Pickering emulsion-enhanced interfacial biocatalysis: tailored alginate microparticles act as particulate emulsifier and enzyme carrier

A robust Pickering emulsion stabilized by lipase-immobilized alginate gel microparticles with a coating of silanized titania nanoparticles is developed for biphasic biocatalysis. The good recyclability and high stability of the proposed interfacial catalysis system have been verified, retaining about 90% of relative enzyme activity in 10 catalytic cycles with operation for 240 h. Meanwhile the Pickering emulsions remain stable during a storage time of one year. The green system can be widely applied to construct powerful platforms for enzyme or microorganism-driven interfacial catalysis

Model estimates of China's terrestrial water storage variation due to reservoir operation

Understanding the role of reservoirs in the terrestrial water cycle is critical to support the sustainable management of water resources especially for China where reservoirs have been extensively built nationwide. However, this has been a scientific challenge due to the limited availability of continuous, long-term reservoir operation records at large scales, and a process-based modeling tool to accurately depict reservoirs as part of the terrestrial water cycle is still lacking. Here, we develop a continental-scale land surface-hydrologic model over the mainland China by explicitly representing 3,547 reservoirs in the model with a calibration-free conceptual operation scheme for ungauged reservoirs and a hydrodynamically based two-way coupled scheme. The model is spatially calibrated and then extensively validated against streamflow observations, reservoir storage observations and GRACE-based terrestrial water storage anomalies. A 30-year simulation is then performed to quantify the seasonal dynamics of China’s reservoir water storage (RWS) and its role in China\u27s terrestrial water storage (TWS) over recent decades. We estimate that, over a seasonal cycle, China\u27s RWS variation is 15%, 16%, and 25% of TWS variation during 1981–1990, 1991–2000, and 2001–2010, respectively, and one-fifth of China’s reservoir capacity are effectively used annually. In most regions, reservoirs play a growing role in modulating the water cycle over time. Despite that, an estimated 80 million people have faced increasing water resources challenges in the past decades due to the significantly weakened reservoir regulation of the water cycle. Our approaches and findings could help the government better address the water security challenges under environmental changes

Effective Long-Context Scaling of Foundation Models

We present a series of long-context LLMs that support effective context windows of up to 32,768 tokens. Our model series are built through continual pretraining from Llama 2 with longer training sequences and on a dataset where long texts are upsampled. We perform extensive evaluation on language modeling, synthetic context probing tasks, and a wide range of research benchmarks. On research benchmarks, our models achieve consistent improvements on most regular tasks and significant improvements on long-context tasks over Llama 2. Notably, with a cost-effective instruction tuning procedure that does not require human-annotated long instruction data, the 70B variant can already surpass gpt-3.5-turbo-16k's overall performance on a suite of long-context tasks. Alongside these results, we provide an in-depth analysis on the individual components of our method. We delve into Llama's position encodings and discuss its limitation in modeling long dependencies. We also examine the impact of various design choices in the pretraining process, including the data mix and the training curriculum of sequence lengths -- our ablation experiments suggest that having abundant long texts in the pretrain dataset is not the key to achieving strong performance, and we empirically verify that long context continual pretraining is more efficient and similarly effective compared to pretraining from scratch with long sequences

China’s internationalized higher education during Covid-19: Collective student autoethnography

This is an accepted manuscript of an article published by Springer in Postdigital Science and Education on 08/05/2020, available online: https://doi.org/10.1007/s42438-020-00128-1 The accepted version of the publication may differ from the final published version.This article presents 15 autoethnographical texts detailing student experiences at Beijing Normal University in the midst of the Covid-19 pandemic. Contributions have been collected over 6 weeks between 15 February and 1 April 2020, edited by Hejia Wang (assisted by Moses Oladele Ogunniran and Yingying Huang), and supervised by Michael Peters. Through shared in-depth empirical feelings and representations from a wide variety of cultural, historical, and social contexts, the article outlines an answer to the question: How do students, connected virtually but separated physically in an internationalized university, deal with disruption brought about by the Covid-19 pandemic? Student testimonies offer reflections on Covid-19 and Chinese international education, experiences of online teaching and learning, reflections on university coping mechanisms, an account of realities and feelings related to changes in academic life, and discussions on coping strategies in Chinese international higher education. Contributors expose their individual feelings, effects, benefits, challenges, and risk management strategies. Collected at the peak of the Covid-19 pandemic, these testimonies are unable to offer systemic answers to challenges facing the whole world. However, these experiences and feelings will provide important inputs to global discussions about the future of the world, after Covid-19.Published onlin

Specific aromatic foldamers potently inhibit spontaneous and seeded Aβ42 and Aβ43 fibril assembly

Amyloid fibrils are self-propagating entities that spread pathology in several devastating disorders including Alzheimer's disease (AD). In AD, amyloid-β (Aβ) peptides form extracellular plaques that contribute to cognitive decline. One potential therapeutic strategy is to develop inhibitors that prevent Aβ misfolding into proteotoxic conformers. Here, we design specific aromatic foldamers, synthetic polymers with an aromatic salicylamide (Sal) or 3-amino benzoic acid (Benz) backbone, short length (four repetitive units), basic arginine (Arg), lysine (Lys) or citrulline (Cit) side chains, and various N- and C-terminal groups that prevent spontaneous and seeded Aβ fibrillization. Ac-Sal-(Lys-Sal)(3)-CONH(2) and Sal-(Lys-Sal)(3)-CONH(2) selectively inhibited Aβ42 fibrillization, but were ineffective against Aβ43, an overlooked species that is highly neurotoxic and frequently deposited in AD brains. By contrast, (Arg-Benz)(4)-CONH(2) and (Arg-Sal)(3)-(Cit-Sal)-CONH(2) prevented spontaneous and seeded Aβ42 and Aβ43 fibrillization. Importantly, (Arg-Sal)(3)-(Cit-Sal)-CONH(2) inhibited formation of toxic Aβ42 and Aβ43 oligomers and proteotoxicity. None of these foldamers inhibited Sup35 prionogenesis, but Sal-(Lys-Sal)(3)-CONH(2) delayed aggregation of fused in sarcoma (FUS), an RNA-binding protein with a prion-like domain connected with amyotrophic lateral sclerosis and frontotemporal dementia. We establish that inhibitors of Aβ42 fibrillization do not necessarily inhibit Aβ43 fibrillization. Moreover, (Arg-Sal)(3)-(Cit-Sal)-CONH(2) inhibits formation of toxic Aβ conformers and seeding activity, properties that could have therapeutic utility

The Spatiotemporal Variability of Evapotranspiration and Its Response to Climate Change and Land Use/Land Cover Change in the Three Gorges Reservoir

Evapotranspiration (ET) has undergone profound changes as a result of global climate change and anthropogenic activities. The construction of the Three Gorges Reservoir (TGR) has led to changes in its land use/land cover (LUCC) and local climate, which in turn has changed ET processes in the TGR region. In this paper, the CLM4.5 land surface model is used to simulate and analyze the spatiotemporal variability of ET between 1993 and 2013. Four experiments were conducted to quantify the contribution rate of climate change and LUCC to changes in ET processes. The results show that the climate showed a warming and drying trend from 1993 to 2013, and the LUCC indicates decreasing cropland with increasing forest, grassland, water bodies and urban areas. These changes increased the mean annual ET by 13.76 mm after impoundment. Spatially, the vegetation transpiration accounts for the largest proportion in ET. The decreasing relative humidity and increasing wind speeds led to an increase in vegetation transpiration and ground evaporation, respectively, in the center of the TGR region, while the LUCC drove changes in ET in water bodies, urban areas and high-altitude regions in the TGR region

Cytosolic Delivery of Inhibitory Antibodies with Cationic Lipids

Antibodies have become powerful therapeutics and research tools because they can be developed to directly inhibit almost any protein, but their inaility to enter the cytosol limits inhibitory antibodies to extracellular targets. Given that roughly two-thirds of drug targets lie inside of cells and many targets lack binding targets for small-molecule drugs, developing a cytosolic antibody delivery system would dramatically expand the druggable proteome. Cytosolic antibodies also offer unique opportunities to directly inhibit and study intracellular protein function. Here we demonstrate that immunoglobulin G (IgG) antibodies that are conjugated with anionic polypeptides (ApPs) can be complexed with cationic lipids through electrostatic interactions, enabling close to 90% cytosolic delivery efficiency with only 500 nM IgG. The ApP is fused to a small photoreactive antibody-binding domain (pAbBD) that can be site-specifically photocrosslinked to nearly all off-the-shelf IgGs without perturbing IgG binding affinity. Furthermore, the pAbBD can be functionalized with chemical moieties such as fluorophores at its C-terminus via proximity-based sortase-mediated ligation (PBSL), a chemoenzymatic bioconjugation approach that we have developed. We show that cytosolically delivered IgGs can inhibit the drug efflux pump multidrug resistance-associated protein 1 (MRP1) and the transcription factor NFκB. This work establishes a new approach for using existing antibody collections to modulate intracellular protein function and provides the foundations for therapeutic cytosolic antibodies

Cytosolic Delivery Of Inhibitory Antibodies With Cationic Lipids

Antibodies have become powerful therapeutics and research tools because they can be developed to directly inhibit almost any protein, but their inaility to enter the cytosol limits inhibitory antibodies to extracellular targets. Given that roughly two-thirds of drug targets lie inside of cells and many targets lack binding targets for small-molecule drugs, developing a cytosolic antibody delivery system would dramatically expand the druggable proteome. Cytosolic antibodies also offer unique opportunities to directly inhibit and study intracellular protein function. Here we demonstrate that immunoglobulin G (IgG) antibodies that are conjugated with anionic polypeptides (ApPs) can be complexed with cationic lipids through electrostatic interactions, enabling close to 90% cytosolic delivery efficiency with only 500 nM IgG. The ApP is fused to a small photoreactive antibody-binding domain (pAbBD) that can be site-specifically photocrosslinked to nearly all off-the-shelf IgGs without perturbing IgG binding affinity. Furthermore, the pAbBD can be functionalized with chemical moieties such as fluorophores at its C-terminus via proximity-based sortase-mediated ligation (PBSL), a chemoenzymatic bioconjugation approach that we have developed. We show that cytosolically delivered IgGs can inhibit the drug efflux pump multidrug resistance-associated protein 1 (MRP1) and the transcription factor NFκB. This work establishes a new approach for using existing antibody collections to modulate intracellular protein function and provides the foundations for therapeutic cytosolic antibodies