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Helander S.,Linkoping University | Montecchio M.,Linkoping University | Lemak A.,University of Toronto | Fares C.,University of Toronto | And 9 more authors.
Biochemical and Biophysical Research Communications | Year: 2014

In this paper, we describe the structure of a N-terminal domain motif in nuclear-localized FKBP251-73, a member of the FKBP family, together with the structure of a sequence-related subdomain of the E3 ubiquitin ligase HectD1 that we show belongs to the same fold. This motif adopts a compact 5-helix bundle which we name the Basic Tilted Helix Bundle (BTHB) domain. A positively charged surface patch, structurally centered around the tilted helix H4, is present in both FKBP25 and HectD1 and is conserved in both proteins, suggesting a conserved functional role. We provide detailed comparative analysis of the structures of the two proteins and their sequence similarities, and analysis of the interaction of the proposed FKBP25 binding protein YY1. We suggest that the basic motif in BTHB is involved in the observed DNA binding of FKBP25, and that the function of this domain can be affected by regulatory YY1 binding and/or interactions with adjacent domains. ©2014 Elsevier Inc. All rights reserved.

Shyn P.B.,Harvard University | Tatli S.,Harvard University | Sainani N.I.,Harvard University | Morrison P.R.,Harvard University | And 3 more authors.
Journal of Vascular and Interventional Radiology | Year: 2011

Purpose: To validate a monitored, breath-hold positron emission tomography (PET)/computed tomography (CT) acquisition technique for the minimization of respiratory PET/CT image misregistration and lesion distortion during PET/CTguided percutaneous interventional procedures. Materials and Methods: Eleven patients referred for percutaneous biopsy or thermal ablation of tumors near the diaphragm were prospectively enrolled. Initial PET/CT scanning was performed by using a bellows device and monitored, same-level breath-holds for PET and CT acquisitions. Breath-hold PET consisted of nine 20-second breath-hold frames, yielding a 3-minute equivalent PET dataset. A second PET/CT scan was obtained without monitoring by using end-expiration breath-hold CT and free-breathing PET. PET/CT tumor misregistration and craniocaudal tumor diameter were measured on monitored and unmonitored PET/CT datasets. Data were analyzed by using nonparametric, two-sided, signed-rank statistical tests. Results: Mean PET/CT image misregistrations in the craniocaudal, anteroposterior, and transverse planes were 2.6 mm (range, 07 mm), 3.3 mm (range, 18 mm), and 2.7 mm (range, 08 mm) with monitoring and 14.7 mm (range, 049 mm), 7.6 mm (range, 124 mm), and 4.0 mm (range, 012 mm) without monitoring, respectively. Differences were significant for craniocaudal (P =.0087) and anteroposterior (P =.014) planes, but not for the transverse plane (P =.23). Mean craniocaudal target diameter was 2.5 mm (range, -2 to 9 mm) larger (ie, distorted) for unmonitored versus monitored PET (P =.061). Conclusions: Acquiring PET/CT datasets with respiratory bellows-assisted, monitored breath-holds improves PET/CT image registration versus unmonitored PET/CT and may facilitate accurate targeting during PET/CTguided interventions in anatomic regions subject to respiratory motion. © 2011 SIR.

Pu C.-L.,Nanjing Southeast University | Pu C.-L.,Northeastern University | Pu C.-L.,DanaFarber Cancer Institute | Zhou S.-Y.,Nanjing Southeast University | And 3 more authors.
Physica A: Statistical Mechanics and its Applications | Year: 2012

Information routing is one of the most important problems in large communication networks. In this paper we propose a novel routing strategy in which the optimal paths between all pairs of nodes are chosen according to a cost function that incorporates degrees of nodes in paths. Results on large scale-free networks demonstrate that our routing strategy is more efficient than the shortest path algorithm and the efficient routing strategy proposed by Yan et al. [Phys. Rev. E 73, 046108 (2006)]. Furthermore our routing strategy has strong robustness against cascading failure attacks on networks. © 2011 Elsevier B.V. All rights reserved.

Duke University, Sloan Kettering Institute For Cancer Research and Danafarber Cancer Institute | Date: 2013-10-28

The present invention relates, in general, to human immunodeficiency virus-1 (HIV-1), and, in particular to a vaccine for HIV-1 and to methods of making and using same. The present invention provides synthetic glycosylated HIV-1 peptides, method for their preparation and use.

Wu H.,Chinese Academy of Sciences | Wu H.,Anhui University of Science and Technology | Wang W.,Chinese Academy of Sciences | Liu F.,Chinese Academy of Sciences | And 26 more authors.
ACS Chemical Biology | Year: 2014

BTK is a member of the TEC family of non-receptor tyrosine kinases whose deregulation has been implicated in a variety of B-cell-related diseases. We have used structure-based drug design in conjunction with kinome profiling and cellular assays to develop a potent, selective, and irreversible BTK kinase inhibitor, QL47, which covalently modifies Cys481. QL47 inhibits BTK kinase activity with an IC50 of 7 nM, inhibits autophosphorylation of BTK on Tyr223 in cells with an EC50 of 475 nM, and inhibits phosphorylation of a downstream effector PLC2 (Tyr759) with an EC50 of 318 nM. In Ramos cells QL47 induces a G1 cell cycle arrest that is associated with pronounced degradation of BTK protein. QL47 inhibits the proliferation of B-cell lymphoma cancer cell lines at submicromolar concentrations. © 2014 American Chemical Society.

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