scholarly journals TAIJI: approaching experimental replicates-level accuracy for drug synergy prediction

2018 ◽  
Vol 35 (13) ◽  
pp. 2338-2339 ◽  
Author(s):  
Hongyang Li ◽  
Shuai Hu ◽  
Nouri Neamati ◽  
Yuanfang Guan
Keyword(s):  
Drug Combination ◽  
High Performance ◽  
Synergistic Effects ◽  
Field Performance ◽  
Supplementary Information ◽  
Drug Synergism ◽  
High Throughput Drug Screening ◽  
Current State ◽  
Candidate Drug ◽  
High Prediction

Abstract Motivation Combination therapy is widely used in cancer treatment to overcome drug resistance. High-throughput drug screening is the standard approach to study the drug combination effects, yet it becomes impractical when the number of drugs under consideration is large. Therefore, accurate and fast computational tools for predicting drug synergistic effects are needed to guide experimental design for developing candidate drug pairs. Results Here, we present TAIJI, a high-performance software for fast and accurate prediction of drug synergism. It is based on the winning algorithm in the AstraZeneca-Sanger Drug Combination Prediction DREAM Challenge, which is a unique platform to unbiasedly evaluate the performance of current state-of-the-art methods, and includes 160 team-based submission methods. When tested across a broad spectrum of 85 different cancer cell lines and 1089 drug combinations, TAIJI achieved a high prediction correlation (0.53), approaching the accuracy level of experimental replicates (0.56). The runtime is at the scale of minutes to achieve this state-of-the-field performance. Availability and implementation TAIJI is freely available on GitHub (https://github.com/GuanLab/TAIJI). It is functional with built-in Perl and Python. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals In Vitro Assessment of Methylene Blue on Chloroquine-Sensitive and -Resistant Plasmodium falciparum Strains Reveals Synergistic Action with Artemisinins

2005 ◽  
Vol 49 (11) ◽  
pp. 4592-4597 ◽  
Author(s):  
Monique Akoachere ◽  
Kathrin Buchholz ◽  
Elisabeth Fischer ◽  
Jürgen Burhenne ◽  
Walter E. Haefeli ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Drug Combination ◽  
High Performance ◽  
Synergistic Effects ◽  
Field Trials ◽  
Drug Candidate ◽  
Therapeutic Effects ◽  
Drug Resistant ◽  
Parasite Strains

ABSTRACT Methylene blue (MB) represents a promising antimalarial drug candidate for combination therapies against drug-resistant parasite strains. To support and facilitate the application of MB in future field trials, we studied its antiparasitic effects in vitro. MB is active against all blood stages of both chloroquine (CQ)-sensitive and CQ-resistant P. falciparum strains with 50% inhibitory concentration (IC50) values in the lower nanomolar range. Ring stages showed the highest susceptibility. As demonstrated by high-performance liquid chromatography-tandem mass spectrometry on different cell culture compartments, MB is accumulated in malarial parasites. In drug combination assays, MB was found to be antagonistic with CQ and other quinoline antimalarials like piperaquine and amodiaquine; with mefloquine and quinine, MB showed additive effects. In contrast, we observed synergistic effects of MB with artemisinin, artesunate, and artemether for all tested parasite strains. Artemisinin/MB combination concentration ratios of 3:1 were found to be advantageous, demonstrating that the combination of artemisinin with a smaller amount of MB can be recommended for reaching maximal therapeutic effects. Our in vitro data indicate that combinations of MB with artemisinin and related endoperoxides might be a promising option for treating drug-resistant malaria and should be studied in future field trials. Resistance development under this drug combination is unlikely to occur.

Morphology of High-Performance Rigid-Rod Polymer Fibers and Molecular Composites

1989 ◽  
Vol 47 ◽  
pp. 338-339
Author(s):  
W.W. Adams ◽  
S. J. Krause
Keyword(s):  
Tensile Strength ◽  
High Performance ◽  
Liquid Crystalline ◽  
Molecular Level ◽  
Synergistic Effects ◽  
Tensile Modulus ◽  
Commercial Development ◽  
The Matrix ◽  
Molecular Composites ◽  
Rigid Rod

Rigid-rod polymers such as PBO, poly(paraphenylene benzobisoxazole), Figure 1a, are now in commercial development for use as high-performance fibers and for reinforcement at the molecular level in molecular composites. Spinning of liquid crystalline polyphosphoric acid solutions of PBO, followed by washing, drying, and tension heat treatment produces fibers which have the following properties: density of 1.59 g/cm3; tensile strength of 820 kpsi; tensile modulus of 52 Mpsi; compressive strength of 50 kpsi; they are electrically insulating; they do not absorb moisture; and they are insensitive to radiation, including ultraviolet. Since the chain modulus of PBO is estimated to be 730 GPa, the high stiffness also affords the opportunity to reinforce a flexible coil polymer at the molecular level, in analogy to a chopped fiber reinforced composite. The objectives of the molecular composite concept are to eliminate the thermal expansion coefficient mismatch between the fiber and the matrix, as occurs in conventional composites, to eliminate the interface between the fiber and the matrix, and, hopefully, to obtain synergistic effects from the exceptional stiffness of the rigid-rod molecule. These expectations have been confirmed in the case of blending rigid-rod PBZT, poly(paraphenylene benzobisthiazole), Figure 1b, with stiff-chain ABPBI, poly 2,5(6) benzimidazole, Fig. 1c A film with 30% PBZT/70% ABPBI had tensile strength 190 kpsi and tensile modulus of 13 Mpsi when solution spun from a 3% methane sulfonic acid solution into a film. The modulus, as predicted by rule of mixtures, for a film with this composition and with planar isotropic orientation, should be 16 Mpsi. The experimental value is 80% of the theoretical value indicating that the concept of a molecular composite is valid.

scholarly journals Comparative Study of the Field Performances of Pressure-Grouted Micropiles Using Gravity and Packers

2021 ◽  
Vol 11 (15) ◽  
pp. 6736
Author(s):  
Ong Heo ◽  
Yeowon Yoon ◽  
Jinung Do
Keyword(s):  
Urban Areas ◽  
High Performance ◽  
Driving Forces ◽  
Field Performance ◽  
Underground Space ◽  
Creep Tests ◽  
Deep Foundation ◽  
Installation Depth ◽  
Pressure Grouting ◽  
The One

When underground space requires excavation in areas below the water table, the foundation system suffers from buoyancy, which leads to the uplifting of the superstructure. A deep foundation system can be used; however, in cases where a hard layer is encountered, high driving forces and corresponding noises cause civil complaints in urban areas. Micropiles can be an effective alternative option, due to their high performance despite a short installation depth. Pressurized grouting is used with a packer to induce higher interfacial properties between micropile and soil. In this study, the field performance of micropiles installed using gravitational grouting or pressure-grouted using either a geotextile packer or rubber packer was comparatively evaluated by tension and creep tests. Micropiles were installed using pressure grouting in weak and fractured zones. As results, the pressure-grouted micropiles showed more stable and stronger behaviors than ones installed using the gravitational grouting. Moreover, the pressure-grouted micropile installed using the rubber packer showed better performance than the one using the geotextile packer.

Low ECD High Performance Invert Emulsion Drilling Fluids: Lab Development and Field Deployment

2021 ◽  
Author(s):  
Vikrant Wagle ◽  
Abdullah Yami ◽  
Michael Onoriode ◽  
Jacques Butcher ◽  
Nivika Gupta
Keyword(s):  
High Performance ◽  
Filter Cake ◽  
Drilling Fluid ◽  
Field Performance ◽  
Superior Performance ◽  
Core Material ◽  
Drilling Fluids ◽  
Invert Emulsion ◽  
Field Deployment ◽  
Permeability Studies

Abstract The present paper describes the results of the formulation of an acid-soluble low ECD organoclay-free invert emulsion drilling fluid formulated with acid soluble manganese tetroxide and a specially designed bridging package. The paper also presents a short summary of field applications to date. The novel, non-damaging fluid has superior rheology resulting in lower ECD, excellent suspension properties for effective hole cleaning and barite-sag resistance while also reducing the risk of stuck pipe in high over balance applications. 95pcf high performance invert emulsion fluid (HPIEF) was formulated using an engineered bridging package comprising of acid-soluble bridging agents and an acid-soluble weighting agent viz. manganese tetroxide. The paper describes the filtration and rheological properties of the HPIEF after hot rolling at 300oF. Different tests such as contamination testing, sag-factor analysis, high temperature-high pressure rheology measurements and filter-cake breaking studies at 300oF were performed on the HPIEF. The 95pcf fluid was also subjected to particle plugging experiments to determine the invasion characteristics and the non-damaging nature of the fluids. The 95pcf HPIEF exhibited optimal filtration properties at high overbalance conditions. The low PV values and rheological profile support low ECDs while drilling. The static aging tests performed on the 95pcf HPIEF resulted in a sag factor of less than 0.53, qualifying the inherent stability for expected downhole conditions. The HPIEF demonstrated resilience to contamination testing with negligible change in properties. Filter-cake breaking experiments performed using a specially designed breaker fluid system gave high filter-cake breaking efficiency. Return permeability studies were performed with the HPIEF against synthetic core material, results of which confirmed the non-damaging design of the fluid. The paper thus demonstrates the superior performance of the HPIEF in achieving the desired lab and field performance.

scholarly journals GWASpro: a high-performance genome-wide association analysis server

2018 ◽  
Vol 35 (14) ◽  
pp. 2512-2514 ◽  
Author(s):  
Bongsong Kim ◽  
Xinbin Dai ◽  
Wenchao Zhang ◽  
Zhaohong Zhuang ◽  
Darlene L Sanchez ◽  
...  
Keyword(s):  
High Performance ◽  
Large Scale ◽  
Linear Mixed Model ◽  
Association Studies ◽  
Learning Curves ◽  
Experimental Designs ◽  
Genome Wide Association ◽  
Supplementary Information ◽  
Genome Wide Association Studies ◽  
Genome Wide

Abstract Summary We present GWASpro, a high-performance web server for the analyses of large-scale genome-wide association studies (GWAS). GWASpro was developed to provide data analyses for large-scale molecular genetic data, coupled with complex replicated experimental designs such as found in plant science investigations and to overcome the steep learning curves of existing GWAS software tools. GWASpro supports building complex design matrices, by which complex experimental designs that may include replications, treatments, locations and times, can be accounted for in the linear mixed model. GWASpro is optimized to handle GWAS data that may consist of up to 10 million markers and 10 000 samples from replicable lines or hybrids. GWASpro provides an interface that significantly reduces the learning curve for new GWAS investigators. Availability and implementation GWASpro is freely available at https://bioinfo.noble.org/GWASPRO. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals HPLC-UV method for quantification of favipiravir in pharmaceutical formulations

2020 ◽  
Author(s):  
İbrahim Bulduk
Keyword(s):  
High Performance ◽  
Potassium Dihydrogen Phosphate ◽  
Pharmaceutical Formulations ◽  
Hplc Method ◽  
Dihydrogen Phosphate ◽  
Potential Candidate ◽  
Column Temperature ◽  
Candidate Drug ◽  
System Suitability ◽  
Relative Standard

AbstractFavipiravir (FVP), a pyrazine analog, has shown antiviral activity against a wide variety of viruses. It is considered to be worth further investigation as a potential candidate drug for COVID-19. It is not officially available in any pharmacopoeia. A rapid, simple, precise, accurate, and isocratic high performance liquid chromatography (HPLC) method has been developed for routine quality control of favipiravir in pharmaceutical formulations. Separation was carried out by C18 column. The mobile phase was a mixture of 50 mM potassium dihydrogen phosphate (pH 2.3) and acetonitrile (90:10, v/v) at a flow rate of 1 mL min−1. The ultraviolet (UV) detection and column temperature were 323 nm, and 30 °C, respectively. The run time was 15 min under these chromatographic conditions. Excellent linear relationship between peak area and favipiravir concentration in the range of 10–100 μg mL−1 has been observed (r2, 0.9999). Developed method has been found to be sensitive (limits of detection and quantification were 1.20 μg mL−1 and 3.60 μg mL−1, respectively), precise (the interday and intraday relative standard deviation (RSD) values for peak area and retention time were less than 0.4 and 0.2%, respectively), accurate (recovery, 99.19–100.17%), specific and robust (% RSD were less than 1.00, for system suitability parameters). Proposed method has been successfully applied for quantification of favipiravir in pharmaceutical formulations.

scholarly journals Ionic-liquid-assisted one-pot synthesis of Cu2O nanoparticles/multi-walled carbon nanotube nanocomposite for high-performance asymmetric supercapacitors

RSC Advances ◽  
2018 ◽  
Vol 8 (36) ◽  
pp. 20182-20189 ◽  
Author(s):  
Ying Lu ◽  
Jian-Long Xu ◽  
Shan Ren ◽  
Ya-Nan Zhong ◽  
Xu Gao ◽  
...  
Keyword(s):  
Ionic Liquid ◽  
Carbon Nanotube ◽  
High Performance ◽  
Room Temperature ◽  
Synergistic Effects ◽  
Asymmetric Supercapacitors ◽  
One Pot ◽  
Multi Walled Carbon Nanotube ◽  
Cu2o Nanoparticles ◽  
Cycling Life

A one-pot room-temperature-ionic-liquid-assisted sputtering approach is designed to synthesize Cu2O/MWCNTs nanocomposite with high capacitance and long cycling life due to synergistic effects of oxygen-deficient Cu2O and conductive MWCNTs.

Your winning business model agenda: four questions to shape growth

2018 ◽  
Vol 46 (4) ◽  
pp. 21-27 ◽  
Author(s):  
Vladyslav Biloshapka ◽  
Oleksiy Osiyevskyy
Keyword(s):  
Business Model ◽  
High Performance ◽  
Design Methodology ◽  
Business Models ◽  
Scale Up ◽  
The Other ◽  
Content Type ◽  
Current State ◽  
Growth Planning ◽  
Practical Implications

Purpose Defines clear steps for growth planning that support answers to the crucial question: How and where are you planning to scale up the business and what talent do you need to implement this? Design/methodology/approach As the “Business model value matrix” shows, having ‘happy customers’ is only one determinant of a business model’s success. The other essential block of diagnostic questions deals with the current state and prospects of the firm’s growth. Findings We found that companies that have found ways to keep their business models in a winner’s state can provide clear, evidence-based answers to questions about growth opportunities and risks, while their less successful peers have difficulty addressing the issues. Continuous collecting and analyzing of this information allows successful companies to embrace the strategy-as-learning model of development, built around active learning and proactive adjustment to evolving environment. Practical implications To develop a strategy for moving to and sustaining the Winner state, managers must clearly articulate and test a set of hypotheses about the mechanisms of their company’s growth. The first step on this path is related to obtaining a clear view on the factors that underpin the current financial performance. Originality/value High-performance cultures make sure that each manager has the clear answers to the questions of value, growth and digitization in order to learn, experiment and implement the company business model agenda. The unproductive cultures, on the other hand, are sustained by managerial teams that usually do not have the answers to these crucial questions, but are very good at political games.

scholarly journals Plant Growth Regulator Effects on Germination and Root Traits of ‘Lambada’ and ‘Don Victor’ Onion Cultivars

HortScience ◽  
2017 ◽  
Vol 52 (12) ◽  
pp. 1759-1764
Author(s):  
Maria A. Macias-Leon ◽  
Daniel I. Leskovar
Keyword(s):  
Seed Germination ◽  
Plant Growth ◽  
Synergistic Effects ◽  
Field Performance ◽  
Root Traits ◽  
Root Surface ◽  
Root Diameter ◽  
Root Surface Area ◽  
Relative Growth ◽  
Relative Growth Rates

Onions (Allium cepa L.) are easily outcompeted by weeds because of slow germination and relative growth rates. Therefore, high percentage of seed germination and root vigor are important traits to improve field performance. The effects of exogenous plant growth regulators (PGRs), 2-chloroethylphosphonic acid (ethephon, Eth), indole-3-acetic acid (IAA), trans-zeatin (tZ), and 1-aminocyclopropane-1-carboxylic acid (ACC) were evaluated on the germination and root growth of ‘Don Victor’ (yellow) and ‘Lambada’ (red) onion seedlings. Seeds were soaked for 10 hours in hormonal solutions and water (hydro-priming). Seed germination improved with Eth (30 and 100 μm), Eth (100 μm) + IAA (10 μm), and IAA (3 μm) treatments. Root surface area (RSA) increased in response to Eth at 30 and 100 μm, Eth + IAA, and 3 μm IAA. Root length (RL) and root diameter (RD) were enhanced by 1 μm tZ and 100 μm ACC. Eth reduced RL and RD, whereas IAA showed no effects. A subsequent experiment evaluated synergistic effects of different PGRs. Treatment of seeds with ACC (250 μm) + tZ (0.5 μm) and ACC (250 μm) + tZ (0.5 μm) + Eth (20 μm) enhanced RL and RD. RSA was unaffected by ACC + tZ + Eth. The results suggest that exogenous PGRs could be useful to enhance germination, RL, and RSA of onion seedlings.

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