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Monoclonal mice generated by nuclear transfer from mature B and T donor cells   总被引:44,自引:0,他引:44  
Hochedlinger K  Jaenisch R 《Nature》2002,415(6875):1035-1038
Cloning from somatic cells is inefficient, with most clones dying during gestation. Cloning from embryonic stem (ES) cells is much more effective, suggesting that the nucleus of an embryonic cell is easier to reprogram. It is thus possible that most surviving clones are, in fact, derived from the nuclei of rare somatic stem cells present in adult tissues, rather than from the nuclei of differentiated cells, as has been assumed. Here we report the generation of monoclonal mice by nuclear transfer from mature lymphocytes. In a modified two-step cloning procedure, we established ES cells from cloned blastocysts and injected them into tetraploid blastocysts to generate mice. In this approach, the embryo is derived from the ES cells and the extra-embryonic tissues from the tetraploid host. Animals cloned from a B-cell nucleus were viable and carried fully rearranged immunoglobulin alleles in all tissues. Similarly, a mouse cloned from a T-cell nucleus carried rearranged T-cell-receptor genes in all tissues. This is an unequivocal demonstration that a terminally differentiated cell can be reprogrammed to produce an adult cloned animal.  相似文献   
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Type VI secretion systems are bacterial virulence-associated nanomachines composed of proteins that are evolutionarily related to components of bacteriophage tails. Here we show that protein secretion by the type VI secretion system of Vibrio cholerae requires the action of a dynamic intracellular tubular structure that is structurally and functionally homologous to contractile phage tail sheath. Time-lapse fluorescence light microscopy reveals that sheaths of the type VI secretion system cycle between assembly, quick contraction, disassembly and re-assembly. Whole-cell electron cryotomography further shows that the sheaths appear as long tubular structures in either extended or contracted conformations that are connected to the inner membrane by a distinct basal structure. These data support a model in which the contraction of the type VI secretion system sheath provides the energy needed to translocate proteins out of effector cells and into adjacent target cells.  相似文献   
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Summary Specimens of the green toad,Bufo viridis, from Morocco to Kirgizistan, have identical DNA amounts per erythrocyte nucleus. 1 specimen from Kirgizistan is a tetraploid. Of 3 closely related species,B. calamita andB. brongersmai have about the same DNA amount asB. viridis, whileB. latastii from Afghanistan has 36% more DNA per nucleus.  相似文献   
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Recent models for credit risk management make use of hidden Markov models (HMMs). HMMs are used to forecast quantiles of corporate default rates. Little research has been done on the quality of such forecasts if the underlying HMM is potentially misspecified. In this paper, we focus on misspecification in the dynamics and dimension of the HMM. We consider both discrete‐ and continuous‐state HMMs. The differences are substantial. Underestimating the number of discrete states has an economically significant impact on forecast quality. Generally speaking, discrete models underestimate the high‐quantile default rate forecasts. Continuous‐state HMMs, however, vastly overestimate high quantiles if the true HMM has a discrete state space. In the reverse setting the biases are much smaller, though still substantial in economic terms. We illustrate the empirical differences using US default data. Copyright © 2008 John Wiley & Sons, Ltd.  相似文献   
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Stem cells: iPS cells under attack   总被引:1,自引:0,他引:1  
Apostolou E  Hochedlinger K 《Nature》2011,474(7350):165-166
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Steel matrix composites (SMCs) reinforced with WC particles were fabricated via selective laser melting (SLM) by employing various laser scan strategies. A detailed relationship between the SLM strategies, defect formation, microstructural evolution, and mechanical properties of SMCs was established. The laser scan strategies can be manipulated to deliberately alter the thermal history of SMC during SLM processing. Particularly, the involved thermal cycling, which encompassed multiple layers, strongly affected the processing quality of SMCs. S-shaped scan sequence combined with interlayer offset and orthogonal stagger mode can effectively eliminate the metallurgical defects and retained austenite within the produced SMCs. However, due to large thermal stress, microcracks that were perpendicular to the building direction formed within the SMCs. By employing the checkerboard filling (CBF) hatching mode, the thermal stress arising during SLM can be significantly reduced, thus preventing the evolution of interlayer microcracks. The compressive properties of fabricated SMCs can be tailored at a high compressive strength (~3031.5 MPa) and fracture strain (~24.8%) by adopting the CBF hatching mode combined with the optimized scan sequence and stagger mode. This study demonstrates great feasibility in tuning the mechanical properties of SLM-fabricated SMCs without varying the set energy input, e.g., laser power and scanning speed.  相似文献   
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