The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease-19 (COVID-19) being associated with severe pneumonia. Like with other viruses, the interaction of SARS-CoV-2 with host cell proteins is necessary for successful replication, and cleavage of cellular targets by the viral protease also may contribute to the pathogenesis, but knowledge about the human proteins that are processed by the main protease (3CLpro) of SARS-CoV-2 is still limited. We tested the prediction potentials of two different in silico methods for the identification of SARS-CoV-2 3CLpro cleavage sites in human proteins. Short stretches of homologous host-pathogen protein sequences (SSHHPS) that are present in SARS-CoV-2 polyprotein and human proteins were identified using BLAST analysis, and the NetCorona 1.0 webserver was used to successfully predict cleavage sites, although this method was primarily developed for SARS-CoV. Human C-terminal-binding protein 1 (CTBP1) was found to be cleaved in vitro by SARS-CoV-2 3CLpro, the existence of the cleavage site was proved experimentally by using a His6-MBP-mEYFP recombinant substrate containing the predicted target sequence. Our results highlight both potentials and limitations of the tested algorithms. The identification of candidate host substrates of 3CLpro may help better develop an understanding of the molecular mechanisms behind the replication and pathogenesis of SARS-CoV-2. 相似文献
The effects of quenching in different ways following solid-solution treatment on properties and precipitation behaviors of 7050 alloy were investigated by transmission electron microscopy (TEM), scanning electron microscopy (SEM), selected area electron diffraction (SAED), hardness and electrical conductivity tests. Results show that after quenching in different ways, electrical conductivity of the alloy decreases rapidly in the first 48 h of natural aging. The electrical conductivity of 7050 alloy in natural aging state is determined by the size and density of GP zones, and the size of GP zones is the main factor. After natural aging for 70 d, the size of GP zones is 1.8–2.6 nm in matrix of the immersion quenched sample and it is 1.4–1.8 nm in matrix of both water mist and forced air quenched samples. After natural and artificial peak aging, the hardness of the water mist quenched sample is HV 193.6 and its electrical conductivity is 30.5% (IACS) which are both higher than those of the immersion quenched sample. Therefore, water mist quenching is an ideal quenching method for 7050 alloy sheets after solid-solution treatment. 相似文献
Exploring efficient and durable non-precious metal catalysts for oxygen reduction reaction (ORR) has long been pursued in the field of metal-air batteries, fuel cells, and solar cells. Rational design and controllable synthesis of desirable catalysts are still a great challenge. In this work, a novel approach is developed to tune the morphologies and structures of Fe–N–C catalysts in combination with the dual nitrogen-containing carbon precursors and the gas-foaming agent. The tailored Fe–N1/N2–C-A catalyst presents gauze-like porous nanosheets with uniformly dispersed tiny nanoparticles. Such architectures exhibit abundant Fe-Nx active sites and high-exposure surfaces. The Fe–N1/N2–C-A catalyst shows extremely high half-wave potential (E1/2, 0.916 V vs. RHE) and large limiting current density (6.3 mA cm−2), far beyond 20 wt% Pt/C catalyst for ORR. This work provides a facile morphological and structural regulation to increase the number and exposure of Fe-Nx active sites. 相似文献
This paper proposes a novel structure to optimize the operational strategies of responsive farms for day‐ahead peak shaving. To achieve the aim, the modern irrigation system of farms, including groundwater, surface water, and booster water pumps, are modeled mathematically. To develop the demand response (DR) potentials of the farms, electrical storage systems, and self‐generation facilities, including thermal distributed generations and on‐farm solar sites, are addressed. In order to facilitate the integration of the agricultural DR programs into the electricity market, a mathematical formulation for agricultural demand response aggregator (ADRA) is suggested. The ADRA participates in the day‐ahead electricity market on behalf of the responsive farms. To overcome the price uncertainty of the electricity market, a robust optimization approach is addressed. This approach determines the robust decisions of farms in the worst‐case realizations of the uncertain electricity price. Regarding on‐farm solar sites located in rural areas, a data‐driven approach is used to estimate the solar power generation of a significant number of sites without needing to install costly communication and measurement infrastructures. Finally, the proposed approach is implemented on agricultural lands in the northeast of Iran. The numerical results show that the suggested approach provides day‐ahead peak shaving for the power systems meeting the crop's water requirements. 相似文献
The Fourth Amendment to the U.S. Constitution functions as a shield against excess governmental or police power by prohibiting unreasonable searches and seizures. Since its ratification, legal challenges have tempered this shield by frequently disputing the application of investigative processes and tools, including those that bypass the traditional – and simpler – analysis that focused on physical trespass. But recent technological advancements have prompted novel challenges and have forced the U.S. Supreme Court to adopt a parallel inquiry that evaluates society’s expectations of privacy as an alternate path to invoke the Fourth Amendment’s protections apart from any physical trespass. As revolutionary technology continues to present unique issues, this 200-year-old shield manifests a reflective luster as if polished by years of legal discourse that reveals the priorities of those who would interpret its text. Viewing the Fourth Amendment’s shield as a mirror illustrates not only the thoughts of the drafters that revolved primarily around protecting property interests but also the expectations of modern society with its insistence on promoting privacy. And where the drafters channeled their outrage against the loathsome writs of assistance in colonial times, later Americans continued to denounce the similarly invasive general warrants and attempts by investigators to expand the tools in their arsenal beyond constitutional bounds, especially in the surveillance context. Yet, the problems posed by new technology upon privacy concerns are best resolved by relying on the core principles supporting the Fourth Amendment, previous U.S. Supreme Court precedent, and current societal perspectives regarding privacy as a top priority proven by recently enacted legislation both foreign and domestic.
By applying a similar method to address advancing communication technology and its use as a surveillance tool in Carpenter v. United States, the Court turned this shield-become-mirror upon society to conclude that cell phone location information deserves Fourth Amendment protection because of its untiring comprehensiveness and its uniquely detailed nature. Moreover, nearly every American adult carries a cell phone with them almost all the time, making it possible to create a time-stamped map of any cell-phone-carrying-individual’s movements reaching back years and years. Unfortunately, the Carpenter Court did not extend this crucial protection far enough to protect all cell phone location data, and the unmistakable gap in its holding leaves a potential privacy vulnerability the exploitation of which could cause greater harm than all previously disputed surveillance technology combined because of cell phone usage’s general – near universal – applicability. Allowing cell phone location information to be obtained without probable cause and a proper search warrant not only fails to meet the spirit of the Fourth Amendment, it also begins to tarnish that shield such that it no longer reflects historical or current societal values, reducing its goal of protecting Americans to a hollow incantation of words left to languish as time (and technology) marches on. 相似文献