36 research outputs found
A novel sensor measuring local voidage profile inside a fluidised bed reactor
Liquid-solid fluidisation is frequently encountered in drinking water treatment processes, often to obtain a large liquid-solid interfacial surface area. A large surface area is crucial for optimal seeded crystallisation in full-scale softening reactors. Due to crystallisation, particles grow and migrate to a lower zone in the reactor which leads to a stratified bed. Larger particles adversely affect the surface area. To maintain optimal process conditions in the fluidised beds, information is needed about the distribution of particle size, local voidage and available surface area, over the reactor height. In this work, a sensor is developed to obtain the hydraulic state gradient, based on Archimedesā principle. A cylindrical heavy object is submerged in the fluidised bed and lowered gradually while its weight is measured at various heights using a sensitive force measuring device. Based on accurate fluidisation experiments with calcite grains, the voidage is determined and a straightforward empirical model is developed to estimate the particle size as a function of superficial fluid velocity, kinematic viscosity, suspension density, voidage and particle density. The surface area and specific space velocity can be estimated accordingly, which represent key performance indicators regarding the hydraulic state of the fluidised bed reactor. The prediction error for voidage is 5 Ā± 2 % and for particle size 9 Ā± 4 %. The newly developed soft sensor is a more time-effective method for obtaining the hydraulic state in full-scale liquid-solid fluidised bed reactors
New Affinity Probe Targeting VEGF Receptors for Kinase Inhibitor Selectivity Profiling by Chemical Proteomics
Solid
tumors are dependent for growth on nutrients and the supply
of oxygen, which they often acquire via neoangiogenesis. Vascular
endothelial growth factors and the corresponding receptors (VEGFRs)
play central roles in this process, and consequently, the blockade
of this pathway is one therapeutic strategy for cancer treatment.
A number of small molecules inhibiting VEGFR inhibitors have been
developed for clinical use, and a comprehensive view of target selectivity
is important to assess the therapeutic as well as risk potential of
a drug molecule. Recent advances in mass spectrometry-based chemical
proteomics allow analyses of drugātarget interactions under
close-to-physiological conditions, and in this study, we report on
the design, synthesis, and application of a small molecule affinity
probe as a tool for the selectivity profiling of VEGFR and other kinase
inhibitors. The probe is capable of binding >132 protein kinases,
including angiokinases such as VEGFRs, PDGFRs, and c-KIT from lysates
of cancer cell lines or human placenta tissue. Combining the new probe
with Kinobeads in competitive binding assays, we were able to identify
nanomolar off-targets of the VEGFR/PDGFR inhibitors pazopanib and
axitinib. Because of its broad binding spectrum, the developed chemical
tool can be generically used for the discovery of kinase inhibitor
targets, which may contribute to a more comprehensive understanding
of the mechanisms of action of such drugs
Composite hydrogeological investigation and characterisation methods applied at a nuclear power plant site in Taiwan
Optimized Chemical Proteomics Assay for Kinase Inhibitor Profiling
Solid supported probes
have proven to be an efficient tool for
chemical proteomics. The kinobeads technology features kinase inhibitors
covalently attached to Sepharose for affinity enrichment of kinomes
from cell or tissue lysates. This technology, combined with quantitative
mass spectrometry, is of particular interest for the profiling of
kinase inhibitors. It often leads to the identification of new targets
for medicinal chemistry campaigns where it allows a two-in-one binding
and selectivity assay. The assay can also uncover resistance mechanisms
and molecular sources of toxicity. Here we report on the optimization
of the kinobead assay resulting in the combination of five chemical
probes and four cell lines to cover half the human kinome in a single
assay (ā¼260 kinases). We show the utility and large-scale applicability
of the new version of kinobeads by reprofiling the small molecule
kinase inhibitors Alvocidib, Crizotinib, Dasatinib, Fasudil, Hydroxyfasudil,
Nilotinib, Ibrutinib, Imatinib, and Sunitinib