The COVID-19 pandemic has resulted in over 33 million confirmed cases and over 1 million deaths globally, as of 1 October 2020. During the lockdown and restrictions placed on public activities and ...gatherings, green spaces have become one of the only sources of resilience amidst the coronavirus pandemic, in part because of their positive effects on psychological, physical and social cohesion and spiritual wellness. This study analyzes the impacts of COVID-19 and government response policies to the pandemic on park visitation at global, regional and national levels and assesses the importance of parks during this global pandemic. The data we collected primarily from Google’s Community Mobility Reports and the Oxford Coronavirus Government Response Tracker. The results for most countries included in the analysis show that park visitation has increased since February 16th, 2020 compared to visitor numbers prior to the COVID-19 pandemic. Restrictions on social gathering, movement, and the closure of workplace and indoor recreational places, are correlated with more visits to parks. Stay-at-home restrictions and government stringency index are negatively associated with park visits at a global scale. Demand from residents for parks and outdoor green spaces has increased since the outbreak began, and highlights the important role and benefits provided by parks, especially urban and community parks, under the COVID-19 pandemic. We provide recommendations for park managers and other decision-makers in terms of park management and planning during health crises, as well as for park design and development. In particular, parks could be utilized during pandemics to increase the physical and mental health and social well-being of individuals.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Accumulating reports evidenced that congenital hypothyroidism (CH) is a kind of endocrine diseases caused by thyroid hormone imperfection. MicroRNAs (miRNAs) were confirmed to exhibit ...protective functions in CH progression. However, the functions and latent mechanism of microRNA-624-5p (miR-624-5p) in CH remains unknown.
Objective
This report was designed to illustrate the potential molecular mechanisms of miR-624-5p on CH.
Methods
Rats were induced by 50 mg/day propylthiouracil to conduct CH models. Free thyroxine (fT4) and thyroid-Stimulating hormone (TSH) concentrations were measured to confirm CH model conduction. The direct target of miR-624-5p was predicted and verified by Starbase and dual luciferase reporter assay. Besides, the levels of miR-624-5p and sirtuin1 (SIRT1) in hippocampus or hippocampal neuronal cells were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot assays. Then CH rat behaviors were evaluated using open field test (OFT) and forced swim test (FST). Furthermore, neuronal cells viability and apoptosis were checked using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-
H
-tetrazolium bromide (MTT) and flow cytometry.
Results
qRT-PCR assay suggested that miR-624-5p was up-regulated and SIRT1 was low-expressed in hippocampus tissues of CH rats. SIRT1 was a direct target of miR-624-5p. MiR-624-5p inhibitor signally enhanced fT4 levels and reduced TSH levels in the plasma of CH rats, and improved CH rat depressive behaviors by targeting SIRT1. Moreover, our data also revealed that miR-624-5p inhibitor increased cell viability and reduced apoptotic neuronal cells, which was reversed by silencing of SIRT1.
Conclusions
Taken together, this research demonstrated that miR-624-5p serves as a promising target for CH treatment.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Sulfated galactofucan (ST-2) was obtained from
. It was then desulfated to obtain ST-2-DS, and autohydrolyzed and precipitated by ethanol to obtain the supernatant (ST-2-S) and precipitate (ST-2-C). ...ST-2-C was further fractionated by gel chromatography into two fractions, ST-2-H (high molecular weight) and ST-2-L (low molecular weight). Mass spectrometry (MS) of ST-2-DS was performed to elucidate the backbone of ST-2. It was shown that ST-2-DS contained a backbone of alternating galactopyranose residues (Gal)
(n ≤ 3) and fucopyranose residues (Fuc)
. In addition, ST-2-S was also determined by MS to elucidate the branches of ST-2. It was suggested that sulfated fuco-oligomers might be the branches of ST-2. Compared to the NMR spectra of ST-2-H, the spectra of ST-2-L was more recognizable. It was shown that ST-2-L contain a backbone of (Gal)
and (Fuc)
, sulfated mainly at C4 of Fuc, and interspersed with galactose (the linkages were likely to be 1→2 and 1→6). Therefore, ST-2 might contain a backbone of (Gal)
(n ≤ 3) and (Fuc)
. The sulfation pattern was mainly at C4 of fucopyranose and partially at C4 of galactopyranose, and the branches were mainly sulfated fuco-oligomers. Finally, the anti-tumor and anti-angiogenic activities of ST-2 and its derivates were determined. It was shown that the low molecular-weight sulfated galactofucan, with higher fucose content, had better anti-angiogenic and anti-tumor activities.
Wildland fires are a vital ecological process in Canada's protected areas (PAs), resulting in both ecological benefits and detrimental disturbances. In the face of rapid global changes, maximizing ...fire's ecological benefits while minimizing its negative impacts is particularly difficult but essential for PA fire management. To facilitate fire management in Canada's PAs, we conducted a comprehensive review of fire regimes and management strategies in PAs using several scholarly sources and national databases. We found that a high proportion of protected areas are in the remote boreal forest region or the Montane Cordillera. Fire regimes varied from the high-intensity fires in the boreal forest region to the more complex mixed-severity fires in the Montane Cordillera ecozone. Numerous fire tools and science-based management plans have been developed to address the varied and complex fire regimes. However, many challenges are still presented under longer fire seasons with increasingly severe burning across the country. To cope with these challenges, we proposed a protection-conservation integrated fire management framework. It is expected to improve the capability of the existing tools in guiding both fire protection and ecological fire use in Canada's PAs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This paper describes an advanced multi-scale weather modeling system, WRF–RTFDDA–LES, designed to simulate synoptic scale (∼2000
km) to small- and micro-scale (∼100
m) circulations of real weather in ...wind farms on simultaneous nested grids. This modeling system is built upon the National Center for Atmospheric Research (NCAR) community Weather Research and Forecasting (WRF) model. WRF has been enhanced with the NCAR Real-Time Four-Dimensional Data Assimilation (RTFDDA) capability. FDDA is an effective data assimilation algorithm, which is capable of assimilating diverse weather measurements on model grids and seamlessly providing realistic mesoscale weather forcing to drive a large eddy simulation (LES) model within the WRF framework. The WRF based RTFDDA LES modeling capability is referred to as WRF–RTFDDA–LES. In this study, WRF–RTFDDA–LES is employed to simulate real weather in a major wind farm located in northern Colorado with six nested domains. The grid sizes of the nested domains are 30, 10, 3.3, 1.1, 0.370 and 0.123
km, respectively. The model results are compared with wind–farm anemometer measurements and are found to capture many intra-farm wind features and microscale flows. Additional experiments are conducted to investigate the impacts of subgrid scale (SGS) mixing parameters and nesting approaches. This study demonstrates that the WRF–RTFDDA–LES system is a valuable tool for simulating real world microscale weather flows and for development of future real-time forecasting system, although further LES modeling refinements, such as adaptive SGS mixing parameterization and wall-effect modeling, are highly desired.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The grasslands of North America are threatened by woody encroachment. Restoring historical fire regimes has been used to manage brush encroachment. However, fire management may be insufficient due to ...the nonlinear and hysteretic responses of vegetation recovery following encroachment and the social–political constraints affecting fire management. We synthesized the fire thresholds required to control woody encroachment by typical encroaching species in North America, especially the Great Plains region, and identified the social–political constraints facing fire management in selected grassland national parks. Our synthesis revealed the resistance, hysteresis, and irreversibility of encroached grasslands using fire and emphasized the need for a combination of brush management methods if the impacts of climate change are to be addressed. Frequent fires alone may maintain grassland states, reflecting resistance. However, high-intensity fires exceeding fire-mortality thresholds are required to exclude non-resprouting shrubs and trees, indicating hysteresis. Fire alone may be insufficient to reverse encroachment by resprouting species, exhibiting reversibility. In practice, appropriate fire management may restore resistant grassland states. However, social–political constraints have restricted the use of frequent and high-intensity fires, thereby reducing the effectiveness of management actions to control woody encroachment of grasslands in national parks. This research proposes a resilience-based framework to manage woody encroachment in grassland national parks and similar protected areas.
The COVID-19 pandemic posed challenges to the tourism sector globally. We investigated changes in visitor demographics, satisfaction level, and its determinants pre- and peri-COVID-19. Data were ...collected using questionnaire surveys in 2019 and 2021 within Banff National Park (BNP). The data analyses were based on a sample size of 1183 respondents by conducting factor analysis, correlation analysis and stepwise regression analysis. Results highlight that there were fewer international visitors and more local and domestic visitors during the pandemic. Park attributes were evaluated at a higher satisfaction level peri-COVID-19. The quality of the Park facilities and services were the most important satisfaction determinants pre- and peri-COVID-19, and all the Park COVID-19 measures and actions received positive experience from visitors. This research fills this knowledge gap by developing a better understanding in the change of visitor demographics and satisfaction level in BNP under the context of the pandemic. It also provides implication for both scholars and practitioners to understand the impacts of the pandemic on Park visitation. The study can provide insights for utilizing the pandemic as a transformative strength and for mitigating its negative impact on tourism industry.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
BackgroundT cell receptor engineered T (TCR-T) cell therapies have demonstrated promising efficacy in the treatment of solid tumors. However, a major challenge in their effectiveness arises from ...tumor antigen escape. One such mechanism involves deficiencies in the antigen presentation machinery (APM). The classical APM requires molecules like proteasome and the peptide transporter TAP. Alterations in these molecules have been observed in various tumor types and contribute to tumor antigen escape. Interestingly, the presentation of some peptide antigens have been shown to utilize an alternative pathway. We hypothesize that TCR-T cells specific for these particular peptide antigens can bypass defects in the classical APM and overcome tumor antigen escape.MethodsWe have previously identified an HLA-A*24:02 restricted alpha-fetoprotein (AFP) peptide (AFP2–11).1 A TCR specific for AFP2–11 was isolated from peripheral blood mononuclear cells of a healthy donor. The TCR was affinity enhanced through phage display. The antitumor activity of the affinity enhanced TCR-T cells was evaluated using tumor cell lines and in vivo tumor models. The specificity of the affinity enhanced TCR was assessed using a panel of primary cells from various tissues and the X-scan method. To determine whether AFP2–11 requires the classical APM, we investigated AFP2–11 presentation on HLA-A*24:02 overexpression T2 cells (a TAP1 deficient cell line) and by knocking out TAP and other key molecules involved in the classical APM in HepG2 cells (an AFP and HLA-A*24:02 positive hepatocellular carcinoma cell line).ResultsThe affinity-enhanced AFP2–11-specific TCR demonstrated significantly enhanced antitumor activities in in vitro assays. Adoptive transfer of TCR-T cells led to inhibition of tumor growth in hepatocellular carcinoma (HCC) tumor models. The affinity-enhanced TCR maintained antigen specificity, as confirmed by cross-reactivity assays using a diverse panel of primary cells and the X-scan method. Furthermore, AFP2–11-specific TCR-transduced T cells effectively responded to AFP overexpressing T2 cells and TAP1-knocked-out HepG2 cells, indicating that AFP2–11 could still be presented on the cell surface despite defects in the classical APM.ConclusionsWe have successfully developed an affinity-enhanced TCR specific for a peptide antigen utilizing the alternative presentation pathway. This TCR has the potential to overcome tumor antigen escape resulting from defects in APM. Our study holds significant implications for TCR-based therapy, suggesting a novel strategy for overcoming tumor escape.ReferencesLi Z, Gong H, Liu Q, Wu W, Cheng J, Mei Y, et al. Identification of an HLA-A*24:02-restricted α-fetoprotein signal peptide-derived antigen and its specific T-cell receptor for T-cell immunotherapy. Immunology. 2020;159:384–92.
There is a growing demand for regional-scale climate predictions and assessments. Quantifying the impacts of uncertainty in initial conditions and lateral boundary forcing data on regional model ...simulations can potentially add value to the usefulness of regional climate modeling. Results from a regional model depend on the realism of the driving data from either global model outputs or global analyses; therefore, any biases in the driving data will be carried through to the regional model. This study used four popular global analyses and achieved 16 driving datasets by using different interpolation procedures. The spread of the 16 datasets represents a possible range of driving data based on analyses to the regional model. This spread is smaller than typically associated with global climate model realizations of the Arctic climate. Three groups of 16 realizations were conducted using the fifth-generation Pennsylvania State University–National Center for Atmospheric Research (PSU–NCAR) Mesoscale Model (MM5) in an Arctic domain, varying both initial and lateral boundary conditions, varying lateral boundary forcing only, and varying initial conditions only. The response of monthly mean atmospheric states to the variations in initial and lateral driving data was investigated.
Uncertainty in the regional model is induced by the interaction between biases from different sources. Because of the nonlinearity of the problem, contributions from initial and lateral boundary conditions are not additive. For monthly mean atmospheric states, biases in lateral boundary conditions generally contribute more to the overall uncertainty than biases in the initial conditions. The impact of initial condition variations decreases with the simulation length while the impact of variations in lateral boundary forcing shows no clear trend. This suggests that the representativeness of the lateral boundary forcing plays a critical role in long-term regional climate modeling. The extent of impact of the driving data uncertainties on regional climate modeling is variable dependent. For some sensitive variables (e.g., precipitation, boundary layer height), even the interior of the model may be significantly affected.
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BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Oceanic overflows are bottom-trapped density currents originating in semienclosed basins, such as the Nordic seas, or on continental shelves, such as the Antarctic shelf. Overflows are the source of ...most of the abyssal waters, and therefore play an important role in the large-scale ocean circulation, forming a component of the sinking branch of the thermohaline circulation. As they descend the continental slope, overflows mix vigorously with the surrounding oceanic waters, changing their density and transport significantly. These mixing processes occur on spatial scales well below the resolution of ocean climate models, with the result that deep waters and deep western boundary currents are simulated poorly. The Gravity Current Entrainment Climate Process Team was established by the U.S. Climate Variability and Prediction (CLIVAR) Program to accelerate the development and implementation of improved representations of overflows within large-scale climate models, bringing together climate model developers with those conducting observational, numerical, and laboratory process studies of overflows. Here, the organization of the Climate Process Team is described, and a few of the successes and lessons learned during this collaboration are highlighted, with some emphasis on the well-observed Mediterranean overflow. The Climate Process Team has developed several different overflow parameterizations, which are examined in a hierarchy of ocean models, from comparatively well-resolved regional models to the largest-scale global climate models.
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BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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