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排序方式: 共有1245条查询结果,搜索用时 15 毫秒
61.
62.
Isabel V. L. Wilkinson Kelly J. Perkins Hannah Dugdale Lee Moir Aini Vuorinen Maria Chatzopoulou Sarah E. Squire Sebastian Monecke Alexander Lomow Marcus Geese Philip D. Charles Peter Burch Jonathan M. Tinsley Graham M. Wynne Stephen G. Davies Francis X. Wilson Fraydoon Rastinejad Shabaz Mohammed Kay E. Davies Angela J. Russell 《Angewandte Chemie (International ed. in English)》2020,59(6):2420-2428
Duchenne muscular dystrophy (DMD) is a fatal muscle‐wasting disease arising from mutations in the dystrophin gene. Upregulation of utrophin to compensate for the missing dystrophin offers a potential therapy independent of patient genotype. The first‐in‐class utrophin modulator ezutromid/SMT C1100 was developed from a phenotypic screen through to a Phase 2 clinical trial. Promising efficacy and evidence of target engagement was observed in DMD patients after 24 weeks of treatment, however trial endpoints were not met after 48 weeks. The objective of this study was to understand the mechanism of action of ezutromid which could explain the lack of sustained efficacy and help development of new generations of utrophin modulators. Using chemical proteomics and phenotypic profiling we show that the aryl hydrocarbon receptor (AhR) is a target of ezutromid. Several lines of evidence demonstrate that ezutromid binds AhR with an apparent KD of 50 nm and behaves as an AhR antagonist. Furthermore, other reported AhR antagonists also upregulate utrophin, showing that this pathway, which is currently being explored in other clinical applications including oncology and rheumatoid arthritis, could also be exploited in future DMD therapies. 相似文献
63.
汾渭盆地地裂缝成因研究中的若干关键问题 总被引:12,自引:0,他引:12
汾渭盆地是我国地裂缝发育最强烈的地区,地裂缝类型多样,成因复杂。本文概述了汾渭盆地地裂缝的分布规律,分析了目前汾渭盆地地裂缝成因研究中存在的主要问题,重点围绕构造型地裂缝的成因问题,提出如下研究思路:通过多学科联合手段,重点研究汾渭盆地地裂缝灾害的分布规律及其与活动构造的分布关系与成生联系,建立构造地裂缝的地质结构模型;将现代物理数值模拟技术与高精度观测技术相结合,分析研究构造活动启动地裂缝灾害的力学机理以及构造作用与抽水作用耦合致裂机理;以GPS观测资料为约束,将汾渭盆地地裂缝的成生与青藏、华北大陆变形的动力学过程联系起来,研究该区地裂缝与现今中国大陆动力学的内在联系,揭示大陆驱动力产生地质灾害的动力学机制与模式。 相似文献
64.
A. M. Polyakov 《Journal of Geometry and Physics》1988,5(4):595-600
We analyze three-dimensional gauge theory with Chern-Simons action, which arises in the context of high Tc superconductivity. We show that the main effect in this theory is the change of spin and statistics of charged particles. Also, the amplitudes of particle propagation acquire phases dependent on the topology of the knot formed by their trajectories. In the end, we discuss possible generalizations of this theory, and their relations to strings. 相似文献
65.
数学建模活动对培养人才的作用 总被引:25,自引:0,他引:25
宿维军 《数学的实践与认识》2002,32(5):867-868
文章论述建模活动对培养人才的作用 ,对专科院校高等数学教学改革具有启发性 . 相似文献
66.
C. Connell McCluskey 《Journal of Mathematical Analysis and Applications》2008,338(1):518-535
A very general compartmental model of the spread of an infectious disease with mass action incidence is given. The global stability of this system is completely determined using Lyapunov functions. The general system exhibits the traditional threshold behaviour. The dimension of the system is arbitrary, allowing, in particular, for detailed modelling of the distribution of latency times for tuberculosis. 相似文献
67.
Coy L. May 《代数通讯》2013,41(11):4078-4095
Let G be a finite group. The symmetric genus σ (G) is the minimum genus of any compact Riemann surface on which G acts faithfully as a group of automorphisms. Here we classify the groups of symmetric genus σ, for all values of σ such that 4 ≤ σ ≤ 8. In addition, we obtain some general results about the partial presentations that groups acting on surfaces must have. We show that a group with even genus and no “large order” elements in its Sylow 2-subgroup has restrictions on its Sylow 2-subgroup. As a consequence, we show that if G is a 2-group with positive symmetric genus, then σ(G) is odd. The software package MAGMA was employed to help with the calculations, and the MAGMA library of small groups was essential to the classification. 相似文献
68.
We consider the initial value problem and its renormalisation in the framework of the two-particle-irreducible (2PI) effective action. We argue that in the case of appropriately chosen self-consistent initial conditions, the counterterms needed to renormalise the system in equilibrium are also sufficient to renormalise its time evolution. In this way we improve on Gaussian initial conditions which have the disadvantage of generically not showing a continuum limit. For a more detailed discussion see [Sz. Borsányi and U. Reinosa, arXiv:0809.0496]. 相似文献
69.
In this paper we apply the assumption of our recent work in noncommutative scalar models to the noncommutative U(1) gauge theories. This assumption is that the noneommutative effects start to be visible continuously from a scale ANC and that below this scale the theory is a commutative one. Based on this assumption and using background field method and loop calculations, an effective action is derived for noncommutative U(1) gauge theory. It will be shown that the corresponding low energy effective theory is asymptotically free and that under this condition the noncommutative quadratic IR divergences will not appear. The effective theory contains higher dimensional terms, which become more important at high energies. These terms predict an elastic photon-photon scattering due to the noncommutativity of space. The coefficients of these higher dimensional terms also satisfy a positivity constraint indicating that in this theory the related diseases of superluminal signal propagating and bad analytic properties of S-matrix do not exist. In the last section, we will apply our method to the noncommutative extra dimension theories. 相似文献
70.
Xiaochun Rong 《Geometriae Dedicata》2002,95(1):157-182
The symmetry rank of a Riemannian manifold is the rank of the isometry group. We determine precisely which closed simply connected 5-manifolds admit positively curved metrics with (almost maximal) symmetry rank two. We also determine the precise Euler characteristic and the fundamental groups of all closed positively curved n-manifolds with almost maximal symmetry rank [(n–1)/2] (n 6, 7). 相似文献