Comparison of the thermodynamics and base-pair dynamics of a full LNA:DNA duplex and of the isosequential DNA:DNA duplex

Locked nucleic acids (LNA), conformationally restricted nucleotide analogues, are known to enhance pairing stability and selectivity toward complementary strands. With the aim to contribute to a better understanding of the origin of these effects, the structure, thermal stability, hybridization thermodynamics, and base-pair dynamics of a full-LNA:DNA heteroduplex and of its isosequential DNA:DNA homoduplex were monitored and compared. CD measurements highlight differences in the duplex structures: the homoduplex and heteroduplex present B-type and A-type helical conformations, respectively. The pairing of the hybrid duplex is characterized, at all temperatures monitored (between 15 and 37 degrees C), by a larger stability constant but a less favorable enthalpic term. A major contribution to this thermodynamic profile emanates from the presence of a hairpin structure in the LNA single strand which contributes favorably to the entropy of interaction but leads to an enthalpy penalty upon duplex formation. The base-pair opening dynamics of both systems was monitored by NMR spectroscopy via imino protons exchange measurements. The measurements highlight that hybrid G-C base-pairs present a longer base-pair lifetime and higher stability than natural G-C base-pairs, but that an LNA substitution in an A-T base-pair does not have a favorable effect on the stability. The thermodynamic and dynamic data confirm a more favorable stacking of the bases in the hybrid duplex. This study emphasizes the complementarities between dynamic and thermodynamical studies for the elucidation of the relevant factors in binding events.

A new proposition on the martingale representation theorem and on the approximate hedging of contingent claim in mean-variance criterion

In this work we revisit the problem of the hedging of contingent claim using mean-square criterion. We prove that in incomplete market, some probability measure can be identified so that becomes -martingale under .This is in fact a new proposition on the martingale representation theorem. The new results also identify a weight function that serves to be an approximation to the Radon-Nikodým derivative of the unique neutral martingale measure.

Coffee Filters and Creativity: The Value of Multiple Filters in the Creative Process

Creativity is often defined as developing something novel or new, that fits its context, and has value. To achieve this, the creative process itself has gained increasing attention as organizational leaders seek competitive advantages through developing new products, services, process, or business models. In this paper, we explore the notion of the creative process as including a series of “filters” or ways to process information as being a critical component of the creative process. We use the metaphor of coffee making and filters because many of our examples come from Vietnam, which is one of the world’s top coffee exporters and which has created a coffee culture rivaling many other countries. We begin with a brief review of the creative process its connection to information processing, propose a tentative framework for integrating the two ideas, and provide examples of how it might work. We close with implications for further practical and theoretical directions for this idea.

Comparison of the experimental, semi-experimental and ab initio equilibrium structures of acetylene: Influence of relativisitic effects and of the diagonal Born-Oppenheimer corrections

The equilibrium structure of acetylene (also named ethyne) has been reinvestigated to resolve the small discrepancies noted between different determinations. The size of the system as well as the large amount of available experimental data provides the quite unique opportunity to check the magnitude and relevance of various contributions to equilibrium structure as well as to verify the accuracy of experimental results. With respect to pure theoretical investigation, quantum-chemical calculations at the coupled-cluster level have been employed together with extrapolation to the basis set limit, consideration of higher excitations in the cluster operator, inclusion of core correlation effects as well as relativistic and diagonal Born-Oppenheimer corrections. In particular, it is found that the extrapolation to the complete basis set limit, the inclusion of higher excitations in the electronic-correlation treatment and the relativistic corrections are of the same order of magnitude. It also appears that a basis set as large as a core-valence quintuple-zeta set is required for accurately accounting for the inner-shell correlation contribution. From a pure experimental point of view, the equilibrium structure has been determined using very accurate rotational constants recently obtained by a global analysis (that is to say that all non-negligible interactions are explicitely included in the Hamiltonian matrix) of rovibrational spectra. Finally, a semi-experimental equilibrium structure (where the equilibrium rotational constants are obtained from the experimental ground state rotational constants and computed rovibrational corrections) has been obtained from the available experimental ground-state rotational constants for ten isotopic species corrected for computed vibrational corrections. Such a determination led to the revision of the ground-state rotational constants of two isotopologues, thus showing that structural determination is a good method to identify errors in experimental rotational constants. The three structures are found in a very good agreement, and our recommended values are rCC 120.2958(7) pm and rCH 106.164(1) pm. © 2011 American Institute of Physics.

Finite groups and geometries: a view on the present state and on the future

The model: groups of Lie-Chevalley type and buildingsThis paper is not the presentation of a completed theory but rather a report on a search progressing as in the natural sciences in order to better understand the relationship between groups and incidence geometry, in some future sought-after theory Τ. The search is based on assumptions and on wishes some of which are time-dependent, variations being forced, in particular, by the search itself.A major historical reference for this subject is, needless to say, Klein's Erlangen Programme. Klein's views were raised to a powerful theory thanks to the geometric interpretation of the simple Lie groups due to Tits (see for instance), particularly his theory of buildings and of groups with a BN-pair (or Tits systems). Let us briefly recall some striking features of this.Let G be a group of Lie-Chevalley type of rank r, denned over GF(q), q = pn, p prime. Let Xr denote the Dynkin diagram of G. To these data corresponds a unique thick building B(G) of rank r over the Coxeter diagram Xr (assuming we forget arrows provided by the Dynkin diagram). It turns out that B(G) can be constructed in a uniform way for all G, from a fixed p-Sylow subgroup U of G, its normalizer NG(U) and the r maximal subgroups of G containing NG(U).

Characteristics of the biphasic action of androgens and of the potent antiproliferative effects of the new pure antiestrogen EM-139 on cell cycle kinetic parameters in LNCaP human prostatic cancer cells

The most potent steroid in human prostatic carcinoma LNCaP cells, i.e. dihydrotestosterone (DHT), has a biphasic stimulatory effect on cell proliferation. At the maximal stimulatory concentration of 0.1 nM DHT, analysis of cell kinetic parameters shows a decrease of the G0-G1 fraction with a corresponding increase of the S and G2 + M fractions. In contrast, concentrations of 1 nM DHT or higher induce a return of cell proliferation to control levels, reflected by an increase in the G0-G1 fraction at the expense of the S and especially the G2 + M fractions. Continuous labeling for 144 h with the nucleotide analogue 5'-bromodeoxyuridine shows that the percentage of cycling LNCaP cells rises more than 90% after treatment with stimulatory concentrations of DHT, whereas in control cells as well as in cells treated with high concentrations of the androgen, this value remains below 50%. Although LNCaP cells do not contain detectable estrogen receptors, the new pure steroidal antiestrogen EM-139 not only reversed the stimulation of cell proliferation and cell kinetics induced by stimulatory doses of DHT but also inhibited basal cell proliferation.