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Faults in brittle rock are shear fractures formed through the interaction and coalescence of many tensile microcracks. The geometry of these microcracks and their surrounding elastic stress fields control the orientation of the final shear fracture surfaces. The classic Coulomb-Mohr failure criterion predicts the development of two conjugate (bimodal) shear planes that are inclined at an acute angle to the axis of maximum compressive stress. This criterion, however, is incapable of explaining the three-dimensional polymodal fault patterns that are widely observed in rocks. Here we show that the elastic stress around tensile microcracks in three dimensions promotes a mutual interaction that produces brittle shear planes oriented obliquely to the remote principal stresses, and can therefore account for observed polymodal fault patterns. Our microcrack interaction model is based on the three-dimensional solution of Eshelby, unlike previous models that employed two-dimensional approximations. Our model predicts that shear fractures formed by the coalescence of interacting mode I cracks will be inclined at a maximum of 26 degrees to the axes of remote maximum and intermediate compression. An improved understanding of brittle shear failure in three dimensions has important implications for earthquake seismology and rock-mass stability, as well as fluid migration in fractured rocks. 相似文献
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Slip on 'weak' faults by the rotation of regional stress in the fracture damage zone 总被引:2,自引:0,他引:2
Slip on unfavourably oriented faults with respect to a remotely applied stress is well documented and implies that faults such as the San Andreas fault and low-angle normal faults are weak when compared to laboratory-measured frictional strength. If high pore pressure within fault zones is the cause of such weakness, then stress reorientation within or close to a fault is necessary to allow sufficient fault weakening without the occurrence of hydrofracture. From field observations of a major tectonic fault, and using laboratory experiments and numerical modelling, here we show that stress rotation occurs within the fractured damage zone surrounding faults. In particular, we find that stress rotation is considerable for unfavourably oriented 'weak' faults. In the 'weak' fault case, the damage-induced change in elastic properties provides the necessary stress rotation to allow high pore pressure faulting without inducing hydrofracture. 相似文献
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Todd JA Walker NM Cooper JD Smyth DJ Downes K Plagnol V Bailey R Nejentsev S Field SF Payne F Lowe CE Szeszko JS Hafler JP Zeitels L Yang JH Vella A Nutland S Stevens HE Schuilenburg H Coleman G Maisuria M Meadows W Smink LJ Healy B Burren OS Lam AA Ovington NR Allen J Adlem E Leung HT Wallace C Howson JM Guja C Ionescu-Tîrgovişte C;Genetics of Type Diabetes in Finland Simmonds MJ Heward JM Gough SC;Wellcome Trust Case Control Consortium Dunger DB Wicker LS Clayton DG 《Nature genetics》2007,39(7):857-864
The Wellcome Trust Case Control Consortium (WTCCC) primary genome-wide association (GWA) scan on seven diseases, including the multifactorial autoimmune disease type 1 diabetes (T1D), shows associations at P < 5 x 10(-7) between T1D and six chromosome regions: 12q24, 12q13, 16p13, 18p11, 12p13 and 4q27. Here, we attempted to validate these and six other top findings in 4,000 individuals with T1D, 5,000 controls and 2,997 family trios independent of the WTCCC study. We confirmed unequivocally the associations of 12q24, 12q13, 16p13 and 18p11 (P(follow-up) 相似文献
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Cyclin D control of growth rate in plants 总被引:49,自引:0,他引:49
The mechanisms by which plants modulate their growth rate in response to environmental and developmental conditions are unknown, but are presumed to involve specialized regions called meristems where cell division is concentrated. The possible role of cell division in influencing meristem activity and overall plant growth rate is controversial, with a prevailing view that cell division is secondary to higher order meristem controls. Here we show that a reduction in the length of the cell-cycle G1 phase and faster cell cycling occur when the rate of cell division in transgenic tobacco plants is increased by the plant D-type cyclin CycD2 (ref. 8). The plants have normal cell and meristem sizes, but elevated overall growth rates, an increased rate of leaf initiation and accelerated development in all stages from seedling to maturity. We conclude that cell division is a principal determinant of meristem activity and overall growth rate, and propose that modulation of plant growth rate is achieved through regulation of G1. 相似文献
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Kukar TL Ladd TB Bann MA Fraering PC Narlawar R Maharvi GM Healy B Chapman R Welzel AT Price RW Moore B Rangachari V Cusack B Eriksen J Jansen-West K Verbeeck C Yager D Eckman C Ye W Sagi S Cottrell BA Torpey J Rosenberry TL Fauq A Wolfe MS Schmidt B Walsh DM Koo EH Golde TE 《Nature》2008,453(7197):925-929
Selective lowering of Abeta42 levels (the 42-residue isoform of the amyloid-beta peptide) with small-molecule gamma-secretase modulators (GSMs), such as some non-steroidal anti-inflammatory drugs, is a promising therapeutic approach for Alzheimer's disease. To identify the target of these agents we developed biotinylated photoactivatable GSMs. GSM photoprobes did not label the core proteins of the gamma-secretase complex, but instead labelled the beta-amyloid precursor protein (APP), APP carboxy-terminal fragments and amyloid-beta peptide in human neuroglioma H4 cells. Substrate labelling was competed by other GSMs, and labelling of an APP gamma-secretase substrate was more efficient than a Notch substrate. GSM interaction was localized to residues 28-36 of amyloid-beta, a region critical for aggregation. We also demonstrate that compounds known to interact with this region of amyloid-beta act as GSMs, and some GSMs alter the production of cell-derived amyloid-beta oligomers. Furthermore, mutation of the GSM binding site in the APP alters the sensitivity of the substrate to GSMs. These findings indicate that substrate targeting by GSMs mechanistically links two therapeutic actions: alteration in Abeta42 production and inhibition of amyloid-beta aggregation, which may synergistically reduce amyloid-beta deposition in Alzheimer's disease. These data also demonstrate the existence and feasibility of 'substrate targeting' by small-molecule effectors of proteolytic enzymes, which if generally applicable may significantly broaden the current notion of 'druggable' targets. 相似文献
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Summary Fructose-1,6-P2 was immobilized by sodium borohydride reduction of the Schiff base formed with aminated agarose (AH-Sepharose 4B®). The coupling occurs with high yield (25 moles immobilized fructose-1,6-P2 per ml packed gel) at neutral pH and room temperature. Schiff base reduction thus provides a convenient and mild coupling procedure for sugar phosphates preserving their labile phospho ester bonds. As exemplified by a new isolation procedure for fructose-1,6-P2 aldolase from yeast, sugar phosphates insolubilized in this manner may be used for affinity chromatography of the corresponding enzymes, provided that contaminating unspecific phosphatases are removed in a preceding fractionation step.This work was supported by the Swiss National Science Foundation, grant No. 3.620-0.75. A preliminary account has been presented at the 10th Int. Congress of Biochemistry, Hamburg, 1976, Abstracts. p. 194.Acknowledgment. The excellent technical assistance of Alice Gasser is gratefully acknowledged 相似文献
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