Assessment of heat-sensitive thiophosphate protecting groups in the development of thermolytic DNA oligonucleotide prodrugs

Heat-sensitive thiophosphate protecting groups derived from the alcohol 4 or 10 have provided insights in the design of DNA oligonucleotide prodrugs. Indeed, functional groups stemming from the alcohol 9, 15, 16 or 22 may be applicable to thiophosphate protection of immunostimulatory CpG DNA motifs, whereas those originating from the alcohol 3, 5, 12, 13, 18, 20 or 22 offer adequate protection of terminal phosphodiester functions against ubiquitous exonucleases that may be found in biological environments. Functional groups derived from the alcohol 9, 15, 16, 19 or 23 are suitable for the protection of phosphodiester functions flanking the CpG motifs of immunomodulatory DNA sequences.     

Rapidity renormalization group

We introduce a systematic approach for the resummation of perturbative series which involves large logarithms not only due to large invariant mass ratios but large rapidities as well. A series of this form can appear in a variety of gauge theory observables. The formalism is utilized to calculate the jet broadening event shape in a systematic fashion to next-to-leading logarithmic order. An operator definition of the factorized cross section as well as a closed form of the next-to-leading-log cross section are presented. The result agrees with the data to within errors.     

Contributions of hydroxyethyl groups to the DNA binding affinities of anthracene probes

Contributions of hydroxyethyl functions to the DNA binding affinities of substituted anthracenes are evaluated by calorimetry and spectroscopy. Isothermal titration calorimetry indicated that binding of the ligands to calf thymus DNA (5 mM Tris buffer, 50 mM NaCl, pH 7.2, 25 degrees C) is exothermic. The binding constants increased from 1.5 x 10(4) to 1.7 x 10(6) M(-1) as a function of increase in the number of hydroxyethyl functions (0-4). DNA binding was accompanied by red-shifted absorption (approximately 630 cm(-1)), strong hypochromism (>65%), positive induced-circular dichroism bands, and negative linear dichroism signals. DNA binding, in general, increased the helix stabilities to a significant extent (DeltaT(m) approximately 7 degrees C, DeltaDeltaH approximately 3 kcal/mol, DeltaDeltaS approximately 6-20 cal/K.mol). The binding constants showed a strong correlation with the number of hydroxyethyl groups present on the anthracene ring system. Analysis of the binding data using the hydrophobicity parameter (Log P) showed a poor correlation between the binding affinity and hydrophobicity. This observation was also supported by a comparison of the affinities of probes carrying N-ethyl (Kb = 0.8 x 10(5) M(-1)) versus N-hydroxyethyl side chains (Kb = 5.5 x 10(5) M(-1)). These are the very first examples of a strong quantitative correlation between the DNA binding affinity of a probe and the number of hydroxyethyl groups present on the probe. These quantitative findings are useful in the rational design of new ligands for high-affinity binding to DNA.     

Spectroscopic identification of binding modes of anthracene probes and DNA sequence recognition

The binding properties of two anthracene derivatives with calf thymus DNA (CT DNA), poly(dA-dT), and poly(dG) x poly(dC) are reported. One contained bulky, cyclic cationic substituents at the 9 and 10 positions, and the other carried acylic, branched, cationic substituents. Binding of the probes to the DNA was examined by calorimetry, spectroscopy and helix melting studies. The cyclic derivative indicated exothermic binding, strong hypochromism, bathochromism, positive induced circular dichroism (CD, 300-400 nm), significant unwinding of the helix, large increases in the helix melting temperature, strong but negative linear dichroism (LD, 300-400 nm) and considerable stabilization of the helix. In contrast, the acyclic analog indicated thermoneutral binding, smaller hypochromism, no bathochromism, very weak induced CD, and no change in the helix melting temperature with any of the DNA polymers. A sharp distinction between the binding properties of the two probes is indicated, and both have intrinsic binding constants of approximately 10(6) M(-1) for the three polymers. However, when the ionic strength of the medium was lowered (10 mM NaCl), the absorption as well as CD spectral changes associated with the binding of the acyclic derivative corresponded with those of the cyclic derivative. The acyclic derivative showed large preference (10-fold) for poly(dG) x poly(dC) over poly(dA-dT), whereas the cyclic analog showed no preference. The characteristic spectroscopic signatures of the two distinct binding modes of these probes will be helpful in deciphering the interaction of other anthracene derivatives with DNA.     

Synthesis and Characterization of Styrene-Isoprene Diblock Copolymers

A simple reusable apparatus for the synthesis of up to 40 g quantities of poly(styrene-b-isoprene) diblock copolymers of reasonably low (1.2 to 1.5) polydispersity has been described. The diblock copolymers synthesized were characterized by gel permeation chromatography (GPC), membrane osmometry, viscosimetry, and nuclear magnetic resonance (NMR) spectroscopy. Number-average molecular weights (M _n) calculated from the raw GPC chromatographs of the diblock copolymers using the summation method and M versus elution volume plots for polystyrene and polyisoprene standards agree well with those measured experimentally with osmometry. It is suggested that for polydisperse block copolymers this method is simpler than the use of a universal calibration curve. Mark-Houwink constants K ans a for polyisoprene having 18% (1,2-), 66% (3,4-), and 16% (1,4-) microstructure were found to be 3.2 × 10^?4 dL/g and 0.67, respectively, in THF at 25°C. In toluene at 30°C, K = 2.0 × 10^?4 dL/g and α = 0.7 were obtained. The diblock copolymers had 26% (1,2-), 60% (3,4-), and 14% (1,4-) microstructure in the isoprene segments, and the values of K and a for these copolymers (PS > 50%, M 20.0 × 10³) in THF at 25°C were 9.0 × 10^?5 dL/g and 0.75. For M < 20.0 × 10³ the value of α was 0.5. The experimental values of [η] were found to be lower than those calculated theoretically, presumably due to the polydisperse nature and the biellipsoidal configuration of the diblock copolymers.     

Incremental Norm Estimation for Dense and Sparse Matrices

We present an incremental approach to 2-norm estimation for triangular matrices. Our investigation covers both dense and sparse matrices which can arise for example from a QR, a Cholesky or a LU factorization. If the explicit inverse of a triangular factor is available, as in the case of an implicit version of the LU factorization, we can relate our results to incremental condition estimation (ICE). Incremental norm estimation (INE) extends directly from the dense to the sparse case without needing the modifications that are necessary for the sparse version of ICE. INE can be applied to complement ICE, since the product of the two estimates gives an estimate for the matrix condition number. Furthermore, when applied to matrix inverses, INE can be used as the basis of a rank-revealing factorization.     

Semilocal and global convergence of the Newton‐HSS method for systems of nonlinear equations

Newton‐HSS methods, which are variants of inexact Newton methods different from the Newton–Krylov methods, have been shown to be competitive methods for solving large sparse systems of nonlinear equations with positive‐definite Jacobian matrices (J. Comp. Math. 2010; 28 :235–260). In that paper, only local convergence was proved. In this paper, we prove a Kantorovich‐type semilocal convergence. Then we introduce Newton‐HSS methods with a backtracking strategy and analyse their global convergence. Finally, these globally convergent Newton‐HSS methods are shown to work well on several typical examples using different forcing terms to stop the inner iterations. Copyright © 2010 John Wiley & Sons, Ltd.     

Piezospectroscopy of the triple acceptor neutral copper in germanium

Experimental and theoretical results are presented for the behaviour of the optical absorption lines of neutral copper, a triple acceptor, in germanium under applied uniaxial compression. The ground state for the three equivalent holes is found to be the four-fold degenerate Λ₈ state of $\text{T}{}_{\mathrm{d}}$. The interpretation of the results requires that, for F6〈111〉, there be no splitting of either the ground state or the excited state of the D-line. However, this interpretation produces a violation of the predicted selection rules for the G components with F6〈100〉.