Identifying Lysophosphatidic Acid Acyltransferase β (LPAAT-β) as the Target of a Nanomolar Angiogenesis Inhibitor from a Phenotypic Screen Using the Polypharmacology Browser PPB2

By screening a focused library of kinase inhibitor analogues in a phenotypic co-culture assay for angiogenesis inhibition, we identified an aminotriazine that acts as a cytostatic nanomolar inhibitor. However, this aminotriazine was found to be completely inactive in a whole-kinome profiling assay. To decipher its mechanism of action, we used the online target prediction tool PPB2 ( http://ppb2.gdb.tools ), which suggested lysophosphatidic acid acyltransferase β (LPAAT-β) as a possible target for this aminotriazine as well as several analogues identified by structure–activity relationship profiling. LPAAT-β inhibition (IC₅₀ ≈15 nm ) was confirmed in a biochemical assay and by its effects on cell proliferation in comparison with a known LPAAT-β inhibitor. These experiments illustrate the value of target-prediction tools to guide target identification for phenotypic screening hits and significantly expand the rather limited pharmacology of LPAAT-β inhibitors.     

Effect of viscosity and applied potential on oscillations at a Pt-Pt dual-electrode in a ferricyanide system

This paper outlines the effect of viscosity and applied potential on oscillations occurring at two platinum electrodes placed proximal to each other. Potential oscillations taking place on the primary electrode (WE1) under galvanostatic control in the ferricyanide system are affected by the solution viscosity as it modifies the convective feedback mechanism necessary for oscillations. Measured transition times correlate with those calculated using Sand equation thus allowing the estimation of current density windows for periodic oscillation for different solution viscosities for pre-determined transition times. Current oscillations on the secondary working electrode (WE2) - under potentiostatic control and induced by the potential oscillations on WE1 - can be tuned through the applied potential. At higher potentials the reaction is oxidation of [Fe(CN)₆]⁴⁻ and the coupling is primarily through the transfer of [Fe(CN)₆]⁴⁻ from WE1 to WE2 via H₂ evolution whilst at more cathodic potentials the reduction of [Fe(CN)₆]³⁻ takes place at both WE1 and WE2 and the convective feedback from WE1 refreshes the surface of both electrodes simultaneously.     

Burnout of pulverized biomass particles in large scale boiler – Single particle model approach

Burning of coal and biomass particles are studied and compared by measurements in an entrained flow reactor and by modelling. The results are applied to study the burning of pulverized biomass in a large scale utility boiler originally planned for coal. A simplified single particle approach, where the particle combustion model is coupled with one-dimensional equation of motion of the particle, is applied for the calculation of the burnout in the boiler. The particle size of biomass can be much larger than that of coal to reach complete burnout due to lower density and greater reactivity. The burner location and the trajectories of the particles might be optimised to maximise the residence time and burnout.     

Thermodynamic analysis of small-scale dimethyl ether (DME) and methanol plants based on the efficient two-stage gasifier

Models of dimethyl ether (DME) and methanol synthesis plants have been designed by combining the features of the simulation tools DNA and Aspen Plus. The plants produce DME or methanol by catalytic conversion of a syngas generated by gasification of woody biomass. Electricity is co-produced in the plants by a gas engine utilizing the unconverted syngas. A two-stage gasifier with a cold gas efficiency of 93% is used, but because of the design of this type of gasifier, the plants have to be of small-scale (5 MWth biomass input). The plant models show energy efficiencies from biomass to DME/methanol + electricity of 51–58% (LHV), which shows to be 6-8%-points lower than efficiencies achievable on large-scale plants based on torrefied biomass pellets. By using waste heat from the plants for district heating, the total energy efficiencies become 87–88%.     

Predicting the number of patients on dialysis and renal transplant recipients in Denmark]

A Markov model was applied in three ways: 1) a deterministic model with fixed rates, 2) a stochastic model using simulated varying rates and 3) a deterministic model with increasing rates. With present rates an increase in the prevalence of renal transplant recipients < 60 years (from 1003 in 1995 to about 1465 in 2006) and the prevalence of haemodialysis patients less than or equal to 60 years (from 456 in 1995 to about 903 in 2006) was predicted. The prevalence in other treatment modalities would change less. The overall prevalence proportion would increase from 539 patients/mio. inhabitants in 1995 to about 777/mio. in 2006. Observed and expected numbers with the stochastic model in 1996 were: haemodialysis: 1053 (1074 +/- 41, 2p = 0.61), peritoneal dialysis: 456 (480 +/- 22, 2p = 0.28) and renal transplant recipients: 1232 (1266 +/- 14, 2p = 0.015). The deterministic model with increasing rates predicted an overall prevalence of 1162 patients/mio. in 2006.     

Beverage clouding agents: Review of principles and current manufacturing

Clouding agents are additives applied in fruit-flavored beverages to achieve a visual appearance similar to fresh juice. They consist of dispersions of small particles that impart turbidity. Use of emulsions is the most well established methodology utilized by the beverage industry, but citrus pulp, pigments, and biopolymer microgels are also employed in the manufacturing of clouding agents.

Long product shelf life is a prime requirement and hence instability is a perpetual concern. Often, clouding agents are produced concentrated, and thus they must be stable both as concentrates and in the final beverage. The composition and manufacturing processes can be adapted to modify the physicochemical characteristics of the clouding agent, and systems that are metastable, but still have sufficient stability can be achieved.

In this review article, the impact of, amongst other parameters, oil, weighting agent, emulsifier, stabilizer, as well as pressure, heat, pH and shear on turbidity and physical product stability will be discussed.     

Effects of altered carcass suspension during rigor mortis on tenderness of pork loin

A total of 32 porcine carcasses from Danish Landrace and Yorkshire breeds, slaughtered at approximately 90 kg live weight, were utilised in two experiments (replicates) to evaluate the effect of altered carcass suspension on Warner-Bratzler (WB) shear force, sarcomere length, myofibrillar fragmentation and cooking loss in the longissimus dorsi (LD). Carcasses used in the experiments all showed pH(1) values above 6·0 and ultimate pH below 5·8. From each replicate, the two sides of 16 carcasses were suspended by one of two methods: conventional suspension from the Achilles tendon or pelvic suspension from the obturator foramen. WB values were measured at three locations taken from the posterior section of the LD muscle. Pelvic suspension decreased WB values (p < 0·001) and increased sarcomere lengths (p < 0·001) whereas cooking loss was unaffected by method of suspension. The significant interactions between suspension and replicate (p < 0·01) and between suspension and sample location (p < 0·001) revealed that the tenderising effect of pelvic suspension increased with increasing WB level in the conventional suspended carcass sides. Myofibril fragmentation showed inconsistent response to suspension method.     

Effect of concentration polarization on the current-voltage characteristics of ion transfer across ities

Current-voltage characteristics of ion transfer across the ITIES was theoretically studied, taking concentration polarization into account through the Nernst-Planck equation in the diffusion boundary layers. In the inner layer transport was modelled using either Butler-Volmer or Nernst-Planck equations. Potential distribution across the ideally polarizable ITIES was calculated from the Poisson-Bolzman equation. The current-voltage curves were of the Butler-Volmer type, but no distinction between the two approaches inside the inner layer could be seen because the permeability of the entire system was determined by the diffusion boundary layers.     

A comparison of warmed-over flavour in pork by sensory analysis, GC/MS and the electronic nose

Pork muscle samples (M. longissimus dorsi and M. psoas major) were obtained from pigs given one of 4 dietary treatments, (i) control diet, (ii) supplemental iron (300 mg iron (II) sulphate/kg feed), (iii) supplemental vitamin E (200 mg dl-α-tocopheryl acetate/kg of feed) and (iv) supplemental vitamin E+supplemental iron. Warmed-over flavour (WOF) was evaluated by a trained sensory panel (n=8) for the four treatments cooked and refrigerated at 4?°C for up to 5 days. Gas chromatography mass spectrometry (GC/MS) and Electronic nose analysis was performed on a subset of the full design which included samples of M. longissimus dorsi, treatments (ii) and (iii) and M. psoas major with treatment (i) for 0 days of WOF development. Day 5 of WOF development was included in the subset and represented by samples of M. longissimus dorsi, treatment (iv) and M. psoas major, treatments (ii) and (iii). Bi-linear modeling was used to determine the correlation of GC/MS and electronic nose data to sensory data. Also, the reproducibility and reliability of electronic nose data was evaluated by repeating the analysis of samples in a different laboratory and with a time difference of approximately 11 months. Mean-centring was used to normalise the data from these two different electronic noise data sets. GC/MS data correlated to sensory data with specific compounds (e.g., pentanal, 2-pentylfuran, octanal, nonanal, 1-octen-3-ol and hexanal), proving to be good indices of oxidation in cooked samples of M. longissimus dorsi and M. psoas major. Electronic nose data correlated to sensory data and separated the sensory variation. The reproducibility of this data was high with the second set of samples being predictive of the first set.