PARENTERAL NUTRITION-ASSOCIATED CHOLESTASIS: THE INCIDENCE AND EXAMINATION OF THE ROLE OF ALUMINUM CONTAMINATION

Parenteral nutritional (PN) support is an essential component in the care of ill neonates. Parenteral nutrition-associated cholestasis (PN-AC) is a complication of PN that was first described in 1971 and still defies clear etiological delineation. The objective of the first project was to establish the prevalence of PN-AC at the Royal University Hospital by retrospectively studying infants. Sixty-four infants with the diagnoses of gastroschisis, intestinal atresia, intestinal stenosis, necrotizing enterocolitis, imperforate anus, or Hirschprung's disease had their medical records reviewed. Cholestasis was diagnosed clinically by a serum direct bilirubin concentration exceeding 34 mmol/L. We found that 16 of the 64 (25%) neonates in our study developed cholestasis. In the neonates who developed cholestasis, the average number of days on parenteral nutrition was 18.4 days (range 5-39 days). A forward stepwise multiple regression analysis was performed revealing that the length of time on parenteral nutrition, gastrointestinal surgery, and birth weight together significantly predict the development of PN-AC (p < 0.001). A second study was to prospectively enrol neonates at risk for intestinal failure with the primary focus being to examine the relationship between serum aluminum concentrations and serum direct bilirubin concentrations. Eight neonates with intestinal failure receiving parenteral nutrition were enrolled. Three of eight (37.5%) of the neonates developed parenteral nutrition-associated cholestasis. Significant differences were found in birth weight, gestational age and number of days on parenteral nutrition between those neonates that developed PNAC and those that did not. No significant relationship between serum direct bilirubin and serum aluminum was found. In conclusion, at least 25% of infants who are born with low birth weight and require gastrointestinal surgery that receive parenteral nutrition therapy for 18 days developed PNAC. Further work examining the relationship between aluminum contamination of parenteral solutions and the development of PNAC is required

Gravitational Techniwaves

We investigate the production and possible detection of gravitational waves stemming from the electroweak phase transition in the early universe in models of minimal walking technicolor. In particular we discuss the two possible scenarios in which one has only one electroweak phase transition and the case in which the technicolor dynamics allows for multiple phase transitions.Comment: 30 pages, 5 figures. v2: minor changes, references added, title changed in journa

Fractionation of Methane Isotopologues during Preparation for Analysis from Ambient Air

Preconcentration of methane (CH4) from air is a critical sampling step in the measurement of singly and doubly substituted isotopologue ratios. We demonstrate the potential for isotope fractionation during preconcentration onto and elution from the common trapping material HayeSep-D and investigate its significance in laser spectroscopy measurements. By altering the trapping temperature for adsorption, the flow direction of CH4 through the trap and the time at which CH4 is eluted during a desorption temperature ramp, we explain the mechanisms behind fractionation affecting δ13C(CH4) and δ2H(CH4). The results highlight that carbon isotope fractionation is driven by advection and diffusion, while hydrogen isotope fractionation is driven by the interaction of CH4 with the adsorbing material (tending to smaller isotopic effects at higher temperatures). We have compared the difference between the measured isotope ratio of sample gases (compressed whole air and a synthetic mixture of CH4 at ambient amount fraction in an N2 matrix) and their known isotopic composition. An open-system Rayleigh model is used to quantify the magnitude of isotopic fractionation affecting measured δ13C(CH4) and δ2H(CH4), which can be used to calculate the possible magnitude of isotopic fractionation given the recovery percentage. These results provide a quantitative understanding of isotopic fractionation during the sample preparation of CH4 from ambient air. The results also provide valuable insights applicable to other cryogenic preconcentration systems, such as those for measurements that probe the distribution of rarer isotopologues

Design and Evaluation of Heterobivalent PAR1–PAR2 Ligands as Antagonists of Calcium Mobilization

A novel class of bivalent ligands targeting putative protease-activated receptor (PAR) heteromers has been prepared based upon reported antagonists for the subtypes PAR1 and PAR2. Modified versions of the PAR1 antagonist RWJ-58259 containing alkyne adapters were connected via cycloaddition reactions to azide-capped polyethylene glycol (PEG) spacers attached to imidazopyridazine-based PAR2 antagonists. Initial studies of the PAR1–PAR2 antagonists indicated that they inhibited G alpha q-mediated calcium mobilization in endothelial and cancer cells driven by both PAR1 and PAR2 agonists. Compounds of this novel class hold promise for the prevention of restenosis, cancer cell metastasis, and other proliferative disorders

Thermophotovoltaic Devices: Combustion Chamber Optimization and Modelling to Maximize Fuel Efficiency

Currently, 110 billion cubic meters of natural gas (primarily methane), a potent greenhouse gas, are flared off for environmental and safety reasons. This process results in enough fuel to provide the combined natural gas consumption of Germany and France. The research team developed a thermophotovoltaic device to convert thermal energy to electricity at a high efficiency using proprietary emitters and combustion system. With the current focus being fuel efficiency and the combustion process, the assembly was simulated using ANSYS Fluent modelling software and the following parameters were optimized: air/fuel ratios, flow rates, and inlet sizes. Simultaneously the heat transfer across the combustion chamber was modeled and its geometry was optimized. Higher flow rates resulted in higher temperatures on the combustion chamber walls; lean mixtures with higher air/fuel ratios also resulted in high exhaust gas temperatures. However, the residual curves hint towards a potentially unstable solution and require more iterations in the simulation process. The results of these efforts indicated that the combustion chamber has been optimized yet further work needs to take place to deem the process to be sufficiently fuel efficient

Thermodynamics of the ATPase Cycle of GlcV, the Nucleotide-Binding Domain of the Glucose ABC Transporter of Sulfolobus solfataricus

ATP-binding cassette transporters drive the transport of substrates across the membrane by the hydrolysis of ATP. They typically have a conserved domain structure with two membrane-spanning domains that form the transport channel and two cytosolic nucleotide-binding domains (NBDs) that energize the transport reaction. Binding of ATP to the NBD monomer results in formation of a NBD dimer. Hydrolysis of the ATP drives the dissociation of the dimer. The thermodynamics of distinct steps in the ATPase cycle of GlcV, the NBD of the glucose ABC transporter of the extreme thermoacidophile Sulfolobus solfataricus, were studied by isothermal titration calorimetry using the wild-type protein and two mutants, which are arrested at different steps in the ATP hydrolytic cycle. The G144A mutant is unable to dimerize, while the E166A mutant is defective in dimer dissociation. The ATP, ADP, and AMP-PNP binding affinities, stoichiometries, and enthalpies of binding were determined at different temperatures. From these data, the thermodynamic parameters of nucleotide binding, NBD dimerization, and ATP hydrolysis were calculated. The data demonstrate that the ATP hydrolysis cycle of isolated NBDs consists of consecutive steps where only the final step of ADP release is energetically unfavorable.

Nitrate reductase 15N discrimination in Arabidopsis thaliana, Zea mays, Aspergillus niger, Pichea angusta, and Escherichia coli

Stable 15N isotopes have been used to examine movement of nitrogen (N) through various pools of the global N cycle. A central reaction in the cycle involves nitrate (NO3–) reduction to nitrite (NO2–) catalyzed via nitrate reductase (NR). Discrimination against 15N by NR is a major determinant of isotopic differences among N pools. Here, we measured in vitro 15N discrimination by several NRs purified from plants, fungi, and a bacterium to determine the intrinsic 15N discrimination by the enzyme and to evaluate the validity of measurements made using 15N-enriched NO3–. Observed NR isotope discrimination ranged from 22‰ to 32‰ (kinetic isotope effects of 1.022 to 1.032) among the different isozymes at natural abundance 15N (0.37%). As the fractional 15N content of substrate NO3– increased from natural abundance, the product 15N fraction deviated significantly from that expected based on substrate enrichment and 15N discrimination measured at natural abundance. Additionally, isotopic discrimination by denitrifying bacteria used to reduce NO3– and NO2– in some protocols became a greater source of error as 15N enrichment increased. We briefly discuss potential causes of artifactual results with enriched 15N and recommend against the use of highly enriched 15N tracers to study N discrimination in plants or soils