Genome-wide single-nucleotide polymorphism arrays demonstrate high fidelity of multiple displacement-based whole-genome amplification

Whole-genome DNA amplification by multiple displacement (MD-WGA) is a promising tool to obtain sufficient DNA amounts from samples of limited quantity. Using Affymetrix' GeneChip Human Mapping 10K Arrays, we investigated the accuracy and allele amplification bias in DNA samples subjected to MD-WGA. We observed an excellent concordance (99.95%) between single-nucleotide polymorphisms (SNPs) called both in the nonamplified and the corresponding amplified DNA. This concordance was only 0.01% lower than the intra-assay reproducibility of the genotyping technique used. However, MD-WGA failed to amplify an estimated 7% of polymorphic loci. Due to the algorithm used to call genotypes, this was detected only for heterozygous loci. We achieved a 4.3-fold reduction of noncalled SNPs by combining the results from two independent MD-WGA reactions. This indicated that inter-reaction variations rather than specific chromosomal loci reduced the efficiency of MD-WGA. Consistently, we detected no regions of reduced amplification, with the exception of several SNPs located near chromosomal ends. Altogether, despite a substantial loss of polymorphic sites, MD-WGA appears to be the current method of choice to amplify genomic DNA for array-based SNP analyses. The number of nonamplified loci can be substantially reduced by amplifying each DNA sample in duplicate.     

Copper(I) and silver(I) complexes of 1,5-methylene- and diethylmethylene-bridged bis(oxazoline) ligands. In situ Cu(II)-catalyzed oxidation of methylene bridge

Silver(I) and copper(I) complexes of C₂-symmetric bis(oxazoline) ligands were studied by UV, NMR, IR, EPR and ES-MS spectroscopies. The stability constants of the Ag-1a and Ag-1b complexes with 1:1 and 1:2 stoichiometries in acetonitrile were determined by NMR spectrometric titrations. The evidence of tetrahedral coordination for complex (Ag(1a)₂(⁺ was obtained from the complexation induced shifts (CIS) and NOEs. Mass spectra revealed the Cu(II) mediated oxidation of methylene bridge in copper complexes of 1a and 1b, which was in accordance with the UV, NMR, IR and EPR findings. The efficiency of Cu(I) complexes of methylene-bridged 1,5-bis(oxazoline)s 1 as chiral catalysts in stereoselective cyclopropanation of styrene with ethyl diazoacetate, was compared to that of the dialkylmethylene-bridged 1,5-bis(oxazoline)s 2.     

Migration Testing of GPPS and HIPS Polymers: Swelling Effect Caused by Food Simulants Compared to Real Foods

Migration kinetic data from general purpose polystyrene (GPPS) and high impact polystyrene (HIPS) were generated for a set of model substances as well as styrene monomer and oligomers at different temperatures (20 °C, 40 °C, 60 °C) using food simulants stipulated in the European Regulation (EU) 10/2011 and real foods like milk, cream and olive oil (20 °C, 40 °C). The extent of polymer swelling was characterized gravimetrically and visual changes of the test specimens after migration contact were recorded. Isooctane and 95% ethanol caused strong swelling and visual changes of HIPS, overestimating real migration into foods especially at high temperatures; GPPS was affected by isooctane only at 60 °C. With 50% ethanol, after 10 days contact at 60 °C or 40 °C both polymers were slightly swollen. Contrary, most of the real foods analyzed caused no detectable swelling or visual changes of the investigated polymers. This study demonstrates that the recommendations provided by EU regulations are not always in agreement with the physicochemical properties of styrenic polymers. The critical point remains the selection of adequate food simulants/testing conditions, since the high overestimation of aggressive media can lead to non-compliance of polystyrene materials even if the migration into real food would be of no concern.     

Synthesis,Kinetics, and Molecular Docking of Novel 9‐(2‐Hydroxypropyl)purine Nucleoside Analogs as Ligands of Herpesviral Thymidine Kinases

In the context of broadening the knowledge on substrate specificity of Herpes simplex virus type 1 thymidine kinase (HSV‐1 TK) and Varicella‐Zoster virus thymidine kinase (VZV TK), new derivatives of 9‐(2‐hydroxypropyl)‐substituted adenine, chloropurine, hypoxanthine, guanine, thiopurine, and (methylsulfanyl)purine were synthesized and subjected to in vitro phosphorylation and binding affinity assays. The interactions between the compounds and the crystallographically determined active site residues of HSV‐1 TK have been studied by molecular modeling with the Lamarckian genetic algorithm of docking program AutoDock 3.0. All compounds mentioned bind to both enzymes in the low mM to sub‐mM range, comparable to binding affinities of existing prodrugs. Findings from the docking procedure indicate multiple binding modes for all of the compounds and are in accordance with the results of phosphorylation and binding‐affinity studies. Furthermore, the studies reveal that hypoxanthine derivatives represent a new class of TK substrates and thiopurine derivatives a new class of TK inhibitors.     

Quantum and Classical Implication Algebras with Primitive Implications

Join in an orthomodular lattice is obtained inthe same form for all five quantum implications. Theform holds for the classical implication in adistributive lattice as well. Even more, the definition added to an ortholattice makes it orthomodularfor quantum implications and distributive for theclassical one. Based on this result a quantumimplication algebra with a single primitive — andin this sense unique — implication is formulated. Acorresponding classical implication algebra is alsoformulated. The algebras are shown to be special casesof a universal implication algebra.     

Magnetic nanostructures as amplifiers of transverse fields in magnetic resonance

We introduce the concept of amplifying the transverse magnetic fields produced and/or detected with inductive coils in magnetic resonance settings by using the reversible transverse susceptibility properties of magnetic nanostructures. First, we describe the theoretical formalism of magnetic flux amplification through the coil in the presence of a large perpendicular DC magnetic field (typical of magnetic resonance systems) achieved through the singularity in the reversible transverse susceptibility in anisotropic single domain magnetic nanoparticles. We experimentally demonstrate the concept of transverse magnetic flux amplification in an inductive coil system using oriented nanoparticles with uni-axial magnetic anisotropy. We also propose a composite ferromagnetic/anti-ferromagnetic core/shell nanostructure system with uni-directional magnetic anisotropy that, in principle, provides maximal transverse magnetic flux amplification.     

Electron slip influence on quasimolecular X-rays in heavy ion collisions

The rotation of the quasimolecular axis in the heavy ion collision is treated dynamically by taking into account the 2pπ-2pσ electron slip. This is done by the correct quantum mechanical method in the perturbation approximation for low ion velocities. The various radiative processes resulting from initial alignments are discussed. The spectra and anisotropies are calculated. Their dependence on the electron slip is investigated.     

Flat-top system of the DC-280 cyclotron

The flat-top cavity of the radio-frequency accelerating system designed at the Flerov Laboratory of Nuclear Reactions, Joint Institute for Nuclear Research, for the DC-280 cyclotron is described. The cyclotron is intended for increasing the capabilities and efficiency of experiments on the synthesis of super-heavy elements and an investigation of their nuclear physical and chemical properties. The DC-280 isochronous heavy-ion cyclotron will produce accelerated beam of ions in the range from neon to uranium. The parameters, design, and results of the experimental and 3D computer modeling of the flat-top cavity of the RF accelerating system of the DC-280 cyclotron are reported.     

Integration of third order ordinary differential equations possessing two-parameter symmetry group by Lie’s method

The solution of a class of third order ordinary differential equations possessing two parameter Lie symmetry group is obtained by group theoretic means. It is shown that reduction to quadratures is possible according to two scenarios: (1) if upon first reduction of order the obtained second order ordinary differential equation besides the inherited point symmetry acquires at least one more new point symmetry (possibly a hidden symmetry of Type II). (2) First, reduction paths of the fourth order differential equations with four parameter symmetry group leading to the first order equation possessing one known (inherited) symmetry are constructed. Then, reduction paths along which a third order equation possessing two-parameter symmetry group appears are singled out and followed until a first order equation possessing one known (inherited) symmetry are obtained. The method uses conditions for preservation, disappearance and reappearance of point symmetries.     

Chiral Hexa‐ and Nonamethylene‐Bridged Bis(L‐Leu‐oxalamide) Gelators: The First Oxalamide Gels Containing Aggregates with a Chiral Morphology

Chiral amino acid‐ and amino alcohol‐oxalamides are well‐known as versatile and efficient gelators of various lipophilic and polar organic solvents and water. To further explore the capacity of the amino acid/oxalamide structural fragment as a gelation‐generating motif, the dioxalamide dimethyl esters 1₆Me and 1₉Me , and dicarboxylic acid 2₆OH / 2₉OH derivatives containing flexible methylene bridges with odd ( 9 ; n=7) and even ( 6 ; n=4) numbers of methylene groups were prepared. Their self‐assembly motifs and gelation properties were studied by using a number of methods (FTIR, ¹H NMR spectroscopy, CD, TEM, DSC, XRPD, molecular modeling, MMFF94, and DFT). In contrast to the previously studied chiral bis(amino acid or amino alcohol) oxalamide gelators, in which no chiral morphology was ever observed in the gels, the conformationally more flexible 1₆Me , 1₉Me , 2₆OH , and 2₉OH provide gelators that are capable of forming diverse aggregates of achiral and chiral morphologies, such as helical fibers, twisted tapes, nanotubules, straight fibers, and tapes, in some cases coexisting in the same gel sample. It is shown that the differential scanning calorimetry (DSC)‐determined gelation enthalpies could not be correlated with gelator and solvent clogP values. Spectroscopic results show that intermolecular hydrogen‐bonding between the oxalamide units provides the major and self‐assembly directing intermolecular interaction in the aggregates. Molecular modeling studies reveal that molecular flexibility of gelators due to the presence of the polymethylene bridges gives three conformations ( zz , p1 , and p2 ) close in energy, which could form oxalamide hydrogen‐bonded layers. The aggregates of the p1 and p2 conformations tend to twist due to steric repulsion between neighboring iBu groups at chiral centers. The X‐ray powder diffraction (XRPD) results of 1₆Me and 1₉Me xerogels prove the formation of p1 and p2 gel aggregates, respectively. The latter results explain the formation of gel aggregates with chiral morphology and also the simultaneous presence of aggregates of diverse morphology in the same gel system.