Kinetic relationship in parallel autocatalytic amplifications of pyridyl alkanol and chiral trigger pyrimidyl alkanol

A large-scale study employing matched molecular pair (MMP) analysis to uncover the contribution of a compound's polarity to its association and dissociation rates.

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Chromatic Regulation of Photosystem Composition in the Cyanobacterial Photosynthetic System: Kinetic Relationship between Change of Photosystem Composition and Cell Proliferation

Plant and Cell Physiology ◽

10.1093/oxfordjournals.pcp.a077288 ◽

1987 ◽

Keyword(s):

Cell Proliferation ◽

Photosynthetic System ◽

Kinetic Relationship

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Heat stability of concentrated skim milk as a function of heating time and temperature on a laboratory scale – Improved methodology and kinetic relationship

International Dairy Journal ◽

10.1016/j.idairyj.2015.05.005 ◽

2015 ◽

Vol 49 ◽

pp. 111-117 ◽

Cited By ~ 17

Author(s):

Joseph Dumpler ◽

Ulrich Kulozik

Keyword(s):

Skim Milk ◽

Heat Stability ◽

Heating Time ◽

Laboratory Scale ◽

Kinetic Relationship

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Structure-kinetic relationship of carbapenem antibacterials permeating throughE. coliOmpC porin

Proteins Structure Function and Bioinformatics ◽

10.1002/prot.24659 ◽

2014 ◽

Vol 82 (11) ◽

pp. 2998-3012 ◽

Cited By ~ 13

Author(s):

Que-Tien Tran ◽

Robert A. Pearlstein ◽

Sarah Williams ◽

John Reilly ◽

Thomas Krucker ◽

...

Keyword(s):

Kinetic Relationship ◽

Relationship Of

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A Novel High-Throughput FLIPR Tetra–Based Method for Capturing Highly Confluent Kinetic Data for Structure–Kinetic Relationship Guided Early Drug Discovery

SLAS DISCOVERY Advancing Life Sciences ◽

10.1177/24725552211000676 ◽

2021 ◽

pp. 247255522110006

Author(s):

Puneet Khurana ◽

Lisa McWilliams ◽

Jonathan Wingfield ◽

Derek Barratt ◽

Bharath Srinivasan

Keyword(s):

Parameter Estimation ◽

Drug Discovery ◽

High Throughput ◽

Kinetic Data ◽

Time Course ◽

Kinetic Studies ◽

Discovery Process ◽

Drug Discovery Process ◽

Traditional Methods ◽

Kinetic Relationship

Target engagement by small molecules is necessary for producing a physiological outcome. In the past, a lot of emphasis was placed on understanding the thermodynamics of such interactions to guide structure–activity relationships. It is becoming clearer, however, that understanding the kinetics of the interaction between a small-molecule inhibitor and the biological target [structure–kinetic relationship (SKR)] is critical for selection of the optimum candidate drug molecule for clinical trial. However, the acquisition of kinetic data in a high-throughput manner using traditional methods can be labor intensive, limiting the number of molecules that can be tested. As a result, in-depth kinetic studies are often carried out on only a small number of compounds, and usually at a later stage in the drug discovery process. Fundamentally, kinetic data should be used to drive key decisions much earlier in the drug discovery process, but the throughput limitations of traditional methods preclude this. A major limitation that hampers acquisition of high-throughput kinetic data is the technical challenge in collecting substantially confluent data points for accurate parameter estimation from time course analysis. Here, we describe the use of the fluorescent imaging plate reader (FLIPR), a charge-coupled device (CCD) camera technology, as a potential high-throughput tool for generating biochemical kinetic data with smaller time intervals. Subsequent to the design and optimization of the assay, we demonstrate the collection of highly confluent time-course data for various kinase protein targets with reasonable throughput to enable SKR-guided medicinal chemistry. We select kinase target 1 as a special case study with covalent inhibition, and demonstrate methods for rapid and detailed analysis of the resultant kinetic data for parameter estimation. In conclusion, this approach has the potential to enable rapid kinetic studies to be carried out on hundreds of compounds per week and drive project decisions with kinetic data at an early stage in drug discovery.

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JOHN RUSKIN: CLIMBING AND THE VULNERABLE EYE

Victorian Literature and Culture ◽

10.1017/s1060150309090044 ◽

2009 ◽

Vol 37 (1) ◽

pp. 43-66 ◽

Cited By ~ 3

Author(s):

Ann C. Colley

Keyword(s):

The Body ◽

John Ruskin ◽

Kinetic Relationship ◽

Mountain Landscape ◽

The Alps

Most readers either overlook or dismissJohn Ruskin's climbs in the Alps as being insignificant compared to his avid interest in geology and mountain form. However, I want to suggest that Ruskin's climbing – his physical and kinetic relationship to the mountains – is essential to his understanding of them. His numerous and repeated ascents in the lower Alps were not always easy: in fact, they were often tough and sometimes dangerous. Through a few select examples, in the first part of the essay, I establish just how difficult many of these scrambles were so that I may proceed, in the body of the paper, to talk about how these strenuous experiences influenced his way of seeing the mountain landscape he admired, and how, in turn, they helped shape his concept of imperfect vision.

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Principles of dose-setting in toxicology studies: the importance of kinetics for ensuring human safety

Archives of Toxicology ◽

10.1007/s00204-021-03155-4 ◽

2021 ◽

Author(s):

C. J. Borgert ◽

C. Fuentes ◽

L. D. Burgoon

Keyword(s):

Blood Level ◽

Maximum Dose ◽

Dose Range ◽

Chemical Toxicity ◽

Regulatory Toxicology ◽

Toxic Dose ◽

Kinetic Relationship ◽

Chemical Hazard ◽

Pharmacology And Toxicology ◽

Safe Dose

AbstractRegulatory toxicology seeks to ensure that exposures to chemicals encountered in the environment, in the workplace, or in products pose no significant hazards and produce no harm to humans or other organisms, i.e., that chemicals are used safely. The most practical and direct means of ensuring that hazards and harms are avoided is to identify the doses and conditions under which chemical toxicity does not occur so that chemical concentrations and exposures can be appropriately limited. Modern advancements in pharmacology and toxicology have revealed that the rates and mechanisms by which organisms absorb, distribute, metabolize and eliminate chemicals—i.e., the field of kinetics—often determine the doses and conditions under which hazard, and harm, are absent, i.e., the safe dose range. Since kinetics, like chemical hazard and toxicity, are extensive properties that depend on the amount of the chemical encountered, it is possible to identify the maximum dose under which organisms can efficiently metabolize and eliminate the chemicals to which they are exposed, a dose that has been referred to as the kinetic maximum dose, or KMD. This review explains the rationale that compels regulatory toxicology to embrace the advancements made possible by kinetics, why understanding the kinetic relationship between the blood level produced and the administered dose of a chemical is essential for identifying the safe dose range, and why dose-setting in regulatory toxicology studies should be informed by estimates of the KMD rather than rely on the flawed concept of maximum-tolerated toxic dose, or MTD.

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Analytical Model for Lattice Thermal Conductivity Predictions of Periodic Nanoporous Structures

Volume 8: Heat Transfer and Thermal Engineering ◽

10.1115/imece2016-65459 ◽

2016 ◽

Author(s):

Qing Hao ◽

Yue Xiao ◽

Hongbo Zhao

Keyword(s):

Thermal Conductivity ◽

Monte Carlo ◽

Monte Carlo Simulations ◽

Lattice Thermal Conductivity ◽

Phonon Transport ◽

Kinetic Relationship ◽

Wide Range ◽

Edge Scattering ◽

Bulk Phonon ◽

Nanoporous Structures

Phonon transport within nanoporous bulk materials or thin films is of importance to applications in thermoelectrics, gas sensors, and thermal insulation materials. Considering classical phonon size effects, the lattice thermal conductivity KL can be predicted assuming diffusive pore-edge scattering of phonons and bulk phonon mean free paths. In the kinetic relationship, kL can be computed by modifying the phonon mean free paths with the characteristic length ΛPore of the porous structure. Despite some efforts using the Monte Carlo ray tracing method to extract ΛPore, the resulting KL often diverges from that predicted by phonon Monte Carlo simulations. In this work, the effective ΛPore is extracted by directly comparing the predictions by the kinetic relationship and phonon Monte Carlo simulations. The investigation covers a wide range of period sizes and volumetric porosities. In practice, these ΛPore values can be used for thermal analysis of general nanoporous materials.

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