Cytosolic delivery of siRNA by ultra-high affinity dsRNA binding proteins

Abstract Protein-based methods of siRNA delivery are capable of uniquely specific targeting, but are limited by technical challenges such as low potency or poor biophysical properties. Here, we engineered a series of ultra-high affinity siRNA binders based on the viral protein p19 and developed them into siRNA carriers targeted to the epidermal growth factor receptor (EGFR). Combined in trans with a previously described endosome-disrupting agent composed of the pore-forming protein Perfringolysin O (PFO), potent silencing was achieved in vitro with no detectable cytotoxicity. Despite concerns that excessively strong siRNA binding could prevent the discharge of siRNA from its carrier, higher affinity continually led to stronger silencing. We found that this improvement was due to both increased uptake of siRNA into the cell and improved pharmacodynamics inside the cell. Mathematical modeling predicted the existence of an affinity optimum that maximizes silencing, after which siRNA sequestration decreases potency. Our study characterizing the affinity dependence of silencing suggests that siRNA-carrier affinity can significantly affect the intracellular fate of siRNA and may serve as a handle for improving the efficiency of delivery. The two-agent delivery system presented here possesses notable biophysical properties and potency, and provide a platform for the cytosolic delivery of nucleic acids

Comparison of Hydrological Patterns between Glacier-Fed and Non-Glacier-Fed Lakes on the Southeastern Tibetan Plateau

Lakes on the Tibetan Plateau have experienced variations over the last several decades, and the delineation of lake dynamics is favorable for the regional water cycle and can serve as important information for plateau environmental research. This study focused on 57 lakes near the Tanggula Mountains on the southeastern Tibetan Plateau. Yearly inundations of the lakes in 1989–2019 and altimeter data available for 2003–2020 were integrated to illustrate the changing patterns of glacier-fed and non-glacier-fed lakes. These two groups of lakes presented very similar evolution stages. They both increased in 1989–1992, decreased in 1992–1996, increased rapidly in 1998–2005, and had batch-wise fluctuations since 2005, with respective areas of around 5305.28 and 1636.79 km2 in the last decade. The non-glacier-fed lakes were more sensitive to precipitation variation, and glacier-fed lakes were more sensitive to temperature changes. Based on lakes with obvious changes in water level, the whole water storage variations of the studied lakes were 1.90 Gt/y in 2003–2009, including 1.80 Gt/y for glacier-fed lakes and 0.10 Gt/y for non-glacier-fed lakes. The contribution from glacier melting in 2003–2009 amounted to 16.11% of the whole lake volume increase. In 2010–2020, water mass changes were 0.42 Gt/y for glacier-fed lakes and −0.14 Gt/y for non-glacier-fed lakes, respectively. The volume increase of glacier-fed lakes in 2010–2020 was mainly due to the expansion of Selin Co. Selin Co experienced a water increase of about 0.46 Gt/y, and the other glacier-fed lakes experienced a decreasing volume of −0.04 Gt/y. In 2010–2020, 99.43% of the glacier contribution supplied Selin Co

Numerical Study on the Influence of Well Layout on Electricity Generation Performance of Enhanced Geothermal Systems

The energy efficiency of the enhanced geothermal system (EGS) measures the economic value of the heat production and electricity generation, and it is a key indicator of system production performance. Presently there is no systematic study on the influence of well layout on the system energy efficiency. In this work we numerically analyzed the main factors affecting the energy efficiency of EGS using the TOUGH2-EOS1 codes at Gonghe Basin geothermal field, Qinghai province. The results show that for the reservoirs of the same size, the electric power of the three horizontal well system is higher than that of the five vertical well system, and the electric power of the five vertical well system is higher than that of the three vertical well system. The energy efficiency of the three horizontal well system is higher than that of the five vertical well system and the three vertical well system. The reservoir impedance of the three horizontal well system is lower than that of the three vertical well system, and the reservoir impedance of the three vertical well system is lower than that of the five vertical system. The sensitivity analysis shows that well spacing has an obvious impact on the electricity production performance; decreasing well spacing will reduce the electric power, reduce the energy efficiency and only have very slight influence on the reservoir impedance. Fracture spacing has an obvious impact on the electricity production performance; increasing fracture spacing will reduce the electric power and reduce the energy efficiency. Fracture permeability has an obvious impact on the electricity production performance; increasing fracture permeability will improve the energy efficiency and reduce the reservoir impedance

A Pixel-Based Vegetation Greenness Trend Analysis over the Russian Tundra with All Available Landsat Data from 1984 to 2018

As Arctic warming continues, its impact on vegetation greenness is complex, variable and inherently scale-dependent. Studies with multiple spatial resolution satellite observations, with 30 m resolution included, on tundra greenness have been implemented all over the North American tundra. However, finer resolution studies on the greenness trends in the Russian tundra have only been carried out at a limited local or regional scale and the spatial heterogeneity of the trend remains unclear. Here, we analyzed the fine spatial resolution dataset Landsat archive from 1984 to 2018 over the entire Russian tundra and produced pixel-by-pixel greenness trend maps with the support of Google Earth Engine (GEE). The entire Russian tundra was divided into six geographical regions based on World Wildlife Fund (WWF) ecoregions. A Theil–Sen regression (TSR) was used for the trend identification and the changed pixels with a significance level p < 0.05 were retained in the final results for a subsequent greening/browning trend analysis. Our results indicated that: (1) the number of valid Landsat observations was spatially varied. The Western and Eastern European Tundras (WET and EET) had denser observations than other regions, which enabled a trend analysis during the whole study period from 1984 to 2018; (2) the most significant greening occurred in the Yamal-Gydan tundra (WET), Bering tundra and Chukchi Peninsula tundra (CT) during 1984–2018. The EET had a greening trend of 2.3% and 6.6% and the WET of 3.4% and 18% during 1984–1999 and 2000–2018, respectively. The area of browning trend was relatively low when we first masked the surface water bodies out before the trend analysis; and (3) the Landsat-based greenness trend was broadly similar to the AVHRR-based trend over the entire region but AVHRR retrieved more browning areas due to spectral mixing adjacent effects. Higher resolution images and field measurement studies are strongly needed to understand the vegetation trend over the Russian tundra ecosystem

Effect of Vertical Permeability Heterogeneity in Stratified Formation on Electricity Generation Performance of Enhanced Geothermal System

Because geologic sedimentation and hydrofracturing processes are not homogeneous, the reservoirs of enhanced geothermal systems (EGSs) are also heterogeneous; this has a significant influence on the electricity generation performance of EGS. Presently, there are a lack of systematic and profound studies on the effect of vertical permeability heterogeneity in stratified formation on the electricity generation performance of EGS. In order to uncover the effect of vertical permeability heterogeneity on electricity generation performance of EGS, in this work we analyzed the influence of vertical permeability heterogeneity on electricity generation performance of EGS through a numerical method based on geological data at the Yangbajing geothermal field. The results indicate that when the average permeability of stratified formations is constant for a homogeneous reservoir, the system attains maximum water production rate, maximum electric power, minimum reservoir impedance and maximum pump power; with the increasing of the vertical permeability heterogeneity, the water production rate gradually decreases, the electric power gradually declines, the reservoir impedance gradually increases and the pump power gradually declines. When the average permeability of stratified formations is constant, with the increasing of the vertical permeability heterogeneity, the injection pressure and energy efficiency only changes very slightly; this indicates that the vertical permeability heterogeneity is not the main factor affecting the system injection pressure and energy efficiency

A Pixel-Based Vegetation Greenness Trend Analysis over the Russian Tundra with All Available Landsat Data from 1984 to 2018

As Arctic warming continues, its impact on vegetation greenness is complex, variable and inherently scale-dependent. Studies with multiple spatial resolution satellite observations, with 30 m resolution included, on tundra greenness have been implemented all over the North American tundra. However, finer resolution studies on the greenness trends in the Russian tundra have only been carried out at a limited local or regional scale and the spatial heterogeneity of the trend remains unclear. Here, we analyzed the fine spatial resolution dataset Landsat archive from 1984 to 2018 over the entire Russian tundra and produced pixel-by-pixel greenness trend maps with the support of Google Earth Engine (GEE). The entire Russian tundra was divided into six geographical regions based on World Wildlife Fund (WWF) ecoregions. A Theil&ndash;Sen regression (TSR) was used for the trend identification and the changed pixels with a significance level p &lt; 0.05 were retained in the final results for a subsequent greening/browning trend analysis. Our results indicated that: (1) the number of valid Landsat observations was spatially varied. The Western and Eastern European Tundras (WET and EET) had denser observations than other regions, which enabled a trend analysis during the whole study period from 1984 to 2018; (2) the most significant greening occurred in the Yamal-Gydan tundra (WET), Bering tundra and Chukchi Peninsula tundra (CT) during 1984&ndash;2018. The EET had a greening trend of 2.3% and 6.6% and the WET of 3.4% and 18% during 1984&ndash;1999 and 2000&ndash;2018, respectively. The area of browning trend was relatively low when we first masked the surface water bodies out before the trend analysis; and (3) the Landsat-based greenness trend was broadly similar to the AVHRR-based trend over the entire region but AVHRR retrieved more browning areas due to spectral mixing adjacent effects. Higher resolution images and field measurement studies are strongly needed to understand the vegetation trend over the Russian tundra ecosystem

Integration of pixel-based and object-based image classification for extraction of water bodies with Landsat imagery

We propose two new methods for fast extraction of water features in remotely sensed imagery. Our first method is a pixel-based procedure that utilizes indices and band values. Based on their characteristic spectral reflectance curves, water bodies are grouped into three types - clear, green, and turbid. We found that the MNDWI is best suited for identifying clear water. Green water has its maximum reflectance occurring in Landsat Thematic Mapper (TM) band 4 (NIR band), while turbid water has its maximum reflectance in TM band 5 (mid-infrared band). Our second method integrates our pixel-based classification with object-based image segmentation. Two Landsat scenes in Shaanxi Province, China were used as the primary data source. Digital elevation models (DEMs) and their derived slope maps were used as ancillary information. To evaluate the performance of the proposed methods, extraction results of the three existing methods and our two new methods were compared and assessed

Numerical Study on Application Conditions of Equivalent Continuum Method for Modeling Heat Transfer in Fractured Geothermal Reservoirs

The equivalent continuum method an effective approach for modeling heat transfer in fractured geothermal reservoirs. However, presently there is a lack of systematical and profound study on application conditions of the equivalent porous media (EPM) method. In this study, we numerically investigated the application conditions of the EPM method based on geological data of Yangbajing geothermal field. The results indicate that when fracture spacing is within 3–25 m, the results of the EPM method are basically in the same levels as those of the MINC method. However, when the fracture spacing is within 25–300 m, differences of the EPM method from the MINC method increase with the fracture spacing, so when the fracture spacing is within 25–300 m, it is unreasonable to adopt the EPM method to simulate the fractured reservoirs. With the fracture spacing increasing within 25–300 m, the system production temperature and electric power will gradually decrease; the injection pressure, reservoir impedance and pump power will gradually increase; and the energy efficiency will gradually decrease

The Changing Trend and Driving Factors of Water Frequency Fluctuations in the Guangdong-Hong Kong-Macao Greater Bay Area

The distribution of surface water is highly dynamic both spatially and temporally, and very sensitive to climate change and anthropogenic interference, especially in highly urbanized regions. The abundance of surface water and its spatiotemporal distribution indicate the availability of water resources and the difficulty of water development and utilization. Consequently, it is essential to perform reconstruction and trend prediction of surface water body changes with high accuracy in time and space for scientific research as well as for practical purposes such as flood prevention, sustainable development of water resource systems, and regional ecological management. The Guangdong-Hong Kong-Macao Greater Bay Area (GBA) is highly developed economically and societally and is characterized by a subtropical humid monsoon climate with an extensive distribution of surface water bodies. Under the integrated pressure of continuous natural environmental change and intense human activity, concerns regarding both the water environment and water security in this area is increasing at an unprecedented rate. In this study, we collected water distribution information from 2001 to 2020 at 5-year intervals, as well as annual and monthly water extent dynamics data for the GBA from the Global Land Analysis & Discovery database. Subsequently, the spatial and temporal changes in water extent, frequency, and distribution characteristics in the last two decades were investigated using remote sensing and geographic information system methods. Finally, elastic analysis was conducted to identify the sensitivity of water body changes to changing environmental parameters, including precipitation, temperature, and urbanization. Focusing on the national and regional strategic needs of GBA, the research objectives of this study were to explore the mechanism of temporal and spatial dynamics of the water extent and frequency, trace the volatile areas of regional water changes, clarify the driving factors of water distribution changes, and provide a basis and guidance for comprehensive management of water resources, flood disaster prevention, and control in areas with high human activity. The first result shows that in the last two decades, the water extent and frequency of the GBA are on a decreasing trend, with an average decreasing rate of 50, 31, and 11 km2/a for maximum, annual, and permanent water extent, respectively, while a large proportion of seasonal water bodies changed into permanent and flood-prone bodies during the same period. Second, although the water frequency showed distinct spatial and urban/rural heterogeneity, it was on a decreasing trend in most of the GBA, except in the eastern region. A steeper decline was observed in urban areas, especially the emerging urban regions. Third, the dike-pond system decreased both in water extent and frequency, while the large and medium-sized lakes and reservoirs in the upper catchment increased in extent. Finally, elastic analysis suggests the dominant driving factor of regional water body change is land use change, which contributed more than 80% to the decrease in water extent, and the reservoir increase is mainly due to precipitation change. The results of this research provide scientific guidance for regional water resource guarantee, water environment optimization, and sustainable development promotion. In addition, this research can serve as a decision-making reference for the development of the "One Belt One Road" national strategy and Guangdong-Hong Kong-Macao Greater Bay Area