Ultrafast excited-state dynamics of adenine and monomethylated adenines in solution: implications for the nonradiative decay mechanism

The DNA base adenine and four monomethylated adenines were studied in solution at room temperature by femtosecond pump-probe spectroscopy. Transient absorption at visible probe wavelengths was used to directly observe relaxation of the lowest excited singlet state (S(1) state) populated by a UV pump pulse. In H(2)O, transient absorption signals from adenine decay biexponentially with lifetimes of 0.18 +/- 0.03 ps and 8.8 +/- 1.2 ps. In contrast, signals from monomethylated adenines decay monoexponentially. The S(1) lifetimes of 1-, 3-, and 9-methyladenine are similar to one another and are all below 300 fs, while 7-methyladenine has a significantly longer lifetime (tau = 4.23 +/- 0.13 ps). On this basis, the biexponential signal of adenine is assigned to an equilibrium mixture of the 7H- and 9H-amino tautomers. Excited-state absorption (ESA) by 9-methyladenine is 50% stronger than by 7-methyladenine. Assuming that ESA by the corresponding tautomers of adenine is unchanged, we estimate the population of 7H-adenine in H(2)O at room temperature to be 22 +/- 4% (estimated standard deviation). To understand how the environment affects nonradiative decay, we performed the first solvent-dependent study of nucleobase dynamics on the ultrafast time scale. In acetonitrile, both lowest energy tautomers of adenine are present in roughly similar proportions as in water. The lifetimes of the 9-substituted adenines depend somewhat more sensitively on the solvent than those of the 7-substituted adenines. Transient signals for adenine in H(2)O and D(2)O are identical. These solvent effects strongly suggest that excited-state tautomerization is not an important nonradiative decay pathway. Instead, the data are most consistent with electronic energy relaxation due to state crossings between the optically prepared (1)pipi* state and one or more (1)npi* states and the electronic ground state. The pattern of lifetimes measured for the monomethylated adenines suggests a special role for the (1)npi* state associated with the N7 electron lone pair.     

Mechanism of azole antifungal activity as determined by liquid chromatographic/mass spectrometric monitoring of ergosterol biosynthesis

A liquid chromatography/mass spectrometry (LC/MS) method for separation and characterization of ergosterol biosynthetic precursors was developed to study the effect of Posaconazole on sterol biosynthesis in fungi. Ergosterol biosynthetic precursors were characterized from their electron ionization mass spectra acquired by a normal-phase chromatography, particle beam LC/MS method. Fragment ions resulting from cleavage across the D-ring and an abundant M - 15 fragment ion were diagnostic for methyl substitution at C-4 and C-14. Comparison of the sterol profile in control and treated Candida albicans incubations showed depletion of ergosterol and accumulation of C-4 and C-14 methyl-substituted sterols following treatment with Posaconazole. These C-4 and C-14 methyl sterols are known to be incapable of sustaining cell growth. The results demonstrate that Posaconazole exerts its antifungal activity by inhibition of ergosterol biosynthesis. Furthermore, Posaconazole appears to disrupt ergosterol biosynthesis by inhibition of lanosterol 14alpha-demethylase.     

Comparative study of the effect of various electrode membranes on biofouling and electrochemical measurements

Stability of sensors in biosamples is a critical issue and can be mitigated by membranes. The effect of different membranes (Nafion, cellulose acetate, chitosan, fibronectin, PSS/PL) on the electrochemistry of an outer-sphere redox couple (ruthenium II/III hexaammine) and on the electrocatalytic reduction of dissolved oxygen are described. Biofouling has been induced by albumin solutions. Results demonstrate good performances of fibronectin in all situations investigated. Other membranes do not provide a satisfactory protection from biofouling and some of them, PSS/PL in particular, seriously disturb electrochemical mechanisms.     

Sparse color-critical hypergraphs

In this paper we obtain estimates for the least number of edges ann-uniformr-color-critical hypergraph of orderm may have.     

Allene-alkyne cross-coupling for stereoselective synthesis of substituted 1,4-dienes and cross-conjugated trienes

Titanium-mediated cross-coupling of allenic alcohols with alkynes has been investigated. Divergent reaction pathways were discovered that provide either stereodefined 1,4-dienes or substituted cross-conjugated trienes. In short, allene substitution plays a critical role in the determination of reaction pathway.     

Assessing the risk of vCJD transmission via surgery: models for uncertainty and complexity

Variant Creutzfeldt–Jakob disease (vCJD) is a fatal degenerative brain disease, which probably passed into humans from cattle infected with bovine spongiform encephalopathy (BSE) or ‘mad cow disease’. Whatever its origins, the question arises of whether vCJD could be spread from person to person. Any such risk is very difficult to quantify, not least because the number of people already infected is unknown. This paper reflects on a study assessing the risk of transmission via instruments used in hospital surgery. The study underpinned a number of policy initiatives, including a £200?m programme to improve instrument decontamination. The methodology had to meet two major challenges. That of dealing with very large and multiple uncertainties was initially addressed using simple spreadsheet-based models to generate alternative scenarios. The complexity in the possible dynamics of vCJD within the population was then tackled. This paper outlines the models built and their use in eliciting expert judgement and informing risk management policy.     

A Discussion on Variational Analysis in Derivative-Free Optimization

Variational Analysis studies mathematical objects under small variations. With regards to optimization, these objects are typified by representations of first-order or second-order information (gradients, subgradients, Hessians, etc). On the other hand, Derivative-Free Optimization studies algorithms for continuous optimization that do not use first-order information. As such, researchers might conclude that Variational Analysis plays a limited role in Derivative-Free Optimization research. In this paper we argue the contrary by showing that many successful DFO algorithms rely heavily on tools and results from Variational Analysis.

     

Algorithmic Construction of the Subdifferential from Directional Derivatives

The subdifferential of a function is a generalization for nonsmooth functions of the concept of gradient. It is frequently used in variational analysis, particularly in the context of nonsmooth optimization. The present work proposes algorithms to reconstruct a polyhedral subdifferential of a function from the computation of finitely many directional derivatives. We provide upper bounds on the required number of directional derivatives when the space is ?¹ and ?², as well as in ? ⁿ where subdifferential is known to possess at most three vertices.