55 research outputs found
Dynamical nucleus-nucleus potential at short distances
The dynamical nucleus-nucleus potentials for fusion reactions 40Ca+40Ca,
48Ca+208Pb and 126Sn+130Te are studied with the improved quantum molecular
dynamics (ImQMD) model together with the extended Thomas-Fermi approximation
for the kinetic energies of nuclei. The obtained fusion barrier for 40Ca+40Ca
is in good agreement with the extracted fusion barrier from the measured fusion
excitation function, and the depth of the fusion pockets are close to the
results of time-dependent Hartree-Fock calculations. The energy dependence of
fusion barrier is also investigated. For heavy fusion system, the fusion pocket
becomes shallow and almost disappears for symmetric systems and the obtained
potential at short distances is higher than the adiabatic potential.Comment: 6 figures, accepted for publication in Phys. Rev.
Plasma Protein Binding (PPB) & Tissue Binding as High-Throughput Assays to Quantify the Free Fraction of Novel Cancer Therapeutics
https://openworks.mdanderson.org/catalyst24/1010/thumbnail.jp
Experimental Investigation for Fault Diagnosis Based on a Hybrid Approach Using Wavelet Packet and Support Vector Classification
To deal with the difficulty to obtain a large number of fault samples under the practical condition for mechanical fault diagnosis, a hybrid method that combined wavelet packet decomposition and support vector classification (SVC) is proposed. The wavelet packet is employed to decompose the vibration signal to obtain the energy ratio in each frequency band. Taking energy ratios as feature vectors, the pattern recognition results are obtained by the SVC. The rolling bearing and gear fault diagnostic results of the typical experimental platform show that the present approach is robust to noise and has higher classification accuracy and, thus, provides a better way to diagnose mechanical faults under the condition of small fault samples
New contributions to the knowledge of Chinese flea beetle fauna (III): revision of Meishania Chen & Wang with description of five new species (Coleoptera: Chrysomelidae: Galerucinae)
The flea beetle genus Meishania Chen & Wang is revised and five new species—M. cangshanensis sp. nov., M. flavipen- nis sp. nov., M. fulvotigera sp. nov., and M. sichuanica sp. nov. from China and M. bhutanensis sp. nov. from Bhutan— are described. All species of Meishania are illustrated and a key to species is provided
New contributions to the knowledge of Chinese flea beetle fauna (III): revision of Meishania Chen & Wang with description of five new species (Coleoptera: Chrysomelidae: Galerucinae)
The flea beetle genus Meishania Chen & Wang is revised and five new species—M. cangshanensis sp. nov., M. flavipen- nis sp. nov., M. fulvotigera sp. nov., and M. sichuanica sp. nov. from China and M. bhutanensis sp. nov. from Bhutan— are described. All species of Meishania are illustrated and a key to species is provided
Comparative Pharmacology of a Bis-Pivaloyloxymethyl Phosphonate Prodrug Inhibitor of Enolase after Oral and Parenteral Administration
Metabolically labile prodrugs can experience stark differences in catabolism incurred by the chosen route of administration. This is especially true for phosph(on)ate prodrugs, in which successive promoiety removal transforms a lipophilic molecule into increasingly polar compounds. We previously described a phosphonate inhibitor of enolase (HEX) and its bis-pivaloyloxymethyl ester prodrug (POMHEX) capable of eliciting strong tumor regression in a murine model of enolase 1 (ENO1)-deleted glioblastoma following parenteral administration. Here, we characterize the pharmacokinetics and pharmacodynamics of these enolase inhibitors in vitro and in vivo after oral and parenteral administration. In support of the historical function of lipophilic prodrugs, the bis-POM prodrug significantly improves cell permeability of and rapid hydrolysis to the parent phosphonate, resulting in rapid intracellular loading of peripheral blood mononuclear cells in vitro and in vivo. We observe the influence of intracellular trapping in vivo on divergent pharmacokinetic profiles of POMHEX and its metabolites after oral and parenteral administration. This is a clear demonstration of the tissue reservoir effect hypothesized to explain phosph(on)ate prodrug pharmacokinetics but has heretofore not been explicitly demonstrated
Targeting Medium-Chain Acyl-CoA Dehydrogenase for Glioblastoma
View full abstracthttps://openworks.mdanderson.org/leading-edge/1041/thumbnail.jp
Multi-disciplinary efforts to evaluate the therapeutic potential of CDK11, a novel transcription associated cyclin dependent kinase.
View full abstracthttps://openworks.mdanderson.org/leading-edge/1043/thumbnail.jp
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An inhibitor of oxidative phosphorylation exploits cancer vulnerability.
Metabolic reprograming is an emerging hallmark of tumor biology and an actively pursued opportunity in discovery of oncology drugs. Extensive efforts have focused on therapeutic targeting of glycolysis, whereas drugging mitochondrial oxidative phosphorylation (OXPHOS) has remained largely unexplored, partly owing to an incomplete understanding of tumor contexts in which OXPHOS is essential. Here, we report the discovery of IACS-010759, a clinical-grade small-molecule inhibitor of complex I of the mitochondrial electron transport chain. Treatment with IACS-010759 robustly inhibited proliferation and induced apoptosis in models of brain cancer and acute myeloid leukemia (AML) reliant on OXPHOS, likely owing to a combination of energy depletion and reduced aspartate production that leads to impaired nucleotide biosynthesis. In models of brain cancer and AML, tumor growth was potently inhibited in vivo following IACS-010759 treatment at well-tolerated doses. IACS-010759 is currently being evaluated in phase 1 clinical trials in relapsed/refractory AML and solid tumors
The Lysosomal v-ATPase-Ragulator Complex Is a Common Activator for AMPK and mTORC1, Acting as a Switch between Catabolism and Anabolism
林圣彩教授课题组长期致力于细胞信号转导的研究。近年来,该课题组潜心研究,不断攻关,取得了一系列重大成果,如揭示细胞如何应对生长因子缺乏的内在机理,发现了细胞自噬“路线图”、还发现了细胞如何感应“饥饿”信号AMP的信号传导通路等。其中,“发现细胞自噬‘路线图’”成果曾登上《科学》杂志,并入选2012年度“中国科学十大进展”。AMPK and mTOR play principal roles in governing metabolic programs; however, mechanisms underlying the coordination of the two inversely regulated kinases remain unclear. In this study we found, most surprisingly, that the late endosomal/lysosomal protein complex v-ATPase-Ragulator, essential for activation of mTORC1, is also required for AMPK activation. We also uncovered that AMPK is a residential protein of late endosome/lysosome. Under glucose starvation, the v-ATPase-Ragulator complex is accessible to AXIN/LKB1 for AMPK activation. Concurrently, the guanine nucleotide exchange factor (GEF) activity of Ragulator toward RAG is inhibited by AXIN, causing dissociation from endosome and inactivation of mTORC1. We have thus revealed that the v-ATPase-Ragulator complex is also an initiating sensor for energy stress and meanwhile serves as an endosomal docking site for LKB1-mediated AMPK activation by forming the v-ATPase-Ragulator-AXIN/LKB1-AMPK complex, thereby providing a switch between catabolism and anabolism. Our current study also emphasizes a general role of late endosome/lysosome in controlling metabolic programs
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