Competitive reactions in solutions of poly-L-histidine, calf thymus DNA, and synthetic polyanions: determining the binding constants of polyelectrolytes

The physicochemical characteristics of a nonviral gene delivery system will govern its functional bioactivity; however, empiricism dominates the literature in this field, and a significant deficiency of quantitative investigation and evaluation of nonviral gene delivery vehicles remains. Herein, we derive a physical model and experimental method to quantitatively determine the binding constants between a model polycationic nonviral gene delivery vehicle poly-L-histidine (PLH) and calf thymus DNA. The approach has utility to a variety of systems and is not limited to the described polymer model. The interaction of PLH with DNA was monitored by fluorescence quenching of an ethidium bromide probe in the pH range 4 to 8. The interaction increased with pH decrease with the most pronounced change between pH 6 and 7. The obtained pH-dependence of fraction of salt bonds formed between PLH and DNA was used to estimate pK(a) of PLH in the presence of DNA, which equaled 6.24. The interaction of PLH with DNA in the presence of added synthetic polyanions was studied by the same approach and found to be controlled by pH, nature of the charge groups of the polyanion, and its degree of polymerization. In the mixture with sodium poly(styrenesulfonate) the interaction was negligible in the whole studied pH range, whereas in the mixtures with sodium poly(acrylate) (PA) or sodium poly(methacrylate), DNA was able to compete effectively for the binding with PLH. For PA samples with degree of polymerization higher than degree of polymerization of PLH, DP(PA) > DP(PLH), the fraction of polycation bound to DNA was constant regardless of DP(PA.) In contrast, at DP(PA) < DP(PLH), a pronounced increase in the bound fraction was observed. It substantiates the notion that the binding energy of two polymers is mainly controlled by the DP of the shorter component of polyelectrolyte complex. The data on PLH distribution between DNA and added polyanion with different values of DP were treated according to the developed procedure to yield the effective binding constants of PLH with DNA and polyanion-competitor, calculated both per mole of interacting units K(1) and mole of interacting chains K(n). In all cases, K(1) had similar numerical values reflecting common type of interaction stabilizing the complexes, i.e., electrostatics. Slight variation of K(1) yielded in drastic changes in K(n) and alteration of dominance of PLH interaction with DNA or synthetic polyanion. The results of the study can have a high impact in deriving the correlation between the binding constant of a polycation to DNA and its ability to serve as gene delivery vehicle.     

Gaussian approximation in the theory of MR signal formation in the presence of structure-specific magnetic field inhomogeneities

A detailed theoretical analysis of the free induction decay (FID) and spin echo (SE) MR signal formation in the presence of mesoscopic structure-specific magnetic field inhomogeneities is developed in the framework of the Gaussian phase distribution approximation. The theory takes into account diffusion of nuclear spins in inhomogeneous magnetic fields created by arbitrarily shaped magnetized objects with permeable boundaries. In the short-time limit the FID signal decays quadratically with time and depends on the objects' geometry only through the volume fraction, whereas the SE signal decays as 5/2 power of time with the coefficient depending on both the volume fraction of the magnetized objects and their surface-to-volume ratio. In the motional narrowing regime, the FID and SE signals for objects of finite size decay mono-exponentially; a simple general expression is obtained for the relaxation rate constant deltaR2. In the case of infinitely long cylinders in the motional narrowing regime the theory predicts non-exponential signal decay lnS approximately -tlnt in accordance with previous results. For specific geometries of the objects (spheres and infinitely long cylinders) exact analytical expressions for the FID and SE signals are given. The theory can be applied, for instance, to biological systems where mesoscopic magnetic field inhomogeneities are induced by deoxygenated red blood cells, capillary network, contrast agents, etc.     

Random Menshov spectra

We show that the spectra of frequencies obtained by random perturbations of the integers allows one to represent any measurable function on by an almost everywhere converging sum of harmonics:

     

Directed flow of lambda hyperons in (2-6 )A GeV Au+Au collisions

Directed flow measurements for Lambda hyperons are presented and compared to those for protons produced in the same Au+Au collisions (2A, 4A, and 6A GeV; b<5-6 fm). The measurements indicate that Lambda hyperons flow consistently in the same direction but with smaller magnitudes. A strong positive flow [for Lambdas] has been predicted in calculations which include the influence of the Lambda-nucleon potential. The experimental flow ratio Lambda/p is in qualitative agreement with expectations (approximately 2/3) from the quark counting rule at 2A GeV but is found to decrease with increasing beam energy.     

How gap genes make their domains: An analytical study based on data driven approximations

We consider a mathematical formulation of the problem of protein production during segment determination in the Drosophila blastoderm, together with some preliminary results of its analytical study. We reformulate the spatial difference equations as a set of nonlinear partial differential equations and obtain their dimensionless form in the continuum limit. Using previous results obtained by the gene circuit method, we find an asymptotic statement of the problem with a small parameter. Some results of the comparison method applied to the model are obtained, and exact stationary upper solutions are derived. They exhibit distinctive features of localized bell-shaped structures. (c) 2001 American Institute of Physics.     

Clusters and fluctuations at mean-field critical points and spinodals

We show that the structure of the fluctuations close to spinodals and mean-field critical points is qualitatively different from the structure close to non-mean-field critical points. This difference has important implications for many areas including the formation of glasses in supercooled liquids. In particular, the divergence of the measured static structure function in near-mean-field systems close to the glass transition is suppressed relative to the mean-field prediction in systems for which a spatial symmetry is broken.     

Homoclinic bifurcation in a Hodgkin-Huxley model of thermally sensitive neurons

We study global bifurcations of the chaotic attractor in a modified Hodgkin-Huxley model of thermally sensitive neurons. The control parameter for this model is the temperature. The chaotic behavior is realized over a wide range of temperatures and is visualized using interspike intervals. We observe an abrupt increase of the interspike intervals in a certain temperature region. We identify this as a homoclinic bifurcation of a saddle-focus fixed point which is embedded in the chaotic attractors. The transition is accompanied by intermittency, which obeys a universal scaling law for the average length of trajectory segments exhibiting only short interspike intervals with the distance from the onset of intermittency. We also present experimental results of interspike interval measurements taken from the crayfish caudal photoreceptor, which qualitatively demonstrate the same bifurcation structure. (c) 2000 American Institute of Physics.     

First observation of the decay B --> J/psistraight phiK

We present the first observation of the decay B-->J/psistraight phiK. Using 9.6x10(6) B&Bmacr; meson pairs collected with the CLEO detector, we have observed ten fully reconstructed B-->J/psistraight phiK candidates, whereas the estimated background is 0.5+/-0.2 event. We obtain a branching fraction of B(B-->J/psistraight phiK) = (8. 8(+3.5)(-3.0)[stat]+/-1.3[syst])x10(-5). This is the first observed B meson decay requiring the creation of an additional s&smacr; quark pair.