Water: a global grand challenge and a path forward

2022 ◽  
pp. 1-35
Author(s):  
Avinash Alagumalai ◽  
Simin Anvari ◽  
Mohamed M. Awad
Keyword(s):  
Grand Challenge

Target manufacturing – A “grand challenge" for inertial fusion

2006 ◽  
Vol 133 ◽  
pp. 35-35
Author(s):  
D. T. Goodin ◽  
R. W. Petzoldt ◽  
B. A. Vermillion ◽  
D. T. Frey ◽  
N. B. Alexander ◽  
...  
Keyword(s):  
Inertial Fusion ◽  
Grand Challenge

D3R Grand Challenge 4: Ligand Similarity and MM-GBSA-Based Pose Prediction and Affinity Ranking for BACE-1 Inhibitors

2019 ◽  
Author(s):  
Sukanya Sasmal ◽  
Léa El Khoury ◽  
David Mobley
Keyword(s):  
Binding Mode ◽  
Energy Estimates ◽  
Poor Correlation ◽  
Grand Challenge ◽  
Pose Prediction ◽  
Design Data ◽  
Data Resource ◽  
Affinity Ranking ◽  
Ligand Similarity ◽  
Bace 1

The Drug Design Data Resource (D3R) Grand Challenges present an opportunity to assess, in the context of a blind predictive challenge, the accuracy and the limits of tools and methodologies designed to help guide pharmaceutical drug discovery projects. Here, we report the results of our participation in the D3R Grand Challenge 4, which focused on predicting the binding poses and affinity ranking for compounds targeting the beta-amyloid precursor protein (BACE-1). Our ligand similarity-based protocol using HYBRID (OpenEye Scientific Software) successfully identified poses close to the native binding mode for most of the ligands with less than 2 A RMSD accuracy. Furthermore, we compared the performance of our HYBRID-based approach to that of AutoDock Vina and Dock 6 and found that HYBRID performed better here for pose prediction. We also conducted end-point free energy estimates on protein-ligand complexes using molecular mechanics combined with generalized Born surface area method (MM-GBSA). We found that the binding affinity ranking based on MM-GBSA scores have poor correlation with the experimental values. Finally, the main lessons from our participation in D3R Grand Challenge 4 suggest that: i) the generation of the macrocycles conformers is a key step for successful pose prediction, ii) the protonation states of the BACE-1 binding site should be treated carefully, iii) the MM-GBSA method could not discriminate well between different predicted binding poses, and iv) the MM-GBSA method does not perform well at predicting protein-ligand binding affinities here.

scholarly journals Photo-Responsive Supramolecular Micelles for Controlled Drug Release and Improved Chemotherapy

2020 ◽  
Vol 22 (1) ◽  
pp. 154
Author(s):  
Fasih Bintang Ilhami ◽  
Kai-Chen Peng ◽  
Yi-Shiuan Chang ◽  
Yihalem Abebe Alemayehu ◽  
Hsieh-Chih Tsai ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Drug Release ◽  
Visible Light ◽  
Cancer Cells ◽  
Laser Irradiation ◽  
Reactive Oxygen ◽  
Controlled Drug Release ◽  
Grand Challenge ◽  
Supramolecular System ◽  
Oxygen Species

Development of stimuli-responsive supramolecular micelles that enable high levels of well-controlled drug release in cancer cells remains a grand challenge. Here, we encapsulated the antitumor drug doxorubicin (DOX) and pro-photosensitizer 5-aminolevulinic acid (5-ALA) within adenine-functionalized supramolecular micelles (A-PPG), in order to achieve effective drug delivery combined with photo-chemotherapy. The resulting DOX/5-ALA-loaded micelles exhibited excellent light and pH-responsive behavior in aqueous solution and high drug-entrapment stability in serum-rich media. A short duration (1–2 min) of laser irradiation with visible light induced the dissociation of the DOX/5-ALA complexes within the micelles, which disrupted micellular stability and resulted in rapid, immediate release of the physically entrapped drug from the micelles. In addition, in vitro assays of cellular reactive oxygen species generation and cellular internalization confirmed the drug-loaded micelles exhibited significantly enhanced cellular uptake after visible light irradiation, and that the light-triggered disassembly of micellar structures rapidly increased the production of reactive oxygen species within the cells. Importantly, flow cytometric analysis demonstrated that laser irradiation of cancer cells incubated with DOX/5-ALA-loaded A-PPG micelles effectively induced apoptotic cell death via endocytosis. Thus, this newly developed supramolecular system may offer a potential route towards improving the efficacy of synergistic chemotherapeutic approaches for cancer.

scholarly journals One size does not fit all: Constructing complementary digital reskilling strategies using online labour market data

2021 ◽  
Vol 8 (1) ◽  
pp. 205395172110031
Author(s):  
Fabian Stephany
Keyword(s):  
Social Transformation ◽  
Grand Challenge ◽  
Policy Makers ◽  
National Education ◽  
Global Challenge ◽  
Cognitive Work ◽  
National Education Systems ◽  
Skill Requirements ◽  
The Individual ◽  
Value Of Learning

Digital technologies are radically transforming our work environments and demand for skills, with certain jobs being automated away and others demanding mastery of new digital techniques. This global challenge of rapidly changing skill requirements due to task automation overwhelms workers. The digital skill gap widens further as technological and social transformation outpaces national education systems and precise skill requirements for mastering emerging technologies, such as Artificial Intelligence, remain opaque. Online labour platforms could help us to understand this grand challenge of reskilling en masse. Online labour platforms build a globally integrated market that mediates between millions of buyers and sellers of remotely deliverable cognitive work. This commentary argues that, over the last decade, online labour platforms have become the ‘laboratories’ of skill rebundling; the combination of skills from different occupational domains. Online labour platform data allows us to establish a new taxonomy on the individual complementarity of skills. For policy makers, education providers and recruiters, a continuous analysis of complementary reskilling trajectories enables automated, individual and far-sighted suggestions on the value of learning a new skill in a future of technological disruption.

scholarly journals OpenKBP: The open‐access knowledge‐based planning grand challenge and dataset

2021 ◽  
Author(s):  
Aaron Babier ◽  
Binghao Zhang ◽  
Rafid Mahmood ◽  
Kevin L. Moore ◽  
Thomas G. Purdie ◽  
...  
Keyword(s):  
Open Access ◽  
Grand Challenge ◽  
Knowledge Based ◽  
Knowledge Based Planning

scholarly journals Metallic surface doping of metal halide perovskites

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuze Lin ◽  
Yuchuan Shao ◽  
Jun Dai ◽  
Tao Li ◽  
Ye Liu ◽  
...  
Keyword(s):  
Metal Ions ◽  
Metallic Surface ◽  
Grand Challenge ◽  
New Device ◽  
Surface Doping ◽  
N Doping ◽  
Halide Perovskites ◽  
Heavily Doped ◽  
Low Solubility ◽  
Striking Contrast

AbstractIntentional doping is the core of semiconductor technologies to tune electrical and optical properties of semiconductors for electronic devices, however, it has shown to be a grand challenge for halide perovskites. Here, we show that some metal ions, such as silver, strontium, cerium ions, which exist in the precursors of halide perovskites as impurities, can n-dope the surface of perovskites from being intrinsic to metallic. The low solubility of these ions in halide perovskite crystals excludes the metal impurities to perovskite surfaces, leaving the interior of perovskite crystals intrinsic. Computation shows these metal ions introduce many electronic states close to the conduction band minimum of perovskites and induce n-doping, which is in striking contrast to passivating ions such as potassium and rubidium ion. The discovery of metallic surface doping of perovskites enables new device and material designs that combine the intrinsic interior and heavily doped surface of perovskites.

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