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B-RAF is the most frequently mutated protein kinase in human cancers. The finding that oncogenic mutations in BRAF are common in melanoma, followed by the demonstration that these tumours are dependent on the RAF/MEK/ERK pathway, offered hope that inhibition of B-RAF kinase activity could benefit melanoma patients. Herein, we describe the structure-guided(More)
Glutamate carboxypeptidase II (GCPII, NAALADase, or NAAG peptidase) is a catalytic zinc metallopeptidase. Its extracellular domain hydrolyzes the abundant neuropeptide, N-acetyl-L-aspartyl-L-glutamate (NAAG), to produce N-acetylaspartate and glutamate following the synaptic release of this transmitter. Thus, GCPII influences the extracellular concentrations(More)
BACKGROUND Expression of the colony-stimulating factor 1 (CSF1) gene is elevated in most tenosynovial giant-cell tumors. This observation has led to the discovery and clinical development of therapy targeting the CSF1 receptor (CSF1R). METHODS Using x-ray co-crystallography to guide our drug-discovery research, we generated a potent, selective CSF1R(More)
Oncogenic activation of BRAF fuels cancer growth by constitutively promoting RAS-independent mitogen-activated protein kinase (MAPK) pathway signalling. Accordingly, RAF inhibitors have brought substantially improved personalized treatment of metastatic melanoma. However, these targeted agents have also revealed an unexpected consequence: stimulated growth(More)
The dynamics of network traffic are complex and nonlinear, and chaotic behaviors and their prediction, which play an important role in local area networks (LANs), are studied in detail, using the largest Lyapunov exponent. With the introduction of phase space reconstruction based on the time sequence, the high-dimensional traffic is projected onto the low(More)
Based on phase space reconstruction and fractal dynamics in nonlinear dynamics, a method is proposed to extract and analyze the dynamics of the rotating stall in the impeller of centrifugal compressor, and some numerical examples are given to verify the results as well. First, the rotating stall of an existing low speed centrifugal compressor (LSCC) is(More)
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