Off-equilibrium response of grafted polymer chains subject to a variable rate of compression

We present Brownian dynamics simulations of single grafted semiflexible chains (i.e., "polymer mushrooms") with varying persistence lengths, intra-chain interactions, and subject to confinement. The results from different rates of compression are presented in the cases of an approaching infinite plane and a paraboloid tip. We discuss the different behaviour observed for grafted chains with strong and weak self-attraction (i.e., "hard" and "soft" polymer mushrooms). In both cases the effect on the size and shape is more pronounced for a slow compression rate, especially for "hard mushrooms". We have also studied the relaxation of the chain while the compressing plane is maintained, and when it is removed suddenly. We find that the response depends strongly on the time allowed for relaxation in the compressed state. When using instead a paraboloid tip, the overall effects are similar yet less pronounced because the chain can dodge the confining object via an "escape transition."     

Optimization of enzymatic biochemical logic for noise reduction and scalability: how many biocomputing gates can be interconnected in a circuit?

We report an experimental evaluation of the "input-output surface" for a biochemical AND gate. The obtained data are modeled within the rate-equation approach, with the aim to map out the gate function and cast it in the language of logic variables appropriate for analysis of Boolean logic for scalability. In order to minimize "analog" noise, we consider a theoretical approach for determining an optimal set for the process parameters to minimize "analog" noise amplification for gate concatenation. We establish that under optimized conditions, presently studied biochemical gates can be concatenated for up to order 10 processing steps. Beyond that, new paradigms for avoiding noise buildup will have to be developed. We offer a general discussion of the ideas and possible future challenges for both experimental and theoretical research for advancing scalable biochemical computing.     

Database diversity assessment: New ideas, concepts, and tools

We present some new ideas for characterizing and comparing largechemical databases. The comparison of the contents of large databases is nottrivial since it implies pairwise comparison of hundreds of thousands ofcompounds. We have developed methods for categorizing compounds into groupsor series based on their ring-system content, using precalculatedstructure-based hashcodes. Two large databases can then be compared bysimply comparing their hashcode tables. Furthermore, the number of distinctring-system combinations can be used as an indicator of database diversity.We also present an indepen- dent technique for diversity assessment calledthe saturation diversity approach. This method is based on picking as manymutually dissimilar compounds as possible from a database or a subsetthereof. We show that both methods yield similar results. Since the twomethods measure very different properties, this probably says more about theproperties of the databases studied than about the methods.     

Aperiodic capillary electrophoresis method using an alternating current electric field for separation of macromolecules

Switching from direct current (DC) to alternating current (AC) electric fields has provided substantial improvements in various instrument techniques that use electric fields for manipulating with various liquid-based systems. For example, AC fields are now used in both light scattering and electroacoustic instruments for measuring xi-potential, largely replacing more traditional microelectrophoresis techniques that use DC fields. In this paper, we suggest a novel way to make a similar transition in the area of separation techniques, capillary electrophoresis (CE) in particular. Dielectrophoresis is one well-known separation effect in which a drifting motion of particles is produced in a "spatially nonhomogeneous" AC electric field. However, there is another field effect that also causes a similar drift of particles. Instead of a "spatially nonhomogeneous" field, this method relies on a "temporally nonhomogeneous" field, normally referred to as "aperiodic electrophoresis". Despite a number of recently published experimental and theoretical papers describing this effect, it is less well-known than dielectrophoresis. We present a short overview of some of the relevant papers. We point out for the first time the idea that "aperiodic electrophoresis" might be useful for separation of macromolecules. We suggest several new mechanisms that could induce this effect in a sufficiently strong AC electric field. This effect can be used as a basis for a new separation method having several important advantages over traditional CE. We present a simple scheme as an example illustrating this new method.     

Surface plasmon resonance spectroscopy-based high-throughput screening of ligands for use in affinity and displacement chromatography

We describe an approach that uses surface plasmon resonance (SPR) spectroscopy and self-assembled monolayers (SAMs) for the high-throughput screening of ligands for use in displacement and affinity chromatographic processes. We identified a set of commercially available organic amines and allowed them to react with SAMs presenting interchain carboxylic anhydride groups; the resulting surfaces presented ligands of interest in a background of carboxylic acid groups. We used SPR spectroscopy to determine the extent of adsorption of two model proteinslysozyme and cytochrome conto these "multimodal" surfaces and to select promising "affinity" ligands for further characterization. The attachment of selected ligands to UltraLink Biosupport resulted in beads with a significantly greater affinity for lysozyme than for cytochrome c that would be suitable for use in affinity chromatographic processes. Furthermore, we also used the screens to design "affinity displacers"small molecules that selectively retain lysozyme on chromatographic resins, while displacing cytochrome c. The combination of SPR spectroscopy and SAMs represents a powerful technique for identifying novel ligands that enable the purification of complex protein mixtures.     

Chemoselective formation of successive triazole linkages in one pot: "click-click" chemistry

A methodology for the successive regiospecific "clicking" together of three components in one pot via two triazole linkages is reported. The protocol utilizes copper(I)-mediated alkyne-azide cycloaddition reactions combined with a silver(I)-catalyzed TMS-alkyne deprotection under mild hydroalcoholic conditions. We exemplify the approach with peptide-based components to illustrate its compatibility with polyfunctionalized biomolecules. The method constitutes a promising tool for peptide ligation. We also provide a procedure for directly using TMS-alkynes as the cycloaddition partner in classical "click" chemistry.     

Electrical bistability and memory phenomenon in carbon nanotube-conjugated polymer matrixes

We have observed electrical bistability and large conductance switching in functionalized carbon nanotube (CNT)-conjugated polymer composites at room temperature. The concentration of the CNTs in the polymer matrix controlled the degree of bistability. Conduction mechanism applicable in each of the conducting states has been identified. The switching had an associated memory phenomenon and was reversible in nature. In the bistable devices, the active layer retained its high-conducting state until a reverse voltage erased it. We could "write" or "erase" a state and "read" it for many cycles for random-access memory applications.     

The end-on mechanism for lattice filling: Comparison with the conventional mechanism and application to the car-parking problem

We present the exact solution for the sequential, random, irreversible filling of one-dimensional lattices by linear n-mers using the end-on filling mechanism. The results are extrapolated to then limit (a variation on the car-parking problem) to yield a saturation coverage (packing density) of 0.7350. The end-on filling mechanism involves two steps for a single filling event. First, the landing site for one endpoint of the filling species is chosen and then the second endpoint is subsequently chosen (fromunfilled sites an appropriate distance from the first endpoint). We compare this mechanism to the conventional, one-step filling mechanism, where both endpoints of the filling species are chosen simultaneously. We present results detailing how the lattice saturation coverage varies for the two mechanisms. In addition, we extend our analysis to consider filling in the presence of a time-dependent, random distribution of inactive sites.     

Discovery of antagonist peptides against bacterial helicase-primase interaction in B. stearothermophilus by reverse yeast three-hybrid

Developing small-molecule antagonists against protein-protein interactions will provide powerful tools for mechanistic/functional studies and the discovery of new antibacterials. We have developed a reverse yeast three-hybrid approach that allows high-throughput screening for antagonist peptides against essential protein-protein interactions. We have applied our methodology to the essential bacterial helicase-primase interaction in Bacillus stearothermophilus and isolated a unique antagonist peptide. This peptide binds to the primase, thus excluding the helicase and inhibiting an essential interaction in bacterial DNA replication. We provide proof of principle that our reverse yeast three-hybrid method is a powerful "one-step" screen tool for direct high-throughput antagonist peptide selection against any protein-protein interaction detectable by traditional yeast two-hybrid systems. Such peptides will provide useful "leads" for the development of new antibacterials.     

The importance of model studies in computational organic synthesis.

We explore a model, the "synthesis engine", for synthesis of arbitrarily complex organic structures in the context of library construction of Grignard cycle compounds. We use the simplest possible governing logic and show that random synthesis produces an extremely uneven distribution of products over several target structure types. We show that the question of "synthetic power" may be addressed computationally in this model system.     

Self-assembly of patchy particles into diamond structures through molecular mimicry

Fabrication of diamond structures by self-assembly is a fundamental challenge in making three-dimensional photonic crystals. We simulate a system of model hard particles with attractive patches and show that they can self-assemble into a diamond structure from an initially disordered state. We quantify the extent to which the formation of the diamond structure can be facilitated by "seeding" the system with small diamond crystallites or by introducing a rotation interaction to mimic a carbon-carbon antibonding interaction. Our results suggest patchy particles may serve as colloidal "atoms" and "molecules" for the bottom-up self-assembly of three-dimensional crystals.     

Oxidation of Polysulfide Ions Induced by CdS Nanoparticles under Pulsed Photolysis Conditions

We have studied the photochemical behavior of colloidal solutions of cadmium sulfide containing polysulfide ions under pulsed irradiation conditions. We have established that the pulsed photolysis product responsible for absorption in the 520-650 nm region is the radical anion S ₃ . We have studied the kinetic characteristics of disappearance of this intermediate under various conditions, and we propose a scheme for the mechanism of these processes.     

On valuation operators in stoichiometry and in reaction syntheses

We investigate physical and chemical quantitative characteristics of species, reactions and mechanisms which are linear (additive and homogeneous) in general, using linear algebraic methods. We call such characteristics here as valuation operators. After revealing the properties of these operators we reach to some practical consequences at the end of our paper which could be used either for calculating or forecasting the behaviour and the magnitude of these characteristics.Though these results might have already been used by experts for a long time, the present paper could serve as a firm theoretical background for their computation methods.     

Total body calcium by neutron activation analysis: Reference data for children

There is a paucity of data on the chemical composition of the humanbody during growth. Total body calcium (TBCa) has been reported for only onemale child, aged 41/2 yr. We have obtained TBCa values for 25 children and27 young women using in vivo neutron activation analysis. Our TBCa resultswere lower than those reported for the one male cadaver, as well as the estimatesderived for the Reference Man model. We conclude that the referencevalues for TBCa may need to be adjusted to appropriately describe skeletalmineralization of contemporary children.     

Long-time and unitary properties of semiclassical initial value representations

We numerically compare the semiclassical "frozen Gaussian" Herman-Kluk propagator [Chem. Phys. 91, 27 (1984)] and the "thawed Gaussian" propagator put forward recently by Baranger et al. [J. Phys. A 34, 7227 (2001)] by studying the quantum dynamics in some nonlinear one-dimensional potentials. The reasons for the lack of long-time accuracy and norm conservation in the latter method are uncovered. We amend the thawed Gaussian propagator with a global harmonic approximation for the stability of the trajectories and demonstrate that this revised propagator is a true alternative to the Herman-Kluk propagator with similar accuracy.     

Second derivative free sixth order continuation method for solving nonlinear equations with applications

In this paper, we deal with the study of convergence analysis of modified parameter based family of second derivative free continuation method for solving nonlinear equations. We obtain the order of convergence is at least five and especially, for parameter \(\alpha =2\) sixth order convergence. Some application such as Max Planck’s conservative law, multi-factor effect are discussed and demonstrate the efficiency and performance of the new method (for \(\alpha =2\)). We compare the absolutely value of function at each iteration \(|f(x_n)|\) and \(|x_n-\xi |\) with our method and Potra and Pták method [1], Kou et al. method [2]. We observed that our method is more efficient than existing methods. Also, the Dynamics of the method are studied for a special case of the parameter in convergence.     

A generalized restricted open-shell Fock operator

We reexamine the open shell restricted Hartree-Fock theory and develop Fock-like operators that are quite general and easy to implement on a computer. We present a table of vector coupling coefficients that define this operator for most of the cases that commonly arise. We compare the form of this operator with that suggested by others, and discuss the orbitals obtained by this procedure with respect to the generalised Brillouin's theorem, and the orbital energies with respect to Koopmans' approximation.Dedicated to Professor J. Koutecký on the occasion of his 65th birthday     

Development of PEG-PLA/PLGA microparticles for pulmonary drug delivery prepared by a novel emulsification technique assisted with amphiphilic block copolymers

We developed a novel "spray dry-based" method for preparing surface-modified particle via "block copolymer-assisted" emulsification/evaporation for pulmonary drug delivery. The method included three steps: (1) o/w emulsion containing both hydrophobic polymers and amphiphilic block copolymers was obtained by emulsification of water and a polymer-containing organic solvent, (2) the o/w emulsion was misted with a nebulizer, and (3) the emulsion mists were dried by a heater. In this way, the hydrophobic polymers and the hydrophobic part of the amphiphilic block copolymers gradually tangled during the evaporation of organic solvents from the o/w emulsion. Consequently, the hydrophilic polymer chain was introduced on the particle surface. The particle surface can be easily modified although there are no reactive groups in the hydrophobic polymer molecules. We successfully obtained dry PEG-PLA/PLGA microparticles by controlling the weight ratio of the block copolymer and the hydrophobic polymer. The introduction of PEG to the particle surface involves an increase in the Zeta potential of the particles. Interestingly, the "dimpled" microparticles having a diameter of approximately 2 μm were obtained. The "dimpled" microparticles can serve as drug carriers for pulmonary drug delivery, because the particles have a large surface area. We expect that this novel surface-modification technique will enable efficient fabrication of particles in drug delivery systems.