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Van Nguyen, T.,Lee, J.,Sweredoski, Michael J.,Yang, S.J.,Jeon, S.J.,Harrison, Joseph S.,Yim, J.H.,Lee, S.,Handa, H.,Kuhlman, B.,Jeong, J.S.,Reitsma, Justin M.,Park, C.S.,Hess, S.,Deshaies, Raymond J. Cell Press 2016 Molecular cell Vol.61 No.6
<P>Cereblon (CRBN), a substrate receptor for the cullin-RING ubiquitin ligase 4 (CRL4) complex, is a direct protein target for thalidomide teratogenicity and antitumor activity of immunomodulatory drugs (IMiDs). Here we report that glutamine synthetase (GS) is an endogenous substrate of CRL4(CRBN). Upon exposing cells to high glutamine concentration, GS is acetylated at lysines 11 and 14, yielding a degron that is necessary and sufficient for binding and ubiquitylation by CRL4 CRBN and degradation by the proteasome. Binding of acetylated degron peptides to CRBN depends on an intact thalidomide-binding pocket but is not competitive with IMiDs. These findings reveal a feedback loop involving CRL4 CRBN that adjusts GS protein levels in response to glutamine and uncover a new function for lysine acetylation.</P>
Harrison,Christine J. 가톨릭중앙의료원 가톨릭암센터 1996 암심포지움 Vol.- No.2
Diagnosis. Specific Cytogenetic Rearrangements. Cytogenetic analysis of haematological malignan-cies plays a major rolo in the diagnosis of the disease. It is well known that a large number of non-random chromosome abnormalities are associa-ted with specific types and sub-types of leukaemia. Often the cytogenetics result provides the definitive diagnosis.
J. A. Harrison,G. Gao,G. M. Chateauneuf,P. T. Mikulski 한국트라이볼로지학회 2002 한국트라이볼로지학회 학술대회 Vol.2002 No.10
In this digest, we briefly review our current molecular dynamics (MD) simulations that utilize both the reactive empirical bond order potential (REBO) and the adaptive intermolecular REBO (AIREBO) potential energy functions. The AIREBO potential includes intermolecular interactions, so that self-assembled monolayers, and liquids, can be modeled. We have examined the mechanical and tribological properties of model self assembled mono layers and amorphous carbon films. Self-assembled mono layers are modeled by covalently bonding hydrocarbon chains to diamond substrates. Because the REBO potentials can model chemical reactions, specific compression and sliding induced chemical reactions were identified.
K_4GeP_4Se_12: a case for phase-change nonlinear optical chalcogenide
Jang, J. I.,Park, S.,Harrison, C. M.,Clark, D. J.,Morris, C. D.,Chung, I.,Kanatzidis, M. G. The Optical Society 2013 Optics letters Vol.38 No.8
<P>We report on broadband nonlinear optical (NLO) responses from a phase-change chalcogenide compound K(4)GeP(4)Se(12). Its glassy phase exhibits unusual second-harmonic generation (SHG) due to the preservation of local crystallographic order. The SHG efficiency of the glassy form can be boosted by more than 2 orders of magnitude by simple heat treatment. Strong SHG and third-harmonic generation from both glassy and crystalline compounds were characterized over a wide wavelength range of 1.2-4.0 μm. Our results imply that K(4)GeP(4)Se(12) can be utilized for various NLO applications in the mid-infrared spectrum.</P>
Reduction of Complex Signaling Networks to a Representative Kernel
Kim, J.-R.,Kim, J.,Kwon, Y.-K.,Lee, H.-Y.,Heslop-Harrison, P.,Cho, K.-H. American Association for the Advancement of Scienc 2011 Science signaling Vol.4 No.175
<P>The network of biomolecular interactions that occurs within cells is large and complex. When such a network is analyzed, it can be helpful to reduce the complexity of the network to a 'kernel' that maintains the essential regulatory functions for the output under consideration. We developed an algorithm to identify such a kernel and showed that the resultant kernel preserves the network dynamics. Using an integrated network of all of the human signaling pathways retrieved from the KEGG (Kyoto Encyclopedia of Genes and Genomes) database, we identified this network's kernel and compared the properties of the kernel to those of the original network. We found that the percentage of essential genes to the genes encoding nodes outside of the kernel was about 10%, whereas similar to 32% of the genes encoding nodes within the kernel were essential. In addition, we found that 95% of the kernel nodes corresponded to Mendelian disease genes and that 93% of synthetic lethal pairs associated with the network were contained in the kernel. Genes corresponding to nodes in the kernel had low evolutionary rates, were ubiquitously expressed in various tissues, and were well conserved between species. Furthermore, kernel genes included many drug targets, suggesting that other kernel nodes may be potential drug targets. Owing to the simplification of the entire network, the efficient modeling of a large-scale signaling network and an understanding of the core structure within a complex framework become possible.</P>