scholarly journals Frontiers in Toxicogenomics – The Grand Challenge: To Understand How the Genome and Epigenome Interact with the Toxic Environment

2011 ◽  
Vol 2 ◽  
Author(s):  
Douglas Mark Ruden
Keyword(s):  
Grand Challenge ◽  
Toxic Environment

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.

Non-Toxic Environment for Ferritic Nitrocarburising Process

2018 ◽  
Vol 69 (9) ◽  
pp. 2416-2419
Author(s):  
Mihai Branzei ◽  
Mihai Ovidiu Cojocaru ◽  
Leontin Nicolae Druga ◽  
Florica Tudose ◽  
Roxana Trusca
Keyword(s):  
Surface Reaction ◽  
Effective Solution ◽  
Reaction Products ◽  
Toxic Reaction ◽  
Wide Range ◽  
Toxic Environment ◽  
Thermochemical Processing ◽  
Surface Saturation ◽  
Gas Molecules ◽  
Toxic Components

Experimental research aimed to find a solution for replacing components with high toxicity (or generating such components as a result of reactions occurring in the environment at processing temperatures) from the environments used for ferritic nitrocarburising process (FNCP) with non-hazardous components, but extremely active during the process. In the temperature range in which this type of processing is applied (lower than the eutectoid transformation temperature in the Fe-N phase diagram), the most commonly used media are liquid or gaseous; liquid ones contain toxic components (sodium or potassium cyanates/cyanides), and gaseous ones require complex equipments. Packing is extremely rarely used, but in this case pack-mix contain toxic components (15 � 20 wt.% sodium or potassium ferrocyanide). Urea also called carbamide (CO (NH2)2) is the active component in the pack-mixing proposed to be used for FNCP. Carbamide is used in low temperature cyanidation thermochemical heat treatment (liquid FNC), together with sodium or potassium carbonates, resulting in very toxic reaction products (sodium or potassium cyanates). Compared to cyanidation, in the version proposed in the paper, the carbamide does not react with carbonates because they are not found in the composition of the environment but decomposes in the presence or absence of oxygen (by a disproportionation reaction) with the formation of some gas molecules interesting for the process. It has been concluded that the use of carbamide together with two other components, activated charcoal (having a triple role - dispersing, storage, surface saturation) and respectively ammonium chloride as surface reaction activator, is an effective solution for achieving the desired goals by applying this type of thermochemical processing to a wide range of products made of quality steels up to alloy miscellaneous steels.

scholarly journals Balancing nutrients in a toxic environment: the challenge of eating

2021 ◽  
Author(s):  
Peng Wang ◽  
Daniel G. Vassão ◽  
Bettina Raguschke ◽  
Michael J. Furlong ◽  
Myron P. Zalucki
Keyword(s):  
Toxic Environment

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.

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