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Carbon nanotubes (CNTs) are promising nanomaterials exhibiting high thermal and electrical conductivities, significant stiffness, and high tensile strength. As a result, CNTs have been utilized as additives to enhance properties of various polymeric materials in a broad range of fields. In this study, we investigated the release of CNTs from CNT epoxy nanocomposites exposed to environmental weathering and mechanical stresses. The presence and amount of CNTs released from degraded polymer nanocomposites is important because CNTs can impact physiological systems in humans and environmental organisms. The weathering experiments in this study included nanocomposite exposure to both UV and a water spray, to simulate sunlight and rain exposure, whereas mechanical stresses were induced by shaking and ultrasonication. CNT release from epoxy nanocomposites was quantified by a 14 C-labeling method that enabled measurement of the CNT release rates after different weathering and mechanical treatments. In this study, a sample oxidizer was used prior to liquid scintillation counting, because it was shown to reduce interferences from the presence of polymeric materials and achieve a high recovery (95%). Polymer nanocomposite degradation was confirmed by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), and light microscopy. A continuous release of 14 C-labeled nanomaterials was observed after each UV and simulated rain exposure period, with 0.23% (mass/mass) of the total embedded mass of CNTs being released from the CNT nanocomposite during the full weathering process, suggesting that the water spray induced sufficient mechanical stress to eliminate the protective effect of the surface agglomerated CNT network. Importantly, additional mechanical stresses imposed on the weathered nanocomposites by shaking and ultrasonication resulted in further release of approximately 0.27% (mass /mass)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Bioaccumulation is a key factor in understanding the potential ecotoxicity of substances. While there are well-developed models and methods to evaluate bioaccumulation of dissolved organic and inorganic substances, it is substantially more challenging to assess bioaccumulation of particulate contaminants such as engineered carbon nanomaterials (CNMs; carbon nanotubes (CNTs), graphene family nanomaterials (GFNs), and fullerenes) and nanoplastics. In this study, the methods used to evaluate bioaccumulation of different CNMs and nanoplastics are critically reviewed. In plant studies, uptake of CNMs and nanoplastics into the roots and stems was observed. For multicellular organisms other than plants, absorbance across epithelial surfaces was typically limited. Biomagnification was not observed for CNTs and GFNs but were observed for nanoplastics in some studies. However, the reported absorption in many nanoplastic studies may be a consequence of an experimental artifact, namely release of the fluorescent probe from the plastic particles and subsequent uptake. We identify that additional work is needed to develop analytical methods to provide robust, orthogonal methods that can measure unlabeled (e.g., without isotopic or fluorescent labels) CNMs and nanoplastics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

The ultraviolet (UV)-induced degradation of graphene/polymer nanocomposites was investigated in this study. Specifically, the effect of few-layer graphene nanofillers on the degradation of a thermoplastic polyurethane (TPU) and the release potential of graphene from the degraded nanocomposite surfaces were assessed. Graphene/TPU (G/TPU) nanocomposites and neat TPU were UV-exposed under both dry and humid conditions in the NIST SPHERE, a precisely controlled, high intensity UV-weathering device. Neat TPU and G/TPU were characterized over the time course of UV exposure using color measurements and infrared spectroscopy, for appearance and chemical changes, respectively. Changes in thickness and surface morphology were obtained with scanning electron microscopy. A new fluorescence quenching measurement approach was developed to identify graphene sheets at the nanocomposite surface, which was supported by contact angle measurements. The potential for graphene release from the nanocomposite surface was evaluated using a tape-lift method followed by microscopy of any particles present on the tape. The findings suggest that graphene improves the service life of TPU with respect to UV exposure, but that graphene becomes exposed at the nanocomposite surface over time, which may potentially lead to its release when exposed to small mechanical forces or upon contact with other materials., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

The interaction of anaerobic microorganisms with carbon nanotube/polymer nanocomposites (CNT/PNC) will play a major role in determining their persistence and environmental fate at the end of consumer use when these nano-enabled materials enter landfills and encounter wastewater. Motivated by the need to understand how different parameters (i.e., polymer type, microbial phenotype, CNT characteristics) influence CNT/PNC biodegradation rates, we have used volumetric biogas measurements and kinetic modeling to study biodegradation as a function of polymer type and CNT properties. In one set of experiments, oxidized multiwall carbon nanotubes (O-MWCNTs) with a range of CNT loadings 0-5% w/w were incorporated into poly-ε-caprolactone (PCL) and polyhydroxyalkanoates (PHA) matrices and subjected to biodegradation by an anaerobic microbial community. For each CNT/PNC, complete polymer biodegradation was ultimately observed, although the rate of biodegradation was inhibited above certain critical CNT loadings dependent upon the polymer type. Higher loadings of pristine MWCNTs were needed to decrease the rate of polymer biodegradation compared to O-MWCNTs, an effect ascribed principally to differences in CNT dispersion within the polymer matrices. Above certain CNT loadings, a CNT mat of similar shape to the initial PNC was formed after polymer biodegradation, while below this threshold, CNT aggregates fragmented in the media. In situations where biodegradation was rapid, methanogen growth was disproportionately inhibited compared to the overall microbial community. Analysis of the results obtained from this study indicates that the inhibitory effect of CNTs on polymer biodegradation rate is greatest under conditions (i.e., polymer type, microbial phenotype, CNT dispersion) where biodegradation of the neat polymer is slowest. This new insight provides a means to predict the environmental fate, persistence, and transformations of CNT-enabled polymer materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Carbon nanotubes (CNTs) have unique physical and chemical properties that drive their use in a variety of commercial and industrial applications. CNTs are commonly oxidized prior to their use to enhance dispersion in polar solvents by deliberately grafting oxygen-containing functional groups onto CNT surfaces. In addition, CNT surface oxides can be unintentionally formed or modified after CNTs are released into the environment through exposure to reactive oxygen species and/or ultraviolet irradiation. Consequently, it is important to understand the impact of CNT surface oxidation on the environmental fate, transport, and toxicity of CNTs. In this review, we describe the specific role of oxygen-containing functional groups on the important environmental behaviors of CNTs in aqueous media (e.g., colloidal stability, adsorption, and photochemistry) as well as their biological impact. We place special emphasis on the value of systematically varying and quantifying surface oxides as a route to identifying quantitative structure-property relationships. The role of oxygen-containing functional groups in regulating the efficacy of CNT-enabled water treatment technologies and the influence of surface oxides on other carbon-based nanomaterials are also evaluated and discussed.

Nanocoatings have numerous potential applications in the indoor environment, such as flooring finishes with increased scratch- and wear-resistance. However, given concerns about the potential environmental and human health effects of nanomaterials, it is necessary to develop standardized methods to quantify nanomaterial release during use of these products. One key choice for mechanical wear studies is the abrasion wheel. Potential limitations of different wheels include the release of fragments from the wheel during abrasion, wearing of the wheel from the abrasion process, or not releasing a sufficient number of particles for accurate quantitative analysis. In this study, we evaluated five different wheels, including a typically used silicon oxide-based commercial wheel and four wheels fabricated at the National Institute of Standards and Technology (NIST), for their application in nanocoating abrasion studies. A rapid, nondestructive laser scanning confocal microscopy method was developed and used to identify released particles on the abraded surfaces. NIST fabricated a high performing wheel: a noncorrosive, stainless-steel abrasion wheel containing a deep cross-patch. This wheel worked well under both wet and dry conditions, did not corrode in aqueous media, did not release particles from itself, and yielded higher numbers of released particles. These results can be used to help develop a standardized protocol for surface release of particles from nanoenabled products using a commercial rotary Taber abraser.

Graphene oxide (GO) is a good nanofiller candidate for waterborne coatings because of its outstanding physical and mechanical properties, good dispersibility in water, and low cost relative to graphene. Here, we report on the performance of a one-part, waterborne polyurethane (WPU) nanocoating formulated with four different GO loadings ([0.4% to 2.0%] by mass). The degree of GO dispersion/adhesion was evaluated using scanning electron microscopy, laser scanning confocal microscopy, and Raman microscopy. Nanocoating performance was evaluated using a dynamic mechanical thermal analyzer for mechanical properties, a customized coulometric permeation apparatus for oxygen barrier properties, a combustion microcalorimeter for flammability, a hot disk analyzer for thermal conductivity, thermogravimetric analysis for thermal stability, and a moisture sorption analyzer for water uptake. The results show that GO sheets were well dispersed in, and have good adhesion to, WPU. At the higher mass loadings ([1.2% or 2%] by mass), GO increased the modulus and yield strength of WPU by 300% and 200%, respectively, increased the thermal conductivity by 38%, reduced the burning heat release rate (flammability) by 43%, and reduced the oxygen permeability by up to sevenfold. The presence of GO, however, increased water vapor uptake at high humidity; the moisture content of 2% mass loading GO/WPU nanocoatings at 90% RH was almost twice that of the moisture content for unfilled WPU. Overall, with the exception of water uptake at very high humidity (> 70% RH), the observed improvements in physical and mechanical properties combined with the ease of processing suggest that GO is a viable nanofiller for WPU coatings.

Pigments with nanoscale dimensions are added to exterior coatings to achieve desirable color and gloss properties. The present study compared the performance, degradation, and release behavior of an acrylic coating that was pigmented by a nanoform of Cu-phthalocyanine after both natural (i.e., outdoor) and accelerated weathering. Samples were weathered outdoors in three geographically distinct locations across the United States (Arizona, Colorado, Maryland) continuously for 15 months. Identically prepared samples were also artificially weathered under accelerated conditions (increased ultraviolet (UV) light intensity and elevated temperatures) for three months, in one-month increments. After exposure, both sets of samples were characterized with color, gloss, and infrared spectroscopy measurements, and selectively with surface roughness measurements. Results indicated that UV-driven coating oxidation was the principal degradation pathway for both natural and accelerated weathering samples, with accelerated weathering leading to an increased rate of oxidation without altering the fundamental degradation pathway. The inclusion of the nanoform pigment reduced the rate of coating oxidation, via UV absorption by the pigment, leading to improved coating integrity compared to non-pigmented samples. Release measurements collected during natural weathering studies indicated there was never a period of weathering, in any location, that led to copper material release above background copper measurements. Lab-based release experiments performed on samples weathered naturally and under accelerated conditions found that the release of degraded coating material after each type of exposure was diminished by the inclusion of the nanoform pigment. Release measurements also indicated that the nanoform pigment remained embedded within the coating and did not release after weathering., Competing Interests: Declaration of competing interest The authors declare the following financial interest/personal relationship which may be considered as potential competing interest: ER, WW, KB, PM, SP, are employees of BASF, a company that produces and markets nanomaterials.

The extent to which hydrophilic GO nanofillers regulate polymer degradation during exposure to a combination of ultraviolet (UV) radiation and moisture is presently unknown. Accordingly, this study systematically evaluated the effect of GO on polymer degradability under both humid UV and dry UV conditions. Both GO accumulation at the polymer nanocomposite (PNC) surface and GO release following degradation were also investigated. Different mass loadings of GO were incorporated into waterborne polyurethane (WBPU), a commonly used exterior coating, and the resulting GO/WBPU nanocomposites were exposed to precisely controlled accelerated weathering conditions using the NIST Simulated Photodegradation via High Energy Radiant Exposure (SPHERE) device. Thickness loss and infrared spectroscopy measurements indicated GO slightly improved the durability of WBPU under dry UV conditions but not under humid UV conditions. Raman spectroscopy, scanning electron microscopy, and atomic force microscopy modulus measurements indicated that GO accumulation occurred at and near the PNC surface under both conditions but to a more rapid extent under humid UV conditions. Minimal GO release occurred under dry UV conditions as measured with Raman spectroscopy of aqueous run-off from a simulated rain spray applied to degraded PNCs. In contrast, PNC surface transformations under humid UV conditions suggested that GO release occurred.

Potential consumer exposure to nanoparticles (NPs) from nanoenabled food contact materials (FCMs) has been a driving force for migration studies of NPs from FCMs. Although NP migration from fresh, unused FCMs was not previously observed, conditions that result in significant changes to the surface of FCMs have not been investigated for NP migration into food. Therefore, a quantitative assessment of nanoparticle release from commercially available nanosilver-enabled FCMs was performed using an abrasion protocol to simulate cleaning, cutting, scraping and other stressful use conditions. Laser scanning confocal microscopy (LSCM) analysis showed a general increase in root mean square (RMS) roughness after FCM abrasion, and particle count (for particle sizes from 80 nm to 960 nm) at the surface was 4 orders of magnitude higher for the abraded FCMs. Migration was evaluated using both water and 3% (v/v, volume fraction) acetic acid as food simulants. Low concentrations of total Ag were detected in water simulants with a small portion (<10 ng dm -2 ) in the form of silver nanoparticles (AgNPs). Median particle diameter ranged from 39 nm to 50 nm with particle number concentrations on the order of 10 6 particles dm - 2 . Total Ag migration into 3% (v/v) acetic acid was significantly higher than in water; however, 3% (v/v) acetic acid was not suitable for evaluation of NP release due to dissolution of AgNPs to Ag + under acidic solution chemistries.

Potential consumer exposure to nanoparticles (NPs) from nanoenabled food contact materials (FCMs) has been a driving force for migration studies of NPs from FCMs. Although NP migration from fresh, unused FCMs was not previously observed, conditions that result in significant changes to the surface of FCMs have not been investigated for NP migration into food. Therefore, a quantitative assessment of nanoparticle release from commercially available nanosilver-enabled FCMs was performed using an abrasion protocol to simulate cleaning, cutting, scraping and other stressful use conditions. Laser scanning confocal microscopy (LSCM) analysis showed a general increase in root mean square (RMS) roughness after FCM abrasion, and particle count (for particle sizes from 80 nm to 960 nm) at the surface was 4 orders of magnitude higher for the abraded FCMs. Migration was evaluated using both water and 3% (v/v, volume fraction) acetic acid as food simulants. Low concentrations of total Ag were detected in water simulants with a small portion (<10 ng dm -2 ) in the form of silver nanoparticles (AgNPs). Median particle diameter ranged from 39 nm to 50 nm with particle number concentrations on the order of 10 6 particles dm - 2 . Total Ag migration into 3% (v/v) acetic acid was significantly higher than in water; however, 3% (v/v) acetic acid was not suitable for evaluation of NP release due to dissolution of AgNPs to Ag + under acidic solution chemistries.

Migration evaluation involving nano-enabled food contact materials (FCMs) mostly focuses on potential nanoparticle release from new unused products. This may not represent consumer use practices encountered by the FCMs in their lifecycle. In order to determine if product use impacts the release of nanoparticles or other FCM components, it is necessary to perform migration evaluations under typical consumer use scenarios. A quantitative assessment of nanoparticle release from a commercially available nanosilver-enabled cutting board was performed under five conditions intended to simulate consumer use. Knife motion, washing and scratching scenarios were simulated by linear abrasion using knife blades, scrubbing pads and tungsten carbide burr attachments, respectively. Migration was evaluated using water and 3% acetic acid as food simulants. Low concentrations of silver (Ag) were detected in water simulants, a small portion (<4 ng dm -2 ) in the form of silver nanoparticles (AgNPs) with particle number concentrations on the order of 10 6 particles dm -2 . Median particle diameter was 40 nm. Nanoparticle release into water was observed under all five consumer use scenarios studied, however there was no correlation with the different levels of stress simulated.

The properties and commercial viability of biodegradable polymers can be significantly enhanced by the incorporation of carbon nanotubes (CNTs). The environmental impact and persistence of these carbon nanotube/polymer nanocomposites (CNT/PNCs) after disposal will be strongly influenced by their microbial interactions, including their biodegradation rates. At the end of consumer use, CNT/PNCs will encounter diverse communities of microorganisms in landfills, surface waters, and wastewater treatment plants. To explore CNT/PNC biodegradation under realistic environmental conditions, the effect of multi-wall CNT (MWCNT) incorporation on the biodegradation of polyhydroxyalkanoates (PHA) was investigated using a mixed culture of microorganisms from wastewater. Relative to unfilled PHA (0% w/w), the MWCNT loading (0.5-10% w/w) had no statistically significant effect on the rate of PHA matrix biodegradation. Independent of the MWCNT loading, the extent of CNT/PNC mass remaining closely corresponded to the initial mass of CNTs in the matrix suggesting a lack of CNT release. CNT/PNC biodegradation was complete in approximately 20 days and resulted in the formation of a compressed CNT mat that retained the shape of the initial CNT/PNC. This study suggests that although CNTs have been shown to be cytotoxic towards a range of different microorganisms, this does not necessarily impact the biodegradation of the surrounding polymer matrix in mixed culture, particularly in situations where the polymer type and/or microbial population favor rapid polymer biodegradation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

An increase in production of commercial products containing graphene-family nanomaterials (GFNs) has led to concern over their release into the environment. The fate and potential ecotoxicological effects of GFNs in the environment are currently unclear, partially due to the limited analytical methods for GFN measurements. In this review, the unique properties of GFNs that are useful for their detection and quantification are discussed. The capacity of several classes of techniques to identify and/or quantify GFNs in different environmental matrices (water, soil, sediment, and organisms), after environmental transformations, and after release from a polymer matrix of a product is evaluated. Extraction and strategies to combine methods for more accurate discrimination of GFNs from environmental interferences as well as from other carbonaceous nanomaterials are recommended. Overall, a comprehensive review of the techniques available to detect and quantify GFNs are systematically presented to inform the state of the science, guide researchers in their selection of the best technique for the system under investigation, and enable further development of GFN metrology in environmental matrices. Two case studies are described to provide practical examples of choosing which techniques to utilize for detection or quantification of GFNs in specific scenarios. Because the available quantitative techniques are somewhat limited, more research is required to distinguish GFNs from other carbonaceous materials and improve the accuracy and detection limits of GFNs at more environmentally relevant concentrations.

The biodegradation rates of carbon nanotube (CNT)/ polymer nanocomposites (PNCs) containing poly-ε-caprolactone (PCL) were investigated using Pseudomonas aeruginosa, a microorganism commonly found in the environment. CNT/PCL nanocomposite mass loss profiles revealed that the rate of PCL matrix biodegradation decreased systematically as the CNT loading increased from 0.1 to 10% w/w. Addition of even a low CNT loading (<1% w/w) caused the CNT/PCL biodegradation rate constant to decrease by more than 50%. Similar trends in biodegradation rate were observed for both pristine and oxidized multiwall CNTs embedded in PCL. During PCL matrix biodegradation, CNT accumulation was observed at the surface of CNT/PCL nanocomposites and single particle inductively coupled-mass spectrometry experiments revealed no measurable CNT release to the culture fluid. Experimental data indicated that biodegradation proceeded as a result of biofilm formation on the CNT/PCL nanocomposites and decreased as a function of CNT loading due to the cytotoxicity of CNTs toward P. aeruginosa and the physical barrier presented by the surface-accumulated CNTs to the underlying PCL substrate. As the CNT loading in the CNT/PCL nanocomposites increased, the microbial proliferation of planktonic cells in the surrounding media also decreased as did the biodegradation rate of PCL samples present in the same reactors. Results from this study demonstrate that the inclusion of CNTs into polymer matrices could increase the environmental persistence of polymers in lakes, landfills, and surface waters.

Lethal influenza A virus infection leads to acute lung injury and possibly lethal complications. There has been a continuous effort to identify the possible predictors of disease severity. Unlike earlier studies, where biomarkers were analyzed on certain time points or days after infection, in this study biomarkers were evaluated over the entire course of infection. Circulating proinflammatory cytokines and/or miRNAs that track with the onset and progression of lethal A/Puerto Rico/8/34 (PR8) influenza A virus infection and their response to oseltamivir treatment were investigated up to 10 days after infection. Changes in plasma cytokines (IL-1β, IL-10, IL-12p70, IL-6, KC, TNF-α, and IFN-γ) and several candidate miRNAs were profiled. Among the cytokines analyzed, IL-6 and KC/GRO cytokines appeared to correlate with peak viral titer. Over the selected 48 miRNAs profiled, certain miRNAs were up- or downregulated in a manner that was dependent on the oseltamivir treatment and disease severity. Our findings suggest that IL-6 and KC/GRO cytokines can be a potential disease severity biomarker and/or marker for the progression/remission of infection. Further studies to explore other cytokines, miRNAs, and lung injury proteins in serum with different subtypes of influenza A viruses with varying disease severity may provide new insight into other unique biomarkers.

In many environmental scenarios, the fate and impact of polymer nanocomposites (PNCs) that contain carbon nanotubes (CNT/PNCs) will be influenced by their interactions with microorganisms, with implications for antimicrobial properties and the long-term persistence of PNCs. Using oxidized single-wall (O-SWCNTs) and multi-wall CNTs (O-MWCNTs), we explored the influence that CNT loading (mass fraction≤0.1%-10%) and type have on the initial interactions of Pseudomonas aeruginosa with O-CNT/poly(vinyl alcohol) (PVOH) nanocomposites containing well-dispersed O-CNTs. LIVE/DEAD staining revealed that, despite oxidation, the inclusion of O-SWCNTs or O-MWCNTs caused PNC surfaces to exhibit antimicrobial properties. The fraction of living cells deposited on both O-SWCNT and O-MWCNT/PNC surfaces decreased exponentially with increasing CNT loading, with O-SWCNTs being approximately three times more cytotoxic on a % w/w basis. Although not every contact event between attached microorganisms and CNTs led to cell death, the cytotoxicity of the CNT/PNC surfaces scaled with the total contact area that existed between the microorganisms and CNTs. However, because the antimicrobial properties of CNT/PNC surfaces require direct CNT-microbe contact, dead cells were able to shield living cells from the cytotoxic effects of CNTs, allowing biofilm formation to occur on CNT/PNCs exposed to Pseudomonas aeruginosa for longer time periods.

Graphene oxide (GO) is promising in scalable production and has useful properties that include semiconducting behavior, catalytic reactivity, and aqueous dispersibility. In this study, we investigated the photochemical fate of GO under environmentally relevant sunlight conditions. The results indicate that GO readily photoreacts under simulated sunlight with the potential involvement of electron-hole pair creation. GO was shown to photodisproportionate to CO2, reduced materials similar to reduced GO (rGO) that are fragmented compared to the starting material, and low molecular-weight (LMW) species. Kinetic studies show that the rate of the initially rapid photoreaction of GO is insensitive to the dissolved oxygen content. In contrast, at longer time points (>10 h), the presence of dissolved oxygen led to a greater production of CO2 than the same GO material under N2-saturated conditions. Regardless, the rGO species themselves persist after extended irradiation equivalent to 2 months in natural sunlight, even in the presence of dissolved oxygen. Overall, our findings indicate that GO phototransforms rapidly under sunlight exposure, resulting in chemically reduced and persistent photoproducts that are likely to exhibit transport and toxic properties unique from parent GO.

Multiwalled carbon nanotubes (MWNTs) are utilized in a number of sectors as a result of their favorable electronic properties. In addition, MWNT antimicrobial properties can be exploited or considered a potential liability depending on their intended application and handling. The ability to tailor electrochemical and antimicrobial properties using economical and conventional treatment processes introduces the potential to significantly enhance product performance. Oxygen functional groups are known to influence several MWNT properties, including redox activity. Here, MWNTs were functionalized with oxygen groups using standard acid treatments followed by selective reduction via annealing. Chemical derivatization coupled to X-ray photoelectron spectroscopy was utilized to quantify specific surface oxygen group concentration after variable treatment conditions, which were then correlated to observed trends in electrochemical and antimicrobial activities. These activities were evaluated as the potential for MWNTs to participate in the oxygen reduction reaction and to have the ability to promote the oxidation of glutathione. The compiled results strongly suggest that the reduction of surface carboxyl groups and the redox activity of carbonyl groups promote enhanced MWNT reactivity and elucidate the opportunity to design functional MWNTs for enhanced performance in their intended electrochemical or antimicrobial application.

We present a method for forming ordered rhodium nanostructures on a solid support. The approach makes use of a block copolymer to create and assemble rhodium chloride nanoparticles from solution onto a surface; subsequent plasma and thermal processing are employed to remove the polymer and fully convert the nanostructures to metallic rhodium. Films cast from a solution of the triblock copolymer poly(styrene-b-2-vinyl pyridine-b-ethylene oxide) dissolved in toluene with rhodium(III) chloride hydrate were capable of producing a monolayer of rhodium nanoparticles of uniform size and interparticle spacing. The nanostructures were characterized by scanning electron microscopy, X-ray photoelectron spectroscopy, and atomic force microscopy. The electrocatalytic performance of the nanoparticles was investigated with AC impedance spectroscopy. We observed that the addition of the particles to a model solid oxide fuel cell anode provided up to a 14-fold improvement in the anode activity as evidenced by a decrease in the AC impedance resistance. Examination of the anode after electrochemical measurement revealed that the basic morphology and distribution of the particles were preserved.

Columnar thin films of undoped ceria were grown by metal-organic chemical vapor deposition. The films, deposited on Pt-coated MgO(100) substrates, display a columnar microstructure with nanometer scale grain size and ~30% overall porosity. Through-plane (thickness mode) electrical conductivity was measured by AC impedance spectroscopy. Proton conduction is observed below 350-400 °C, with a magnitude that depends on gas-phase water vapor pressure. The overall behavior suggests proton transport that occurs along exposed grain surfaces and parallel grain boundaries. No impedance due to grain boundaries normal to the direction of transport is observed. The proton conductivity in the temperature range of 200-400 °C is approximately four times greater than that of nanograined bulk ceria, consistent with enhanced transport along aligned grain surfaces in the CVD films.

Detection of single walled carbon nanotubes (CNTs) was performed using single particle-inductively coupled plasma-mass spectrometry (spICPMS). Due to the ambiguities inherent in detecting CNTs by carbon analysis, particularly in complex environmental matrices, this study focuses on using trace catalytic metals intercalated in the CNT structure as proxies for the nanotubes. Using a suite of commercially available CNTs, the monoisotopic elements Co and Y were found to be the most effective for differentiation of particulate pulses from background. The small, variable, amount of trace metal in each CNT makes separation from instrumental background challenging; multiple cut-offs for determining CNT number concentration were investigated to maximize the number of CNTs detected and minimize the number of false positives in the blanks. In simple solutions the number of CNT pulses detected increased linearly with concentration in the ng L−1 range. However, analysis of split samples by both spICPMS and Nanoparticle Tracking Analysis (NTA) showed the quantification of particle number concentration by spICPMS to be several orders of magnitude lower than by NTA. We postulate that this is a consequence of metal content and/or size, caused by the presence of many CNTs that do not contain enough metal to be above the instrument detection limit, resulting in undercounting CNTs by spICPMS. However, since the detection of CNTs at low ng L−1 concentrations is not possible by other techniques, spICPMS is still a more sensitive technique for detecting the presence of CNTs in environmental, materials, or biological applications. To highlight the potential of spICPMS in environmental studies the release of CNTs from polymer nanocomposites into solution was monitored, showcasing the technique's ability to detect changes in released CNT concentrations as a function of CNT loading.

Toxoplasma gondii is an obligate intracellular parasite often found in the brain of humans. Research has shown a correlation between prevalence of antibody titers to T. gondii and psychological illness in humans. Recent studies indicate that individuals seropositive for T. gondii antibodies are more likely to develop psychotic disorders including schizophrenia, which is associated with changes in the dopamine neurotransmitter system. Dopamine in the brain may play a role in proliferation, chemoattraction, infection efficiency, or stage conversion of T. gondii . Because tachyzoites are the first developmental stage to reach the brain, the present study was conducted to determine the effects of dopamine on their development in vitro. In human fibroblast host cells, dopamine was added at either 100 nM or 250 nM to cell culture media, and the numbers of tachyzoites produced at 48 hr were determined and compared to vehicle-treated controls. An increase of tachyzoite numbers and increased destruction in cell monolayer were observed at both concentrations of dopamine. Dopamine used at 250 nM caused a significant (P < 0.05) increase in tachyzoites counts compared to controls. Dopamine antagonists (10 μM) did not significantly alter dopamine-stimulated tachyzoite production in human fibroblasts. In primary neonatal rat astrocyte cell cultures, dopamine (200 μM) significantly (P < 0.05) increased numbers of intracellular tachyzoites after 24 hr. The role that this increase plays in tachyzoite production under the stimulus of dopamine in the modulation of neural infection in humans awaits further studies.

A two-dimensional, small-bias model has been developed for describing transport through a mixed ionic and electronic conductor (MIEC) with electrochemically-active surfaces, a system of particular relevance to solid oxide fuel cells. Utilizing the h-adaptive finite-element method, we solve the electrochemical potential and flux for both ionic and electronic species in the MIEC, taking the transport properties of Sm(0.15)Ce(0.85)O(1.925-δ) (SDC15). In addition to the ionic flux that flows between the two sides of the cell, there are two types of electronic fluxes: (1) cross-plane current that flows in the same general direction as the ionic current, and (2) in-plane current that flows between the catalytically-active MIEC surface and the metal current collectors. From an evaluation of these fluxes, the macroscopic interfacial resistance is decomposed into an electrochemical reaction resistance and an electron diffusion-drift resistance, the latter associated with the in-plane electronic current. Analysis of the experimental data for the interfacial resistance for hydrogen electro-oxidation on SDC15 having either Pt or Au current collectors (W. Lai and S. M. Haile, J. Am. Ceram. Soc., 2005, 88, 2979-2997; W. C. Chueh, W. Lai and S. M. Haile, Solid State Ionics, 2008, 179, 1036-1041) indicates that surface reaction rather than electron migration is the overall rate-limiting step, and suggests furthermore that the surface reaction rate, which has not been directly measured in the literature, scales with pO2(-1/4). The penetration depth for the in-plane electronic current is estimated at 0.6 μm for the experimental conditions of interest to SDC15, and is found to attain a value as high as 4 μm within the broader range of computational conditions.

An increasing interest in the association of the presence of antibodies to Toxoplasma gondii and the development of schizophrenia in patients has been generated over the last several years. Some antischizophrenia agents have been shown to have activity against T. gondii in cell culture assays and to ameliorate behavioral changes associated with chronic T. gondii infection in rats. In the present study, we examined the effects of commonly used antipsychotic and mood stabilizing agents (haloperidol, clozapine, fluphenazine, trifluoperazine, and thioridazine) for activity against developing tachyzoites of the RH strain of T. gondii in human fibroblast cell cultures. Neither haloperidol nor clozapine had a measurable effect. Fluphenazine had an IC(50) of 1.7 µM, thioridazine had an IC(50) of 1.2 µM, and trifluoperazine had an IC(50) of 3.8 µM. Our study demonstrates that some agents used to treat schizophrenia have the ability to inhibit T. gondii proliferation in cell culture.

We examined the prevalence of antibodies to zoonotic protozoan parasites ( Trypanosoma cruzi, Toxoplasma gondii, and Encephalitozoon cuniculi) and protozoans of veterinary importance ( Neospora caninum, Sarcocystis neurona, and Besnoitia darlingi) in a population of North American opossums ( Didelphis virginiana) from Louisiana. Samples from 30 opossums were collected as part of a survey for T. cruzi in Louisiana. Frozen sera from these 30 opossums were examined using an indirect immunofluorescent antibody test (IFAT) against in vitro-produced antigenic stages of these protozoans. Additionally, 24 of the 30 samples were examined using hemoculture, and all 30 were examined in the modified direct agglutination test (MAT) for antibodies to To. gondii. The prevalences of reactive IFAT samples were as follows: 60% for T. cruzi, 27% for To. gondii, 23% for E. cuniculi, 17% for S. neurona, 47% for B. darlingi, and 0% for N. caninum. Hemoculture revealed that 16 (67%) of 24 samples were positive for T. cruzi, compared to 18 of 30 (60%) by IFAT. The sensitivity and specificity for the IFAT compared to hemoculture was 100% for each. The modified direct agglutination test revealed that 9 (30%) of the 30 samples from opossums had antibodies to To. gondii , compared to 8 (27%) using the IFAT. The sensitivity and specificity of the IFAT compared to the MAT was 100% and 72%, respectively.

IL-22 is made by a unique set of innate and adaptive immune cells, including the recently identified noncytolytic NK, lymphoid tissue-inducer, Th17, and Th22 cells. The direct effects of IL-22 are restricted to nonhematopoietic cells, its receptor expressed on the surface of only epithelial cells and some fibroblasts in various organs, including parenchymal tissue of the gut, lung, skin, and liver. Despite this cellular restriction on IL-22 activity, we demonstrate that IL-22 induces effects on systemic biochemical, cellular, and physiological parameters. By utilizing adenoviral-mediated delivery of IL-22 and systemic administration of IL-22 protein, we observed that IL-22 modulates factors involved in coagulation, including fibrinogen levels and platelet numbers, and cellular constituents of blood, such as neutrophil and RBC counts. Furthermore, we observed that IL-22 induces thymic atrophy, body weight loss, and renal proximal tubule metabolic activity. These cellular and physiological parameters are indicative of a systemic inflammatory state. We observed that IL-22 induces biochemical changes in the liver including induction of fibrinogen, CXCL1, and serum amyloid A that likely contribute to the reported cellular and physiological effects of IL-22. Based on these findings, we propose that downstream of its expression and impact in local tissue inflammation, circulating IL-22 can further induce changes in systemic physiology that is indicative of an acute-phase response.

Objective: All gamma-chain cytokines signal through JAK-3 and JAK-1 acting in tandem. We undertook this study to determine whether the JAK-3 selective inhibitor WYE-151650 would be sufficient to disrupt cytokine signaling and to ameliorate autoimmune disease pathology without inhibiting other pathways mediated by JAK-1, JAK-2, and Tyk-2., Methods: JAK-3 kinase selective compounds were characterized by kinase assay and JAK-3-dependent (interleukin-2 [IL-2]) and -independent (IL-6, granulocyte-macrophage colony-stimulating factor [GM-CSF]) cell-based assays measuring proliferation or STAT phosphorylation. In vivo, off-target signaling was measured by IL-22- and erythropoietin (EPO)-mediated models, while on-target signaling was measured by IL-2-mediated signaling. Efficacy of JAK-3 inhibitors was determined using delayed-type hypersensitivity (DTH) and collagen-induced arthritis (CIA) models in mice., Results: In vitro, WYE-151650 potently suppressed IL-2-induced STAT-5 phosphorylation and cell proliferation, while exhibiting 10-29-fold less activity against JAK-3-independent IL-6- or GM-CSF-induced STAT phosphorylation. Ex vivo, WYE-151650 suppressed IL-2-induced STAT phosphorylation, but not IL-6-induced STAT phosphorylation, as measured in whole blood. In vivo, WYE-151650 inhibited JAK-3-mediated IL-2-induced interferon-gamma production and decreased the natural killer cell population in mice, while not affecting IL-22-induced serum amyloid A production or EPO-induced reticulocytosis. WYE-151650 was efficacious in mouse DTH and CIA models., Conclusion: In vitro, ex vivo, and in vivo assays demonstrate that WYE-151650 is efficacious in mouse CIA despite JAK-3 selectivity. These data question the need to broadly inhibit JAK-1-, JAK-2-, or Tyk-2-dependent cytokine pathways for efficacy.

Delayed-type hypersensitivity (DTH) is classically defined as inflammation involving activated Th1 cells and cytokine production. DTH paw swelling, along with the cytokines IL-2, IFNγ, MCP-1 and TNFα, were inhibited in Balb/c mice by cyclosporine A (CsA). Surprisingly, the DTH response in the B6D2F1 mice was unaffected by CsA, despite a decrease in TNFα and IFNγ levels. IL-2 levels, however, were not decreased. To determine if the IL-2 production in the B6D2F1 strain is occurring through CD28-mediated costimulation, both CsA and CTLA-4Ig were administered. Paw swelling and IL-2 levels were decreased, indicating a role for costimulation. Co-administration of temsirolimus and CsA also reduced DTH and IL-2 levels in B6D2F1 mice, demonstrating involvement of the mTORC1 pathway. These results indicate that the cell activation pathways responsible for DTH differ with mouse strain. It is important to understand these differences in order to accurately interpret the results using potential therapeutic agents., (Copyright © 2010 Elsevier Inc. All rights reserved.)

In this paper we develop an analytical framework for the study of electrochemical impedance of mixed ionic and electronic conductors (MIEC). The framework is based on non-equilibrium thermodynamics and it features the coupling of electrochemical reactions, surface transport and bulk transport processes. We utilize this work to analyze two-dimensional systems relevant for fuel cell science via the finite element method (FEM). Alternate current impedance spectroscopy (AC-IS or IS) of a ceria symmetric cell is simulated near equilibrium conditions (zero bias) for a wide array of working conditions including variations of temperature and H(2) partial pressure on a two-dimensional doped ceria sample with patterned metal electrodes. The model shows agreement between computed IS curves and the experimental literature where the relative error on the impedance is consistently below 2%. Important two-dimensional effects such as the impact of thickness decrease and the influence of variable electronic and ionic diffusivities on the impedance spectra are also explored.

We introduce a new method for performing and miniaturizing many types of heterogeneous catalysis involving nanoparticles. The method makes use of the plasmon resonance present in nanoscale metal catalysts to provide the necessary heat of reaction when illuminated with a low-power laser. We demonstrate our approach by reforming a flowing, liquid mixture of ethanol and water over gold nanoparticle catalysts in a microfluidic channel. Plasmon heating of the nanoparticles provides not only the heat of reaction but the means to generate both water and ethanol vapor locally over the catalysts, which in turn allows the chip and the fluid lines to remain at room temperature. The measured products of the reaction, CO(2), CO, and H(2), are consistent with catalytic steam reforming of ethanol. The approach, which we refer to as plasmon-assisted catalysis, is general and can be used with a variety of endothermic catalytic processes involving nanoparticles.

There are 3 strains of Encephalitozoon cuniculi that occur in mammals. Strain III is associated with clinical disease in dogs, although some can be asymptomatic carriers and excrete spores in their urine. Several cases of human E. cuniculi infection caused by strain III have been observed in immunocompromised patients, indicating that E. cuniculi should be considered a zoonotic agent. Encephalitozoon cuniculi can cause fatal disease in maternally-infected or young dogs. Clinical signs in these animals included blindness, encephalitis, retarded growth rate, and nephritis. Encephalitozoon cuniculi has also been associated with primary renal failure in adult dogs. The present study used the direct agglutination test (DAT, cut-off 1:50) and the indirect fluorescent antibody test (IFAT, cut-off 1:10) to examine the prevalence of antibodies to E. cuniculi in dogs from Brazil and Colombia. Using the DAG, 31 (27.4%) of 113 dogs from Brazil and 47 (18.5%) of 254 dogs from Colombia were seropositive. Nine (14.3%) of 63 dogs from Brazil and 18 (35.3%) of the 51 dogs from Colombia were seropositive by indirect immunofluorescent antibody test. These results indicate that dogs from Brazil and Colombia are exposed to E. cuniculi.

The cPLA(2)alpha inhibitors we reported earlier were potent in both isolated enzyme and rat whole blood assays but have high plogD(7.4). To address these issues, reactions of electrophilic sulfonamides 9-12 were employed to incorporate various heterocyclic or heteroatom-based reagents into cPLA(2)alpha inhibitors. For example, reactions of 9 with sulfur nucleophiles such as thiophenol allowed rapid assembly of thioether analogues that were converted into the corresponding sulfoxides to afford less lipophilic derivatives. Reactions of 10 and 11 with various nitrogen nucleophiles, including aromatic heterocycles and aliphatic amines, provided an efficient way to introduce polarity into cPLA(2)alpha inhibitors. Finally, we report the first application of (2-formylphenyl)methanesulfonyl chloride, 13. Reductive amination of 2-formylphenylmethane sulfonamides allowed the introduction of various nitrogen nucleophiles. Several inhibitors obtained herein have plogD(7.4) values 3-4 units lower than previously synthesized compounds and yet maintain in vitro potency.

The optimization of a class of indole cPLA 2 alpha inhibitors is described herein. The importance of the substituent at C3 and the substitution pattern of the phenylmethane sulfonamide region are highlighted. Optimization of these regions led to the discovery of 111 (efipladib) and 121 (WAY-196025), which are shown to be potent, selective inhibitors of cPLA 2 alpha in a variety of isolated enzyme assays, cell based assays, and rat and human whole blood assays. The binding of these compounds has been further examined using isothermal titration calorimetry. Finally, these compounds have shown efficacy when dosed orally in multiple acute and chronic prostaglandin and leukotriene dependent in vivo models.

Oocysts are the environmentally resistant life stage of Toxoplasma gondii. Humans can become infected by accidentally ingesting the oocysts in water or from contaminated produce. Severe disease can occur in immunocompromised individuals, and nonimmune pregnant women can infect their offspring. Chronic infection is associated with decreased mental functions, vision and hearing problems, and some mental disorders such as schizophrenia. High pressure processing (HPP) is a commercial method used to treat food to eliminate pathogens. Treatment of produce to eliminate viable T. gondii oocysts would provide a means to protect consumers. The present study was done to better define the effects of HPP on oocysts placed on raspberries. Raspberries were chosen because they are a known source of a related human intestinal parasite, Cyclospora cayetanensis. Raspberries were inoculated with 5 x 10(4) oocysts of the VEG strain of T. gondii for 20 hr prior to HPP. Individual raspberries were exposed to 500 MPa, 400 MPa, 340 MPa, 300 MPa, 270 MPa, 250 MPa, 200 MPA, 100 MPa, or no MPa treatment for 60 sec in a commercial HPP unit (1 MPa = 10 atm = 147 psi). Treatment of raspberries with 340 MPa for 60 sec was needed to render oocysts spot inoculated on the raspberries noninfectious for mice. Treatment of raspberries with 200 MPa or less for 60 sec was not effective in rendering oocysts noninfectious for mice.

Toxoplasma gondii is a common intracellular protozoan infection of humans worldwide. Severe disease can occur in immunocompromised individuals and the in the fetuses of nonimmune pregnant women. Chronic infection is associated with vision and hearing problems, and functional mental alterations, including schizophrenia. The mood-stabilizing agent valproic acid has been shown to inhibit the development of T. gondii in vitro at dosages that are normally achieved in the serum and cerebral spinal fluid of human patients and to have positive effects on the behavior of rats chronically infected with T. gondii. The present study was done to examine the in vivo activity of valproic acid against acute toxoplasmosis in mice. Two studies were done with valproic acid given in the drinking water at concentrations of 1.5 mg/ml (Experiment 1) or 3.0 mg/ml (Experiment 2). In a third experiment (Experiment 3), valproic acid was injected intraperitoneally (i.p.) at doses of 200 or 300 mg/kg every 12 hr. Valproic acid was not effective in preventing acute toxoplasmosis. All mice treated with valproic acid died or were killed and did not (P > 0.05) live significantly longer than the controls. Tachyzoites were demonstrated in the tissues of infected valproic-acid-treated mice. A fourth study was done to determine if valproic acid has activity against T. gondii tissue cysts in chronically infected mice. Mice were chronically infected with the ME-49 strain of T. gondii for 8 wk and then treated orally with valproic acid at approximately 6.6 mg/ml (800 mg/kg/day) in the drinking water for 10 wk (amount was varied due to increasing mouse weights). No significant differences (P > 0.05) were present in tissue cyst numbers in valproic-acid-treated T. gondii chronically infected mice and in mice chronically infected with T. gondii but not given valproic acid. Our results indicate that valproic acid, although effective in vitro against T. gondii tachyzoites, is not effective as a preventative in mice inoculated with T. gondii tachyzoites. Additionally, no activity against tissue cysts was observed in chronically T. gondii-infected valproic-acid-treated mice.

We show that when a small amount of heat is added close to a liquid-vapor interface of a captive gas bubble in a microchannel, interphase mass-transfer through the bubble can occur in a controlled manner with only a slight change in the temperature of the fluid. We demonstrate that this method, which we refer to as bubble-assisted interphase mass-transfer (BAIM), can be applied to interphase chemical separations, e.g., simple distillation, without the need for high temperatures, vacuum, or active cooling. Although any source of localized heating could be used, we illustrate BAIM with an all-optical technique that makes use of the plasmon resonance in an array of nanoscale metal structures that are incorporated into the channel to produce localized heating of the fluid when illuminated by a stationary low-power laser.

Metastatic sarcomas are commonly resistant to chemotherapy. The serine/threonine kinase, mammalian target of rapamycin (mTOR), is a protein kinase of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway thought to have a key role in controlling cancer growth and thus is an important target for cancer therapy. Several inhibitors of mTOR are in clinical trials, including AP23573, which is being tested on metastatic sarcomas and other tumors. We hypothesized that a marker for the activity of mTOR, phosphorylated S6 ribosomal protein, would be predictive of clinical response to the drug, that is, high tumor expression would signify better response than low expression. This was a blinded study. Of 26 patients treated, 20 remained on study, with available paraffin blocks. Fourteen patients received AP23573 alone and six patients received AP23573 in combination with adriamycin. An antibody to the phosphorylated S6 ribosomal protein was used to stain the tumors, all high-grade sarcomas. Pretreatment biopsy or resection material was tested: the original tumor (n=6) or tumor recurrence/metastasis (n=14); either of these may have been after treatment with other agents. Staining was scored for both quantity/percentage of tumor cells and intensity. Scoring was performed without knowledge of tumor response. Staining quantity could be categorized into two natural groups: high expressors (> or =20% of tumor cells, 11 cases) and low expressors (0-10% of tumor cells, 9 cases). The high-expression group had eight stable and three progressive cases (73% stable disease); the low-expression group had three stable and six progressive cases (67% progressive disease). Chi-square analysis showed statistical significance (P< or =0.05) at this initial cutoff (10%) selected blindly. The level of phosphorylated S6 ribosomal protein expression was predictive of early tumor response to the mTOR inhibitor, suggesting that this is a promising new predictive sarcoma marker for targeted mTOR inhibitor therapy.

The synthesis and structure-activity relationship of a series of benzenesulfonamide indole inhibitors of cPLA(2)alpha are described. Substitution of the benzenesulfonamide led to analogues with 50-fold improvement in potency versus the unsubstituted benzenesulfonamide lead compound. Rat pharmacokinetics in a minimal formulation was used to prioritize compounds, leading to the discovery of a potent inhibitor of cPLA(2)alpha with oral efficacy in models of rat carrageenan paw edema and Ascaris suum airway challenge in naturally sensitized sheep.

The synthesis and structure-activity relationship of a series of indole inhibitors of cytosolic phospholipase A2alpha (cPLA2alpha, type IVA phospholipase) are described. Inhibitors of cPLA2alpha are predicted to be efficacious in treating asthma as well as the signs and symptoms of osteoarthritis, rheumatoid arthritis, and pain. The introduction of a benzyl sulfonamide substituent at C2 was found to impart improved potency of these inhibitors, and the SAR of these sulfonamide analogues is disclosed. Compound 123 (Ecopladib) is a sub-micromolar inhibitor of cPLA2alpha in the GLU micelle and rat whole blood assays. Compound 123 displayed oral efficacy in the rat carrageenan air pouch and rat carrageenan-induced paw edema models.

We introduce a new chemical vapor deposition (CVD) process that can be used to selectively deposit materials of many different types. The technique makes use of the plasmon resonance in nanoscale metal structures to produce the local heating necessary to initiate deposition when illuminated by a focused low-power laser. We demonstrate the technique, which we refer to as plasmon-assisted CVD (PACVD), by patterning the spatial deposition of PbO and TiO(2) on glass substrates coated with a dispersion of 23 nm gold particles. The morphology of both oxide deposits is consistent with local laser-induced heating of the gold particles by more than 150 degrees C. We show that temperature changes of this magnitude are consistent with our analysis of the heat-loss mechanisms. The technique is general and can be used to spatially control the deposition of virtually any material for which a CVD process exists.

Venous ulcer fibroblasts have been demonstrated to have low growth rates in response to platelet-derived growth factor (PDGF). Mitogen-activated protein kinase (MAPK) is an important signal transduction mechanism that regulates growth, differentiation, and apoptosis in eukaryotic cells. PDGF binds PDGF receptors that activate a multitiered signaling cascade involving MAPK. We hypothesize that the growth regulation in venous ulcer fibroblasts is dependent on the MAPK extracellular signal-regulated kinase (ERK) pathway in the presence of PDGF. Fibroblasts (fb) were isolated from 8 patients with venous ulcers (w-fb) and the normal skin (n-fb) of the ipsilateral thigh via punch biopsies. Fb were plated at 1,500 cells/dish and treated with PDGF-AB (10 ng/mL) for 15 days. Growth rates were determined. Immunoblot analysis of MAPK ERK for n-fb and w-fb were analyzed. To determine if PDGF-stimulated w-fb and n-fb utilized the MAPK ERK pathway in a dependent manner, the upstream kinase MAPK kinase 1 (MEK 1) was inhibited by PD 98059. In addition, fb were treated with chronic venous ulcer wound fluid (WF) to study its effect on MAPK ERK. In the presence of PDGF, growth rates were substantially lower in w-fb than in n-fb, and MAPK was activated in 6/8 w-fb and in only 2/8 n-fb. Fibroblasts expressing MAPK had significantly reduced cell proliferation compared to fibroblasts not expressing MAPK (p = 0.023). PD 98059 significantly inhibited w-fb and n-fb cell proliferation from basal level, which was reversible with addition of PDGF. In neonatal fibroblasts WF demonstrated inhibition of MAPK ERK over time and addition of PD98059 was not additive. This study suggests that the MAPK ERK pathway is important for cell proliferation in venous ulcer fibroblasts. In the presence of PDGF, fibroblasts with decreased growth rate express MAPK, and proliferation is further abrogated with addition of MEK 1 inhibitor, suggesting the importance of the MAPK ERK pathway regulating w-fb and n-fb proliferation. Although the majority of w-fb activated the MAPK ERK pathway in the presence of PDGF, proliferation was significantly attenuated, indicating that other MAPK inhibitory pathways are competing. Venous ulcer wound fluid directly inhibits the MAPK ERK pathway, suggesting that the venous ulcer wound environment has negative trophic factors that effect fibroblasts proliferation and ulcer healing.

Groups of mice were infected with tachyzoites of the RH strain of Toxoplasma gondii, treated with the opioid analgesic buprenorphine, sodium sulfadiazine, a combination of buprenorphine and sodium sulfadiazine, or nothing in the drinking water, on days -1 to 12 postinfection. Mice in the T. gondii-infected buprenorphine-treated group did not live significantly longer (P > 0.05) than mice given T. gondii and not treated with buprenorphine. Clinical observations of mice indicated that buprenorphine treatment reduced distress and pain in mice with acute toxoplasmosis. Mice treated with sodium sulfadiazine alone or sodium sulfadiazine combined with buprenorphine survived the 28-day study. Mice treated with buprenorphine and not infected with T. gondii also survived the 28 days. This study demonstrates that buprenorphine does not adversely interfere with acute T. gondii infection and indicates that buprenorphine can be given to mice to alleviate pain and distress associated with a T. gondii infection, and not adversely influence the results of toxoplasmosis studies. Analgesic (buprenorphine) treatment should now be the standard of care for mice in acute toxoplasmosis studies.

An experimental and numerical study of impinging, incompressible, axisymmetric, laminar jets is described, where the jet axis of symmetry is aligned normal to the wall. Particle streak velocimetry (PSV) is used to measure axial velocities along the centerline of the flow field. The jet-nozzle pressure drop is measured simultaneously and determines the Bernoulli velocity. The flow field is simulated numerically by an axisymmetric Navier-Stokes spectral-element code, an axisymmetric potential-flow model, and an axisymmetric one-dimensional stream-function approximation. The axisymmetric viscous and potential-flow simulations include the nozzle in the solution domain, allowing nozzle-wall proximity effects to be investigated. Scaling the centerline axial velocity by the Bernoulli velocity collapses the experimental velocity profiles onto a single curve that is independent of the nozzle-to-plate separation distance. Axisymmetric direct numerical simulations yield good agreement with experiment and confirm the velocity profile scaling. Potential-flow simulations reproduce the collapse of the data; however, viscous effects result in disagreement with experiment. Axisymmetric one-dimensional stream-function simulations can predict the flow in the stagnation region if the boundary conditions are correctly specified. The scaled axial velocity profiles are well characterized by an error function with one Reynolds-number-dependent parameter. Rescaling the wall-normal distance by the boundary-layer displacement-thickness-corrected diameter yields a collapse of the data onto a single curve that is independent of the Reynolds number. These scalings allow the specification of an analytical expression for the velocity profile of an impinging laminar jet over the Reynolds number range investigated of .

Growth factors have been demonstrated to increase the proliferation of wound fibroblasts. Platelet-derived growth factor (PDGF) is a potent cell mitogen. However, the role of PDGF in chronic venous ulcers is inconclusive. This study investigated whether PDGF stimulates venous ulcer fibroblasts to proliferate. Fibroblasts (fb) were isolated from 8 venous ulcers wounds (w-fb) and normal skin (n-fb) of the ipsilateral thigh via punch biopsies. Fibroblasts were plated at 1,500 cells/dish in Dulbecco's Modified Eagle Medium + 10% calf serum (CM) and treated with/without PDGF-alphabeta (10 ng/mL) for 15 days. Growth rates were calculated. Western blotting and immunocytochemistry staining determined basal levels for PDGF-alpha and -beta receptors, respectively. Growth rates were significantly lower in w-fb than in n-fb (1,579 +/-546 vs 13,782 +/-5,882 cells/day, p=0.019). PDGF-alphabeta treatment caused n-fb to increase their proliferative capacity relative to complete media (20,393 +/-6,572 vs 13,782 +/-5,882 cells/day, p=0.005). However, PDGF-alphabeta had no significant effect on w-fb proliferation over CM (1,030 +/-264 and 1,579 +/-546 cells/day, p=0.15). In the presence of PDGF-alphabeta, w-fb had a significantly attenuated growth rate over n-fb (1,030 +/-264 vs 20,393 +/-6,572 cells/day, p=0.019). Western blot and immunocytochemistry analysis revealed diminished basal levels of PDGF-alpha and -beta receptors, respectively, in ulcer fibroblasts. Venous ulcer fibroblasts had decreased proliferation. PDGF-alphabeta had no effect on the growth rate of venous ulcer fibroblasts. In venous ulcers, decreased basal levels of fibroblast PDGF-alpha and -beta receptors may explain reduced proliferation. Further clinical studies are needed to elucidate the role growth factors may play in venous ulcers.

A nonlinear optical spectroscopy based on degenerate four-wave mixing has made possible direct measurements of species temperature and concentration profiles through the boundary layer of a reactive plasma at atmospheric pressure. Spectra were obtained for CH and C(2) radicals over a range of conditions including those for the plasma chemical vapor deposition of diamond films. Numerical simulations based on a one-dimensional stagnation-point flow model are in good agreement with the measurements. The CH mole fraction is shown to rise and fall as a function of distance from the substrate, which is compelling experimental evidence for the complex chemistry that is occurring in the plasma boundary layer.

Incubator-hatched bobwhite quail neonates were tested individually in a variety of single call and simultaneous auditory choice tests involving 6 adult quail vocalizations and a chicken exodus call. The quail showed a high degree of responsiveness (100%) to 3 adult quail vocalizations and significantly less responsiveness (40-50%) to 3 other quail calls and to the chicken exodus call in single call tests. In simultaneous choice tests, the quail were selectively responsive to a call of their own species over the chicken call, and they also showed certain intraspecific preferences. Because of their high degree of responsiveness, coupled with selectivity of their approach responses, bobwhite quail neonates are ideal for the laboratory investigation of the development of auditory perception.