Chen Dan

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The efficacy of therapeutics is dependent on a drug binding to its cognate target. Optimization of target engagement by drugs in cells is often challenging, because drug binding cannot be monitored inside cells. We have developed a method for evaluating drug binding to target proteins in cells and tissue samples. This cellular thermal shift assay (CETSA) is(More)
Mounting evidence supports the involvement of brain inflammation and the associated blood–brain barrier damage from which spontaneous and recurrent seizures originate. Detection of the soluble form of adhesion molecules (AM) has also been proven to predict outcomes in central nervous system (CNS) disorders. A recent study has shown that expression of AM in(More)
In response to injury, synapse alteration may occur earlier than the changes in the cell body of neurons. Although retinal ganglion cell death and thinning of the inner part of retina were found after acute high intraocular pressure (HIOP), the structural and functional changes of synapses in the retina remain unknown. In the present study, we investigated(More)
Acetylcholinesterase is the enzyme that terminates neurotransmission by hydrolyzing the acetylcholine released by the motoneurons at the neuromuscular junctions. Although acetylcholinesterase has been studied for almost a century, the underlying relationship between exercise-induced fatigue and acetylcholinesterase activity at the synaptic cleft is not(More)
To visualize completely rat retinal microvessels, the gelatin-ink perfusion condition was systematically optimized using von Willebrand factor (vWf) immunostaining as control. Whether the vessel showed by the new perfusion condition can be used for double label with neurons or glial cells in the same retina was also tested. Our results showed that infusing(More)
MicroRNAs (miRNAs) are short, endogenously expressed RNAs (∼21–22 nt) processed from stem-loop regions of longer RNA precursors by a Dicer-like enzyme (Jones-Rhoades et al., 2006). In plants, microRNAs play an essential role in regulating many fundamental molecular interactions , including plant growth, development and response to environmental stress(More)
Target engagement is a critical factor for therapeutic efficacy. Assessment of compound binding to native target proteins in live cells is therefore highly desirable in all stages of drug discovery. We report here the first compound library screen based on biophysical measurements of intracellular target binding, exemplified by human thymidylate synthase(More)
We consider the problem of low rank approximation of binary matrices. Here we are given a d × n binary matrix A and a small integer k < d. The goal is to find two binary matrices U and V of sizes d × k and k × n respectively, so that the Frobenius norm of A − UV is minimized. There are two models of this problem, depending on the definition of the product(More)