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Superman : American alien
\"Hollywood screenwriter and Eisner Award nominee Max Landis (Chronicle, American Ultra, Adventures of Superman) joins forces with top comics artists including Jock, Francis Manapul and Jae Lee to bring you Superman: American Alien, a new epic that chronicles the life of Clark Kent and his development into the archetypal hero he will eventually become. But these are not the stories of the iconic \"Superman\" as you know him, but of the soft-spoken, charming, often-funny Kansas farm-boy behind the Man of Steel. With the tone of each issue ranging from heartwarming and simple, to frighteningly gritty and violent, to sexy, sun-kissed and funny, Superman: American Alien is unlike anything you've seen before.\"-- Provided by publisher.
Book
Exploiting machine learning for end-to-end drug discovery and development
A variety of machine learning methods such as naive Bayesian, support vector machines and more recently deep neural networks are demonstrating their utility for drug discovery and development. These leverage the generally bigger datasets created from high-throughput screening data and allow prediction of bioactivities for targets and molecular properties with increased levels of accuracy. We have only just begun to exploit the potential of these techniques but they may already be fundamentally changing the research process for identifying new molecules and/or repurposing old drugs. The integrated application of such machine learning models for end-to-end (E2E) application is broadly relevant and has considerable implications for developing future therapies and their targeting.This Perspective describes the application of machine learning models in the design, synthesis and characterisation of molecules at different stages in the drug discovery and development process.
Journal Article
Argentina
Lonely Planet's Argentina is your passport to the most relevant, up-to-date advice on what to see and skip, and what hidden discoveries await you. Watch enormous icebergs calve from Glaciar Perito Moreno, tour wineries and enjoy the finished product around Mendoza, and hike the rugged Fitz Roy Range for stunning mountain views - all with your trusted travel companion. Get to the heart of Argentina and begin your journey now!
Book
Estimating the Employment and Fiscal Consequences of Thermal Coal Phase-Out in China
China hosts over half of global coal-fired power generation capacity and has the world’s largest coal reserves. Its 2060 carbon neutrality goal will require coal-fired electricity generation to shrink dramatically, with or without carbon capture and storage technology. Two macroeconomic areas in which the socioeconomic impact of this decline is felt are losses in jobs and tax revenues supported by thermal coal mining, transport and power generation. At the national level, under a ‘baseline’ (B) scenario consistent with China’s carbon neutrality goal, labour productivity growth in coal mining implies that significant job losses will occur nationally in the medium term, even if all coal plants continue operating as planned. Jobs supported by the coal power industry would decline from an estimated 2.7 million in 2021, to 1.44 million in 2035 and 94,000 in 2050, with jobs losses from mining alone expected to exceed 1.1 million by 2035. Tax revenues from thermal coal would total approximately CNY 300 billion annually from 2021–2030, peaking in 2023 at CNY 340 billion. This is significantly less than estimated subsidies of at least CNY 480 billion, suggesting coal is likely a net fiscal drain on China’s public finances, even without accounting for the costs of local pollution and the social cost of carbon. As coal plant retirements accelerate, from 2034 onwards, fiscal revenues begin to fall more rapidly, with rates of decline rising from 1% in the 2020s to over 10% a year by the 2040s. More aggressive climate policy and technology scenarios bring job and tax losses forward in time, while a No Transition policy, in which all currently planned coal plants are built, delays but does not ultimately prevent these losses. At the provincial level, China’s major coal-producing provinces will likely face challenges in managing the localised effects of expected job losses and finding productive alternative uses for this labour. Governments of coal-producing provinces like Inner Mongolia, with an industry highly dependent on exports to other provinces, are more exposed than others to declining tax revenues from coal, and more insulated from job losses, given their high current degree of labour efficiency. Although their provincial revenues are likely to remain stable until the early 2030s under the B scenario, the possibility of increasing policy stringency underlines the need for revenue and skill base diversification. At the firm level, China’s ‘Big Five’ state-owned power companies were responsible for over 40% of both jobs and tax revenues in 2021. The number of jobs supported by the activities of each of the largest ten firms, with one exception, will decline by 71–84% by the early 2040s, with the tax contribution of each declining by 43–69% in the same period.
Journal Article
Our stories carried us here : a graphic novel anthology
The first national graphic anthology of 10 U.S. immigrants and refugees illustrated by 10 immigrants and refugees from all over the world.
Book
A human three-dimensional neural-perivascular ‘assembloid’ promotes astrocytic development and enables modeling of SARS-CoV-2 neuropathology
Clinical evidence suggests the central nervous system is frequently impacted by SARS-CoV-2 infection, either directly or indirectly, although the mechanisms are unclear. Pericytes are perivascular cells within the brain that are proposed as SARS-CoV-2 infection points. Here we show that pericyte-like cells (PLCs), when integrated into a cortical organoid, are capable of infection with authentic SARS-CoV-2. Before infection, PLCs elicited astrocytic maturation and production of basement membrane components, features attributed to pericyte functions in vivo. While traditional cortical organoids showed little evidence of infection, PLCs within cortical organoids served as viral ‘replication hubs’, with virus spreading to astrocytes and mediating inflammatory type I interferon transcriptional responses. Therefore, PLC-containing cortical organoids (PCCOs) represent a new ‘assembloid’ model that supports astrocytic maturation as well as SARS-CoV-2 entry and replication in neural tissue; thus, PCCOs serve as an experimental model for neural infection.
Findings from a pericyte-containing cortical organoid model suggests that pericytes provide an infection portal for SARS-CoV-2 and can serve as a viral amplification hub within neural tissue.
Journal Article
Entanglement-inspired frequency-agile rangefinding
Entanglement, a key feature of quantum mechanics, is recognized for its non-classical correlations which have been shown to provide significant noise resistance in single-photon rangefinding and communications. Drawing inspiration from the advantage given by energy-time entanglement, we developed an energy-time correlated source based on a classical laser that preserves the substantial noise reduction typical of quantum illumination while surpassing the quantum brightness limitation by over six orders of magnitude, making it highly suitable for practical remote sensing applications. A frequency-agile pseudo-random source is realized through fiber chromatic dispersion and pulse carving using an electro-optic intensity modulator. Operating at a faint transmission power of 48
μ
W, the distance between two buildings 154.8182 m apart can be measured with a precision better than 0.1 mm, under varying solar background levels and weather conditions with an integration time of only 100 ms. These trials verified the predicted noise reduction of this system, demonstrating advantages over quantum illumination-based rangefinding and highlighting its potential for practical remote sensing applications.
Quantum range finding struggles in bright background and at long distance. Here, the authors demonstrate a quantum-inspired, energy-time correlated classical rangefinder. It preserves quantum noise suppression, works at low power, and enables robust daylight remote ranging in real-world environments
Journal Article
Multi-clonal SARS-CoV-2 neutralization by antibodies isolated from severe COVID-19 convalescent donors
The interactions between antibodies, SARS-CoV-2 and immune cells contribute to the pathogenesis of COVID-19 and protective immunity. To understand the differences between antibody responses in mild versus severe cases of COVID-19, we analyzed the B cell responses in patients 1.5 months post SARS-CoV-2 infection. Severe, and not mild, infection correlated with high titers of IgG against Spike receptor binding domain (RBD) that were capable of ACE2:RBD inhibition. B cell receptor (BCR) sequencing revealed that VH3-53 was enriched during severe infection. Of the 22 antibodies cloned from two severe donors, six exhibited potent neutralization against authentic SARS-CoV-2, and inhibited syncytia formation. Using peptide libraries, competition ELISA and mutagenesis of RBD, we mapped the epitopes of the neutralizing antibodies (nAbs) to three different sites on the Spike. Finally, we used combinations of nAbs targeting different immune-sites to efficiently block SARS-CoV-2 infection. Analysis of 49 healthy BCR repertoires revealed that the nAbs germline VHJH precursors comprise up to 2.7% of all VHJHs. We demonstrate that severe COVID-19 is associated with unique BCR signatures and multi-clonal neutralizing responses that are relatively frequent in the population. Moreover, our data support the use of combination antibody therapy to prevent and treat COVID-19.
Journal Article
Interactions of SARS-CoV-2 envelope protein with amilorides correlate with antiviral activity
SARS-CoV-2 is the novel coronavirus that is the causative agent of COVID-19, a sometimes-lethal respiratory infection responsible for a world-wide pandemic. The envelope (E) protein, one of four structural proteins encoded in the viral genome, is a 75-residue integral membrane protein whose transmembrane domain exhibits ion channel activity and whose cytoplasmic domain participates in protein-protein interactions. These activities contribute to several aspects of the viral replication-cycle, including virion assembly, budding, release, and pathogenesis. Here, we describe the structure and dynamics of full-length SARS-CoV-2 E protein in hexadecylphosphocholine micelles by NMR spectroscopy. We also characterized its interactions with four putative ion channel inhibitors. The chemical shift index and dipolar wave plots establish that E protein consists of a long transmembrane helix (residues 8–43) and a short cytoplasmic helix (residues 53–60) connected by a complex linker that exhibits some internal mobility. The conformations of the N-terminal transmembrane domain and the C-terminal cytoplasmic domain are unaffected by truncation from the intact protein. The chemical shift perturbations of E protein spectra induced by the addition of the inhibitors demonstrate that the N-terminal region (residues 6–18) is the principal binding site. The binding affinity of the inhibitors to E protein in micelles correlates with their antiviral potency in Vero E6 cells: HMA ≈ EIPA > DMA >> Amiloride, suggesting that bulky hydrophobic groups in the 5’ position of the amiloride pyrazine ring play essential roles in binding to E protein and in antiviral activity. An N15A mutation increased the production of virus-like particles, induced significant chemical shift changes from residues in the inhibitor binding site, and abolished HMA binding, suggesting that Asn15 plays a key role in maintaining the protein conformation near the binding site. These studies provide the foundation for complete structure determination of E protein and for structure-based drug discovery targeting this protein.
Journal Article
Ferroelectric nanosheets boost nonlinearity
Multilayered ferroelectric NbOI2 crystals with sub-100-nm thickness exhibit efficient second harmonic generation, paving the way for on-chip nonlinear optical components.
Journal Article