Affinity of the anthracycline antitumor drugs Doxorubicin and Sabarubicin for human telomeric G-quadruplex structures

Combining various techniques in solution we proved that Doxorubicin, also called Adriamycin, and Sabarubicin, also known as MEN 10755, bind to the human telomeric sequence, 5'-d[GGG(TTAGGG)(3)]-3' (21-mer), assuming a G-quadruplex structure in the presence of K(+). Complexes of drugs with the 21-mer in 1?:?1 and 2?:?1 stoichiometry coexist in solution. Association constants were obtained from titration experiments and confirmed by isothermal titration calorimetry. The fluorescence of the drugs was quenched upon complexation. UV circular dichroism (CD) spectra of the complexes were characterized by the G-quadruplex signal and indicated that drug binding influences the equilibrium between quadruplex conformations. The visible CD spectra were exclusively due to the drug and show differences in the complexation modes of the two drugs. Spectroscopic and thermodynamic parameters of the 1?:?1 complexes point to drug stacking with the G-quadruplex top or bottom tetrad. Thermodynamic data suggests that the binding of the second drug molecule in the 2?:?1 complex may occur in a groove. Complexation caused a small increase in the thermal stability of the G-quadruplex main conformation, shifting T(m) from 62 to 67 °C.     

Foreword

Steve Smale set the agenda for FoCM in his call for the 1995 conference in Park City, Utah. No stranger he to ambitious agendas and extraordinary accomplishments. He is one of the dominant figures in the mathematics of the second half of the twentieth century. Smale’s theory of immersions, the generalized Poincare conjecture, and H-cobordism theorems with their far-reaching consequences are the bedrock of differential topology. His horseshoe is the hallmark of chaos, and his hyperbolic dynamics the rejuvenation of the geometric theory of dynamical systems. He is one of the pioneers in the introduction of infinite-dimensional manifolds for the study of nonlinear problems in the calculus of variations and partial differential equations. The list goes on: the systematic use of differential techniques in microeconomics, electrical circuit theory, chaos in predator–prey equations and, finally, for the twentieth century, the foundations of computational mathematics and complexity theory, and now, in the twenty-first century, the theory of learning. It has been our privilege to be among his collaborators and students in the broadest sense of the word. With these issues (Volume 5 Number 4 and Volume 6 Number 1, as well as an earlier article appearing in Volume 5 Number 2, are dedicated to Steve Smale’s 75th Birthday) we celebrate Steve’s 75th birthday and continuing vitality. He sets the bar high. We do our best.     

The Interaction Between N–Isopropylacrylamide-Acrylic Acid-Ethyl Methacrylate Thermosensitive Polymers and Cationic Surfactants

The interaction between cationic surfactants and isopropylacrylamide-acrylic acid-ethyl methacrylate (IPA:AA:EMA) terpolymers has been investigated using steady-state fluorescence and spectrophotometric measurements to assess the effect of the polymer composition on the aggregation process and terpolymers’ thermosensitivities. Micropolarity studies using pyrene show that the interaction of cationic surfactants with IPA:AA:EMA terpolymers occurs at surfactant concentrations much smaller than that observed for the pure surfactant in aqueous solution. The critical aggregation concentration (CAC) values decrease with both the hydrocarbon length of the surfactant and the content of ethyl methacrylate. These results were interpreted as a manifestation of the increasing contribution of attractive hydrophobic and electrostatic forces between negatively charged polymer chains and positively charged surfactant molecules. The increase of ethyl methacrylate in the copolymers lowers the CAC due to the larger hydrophobic character of the polymer backbone. The cloud point determination reveals that the lower critical solution temperatures (LCST) depend strongly on the copolymer composition and surfactant nature. The binding of surfactants molecules to the polymer chain screens the electrostatic repulsion between the carboxylic groups inducing a conformational transition and the dehydration of the polymer chain.     

INAA at the top of the world: Elemental characterization and analysis of airborne particulate matter collected in the Himalayas at 5,100 m high

A magnetic filter — continuous electrodeionization (CEDI) hybrid separation system was investigated for the purification of the primary coolant in a nuclear power plant. A magnetic filter system with a 3000 Gauss magnetic field and a CEDI system with a cell consisting of 3 compartments were used for the removal of magnetite and nickel ions, respectively. The hybrid separation system achieved removal rates of 98% for magnetite and 99% for the nickel ions demonstrating its feasibility for the purification of primary coolant.The authors gratefully acknowledge the Basic Atomic Energy Research Institute (BAERI) program at the Korea Institute of Science and Technology Evaluation and Planning (KISTEP) for the financial support to carry out this work.     

Onset of mechanical stability in random packings of frictional spheres

Using sedimentation to obtain precisely controlled packings of noncohesive spheres, we find that the volume fraction phiRLP of the loosest mechanically stable packing is in an operational sense well defined by a limit process. This random loose packing volume fraction decreases with decreasing pressure p and increasing interparticle friction coefficient mu. Using x-ray tomography to correct for a container boundary effect that depends on particle size, we find for rough particles in the limit p-->0 a new lower bound, phiRLP=0.550+/-0.001.     

Overcritical rotation of a trapped Bose-Einstein condensate

The rotational motion of an interacting Bose-Einstein condensate confined by a harmonic trap is investigated by solving the hydrodynamic equations of superfluids, with the irrotationality constraint for the velocity field. We point out the occurrence of an overcritical branch where the system can rotate with angular velocity larger than the oscillator frequencies. We show that in the case of isotropic trapping the system exhibits a bifurcation from an axisymmetric to a triaxial configuration, as a consequence of the interatomic forces. The dynamical stability of the rotational motion with respect to the dipole and quadrupole oscillations is explicitly discussed.