Structure-based validation of the 3D-QSAR technique MaP

For three target proteins with different binding pocket characteristics (size and shape, hydrophobicity, hydrogen-bonding) a structure-based validation of the translationally and rotationally invariant 3D-QSAR technique MaP is performed (MaP: Mapping Property distributions of molecular surfaces). The structure-based validation procedure comprises two steps: first, QSAR models are derived without using the information of the target protein. Second, the models are back-projected into the crystal structure of the binding pockets and interpreted. It is demonstrated that MaP is able to identify characteristics important for ligand binding in the cases studied here. Moreover, it is demonstrated that MaP is a versatile 3D-QSAR technique since good, predictive models could be obtained for all three data sets showing distinct characteristics.     

Nitrogen isotope analysis of ammonium in aqueous solutions using a perfluorosulfonated ionomer membrane for solid-phase microextraction

The use of custom-made solid-phase microextraction (SPME) fibers coated with a perfluorosulfonated ionomer, Nafion, was investigated for nitrogen isotopic analysis of ammonium in aqueous solutions. Aqueous ammonium was converted to ammonia by addition of a base, followed by absorption from the headspace, desorption in the injection port of a gas chromatograph, and analysis by gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). Fibers coated with a Nafion tubing were chosen due to a higher fiber-gas distribution constant and a higher Nafion thickness than fibers coated with Nafion solution, both leading to a higher amount of ammonia absorbed at equilibrium. The Nafion membrane-coated fiber absorbed approximately 20 times more than a commercial polydimethylsiloxane (PDMS) fiber. The isotopic fractionation between fiber and gas was 1.0117 +/- 0.0009 (standard deviation, SD, of all measurements) at an initial ammonia gas concentration of 21-210 microM. At 390 microM initial gas concentration it was slightly lower. When sampling from liquid samples, an ammonium concentration of 10 mM was needed to obtain a sufficient amount of ammonia absorbed. Modeling of the absorption at different temperatures showed that the absorption was approximately constant in the temperature range suitable for SPME experiments. Absorption at room temperature was therefore used for simplicity. A pilot study was conducted in which absorption was achieved from a single 9 microL droplet of sample. The preliminary results showed that delta(15)N analysis was possible for only 0.4-0.5 micromol of ammonium with a SD of 0.8 per thousand (n = 5).     

Studies on the conformation of α-arylcinnamic acids and their esters: Crystal structures of methyl (E)-2,3-bis(3,4-dimethoxyphenyl)propenoate and methyl (Z)-2,3-bis(3,4-dimethoxyphenyl)propenoate

The conformations of stereoisomers of -arylcinnamic acids and their esters are discussed based on crystal structures of the E and Z forms of 2,3-bis(3,4-dimethoxyphenyl)propenoic acid and its methyl ester. In the E forms of the cinnamic acid and the cinnamic acid ester, the plane of the -aryl substituent is approximately perpendicular to that of the rest of the molecule. In the Z forms the plane of the carboxyl or methoxycarbonyl group is approximately perpendicular to that of the ethylenic group, and both the aromatic group planes are significantly twisted out of the ethylenic group plane. Crystal structures of methyl (E)-2,3-bis(3,4-dimethoxyphenyl)propenoate (space group P2₁/n with a = 8.1697(5), b = 11.3882(9), c = 19.7766(9) Å, = 90.058(4)°, V = 1840.0(2) ų, and Z = 4), monoclinic methyl (Z)-2,3-bis(3,4-dimethoxyphenyl)propenoate (space group P2₁/n with a = 11.183(2), b = 5.640(2), c = 29.737(7) Å, = 99.19(2)°, V = 1851.4(9) ų, and Z = 4), and orthorhombic methyl (Z)-2,3-bis(3,4-dimethoxyphenyl)propenoate (space group P2₁2₁2₁ with a = 8.849(4), b = 24.288(9), c = 8.734(3) Å, V = 1877(1) ų, and Z = 4) are reported.     

Using the Donsker Delta Function to Compute Hedging Strategies

We use white noise calculus and the Donsker Delta Function to find explicit formulas for the replicating portfolios in a Black–Scholes market for a class of contingent T-claims.     

Sample cleanup-free determination of mycophenolic acid and its glucuronide in serum and plasma using the novel technology of ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry

Mycophenolic acid (MPA) is an immunosuppressant drug which powerfully inhibits lymphocyte proliferation. Since the early 1990s it has been used to prevent rejection in organ transplantation. The requirement of therapeutic drug monitoring shown in previous studies raises the necessity of acquiring accurate and sensitive methods to measure MPA and its major metabolite mycophenolic acid glucuronide (MPAG).The authors developed a sample cleanup-free, rapid, and highly specific method for simultaneous measurement of MPA and MPAG in human plasma and serum using the novel technology of ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry. MPA- and MPAG-determinations were performed during a 2.0-min run time. Multiple calibration curves for the analysis of MPA and MPAG exhibited consistent linearity and reproducibility in the range of 0.05-100 (r > 0.999) mg L⁻¹ and 4-4000 mg L⁻¹ (r > 0.999), respectively. Limits of Detection were 0.014 mg L⁻¹ for MPA and 1.85 mg L⁻¹ for MPAG. Lower Limits of Quantification were 0.05 mg L⁻¹ for MPA and 2.30 mg L⁻¹ for MPAG. Interassay imprecision was <10% for both substances. Mean recovery was 103.6% (range 78.1-129.7%) for MPA and 111.1% (range 73.0-139.6%) for MPAG. Agreement was good for MPA and MPAG between the presented method and a validated HPLC-MS/MS method. The Passing-Bablok regression line for MPA and MPAG was HPLC-MS/MS = 1.14 UPLC-MS/MS—0.14 [mg L⁻¹], r = 0.96, and HPLC-MS/MS = 0.77 UPLC-MS/MS + 0.50 [mg L⁻¹], r = 0.97, respectively. This sample cleanup-free and robust LC-MS/MS assay facilitates the rapid, accurate and simultaneous determination of MPA and MPAG in human body fluids.     

A diffuse-interface method for two-phase flows with soluble surfactants

A method is presented to solve two-phase problems involving soluble surfactants. The incompressible Navier-Stokes equations are solved along with equations for the bulk and interfacial surfactant concentrations. A non-linear equation of state is used to relate the surface tension to the interfacial surfactant concentration. The method is based on the use of a diffuse interface, which allows a simple implementation using standard finite difference or finite element techniques. Here, finite difference methods on a block-structured adaptive grid are used, and the resulting equations are solved using a non-linear multigrid method. Results are presented for a drop in shear flow in both 2D and 3D, and the effect of solubility is discussed.     

Generation and characterization of stable, highly concentrated titanium dioxide nanoparticle aerosols for rodent inhalation studies

The intensive use of nano-sized titanium dioxide (TiO₂) particles in many different applications necessitates studies on their risk assessment as there are still open questions on their safe handling and utilization. For reliable risk assessment, the interaction of TiO₂ nanoparticles (NP) with biological systems ideally needs to be investigated using physico-chemically uniform and well-characterized NP. In this article, we describe the reproducible production of TiO₂ NP aerosols using spark ignition technology. Because currently no data are available on inhaled NP in the 10?C50 nm diameter range, the emphasis was to generate NP as small as 20 nm for inhalation studies in rodents. For anticipated in vivo dosimetry analyses, TiO₂ NP were radiolabeled with ⁴⁸V by proton irradiation of the titanium electrodes of the spark generator. The dissolution rate of the ⁴⁸V label was about 1% within the first day. The highly concentrated, polydisperse TiO₂ NP aerosol (3?C6 × 10⁶ cm^?3) proved to be constant over several hours in terms of its count median mobility diameter, its geometric standard deviation, and number concentration. Extensive characterization of NP chemical composition, physical structure, morphology, and specific surface area was performed. The originally generated amorphous TiO₂ NP were converted into crystalline anatase TiO₂ NP by thermal annealing at 950 °C. Both crystalline and amorphous 20-nm TiO₂ NP were chain agglomerated/aggregated, consisting of primary particles in the range of 5 nm. Disintegration of the deposited TiO₂ NP in lung tissue was not detectable within 24 h.     

Distributed Solution of Constrained Optimal Control Problems Using the Alternating Direction Method of Multipliers

Many control problems in science and engineering can be formulated as optimal control problems (OCP) such as load changes in process control or point-to-point motion of industrial robots in a time-optimal or energy-optimal way while accounting for physical or security constraints. Hence, an efficient way to handle constrained OCPs is an important topic of research. A promising approach to address this issue is a transformation technique allowing to reformulate an inequality constrained OCP into an equality constrained counterpart. The reformulated OCP reveals to possess a particular structure that is favorable for a decomposition and the application of distributed optimization methods. Motivated by the Augmented Lagrangian approach, the structure of the reformulated OCP can be exploited to derive a decomposition method for splitting up the entire OCP into smaller subproblems. In addition, an algorithm is presented that follows the ideas of the Alternating Direction Method of Multipliers (ADMM) and solves the resulting subproblems in a distributed manner. The approach is applied to a mechatronic example system to demonstrate the performance of the presented method. (© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Differences in porous characteristics of styrenic monoliths prepared by controlled thermal polymerization in molds of varying dimensions

Nitroxide‐mediated polymerization was used as a model system for preparing styrenic monolithic materials with significant mesopore contents in different mold formats, with the aim of assessing the validity of pore characterization of capillary monoliths by analysis of parallel bulk polymerized precursor solution. Capillary monoliths were prepared in 250 μm id fused silica tubes (quadruplicate samples, in total 17 m), and the batch polymerizations were carried out in parallel in 100 μL microvials and regular 2 mL glass vials, both in quintuplicate. The monoliths recovered from the molds were characterized for their meso‐ and macroporous properties by nitrogen sorptiometry (three repeated runs on each sample), followed by a single analysis by mercury intrusion porosimetry. A total of 14 monolith samples were thus analyzed. A Grubbs' test identified one regular vial sample as an outlier in the sorptiometric surface area measurements, and data from this sample were consequently excluded from the pore size calculations, which are based on the same nitrogen sorption data, and also from the mercury intrusion data set. The remaining data were subjected to single factor analyses of variance analyses to test if the porous properties of the capillary monoliths were different from those of the bulk monoliths prepared in parallel. Significant differences were found between all three formats both in their meso‐ and macroporous properties. When the dimension was shrunk from conventional vial to capillary size, the specific surface area decreased from 52.2±4.7 to 34.6±1.7 m²/g. This decrease in specific surface area was accompanied by a significant shift in median diameter of the through‐pores, from 310±3.9 to 544±13 nm. None of these differences were obvious from the scanning electron micrographs that were acquired for each sample type. The common practice of determining the mesopore characteristics from analysis of samples prepared by parallel bulk polymerization and looking for changes in the macropore structure by visual assessment of SEMs are therefore both rather questionable, at least for monoliths of the kind used in this study.