Sustainable and Low-Cost Electrodes for Photocatalytic Fuel Cells.

Water pollutants harm ecosystems and degrade water quality. At the same time, many pollutants carry potentially valuable chemical energy, measured by chemical oxygen demand (COD). This study highlights the potential for energy harvesting during remediation using photocatalytic fuel cells (PCFCs), stressing the importance of economically viable and sustainable materials. To achieve this, this research explores alternatives to platinum cathodes in photocathodes and aims to develop durable, cost-effective photoanode materials. Here, zinc oxide nanorods of high density are fabricated on carbon fiber surfaces using a low-temperature aqueous chemical growth method that is simple, cost-efficient, and readily scalable. Alternatives to the Pt cathodes frequently used in PCFC research are explored in comparison with screen-printed PEDOT:PSS cathodes. The fabricated ZnO/carbon anode (1.5 × 2 cm2) is used to remove the model pollutant used here and salicylic acid from water (30 mL, 70 µM) is placed under simulated sunlight (0.225 Sun). It was observed that salicylic acid was degraded by 23 ±0.46% at open voltage (OV) and 43.2 ± 0.86% at 1 V with Pt as the counter electrode, degradation was 18.5 ± 0.37% at open voltage (OV) and 44.1 ± 0.88% at 1 V, while PEDOT:PSS was used as the counter electrode over 120 min. This shows that the PEDOT:PSS exhibits an excellent performance with the full potential to provide low-environmental-impact electrodes for PCFCs.

Therapeutic Effect of Nicotinamide Mononucleotide for Hypoxic-Ischemic Brain Injury in Neonatal Mice.

SUMMARY STATEMENT: Neonatal hypoxia-ischemia reduces nicotinamide adenine dinucleotide (NAD+) and SIRT6 levels in the injured hippocampus.Hippocampal high mobility group box-1 (HMGB1) release is significantly increased after neonatal hypoxia-ischemia.Nicotinamide mononucleotide (NMN) treatment normalizes hippocampal NAD+ and SIRT6 levels, with significant decrease in caspase-3 activity and HMGB1 release.NMN improves early developmental behavior, as well as motor and memory function.

Rigorous mathematical formulation of net escape velocity and net escape probability determining a macroscopic concentration.

Net escape velocity (NEV) and net escape probability (NEP) are concepts that describe that scalar quantity discharged from a source in an indoor air environment is expressed by the unique velocity scales of the returning and escaping populations. Despite the conceptual description and applications of several numerical simulations, the definitions were not precisely explained using a mathematical formula. Here, we derive rigorous mathematical formulations of the NEV and NEP. These formulations provide us with the physical interpretation of NEV, clarify the sufficient condition of perfect escape, and lead to a further formulation of the transfer probability of the scalar. To justify and apply the derived relationships, two simple problems were numerically solved: One was a diffusion equation, and the other was an advection-diffusion equation. The results of the diffusion problem clearly demonstrate that only the outgoing scalar flux exists on the surface of the control volume, covering the source at any location. In contrast, the advection-diffusion problem reveals that there is a returning population of the scalar in most locations, despite both diffusion and turbulent parts working to remove the scalar. This rigorous formulation contributes to apply NEV as an appropriate air quality index with the clear physical interpretation to determine the local scalar concentration.

N-Acetyl Cysteine Restores Sirtuin-6 and Decreases HMGB1 Release Following Lipopolysaccharide-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Mice.

Inflammation and neonatal hypoxia-ischemia (HI) are important etiological factors of perinatal brain injury. However, underlying mechanisms remain unclear. Sirtuins are a family of nicotinamide adenine dinucleotide (NAD)+-dependent histone deacetylases. Sirtuin-6 is thought to regulate inflammatory and oxidative pathways, such as the extracellular release of the alarmin high mobility group box-1 (HMGB1). The expression and role of sirtuin-6 in neonatal brain injury are unknown. In a well-established model of neonatal brain injury, which encompasses inflammation (lipopolysaccharide, LPS) and hypoxia-ischemia (LPS+HI), we investigated the protein expression of sirtuin-6 and HMGB1, as well as thiol oxidation. Furthermore, we assessed the effect of the antioxidant N-acetyl cysteine (NAC) on sirtuin-6 expression, nuclear to cytoplasmic translocation, and release of HMGB1 in the brain and blood thiol oxidation after LPS+HI. We demonstrate reduced expression of sirtuin-6 and increased release of HMGB1 in injured hippocampus after LPS+HI. NAC treatment restored sirtuin-6 protein levels, which was associated with reduced extracellular HMGB1 release and reduced thiol oxidation in the blood. The study suggests that early reduction in sirtuin-6 is associated with HMGB1 release, which may contribute to neonatal brain injury, and that antioxidant treatment is beneficial for the alleviation of these injurious mechanisms.

Returning characteristics of pollutants for a local domain in the presence of returning and recirculating airflow in indoor environments.

Heating, ventilating, and air-conditioning (HVAC) systems usually supply air, which is a mixture of fresh air from the outdoor environment, and return air from rooms via the ventilation ductwork. This air reduces the heat load and cost impact of air conditioning using outdoor air. This recirculation of room air in air-conditioning systems is reasonable in terms of energy saving; however, the deterioration of air quality might be a concern because of the recirculation of contaminated room air. Here, we numerically investigate the effect of pollutant recirculation/return on the formation of concentration distributions of local pollutants in indoor environments when the mixing ratio of recirculated air in the HVAC system changes. We discuss the detailed structure of the formation mechanism of local pollutant concentration distributions using various indices for indoor ventilation efficiency in simplified room models. Among the indices, visitation frequency and net escape probability are the ones that directly assist in evaluating the recirculation/return characteristics of indoor pollutants. As a result, when the proportion of air that is recirculated becomes large, the number of pollutants returning to a target local domain, the visitation frequency, increases exponentially, and the net escape probability-which directly expresses the probability of pollutant discharged from the target domain-is close to zero.

Formation of Monolithic Ion-Selective Transport Media Based on "Click" Cross-Linked Hyperbranched Polyglycerol.

In the emerging field of organic bioelectronics, conducting polymers and ion-selective membranes are combined to form resistors, diodes, transistors, and circuits that transport and process both electronic and ionic signals. Such bioelectronics concepts have been explored in delivery devices that translate electronic addressing signals into the transport and dispensing of small charged biomolecules at high specificity and spatiotemporal resolution. Manufacturing such "iontronic" devices generally involves classical thin film processing of polyelectrolyte layers and insulators followed by application of electrolytes. This approach makes miniaturization and integration difficult, simply because the ion selective polyelectrolytes swell after completing the manufacturing. To advance such bioelectronics/iontronics and to enable applications where relatively larger molecules can be delivered, it is important to develop a versatile material system in which the charge/size selectivity can be easily tailormade at the same time enabling easy manufacturing of complex and miniaturized structures. Here, we report a one-pot synthesis approach with minimal amount of organic solvent to achieve cationic hyperbranched polyglycerol films for iontronics applications. The hyperbranched structure allows for tunable pre multi-functionalization, which combines available unsaturated groups used in crosslinking along with ionic groups for electrolytic properties, to achieve a one-step process when applied in devices for monolithic membrane gel formation with selective electrophoretic transport of molecules.

The Role of Mitochondrial and Endoplasmic Reticulum Reactive Oxygen Species Production in Models of Perinatal Brain Injury.

Significance: Perinatal brain injury is caused by hypoxia-ischemia (HI) in term neonates, perinatal arterial stroke, and infection/inflammation leading to devastating long-term neurodevelopmental deficits. Therapeutic hypothermia is the only currently available treatment but is not successful in more than 50% of term neonates suffering from hypoxic-ischemic encephalopathy. Thus, there is an urgent unmet need for alternative or adjunct therapies. Reactive oxygen species (ROS) are important for physiological signaling, however, their overproduction/accumulation from mitochondria and endoplasmic reticulum (ER) during HI aggravate cell death. Recent Advances and Critical Issues: Mechanisms underlying ER stress-associated ROS production have been primarily elucidated using either non-neuronal cells or adult neurodegenerative experimental models. Findings from mature brain cannot be simply transferred to the immature brain. Therefore, age-specific studies investigating ER stress modulators may help investigate ER stress-associated ROS pathways in the immature brain. New therapeutics such as mitochondrial site-specific ROS inhibitors that selectively inhibit superoxide (O2•-)/hydrogen peroxide (H2O2) production are currently being developed. Future Directions: Because ER stress and oxidative stress accentuate each other, a combinatorial therapy utilizing both antioxidants and ER stress inhibitors may prove to be more protective against perinatal brain injury. Moreover, multiple relevant targets need to be identified for targeting ROS before they are formed. The role of organelle-specific ROS in brain repair needs investigation. Antioxid. Redox Signal. 31, 643-663.

Entrainment and its implications on microclimate ventilation systems: Scaling the velocity and temperature field of a round free jet.

Research on microclimate ventilation systems, which mostly involve free jets, points to delivery of better ventilation in breathing zones. While the literature is comprehensive, the influence of contaminant entrainment in jet flows and its implications on the delivery of supplied air is not fully addressed. This paper presents and discusses entrainment characteristics of a jet issued from a round nozzle (0.05 m diameter), in relation to ventilation, by exploring the velocity and temperature fields of the jet flow. The results show a trend suggesting that increasing the Reynold number (Re) reduces ambient entrainment. As shown herein, about 30% concentration of ambient air entrained into the bulk jet flow at Re 2541 while Re 9233 had about 13% and 19% for Re = 6537/12 026 at downstream distance of 8 diameters (40 cm). The study discusses that "moderate to high" Re may be ideal to reduce contaminant entrainment, but this is limited by delivery distance and possibly the risk of occupant discomfort. Incorporating the entrainment mixing factor (the ratio of room contaminants entrained into a jet flow) in performance measurements is proposed, and further studies are recommended to verify results herein and test whether this is general to other nozzle configurations.

Spirulina diet to lactating mothers protects the antioxidant system and reduces inflammation in post-natal brain after systemic inflammation.

OBJECTIVES: This study concerns: (1) the long-term effects of peripheral lipopolysaccharide (LPS) in neonatal rats on inflammation and antioxidant parameters in brain and (2) the effects of a Spirulina-enriched diet given to lactating mothers on protective and inflammatory parameters in brains of suckling pups subjected to peripheral inflammation. METHODS: Five-day old rat pups were treated with LPS (i.p. 2 mg/kg). After 3, 7, 30, and 65 days, mRNA, miRNA, and protein levels of pro-inflammatory cytokines and the Nuclear factor E2-related factor 2 (Nrf2)-system were examined. In a sub-group, a Spirulina-enriched diet was given to the mothers 24 hours before the pups were treated with LPS, then the effects on antioxidant and inflammatory parameters were evaluated. RESULTS: The main findings were: (1) interleukin 1 beta (IL-1ß) was upregulated in cortex 3, 7, and 30 days after LPS treatment, (2) Nrf2 and the catalytic subunit of γ-glutamylcysteinyl ligase were decreased in cortex 7 days after LPS in parallel with increased levels of phosphorylated p38 and decreased levels of histone H3 acetylation, and (3) a Spirulina-enriched diet to lactating mothers normalized both the increased IL-1ß expression and the decreased antioxidant parameters after LPS. The protective effects of Spirulina were correlated with decreased levels of phosphorylated p38 and high levels of the antioxidant miRNA-146a. DISCUSSION: A Spirulina diet given to lactating mothers can protect against neuroinflammation and decreased antioxidant defence in brain of suckling pups subjected to peripheral inflammation, possibly via decreased activation of p38 and high levels of the antioxidant miRNA-146a.

Differences in Reperfusion-Induced Mitochondrial Oxidative Stress and Cell Death Between Hippocampal CA1 and CA3 Subfields Are Due to the Mitochondrial Thioredoxin System.

AIMS: The susceptibility of CA1 over CA3 to damage from cerebral ischemia may be related to the differences in reactive oxygen species (ROS) production/removal between the two hippocampal subfields. We aimed to measure CA1/CA3 differences in net ROS production in real time in the first 30 min of reperfusion in pyramidal cells. We aimed to determine the underlying cause of the differential vulnerability of CA1 and CA3. RESULTS: Real-time determinations of mitochondrial H2O2 and, independently, glutathione (GSH) redox status from roGFP-based probes in individual pyramidal cells in organotypic hippocampal cultures during oxygen-glucose deprivation (OGD)-reperfusion (RP) demonstrate a significantly more oxidizing environment during RP in CA1 than CA3 mitochondria. Protein levels (immunohistochemistry and Western blots), roGFP2-based probe measurements during controlled mitochondrial production of ROS, and thioredoxin reductase (TrxR) inhibition by auranofin are consistent with a more effective mitochondrial thioredoxin (Trx) system in CA3. Inhibition of TrxR eliminates the differences in redox status and cell death between the regions. Overexpression of cytosolic Trx1 does not influence mitochondrial H2O2 production. INNOVATION: Real-time changes of mitochondrial H2O2 and GSH in tissue cultures during early RP, and also during controlled production of superoxide and peroxide, reveal significant differences between CA1 and CA3. The mitochondrial Trx system is responsible for the observed differences during RP as well as for delayed cell death 18 h afterward. CONCLUSION: Greater mitochondrial Trx efficacy in CA3 pyramidal cells results in less vulnerability to ischemia/reperfusion because of the less oxidizing environment in CA3 mitochondria during RP. Antioxid. Redox Signal. 27, 534-549.

Sustained Effects of Neonatal Systemic Lipopolysaccharide on IL-1ß and Nrf2 in Adult Rat Substantia Nigra Are Partly Normalized by a Spirulina-Enriched Diet.

BACKGROUND/AIM: Neonatal infection can sensitize the adult substantia nigra (SN) to secondary insults, causing a decrease in antioxidant capacity which may lead to Parkinson's disease in adults. We studied the prolonged effect of systemic infection by (i.p.) administration of lipopolysaccharide (LPS) on interleukin (IL)-1ß, the antioxidant regulator nuclear factor-erythroid 2-related factor 2 (Nrf2), and the peroxisome proliferator-activated receptor γ coactivator (PGC)-1α in rat SN. METHOD AND RESULTS: Five-day-old rat pups were treated with LPS (i.p. 2 mg/kg). After 65 days, the mRNA level of IL-1ß was significantly increased, in parallel with a decrease in that of the rate-limiting enzyme in glutathione synthesis, the γ-glutamylcysteine ligase catalytic subunit (γGCLc), Nrf2, and brain-derived neurotrophic factor (BDNF). Protein levels of γGCLc and Nrf2 were decreased while IL-1ß protein was significantly increased. These LPS-induced long-term changes correlated with a decrease in phosphorylated (active) AKT (pAKT) and phosphorylated (inactive) GSK-3ß (pGSK-3ß). In another set of experiments, a 0.1% Spirulina-containing diet was given to lactating mothers 24 h before the LPS treatment of the pups. The Spirulina-supplemented diet decreased IL-1ß protein expression in SN and elevated the mRNA level of γGCLc, Nrf2 protein, PGC-1α protein, and pAKT. CONCLUSION: Early-life infection can negatively affect Nrf2, pAKT, and pGSK-3ß for a long time in SN. A diet enriched with antioxidant and anti-inflammatory phytochemicals can partly restore some, but not all, of the effects on the antioxidant defense, possibly via normalizing effects on pAKT.

GSK3ß inhibition protects the immature brain from hypoxic-ischaemic insult via reduced STAT3 signalling.

Hypoxic-ischaemic (HI) injury is an important cause of neurological morbidity in neonates. HI leads to pathophysiological responses, including inflammation and oxidative stress that culminate in cell death. Activation of glycogen synthase kinase 3ß (GSK3ß) and the signal transducer and activator of transcription (STAT3) promotes brain inflammation. The purpose of this study was to test whether inhibition of GSK3ß signalling protects against neonatal HI brain injury. Mice were subjected to HI at postnatal day (PND) 9 and treated with a selective GSK3ß inhibitor, SB216763. Brain injury and caspase-3 activation, anti-oxidant and inflammatory mRNA responses and activation of STAT3 were analysed. Our results show that HI reduced phosphorylation of GSK3ß, thus promoting its kinase activity. The GSK3ß inhibitor reduced caspase-3 activation and neuronal cell death elicited by HI and reverted the effects of HI on gene expression of the anti-oxidant enzyme sod2 and mitochondrial factor pgc1α. The HI insult activated STAT3 in glial cells and GSK3ß inhibition attenuated STAT3 phosphorylation and its nuclear translocation following HI. Further, GSK3ß inhibition reduced HI-induced gene expression of pro-inflammatory cytokines tnfα and Il-6, while promoted the anti-inflammatory factor Il-10. In summary, data show that GSK3ß inhibition is neuroprotective in neonatal HI brain injury likely via reduced pro-inflammatory responses by blocking STAT3 signalling. Our study suggests that pharmacological interventions built upon GSK3ß silencing strategies could represent a novel therapy in neonatal brain injury.

Electroosmotic perfusion of tissue: sampling the extracellular space and quantitative assessment of membrane-bound enzyme activity in organotypic hippocampal slice cultures.

This review covers recent advances in sampling fluid from the extracellular space of brain tissue by electroosmosis (EO). Two techniques, EO sampling with a single fused-silica capillary and EO push-pull perfusion, have been developed. These tools were used to investigate the function of membrane-bound enzymes with outward-facing active sites, or ectoenzymes, in modulating the activity of the neuropeptides leu-enkephalin and galanin in organotypic-hippocampal-slice cultures (OHSCs). In addition, the approach was used to determine the endogenous concentration of a thiol, cysteamine, in OHSCs. We have also investigated the degradation of coenzyme A in the extracellular space. The approach provides information on ectoenzyme activity, including Michaelis constants, in tissue, which, as far as we are aware, has not been done before. On the basis of computational evidence, EO push-pull perfusion can distinguish ectoenzyme activity with a ~100 µm spatial resolution, which is important for studies of enzyme kinetics in adjacent regions of the rat hippocampus.

NRF2-regulation in brain health and disease: implication of cerebral inflammation.

The nuclear factor erythroid 2 related factor 2 (NRF2) is a key regulator of endogenous inducible defense systems in the body. Under physiological conditions NRF2 is mainly located in the cytoplasm. However, in response to oxidative stress, NRF2 translocates to the nucleus and binds to specific DNA sites termed "anti-oxidant response elements" or "electrophile response elements" to initiate transcription of cytoprotective genes. Acute oxidative stress to the brain, such as stroke and traumatic brain injury is increased in animals that are deficient in NRF2. Insufficient NRF2 activation in humans has been linked to chronic diseases such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. New findings have also linked activation of the NRF2 system to anti-inflammatory effects via interactions with NF-κB. Here we review literature on cellular mechanisms of NRF2 regulation, how to maintain and restore NRF2 function and the relationship between NRF2 regulation and brain damage. We bring forward the hypothesis that inflammation via prolonged activation of key kinases (p38 and GSK-3ß) and activation of histone deacetylases gives rise to dysregulation of the NRF2 system in the brain, which contributes to oxidative stress and injury.

Integrated electroosmotic perfusion of tissue with online microfluidic analysis to track the metabolism of cystamine, pantethine, and coenzyme A.

We have developed an approach that integrates electroosmotic perfusion of tissue with a substrate-containing solution and online microfluidic analysis of products, in this case thiols. Using this approach we have tracked the metabolism of cystamine, pantethine and CoA in the extracellular space of organotypic hippocampal slice cultures (OHSCs). Currently, little is known about coenzyme A (CoA) biodegradation and even less is known about the regulation and kinetic characteristics for this sequential multienzyme reaction. We found that the steady state percentage yields of cysteamine from cystamine and pantethine during the transit through OHSCs were 91% ± 4% (SEM) and 0.01%-0.03%, respectively. The large difference in the yields of cysteamine can be used to explain the drugs' different toxicities and clinical effectiveness against cystinosis. The kinetic parameters of the enzyme reaction catalyzed by the ectoenzyme pantetheinase are KM,C/α = 4.4 ± 1.1 mM and Vmax,C = 29 ± 3 nM/s, where α is the percentage yield of pantethine to pantetheine through disulfide exchange. We estimate that the percentage yield of pantethine to pantetheine through disulfide exchange is approximately 0.5%. Based on the formation rate of cysteamine in the OHSCs, we obtained the overall apparent Michaelis constant and maximum reaction rate for sequential, extracellular CoA degradation in an in situ environment, which are K'M = 16 ± 4 µM, V'max = 7.1 ± 0.5 nM/s. Kinetic parameters obtained in situ, although difficult to measure, are better representations of the biochemical flux in the living organism than those from isolated enzymes in vitro.

Time-dependent effects of systemic lipopolysaccharide injection on regulators of antioxidant defence Nrf2 and PGC-1α in the neonatal rat brain.

BACKGROUND/AIMS: Both excitotoxicity and neuroinflammation are associated with oxidative stress. One transcription factor, nuclear factor E2-related factor 2 (Nrf2), and one transcription cofactor, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), increase the endogenous antioxidant defence and can thus modulate neuronal cell death. Here, we investigated the temporal effects (after 24 and 72 h) of systemic (i.p.) administration of lipopolysaccharide (LPS) on the cerebral Nrf2 and PGC-1α systems. METHODS AND RESULTS: Seven-day-old rat pups were injected with LPS (0.3 mg/kg). After 24 h, the protein levels of γ-glutamylcysteine ligase modulatory subunit, γ-glutamylcysteine ligase catalytic subunit, Nrf2, PGC-1α and manganese superoxide dismutase (MnSOD) were increased in parallel with decreased levels of Keap1. These effects were correlated with an increased level of phosphorylated Akt and elevated acetylation of histone 4. In contrast, 72 h following LPS, a decrease in the components of the Nrf2 system in parallel with an increase in Keap1 was observed. The down-regulation after 72 h correlated with phosphorylation of p38 mitogen-activated protein kinase, while there were no changes in PGC-1α and MnSOD protein levels or the acetylation/methylation pattern of histones. CONCLUSION: Systemic LPS in neonatal rats induced time-dependent changes in brain Nrf2 and PGC-1α that correlated well with the protective effect observed after 24 h (pre-conditioning) and the deleterious effects observed after 72 h (sensitizing) of systemic LPS reported earlier. Collectively, the results point towards Nrf2 and PGC-1α as a possible mechanism behind these effects.

Expression of the Nrf2-system at the blood-CSF barrier is modulated by neonatal inflammation and hypoxia-ischemia.

Transcription factor NF-E2-related factor-2 (Nrf2) is a key regulator of endogenous anti-oxidant systems shown to play a neuroprotective role in the adult by preserving blood-brain barrier function. The choroid plexus, site for the blood-CSF barrier, has been suggested to be particularly important in maintaining brain barrier function in development. We investigated the expression of Nrf2- and detoxification-system genes in choroid plexus following systemic LPS injections, unilateral cerebral hypoxia-ischemia (HI) as well as the combination of LPS and HI (LPS/HI). Plexuses were collected at different time points after LPS, HI and LPS/HI in 9-day old mice. mRNA levels of Nrf2 and many of its target genes were analyzed by quantitative PCR. Cell death was analyzed by caspase-3 immunostaining and TUNEL. LPS caused down-regulation of the Nrf2-system genes while HI increased expression at earlier time points. LPS exposure prior to HI prevented many of the HI-induced gene increases. None of the insults resulted in any apparent cell death to choroidal epithelium. These data imply that the function of the inducible anti-oxidant system in the choroid plexus is down-regulated by inflammation, even if choroid cells are not structurally damaged. Further, LPS prevented the endogenous antioxidant response following HI, suggesting the possibility that the choroid plexus may be at risk if LPS is united with an insult that increases oxidative stress such as hypoxia-ischemia.

Dual TNFα-induced effects on NRF2 mediated antioxidant defence in astrocyte-rich cultures: role of protein kinase activation.

Tumor necrosis factor-α (TNFα) is a pleiotropic molecule that can have both protective and detrimental effects in neurodegeneration. Here we have investigated the temporal effects of TNFα on the inducible Nrf2 system in astrocyte-rich cultures by determination of glutathione (GSH) levels, γglutamylcysteine ligase (γGCL) activity, the protein levels of Nrf2, Keap1, the catalytic and modulatory subunit of γGCL (γGCL-C and γGCL-M respectively). Astrocyte-rich cultures were exposed for 24 or 72 h to different concentrations of TNFα. Acute exposure (24 h) of astrocyte-rich cultures to 10 ng/mL of TNFα increased GSH, γGCL activity, the protein levels of γGCL-M, γGCL-C and Nrf2 in parallel with decreased levels of Keap1. Antioxidant responsive element (ARE)-mediated transcription was blocked by inhibitors of ERK1/2, JNK and Akt whereas inactivation of p38 and GSK3ß further enhanced transcription. In contrast treatment with TNFα for 72 h decreased components of the Nrf2 system in parallel with an increase of Keap1. Stimulation of the Nrf2 system by tBHQ was intact after 24 h but blocked after 72 h treatment with TNFα. This down-regulation after 72 h correlated with activation of p38 MAPK and GSK3ß, since inhibition of these signalling pathways reversed this effect. The upregulation of the Nrf2 system by TNFα (24 h treatment) protected the cells from oxidative stress through elevated γGCL activity whereas the down-regulation (72 h treatment) caused pronounced oxidative toxicity. One of the important implications of the results is that in a situation where Nrf2 is decreased, such as in Alzheimer's disease, the effect of TNFα is detrimental.

On the contribution of mean flow and turbulence to city breathability: the case of long streets with tall buildings.

This paper analyses the contribution of mean flow and turbulence to city breathability within urban canopy layers under the hypothesis that winds from rural/marine areas are sources of clean air (inhale effect) and main contributors to local-scale pollutant dilution (exhale effect). Using Computational Fluid Dynamics (CFD) simulations, several idealized long streets flanked by tall buildings are investigated for wind flow parallel to the street axis. Aspect ratios (building height/street width) ranging from 2 to 4 and street lengths ranging from neighborhood scales (~1km in full scale) to city scales (~10km in full scale) are analyzed. To assess the inhale effect, the age of air concept is applied to quantify the time taken by a parcel of rural/marine air to reach a reference location within the urban canopy layer. To simulate the exhale effect, removal of pollutants released from a ground level source is considered. Numerical results agree with wind tunnel observations showing that a bulk portion of rural/marine air enters the streets through windward entries, a smaller part of it leaves through street roofs and the remaining fraction blows through the street aiding pollutant dilution. Substantial differences between neighborhood-scale and city-scale configurations are found. For neighborhood-scale models, pollutant removal by rural/marine air is mainly associated to mean flow along the streets. Breathability improves in streets flanked by taller buildings since in this case more rural/marine air is captured inside canyons leading to stronger wind along the street. For city-scale models, pollutant removal due to turbulent fluctuations across street roofs competes with that due to mean flows along the street. Breathability improves in streets flanked by lower buildings in which less rural/marine air is driven out and pollutant removal by turbulent fluctuations is more effective. Based on these findings, suggestions for ventilation strategies for urban areas with tall buildings are provided.

Polycation stabilization of graphene suspensions.

Graphene is a leading contender for the next-generation electronic devices. We report a method to produce graphene membranes in the solution phase using polymeric imidazolium salts as a transferring medium. Graphene membranes were reduced from graphene oxides by hydrazine in the presence of the polyelectrolyte which is found to be a stable and homogeneous dispersion for the resulting graphene in the aqueous solution. A simple device with gold contacts on both sides was fabricated in order to observe the electronic properties.