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In-stent restenosis (ISR) is the leading cause of stent failure and is a direct result of a dysfunctional vascular endothelium and subsequent overgrowth of vascular smooth muscle tissue. TiO 2 nanotubular (NT) arrays have been shown to affect vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) in vitro by accelerating VEC cell proliferation and migration while suppressing VSMCs. This study investigates for the first time the potentially beneficial effects of TiO 2 NT arrays on vascular tissue in vivo. TiO 2 NT arrays (NT diameter: 90 ± 5 nm, height: 1800 ± 300 nm) were grown on the surface of titanium stents and characterized in terms of surface morphology and stability. Stents were implanted into the iliofemoral artery using an overinflation model (rabbit). After 28 days, stenosis rates were determined. The data show a statistically significant reduction of stenosis by 30% compared to the control. Tissue in the presence of TiO 2 NTs appears more mature, and less neointima is present between struts. In addition, the extra cellular matrix secreted by cells at the interface of the NT arrays shows complete integration into the nanostructured surface. These results document the accelerated restoration of a functional endothelium in the presence of TiO 2 NT arrays and substantiate their beneficial impact on vascular tissue in vivo. Our findings suggest that TiO 2 NT arrays can be used as a drug-free approach for keeping stents patent long-term and have the potential to address ISR.

Resolvin D1 (RvD1) belongs to a family of endogenously derived proresolving lipid mediators that have been shown to attenuate inflammation, activate proresolution signaling, and promote homeostasis and recovery from tissue injury. In this study we present a poly(lactic-co-glycolic acid) (PLGA) based thin-film device composed of layers of varying ratios of lactic and glycolic acid that elutes RvD1 unidirectionally to target tissues. The device demonstrated sustained release in vitro for 56 days with an initial burst of release over 14 days. The asymmetric design of the device released 98% of RvD1 through the layer with the lowest molar ratio of lactic acid to glycolic acid, and the remainder through the opposite side. We validated structural integrity of RvD1 released from the device by mass spectrometry and investigated its bioactivity on human vascular endothelial (EC) and smooth muscle cells (VSMC). RvD1 released from the device attenuated VSMC migration, proliferation, and TNF-α induced NF-κB activation, without evidence of cytotoxicity. Delivery of RvD1 to blood vessels was demonstrated ex vivo in a flow chamber system using perfused rabbit aortas and in vivo in a rat carotid artery model, with the devices applied as an adventitial wrap. Our results demonstrate a novel approach for sustained, local delivery of Resolvin D1 to vascular tissue at therapeutically relevant levels. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 31-41, 2017., (© 2016 Wiley Periodicals, Inc.)

A non-destructive diagnostic method for the characterization of circularly polarized, ultraintense, short wavelength free-electron laser (FEL) light is presented. The recently installed Delta undulator at the LCLS (Linac Coherent Light Source) at SLAC National Accelerator Laboratory (USA) was used as showcase for this diagnostic scheme. By applying a combined two-color, multi-photon experiment with polarization control, the degree of circular polarization of the Delta undulator has been determined. Towards this goal, an oriented electronic state in the continuum was created by non-resonant ionization of the O2 1s core shell with circularly polarized FEL pulses at hν ≃ 700 eV. An also circularly polarized, highly intense UV laser pulse with hν ≃ 3.1 eV was temporally and spatially overlapped, causing the photoelectrons to redistribute into so-called sidebands that are energetically separated by the photon energy of the UV laser. By determining the circular dichroism of these redistributed electrons using angle resolving electron spectroscopy and modeling the results with the strong-field approximation, this scheme allows to unambiguously determine the absolute degree of circular polarization of any pulsed, ultraintense XUV or X-ray laser source.

The Linac Coherent Light Source has added a self-seeding capability to the soft x-ray range using a grating monochromator system. We report the demonstration of soft x-ray self-seeding with a measured resolving power of 2000-5000, wavelength stability of 10(-4), and an increase in peak brightness by a factor of 2-5 across the photon energy range of 500-1000 eV. By avoiding the need for a monochromator at the experimental station, the self-seeded beam can deliver as much as 50-fold higher brightness to users.

A scheme for generating two simultaneous hard-x-ray free-electron laser pulses with a controllable difference in photon energy is described and then demonstrated using the self-seeding setup at the Linac Coherent Light Source (LCLS). The scheme takes advantage of the existing LCLS equipment, which allows two independent rotations of the self-seeding diamond crystal. The two degrees of freedom are used to select two nearby crystal reflections, causing two wavelengths to be present in the forward transmitted seeding x-ray pulse. The free-electron laser system must support amplification at both desired wavelengths.

One of the major challenges in regenerative medicine is the ability to recreate the stem cell niche, which is defined by its signaling molecules, the creation of cytokine gradients, and the modulation of matrix stiffness. A wide range of scaffolds has been developed in order to recapitulate the stem cell niche, among them hydrogels. This paper reports the development of a new silk-alginate based hydrogel with a focus on stem cell culture. This biocomposite allows to fine tune its elasticity during cell culture, addressing the importance of mechanotransduction during stem cell differentiation. The silk-alginate scaffold promotes adherence of mouse embryonic stem cells and cell survival upon transplantation. In addition, it has tunable stiffness as function of the silk-alginate ratio and the concentration of crosslinker--a characteristic that is very hard to accomplish in current hydrogels. The hydrogel and the presented results represents key steps on the way of creating artificial stem cell niche, opening up new paths in regenerative medicine., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

We show that the spectral properties of a self-amplified spontaneous emission x-ray free-electron laser can be controlled by modulating the gain in magnetic undulators, thus producing one or several spectral lines within a single few femtosecond pulse. By varying the magnetic field along the undulator and the electron beam transport line, the system we demonstrate can tailor the x-ray spectrum to optimally meet numerous experimental requirements for multicolor operation.

With an eye toward extending optical wave-mixing techniques to the x-ray regime, we present the first experimental demonstration of a two-color x-ray free-electron laser at the Linac Coherent Light Source. We combine the emittance-spoiler technique with a magnetic chicane in the undulator section to control the pulse duration and relative delay between two intense x-ray pulses and we use differently tuned canted pole undulators such that the two pulses have different wavelengths as well. Two schemes are shown to produce two-color soft x-ray pulses with a wavelength separation up to ∼1.9% and a controllable relative delay up to 40 fs.

The Linac Coherent Light Source (LCLS) is an x-ray free-electron laser project presently in a commissioning phase at the SLAC National Accelerator Laboratory. We report here on very low-emittance measurements made at low bunch charge, and a few femtosecond bunch length produced by the LCLS bunch compressors. Start-to-end simulations associated with these beam parameters show the possibilities of generating hundreds of GW at 1.5 A x-ray wavelength and nearly a single longitudinally coherent spike at 1.5 nm with 2-fs duration.

This contribution investigates the effects of chain length and chemical composition on the secondary structure and LCST behavior of a library of short, elastin-like peptides based on the GVGVP motif. CD experiments revealed that most of the investigated peptides showed the typical elastin conformational behavior with a decrease in random coil and an increase in beta-turn character with increasing temperature. For several peptides, LCST behavior was observed in aqueous NaCl solutions containing 10 mg/mL peptide. By extrapolation of the LCSTs measured at different NaCl concentrations to zero-salt concentration, apparent LCSTs were determined. The apparent LCST was found to decrease with increasing peptide chain length, which correlated well with the trend in the predicted partition coefficients. The apparent LCST of the peptides could be manipulated by successive replacement of the valine residues by more hydrophobic isoleucine, leucine, or phenylalanine residues. Within a particular series of variants, the apparent LCST was found to decrease with an increasing number of valine replacements, which also correlated well with the predicted evolution of the partition coefficient. Although the relative importance of the overall peptide hydrophobicity and the conformational preferences of the constituent amino acids on the LCST behavior still remains an open question, the results described in this contribution clearly demonstrate that short, elastin-like peptides are potentially attractive building blocks for a range of materials applications in biomedicine and engineering.

This report describes the aqueous solution self-assembly of a series of polystyrene(m)-b-poly(L-lysine)n block copolymers (m = 8-10; n = 10-70). The polymers are prepared by ring-opening polymerization of epsilon-benzyloxycarbonyl-L-lysine N-carboxyanhydride using amine terminated polystyrene macroinitiators, followed by removal of the benzyloxycarbonyl side chain protecting groups. The critical micelle concentration of the block copolymers determined using the pyrene probe technique shows a parabolic dependence on peptide block length exhibiting a maximum at n = approximately 20 (m = 8) or n = approximately 60 (m = 10). The shape and size of the aggregates has been studied by dynamic and static light scattering, small-angle neutron scattering (SANS), and analytical ultracentrifugation (AUC). Surprisingly, Holtzer and Kratky analysis of the static light scattering results indicates the presence of nonspherical, presumably cylindrical objects independent of the poly(L-lysine)n block length. This is supported by SANS data, which can be fitted well by assuming cylindrical scattering objects. AUC analysis allows the molecular weight of the aggregates to be estimated as several million g/mol, corresponding to aggregation numbers of several 10s to 100s. These aggregation numbers agree with those that can be estimated from the length and diameter of the cylinders obtained from the scattering results.

The self-assembly in aqueous solution of hybrid block copolymers consisting of amphiphilic beta-strand peptide sequences flanked by one or two PEG chains was investigated by means of circular dichroism spectroscopy, small-angle X-ray scattering, and transmission electron microscopy. In comparison with the native peptide sequence, it was found that the peptide secondary structure was stabilized against pH variation in the di- and tri-block copolymers with PEG. Small-angle X-ray scattering indicated the presence of fibrillar structures, the dimensions of which are comparable to the estimated width of a beta-strand (with terminal PEG chains in the case of the copolymers). Transmission electron microscopy on selectively stained and dried specimens shows directly the presence of fibrils. It is proposed that these fibrils result from the hierarchical self-assembly of peptide beta-strands into helical tapes, which then stack into fibrils.

Biologically-inspired peptide sequences have been explored as auxiliaries to mediate self-assembly of synthetic macromolecules into hierarchically organized solution and solid state nanostructures. Peptide sequences inspired by the coiled coil motif and "switch" peptides, which can adopt both amphiphilic alpha-helical and beta-strand conformations, were conjugated to poly(ethylene glycol) (PEG). The solution and solid state self-assembly of these materials was investigated using a variety of spectroscopic, scattering and microscopic techniques. These experiments revealed that the folding and organization properties of the peptide sequences are retained upon conjugation of PEG and that they provide the driving force for the formation of the different nanoscale structures which were observed. The possibility of using defined peptide sequences to direct structure formation of synthetic polymers together with the potential of peptide sequences to induce a specific biological response offers interesting prospects for the development of novel self-assembled and biologically active materials.

A study of the potential for the development of the Linac Coherent Light Source (LCLS) beyond the specifications of the baseline design is presented. These future developments include delivery of X-ray pulses in the 1 fs regime, extension of the spectral range, increase of the FEL power, exploitation of the spontaneous emission, and a more flexible time structure. As this potential is exploited, the LCLS can maintain its role as a world-leading instrument for many years beyond its commissioning in 2008 and initial operation as the world's first X-ray free-electron laser.

VISA (Visible to Infrared SASE Amplifier) is a high-gain self-amplified spontaneous emission (SASE) free-electron laser (FEL), which achieved saturation at 840 nm within a single-pass 4-m undulator. The experiment was performed at the Accelerator Test Facility at BNL, using a high brightness 70-MeV electron beam. A gain length shorter than 18 cm has been obtained, yielding a total gain of 2 x 10(8) at saturation. The FEL performance, including the spectral, angular, and statistical properties of SASE radiation, has been characterized for different electron beam conditions. Results are compared to the three-dimensional SASE FEL theory and start-to-end numerical simulations of the entire injector, transport, and FEL systems. An agreement between simulations and experimental results has been obtained at an unprecedented level of detail.

Electron beam microbunching in both the fundamental and second harmonic in a high-gain self-amplified spontaneous emission free-electron laser (SASE FEL) was experimentally characterized using coherent transition radiation. The microbunching factors for both modes (b(1) and b(2)) approach unity, an indication of FEL saturation. These measurements are compared to the predictions of FEL simulations. The simultaneous capture of the microbunching and SASE radiation for individual micropulses correlate the longitudinal electron beam structure with the FEL gain.

Nonlinear harmonic radiation was observed using the VISA self-amplified, spontaneous emission (SASE) free-electron laser (FEL) at saturation. The gain lengths, spectra, and energies of the three lowest SASE FEL modes were experimentally characterized. The measured nonlinear harmonic gain lengths and center spectral wavelengths decrease with harmonic number, n, which is consistent with nonlinear harmonic theory. Both the second and third nonlinear harmonics energies are about 1% of the fundamental energy. These experimental results demonstrate for the first time the feasibility of using nonlinear harmonic SASE FEL radiation to produce coherent, femtosecond x rays.