Theoretical Study of the 4He(γ, p)3H and 4He(γ, n)3He Reactions

Ab initio calculation of the total cross section for the reactions ⁴He(γ, p)³H and ⁴He(γ, n)³He is presented, using state-of-the-art nuclear forces. The Lorentz integral transform (LIT) method is applied, which allows exact treatment of the final state interaction (FSI). The dynamic equations are solved using the effective interaction hyperspherical harmonics method. In this calculation of the cross sections the three-nucleon force is fully taken into account, except in the source term of the LIT equation for the FSI transition matrix element.     

Rationally designed macrocyclic peptides as synergistic agonists of LPS-induced inflammatory response

Toll-like receptor 4 (TLR4) plays an important role in the regulation of the innate and adaptive immune response. Both agonists and antagonists of TLR4 are of considerable interest as drug leads for various disease indications. We herein report the rational design of two myeloid differentiation factor 2 (MD2)-derived macrocyclic peptides as TLR4 modulators, using the Rosetta Macromolecular Modeling software. The designed cyclic peptides, but not their linear counterparts, displayed synergistic activation of TLR signaling when co-administered with lipopolysaccharide (LPS). Although the understanding of the mechanism of action of these peptides remains elusive, these results underscore the utility of peptide cyclization for the discovery of biologically active agents, and also provide valuable tools for the investigation of TLR4 signaling.     

Engineered Substrate‐Specific Delta PKC Antagonists to Enhance Cardiac Therapeutics

Most protein kinases phosphorylate multiple substrates, each of which induces different and sometimes opposing functions. Determining the role of phosphorylation of each substrate following a specific stimulus is challenging but is essential to elucidate the role of that substrate in the signaling event. Here we describe a rational approach to identify inhibitors of delta protein kinase C (δPKC), each inhibiting the phosphorylation of only one of δPKC′s substrates. δPKC regulates many signaling events and we hypothesized that a docking inhibitor of a given substrate to δPKC should selectively abrogate the phosphorylation of only that substrate, without affecting the phosphorylation of the other δPKC substrates. Here we report the development of selective inhibitors of three δPKC substrates (in vitro K_d≈3 nm ); two greatly reduced ischemia‐induced cardiac injury with an IC₅₀ of ≈200 nm and the third had no effect, indicating that its respective substrate phosphorylation by δPKC has no role in the response to cardiac ischemia and reperfusion. The three inhibitors are highly specific; even at 1 μm , the phosphorylation of other δPKC protein substrates was unaffected. The rationale we describe is likely applicable for the development of other substrate‐specific inhibitors as well.     

Normal and frictional forces between surfaces bearing polyelectrolyte brushes

Normal and shear forces were measured as a function of surface separation, D, between hydrophobized mica surfaces bearing layers of a hydrophobic-polyelectrolytic diblock copolymer, poly(methyl methacrylate)- block-poly(sodium sulfonated glycidyl methacrylate) copolymer (PMMA- b-PSGMA). The copolymers were attached to each hydrophobized surface by their hydrophobic PMMA moieties with the nonadsorbing polyelectrolytic PSGMA tails extending into the aqueous medium to form a polyelectrolyte brush. Following overnight incubation in 10 (-4) w/v aqueous solution of the copolymer, the strong hydrophobic attraction between the hydrophobized mica surfaces across water was replaced by strongly repulsive normal forces between them. These were attributed to the osmotic repulsion arising from the confined counterions at long-range, together with steric repulsion between the compressed brush layers at shorter range. The corresponding shear forces on sliding the surfaces were extremely low and below our detection limit (+/-20-30 nN), even when compressed down to a volume fraction close to unity. On further compression, very weak shear forces (130 +/- 30 nN) were measured due to the increase in the effective viscous drag experienced by the compressed, sliding layers. At separations corresponding to pressures of a few atmospheres, the shearing motion led to abrupt removal of most of the chains out of the gap, and the surfaces jumped into adhesive contact. The extremely low frictional forces between the charged brushes (prior to their removal) is attributed to the exceptional resistance to mutual interpenetration displayed by the compressed, counterion-swollen brushes, together with the fluidity of the hydration layers surrounding the charged, rubbing polymer segments.     

Ultrafast transformation of graphite to diamond: an ab initio study of graphite under shock compression

We report herein ab initio molecular dynamics simulations of graphite under shock compression in conjunction with the multiscale shock technique. Our simulations reveal that a novel short-lived layered diamond intermediate is formed within a few hundred of femtoseconds upon shock loading at a shock velocity of 12 kms (longitudinal stress>130 GPa), followed by formation of cubic diamond. The layered diamond state differs from the experimentally observed hexagonal diamond intermediate found at lower pressures and previous hydrostatic calculations in that a rapid buckling of the graphitic planes produces a mixture of hexagonal and cubic diamond (layered diamond). Direct calculation of the x-ray absorption spectra in our simulations reveals that the electronic structure of the final state closely resembles that of compressed cubic diamond.     

Efficient coherent addition of fiber lasers in free space

An efficient technique in which fiber lasers are coherently added in free space is presented. Since the high power of the combined output light propagates in free space rather than inside, fiber optical damage and deleterious nonlinear effects are substantially reduced. Two different configurations are investigated. One involves conventional intracavity coupling between the lasers. The other is a novel configuration where the coupling is done out of the combined cavities. The latter configuration requires much less coupling for obtaining the same output power, so the damage to the fiber is further reduced.     

Force balance and membrane shedding at the red-blood-cell surface

During the aging of the red-blood cell, or under conditions of extreme echinocytosis, membrane is shed from the cell plasma membrane in the form of nanovesicles. We propose that this process is the result of the self-adaptation of the membrane surface area to the elastic stress imposed by the spectrin cytoskeleton, via the local buckling of membrane under increasing cytoskeleton stiffness. This model introduces the concept of force balance as a regulatory process at the cell membrane and quantitatively reproduces the rate of area loss in aging red-blood cells.     

The Isoscalar Monopole Resonance of 4He

The transition form factor to the 0⁺ resonance of ⁴He at 20.10 MeV is studied using different realistic potential models. A large dependence on these models is found. The results are compared to experimental data. The Lorentz integral transform (LIT) approach has allowed the separation of resonance and background contributions.