Structure, dynamics, and energetics of siRNA-cationic vector complexation:a molecular dynamics study

The design and synthesis of safe and efficient nonviral vectors for gene delivery has attracted significant attention in recent years. Previous experiments have revealed that the charge density of a polycation (the carrier) plays a crucial role in complexation and the release of the gene from the complex in the cytosol. In this work, we adopt an atomistic molecular dynamics simulation approach to study the complexation of short strand duplex RNA with six cationic carrier systems of varying charge and surface topology. The simulations reveal detailed molecular-level pictures of the structures and dynamics of the RNA-polycation complexes. Estimates for the binding free energy indicate that electrostatic contributions are dominant followed by van der Waals interactions. The binding free energy between the 8(+)polymers and the RNA is found to be larger than that of the 4(+)polymers, in general agreement with previously published data. Because reliable binding free energies provide an effective index of the ability of the polycationic carrier to bind the nucleic acid and also carry implications for the process of gene release within the cytosol, these novel simulations have the potential to provide us with a much better understanding of key mechanistic aspects of gene-polycation complexation and thereby advance the rational design of nonviral gene delivery systems.

Structure and dynamics of multiple cationic vectors-siRNA complexation by all-atomic molecular dynamics simulations

Understanding the molecular mechanism of gene condensation is a key component to rationalizing gene delivery phenomena, including functional properties such as the stability of the gene-vector complex and the intracellular release of the gene. In this work, we adopt an atomistic molecular dynamics simulation approach to study the complexation of short strand duplex RNA with four cationic carrier systems of varying charge and surface topology at different charge ratios. At lower charge ratios, polymers bind quite effectively to siRNA, while at high charge ratios, the complexes are saturated and there are free polymers that are unable to associate with RNA. We also observed reduced fluctuations in RNA structures when complexed with multiple polymers in solution as compared to both free siRNA in water and the single polymer complexes. These novel simulations provide a much better understanding of key mechanistic aspects of gene-polycation complexation and thereby advance progress toward rational design of nonviral gene delivery systems.

Efficient Computing of some Vector Operations over GF(3) and GF(4)

The problem of efficient computing of the affine vector operations (addition of two vectors and multiplication of a vector by a scalar over GF (q)), and also the weight of a given vector, is important for many problems in coding theory, cryptography, VLSI technology etc. In this paper we propose a new way of representing vectors over GF (3) and GF (4) and we describe an efficient performance of these affine operations. Computing weights of binary vectors is also discussed.

On the Hyperbolicity Domain of the Polynomial x^n + a1x^(n-1) + 1/4+ an

∗ Partially supported by INTAS grant 97-1644

Equivariant Embeddings of Differentiable Spaces

Given a differentiable action of a compact Lie group G on a compact smooth manifold V , there exists [3] a closed embedding of V into a finite-dimensional real vector space E so that the action of G on V may be extended to a differentiable linear action (a linear representation) of G on E. We prove an analogous equivariant embedding theorem for compact differentiable spaces (∞-standard in the sense of [6, 7, 8]).

P-Sequential Spaces and Cleavability

∗ Supported by the Serbian Scientific Foundation, grant No 04M01

Conjugate Compositions in Even-Dimensional Affinely Connected Spaces without a Torsion

Let in even-dimensional a±nely connected space without a torsion A2m be given a composition Xm£Xm by the affinor a¯ ®. The affinor b¯ ®, determined with the help of the eigen-vectors of the matrix (a¯ ®), de¯nes the second composition Ym £ Y m. Conjugate compositions are introduced by the condition: the a±nors of any of both compositions transform the vectors from the one position of the composition, generated by the other a±nor, in the vectors from the another its position. It is proved that the compositions de¯ne by a±nors a¯ ® and b¯ ® are conjugate. It is proved also that if the composition Xm£Xm is Cartesian and composition Ym£Y m is Cartesian or chebyshevian, or geodesic than the space A2m is affine.

Upper and Lower Bounds in Relator Spaces

2000 Mathematics Subject Classification: 06A06, 54E15

A Note On Quasi-Lindelöf Spaces

Петра Г. Стайнова - Квази-линдельофовите пространства са въведени от Архангелски като усилване на слабо-линдельофовите. В тази статия се разглеждат няколко свойства на квази-линдельофовите пространства и се правят сравнения със съответни ре- зултати за линдельофовите и слабо-линдельофовите пространства. Дадени са няколко примера, включително на слабо-линдельофово пространство, което не е квази-линдельофово; на пространство, което е топологично произведение на две линдельофови, но не е дори квази-линдельофово, и на пространство, което е квази-линдельофово, но не Суслиново. Накрая са поставени няколко отворени въпроси.

Multipliers on Spaces of Functions on a Locally Compact Abelian Group with Values in a Hilbert Space

2000 Mathematics Subject Classification: Primary 43A22, 43A25.

Fast polarimetry of multipulse vector soliton operation

Applying high-speed polarimetery we experimentally demonstrate new types of vector solitons for multipulse operation in an erbium doped carbon nanotube mode-locked laser. The observed states of polarisation reveal either fast pulse-to-pulse polarisation switching between crosspolarised modes or slow cyclic evolution.

Special compositions in affinely connected spaces without a torsion

2000 Mathematics Subject Classification: 53B05, 53B99.

The existence of an inverse limit of inverse system of measure spaces - a purely measurable case

The existence of an inverse limit of an inverse system of (probability) measure spaces has been investigated since the very beginning of the birth of the modern probability theory. Results from Kolmogorov [10], Bochner [2], Choksi [5], Metivier [14], Bourbaki [3] among others have paved the way of the deep understanding of the problem under consideration. All the above results, however, call for some topological concepts, or at least ones which are closely related topological ones. In this paper we investigate purely measurable inverse systems of (probability) measure spaces, and give a sucient condition for the existence of a unique inverse limit. An example for the considered purely measurable inverse systems of (probability) measure spaces is also given.

Ornamental plants as climatic indicators of arthropod vectors

The importance and risk of vector-borne diseases (eg. leishmaniasis, West Nile Virus, Lyme borreliosis) is going to increase in the European temperate areas due to climate change. Our previous studies have shown that the potential distribution of Leishmania infantum and some Phlebotomus (sand fly) species – a parasite of leishmaniasis, and its vectors – may be expanded even to the southern coastline of the Baltic Sea by the end of the 21st century. The lowland areas of the Carpathian Basin and the main part of Hungary are projected to be suitable for the studied sand fly vectors in the near future. It is important to find some indicator plants to examine whether the sand flies are able to live in a certain climate at a certain time. We studied several Mediterranean and Sub-Mediterranean plant species, and we found that the aggregated distribution of three ligneous species (Juniperus oxycedrus L., Quercus ilex L. and Pinus brutia Ten.) shows high correlation with the union distribution of five sand flies (Phlebotomus ariasi Tonn., Ph. neglectus Tonn., Ph. perfiliewi Parrot, Ph. perniciosus Newst. and Ph. tobbi Adler, Theodor et Lourie). Since these Mediterranean species are highly tolerant of the edaphic characteristics of the planting site, they may prove to be good indicators. The present and upcoming climate of Hungary is seen to be suitable for the selected indicator plant species, and it draws attention to and verifies the potential of the expansion of sand flies, which has been proved by some recent observations of the vectors in Southern Hungary.

Ornamental plants as climatic indicators of arthropod vectors

The importance and risk of vector-borne diseases (e.g., leishmaniasis, West Nile Virus, Lyme borreliosis) is going to increase in the European temperate areas due to climate change. Our previous studies have shown that the potential distribution of Leishmania infantum and some Phlebotomus (sand fly) species – a parasite of leishmaniasis, and its vectors – may be expanded even to the southern coastline of the Baltic Sea by the end of the 21st century. The lowland areas of the Carpathian Basin and the main part of Hungary are projected to be suitable for the studied sand fly vectors in the near future. It is important to find some indicator plants to examine whether the sand flies are able to live in a certain climate at a certain time. We studied several Mediterranean and Sub-Mediterranean plant species, and we found that the aggregated distribution of three ligneous species (Juniperus oxycedrus L., Quercus ilex L. and Pinus brutia Ten.) shows high correlation with the union distribution of five sand flies (Phlebotomus ariasi Tonn., Ph. neglectus Tonn., Ph. perfiliewi Parrot, Ph. perniciosus Newst. and Ph. tobbi Adler, Theodor et Lourie). Since these Mediterranean species are highly tolerant of the edaphic characteristics of the planting site, they may prove to be good indicators. The present and upcoming climate of Hungary is seen to be suitable for the selected indicator plant species, and it draws attention to and verifies the potential of the expansion of sand flies, which has been proved by some recent observations of the vectors in Southern Hungary.