Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases. 相似文献
Large scale wireless sensor networks raise many challenges in the design of efficient and effective routing algorithm due to their complexity and hardware constraints. However, the scalability challenge may be mitigated from a macroscopic perspective. One example is the distributed De la Garza iteration (DDLGI) algorithm for global routing load-balancing, based on a set of partial differential equations iteratively solved by the De la Garza method. We theoretically analyze the parallelism of DDLGI and illustrate that the region of interest may impact the degree of parallelism and error. Furthermore, though DDLGI always converges, the slow convergence and long-range information exchange problems may lead to excess energy consumption in communication. Thus, we propose various enhanced De la Garza routing (E-DLGR) algorithms to alleviate the energy consumption problem by which nodes may exchange less information and only need to exchange information with closer nodes to complete each iteration. Our theoretical analysis and simulation results show that the proposed E-DLGR algorithms may have less transmission overhead, thus further reducing energy consumption, and converge faster while still maintaining adequate accuracy.
We demonstrate the structural evolution of polymorphic phases in Al2O3-inserted SrMnO3 ceramics synthesized by solid state reaction. While the 4H-hexagonal phase is predominant in pure SrMnO3 ceramics, a small amount of 6H-hexagonal polymorph is identified in addition to the primary 4H-hexagonal SrMnO3 and the secondary hexagonal SrAl2O4 phases in the as-sintered ceramics, evidenced by x-ray diffraction and subsequent Rietveld refinement analyses. The existence of the 6H-hexagonal SrMnO3 phase is corroborated using Raman spectroscopy. The chemical compositions and electronic structures of the Al2O3-inserted SrMnO3 compounds are also examined using energy dispersive spectroscopy and x-ray photoelectron spectroscopy, respectively. The first-principles calculations reveal that there is no clear difference between the total energies of 4H- and 6H-hexagonal polymorphs regardless of the presence/absence of Sr and oxygen vacancies. Possible origins are discussed with the estimation of actual strain based on the refined lattice parameter of 6H SrMnO3. 相似文献
This paper presents a new heuristic method for quickly finding a good feasible solution to the channel assignment problem
(CAP). Like many other greedy-type heuristics for CAP, the proposed method also assigns a frequency to a call, one at a time.
Hence, the method requires computational time that increases only linear to the number of calls. However, what distinguishes
the method from others is that it starts with a narrow enough frequency band so as to provoke violations of constraints that
we need to comply with in order to avoid radio interference. Each violation is then resolved by inserting frequencies at the
most appropriate positions so that the band of frequencies expands minimally. An extensive computational experiment using
a set of randomly generated problems as well as the Philadelphia benchmark instances shows that the proposed method perform
statistically better than existing methods of its kind and even yields optimum solutions to most of Philadelphia benchmark
instances among which two cases are reported for the first time ever, in this paper.
Won-Young Shin was born in Busan, Korea in 1978. He received B.S. in industrial engineering from Pohang University of Science and Technology
(POSTECH) in 2001 and M.S in operation research and applied statistics from POSTECH in 2003. Since 2003 he has been a researcher
of Agency for Defense Development (ADD) in Korea. He is interested in optimization of communication system and applied statistics.
Soo Y. Chang is an associate professor in the Department of Industrial Engineering at Pohang University of Science and Technology (POSTECH),
Pohang, Korea. He teaches linear programming, discrete optimization, network flows and operations research courses. His research
interests include mathematical programming and scheduling. He has published in several journals including Discrete Applied
Mathematics, Computers and Mathematics with Application, IIE Transactions, International Journal of Production Research, and
so on. He is a member of Korean IIE, and ORMSS.
Jaewook Lee is an assistant professor in the Department of Industrial Engineering at Pohang University of Science and Technology (POSTECH),
Pohang, Korea. He received the B.S. degree in mathematics with honors from Seoul National University, and the Ph.D. degree
from Cornell University in applied mathematics in 1993 and 1999, respectively. He is currently an assistant professor in the
department of industrial engineering at the Pohang University of Science and Technology (POSTECH). His research interests
include nonlinear systems, neural networks, nonlinear optimization, and their applications to data mining and financial engineering.
Chi-Hyuck Jun was born in Seoul, Korea in 1954. He received B.S. in mineral and petroleum engineering from Seoul National University in
1977, M.S. in industrial engineering from Korea Advanced Institute of Science and Technology in 1979 and Ph.D. in operations
research from University of California, Berkeley, in 1986. Since 1987 he has been with the department of industrial engineering,
Pohang University of Science and Technology (POSTECH) and he is now a professor and the department head. He is interested
in performance analysis of communication and production systems. He has published in several journals including IIE Transactions,
IEEE Transactions, Queueing Systems and Chemometrics and Intelligent Laboratory Systems. He is a member of IEEE, INFORMS and
ASQ. 相似文献
The adverse effect of nitrate on the phosphate release rate in the anaerobic phase was observed and was hardly explainable with conventional EBPR process models. Four possible mechanisms were proposed including substrate competition, reduced fermentation, parallel reaction and sequential reaction. Batch experiments were designed and conducted to identify the dominant mechanism. Results showed that the sequential reaction was the only possible mechanism where only denitrification occurred if any nitrate existed in the anaerobic phase. Then the phosphate release following after the nitrate was completely removed. Nitrate inhibition effect was added into the PHA storage rate to incorporate the sequential reaction in the conventional ASM3 plus EAWAG bio-P module (ASM3 + P). Nitrate inhibition coefficient, K(I,NO,PAO) was found to be as low as 0.05 mg/L. This correlated well with experimental observation where no also meant that the anaerobic compartment of a continuous flow reactor could be seriously affected by the residual nitrate contained in the sludge recycle flow. This phenomenon caused overestimation of the phosphate uptake rate and consequently underestimation of PO4(3-) -P concentration. This problem was resolved by incorporation of a nitrate inhibition term in the ASM3 + P for more accurate simulation of the EBPR process. 相似文献
Supported zirconcene catalysts on a new support, MgO, were prepared and tested in ethylene polymerization. Three types of impregnation methods were employed to find an optimum supporting method for MgO. The direct impregnation of Cp2ZrCl2 on MgO showed low metal loading and polymerization activity, while the catalyst had a higher metal loading and polymerization activity when MgO was treated with methylaluminoxane (MAO) before supporting. Treatment of MgO with MAO during the supporting step invoked two types of catalytic sites, which was evidenced by the bimodal molecular weight distribution of the polymer products. MgO is considered to have potential as a support for metallocenes. 相似文献