Immunogene therapy with fusogenic nanoparticles modulates macrophage response to Staphylococcus aureus.

The incidence of adverse effects and pathogen resistance encountered with small molecule antibiotics is increasing. As such, there is mounting focus on immunogene therapy to augment the immune system's response to infection and accelerate healing. A major obstacle to in vivo gene delivery is that the primary uptake pathway, cellular endocytosis, results in extracellular excretion and lysosomal degradation of genetic material. Here we show a nanosystem that bypasses endocytosis and achieves potent gene knockdown efficacy. Porous silicon nanoparticles containing an outer sheath of homing peptides and fusogenic liposome selectively target macrophages and directly introduce an oligonucleotide payload into the cytosol. Highly effective knockdown of the proinflammatory macrophage marker IRF5 enhances the clearance capability of macrophages and improves survival in a mouse model of Staphyloccocus aureus pneumonia

Soluble polyacetylenes derived from the ring-opening metathesis polymerization of substituted cyclooctatetraenes: electrochemical characterization and Schottky barrier devices

Recent developments in ring-opening metathesis polymerization (ROMP) have enabled the synthesis of poly-cyclooctatetraene (poly-COT), a material which is isostructural to polyacetylene. This liquid-phase polymerization method allows facile construction of interfaces, films, and devices with polyacetylene-like materials. The ROMP method also allows the preparation of soluble, yet highly conjugated polyacetylene analogs from substituted cyclooctatetraenes (R-COT). The redox characteristics of R-COT polymers were investigated at electrodes modified with thin polymer films. Voltammetric methods were used to characterize the redox response, band gap, electrochemical doping, and cis-trans isomerization properties of these polyenes. We have applied poly-COT technology to the fabrication of Schottky diodes and photoelectrochemical cells, by forming poly-COT films on semiconductor surfaces. The resultant semiconductor/organic-metal interfaces behave more ideally than semiconductor contacts with conventional metals, in that changes in the work function of the conducting polymer exert a large and predictable effect on the electrical properties of the resulting Schottky diodes. Transparent films of the solution-processible polymer poly- trimethylsilyl-cyclooctatetraene (poly-TMS-COT) have been cast onto n-silicon substrates and doped with iodine to form surface barrier solar cells. These devices produce photovoltages that are much larger than can be obtained from n-silicon contacts with conventional metals

Monitoring of degradation of porous silicon photonic crystals using digital photography

We report the monitoring of porous silicon (pSi) degradation in aqueous solutions using a consumer-grade digital camera. To facilitate optical monitoring, the pSi samples were prepared as one-dimensional photonic crystals (rugate filters) by electrochemical etching of highly doped p-type Si wafers using a periodic etch waveform. Two pSi formulations, representing chemistries relevant for self-reporting drug delivery applications, were tested: freshly etched pSi (fpSi) and fpSi coated with the biodegradable polymer chitosan (pSi-ch). Accelerated degradation of the samples in an ethanol-containing pH 10 aqueous basic buffer was monitored in situ by digital imaging with a consumer-grade digital camera with simultaneous optical reflectance spectrophotometric point measurements. As the nanostructured porous silicon matrix dissolved, a hypsochromic shift in the wavelength of the rugate reflectance peak resulted in visible color changes from red to green. While the H coordinate in the hue, saturation, and value (HSV) color space calculated using the as-acquired photographs was a good monitor of degradation at short times (t  pSi-ch.We acknowledge the financial support from Ministerio de Educación y Ciencia (Spain), Dirección General de Enseñanza Superior (Spain) (CTQ2009-14428-C02-01), and Junta de Andalucía (Spain) (P10-FQM-5974). A.N. wants to acknowledge Fundación Alfonso Martín Escudero for a postdoctoral fellowship. This material is based upon the work supported by the U.S. National Science Foundation under Grant No. DMR-1210417

Gas adsorption and capillary condensation in nanoporous alumina films

"Gas adsorption and capillary condensation of organic vapors are studied by optical interferometry, using anodized nanoporous alumina films with controlled geometry (cylindrical pores with diameters in the range of 10-60 nm). The optical response of the film is optimized with respect to the geometric parameters of the pores, for potential performance as a gas sensor device. The average thickness of the adsorbed film at low relative pressures is not affected by the pore size. Capillary evaporation of the liquid from the nanopores occurs at the liquid-vapor equilibrium described by the classical Kelvin equation with a hemispherical meniscus. Due to the almost complete wetting, we can quantitatively describe the condensation for isopropanol using the Cohan model with a cylindrical meniscus in the Kelvin equation. This model describes the observed hysteresis and allows us to use the adsorption branch of the isotherm to calculate the pore size distribution of the sample in good agreement with independent structural measurements. The condensation for toluene lacks reproducibility due to incomplete surface wetting. This exemplifies the relevant role of the fluid-solid (van der Waals) interactions in the hysteretic behavior of capillary condensation."http://deepblue.lib.umich.edu/bitstream/2027.42/64187/1/nano8_31_315709.pd

National Urban Database and Access Portal Tool, NUDAPT

Based on the need for advanced treatments of high resolution urban morphological features (e.g., buildings, trees) in meteorological, dispersion, air quality and human exposure modeling systems for future urban applications, a new project was launched called the National Urban Database and Access Portal Tool (NUDAPT). NUDAPT is sponsored by the U.S. Environmental Protection Agency (USEPA) and involves collaborations and contributions from many groups including federal and state agencies and from private and academic institutions here and in other countries. It is designed to produce and provide gridded fields of urban canopy parameters for various new and advanced descriptions of model physics to improve urban simulations given the availability of new high-resolution data of buildings, vegetation, and land use. Additional information include gridded anthropogenic heating and population data is incorporated to further improve urban simulations and to encourage and facilitate decision support and application linkages to human exposure models. An important core-design feature is the utilization of web portal technology to enable NUDAPT to be a Community based system. This web-based portal technology will facilitate customizing of data handling and retrievals (http://www.nudapt.org). This article provides an overview of NUDAPT and several example applications

Close Correlation of Monoamine Oxidase Activity with Progress of Alzheimer’s Disease in Mice, Observed by in Vivo Two-Photon Imaging

Monoamine oxidases (MAOs) play an important role in Alzheimer's disease (AD) pathology. We report in vivo comonitoring of MAO activity and amyloid-beta (A beta) plaques dependent on the aging of live mice with AD, using a two-photon fluorescence probe. The probe under the catalytic action of MAO produces a dipolar fluorophore that senses A beta plaques, a general AD biomarker, enabling us to comonitor the enzyme activity and the progress of AD indicated by A beta plaques. The results show that the progress of AD has a close correlation with MAO activity, which can be categorized into three stages: slow initiation stage up to three months, an aggressive stage, and a saturation stage from nine months. Histological analysis also reveals elevation of MAO activity around A beta plaques in aged mice. The close correlation between the MAO activity and AD progress observed by in vivo monitoring for the first time prompts us to investigate the enzyme as a potential biomarker of AD.1195Ysciescopu

Porous Silicon Nanoparticles Embedded in Poly(lactic‐ co ‐glycolic acid) Nanofiber Scaffolds Deliver Neurotrophic Payloads to Enhance Neuronal Growth

Scaffolds made from biocompatible polymers provide physical cues to direct the extension of neurites and to encourage repair of damaged nerves. The inclusion of neurotrophic payloads in these scaffolds can substantially enhance regrowth and repair processes. However, many promising neurotrophic candidates are excluded from this approach due to incompatibilities with the polymer or with the polymer processing conditions. This work provides one solution to this problem by incorporating porous silicon nanoparticles (pSiNPs) that are pre-loaded with the therapeutic into a polymer scaffold during fabrication. The nanoparticle-drug-polymer hybrids are prepared in the form of oriented poly(lactic-co-glycolic acid) nanofiber scaffolds. We test three different therapeutic payloads: bpV(HOpic), a small molecule inhibitor of phosphatase and tensin homolog (PTEN); an RNA aptamer specific to tropomyosin-related kinase receptor type B (TrkB); and the protein nerve growth factor (NGF). Each therapeutic is loaded using a loading chemistry that is optimized to slow the rate of release of these water-soluble payloads. The drug-loaded pSiNP-nanofiber hybrids release approximately half of their TrkB aptamer, bpV(HOpic), or NGF payload in 2, 10, and >40 days, respectively. The nanofiber hybrids increase neurite extension relative to drug-free control nanofibers in a dorsal root ganglion explant assay

Soluble polyacetylenes derived from the ring-opening metathesis polymerization of substituted cyclooctatetraenes: electrochemical characterization and Schottky barrier devices

Recent developments in ring-opening metathesis polymerization (ROMP) have enabled the synthesis of poly-cyclooctatetraene (poly-COT), a material which is isostructural to polyacetylene. This liquid-phase polymerization method allows facile construction of interfaces, films, and devices with polyacetylene-like materials. The ROMP method also allows the preparation of soluble, yet highly conjugated polyacetylene analogs from substituted cyclooctatetraenes (R-COT). The redox characteristics of R-COT polymers were investigated at electrodes modified with thin polymer films. Voltammetric methods were used to characterize the redox response, band gap, electrochemical doping, and cis-trans isomerization properties of these polyenes. We have applied poly-COT technology to the fabrication of Schottky diodes and photoelectrochemical cells, by forming poly-COT films on semiconductor surfaces. The resultant semiconductor/organic-metal interfaces behave more ideally than semiconductor contacts with conventional metals, in that changes in the work function of the conducting polymer exert a large and predictable effect on the electrical properties of the resulting Schottky diodes. Transparent films of the solution-processible polymer poly- trimethylsilyl-cyclooctatetraene (poly-TMS-COT) have been cast onto n-silicon substrates and doped with iodine to form surface barrier solar cells. These devices produce photovoltages that are much larger than can be obtained from n-silicon contacts with conventional metals

Designed 2D protein crystals as dynamic molecular gatekeepers for a solid-state device

The sensitivity and responsiveness of living cells to environmental changes are enabled by dynamic protein structures, inspiring efforts to construct artificial supramolecular protein assemblies. However, despite their sophisticated structures, designed protein assemblies have yet to be incorporated into macroscale devices for real-life applications. We report a 2D crystalline protein assembly of C98/E57/E66L-rhamnulose-1-phosphate aldolase (CEERhuA) that selectively blocks or passes molecular species when exposed to a chemical trigger. CEERhuA crystals are engineered via cobalt(II) coordination bonds to undergo a coherent conformational change from a closed state (pore dimensions <1 nm) to an ajar state (pore dimensions ~4 nm) when exposed to an HCN(g) trigger. When layered onto a mesoporous silicon (pSi) photonic crystal optical sensor configured to detect HCN(g), the 2D CEERhuA crystal layer effectively blocks interferents that would otherwise result in a false positive signal. The 2D CEERhuA crystal layer opens in selective response to low-ppm levels of HCN(g), allowing analyte penetration into the pSi sensor layer for detection. These findings illustrate that designed protein assemblies can function as dynamic components of solid-state devices in non-aqueous environments

Meeting reports: Research on Coupled Human and Natural Systems (CHANS): Approach, Challenges, and Strategies

Understanding the complexity of human–nature interactions is central to the quest for both human well-being and global sustainability. To build an understanding of these interactions, scientists, planners, resource managers, policymakers, and communities increasingly are collaborating across wide-ranging disciplines and knowledge domains. Scientists and others are generating new integrated knowledge on top of their requisite specialized knowledge to understand complex systems in order to solve pressing environmental and social problems (e.g., Carpenter et al. 2009). One approach to this sort of integration, bringing together detailed knowledge of various disciplines (e.g., social, economic, biological, and geophysical), has become known as the study of Coupled Human and Natural Systems, or CHANS (Liu et al. 2007a, b). In 2007 a formal standing program in Dynamics of Coupled Natural and Human Systems was created by the U.S. National Science Foundation. Recently, the program supported the launch of an International Network of Research on Coupled Human and Natural Systems (CHANS-Net.org). A major kick-off event of the network was a symposium on Complexity in Human–Nature Interactions across Landscapes, which brought together leading CHANS scientists at the 2009 meeting of the U.S. Regional Association of the International Association for Landscape Ecology in Snowbird, Utah. The symposium highlighted original and innovative research emphasizing reciprocal interactions between human and natural systems at multiple spatial, temporal, and organizational scales. The presentations can be found at ‹http://chans- net.org/Symposium_2009.aspx›. The symposium was accompanied by a workshop on Challenges and Opportunities in CHANS Research. This article provides an overview of the CHANS approach, outlines the primary challenges facing the CHANS research community, and discusses potential strategies to meet these challenges, based upon the presentations and discussions among participants at the Snowbird meeting