Noise in temporal analysis of products (TAP) pulse responses

Pulse responses recorded by the mass spectrometer of a TAP apparatus are subjected to noise. A general theoretical framework for noise studies and classification has been developed and applied to experimental data obtained at Ghent University (Belgium) and Washington University in St. Louis (USA). Two types of noise have been distinguished: Gaussian noise and spectrally localized noise. While the first one is believed to be essential, the second one is due to mains frequency interference. These types of noise are clearly distinguished from uncertainty caused by a variable pulse intensity. Analytical expressions are presented, and a regression is found to enable the experimentalist to analyze the noise quantitatively. This can be used as troubleshooting tool for the functioning of the TAP-setup. Increasing the sampling frequency can improve the precision by which physico-chemical parameters are estimated by regression of the pulse responses. When Gaussian noise is dominant, its correlation time determines up to which frequency this improvement is possible.     

The hERG Potassium Channel and Drug Trapping: Insight from Docking Studies with Propafenone Derivatives

The inner cavity of the hERG potassium ion channel can accommodate large, structurally diverse compounds that can be trapped in the channel by closure of the activation gate. A small set of propafenone derivatives was synthesized, and both use‐dependency and recovery from block were tested in order to gain insight into the behavior of these compounds with respect to trapping and non‐trapping. Ligand–protein docking into homology models of the closed and open state of the hERG channel provides the first evidence for the molecular basis of drug trapping.     

Discovery of potent, orally bioavailable small-molecule inhibitors of the human CCR2 receptor

We recently reported the discovery of a series of 2-thioimidazoles as CCR2 antagonists. The most potent molecules of this series, the 4,5-diesters, were rapidly hydrolyzed to the inactive acids and were found to be metabolically unstable. Herein we describe the synthesis of a number of analogues with heterocyclic bioisosteric replacements of the ester group(s). Small 5-membered heterocyclic substituents at the 4-position gave highly potent CCR2 antagonists. Hydrolysis of the 5-ester is diminished, thus imparting these compounds with sufficient stability and systemic exposure after oral administration to warrant further study of the in vivo pharmacology of these functional CCR2 inhibitors.     

Comparison of visual and automated colorimeters—An international collaborative study

Color as a fundamental quality of edible oils has been determined primarily by visual comparison methods for many decades. The automatic colorimeters introduced recently made it possible to replace the manually operated visual color instrument, which requires experience to master and is often subject to operator variabilities. A previous study with an automatic colorimeter, Colourscan, to measure the colors of refined and refined bleached cottonseed oils showed good agreement (r ²=0.99) with visual color measurements by means of the Lovibond-AOCS Color Scale. The current work is to establish a broad-scale correlation between the automated colorimeter and visual color measurements. In this international effort, factory-processed refined and refined, bleached, deodorized (RBD) canola, corn, cottonseed, peanut, sunflower and soybean oils, as well as refined palm olein, RBD palm oil, and washed, dried, filtered and deodorized tallow were used. A total of 14 laboratories from the United States and Canada, and 16 laboratories from 12 countries outside of North America, participated in this collaborative study. The results of this study, with statistical analyses, are reported.     

Low strength graywater characterization and treatmentby direct membrane filtration

The potential of direct membrane filtration on either ultrafiltration (30,200 and 400 kDa MWCO) or nanofiltration (200 Da MWCO) membranes was studied as a method of treatment of low load graywater for on site reuse. The graywater collected from a sports center's public showers and characterized for its chemical composition and physical properties fitted well to a low strength type (29.8 mg/l TSS and 170.3 mg/l as COD). Particle distribution analysis showed that colloidal size particles are the dominant fraction in terms of number distribution, while the much fewer, larger particles make up most of the particle volume (mean particle diameter0.1 μm). When treated by ultrafiltration, COD and turbidity concentration of permeates complied with established restrictions (45-70% and 92–97% reduction range, respectively), however BOD values were still above the requirements in all cases. Permeate produced by nanofiltration was of high quality with high rejection of soluble organic matter (>90%) and ionic species (50%). It can be concluded that direct dense-membrane filtration is a favorable candidate for efficient treatment of graywater for unrestricted reuse. MWCO optimization still needs to be done in order to achieve better economics at an acceptable quality of permeate produced.     

Osteogenic properties of calcium phosphate ceramics and fibrin glue based composites

Calcium phosphate (Ca-P) ceramics are currently used in various types of orthopaedic and maxillofacial applications because of their osteoconductive properties. Fibrin glue is also used in surgery due to its haemostatic, chemotactic and mitogenic properties and also as scaffolds for cell culture and transplantation. In order to adapt to surgical sites, bioceramics are shaped in blocks or granules and preferably in porous forms. Combining these bioceramics with fibrin glue provides a mouldable and self-hardening composite biomaterial. The aim of this work is to study the osteogenic properties of this composite material using two different animal models. The formation of newly formed bone (osteoinduction) and bone healing capacity (osteconduction) have been study in the paravertebral muscles of sheep and in critical sized defects in the femoral condyle of rabbits, respectively. The different implantations sites were filled with composite material associating Ca-P granules and fibrin glue. Ca-P granules of 1–2 mm were composed with 60% of hydroxyapatite and 40% of beta tricalcium phosphate in weight. The fibrin glue was composed of fibrinogen, thrombin and other biological factors. After both intramuscular or intraosseous implantations for 24 weeks and 3, 6, 12 and 24 weeks, samples were analyzed using histology and histomorphometry and mechanical test. In all cases, the newly formed bone was observed in close contact and around the ceramic granules. Depending on method of quantification, 6.7% (with BSEM) or 17% (with μ CT) of bone had formed in the sheep muscles and around 40% in the critical sized bone rabbit defect after 24 weeks. The Ca-P/fibrin material could be used for filling bone cavities in various clinical indications.     

Convenient conversion of calcium carbonate to hydroxyapatite at ambient pressure

The synthesis of hydroxyapatite is described starting from calcium carbonate and monoammoniumphosphate in stoichiometric amounts. The novel aspect concerns the reaction conditions which are simple mixing in water at ambient pressure and 60 °C. The calcium carbonate solid phase slowly evolves CO₂ gas and buffers the solution at a pH value of 8.05 where hydroxyapatite precipitates. The main advantages of this reaction pathway are the absence of nitrate salts, the availability of the starting materials and the purity of the final product.     

Aspects of linear and nonlinear instabilities leading to transition in pipe and channel flows

The failure of normal-mode linear stability analysis to predict a transition Reynolds number (Retr) in pipe flow and subcritical transition in plane Poiseuille flow (PPF) has led to the search of other scenarios to explain transition to turbulence in both flows. In this work, various results associated with linear and nonlinear mechanisms of both flows are presented. The results that combine analytical and experimental approaches indicate the strong link between the mechanisms governing the transition of both flows. It is demonstrated that the linear transient growth mechanism is based on the existence of a pair of least stable nearly parallel modes (having opposite phases and almost identical amplitude distributions). The analysis that has been applied previously to pipe flow is extended here to a fully developed channel flow predicting the shape of the optimized initial disturbance (a pair of counter-rotating vortices, CVP), time for maximum energy amplification and the dependence of the latter on Re. The results agree with previous predictions based on many modes. Furthermore, the shape of the optimized initial disturbance is similar in both flows and has been visualized experimentally. The analysis reveals that in pipe flow, the transient growth is a consequence of two opposite running modes decaying with an equal decay rate whereas in PPF it is due to two stationary modes decaying with different decay rates. In the first nonlinear scenario, the breakdown of the CVPs (produced by the linear transient growth mechanism) into hairpin vortices is followed experimentally. The associated scaling laws, relating the minimal disturbance amplitude required for the initiation of hairpins and the Re, are found experimentally for both PPF and pipe flow. The scaling law associated with PPF agrees well with the previous predictions of Chapman, whereas the scaling of the pipe flow is the same as the one previously obtained by Hof et al. indicating transition to a turbulent state. In the second nonlinear scenario, the base flow of pipe when it is mildly deviated from the Poiseuille profile by an axisymmetric distortion is examined. The nonlinear features reveal a Retr of approximately 2000 associated with the bifurcation between two deviation solutions.