Biomimetic proteolipid vesicles for targeting inflamed tissues.

A multitude of micro- and nanoparticles have been developed to improve the delivery of systemically administered pharmaceuticals, which are subject to a number of biological barriers that limit their optimal biodistribution. Bioinspired drug-delivery carriers formulated by bottom-up or top-down strategies have emerged as an alternative approach to evade the mononuclear phagocytic system and facilitate transport across the endothelial vessel wall. Here, we describe a method that leverages the advantages of bottom-up and top-down strategies to incorporate proteins derived from the leukocyte plasma membrane into lipid nanoparticles. The resulting proteolipid vesicles-which we refer to as leukosomes-retained the versatility and physicochemical properties typical of liposomal formulations, preferentially targeted inflamed vasculature, enabled the selective and effective delivery of dexamethasone to inflamed tissues, and reduced phlogosis in a localized model of inflammation.

Low-power-threshold photonic saturable absorber in nonlinear chalcogenide glass.

We experimentally demonstrate controllable nonlinear modulation of optical guiding in ultrafast laser-written evanescently coupled waveguide arrays in bulk gallium lanthanum sulfide chalcogenide glass. The intensity-dependent response is validated by simulating light propagation in waveguide arrays with instantaneous Kerr nonlinearity using a discrete-continuous spatiotemporal unidirectional Maxwell equation model. The intensity-driven modulation of transmission in multicore structures acts as a potential saturable absorber at kilowatt threshold levels.

Three-dimensional light bullets in arrays of waveguides.

We report the first experimental observation of three-dimensional light bullets, excited by femtosecond pulses in a system featuring quasi-instantaneous cubic nonlinearity and a periodic, transversally modulated refractive index. Stringent evidence of the excitation of light bullets is based on time-gated images and spectra which perfectly match our numerical simulations. Furthermore, we reveal a novel evolution mechanism forcing the light bullets to follow varying dispersion or diffraction conditions, until they leave their existence range and decay.

Fast advection of magnetic fields by hot electrons.

Experiments where a laser-generated proton beam is used to probe the megagauss strength self-generated magnetic fields from a nanosecond laser interaction with an aluminum target are presented. At intensities of 10(15) W cm(-2) and under conditions of significant fast electron production and strong heat fluxes, the electron mean-free-path is long compared with the temperature gradient scale length and hence nonlocal transport is important for the dynamics of the magnetic field in the plasma. The hot electron flux transports self-generated magnetic fields away from the focal region through the Nernst effect [A. Nishiguchi, Phys. Rev. Lett. 53, 262 (1984)] at significantly higher velocities than the fluid velocity. Two-dimensional implicit Vlasov-Fokker-Planck modeling shows that the Nernst effect allows advection and self-generation transports magnetic fields at significantly faster than the ion fluid velocity, v(N)/c(s)≈10.

Biomimetic hydroxyapatite/collagen composite drives bone niche recapitulation in a rabbit orthotopic model.

Synthetic osteoinductive materials that mimic the human osteogenic niche have emerged as ideal candidates to address this area of unmet clinical need. In this study, we evaluated the osteoinductive potential in a rabbit orthotopic model of a magnesium-doped hydroxyapatite/type I collagen â€‹(MHA/Coll) composite. The composite was fabricated to exhibit a highly fibrous structure of carbonated MHA with 70% (±2.1) porosity and a Ca/P ratio of 1.5 (±0.03) as well as a diverse range of elasticity separated to two distinct stiffness peaks of low (2.35 â€‹± â€‹1.16 â€‹MPa) and higher (9.52 â€‹± â€‹2.10 â€‹MPa) Young's Modulus. Data suggested that these specific compositional and nanomechanical material properties induced the deposition of de novo mineral phase, while modulating the expression of early and late osteogenic marker genes, in a 3D in vitro model using human bone marrow-derived mesenchymal stem cells (hBM-MSCs). When tested in the rabbit orthotopic model, MHA/Col1 scaffold induction of new trabecular bone mass was observed by DynaCT scan, only 2 weeks after implantation. Bone histomorphometry at 6 weeks revealed a significant amount of de novo bone matrix formation. qPCR demonstrated MHA/Coll scaffold full cellularization in vivo and the expression of both osteogenesis-associated genes (Spp1, Sparc, Col1a1, Runx2, Dlx5) as well as hematopoietic (Vcam1, Cd38, Sele, Kdr) and bone marrow stromal cell marker genes (Vim, Itgb1, Alcam). Altogether, these data provide â€‹evidence of the solid osteoinductive potential of MHA/Coll and its suitability for multiple approaches of bone regeneration.

Demonstration of vortex-induced beam shaping in seeded second-harmonic generation.

We report the experimental demonstration of a method that allows the simultaneous frequency-doubling and the shaping of a light beam into a variety of patterns. The technique is based on the controllable generation of multiple-vortex patterns in seeded schemes. Our observations were performed under conditions of second-harmonic generation pumped by picosecond pulses at 1055 nm, but the scheme can be extended to all parametric processes.

Observation of quadratic optical vortex solitons

We report on the generation of stable dark-vortex solitons in large-phase-mismatched second-harmonic generation of self-defocusing type, sustained by a combined effect of transverse walk-off and finite beam size.

Genomic characterization of asymptomatic CT-detected lung cancers.

Computed tomography (CT) screening of lung cancer allows the detection of early tumors. The objective of our study was to verify whether initial asymptomatic lung cancers, identified by high-resolution low-dose CT (LD-CT) on a high-risk population, show genetic abnormalities that could be indicative of the early events of lung carcinogenesis. We analyzed 78 tumor samples: 21 (pilot population) from heavy smokers with asymptomatic non-screening detected early-stage lung cancers and 57 from 5203 asymptomatic heavy smoker volunteers, who underwent a LD-CT screening study. During surgical resection of the detected tumors, tissue samples were collected and short-term cultures were started for karyotype evaluation. Samples were classified according to the normal (NK) or aneuploid (AK) karyotype. The NK samples were further analyzed by the Affymetrix single-nucleotide polymorphisms (SNPs) technology. Metaphase spreads were obtained in 73.0% of the selected samples: 80.7% showed an AK. A statistically significant correlation was found between presence of vascular invasion and abnormal karyotype. A total of 10 NK samples were suitable for SNPs analysis. Subtle genomic alterations were found in eight tumors, the remaining two showing no evidence to date of chromosomal aberrations anywhere in the genome. Two common regions of amplification were identified at 5p and 8p11. Mutation analysis by direct sequencing was conducted for the K-RAS, TP53 and EGFR genes, confirming data already described for heavy smokers. We show that: (i) the majority of screening-detected tumors are aneuploid; (ii) early-stage tumors tend to harbor a less abnormal karyotype; (iii) whole genome analysis of NK tumors allows for the detection of common regions of copy number variation (such as amplifications at 5p and 8p11), highlighting genes that might be considered candidate markers of early events in lung carcinogenesis.

Observation of three-dimensional discrete-continuous x waves in photonic lattices.

We report on the generation of three-dimensional discrete X waves in a femtosecond laser-written waveguide array. Our measurements constitute the first experimental observation of temporally localized three-dimensional discrete-continuous entities. The X waves spontaneously emerge from a single-site excitation due to the discrete diffraction of the lattice and the normally dispersive as well as cubically nonlinear properties of the fused silica used as host material.

Magnetic reconnection and plasma dynamics in two-beam laser-solid interactions.

We present measurements of a magnetic reconnection in a plasma created by two laser beams (1 ns pulse duration, 1 x 10(15) W cm(-2)) focused in close proximity on a planar solid target. Simultaneous optical probing and proton grid deflectometry reveal two high velocity, collimated outflowing jets and 0.7-1.3 MG magnetic fields at the focal spot edges. Thomson scattering measurements from the reconnection layer are consistent with high electron temperatures in this region.

Quantum-noise-initiated symmetry breaking of spatial solitons.

The spectra of chi(2) spatial solitons are measured close to the soliton-formation threshold and show the presence of sidebands, shifted by 39 THz from the laser line. By comparing with the predictions of a quantum optical field model, solved numerically in the full (3 + 1)-dimensional space, it is claimed that the observed temporal instability of the spatial soliton is seeded by vacuum state fluctuations of the electromagnetic field.

Reconstruction of blurred images by controlled formation of spatial solitons.

Diffracted digital images are reconstructed by excitation of spatial solitons in a bulk chi((2)) crystal, in the regime of single-pass parametric amplification of the quantum noise.

Pixellike parametric generator based on controlled spatial-soliton formation.

We report the observation of a stable matrix of diffraction-limited solitary beams in a monolithic, single-pass, parametric amplifier pumped by a spatially modulated beam.

Soliton algebra by vortex-beam splitting.

We experimentally demonstrate the possibility of breaking up intense vortex light beams into stable and controllable sets of parametric solitons. We report observations performed in seeded second-harmonic generation, but the scheme can be extended to all parametric processes. The number of generated solitons is shown to be determined by a robust arithmetic rule.

Upon dendritic cell (DC) activation chemokines and chemokine receptor expression are rapidly regulated for recruitment and maintenance of DC at the inflammatory site.

Dendritic cells (DC) are highly motile antigen-presenting cells that are recruited to sites of infection and inflammation to antigen uptake and processing. Then, to initiate T cell-dependent immune responses, they migrate from non-lymphoid organs to lymph nodes and the spleen. Since chemokines have been involved in human DC recruitment, we investigated the role of chemokines on mouse DC migration using the mouse growth factor-dependent immature DC line (D1). In this study, we characterized receptor expression, responsiveness to chemoattractants and chemokine expression of D1 cells during the maturation process induced by lipopolysaccharide (LPS). MIP-1alpha and MIP-5 were found to be the most effective chemoattractants, CCR1 was the main receptor expressed and modulated during LPS treatment, and MIP-2, RANTES, IP-10 and MCP-1 were the chemokines modulated during DC maturation. Thus, murine DC respond to a unique set of CC and CXC chemokines, and the maturational stage determines the program of chemokine receptors and chemokines that are expressed. Since CCR1 is modulated during the early phases of DC maturation, our results indicate that the CCR1 receptor may participate in the recruitment and maintenance of DC at the inflammatory site.

Spatial versus temporal deterministic wave breakup of nonlinearly coupled light waves.

We investigate experimentally the competition between spatial and temporal breakup due to modulational instability in chi((2)) nonlinear mixing. The modulation of the wave packets caused by the energy exchange between fundamental and second-harmonic components is found to be the prevailing trigger mechanism which, according to the relative weight of diffraction and dispersion, leads to the appearance of a multisoliton pattern in the low-dimensional spatial or temporal domain.