numerous variables acquired synchronously from the Driver, the Vehicle and the Environment (DVE). The system then segments out the manoeuvres within a drive. This paper further presents the usage of fuzzy set theory to develop the safety inference rules for each manoeuvre executed during the drive. This paper presents a framework and its associated prototype that can be used to comprehensively view and assess complex driving manoeuvres and then provide a comprehensive analysis of the drive used to give feedback to novice drivers.

Association of the SNP rs2623047 in the HSPG modification enzyme SULF1 with an Australian Caucasian Breast Cancer Cohort

Breast cancer is the second most common cancer worldwide and the most common cancer reported in women. This malignant tumour is characterised by a number of specific features including uncontrolled cell proliferation. It ranks fifth in the world as a cause of cancer death in women. Early diagnosis increases 5 year survival rates up to 95%. Heparan sulfate proteoglycans (HSPGs) are complex proteins composed of a core protein to which a number of highly sulfated side chains are synthesised by a highly co-ordinated process resulting in distinct sulfation patterns, which determine specific interations with cell-signaling partners including growth factors, their receptors, ligands and morphogens. The enzymes responsible for chain initiation, elongation and sulfation are critical for creating HS chain variability conferring biological functionality. This study investigated single nucleotide polymorphism in SULF1, the enzyme responsible for the 6-0 desulfation of heparan sulfate side chains. We investigated this SNP in an Australian Caucasian case-control breast cancer population and found a significant association between SULF1 and breast cancer at both the allelic and genotypic level (allele, p=0.016; genotype, p=0.032). Our results suggest the res2623047 SNP in SULF1 may impact breast cancer susceptibility. Specifically, the T allele of rs2623047 in SULF1 is associated with a increased risk of developing breast cancer in our cohort. The identification of markers including SULF1 may improve detection of this disease at its earliest stages improving patient treatment and prognosis.

The suitability of DEAE-Cl active groups on customized poly(GMA-co-EDMA) continuous stationary phase for fast enzyme-free isolation of plasmid DNA

The creation of a commercially viable and a large-scale purification process for plasmid DNA (pDNA) production requires a whole-systems continuous or semi-continuous purification strategy employing optimised stationary adsorption phase(s) without the use of expensive and toxic chemicals, avian/bovine-derived enzymes and several built-in unit processes, thus affecting overall plasmid recovery, processing time and economics. Continuous stationary phases are known to offer fast separation due to their large pore diameter making large molecule pDNA easily accessible with limited mass transfer resistance even at high flow rates. A monolithic stationary sorbent was synthesised via free radical liquid porogenic polymerisation of ethylene glycol dimethacrylate (EDMA) and glycidyl methacrylate (GMA) with surface and pore characteristics tailored specifically for plasmid binding, retention and elution. The polymer was functionalised with an amine active group for anion-exchange purification of pDNA from cleared lysate obtained from E. coli DH5α-pUC19 pellets in RNase/protease-free process. Characterization of the resin showed a unique porous material with 70% of the pores sizes above 300 nm. The final product isolated from anion-exchange purification in only 5 min was pure and homogenous supercoiled pDNA with no gDNA, RNA and protein contamination as confirmed with DNA electrophoresis, restriction analysis and SDS page. The resin showed a maximum binding capacity of 15.2 mg/mL and this capacity persisted after several applications of the resin. This technique is cGMP compatible and commercially viable for rapid isolation of pDNA.

Fuzzy-logic based frequency controller for wind farms augmented with energy storage systems

Displacement of conventional synchronous generators by non-inertial units such as wind or solar generators will result in reduced-system inertia affecting under-frequency response. Frequency control is important to avoid equipment damage, load shedding, and possible blackouts. Wind generators along with energy storage systems can be used to improve the frequency response of low-inertia power system. This paper proposes a fuzzy-logic based frequency controller (FFC) for wind farms augmented with energy storage systems (wind-storage system) to improve the primary frequency response in future low-inertia hybrid power system. The proposed controller provides bidirectional real power injection using system frequency deviations and rate of change of frequency (RoCoF). Moreover, FFC ensures optimal use of energy from wind farms and storage units by eliminating the inflexible de-loading of wind energy and minimizing the required storage capacity. The efficacy of the proposed FFC is verified on the low-inertia hybrid power system.

Expression and characterization of digestive enzyme genes from hepatopancreatic transcripts from redclaw crayfish (Cherax quadricarinatus)

Redclaw crayfish, Cherax quadricarinatus, possess a number of biological and commercial attributes that make them ideal for commercial aquaculture. While some studies have investigated digestive enzyme activity and nutritional requirements of this species, little information exists about the expression of digestive enzyme genes and their role in regulating digestive capacity. The current study therefore sequenced and annotated a RNASeq library constructed from a redclaw hepatopancreas to identify genes involved in digestive enzyme production. We observed that most of the transcripts that were annotated as digestive enzyme genes are associated with carbohydrate metabolism, thus confirming that redclaw have an innate capacity to digest a range of carbohydrate substrates. While endoglucanases were the most abundant group of digestive enzymes found, a number of novel transcripts were also detected. Here, we provide the first report for the presence and expression of endo-b-mannanase in freshwater crayfish. This novel gene showed significant alignment with a GH5 family protein from marine Limnoriids, wood borers that do not possess symbiotic microbes in their gut system. Overall, the data generated here provide an important resource to better understand the suite of digestive enzymes in redclaw that are very useful to fully utilize the species’ digestive capacity and will assist development of specific artificial feeds.

A novel fluorescent probe involving a graphene quantum dot-enzyme hybrid system for the analysis of hydroquinone in the presence of toxic resorcinol and catechol

An efficient method for the analysis of hydroquinone at trace levels in water samples has been developed in the form of a fluorescent probe based on graphene quantum dots (GQDs). The analytical variable, fluorescence quenching, was generated from the formation of benzoquinone intermediates, which formed during the catalytic oxidation of hydroquinone by horseradish peroxidase (HRP). In general, the reaction mechanism involved hydroquinone, as an electron acceptor, which affected the surface state of GQDs via an electron transfer effect. The water-soluble GQDs were directly prepared by the pyrolysis of citric acid and with the use of the mentioned hybrid enzyme system, the detection limit for hydroquinone was as low as 8.4 × 10−8 M. Furthermore, this analysis was almost unaffected by other phenol and quinine compounds, such as phenol, resorcinol and other quinines, and therefore, the developed GQD method produced satisfactory results for the analysis of hydroquinone in several different lake water samples.

Serum immunoglobulin G directed against porcine trypsin in the serum of cystic fibrosis children receiving porcine pancreatic enzyme supplements

Cystic fibrosis (CF) patients require pancreatic enzyme replacement therapy to correct pancreatic insufficiency. These enzymes are derived from porcine pancreas and are known to be antigenic. To determine the possible clinical consequences, a specific ELISA was developed to detect IgG antibody directed against porcine trypsin (PTAb) in the sera of CF patients. The assay was used to evaluate the occurrence of PTAb in a cross sectional study of 103 CF patients in relation to the introduction of porcine enzyme therapy, clinical status and genotype. Antibodies against porcine trypsin were detected in the sera of 63% of patients unrelated to the age of commencement or the duration of enzyme therapy. No differences were observed in the clinical status of CF patients who had developed PTAb (n = 65) and those who had no detectable PTAb (n = 38) as determined from: the current prescribed dose of porcine pancreatic enzyme capsules; Z scores for height and weight; and respiratory function tests. It is suggested that the PTAb commonly found in the sera of CF patients are of doubtful clinical significance but the prospect of PTAb contributing to immune complex disease should be examined further.

The use of a synthetic prostaglandin e1 analogue (misoprostol) as an adjunct to pancreatic enzyme replacement in cystic fibrosis

Eleven cystic fibrosis children (mean age, 9.6 years) were chosen at random to participate in a study to observe the effects of concurrently stimulating gastric/duodenal bicarbonate secretion and inhibiting gastric acid secretion, using a methylated prostaglandin E1 analogue in patients with pancreatic insufficiency and taking pancreatic enzymes. Percentage fat absorption in 3-day stool collections were calculated before and after commencing therapy with misoprostol, 400 μg/day in divided doses. We found a significant reduction in fat output (14.7 ± 11.7 versus 7.5 ± 3.5 g/day, p < 0.05) in the study group as a whole and a significant reduction in steatorrhoeic level as a percentage of fat intake in all of the patients with abnormal base-line collections (23.1% versus 9.2% p < 0.002). We conclude that misoprostol should be considered in cystic fibrosis patients with steatorrhoea as a means of improving nutrient absorption. © 1988 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

The use of a synthetic prostaglandin-E1 analog (misoprostol) as an adjunct to pancreatic-enzyme replacement in cystic-fibrosis

Eleven cystic fibrosis children (mean age, 9.6 years) were chosen at random to participate in a study to observe the effects of concurrently stimulating gastric/duodenal bicarbonate secretion and inhibiting gastric acid secretion, using a methylated prostaglandin E1 analogue in patients with pancreatic insufficiency and taking pancreatic enzymes. Percentage fat absorption in 3-day stool collections were calculated before and after commencing therapy with misoprostol, 400 μg/day in divided doses. We found a significant reduction in fat output (14.7 ± 11.7 versus 7.5 ± 3.5 g/day, p < 0.05) in the study group as a whole and a significant reduction in steatorrhoeic level as a percentage of fat intake in all of the patients with abnormal base-line collections (23.1% versus 9.2%, p < 0.002). We conclude that misoprostol should be considered in cystic fibrosis patients with steatorrhoea as a means of improving nutrient absorption.

The logic of data-sense: Thinking through Learning Personalisation

Big Data and Learning Analytics’ promise to revolutionise educational institutions, endeavours, and actions through more and better data is now compelling. Multiple, and continually updating, data sets produce a new sense of ‘personalised learning’. A crucial attribute of the datafication, and subsequent profiling, of learner behaviour and engagement is the continual modification of the learning environment to induce greater levels of investment on the parts of each learner. The assumption is that more and better data, gathered faster and fed into ever-updating algorithms, provide more complete tools to understand, and therefore improve, learning experiences through adaptive personalisation. The argument in this paper is that Learning Personalisation names a new logistics of investment as the common ‘sense’ of the school, in which disciplinary education is ‘both disappearing and giving way to frightful continual training, to continual monitoring'.

Logic of aid in an intertemporal setting

The paper studies the welfare implications of temporary foreign aid in the context of a simple two-country model of trade. In addition to its usual effects, a transfer of income in one period is assumed to influence the preferences of the recipient country in the following period. The implied changes in the terms of trade over the two periods are consistent with a number of possible outcomes with respect to the intertemporal welfare of the donor, the recipient, and the world as a whole. Particular attention is devoted to the conditions for strict Pareto improvement and the circumstances under which temporary aid transactions are likely to occur.