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Metabolic acidosis induces osteoclastic bone resorption and inhibits osteoblastic bone formation. Previously we found that mice with a global deletion of the proton receptor OGR1 had increased bone density although both osteoblast and osteoclast activity were increased. To test whether direct effects on osteoclast OGR1 are critical for metabolic acidosis stimulated bone resorption, we generated knockout mice with an osteoclast-specific deletion of OGR1 (knockout mice). We studied bones from three-month old female mice and the differentiated osteoclasts derived from bone marrow of femurs from these knockout and wild type mice. MicroCT demonstrated increased density in tibiae and femurs but not in vertebrae of the knockout mice. Tartrate resistant acid phosphatase staining of tibia indicated a decrease in osteoclast number and surface area/bone surface from knockout compared to wild type mice. Osteoclasts derived from the marrow of knockout mice demonstrated decreased pit formation, osteoclast staining and osteoclast-specific gene expression compared to those from wild type mice. In response to metabolic acidosis, osteoclasts from knockout mice had decreased nuclear translocation of NFATc1, a transcriptional regulator of differentiation, and no increase in size or number compared to osteoclasts from wild type mice. Thus, loss of osteoclast OGR1 decreased both basal and metabolic acidosis-induced osteoclast activity indicating osteoclast OGR1 is important in mediating metabolic acidosis-induced bone resorption. Understanding the role of OGR1 in metabolic acidosis-induced bone resorption will provide insight into bone loss in acidotic patients with chronic kidney disease.

Autoreactive B cell-derived antibodies form immune complexes that likely play a pathogenic role in autoimmune diseases. In systemic lupus erythematosus (SLE), these antibodies bind Fc receptors on myeloid cells and induce proinflammatory cytokine production by monocytes and NETosis by neutrophils. Bruton's tyrosine kinase (BTK) is a non-receptor tyrosine kinase that signals downstream of Fc receptors and plays a transduction role in antibody expression following B cell activation. Given the roles of BTK in both the production and sensing of autoreactive antibodies, inhibitors of BTK kinase activity may provide therapeutic value to patients suffering from autoantibody-driven immune disorders. Starting from an in-house proprietary screening hit followed by structure-based rational design, we have identified a potent, reversible BTK inhibitor, BIIB068 (1), which demonstrated good kinome selectivity with good overall drug-like properties for oral dosing, was well tolerated across preclinical species at pharmacologically relevant doses with good ADME properties, and achieved >90% inhibition of BTK phosphorylation (pBTK) in humans.

Skeletal muscle is a major determinant of systemic metabolic homeostasis that plays a critical role in glucose metabolism and insulin sensitivity. By contrast, despite being a major user of fatty acids, and evidence that muscular disorders can lead to abnormal lipid deposition (e.g., nonalcoholic fatty liver disease in myopathies), our understanding of skeletal muscle regulation of systemic lipid homeostasis is not well understood. Here we show that skeletal muscle Krüppel-like factor 15 (KLF15) coordinates pathways central to systemic lipid homeostasis under basal conditions and in response to nutrient overload. Mice with skeletal muscle-specific KLF15 deletion demonstrated (a) reduced expression of key targets involved in lipid uptake, mitochondrial transport, and utilization, (b) elevated circulating lipids, (c) insulin resistance/glucose intolerance, and (d) increased lipid deposition in white adipose tissue and liver. Strikingly, a diet rich in short-chain fatty acids bypassed these defects in lipid flux and ameliorated aspects of metabolic dysregulation. Together, these findings establish skeletal muscle control of lipid flux as critical to systemic lipid homeostasis and metabolic health.

The Drp1-HK1-NLRP3 axis is a key mechanism of oligodendrocyte damage and white matter degeneration in AD., Myelin degeneration and white matter loss resulting from oligodendrocyte (OL) death are early events in Alzheimer’s disease (AD) that lead to cognitive deficits; however, the underlying mechanism remains unknown. Here, we find that mature OLs in both AD patients and an AD mouse model undergo NLR family pyrin domain containing 3 (NLRP3)–dependent Gasdermin D–associated inflammatory injury, concomitant with demyelination and axonal degeneration. The mature OL-specific knockdown of dynamin-related protein 1 (Drp1; a mitochondrial fission guanosine triphosphatase) abolishes NLRP3 inflammasome activation, corrects myelin loss, and improves cognitive ability in AD mice. Drp1 hyperactivation in mature OLs induces a glycolytic defect in AD models by inhibiting hexokinase 1 (HK1; a mitochondrial enzyme that initiates glycolysis), which triggers NLRP3-associated inflammation. These findings suggest that OL glycolytic deficiency plays a causal role in AD development. The Drp1-HK1-NLRP3 signaling axis may be a key mechanism and therapeutic target for white matter degeneration in AD.

A combined experimental and computational study is reported on a hitherto unrecognised single lanthanide catalyst for the breaking of molecular nitrogen and formation of ammonia at ambient temperature and low pressure. We combine in situ electrical conductance and electron diffraction measurements to track the conversion from the lanthanide metals to the insulating lanthanide nitrides. The efficiency of the conversion is then interpreted using $\mathrm{DFT}+U$ calculations, suggesting a molecular nitrogen dissociation pathway separate from that well established for transition metals. Finally, we show that exposure of the lanthanide surfaces to both molecular nitrogen and hydrogen results in the formation of ammonia.

This paper presents pollutant concentrations and performance data for code-required mechanical ventilation equipment in 23 low-income apartments at 4 properties constructed or renovated 2013-2017. All apartments had natural gas cooking burners. Occupants pledged to not use windows for ventilation during the study but several did. Measured airflows of range hoods and bathroom exhaust fans were lower than product specifications. Only eight apartments operationally met all ventilation code requirements. Pollutants measured over one week in each apartment included time-resolved fine particulate matter (PM2.5 ), nitrogen dioxide (NO2 ), formaldehyde and carbon dioxide (CO2 ) and time-integrated formaldehyde, NO2 and nitrogen oxides (NOX ). Compared to a recent study of California houses with code-compliant ventilation, apartments were smaller, had fewer occupants, higher densities, and higher mechanical ventilation rates. Mean PM2.5 , formaldehyde, NO2 , and CO2 were 7.7µg/m3 , 14.1, 18.8, and 741ppm in apartments; these are 4% lower, 25% lower, 165% higher, and 18% higher compared to houses with similar cooking frequency. Four apartments had weekly PM2.5 above the California annual outdoor standard of 12µg/m3 and also discrete days above the World Health Organization 24-hour guideline of 25µg/m3 . Two apartments had weekly NO2 above the California annual outdoor standard of 30ppb.

We estimate postmeter methane (CH4) emissions from California's residential natural gas (NG) system using measurements and analysis from a sample of homes and appliances. Quiescent whole-house emissions (i.e., pipe leaks and pilot lights) were measured using a mass balance method in 75 California homes, while CH4 to CO2 emission ratios were measured for steady operation of individual combustion appliances and, separately, for transient operation of three tankless water heaters. Measured quiescent whole-house emissions are typically 10 g CH4/day. Most operating appliances yield undetectable CH4 to CO2 enhancements in steady operation (

Wastewaters contaminated with nitrogenous pollutants, derived from anthropogenic activities, have exacerbated our ecosystems sparking environmental problems, such as eutrophication and acidification of water reservoirs, emission of greenhouse gases, death of aquatic organisms, among others. Wastewater treatment facilities (WWTF) combining nitrification and denitrification, and lately partial nitrification coupled to anaerobic ammonium oxidation (anammox), have traditionally been applied for the removal of nitrogen from wastewaters. The present work provides a comprehensive review of the recent biotechnologies developed in which nitrogen-removing processes are relevant for the treatment of both wastewaters and gas emissions. These novel processes include the anammox process with alternative electron acceptors, such as sulfate (sulfammox), ferric iron (feammox), and anodes in microbial electrolysis cells (anodic anammox). New technologies that couple nitrate/nitrite reduction with the oxidation of methane, H2S, volatile methyl siloxanes, and other volatile organic compounds are also described. The potential of these processes for (i) minimizing greenhouse gas emissions from WWTF, (ii) biogas purification, and (iii) air pollution control is critically discussed considering the factors that might trigger N2O release during nitrate/nitrite reduction. Moreover, this review provides a discussion on the main challenges to tackle towards the consolidation of these novel biotechnologies.

Author(s): Chan, Wanyu; Kumar, Sangeetha; Johnson, Alexandra; Singer, Brett | Abstract: The California building code requires all new or renovated residential dwelling units to have kitchen exhaust ventilation to manage air pollutants and moisture generated during cooking. Current performance requirements are specified as a minimum airflow and maximum sound level. This report presents an analysis to support consideration of adding a capture efficiency requirement to the code. The analysis uses a physics-based simulation model to calculate air pollutant concentrations in homes that result from cooking and the inflow of outdoor air, mediated by loss and removal process including deposition, dwelling unit ventilation, and the use of a range hood with varying levels of capture efficiency. Calculated pollutant concentrations are compared to relevant, health-based guidelines. The analysis considers the highest 1-hour concentration of nitrogen dioxide (NO2), which is a product of natural gas combustion and the highest 24-hour concentrations of fine particulate matter (PM2.5) which is emitted in substantial quantities from frying, broiling and grilling among other cooking activities. For NO2, the analysis considers cooking of a dinner for 3-4 persons consisting of pasta, meat sauce, a par-boiled vegetable, and baked garlic bread. For PM2.5, the analysis considers a day in which breakfast emitted particles at the 80th percentile and lunch and dinner entailed particle emissions at the 50th percentile of cooking emission events reported in the literature. Model simulations were performed to determine the level of range hood capture efficiency that will allow these cooking scenarios to occur in the vast majority (g99%) of new homes being built in California while maintaining pollutant concentrations below the health-based guidelines, if the range hood is used throughout cooking. All homes were assumed to have dwelling unit ventilation at the rate required in the building code. Simulation model input parameters were specified using a Monte Carlo approach to represent a range of housing characteristics, outdoor conditions, and indoor pollutant dynamics. Simulation results suggest that requiring a minimum capture efficiency of at least 70% is needed to avoid unacceptably high NO2 (1-h average concentration of 100 ppb or higher) and at least 60% to avoid unacceptably high PM2.5 (24-h average of 25 ug/m3 or higher). These results were driven by multi-family homes, which have a smaller volume of air to dilute any pollutants not captured and removed at the cooking area, resulting in higher concentrations.

The strongly correlated rare earth nitrides display unusual coupled magnetic, electronic and superconducting properties, with predicted topological states. However, their air-sensitiveness has prevented in-depth investigations of their properties. In this paper, we show that a 100 nm thick epitaxial samarium layer provides adequate passivation of 100 nm thick thin films of gadolinium nitride (GdN), the prototypical rare earth nitride, enabling ex-situ magnetic and structural characterizations. Using reflection high-energy electron diffraction, atomic force microscopy and energy dispersive x-ray spectroscopy, we investigate the thermal desorption of the samarium layer under vacuum. We finally demonstrate successful removal of the samarium capping layer in a separate vacuum chamber after exposure to air using a combination of argon ion sputtering and thermal desorption at 400 °C, recovering the GdN surface.

Data were collected in 70 detached houses built in 2011-2017 in compliance with the mechanical ventilation requirements of California's building energy efficiency standards. Each home was monitored for a 1-week period with windows closed and the central mechanical ventilation system operating. Pollutant measurements included time-resolved fine particulate matter (PM2.5 ) indoors and outdoors and formaldehyde and carbon dioxide (CO2 ) indoors. Time-integrated measurements were made for formaldehyde, NO2 , and nitrogen oxides (NOX ) indoors and outdoors. Operation of the cooktop, range hood, and other exhaust fans was continuously recorded during the monitoring period. Onetime diagnostic measurements included mechanical airflows and envelope and duct system air leakage. All homes met or were very close to meeting the ventilation requirements. On average, the dwelling unit ventilation fan moved 50% more airflow than the minimum requirement. Pollutant concentrations were similar to or lower than those reported in a 2006-2007 study of California new homes built in 2002-2005. Mean and median indoor concentrations were lower by 44% and 38% for formaldehyde and 44% and 54% for PM2.5 . Ventilation fans were operating in only 26% of homes when first visited, and the control switches in many homes did not have informative labels as required by building standards.

As one special type of sustainable energy source, radioisotopes have extremely high energy densities. Electrical generators using the decay heat from these radioisotopes can provide long-lasting power when other types of energy, such as solar or chemical energy, are not available. Starting from the 1960s, radioisotope generators were safely used in numerous space and terrestrial missions, and have powered systems from interstellar spacecraft to lighthouses along the arctic coast. This work reviewed the generator development and critical components that constitute a functional system. Started with a brief generator history, the paper focused on technological aspects including fuel manufacturing, energy conversion elements, thermal insulation, structural materials, prototype measurements, future improvements, and concluded with the safety aspects for both space and terrestrial applications. Radioisotope generators are one example of using nuclear energy in a peaceful way to benefit human be-ings. Plutonium fuel productions were resumed and accelerated in the United States and americium fuel research was actively sponsored by the European Space Agency. It is promis-ing that more and more high performance generators will be used in future land and space missions., Army Research Office through the Institute for Soldier Nanotechnologies (Contracts W911NF-07-D0004, MAST 892730 and S3TEC DE-SC0001299)

RNA Polymerase II (RNAPII) transcription termination is regulated by the phosphorylation status of the C-terminal domain (CTD). Using disruption-compensation (DisCo) protein-protein interaction network analysis, interaction changes were observed within the termination machinery as a consequence of deletion of the serine 5 RNAPII CTD phosphatase Rtr1. Interactions between RNAPII and the cleavage factor IA (CF1A) subunit Pcf11 were reduced in rtr1Δ, whereas interactions with the CTD and RNA-binding termination factor Nrd1 were increased. These changes could be the result of altered interactions between the termination machinery and/or increased levels of premature termination of RNAPII. Transcriptome analysis in rtr1Δ cells found decreased pervasive transcription and a shift in balance of expression of sense and antisense transcripts. Globally, rtr1Δ leads to decreases in noncoding RNAs that are linked to the Nrd1, Nab3 and Sen1 (NNS)-dependent RNAPII termination pathway. Genome-wide analysis of RNAPII and Nrd1 occupancy suggests that loss of RTR1 leads to increased termination at noncoding genes and increased efficiency of snRNA termination. Additionally, premature termination increases globally at protein-coding genes where NNS is recruited during early elongation. The effects of rtr1Δ on RNA expression levels were erased following deletion of the exosome subunit Rrp6, which works with the NNS complex to rapidly degrade terminated noncoding RNAs. Overall, these data suggest that Rtr1 restricts the NNS-dependent termination pathway in WT cells to prevent premature RNAPII termination of mRNAs and ncRNAs. Additionally, Rtr1 phosphatase activity facilitates low-level elongation of noncoding transcripts that impact the transcriptome through RNAPII interference.AUTHOR SUMMARYMany cellular RNAs including those that encode for proteins are produced by the enzyme RNA Polymerase II. In this work, we have defined a new role for the phosphatase Rtr1 in the regulation of RNA Polymerase II progression from the start of transcription to the 3’ end of the gene where the nascent RNA from protein-coding genes is typically cleaved and polyadenylated. Deletion of the gene that encodes RTR1 leads to changes in the interactions between RNA polymerase II and the termination machinery. Rtr1 loss also causes early termination of RNA Polymerase II at many of its target gene types including protein coding genes and noncoding RNAs. Evidence suggests that the premature termination observed in RTR1 knockout cells occurs through the termination factor and RNA binding protein Nrd1 and its binding partner Nab3. Additionally, many of the prematurely terminated noncoding RNA transcripts are degraded by the Rrp6-containing nuclear exosome, a known component of the Nrd1-Nab3 termination coupled RNA degradation pathway. These findings suggest that Rtr1 normally promotes elongation of RNA Polymerase II transcripts through preventation of Nrd1-directed termination.

Hypercalcemia most often results from primary hyperparathyroidism and malignancy. Adynamic bone disease (ABD) is a form of renal osteodystrophy characterized by reduced bone turnover, which can limit the ability of bone to release or store calcium, potentially leading to low, normal, or high serum calcium levels. We describe a 51‐year‐old dialysis‐dependent female with hypercalcemia after parathyroidectomy. A demeclocycline‐labeled bone biopsy confirmed adynamic bone disease. Teriparatide, a recombinant form of parathyroid hormone (PTH) used to treat postmenopausal osteoporosis, was prescribed for 12 months and normalized serum calcium levels. Although previous case reports and series have described favorable changes in spine bone mineral density when teriparatide was prescribed for ABD, ours is the first documented case in which teriparatide resolved hypercalcemia due to ABD. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

We report on the structural and electrical properties of epitaxial SmN thin films grown by molecular beam epitaxy. The effect of the growth temperature and nitrogen precursor, either pure molecular N 2 or NH 3 was investigated. The structural quality of SmN was assessed by X-ray diffraction and the epitaxial growth character is observed over the entire range of growth temperatures, from 300°C to 800°C, with both nitrogen precursors. The highest quality films are produced at a growth temperature of about 430°C by using N 2 as a nitrogen precursor. Hall Effect and resistivity measurements establish that SmN films are heavily n-type doped semiconductors, suggesting the presence of nitrogen vacancies, a recurring phenomenon in rare earth nitride compounds.

This work describes RTPV-PhC-1, an initial prototype for a radioisotope thermophotovoltaic (RTPV) system using a two-dimensional photonic crystal emitter and low bandgap thermophotovoltaic (TPV) cell to realize spectral control. We validated a system simulation using the measurements of RTPV-PhC-1 and its comparison setup RTPV-FlatTa-1 with the same configuration except a polished tantalum emitter. The emitter of RTPV-PhC-1 powered by an electric heater providing energy equivalent to one plutonia fuel pellet reached 950 °C with 52 W of thermal input power and produced 208 mW output power from 1 cm2 TPV cell. We compared the system performance using a photonic crystal emitter to a polished flat tantalum emitter and found that spectral control with the photonic crystal was four times more efficient. Based on the simulation, with more cell areas, better TPV cells, and improved insulation design, the system powered by a fuel pellet equivalent heat source is expected to reach an efficiency of 7.8%.

We report on the occurrence of rotational domains involving 4-fold symmetric epitaxy on a hexagonal net, a rare case in the literature. A temperature-driven crossover from fully (111)- to (001)-oriented samarium nitride grown by molecular beam epitaxy on hexagonal (0001) aluminum nitride is observed by means of in situ reflection high energy electron diffraction, scanning tunnelling microscopy studies, and ex situ X-ray diffraction. Using an especially rich set of growth conditions and nitrogen precursors, we observe the key role played by the growth kinetics, with a strong thermal cracking of the ammonia source and a re-evaporation of Sm adatoms occurring in the same temperature range of the orientation crossover.

We report on the effect of the nitrogen to rare earth (N2/RE) flux ratio on the structural, transport, and magnetic properties of samarium nitride (SmN) and dysprosium nitride (DyN) thin films. Both materials display a reduced lattice constant when the N2/RE flux ratio decreases, i.e., with increased nitrogen vacancies (VN) concentration. The films show several orders of magnitude increase in the electrical resistivity with increased N2/RE flux ratio. Finally, magnetic measurements on DyN films display a deviation from the free ion moment at low temperature, which is eased in more conductive films. This was interpreted as a further reduction in the quenching of the orbital angular momentum caused by the increased VN concentration. The Curie temperature was also found to increase with VN.

We present a study of polycrystalline thin films of the rock salt rare earth nitride GdN grown on amorphous fused silica at ambient temperature with varying N2 pressure. X-ray diffraction measurements show a strong (111) preferential orientation for all N2 pressure and the signature of a secondary phase of GdN that develops as the N2 pressure decreases. The secondary phase is found to have a smaller lattice parameter than the near-stoichiometric GdN. Raman spectroscopy, electrical and magnetic results support the coexistence of such mixed-phase samples with the lattice distortion originating from nitrogen vacancies. Significantly the magnetic data show an increase of the ferromagnetic onset temperature as the secondary phase develops, without affecting the soft ferromagnetic character of GdN.

Protein interacting with C kinase (PICK1) is a scaffolding protein that is present in dendritic spines and interacts with a wide array of proteins through its PDZ domain. The best understood function of PICK1 is regulation of trafficking of AMPA receptors at neuronal synapses via its specific interaction with the AMPA GluA2 subunit. Disrupting the PICK1-GluA2 interaction has been shown to alter synaptic plasticity, a molecular mechanism of learning and memory. Lack of potent, selective inhibitors of the PICK1 PDZ domain has hindered efforts at exploring the PICK1-GluA2 interaction as a therapeutic target for neurological diseases. Here, we report the discovery of PICK1 small molecule inhibitors using a structure-based drug design strategy. The inhibitors stabilized surface GluA2, reduced Aβ-induced rise in intracellular calcium concentrations in cultured neurons, and blocked long term depression in brain slices. These findings demonstrate that it is possible to identify potent, selective PICK1-GluA2 inhibitors which may prove useful for treatment of neurodegenerative disorders.

Recent advances in photonic crystals have enabled high-efficiency thermophotovoltaic (TPV) energy conversion by allowing near-perfect spectral control. In this paper, photonic crystals fabricated in thick tantalum (Ta) coatings, sputtered onto a metallic substrate, were investigated as a potential replacement for photonic crystals fabricated in bulk refractory metal substrates in TPV applications. A 2-D photonic crystal was fabricated in a 30- $\mu \rm m$ thick Ta sputtered coating using standard semiconductor processes as a proof-of-concept for a selective emitter/solar absorber. The reflectance of the fabricated photonic crystal coating was characterized before and after 1 h anneals at 700, 900, and 1100 $^\circ$ C, and after a 24 h anneal at 900 $^\circ$ C. To protect its surface during the anneals, a thin conformal hafnia (HfO $_2)$ layer was deposited by atomic layer deposition on the photonic crystal. The photonic crystal showed high spectral selectivity in good agreement with numerical simulations and sustained the anneals with minimal structural degradation or change in its optical properties. This study presents a promising alternative to bulk substrates as a relatively low-cost and easily integrated platform for nanostructured devices in high-temperature energy conversion systems.

A route to break molecular nitrogen (N2) under mild conditions is demonstrated by N2 gas cracking on, and incorporation into, lanthanide films. Successful growth of lanthanide nitride thin films, made by evaporation of lanthanides in a partial N2 atmosphere at room temperature and pressure as low as 10-4 Torr, is confirmed using X-ray diffraction. In-situ conductance measurements of pure lanthanide thin films exposed to N2 gas show an immediate surface reaction and a slower bulk reaction. Finally, we report partial reversal of the nitrogen incorporation in a lanthanide nitride by cycling vacuum and nitrogen conditions in the sample chamber.A route to break molecular nitrogen (N2) under mild conditions is demonstrated by N2 gas cracking on, and incorporation into, lanthanide films. Successful growth of lanthanide nitride thin films, made by evaporation of lanthanides in a partial N2 atmosphere at room temperature and pressure as low as 10-4 Torr, is confirmed using X-ray diffraction. Insitu conductance measurements of pure lanthanide thin films exposed to N2 gas show an immediate surface reaction and a slower bulk reaction. Finally, we report partial reversal of the nitrogen incorporation in a lanthanide nitride by cycling vacuum and nitrogen conditions in the sample chamber.

UNLABELLED This field study measured ventilation rates and indoor air quality in 21 visits to retail stores in California. Three types of stores, such as grocery, furniture/hardware stores, and apparel, were sampled. Ventilation rates measured using a tracer gas decay method exceeded the minimum requirement of California's Title 24 Standard in all but one store. Concentrations of volatile organic compounds (VOCs), ozone, and carbon dioxide measured indoors and outdoors were analyzed. Even though there was adequate ventilation according to standard, concentrations of formaldehyde and acetaldehyde exceeded the most stringent chronic health guidelines in many of the sampled stores. The whole-building emission rates of VOCs were estimated from the measured ventilation rates and the concentrations measured indoor and outdoor. Estimated formaldehyde emission rates suggest that retail stores would need to ventilate at levels far exceeding the current Title 24 requirement to lower indoor concentrations below California's stringent formaldehyde reference level. Given the high costs of providing ventilation, effective source control is an attractive alternative. PRACTICAL IMPLICATIONS Field measurements suggest that California retail stores were well ventilated relative to the minimum ventilation rate requirement specified in the Building Energy Efficiency Standards Title 24. Concentrations of formaldehyde found in retail stores were low relative to levels found in homes but exceeded the most stringent chronic health guideline. Looking ahead, California is mandating zero energy commercial buildings by 2030. To reduce the energy use from building ventilation while maintaining or even lowering formaldehyde in retail stores, effective formaldehyde source control measures are vitally important.

A biodegradable alternative material to synthetic plastics was explored in this study through the extrusion of soy protein isolate (SPI) composite films containing soy cellulose microfibers (SMF). SMF were isolated from soy pods and stems using a chemo-mechanical method. The fibers produced through successive treatments were characterized by microscopy, x-ray diffraction, and Fourier transform infrared analysis. SMF/SPI composite films (0.08 to 0.3 mm thick), containing different concentrations of cellulose fibers, were produced using a single-screw extruder (0.625″ screw; 24 : 1 L/D ratio; 100 – 120 min−1; 120 to 150 °C barrel temperature) and characterized. Homogenous films with uniform distribution of SMF were obtained with the highest concentration of 0.5 % w/w SMF/SPI. Increasing fiber content resulted in the formation of aggregates. As with other protein films, mechanical properties of the extruded pristine SPI and composite films were negatively affected by humidity. At the optimal concentration of 0.25 % w/w SMF/SPI, films exhibited improved mechanical performance at elevated relative humidity (84 %) when compared to the pristine SPI films.

Survival of tissue engineered constructs after implantation depends on proper vascularization. The differentiation of endothelial cells into mature microvasculature requires dynamic interactions between cells, scaffold, and growth factors, which are difficult to recapitulate in artificial systems. Previously, we reported photocrosslinked poly(ethylene glycol) diacrylate (PEGDA) hydrogels displaying collagen mimetic peptides (CMPs), dubbed PEGDA-CMP, that can be further conjugated with bioactive molecules via CMP-CMP triple helix hybridization. Here, we report that a bifunctional peptide featuring pro-angiogenic domain mimicking vascular endothelial growth factor (VEGF), and a collagen mimetic domain that can fold into a triple helix conformation can hybridize with CMP side chains of the PEGDA-CMP hydrogel, which results in presentation of insoluble VEGF-like signals to endothelial cells. Presentation of VEGF-like signals on the surface of micropatterned scaffolds in this way transforms cells from a quiescent state to elongated and aligned phenotype suggesting that this system could be used to engineer organized microvasculature. We also show that the pro-angiogenic peptide, when applied topically in combination with modified dextran/PEGDA hydrogels, can enhance neovascularization of burn wounds in mice demonstrating the potential clinical use of CMP-mediated matrix-bound bioactive molecules for dermal injuries.

An analogue of the anticancer drug cisplatin (mtPt) was delivered to mitochondria of human cells using a peptide specifically targeting this organelle. mtPt induces apoptosis without damaging nuclear DNA, indicating that mtDNA damage is sufficient to mediate the activity of a platinum-based chemotherapeutic. This study is the first to demonstrate specific delivery of a platinum drug to mitochondria and to investigate the effects of directing this agent outside the nucleus.

While DeKalb County, Georgia, offers free radon screening for all eligible residents, portions of the county remain relatively under-sampled. This pilot study focused on 10% of the census tracts in the county with the lowest proportion of radon testing; most were in southern DeKalb County. In total, 217 households were recruited and homes were tested for indoor radon concentrations on the lowest livable floor over an eight-week period from March–May 2015. Tract-level characteristics were examined to understand the differences in socio-demographic and economic factors between the pilot study area and the rest of the county. The pilot study tracts had a higher proportion of African Americans compared to the rest of DeKalb County (82% versus 47%). Radon was detected above 11.1 Bq/m3 (0.3 pCi/L) in 73% of the indoor samples and 4% of samples were above 148 Bq/m3 (4 pCi/L). Having a basement was the strongest predictive factor for detectable and hazardous levels of radon. Radon screening can identify problems and spur homeowners to remediate but more research should be done to identify why screening rates vary across the county and how that varies with radon levels in homes to reduce radon exposure.

Author(s): Chan, Wanyu R.; Maddalena, Randy L; Stratton, Chris; Hotchi, Toshifumi; Singer, Brett C.; Walker, Iain S.; Sherman, Max H. | Abstract: The Healthy Efficient New Gas Homes (HENGH) is a field study that will collect data on ventilation systems and indoor air quality (IAQ) in new California homes that were built to 2008 Title 24 standards. A pilot test was performed to help inform the most time and cost effective approaches to measuring IAQ in the 100 test homes that will be recruited for this study. Two occupied, single-family detached homes built to 2008 Title 24 participated in the pilot test. One of the test homes uses exhaust-only ventilation provided by a continuous exhaust fan in the laundry room. The other home uses supply air for ventilation. Measurements of IAQ were collected for two weeks. Time-resolved concentrations of particulate matter (PM), nitrogen dioxide (NO2), carbon dioxide (CO2), carbon monoxide (CO), and formaldehyde were measured. Measurements of IAQ also included time-integrated concentrations of volatile organic compounds (VOCs), volatile aldehydes, and NO2. Three perfluorocarbon tracers (PFTs) were used to estimate the dilution rate of an indoor emitted air contaminant in the two pilot test homes. Diagnostic tests were performed to measure envelope air leakage, duct leakage, and airflow of range hood, exhaust fans, and clothes dryer vent when accessible. Occupant activities, such as cooking, use of range hood and exhaust fans, were monitored using various data loggers. This document describes results of the pilot test.

The integration of functional polymers and semiconducting nanorods can lead to properties unattainable by either of the components independently. Elongated nanocrystals provide advantageous anisotropic physical properties which could be uniquely harnessed via integration into hybrid materials, if control over their orientation could be imposed. Controlling this orientation of anisotropic nanocrystals in polymer composites is challenging due to the presence of multiple interactions between the nanorods, polymer, and surfaces of the films. This study demonstrates a simple yet versatile method to obtain vertically aligned nanorod arrays in polymer composites over large areas. Comparison of systems consisting of rods of varying geometry and chemistry of ligand and/or polymer indicates that nanorod–nanorod interactions dominate the self-assembly behavior of the nanocrystals, while weak polymer–nanorod interactions can lead to independent co-self-assembly of each of the components in the system and allow for th...

MR techniques using hyperpolarized (13)C have successfully produced examples of angiography and intermediary metabolic imaging, but, to date, no receptor imaging has been attempted. The goal of this study was to synthesize and evaluate a novel hyperpolarizable molecule, 2,2,3,3-tetrafluoropropyl 1-(13)C-propionate-d(2,3,3) (TFPP), for the detection of atheromatous plaques in vivo. TFPP binds to lipid bilayers and its use in hyperpolarized MR could prove to be a major step towards receptor imaging. The precursor, 2,2,3,3-tetrafluoropropyl 1-(13)C-acrylate-d(2,3,3) (TFPA), binds to 1,2-dimyristoylphosphatidylcholine lipid bilayers with a 1.6-ppm chemical shift in the (19)F MR spectrum. This molecule was designed to be hyperpolarized through the addition of parahydrogen to the (13)C-acrylate moiety by parahydrogen-induced polarization. TFPA was hyperpolarized to TFPP to an extent similar to that of the hydroxyethylacrylate to hydroxyethylpropionate transition: 17 ± 4% for TFPP versus 20% for hydroxyethylpropionate; T(1) relaxation times (45 ± 2 s versus 55 ± 2 s) were comparable and the hyperpolarized properties of TFPP were characterized. Hydroxyethylacrylate, like TFPA, has a chemical structure with an acrylate moiety, but does not contain the lipid-binding tetrafluoropropyl functional group. Hyperpolarized TFPP binds to the lipid bilayer, appearing as a second, chemically shifted (13)C hyperpolarized MR signal with a further reduction in the longitudinal relaxation time (T(1) = 21 ± 1 s). In aortas harvested from low-density lipoprotein receptor knock-out mice fed with a high-fat diet for 9 months, and in which atheroma is deposited in the aorta and heart, TFPP showed greater binding to lipid on the intimal surface than in control mice fed a normal diet. When TFPP was hyperpolarized and administered in vivo to atheromatous mice in a pilot study, increased binding was observed on the endocardial surface of the intact heart compared with normally fed controls. Hyperpolarized TFPP has bio-sensing specificity for lipid, coupled with a 42,000-fold sensitivity gain in the MR signal at 4.7 T. Binding of TFPP with lipids results in the formation of a characteristic second peak in MRS. TFPP therefore has the potential to act as an in vivo molecular probe for atheromatous plaque imaging and may serve as a model of receptor-targeted bio-imaging with enhanced MR sensitivity.

Thermophotovoltaic (TPV) systems are promising for harnessing solar energy, waste heat, and heat from radioisotope decay or fuel combustion. TPV systems work by heating an emitter that emits light that is converted to electricity. One of the key challenges is designing an emitter that not only preferentially emits light in certain wavelength ranges but also simultaneously satisfies other engineering constraints. To elucidate these engineering constraints, we first provide an overview of the state of the art, by classifying emitters into three categories based on whether they have been used in prototype system demonstrations, fabricated and measured, or simulated. We then present a systematic approach for assessing emitters. This consists of five metrics: optical performance, ability to scale to large areas, stability at high temperatures, ability to integrate into the system, and cost. Using these metrics, we evaluate and discuss the reported results of emitters used in system demonstrations. Although there are many emitters with good optical performance, more studies on their practical attributes are required, especially for those that are not yet used in prototype systems. This framework can serve as a guide for the development of emitters for long-lasting, high-performance TPV systems.

Applications for noninvasive real-time imaging of apoptosis and neuronal degeneration are hindered by technical limitations in imaging strategies and by existing probes. Monitoring the progression of a cell through apoptosis could provide valuable insight into the temporal events that initiate cell death as well as the potential for rescue of apoptotic cells. We engineered an annexin-based biosensor to function as a polarity-sensitive indicator for viability and apoptosis (known as psIVa) by binding to externalized phosphatidylserine (ps) exposed on apoptotic cell membranes. constructed from a structure-based design strategy, psIVa fluoresces only when bound to ps and remains effectively undetectable in solution. In this paper, we describe protocols for the design, expression, purification and labeling of psIVa as well as for its application in time-lapse imaging of degenerating neurons in culture; the entire protocol can be completed in 2 weeks. the primary advantage of this method is the flexibility to use psIVa, in combination with other probes and without perturbing experimental conditions, to explore the cellular mechanisms involved in apoptosis and degeneration in real time.

A molecular simulation study of the mesoscale self-assembly of tethered nanoparticles having a cubic geometry is presented. Minimal models of the tethered nanocubes are developed to represent a polyhedral oligomeric silsesquioxane (POSS) molecule with polymeric substituents. The models incorporate some of the essential structural features and interaction specificity of POSS molecules, and facilitate access to the long length and timescales pertinent to the assembly process while foregoing atomistic detail. The types of self-assembled nanostructures formed by the tethered nanocubes in solution are explored via Brownian dynamics simulations using these minimal models. The influence of various parameters, including the conditions of the surrounding medium, the molecular weight and chemical composition of the tether functionalities, and the number of tethers on the nanocube, on the formation of specific structures is demonstrated. The role of cubic nanoparticle geometry on self-assembly is also assessed by comparing the types of structures formed by tethered nanocubes and by their flexible coil triblock copolymer and tethered nanosphere counterparts. Morphological phase diagrams are proposed to describe the behavior of the tethered nanocubes.

Hg vapor concentrations were measured in an indoor full-scale test environment representative of homes in the rural highlands of Peru, the location of an Hg spill in June 2000. We tested several scenarios of liquid Hg spilled onto a compacted dirt floor in a test room to determine the effect of various parameters, including liquid Hg surface area, temperature, air change rate, and Hg oxidation on room vapor concentrations. The measurements demonstrated that an increase in surface area and/or temperature significantly increased the evaporation rate, whereas oxidation (or age of the Hg) reduced the evaporation rate. We also verified that the Hg vapor analyzers used to test indoor air were capable of detecting very small spills.

Purpose: The energy-yielding mitochondrial Krebs cycle has been shown in many cancers and other diseases to be inhibited or mutated. In most cells, the Krebs cycle with oxidative phosphorylation generates approximately 90% of the adenosine triphosphate in the cell. We designed and hyperpolarized carbon-13 labeled Succinate (SUC) and its Derivative Diethyl Succinate (DES) to interrogate the Krebs cycle in real-time in cancer animal models. Procedures: Using Parahydrogen Induced Polarization (PHIP), we generated hyperpolarized SUC and DES by hydrogenating their respective fumarate precursors. DES and SUC metabolism was studied in five cancer allograft animal models: breast (4T1), Renal Cell Carcinoma (RENCA), colon (CT26), lymphoma NSO, and lymphoma A20. Results: The extent of hyperpolarization was 8 ± 2% for SUC and 2.1 ± 0.6% for DES. The metabolism of DES and SUC in the Krebs cycle could be followed in animals 5 s after tail vein injection. The biodistribution of the compounds was observed using 13C FISP imaging. We observed significant differences in uptake and conversion of both compounds in different cell types both in vivo and in vitro. Conclusion: With hyperpolarized DES and SUC, we are able to meet many of the requirements for a useable in vivo metabolic imaging compound – high polarization, relatively long T1 values, low toxicity and high water solubility. However, succinate and its derivative DES are metabolized robustly by RENCA but not by the other cancer models. Our results underscore the heterogeneity of cancer cells and the role cellular uptake plays in hyperpolarized metabolic spectroscopy.

Polyhedral oligomeric silsesquioxanes (POSS) are multifunctional molecules that can be employed as building blocks to develop nanocomposite materials whose mechanical properties often improve upon those of traditional polymeric materials. We report here molecular simulation results for the effective potential of mean force between octamethyl POSS monomers and between POSS monomers in which one methyl group has been substituted by a linear alkane chain of nine carbon atoms in liquid normal hexane at 300 and 400 K. The results are discussed and compared to available data for the effective interactions between octamethyl POSS monomers in normal hexadecane. Our results show that the effective short-ranged POSS-POSS attraction is significantly weaker in hexane than it is in hexadecane, perhaps explaining why normal hexane is often the solvent of choice for the preparation of POSS-containing materials. Additionally, we provide results for the radial distribution functions between selected sites in the POSS monomers that can be used both to understand the association between POSS monomers in solution and to parametrize coarse-grained simulation models. Such models will be used to study the formation of POSS-containing supramolecular structures such as lamellae or micelles that are currently not accessible by atomistic simulation and can be compared to experimental observations.

Cubic symmetry in octasilsesquioxanes ([RSiO1.5]8, diameter 1 nm) places functionality in each octant in Cartesian space, enabling nanometer-scale construction of materials with subtle tailoring of global properties. Diverse studies of OPS (octasilsesquioxanes) range from their ordering in solids (nanocomposites) to catalysts, NMR standards, and spacecraft coatings. The prototypical OPS (R = phenyl) is air-stable to temperatures above 500 °C; however, high symmetry and crystallinity limit its maximum solubility to 100 mg per 100 mL CH2Cl2, rendering attempts at functionalization very difficult. In an effort to couple early work on liquid-crystalline (LC) silsesquioxanes with recent efforts to functionalize OPS, we explored Friedel–Crafts alkylation by AlCl3, despite the potential for Si–C bond cleavage. However, its easy nitration in fuming HNO3 offered encouragement. The impetus was to add sufficient alkyl groups to disrupt registry between OPS molecules, thereby reducing crystallinity to produce LC and/or high-temperature lubricants. Here, we report that Friedel–Crafts alkylation of OPS leads to alkylxOPS materials with rigid 1 nm cores, which are surrounded by a hydrocarbon layer that acts as a lubricant to these hard spheres or nano-ball-bearings. Surprisingly, the butyl and hexyl derivatives are air-stable and liquid over a 70–400 °C range, whereas the octyl and decyl derivatives are stable only over a 30–300 °C range. Molecular modeling studies suggest that the unusual 100 °C difference in thermal stability arises because the shorter chains interdigitate even in the liquid state. This behavior is similar to that predicted and seen recently for alkylthiol-modified superlattices, suggesting that alkylxOPS materials may serve as models of superlattices. These materials offer potential as high-temperature lubricants. Furthermore, interdigitation suggests that alkylxOPS-based systems might serve as nanogears or as nanoscale Velcro when affixed to surfaces. Friedel–Crafts alkylation (nRBr, see Supporting Information) of OPS produces alkylxOPS, with typical 7:3 ratios of branched/normal alkyl groups. Cleavage of Si–C bonds (by using nBu4NF) coupled with analysis by C NMR and matrixassisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS, see Fig. S1 in the Supporting Information) distinguish individual alkylation products and the average numbers of alkyl groups per phenyl for each nRBr. Table 1 summarizes the results of gel-permeation chromatography (GPC) and viscosity measurements. Table 2 C M M U N IC A TI O N

Using matrix assisted laser desorption ionisation mass spectrum (MALDI-MS), this study reports the observations of the fouling distribution and composition along the membrane channel after the membranes were subjected to ultrafiltration of protein mixture solution in a crossflow module with and without spacer. In the fouling layer on a fully retentive membrane, the protein components with high molecular weight has higher presentation after 2 h of filtration and the presentation reduced to be lower than the smaller components after 6 h of filtration due to protein exchange and displacement phenomena in deposition layer caused by the differences in structure and diffusivity of different components. The protein exchange and replacement in the deposition layer was also observed on partial retentive membrane using a sequential fouling procedure. Fouling distribution along the membrane channel with spacer inserted in the module was more uniform and the flux was higher than that without spacer despite higher protein deposition observed in some cases.

Long term survival and success of artificial tissue constructs depend greatly on vascularization. Endothelial cell (EC) differentiation and vasculature formation are dependent on spatio-temporal cues in the extracellular matrix that dynamically interact with cells, a process difficult to reproduce in artificial systems. Here we present a novel bifunctional peptide that mimics matrix-bound vascular endothelial growth factor (VEGF) and can be used to encode spatially controlled angiogenic signals in collagen scaffolds. The peptide is comprised of a collagen mimetic domain that was previously reported to bind to type I collagen by a unique hybridization mechanism, and a VEGF mimetic domain with pro-angiogenic activity. Circular dichroism and collagen binding studies confirm the triple helical structure and the collagen binding affinity of the collagen mimetic domain, and EC culture studies demonstrate the peptide's ability to induce endothelial cell morphogenesis and network formation as a matrix-bound factor in 2D and 3D collagen scaffolds. We also show spatial modification of collagen substrates with this peptide that allows localized EC activation and network formation. These results demonstrate that the peptide can be used to present spatially directed angiogenic cues in collagen scaffolds, which may be useful for engineering organized microvasculature.

Thick sputtered tantalum (Ta) photonic crystal (PhC) coatings on Inconel were investigated as a potential replacement for bulk refractory metal substrates used for high-temperature emitters and absorbers in thermophotovoltaic energy conversion applications, where high-temperature stability and high reflectance of the surface in the infrared wavelength range are critical in order to sustain high operational temperatures and reduce losses due to waste heat. A selective emitter and solar absorber 2D PhC were fabricated in 8 and 30 micron sputtered Ta coatings, respectively, using standard semiconductor processes as a proof of concept. The fabricated PhCs showed high spectral selectivity in good agreement with the numerical simulations. The PhCs, coated with a thin HfO2 protective layer, sustained one hour anneals at 700, 900, and 1100°C with very little structural degradation or change in their optical properties. This study presents a promising alternative to bulk substrates as a relatively low-cost and easily integrated platform for nano-structured devices for high-temperature applications.

Hard red spring wheat (Triticum aestivum cv Butte86) was grown under controlled environmental conditions and grain produced under 24/17 °C, 37/17 °C or 37/28 °C day/night regimens with or without post-anthesis N supplied as NPK. Flour proteins were analyzed and quantified by differential fractionation and RP-HPLC, and endosperm proteins were assessed by two-dimensional gel electrophoresis (2-DE). High temperature or NPK during grain fill increased protein percentage and altered the proportions of S-rich and S-poor proteins. Addition of NPK increased protein accumulation per grain under the 24/17 °C but not the 37/28 °C regimen. However, flour protein composition was similar for grain produced with NPK at 24/17 °C or 37/28 °C. 2-DE of gluten proteins during grain development revealed that NPK or high temperature increased the accumulation rate for S-poor proteins more than for S-rich proteins. Flour S content did not indicate S-deficiency, however, and addition of post-anthesis S had no effect on protein composition. Although, high-protein flour from grain produced under the 37/28 °C regimen with or without NPK had loaf volumes comparable to flour produced at 24/17 °C with NPK, mixing tolerance was decreased by the high temperature regimen.

We perform molecular simulations to study the self-assembly of tetratethered nanoparticles with a cubic geometry. We develop a minimal model of the tethered nanoscale building block (NBB) to represent a polyhedral oligomeric silsesquioxane (POSS) molecule with polymeric functionalities based on information about the molecular structure and interactions obtained from ab initio density functional theory calculations. Using this model, we explore the rich nanostructures formed from self-assembly of the NBBs and make analogies with the morphologies observed in block copolymer, surfactant, and liquid crystalline systems. On the basis of the assembled structures produced and determination of the location and nature of the order-disorder transitions in the system, we propose phase diagrams to describe the behavior of these molecules. We find that qualitative similarities exist between the phase diagrams for the tetratethered NBBs and those for block copolymer and surfactant systems.

During the development of the peripheral nervous system, Schwann cells, the myelin-forming glia, migrate along axons before initiating myelination. We previously demonstrated that endogenous neurotrophin-3 (NT3) acting through the TrkC tyrosine kinase receptor enhances migration of premyelinating Schwann cells. This signaling pathway is mediated by the c-Jun N-terminal kinase (JNK) cascade regulated by the Rho GTPases Rac1 and Cdc42. However, missing is the link between TrkC and the GTPases. Here, we show that a guanine-nucleotide exchange factor (GEF), Dbl's big sister (Dbs), couples with TrkC to activate Cdc42 in Schwann cells. Furthermore, TrkC directly phosphorylates Dbs, thereby inducing the Cdc42-GEF activity. Taken together, activation of TrkC triggers Schwann cell migration by regulating Dbs upon direct tyrosine phosphorylation, providing a mechanism whereby a membrane receptor tyrosine kinase can induce the activation of Rho GTPase-GEFs.

Properties of phosphatidylinositol synthase (PtdIns-synthase) from the ciliate Tetrahymena were investigated using microsomal fractions enriched for the enzyme. Optimum conditions for PtdIns-synthase activity as assayed in a Triton X-100/CDP-DAG mixed micelle system with [3H] myo-Ins as co-substrate were a pH of 8.0 using 50 mM Tris-HCl buffer and a temperature of 30°C. Incubation of PtdIns-synthase at pre-selected temperatures prior to assay at 30°C showed that the enzyme was stable for at least 20 min at 40°C. A sharp decline in activity was seen after incubation at 50°C for 20 min. Activity was stimulated by 2 mM Mg2+, and stimulated to a slightly lesser degree by 1 mM Mn2+; however, these two ions in combination were synergistic. Other metal cations (Ca, Co, Cu, Fe, Mo, Zn, and Li) at a concentration of 2 mM had no appreciable effect on activity. Under optimum assay conditions, Tetrahymena PtdIns-synthase activity was linear over at least 20 min and was linear with increasing concentrations of the enzyme. The enzyme was capable of utilizing both [3H]scyllo-and [3H] (1D) chiro-Ins as substrate to form phosphatidyl-[3H]scyllo-and phosphatidyl-[3H](1D) chiro-inositol, respectively, with (1D)chiro-inositol being the least preferred substrate. The in vitro synthesized myo-and scyllo-inositol-containing phosphoinositides were susceptible to hydrolysis by Bacillus cereus phosphatidylinositol-specific phospholipase C, but the (1D) chiro-inositol phosphoinositide was resistant. We hypothesize that putative DAG and scyllo-IP3 second messengers produced by the cleavage of polyphospho-scyllo-inositides may function in novel transmembrane signaling cascades.

Hygroscopic growth of atmospheric particles affects a number of environmentally important aerosol properties. Due to the hysteresis exhibited by the aerosol hygroscopic growth, the physical state of particles and the amount of aerosol water are uncertain within a wide range of relative humidities (RHs) found in the troposphere, leading to uncertainties in optical and chemical properties of the aerosol. Here we report the design and tests of an automated system that was built to assess the amount of aerosol water at atmospheric conditions. The system consists of two scanning mobility particle sizers (SMPS) and an aerodynamic particle sizer (APS) that measure the aerosol size distribution between 3 nm and 10 μm in diameter. The inlets of the instruments and their sheath air lines are equipped with computer-controlled valves that direct air through Nafion dryers or bypass them. The Nafion dryers dehydrate the air streams to below 30% RH at which point ambient particles are expected to lose most or all water....

Glia constitute 90% of cells in the human nervous system, but relatively little is known about their functions. We have been focusing on the potential synaptic roles of glia in the CNS. We recently found that astrocytes increase the number of mature, functional synapses on retinal ganglion cells (RGCs) by sevenfold and are required for synaptic maintenance in vitro. These observations raised the question of whether glia similarly enhance synapse formation by other neuron types. Here we have investigated whether highly purified motor neurons isolated from developing rat spinal cords are able to form synapses in the absence of glia or whether glia similarly enhance synapse number. We show that spinal motor neurons (SMNs) form few synapses unless Schwann cells or astrocytes are present. Schwann cells increase the number of functional synapses by ninefold as measured by immunostaining, and increase spontaneous synaptic activity by several hundredfold. Surprisingly, the synapses formed between spinal motor neurons were primarily glutamatergic, as they could be blocked by CNQX. This synapse-promoting activity is not mediated by direct glial-neuronal cell contact but rather is mediated by secreted molecule(s) from the Schwann cells, as we previously found for astrocytes. Interestingly, the synapse-promoting activity from astrocytes and Schwann cells was functionally similar: Schwann cells also promoted synapse formation between retinal ganglion cells, and astrocytes promoted synapse formation between spinal motor neurons. These studies show that both astrocytes and Schwann cells strongly promote synapse formation between spinal motor neurons and demonstrate that glial regulation of synaptogenesis extends to other neuron types.

This paper investigates the performance and lifetime of a metal-to-metal shunt RF MEMS switch fabricated on an SI-GaAs substrate. The switch is a shunt bridge design that is compatible with standard microelectronic processing techniques. The RF performance of the switch includes actuation voltages of less than 15 V, isolation better than 20 dB from 0.25 to 40 GHz, and switching speeds of less than 22 /spl mu/s. Varying the geometry of the switch affects both switching voltage and reliability, and the tradeoffs are discussed. We have developed a cold switching test method to identify the root cause of sticking as a failure mechanism. The switch structure includes "separation posts" that eliminate sticking failure and has demonstrated lifetimes as high as 7/spl times/10/sup 9/ cold switching cycles. These results show that good reliability is possible with a metal-to-metal RF MEMS switch operated with a low actuation voltage.