基于Wiener滤波器的波形比较方法及其在最坏情况分析中的应用

提出一种基于Wiener滤波器的波形比较方法,应用于数模混合电路的最坏情况分析.该方法能考虑一定的时间容限和信号容限,自动比较电路在不同的工艺参数、电压和温度(PVT)组合下的仿真波形,通过波形形状的比较来实现电路性能验证,有效地提高了电路验证效率.此方法成功地运用到波形比较软件系统中,并已在Intel技术开发(上海)公司内部推广使用.     

Glycine binding primes NMDA receptor internalization

NMDA (N-methyl-d-aspartate) receptors (NMDARs) are a principal subtype of excitatory ligand-gated ion channel with prominent roles in physiological and disease processes in the central nervous system. Recognition that glycine potentiates NMDAR-mediated currents as well as being a requisite co-agonist of the NMDAR subtype of 'glutamate' receptor profoundly changed our understanding of chemical synaptic communication in the central nervous system. The binding of both glycine and glutamate is necessary to cause opening of the NMDAR conductance pore. Although binding of either agonist alone is insufficient to cause current flow through the channel, we report here that stimulation of the glycine site initiates signalling through the NMDAR complex, priming the receptors for clathrin-dependent endocytosis. Glycine binding alone does not cause the receptor to be endocytosed; this requires both glycine and glutamate site activation of NMDARs. The priming effect of glycine is mimicked by the NMDAR glycine site agonist d-serine, and is blocked by competitive glycine site antagonists. Synaptic as well as extrasynaptic NMDARs are primed for internalization by glycine site stimulation. Our results demonstrate transmembrane signal transduction through activating the glycine site of NMDARs, and elucidate a model for modulating cell-cell communication in the central nervous system.     

Serum prolactin levels and maintenance of progeny by prenatally-stressed female offspring

Summary Prenatal stress significantly reduced the number of progeny born to 47% of the female offspring and significantly increased the incidence of low birthweight young. None of these litters survived by the tenth postpartum day when serum prolactin levels were significantly reduced. Upon autopsy, these females had twice as many uterine implantation sites than the number of fetuses they bore, suggesting that a) the reduced postpartum serum prolactin most likely was the cause rather than the effect of the neonatal mortality and b) major hormonal deficiencies (possibly gonadotropic-related) were present even before giving birth.     

RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems

The immune system consists of two evolutionarily different but closely related responses, innate immunity and adaptive immunity. Each of these responses has characteristic receptors-Toll-like receptors (TLRs) for innate immunity and antigen-specific receptors for adaptive immunity. Here we show that the caspase recruitment domain (CARD)-containing serine/threonine kinase Rip2 (also known as RICK, CARDIAK, CCK and Ripk2) transduces signals from receptors of both immune responses. Rip2 was recruited to TLR2 signalling complexes after ligand stimulation. Moreover, cytokine production in Rip2-deficient cells was reduced on stimulation of TLRs with lipopolysaccharide, peptidoglycan and double-stranded RNA, but not with bacterial DNA, indicating that Rip2 is downstream of TLR2/3/4 but not TLR9. Rip2-deficient cells were also hyporesponsive to signalling through interleukin (IL)-1 and IL-18 receptors, and deficient for signalling through Nod proteins-molecules also implicated in the innate immune response. Furthermore, Rip2-deficient T cells showed severely reduced NF-kappaB activation, IL-2 production and proliferation on T-cell-receptor (TCR) engagement, and impaired differentiation to T-helper subtype 1 (TH1) cells, indicating that Rip2 is required for optimal TCR signalling and T-cell differentiation. Rip2 is therefore a signal transducer and integrator of signals for both the innate and adaptive immune systems.     

Atlantic overturning responses to Late Pleistocene climate forcings

The factors driving glacial changes in ocean overturning circulation are not well understood. On the basis of a comparison of 20 climate variables over the past four glacial cycles, the SPECMAP project proposed that summer insolation at high northern latitudes (that is, Milankovitch forcing) drives the same sequence of ocean circulation and other climate responses over 100-kyr eccentricity cycles, 41-kyr obliquity cycles and 23-kyr precession cycles. SPECMAP analysed the circulation response at only a few sites in the Atlantic Ocean, however, and the phase of circulation response has been shown to vary by site and orbital band. Here we test the SPECMAP hypothesis by measuring the phase of orbital responses in benthic delta(13)C (a proxy indicator of ocean nutrient content) at 24 sites throughout the Atlantic over the past 425 kyr. On the basis of delta(13)C responses at 3,000-4,010 m water depth, we find that maxima in Milankovitch forcing are associated with greater mid-depth overturning in the obliquity band but less overturning in the precession band. This suggests that Atlantic overturning is strongly sensitive to factors beyond ice volume and summer insolation at high northern latitudes. A better understanding of these processes could lead to improvements in model estimates of overturning rates, which range from a 40 per cent increase to a 40 per cent decrease at the Last Glacial Maximum and a 10-50 per cent decrease over the next 140 yr in response to projected increases in atmospheric CO(2) (ref. 4).     

Northern Hemisphere forcing of climatic cycles in Antarctica over the past 360,000 years

The Milankovitch theory of climate change proposes that glacial-interglacial cycles are driven by changes in summer insolation at high northern latitudes. The timing of climate change in the Southern Hemisphere at glacial-interglacial transitions (which are known as terminations) relative to variations in summer insolation in the Northern Hemisphere is an important test of this hypothesis. So far, it has only been possible to apply this test to the most recent termination, because the dating uncertainty associated with older terminations is too large to allow phase relationships to be determined. Here we present a new chronology of Antarctic climate change over the past 360,000 years that is based on the ratio of oxygen to nitrogen molecules in air trapped in the Dome Fuji and Vostok ice cores. This ratio is a proxy for local summer insolation, and thus allows the chronology to be constructed by orbital tuning without the need to assume a lag between a climate record and an orbital parameter. The accuracy of the chronology allows us to examine the phase relationships between climate records from the ice cores and changes in insolation. Our results indicate that orbital-scale Antarctic climate change lags Northern Hemisphere insolation by a few millennia, and that the increases in Antarctic temperature and atmospheric carbon dioxide concentration during the last four terminations occurred within the rising phase of Northern Hemisphere summer insolation. These results support the Milankovitch theory that Northern Hemisphere summer insolation triggered the last four deglaciations.     

Template switching during break-induced replication

DNA double-strand breaks (DSBs) are potentially lethal lesions that arise spontaneously during normal cellular metabolism, as a consequence of environmental genotoxins or radiation, or during programmed recombination processes. Repair of DSBs by homologous recombination generally occurs by gene conversion resulting from transfer of information from an intact donor duplex to both ends of the break site of the broken chromosome. In mitotic cells, gene conversion is rarely associated with reciprocal exchange and thus limits loss of heterozygosity for markers downstream of the site of repair and restricts potentially deleterious chromosome rearrangements. DSBs that arise by replication fork collapse or by erosion of uncapped telomeres have only one free end and are thought to repair by strand invasion into a homologous duplex DNA followed by replication to the chromosome end (break-induced replication, BIR). BIR from one of the two ends of a DSB would result in loss of heterozygosity, suggesting that BIR is suppressed when DSBs have two ends so that repair occurs by the more conservative gene conversion mechanism. Here we show that BIR can occur by several rounds of strand invasion, DNA synthesis and dissociation. We further show that chromosome rearrangements can occur during BIR if dissociation and reinvasion occur within dispersed repeated sequences. This dynamic process could function to promote gene conversion by capture of the displaced invading strand at two-ended DSBs to prevent BIR.