Recently, a novel cationic polymer, dextran-spermine (D-SPM) was developed for gene delivery. An efficient transfection was obtained using this polycation for a variety of genes and cell lines in serum-free or serum-poor medium. However, transfection using the water-soluble D-SPM-based polyplexes decreased with increasing serum concentration in cell culture in a concentration-dependent manner, reaching 95% inhibition at 50% serum in the cell growth medium. In order to overcome this obstacle, oleyl derivatives of D-SPM (which form micelles in aqueous phase) were synthesized at 1, 10, and 20 mol% of oleyl moiety to polymer epsilon-NH2 to form N-oleyl-D-SPM (ODS). Polyplexes based on ODS transfected well in medium containing 50% serum. Comparison with polyplexes based on well-established polymers (branched and linear polyethyleneimine) and with DOTAP/Cholesterol lipoplexes showed that regarding beta-galactosidase transgene expression level and cytotoxicity in tissue culture, the D-SPM and ODS compare well with the above polyplexes and lipoplexes. Intracellular trafficking using FITC-labeled ODS and Rhodamine-labeled pGeneGrip plasmid cloned with hBMP2 monitored by confocal microscopy revealed that during the transfection process the fluorescent-labeled polymer concentrates in the Golgi apparatus and around the nucleus, while the cell cytoplasm was free of fluorescent particles, suggesting that the polyplexes move in the cell toward the nucleus by vesicular transport through the cytoplasm and not by a random diffusion. We found that the plasmids penetrate the cell nucleus without the polymer. Preliminary results in zebra fish and mice demonstrate the potential of ODS to serve as an efficient nonviral vector for in vivo transfection.
Yosef Gruenbaum, Ayelet Margalit, Robert D Goldman, Dale K Shumaker, and Katherine L Wilson. 2005. “The nuclear lamina comes of age..” Nat Rev Mol Cell Biol, 6, 1, Pp. 21-31. Abstract
Many nuclear proteins form lamin-dependent complexes, including LEM-domain proteins, nesprins and SUN-domain proteins. These complexes have roles in chromatin organization, gene regulation and signal transduction. Some link the nucleoskeleton to cytoskeletal structures, ensuring that the nucleus and centrosome assume appropriate intracellular positions. These complexes provide new insights into cell architecture, as well as a foundation for the understanding of the molecular mechanisms that underlie the human laminopathies - clinical disorders that range from Emery-Dreifuss muscular dystrophy to the accelerated ageing seen in Hutchinson-Gilford progeria syndrome.
We investigate experimentally the energy exchange patterns and consequent propagation dynamics of an extended hybrid-dimensional interaction between a one-dimensional and a two-dimensional spatial soliton in a biased photorefractive crystal. Results show that conditions can be found in which the coupling manifests propagation invariant features. The mechanism hinges on mutual distortion through spatially nonlocal components of response, as opposed to standard wave overlap, which would lead to a diffusion of the needle into the slab mode. These nonlocal-nonlinearity-driven ridge modes represent the instrument for writing fiber-slab couplers, the key to attaining soliton-based wavelength selectivity with electroactivated features. [ABSTRACT FROM AUTHOR]Copyright of Applied Physics Letters is the property of American Institute of Physics and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
M. E. Franklin, J.D. Huppert, and D. A. Roth. 2005. “Obsessions and Compulsions.” In Using homework assignments in cognitive-behavior therapy, Pp. 219-236. New York: Brunner-Routledge. click here for the chapter
Proponents of offense-defense theory (ODT) contend that the offense-defense balance (ODB) forms the “master key” to understanding the question of peace and war. Time-series event count models of war and militarized interstate disputes at the systemic level are used to test the theory’s claims that shifts in the ODB have an important effect on the likelihood of internationalwar and militarized disputes and thatODToffers a more powerful explanation for conflict than other explanations in the international relations (IR) literature. Results cast doubt on the empirical validity of the ODT and indicate that other IR theories have important explanatory power.
A Self-Assembly oriented technique from the vapor-phase, Molecular Layer Epitaxy (MLE), was utilized for the buildup of organic multilayers as the active channel in organic field effect transistors (OFET). Carrier gas-assisted chemical vapor deposition (C
Background Bilateral internal thoracic artery (BITA) grafting with a composite T-graft enables right coronary artery (RCA) system revascularization with the distal end of the free right internal thoracic artery (RITA). This study compares this grafting technique to left-sided BITA grafting and RCA revascularization with the right gastroepiploic artery (RGEA) and saphenous vein grafts (SVG).
A classical, three-dimensional analysis of excitation and control of vibrational-rotational degrees of freedom of a polar diatomic molecule by chirped laser field is presented. The control strategy is based on autoresonance (adiabatic nonlinear synchronization) phenomenon, in which the molecule automatically adjusts its state for staying in a persistent resonance with the laser field despite variation of the laser frequency. Thresholds on driving field amplitudes for entering the autoresonant excitation regime by passage through different resonances are calculated. In autoresonance, the molecule can be excited to large energies and approach the dissociation limit by substantially weaker laser fields than with constant-frequency drives.
This study addresses one central problem and two major controversies in the study of political personalization. The central problem is that of mixing different types of political personalization. This research suggests a typology that distinguishes between various types of political personalization: institutional, media and behavioral. The first controversy concerns the very occurrence of the process of personalization. This study identifies personalization(s) in Israel in all three realms: institutional personalization, expressed in the democratization of candidate selection methods; personalization in the media, expressed in an increase in the focus of media coverage on individual politicians and a decrease in focusing on political parties; and personalization in the behavior of politicians, expressed in an increase in the share of legislation that is initiated through private member bills. The second controversy concerns the causal relationship between the different types of person
We study the structural and energetic consequences of (α-helical) amphipathic peptide adsorption onto a lipid membrane and the subsequent formation of a transmembrane peptide pore. Initially, each peptide binds to the membrane surface, with the hydrophobic face of its cylinder-like body inserted into the hydrocarbon core. Pore formation results from subsequent peptide crowding, oligomerization, and eventually reorientation along the membrane normal. We have theoretically analyzed three peptide-membrane association states: interfacially-adsorbed monomeric and dimeric peptides, and the multi-peptide transmembrane pore state. Our molecular-level model for the lipid bilayer is based on a combination of detailed chain packing theory and a phenomenological description of the headgroup region. We show that the membrane perturbation free energy depends critically on peptide orientation: in the transmembrane pore state the lipid perturbation energy, per peptide, is smaller than in the adsorbed state. This suggests that the gain in conformational freedom of the lipid chains is a central driving force for pore formation. We also find a weak, lipid-mediated, gain in membrane perturbation free energy upon dimerization of interfacially-adsorbed peptides. Although the results pertain mainly to weakly-charged peptides, they reveal general properties of the interaction of amphipathic peptides with lipid membranes.
A method for generation of a chirped, ultrawideband infrared source by use of optical parametric generation in periodically poled crystals and pumped by a chirped Ti:sapphire laser is described. A similar to35% bandwidth in the idler branch was demonstrated in a periodically poled LiTaO3 crystal pumped by a chirped Ti:sapphire laser with 2.1% bandwidth. Optical parametric generation and optical parametric amplification configuration allowed us to generate up to a similar to250-muJ chirped pulse from 2.1 to 3 mum. (C) 2005 Optical Society of America.
Dynamics of glycine chemisorbed on the surface of a silicon cluster is studied for a process that involves single-photon ionization, followed by recombination with the electron after a selected time delay. The process is studied by ``on-the-fly'' molecular dynamics simulations, using the semiempirical parametric method number 3 (PM3) potential energy surface. The system is taken to be in the ground state prior to photoionization, and time delays from 5 to 50 fs before the recombination are considered. The time evolution is computed over 10 ps. The main findings are (1) the positive charge after ionization is initially mostly distributed on the silicon cluster. (2) After ionization the major structural changes are on the silicon cluster. These include Si-Si bond breaking and formation and hydrogen transfer between different silicon atoms. (3) The transient ionization event gives rise to dynamical behavior that depends sensitively on the ion state lifetime. Subsequent to 45 fs evolution in the charged state, the glycine molecule starts to rotate on the silicon cluster. Implications of the results to various processes that are induced by transient transition to a charged state are discussed. These include inelastic tunneling in molecular devices, photochemistry on conducting surfaces, and electron-molecule scattering. (c) 2005 American Institute of Physics.
Dynamics of glycine chemisorbed on the surface of a silicon cluster is studied for a process that involves single-photon ionization, followed by recombination with the electron after a selected time delay. The process is studied by “on-the-fly” molecular dynamics simulations, using the semiempirical parametric method number 3 (PM3) potential energy surface. The system is taken to be in the ground state prior to photoionization, and time delays from 5 to 50 fs before the recombination are considered. The time evolution is computed over 10 ps. The main findings are (1) the positive charge after ionization is initially mostly distributed on the silicon cluster. (2) After ionization the major structural changes are on the silicon cluster. These include Si–Si bond breaking and formation and hydrogen transfer between different silicon atoms. (3) The transient ionization event gives rise to dynamical behavior that depends sensitively on the ion state lifetime. Subsequent to 45 fs evolution in the charged state, the glycine molecule starts to rotate on the silicon cluster. Implications of the results to various processes that are induced by transient transition to a charged state are discussed. These include inelastic tunneling in molecular devices, photochemistry on conducting surfaces, and electron-molecule scattering.
