Targeting DNA bulged microenvironments with synthetic agents: lessons from a natural product

Bulged regions of nucleic acids are important structural motifs whose function has been linked to a number of key nuclear processes. Additionally, bulged intermediates have been implicated in the etiology of several genetic diseases and as targets for viral regulation. Despite these obvious ramifications, few molecules are capable of selective binding to bulged sequences. Prompted by the remarkable affinity of a natural product metabolite, we have designed and prepared a series of readily accessible synthetic agents with selective bulge binding activity. Furthermore, by screening a library of bulge-containing oligodeoxynucelotides, correlations between structure and affinity of the agents can be drawn. In addition to potential applications in molecular biology, the availability of these spirocyclic agents now opens the door for rational drug design.     

Laccase‐Catalyzed Synthesis of Low‐Molecular‐Weight Lignin‐Like Oligomers and their Application as UV‐Blocking Materials

The laccase‐catalyzed oxidative polymerization of monomeric and dimeric lignin model compounds was carried out with oxygen as the oxidant in aqueous medium. The oligomers were characterized by using gel permeation chromatography (GPC) and matrix‐assisted laser desorption ionization time‐of‐flight mass spectroscopy (MALDI‐TOF MS) analysis. Oxidative polymerization led to the formation of oligomeric species with a number‐average molecular weight (M_n) that ranged from 700 to 2300 Da with a low polydispersity index. Spectroscopic analysis provided insight into the possible modes of linkages present in the oligomers, and the oligomerization is likely to proceed through the formation of C?C linkages between phenolic aromatic rings. The oligomers were found to show good UV light absorption characteristics with high molar extinction coefficient (5000–38 000 m ^?1 cm^?1) in the UV spectral region. The oligomers were blended independently with polyvinyl chloride (PVC) by using solution blending to evaluate the compatibility and UV protection ability of the oligomers. The UV/Vis transmittance spectra of the oligomer‐embedded PVC films indicated that these lignin‐like oligomers possessed a notable ability to block UV light. In particular, oligomers obtained from vanillyl alcohol and the dimeric lignin model were found to show good photostability in accelerated UV weathering experiments. The UV‐blocking characteristics and photostability were finally compared with the commercial low‐molecular‐weight UV stabilizer 2,4‐dihydroxybenzophenone.     

Design,Synthesis of Novel Thiourea and Pyrimidine Derivatives as Potential Antitumor Agents

1,3‐Bis‐(arylidene)thiourea derivatives ( 11a‐c ) were prepared by reacting thiourea ( 9 ) with bezaldehyde, p‐chlorobenzaldehyde or p‐anisaldehyde ( 10a‐c ) respectively. Further reaction of ( 11b ) with acetyl acetone, ethyl acetoacetate, malononitrile and acetic anhydride gave tetrahydropyrimidine‐2‐thiones ( 12‐14 ) and 1,3‐diacetyl thiourea ( 15 ). Compound ( 11b ) reacted with chloroacetyl chloride to give the corresponding pyrimidin‐4‐one derivative ( 16 ). Reaction of ( 12‐14 ) with acetic acid in aqueous sodium nitrite yielded the corresponding oxime derivatives ( 17‐19 ). The triazole ( 20 ) was achieved via refluxing of ( 19 ) in dimethylformamide. Reaction of ( 16 ) with mercaptoacetyl chloride gave the sulfanyl‐acetic acid ( 21 ) which afforded the dihydrazinyl ( 22 ) up on treatment with hydrazine hydrate. Newly synthesized compounds ware characterized by elemental analyses and spectral data (IR, ¹H‐NMR, ¹³C‐NMR and mass spectra). The investigated compounds were screened for their cytotoxicity, i.e. compounds 19 , 20 and 22 exhibited highly potential antitumor activity.     

Elasto-visco-plastic modeling of mild steels for sheet forming applications over a large range of strain rates

A physically based elasto-visco-plastic constitutive model is presented and compared to experimental results for three different mild steels. The experiments consist of tensile tests ranging from quasi-static conditions up to strain rates of 10³ s^?1 as well as quasi-static simple and reverse shear tests at different amounts of pre-strain. Additional two-step sequential mechanical tests (Bauschinger and orthogonal effects) have been performed to further evaluate the ability of the model to describe strain-path changes at moderate/large strains. The model requires significantly fewer material parameters compared to other visco-plasticity models from the literature, while being able to describe some of the main features of the strain-rate sensitivity of mild steels. Accordingly, the parameter identification is simple and intuitive, requiring a relatively small set of experiments. The strain-rate sensitivity modeling is not restricted to a particular hardening law and thus provides a general framework in which advanced hardening equations can be adopted.     

How fast can cracks move? A research adventure in materials failure using millions of atoms and big computers

During the last decade, we have been simulating the dynamic failure of brittle and ductile solids at the atomic level using some of the world's fastest computers. Computer experiments encompassing crack dynamics in brittle fracture, crack blunting in ductile failure, and multi-dislocation entanglement in work-hardening are some examples and have given new and exciting insights into the failure processes of solids. Our presentation begins at an introduction level where basic concepts are presented before their application is needed for the understanding of specific phenomena. The story is primarily based on our past experiences, and our goal is to give the reader a fundamental appreciation for how materials fail.     

Effect of electron phonon interaction on the optical conductivity of zigzag carbon nanotubes

Optical conductivity of a zigzag carbon nanotube is investigated in the context of the Holstein model. Green??s function approach is applied to calculate the optical conductivity as a function of photon frequency, temperature, and electron?Cphonon coupling strength. Based on our results, optical conductivity decreases with electron?Cphonon coupling constant for both metallic and semiconducting carbon nanotubes. Our results show that temperature yields shortening the height of peaks of zigzag CNT optical absorption.     

Optimal crop planting schedules and financial hedging strategies under ENSO-based climate forecasts

This paper investigates the impact of ENSO-based climate forecasts on optimal planting schedules and financial yield-hedging strategies in a framework focused on downside risk. In our context, insurance and futures contracts are available to hedge against yield and price risks, respectively. Furthermore, we adopt the Conditional-Value-at-Risk (CVaR) measure to assess downside risk, and Gaussian copula to simulate scenarios of correlated non-normal random yields and prices. The resulting optimization problem is a mixed 0?C1 integer programming formulation that is solved efficiently through a two-step procedure, first through an equivalent linear form by disjunctive constraints, followed by decomposition into sub-problems identified by hedging strategies. With data for a representative cotton producer in the Southeastern United States, we conduct a study that considers a wide variety of optimal planting schedules and hedging strategies under alternative risk profiles for each of the three ENSO phases (Niña, Niño, and Neutral.) We find that the Neutral phase generates the highest expected profit with the lowest downside risk. In contrast, the Niña phase is associated with the lowest expected profit and the highest downside risk. Additionally, yield-hedging insurance strategies are found to vary significantly, depending critically on the ENSO phase and on the price bias of futures contracts.     

Uniqueness for an overdetermined boundary value problem for the p-Laplacian

For set , and let be a measure with compact support. Suppose, for , there are functions and (bounded) domains , both containing the support of with the property that in (weakly) and in the complement of . If in addition is convex, then and .

     

Estimating arrival rate of nonhomogeneous Poisson processes with semidefinite programming

We present a summary of methods based on semidefinite programming for estimating arrival rate of nonhomogeneous Poisson processes from a finite set of observed data. Both one-dimensional time dependent, and multi-dimensional time and location dependent rates are considered. The arrival rate is a nonnegative function of time (or time and location). We also assume that it is a smooth function with continuous derivatives of up to certain order k. We estimate the rate function by one or multi-dimensional splines, with the additional condition that the underlying rate function is nonnegative. This approach results in an optimization problem over nonnegative polynomials, which can be modeled and solved using semidefinite programming. We also describe a method which requires only linear constraints. Numerical results based on e-mail arrival and highway accidents are presented.     

On the Numerical Range of Operator Polynomials

An upper bound for the number of components of the numerical range of matrix polynomials is established. We also establish a necessary condition and a sufficient condition for the connectedness of the numerical range of a quadratic selfadjoint matrix polynomial. The boundary of the numerical range of linear matrix polynomials is also considered.