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961.
962.
Coulomb blockade and the Kondo effect in single-atom transistors 总被引:7,自引:0,他引:7
Park J Pasupathy AN Goldsmith JI Chang C Yaish Y Petta JR Rinkoski M Sethna JP Abruña HD McEuen PL Ralph DC 《Nature》2002,417(6890):722-725
Using molecules as electronic components is a powerful new direction in the science and technology of nanometre-scale systems. Experiments to date have examined a multitude of molecules conducting in parallel, or, in some cases, transport through single molecules. The latter includes molecules probed in a two-terminal geometry using mechanically controlled break junctions or scanning probes as well as three-terminal single-molecule transistors made from carbon nanotubes, C(60) molecules, and conjugated molecules diluted in a less-conducting molecular layer. The ultimate limit would be a device where electrons hop on to, and off from, a single atom between two contacts. Here we describe transistors incorporating a transition-metal complex designed so that electron transport occurs through well-defined charge states of a single atom. We examine two related molecules containing a Co ion bonded to polypyridyl ligands, attached to insulating tethers of different lengths. Changing the length of the insulating tether alters the coupling of the ion to the electrodes, enabling the fabrication of devices that exhibit either single-electron phenomena, such as Coulomb blockade, or the Kondo effect. 相似文献
963.
Peat record reflecting Holocene climatic change in the Zoigê Plateau and AMS radiocarbon dating 总被引:2,自引:0,他引:2
Weijian?ZhouEmail author Xuefeng?Lu Zhengkun?Wu Lin?Deng A.?J.?T.?Jull D.?Donahue W.?Beck 《科学通报(英文版)》2002,47(1):66-70
Through the use of reliable AMS dating of high resolution (15–30 years) peat and the establishment of monsoon climate proxies
sequence, we have been able to recognize several cold, dry events in the Tibetan Plateau during the Holocene. The more obvious
ones occurred around 12800, 11300, 10200, 9580, 8900, 6400, 4400, 3700, 2800 and 1500 cal. aBP. These events correlate well
with both ice rafting events recorded in high latitude North Atlantic Ocean sediment cores and cooling events in the low latitude
SST. Spectral analysis indicates high frequency climate variation on centennial-millennial time scale during the Holocene.
This further reflects Holocene climate instability and the existence of centennial-millenium scale rhythm in mid latitude
areas as well. 相似文献
964.
965.
Genetic analysis of the mouse brain proteome 总被引:24,自引:0,他引:24
Klose J Nock C Herrmann M Stühler K Marcus K Blüggel M Krause E Schalkwyk LC Rastan S Brown SD Büssow K Himmelbauer H Lehrach H 《Nature genetics》2002,30(4):385-393
Proteome analysis is a fundamental step in systematic functional genomics. Here we have resolved 8,767 proteins from the mouse brain proteome by large-gel two-dimensional electrophoresis. We detected 1,324 polymorphic proteins from the European collaborative interspecific backcross. Of these, we mapped 665 proteins genetically and identified 466 proteins by mass spectrometry. Qualitatively polymorphic proteins, to 96%, reflect changes in conformation and/or mass. Quantitatively polymorphic proteins show a high frequency (73%) of allele-specific transmission in codominant heterozygotes. Variations in protein isoforms and protein quantity often mapped to chromosomal positions different from that of the structural gene, indicating that single proteins may act as polygenic traits. Genetic analysis of proteomes may detect the types of polymorphism that are most relevant in disease-association studies. 相似文献
966.
Polyisoprenyl phosphates: natural antiinflammatory lipid signals 总被引:1,自引:0,他引:1
Lipoxins (LX) and aspirin-triggered 15-epimer LX are leukocyte-derived eicosanoids generated during host defense that serve
as down-regulatory signals. The specific intracellular events that govern cellular responses to inhibitory extracellular signals
are of wide interest in order to understand pivotal intracellular events in diseases characterized by enhanced inflammatory
responses, such as asthma, rheumatoid arthritis and atherosclerosis. We recently uncovered a novel role for polyisoprenyl
phosphates, in particular presqualene diphosphate (PSDP), as natural down-regulatory signals in human neutrophils that directly
inhibit phospholipase D and superoxide anion generation. Activation of LXA4 receptors (ALXR) reverses proinflammatory receptor-initiated decrements in PSDP and inhibits cellular responses. These findings
represent evidence for a novel paradigm for lipid-protein interactions in the control of cellular responses, namely receptor-initiated
degradation of repressor lipids that is subject to regulation by aspirin treatment via the actions of aspirin-triggered 15-epimer
LX at the ALXR, and identify new templates for antiinflammatory drugs by design. 相似文献
967.
Harroch S Furtado GC Brueck W Rosenbluth J Lafaille J Chao M Buxbaum JD Schlessinger J 《Nature genetics》2002,32(3):411-414
Several lines of evidence suggest that tyrosine phosphorylation is a key element in myelin formation, differentiation of oligodendrocytes and Schwann cells, and recovery from demyelinating lesions. Multiple sclerosis is a demyelinating disease of the human central nervous system, and studies of experimental demyelination indicate that remyelination in vivo requires the local generation, migration or maturation of new oligodendrocytes, or some combination of these. Failure of remyelination in multiple sclerosis could result from the failure of any of these processes or from the death of oligodendrocytes. Ptprz encodes protein tyrosine phosphatase receptor type Z (Ptpz, also designated Rptpbeta), which is expressed primarily in the nervous system but also in oligodendrocytes, astrocytes and neurons. Here we examine the susceptibility of mice deficient in Ptprz to experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. We observe that mice deficient in Ptprz show impaired recovery from EAE induced by myelin oligodendrocyte glycoprotein (MOG) peptide. This sustained paralysis is associated with increased apoptosis of mature oligodendrocytes in the spinal cords of mutant mice at the peak of inflammation. We further demonstrate that expression of PTPRZ1, the human homolog of Ptprz, is induced in multiple sclerosis lesions and that the gene is specifically expressed in remyelinating oligodendrocytes in these lesions. These results support a role for Ptprz in oligodendrocyte survival and in recovery from demyelinating disease. 相似文献
968.
Rosenberg MJ Agarwala R Bouffard G Davis J Fiermonte G Hilliard MS Koch T Kalikin LM Makalowska I Morton DH Petty EM Weber JL Palmieri F Kelley RI Schäffer AA Biesecker LG 《Nature genetics》2002,32(1):175-179
The disorder Amish microcephaly (MCPHA) is characterized by severe congenital microcephaly, elevated levels of alpha-ketoglutarate in the urine and premature death. The disorder is inherited in an autosomal recessive pattern and has been observed only in Old Order Amish families whose ancestors lived in Lancaster County, Pennsylvania. Here we show, by using a genealogy database and automated pedigree software, that 23 nuclear families affected with MCPHA are connected to a single ancestral couple. Through a whole-genome scan, fine mapping and haplotype analysis, we localized the gene affected in MCPHA to a region of 3 cM, or 2 Mb, on chromosome 17q25. We constructed a map of contiguous genomic clones spanning this region. One of the genes in this region, SLC25A19, which encodes a nuclear mitochondrial deoxynucleotide carrier (DNC), contains a substitution that segregates with the disease in affected individuals and alters an amino acid that is highly conserved in similar proteins. Functional analysis shows that the mutant DNC protein lacks the normal transport activity, implying that failed deoxynucleotide transport across the inner mitochondrial membrane causes MCPHA. Our data indicate that mitochondrial deoxynucleotide transport may be essential for prenatal brain growth. 相似文献
969.
Evidence of cis-acting factors in replication-mediated trinucleotide repeat instability in primate cells 总被引:7,自引:0,他引:7
The mechanism of disease-associated trinucleotide repeat instability involves cis-acting factors (cis-elements) in the vicinity of the repeat, but the nature of these elements is unknown. One cis-element may be the location of the replication origin relative to the repeat. We have used an SV40 DNA replication system to investigate the effect of the location of replication initiation on (CTG)(n)*(CAG)(n) stability in primate cells. Depending on the distance between the SV40 replication origin and the repeat tract, templates with 79 repeats yield predominantly expansions or predominantly deletions or remain intact. All templates with 17 repeats are stable. Thus, cis-elements that affect the sites of Okazaki fragment initiation relative to the repeat are crucial determinants of instability. This model system recapitulates the bias for expansions observed in many of the diseases associated with trinucleotide repeats. Our results might explain the variable amounts of CTG/CAG instability that are observed in different chromosomal contexts. 相似文献
970.