Resveratrol alleviates endoplasmic reticulum stress-induced cell death and improves functional prognosis after traumatic brain injury in mice.

Resveratrol (RSV) is a polyphenol antioxidant that has been shown to have neuroprotective effects. We sought molecular mechanisms that emphasize the anti-inflammatory activity of RSV in traumatic brain injury (TBI) in mice associated with endoplasmic reticulum stress (ERS). After establishing three experimental groups (sham, TBI, and TBI+RSV), we explored the results of RSV after TBI on ERS and caspase-12 apoptotic pathways. The expression levels of C/EBP homologous protein (CHOP), glucose regulated protein 78kD (GRP78), caspase-3, and caspase-12 in cortical brain tissues were assessed by western blotting. The qPCR analysis was also performed on mRNA expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in cortical brain tissue. In addition, the expression of GRP78 in microglia (ionized calcium binding adaptor molecule 1; Iba-1) and neurons (neuronal nuclei; NeuN) was identified by immunofluorescence staining. The neurological function of mice was assessed by modified neurological severity scores (mNSS). After drug treatment, the expression of CHOP, GRP78, caspase-3 and caspase-12 decreased, and qPCR results showed that TNF-α and IL-1ß were down-regulated. Immunofluorescence staining showed down-regulation of Iba-1+/GRP78+ and NeuN+/GRP78+ cells after RSV treatment. The mNSS analysis confirmed improvement after RSV treatment. RSV improved apoptosis by downregulating the ERS signaling pathway and improved neurological prognosis in mice with TBI.

Evaluating SARS-CoV-2 airborne quanta transmission and exposure risk in a mechanically ventilated multizone office building.

The world has faced tremendous challenges during the COVID-19 pandemic since 2020, and effective clean air strategies that mitigate infectious risks indoors have become more essential. In this study, a novel approach based on the Wells-Riley model applied to a multizone building was proposed to simulate exposure to infectious doses in terms of "quanta". This modeling approach quantifies the relative benefits of different risk mitigation strategies so that their effectiveness could be compared. A case study for the US Department of Energy large office prototype building was conducted to illustrate the approach. The infectious risk propagation from the infection source throughout the building was evaluated. Different mitigation strategies were implemented, including increasing outdoor air ventilation rates and adding air-cleaning devices such as Minimum Efficiency Reporting Value (MERV) filters and portable air cleaners (PACs) with HEPA filters in-room/in-duct germicidal ultraviolet (GUV) lights, layering with wearing masks. Results showed that to keep the risk of the infection propagating low the best strategy without universal masking was the operation of in-room GUV or a large industrial-sized PAC; whereas with masking all strategies were acceptable. This study contributes to a better understanding of the airborne transmission risks in multizone, mechanically ventilated buildings and how to reduce infection risk from a public health perspective of different mitigation strategies.

Indoor thermal stratification and its statistical distribution.

Thermal stratification is established when warmer air rises and cooler air descends under thermal buoyancy. It occurs in indoor environment situations including large warehouse-type buildings, buoyancy-driven ventilated spaces with displacement, underfloor ventilation, and/or natural ventilation, and enclosure fires with hot smoke layer on top of cold air layer. This paper reports a recent study that thermal stratification of indoor environment follows the statistical Beta distribution so the vertical temperature distribution is the Cumulative Distribution Function of the Beta distribution defined by two shape parameters, Alpha (α) and Beta (ß), despite ventilation types, heat source and other details. It is then possible to estimate a complete vertical temperature profile under thermal stratification by four temperature points (ie, 4-point Beta distribution), or as few as two points (ie, 2-point Beta distribution) with a slight loss of accuracy. The study was confirmed by the field measurement data of five warehouse-type buildings, and eleven thermal stratification studies from the literature. A few applications were demonstrated including quantitative characterization of thermal stratification; estimation of mean and spatial temperature uniformities and other key parameters. The dimensionless nature of the methodology may also be potentially applied to other indoor stratification phenomena.

Typical and extreme weather datasets for studying the resilience of buildings to climate change and heatwaves.

We present unprecedented datasets of current and future projected weather files for building simulations in 15 major cities distributed across 10 climate zones worldwide. The datasets include ambient air temperature, relative humidity, atmospheric pressure, direct and diffuse solar irradiance, and wind speed at hourly resolution, which are essential climate elements needed to undertake building simulations. The datasets contain typical and extreme weather years in the EnergyPlus weather file (EPW) format and multiyear projections in comma-separated value (CSV) format for three periods: historical (2001-2020), future mid-term (2041-2060), and future long-term (2081-2100). The datasets were generated from projections of one regional climate model, which were bias-corrected using multiyear observational data for each city. The methodology used makes the datasets among the first to incorporate complex changes in the future climate for the frequency, duration, and magnitude of extreme temperatures. These datasets, created within the IEA EBC Annex 80 "Resilient Cooling for Buildings", are ready to be used for different types of building adaptation and resilience studies to climate change and heatwaves.

Evolution of the local climate in Montreal and Ottawa before, during and after a heatwave and the effects on urban heat islands.

The heatwave event to which the Ontario-Quebec area was subjected in 2018 resulted in significant morbidity and mortality. In this study, an investigation was conducted on how this heatwave affected the respective urban heat islands (UHIs) in Montreal and Ottawa. The modelled urban climates were compared before, during and after the heatwave using a Weather Research and Forecast (WRF) model having a 1 km spatial resolution. The UHI was calculated using two methods. As a first method, the "rural-ring" method was used to calculate the UHI in regard to temperature differences between urban and surrounding rural areas. The second method used the "urban-increment" approach where simulation results were compared to another simulation in which urban cells are replaced by croplands. Results show that urban land can raise temperatures by up to 12 °C at surfaces and 6 °C in the near-surface air. A synoptic anticyclone in the lower atmosphere was responsible for the heatwave, although both cities were located in areas peripheral to the anticyclone. During the heatwave, precipitation at the initial stage of the event and low wind conditions largely varied the pattern of the UHI effect within each urban center. The UHI was generally unchanged or even reduced during this heatwave, but there was substantial diurnal variation. Around noon and in the afternoon, the UHI was amplified by up to 3 °C, whereas it was suppressed or even negative at sunrise.

Development and performance assessment of a new opensource Bayesian inference R platform for building energy model calibration.

Many factors contribute to the inherent uncertainty of energy consumption modeling in buildings. It is essential to perform a calibration and sensitivity analysis in order to manage these uncertainties. Despite the availability of several calibration methods, they are often deterministic and lack quantified uncertainties. Moreover, the selection of parameters in building energy modeling for calibration depends on the user's experience. Therefore, a more rigorous selection process is required. This study developed a new automated Bayesian Inference calibration platform running as an R package. A sensitivity analysis module and a Bayesian inference module determine the calibration parameters and uncertainties, respectively. The Meta-model module is developed to replace the building energy model for the Markov Chain Monte Carlo process to save computing time. The proposed platform is successfully demonstrated on a synthetic high-rise office building and a real high-rise residential building in a hot and arid climate. The relationship between the number of calibration parameters, calibration performance, and the accuracy of the Meta-model is further discussed. The developed calibration platform in this study proved to have clear advantages over the existing platforms, with the ability to reasonably estimate building energy performance in a short computing time.

Outdoor heat stress assessment using an integrated multi-scale numerical weather prediction system: A case study of a heatwave in Montreal.

More frequent and severe extreme weather events such as heatwaves are among the most serious challenges to society in coping with the changing climate. To evaluate the impacts of the heatwave on large-scale urban areas, a multi-scale weather forecasting system is designed by integrating different resolutions of the Canadian urbanized version of the Global Environmental Multiscale (GEM) Numerical Weather Prediction (NWP) model, cascading from 10 km to 2.5 km, and 250 m. The multi-scale model is implemented in Montreal, Canada, for modeling the 2018 heatwave. Simulation results are well-validated against measurement data, including Moderate Resolution Imaging Spectroradiometer (MODIS) satellite imagery and ten weather stations in the city. The Universal Thermal Climate Index (UTCI) map was calculated to identify vulnerable regions in the city against the heatwave. Land-use types in hotspots and coldspots are analyzed to find dominant factors in the formation of hot and cold areas. It is found that natural landscapes such as vegetation, trees, and water bodies are the dominant features of most coldspots. On the other hand, roads, parking lots, less tree covers, and industrial activities are the common land use features in the hotspots. A weak correlation is found between heat-related death locations and the outdoor UTCI map, implying that the assessment of an outdoor heatwave may not address overheated buildings and communities. This paper shows the importance of built environments - their properties and occupants' socio-demographic factors in the study of heat-related mortalities in cities.

Development of a Bayesian inference model for assessing ventilation condition based on CO2 meters in primary schools.

Outdoor fresh air ventilation plays a significant role in reducing airborne transmission of diseases in indoor spaces. School classrooms are considerably challenged during the COVID-19 pandemic because of the increasing need for in-person education, untimely and incompleted vaccinations, high occupancy density, and uncertain ventilation conditions. Many schools started to use CO2 meters to indicate air quality, but how to interpret the data remains unclear. Many uncertainties are also involved, including manual readings, student numbers and schedules, uncertain CO2 generation rates, and variable indoor and ambient conditions. This study proposed a Bayesian inference approach with sensitivity analysis to understand CO2 readings in four primary schools by identifying uncertainties and calibrating key parameters. The outdoor ventilation rate, CO2 generation rate, and occupancy level were identified as the top sensitive parameters for indoor CO2 levels. The occupancy schedule becomes critical when the CO2 data are limited, whereas a 15-min measurement interval could capture dynamic CO2 profiles well even without the occupancy information. Hourly CO2 recording should be avoided because it failed to capture peak values and overestimated the ventilation rates. For the four primary school rooms, the calibrated ventilation rate with a 95% confidence level for fall condition is 1.96±0.31 ACH for Room #1 (165 m3 and 20 occupancies) with mechanical ventilation, and for the rest of the naturally ventilated rooms, it is 0.40±0.08 ACH for Room #2 (236 m3 and 21 occupancies), 0.30±0.04 or 0.79±0.06 ACH depending on occupancy schedules for Room #3 (236 m3 and 19 occupancies), 0.40±0.32,0.48±0.37,0.72±0.39 ACH for Room #4 (231 m3 and 8-9 occupancies) for three consecutive days.

A real-time web tool for monitoring and mitigating indoor airborne COVID-19 transmission risks at city scale.

Airborne transmission of aerosols contributes to a large portion of the SARS-CoV-2 spread indoors. This study develops a real-time interactive web-based platform for the public to compare various strategies to curb indoor airborne transmission of COVID-19 in different archetype buildings at a city scale. Although many countries have started vaccination and a gradual re-opening, because of emerging new variants of the virus and the possibility of future pandemics, a lively updated tool for monitoring and mitigation of infection risk is essential. As a demonstration, we evaluated the impacts of six mitigation measures on the infection risks in various building types in a city. It shows that the same strategy could perform quite differently, depending on building types and properties. All strategies are shown to reduce the infection risk but wearing a mask and reducing exposure time are the most effective strategies in many buildings, with around 60% reduction. Doubling the minimum required outdoor air ventilation rate is not as effective as other strategies to reduce the risk. It also causes considerable penalties on energy consumption. Therefore, new building ventilation standards, control actions, and design criteria should be considered to mitigate the infection risk and save energy.

In situ experimental study of carbon monoxide generation by gasoline-powered electric generator in an enclosed space.

On the basis of currently available data, approximately 97% of generator-related carbon monoxide (CO) fatalities are caused by operating currently marketed, carbureted spark-ignited gasoline-powered generators (not equipped with emission controls) in enclosed spaces. To better understand and to reduce the occurrence of these fatalities, research is needed to quantify CO generation rates, develop and test CO emission control devices, and evaluate CO transport and exposure when operating a generator in an enclosed space. As a first step in these efforts, this paper presents measured CO generation rates from a generator without any emission control devices operating in an enclosed space under real weather conditions. This study expands on previously published information from the U.S. Consumer Product Safety Commission. Thirteen separate tests were conducted under different weather conditions at half and full generator load settings. It was found that the CO level in the shed reached a maximum value of 29,300 +/- 580 mg/m3, whereas the oxygen (O2) was depleted to a minimum level of 16.2 +/- 0.02% by volume. For the test conditions of real weather and generator operation, the CO generation and the O2 consumption could be expressed as time-averaged generation/consumption rates. It was also found that the CO generation and O2 consumption rates can be correlated to the O2 levels in the space and the actual load output from the generator. These correlations are shown to agree well with the measurements.

Effects of pool size and spacing on burning rate and flame height of two square heptane pool fires.

The interaction of multiple pool fires might lead to higher burning rate and flame height than single pool fire, raising the possibility of fire ignition and flame spread and increasing the risks to people, buildings and environment. To quantify the burning rate and flame height of multiple pool fires from the view of physical mechanism, this paper presents an experimental study on two identical square pool fires. Heptane was used as fuel. The pool size and spacing were varied. Results showed that both the burning rate and flame height change non-monotonically with spacing. From the view of air entrainment, a correlation for the flame height of two pool fires is developed involving pool size, spacing and the flame height of zero spacing. The comparison with experimental results shows that the developed correlation is suitable for two heptane or propane fires. A theoretical study based on energy balance at one of the pool surfaces is performed to evaluate the burning rate of two fires, which is finally expressed as a function of pool size, spacing, burning rate and the flame height of single fire. The proposed model is validated using the experimental and literature data, which presents a reasonable reliability.

Inhibition of Connexin43 hemichannels with Gap19 protects cerebral ischemia/reperfusion injury via the JAK2/STAT3 pathway in mice.

Functional disruption of the neurovascular unit may lead to aggravation of ischemic cerebral injury. Connexin43 (Cx43)-dependent gap junctional channels (GJCs) are critical in maintaining brain homeostasis. However, excessive opening of hemichannels (HCs) after cerebral ischemia may cause apoptosis and finally lead to amplification of ischemic injury. Previous studies indicated that Cx43 mimetic peptides Gap26 and Gap27 may protect cerebral ischemic injury, but the latest studies showed they also inhibit the opening of GJCs, which are beneficial for neuroprotection. Recent studies showed that Gap19 is a new specific inhibitor of Cx43 HCs. We investigated the role of Gap19 on cerebral ischemia/reperfusion (I/R) injury in a mouse model of middle cerebral artery occlusion (MCAO). Ventricle-injected Gap19 significantly alleviated infarct volume, neuronal cell damage and neurological deficits after ischemia, the neuroprotective effect of Gap19 was significant stronger than Gap26. Post-treatment with TAT-Gap19 still provided neuroprotection when it was administered intraperitoneally at 4 h after reperfusion. In addition, we found that Gap19 decreased the levels of cleaved caspase-3 and Bax and increased the level of Bcl-2, suggesting the anti-apoptotic activity of specifically blocking the Cx43 HCs. Furthermore, our data indicate that Gap19 treatment increased the levels of phosphorylated JAK2 and STAT3 both in vivo and in vitro. Gap19 inhibited hemichannel activity assessed by dye uptake in astrocytes. And we detected that pSTAT3 co-localized with Cx43 together in astrocytes after oxygen glucose deprivation (OGD) injury. Finally, AG490, a blocker of the JAK2/STAT3 pathway, could reverse the neuroprotective effects of Gap19 both in vivo and in vitro. Our experiment investigated the anti-apoptotic activity of Gap19, the specific inhibitor of Cx43 HCs, and the potential mechanisms. Our results demonstrated that Gap19 plays an anti-apoptotic role via activating the JAK2/STAT3 pathway after cerebral I/R injury, indicating that specific blocking of Cx43 HCs is a potential target for ischemic stroke.

Predictive value of the THRIVE score for outcome in patients with acute basilar artery occlusion treated with thrombectomy.

BACKGROUND AND PURPOSE: A higher Totaled Health Risks in Vascular Events (THRIVE) score has been shown to predict poor functional outcome in patients with acute ischemic stroke (AIS) and anterior circulation large vessel occlusions undergoing thrombectomy treatment. We attempted to evaluate the value of the THRIVE score in predicting the outcome of thrombectomy treatment in AIS patients with basilar artery occlusion (BAO). METHODS: A total of 68 AIS patients with BAO who underwent thrombectomy treatment from May 2014 to August 2018 were included in the present study. Multivariable logistic regression was performed to determine the predictive value of the THRIVE score for poor functional outcome (defined as modified Rankin Scale score ≥ 3), all-cause mortality, and hemorrhage transformation (HT) at 3 months. RESULTS: A total of 42 (61.8%) participants experienced poor functional outcomes, 25 (36.8%) patients died from all causes, and 21 (30.9%) patients had HT during the 3-month follow-up. Multivariable logistic regression showed that a higher THRIVE score was significantly associated with poor functional outcome (odds ratio [OR] 5.86, 95% confidence interval [CI], 2.28-14.91, p < .001) as well as all-cause mortality (OR 2.40, 95% CI, 1.32-4.34, p = .004) but not HT (p = .607). The C-statistic of the THRIVE score was significantly larger than that of the NIHSS score for predicting poor functional outcome (AUC = 0.913; cutoff > 5; sensitivity, 88.5%; specificity, 83.3%, p = .007) and all-cause mortality (AUC = 0.768; cutoff > 5; sensitivity, 92.0%; specificity, 65.1%, p = .018). CONCLUSIONS: A high THRIVE score was independently associated with an increased risk of poor functional outcome and all-cause mortality in AIS patients with BAO who underwent thrombectomy treatment. Moreover, the THRIVE score appeared to be a better predictor of clinical outcome than the NIHSS score.

ESE1 expression correlates with neuronal apoptosis in the hippocampus after cerebral ischemia/reperfusion injury.

Epithelial-specific ETS-1 (ESE1), a member of the ETS transcription factor family, is widely expressed in multiple tissues and performs various functions in inflammation. During neuroinflammation, ESE1 promotes neuronal apoptosis; however, the expression and biological functions of ESE1 remain unclear after cerebral ischemia/reperfusion. We performed in vivo and in vitro experiments to explore the role of ESE1 in cerebral ischemic injury. A modified four vessel occlusion method was used in adult Sprague-Dawley rats. At 6, 12, 24, 48, and 72 hours after model induction, the hippocampus was collected for analysis. Western blot assays and immunohistochemistry showed that the expression of ESE1, phosphorylated p65 and active caspase-3 was significantly up-regulated after ischemia. Double immunofluorescence staining indicated that ESE1 and NeuN were mostly co-located in the hippocampus after ischemia. Furthermore, ESE1 was also co-expressed with active caspase-3. PC12 cells were stimulated with cobalt chloride (CoCl2) to establish a chemical hypoxia model. After ESE1 knockdown by siRNA for 6 hours, cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays. The levels of ESE1, phosphorylated p65 and active caspase-3 were also remarkably increased in PC12 cells after CoCl2 stimulation. After ESE1 knockdown, PC12 cell viability was increased after hypoxia. siRNA knockdown of ESE1 decreased the level of p-p65 and active caspase-3 after CoCl2 stimulation. These data reveal that ESE1 levels are elevated in the hippocampus after cerebral ischemia/reperfusion injury. This may play a role in neuronal apoptosis via activation of the nuclear factor-κB pathway.

Inhibition of Connexin 43 Hemichannels Alleviates Cerebral Ischemia/Reperfusion Injury via the TLR4 Signaling Pathway.

Connexin 43 (Cx43) widely exists in all components of the neurovascular unit (NVU) and is a constituent of gap junctions and hemichannels. In physiological states, gap junctions are open for regular intercellular communication, and the hemichannels present low open probability in astrocytes. After cerebral ischemia, a large number of hemichannels are unusually opened, leading to cell swelling and even death. Most known hemichannel blockers also inhibit gap junctions and sequentially obstruct normal electrical cell-cell communication. In this study, we tested the hypothesis that Gap19, a selective Cx43-hemichannel inhibitor, exhibited neuroprotective effects on cerebral ischemia/reperfusion (I/R). An obvious improvement in neurological scores and infarct volume reduction were observed in Gap19-treated mice after brain ischemia induced by middle cerebral artery occlusion (MCAO). Gap19 treatment attenuated white matter damage. Moreover, Gap19 treatment suppressed the expression of Cx43 and Toll-like receptor 4 (TLR4) pathway-relevant proteins and prevented the overexpression of tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). To further explore downstream signaling, we established an in vitro model-oxygen glucose deprivation (OGD) to simulate ischemic conditions. Immunofluorescence staining showed that Cx43 co-existed with TLR4 in astrocytes. The hemichannel activity was increased after OGD and Gap19 could inhibit this effect on astrocytes. Gap19 substantially improved relative cell vitality and decreased the expression of Cx43, TLR4 and inflammatory cytokines in vitro. In addition, in the lipopolysaccharide (LPS) stimulation OGD model, Gap19 also exhibited a protective effect via inhibiting TLR4 pathway activation. In summary, our results showed that Gap19 exerted a neuroprotective effect after stroke via inhibition of the TLR4-mediated signaling pathway.