Mutagenicity and DNA damage studies of N-acyloxy-N-alkoxyamides--the role of electrophilic nitrogen

N-Acyloxy-N-alkoxyamides are anomeric amides that are direct-acting mutagens. They have been shown to damage DNA in the major and the minor grooves in a pH and sequence-selective manner. In acidic media, they damage adenines at N3 in the minor groove but above neutral pH, only guanine is damaged at N7 in the major groove. Both the acyloxy leaving group and the alkoxy group at the amide nitrogen are responsible for their electrophilicity and Salmonella mutagenicities in TA 100 and DNA damage data confirm that the mutagens react with DNA in an intact form, rather than by solvolysis to electrophilic nitrenium ions in the cytosol, or in vitro, prior to reacting with DNA. Hydrophobicity plays a role in both mutagenicity and DNA damage.     

CARS methane spectra: Experiments and simulations for temperature diagnostic purposes

CARS laboratory experiments were done in the 2905–2925 cm⁻¹ range, in the vicinity of the ν₁ band of the methane molecule, for pressures ranging from 1 to 50 bar, and temperatures up to 1100 K. These experiments were carried out in order to retrieve the pressure evolution of the CH₄ spectrum, as well as to confirm its temperature dependance. After a brief recall on the theory used to compute pressure broadening coefficients and relaxation rates, we consider the ν₃ and ν₄ infrared bands of methane for benchmark calculations purposes. Next, we present recent experimental CARS spectra and calculated ones. Lastly, we discuss flame experiments as well as comparisons of temperature retrieval using N₂ and CH₄ as probe molecules.     

Ultraviolet Photodissociation: Developments towards Applications for Mass‐Spectrometry‐Based Proteomics

Unraveling of all of the information contained in proteomes poses a tremendous chemical challenge, which is balanced by the promise of potentially transformational knowledge. Mass spectrometry offers an unprecedented arsenal of tools for diverse proteomic investigations. Recently, it was demonstrated that ultraviolet light can be utilized to initiate unique and potentially useful fragmentations in peptides and proteins. Either nonspecific dissociation or highly specific dissociation at engineered chromophoric sites is possible following photon absorption. The level of specificity and control over fragmentation in these experiments is greater than with other fragmentation methods. Novel techniques made possible by this technology are poised to make substantial contributions to the field of proteomics.     

Projection of diffusions on submanifolds: Application to mean force computation

We consider the problem of sampling a Boltzmann‐Gibbs probability distribution when this distribution is restricted (in some suitable sense) on a submanifold Σ of ?ⁿ implicitly defined by N constraints q₁(x) = ? = q_N(x) = 0 (N < n). This problem arises, for example, in systems subject to hard constraints or in the context of free energy calculations. We prove that the constrained stochastic differential equations (i.e., diffusions) proposed in [7, 13] are ergodic with respect to this restricted distribution. We also construct numerical schemes for the integration of the constrained diffusions. Finally, we show how these schemes can be used to compute the gradient of the free energy associated with the constraints. © 2007 Wiley Periodicals, Inc.     

Synthesis of 2′-C-methyl-branched isonucleosides

Novel regioisomers of 2′-methyl-branched nucleosides were designed and synthesized to mimic potent anti-viral drugs like Valopicitabine. The short and efficient synthesis of the targets involves a one-pot tosylation/cyclization step that leads to an activated furan scaffold on which the isonucleosides were built.     

Waves on vortex cores

Here we discuss the types of waves which can be supported on compact regions of vorticity. This is a subject first studied by Lord Kelvin for waves propagating along the vortex lines of the Rankine and hollow-core vorticity distributions. Kelvin's major interest was in the stability of vortex rings and the numerous resurgencies in interest have usually been driven by practically important phenomena, e.g., the observations of vortex breakdown and waves on tornado and aircraft vortices in the early 1960's and more recently in technologically and geophysically significant flows and on the quantised vortices of super fluid HeII.

The major wave-types of interest are of varicose, helicoidal and fluted form and represent a periodic swelling and contraction, a bending and a “krinkling” of the core, respectively. The first two propagate along and the third around the vortex lines. All have been studied theoretically, experimentally and numerically in the limit of small wave amplitude and their major characteristics are now clear. Of particular interest is the extension of these results to the non-linear regime in which case the two first types are known to exhibit solitary wave or soliton characteristics in certain parameter ranges. It is these non-linear waves which often dominate observations of vortex flows both in nature and in technological applications and which have caused much controversy in the interpretation of results found under complex circumstances of flow and apparatus geometry.