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Coronavirus infection induces the unfolded protein response (UPR), a cellular signalling pathway composed of three branches, triggered by unfolded proteins in the endoplasmic reticulum (ER) due to high ER load. We have used RNA sequencing and ribosome profiling to investigate holistically the transcriptional and translational response to cellular infection by murine hepatitis virus (MHV), often used as a model for the Betacoronavirus genus to which the recently emerged SARS-CoV-2 also belongs. We found the UPR to be amongst the most significantly up-regulated pathways in response to MHV infection. To confirm and extend these observations, we show experimentally the induction of all three branches of the UPR in both MHV- and SARS-CoV-2-infected cells. Over-expression of the SARS-CoV-2 ORF8 or S proteins alone is itself sufficient to induce the UPR. Remarkably, pharmacological inhibition of the UPR greatly reduced the replication of both MHV and SARS-CoV-2, revealing the importance of this pathway for successful coronavirus replication. This was particularly striking when both IRE1α and ATF6 branches of the UPR were inhibited, reducing SARS-CoV-2 virion release (~1,000-fold). Together, these data highlight the UPR as a promising antiviral target to combat coronavirus infection.

Hydropower has been the leading source of renewable energy across the world, accounting for up to 71% of this supply as of 2016. This capacity was built up in North America and Europe between 1920 and 1970 when thousands of dams were built. Big dams stopped being built in developed nations, because the best sites for dams were already developed and environmental and social concerns made the costs unacceptable. Nowadays, more dams are being removed in North America and Europe than are being built. The hydropower industry moved to building dams in the developing world and since the 1970s, began to build even larger hydropower dams along the Mekong River Basin, the Amazon River Basin, and the Congo River Basin. The same problems are being repeated: disrupting river ecology, deforestation, losing aquatic and terrestrial biodiversity, releasing substantial greenhouse gases, displacing thousands of people, and altering people’s livelihoods plus affecting the food systems, water quality, and agriculture near them. This paper studies the proliferation of large dams in developing countries and the importance of incorporating climate change into considerations of whether to build a dam along with some of the governance and compensation challenges. We also examine the overestimation of benefits and underestimation of costs along with changes that are needed to address the legitimate social and environmental concerns of people living in areas where dams are planned. Finally, we propose innovative solutions that can move hydropower toward sustainable practices together with solar, wind, and other renewable sources.

Described in the New York Times as \"an astonishingly clear 'user's manual' that explains our health care system and the policies that will change it,\" The Health Care Handbook, by Drs. Elisabeth Askin and Nathan Moore, offers a practical, neutral, and readable overview of the U.S. health care system in a compact, convenient format. The fully revised third edition provides concise coverage on health care delivery, insurance and economics, policy, and reform-all critical components of the system in which health care professionals work. Written in a conversational and accessible tone, this popular, highly regarded handbook serves as a \"one stop shop\" for essential facts, systems, concepts, and analysis of the U.S. health care system, providing the tools you need to confidently evaluate current health care policy and controversies. 

Spatial and temporal patterns of rainfall are governed by complex interactions between climate and landscape perturbations including deforestation, fire, and drought. Previous research demonstrated that rainfall in portions of the Amazon Basin has intensified, resulting in more extreme droughts and floods. The basin has global impacts on climate and hydrologic cycles; thus, it is critical to understand how precipitation patterns and intensity are changing. Due to insufficient precipitation gauges, we analyzed the variability and seasonality of rainfall over the Amazon Basin from 1982 to 2018 using high-resolution gridded precipitation products. We developed several precipitation indices and analyzed their trends using the Mann–Kendall test (Mann 1945; Kendall, 1975) to identify significant changes in rainfall patterns over time and space. Our results show landscape scale changes in the timing and intensity of rainfall events. Specifically, wet areas of the western Basin have become significantly wetter since 1982, with an increase of 182 mm of rainfall per year. In the eastern and southern regions, where deforestation is widespread, a significant drying trend is evident. Additionally, local alterations to precipitation patterns were also observed. For example, the Tocantins region has had a significant increase in the number of dry days during both wet and dry seasons, increasing by about 1 day per year. Surprisingly, changes in rainfall amount and number of dry days do not consistently align. Broadly, over this 37-year period, wet areas are trending wetter and dry areas are trending drier, while spatial anomalies show structure at the scale of hundreds of kilometers.

Women have achieved parity with men among biomedical science degree holders but remain underrepresented in academic positions. The National Institutes of Health (NIH)—the world’s largest public funder of biomedical research—receives less than one-third of its new grant applications from women. Correspondingly, women compose less than one-third of NIH research grantees, even though they are as successful as men in obtaining first-time grants. Our study examined women’s and men’s NIH funding trajectories over time (n = 34,770), exploring whether women remain funded at the same rate as men after receiving their first major research grants. A survival analysis demonstrated a slightly lower funding longevity for women. We next examined gender differences in application, review, and funding outcomes. Women individually held fewer grants, submitted fewer applications, and were less successful in renewing grants—factors that could lead to gender differences in funding longevity. Finally, two adjusted survival models that account for initial investigator characteristics or subsequent application behavior showed no gender differences, suggesting that the small observed longevity differences are affected by both sets of factors. Overall, given men’s and women’s generally comparable funding longevities, the data contradict the common assumption that women experience accelerated attrition compared with men across all career stages. Women’s likelihood of sustaining NIH funding may be better than commonly perceived. This suggests a need to explore women’s underrepresentation among initial NIH grantees, as well as their lower rates of new and renewal application submissions.

Many developing nations are facing severe food insecurity partly because of their dependence on rainfed agriculture. Climate variability threatens agriculture-based community livelihoods. With booming population growth, agricultural land expands, and natural resource extraction increases, leading to changes in land use and land cover characterized by persistent vegetation greening and browning. This can modify local climate variability due to changing land–atmosphere interactions. Yet, for landscapes with significant interannual variability, such as the Mount Elgon ecosystem in Kenya and Uganda, characterizing these changes is a difficult task and more robust methods have been recommended. The current study combined trend (Mann–Kendall and Sen’s slope) and breakpoint (bfast) analysis methods to comprehensively examine recent vegetation greening and browning in Mount Elgon at multiple time scales. The study used both Moderate Resolution Imaging Spectroradiometer (MODIS) Normalized Difference Vegetation Index (NDVI) and Climate Hazards group Infrared Precipitation with Stations (CHIRPS) data and attempted to disentangle nature- versus human-driven vegetation greening and browning. Inferences from a 2019 field study were valuable in explaining some of the observed patterns. The results indicate that Mount Elgon vegetation is highly variable with both greening and browning observable at all time scales. Mann–Kendall and Sen’s slope revealed major changes (including deforestation and reforestation), while bfast detected most of the subtle vegetation changes (such as vegetation degradation), especially in the savanna and grasslands in the northeastern parts of Mount Elgon. Precipitation in the area had significantly changed (increased) in the post-2000 era than before, particularly in 2006–2010, thus influencing greening and browning during this period. The greenness–precipitation relationship was weak in other periods. The integration of Mann–Kendall and bfast proved useful in comprehensively characterizing vegetation greenness. Such a comprehensive description of Mount Elgon vegetation dynamics is an important first step to instigate policy changes for simultaneously conserving the environment and improving livelihoods that are dependent on it.

Irrigation’s effects on precipitation during an exceptionally dry summer (June–August 2012) in the United States were quantified by incorporating a novel dynamic irrigation scheme into the Weather Research and Forecasting (WRF) Model. The scheme is designed to represent a typical application strategy for farmlands across the conterminous United States (CONUS) and a satellite-derived irrigation map was incorporated into the WRF-Noah-Mosaic module to realistically trigger the irrigation. Results show that this new irrigation approach can dynamically generate irrigation water amounts that are in close agreement with the actual irrigation water amounts across the high plains (HP), where the prescribed scheme best matches real-world irrigation practices. Surface energy and water budgets have been substantially altered by irrigation, leading to modified large-scale atmospheric circulations. In the studied dry summer, irrigation was found to strengthen the dominant interior high pressure system over the southern and central United States and deepen the trough over the upper Midwest. For the HP and central United States, the rainfall amount is slightly reduced over irrigated areas, likely as a result of a reduction in both local convection and large-scale moisture convergence resulting from interactions and feedbacks between the land surface and atmosphere. In areas downwind of heavily irrigated regions, precipitation is enhanced, resulting in a 20%–100% reduction in the dry biases (relative to the observations) simulated over a large portion of the downwind areas without irrigation in the model. The introduction of irrigation reduces the overall mean biases and root-mean-square errors in the simulated daily precipitation over the CONUS.

The effect of degree of roast on resulting caffeine content in brewed coffee has been extensively researched, but conflicting methodologies and results have muddled development of a general conclusion. In this study, 30 unique combinations of green coffee variety, degree of roast, and brew time were investigated regarding extraction yield and caffeine content. An AeroPress brewer was used to prepare brew samples using a 15:1 mass ratio of brew water to ground coffee. Refractometry and HPLC were respectively used to measure extraction yield and caffeine content of brewed samples. Scanning electron microscopy was used to measure porosity of roasted seeds and showed increasing porosity with the degree of roast. Extraction yields generally decreased for roast batches with roasting mass losses greater than ∼ 12–14%, and caffeine concentrations in 10-min brews decreased for roast batches with drop temperatures greater than ∼ 400–420  ∘ F. Under identical brewing conditions, caffeine concentrations in brewed samples were generally lower for dark roasts than light and medium roasts. However, at identical extraction yields, dark roasts generally exhibited higher caffeine concentrations than lighter roasted coffees. It is likely that the volatilization or decomposition of soluble compounds and increased porosity due to roasting act as competing mechanisms that determine compound concentrations in resulting brews.

Shadow is one of the major problems in remotely sensed imagery which hampers the accuracy of information extraction and change detection. In these images, shadow is generally produced by different objects, namely, cloud, mountain and urban materials. The shadow correction process consists of two steps: detection and de-shadowing. This paper reviews a range of techniques for both steps, focusing on urban regions (urban shadows), mountainous areas (topographic shadow), cloud shadows and composite shadows. Several issues including the problems and the advantages of those algorithms are discussed. In recent years, thresholding and recovery techniques have become important for shadow detection and de-shadowing, respectively. Research on shadow correction is still an important topic, particularly for urban regions (in high spatial resolution data) and mountainous forest (in high and medium spatial resolution data). Moreover, new algorithms are needed for shadow correction, especially given the advent of new satellite images.