The nature of endothelium-derived vascular relaxant factor

The existence of endothelium-derived vascular relaxant factor (EDRF) was postulated by Furchgott and colleagues when they observed that acetylcholine paradoxically relaxed preconstricted aortic strip preparations by an endothelium-dependent mechanism. This phenomenon has since been demonstrated in different blood vessels and mammalian species and it can be elicited by several other agents. EDRF has been thought to be a humoral agent, a lipoxygenase derivative and possibly a free radical. In the study reported here, by using aortic preparations from the rabbit, alone and in cascade experiments with isolated perfused coronary preparations, we demonstrate definitively that EDRF is a humoral agent. It is released from unstimulated aortic preparations containing endothelium, its release can be stimulated for prolonged periods by acetylcholine, and it is not a lipoxygenase derivative or free radical but an unstable compound with a carbonyl group at or near its active site.     

Low-density lipoproteins inhibit endothelium-dependent relaxation in rabbit aorta

The vascular endothelium, in response to pulsatile flow and vasoactive agents including acetylcholine, secretes the endothelium-derived relaxing factor (EDRF), a substance which regulates vascular tone. Recent interest in EDRF has focused on its possible dysfunction in atherosclerosis. In animal models of the disease, endothelium-dependent relaxation is markedly reduced. The continuous exposure of the endothelium in hyperlipidaemia to high concentrations of low-density lipoprotein (LDL), a known atherogenic risk factor, may explain this dysfunction. Here, we demonstrate that pathophysiological concentrations of LDL directly inhibit endothelium-dependent relaxation. Chemically modified LDL, in contrast, is inactive, implying that the inhibition is through a receptor-dependent mechanism.     

Ultrastructural localization of choline acetyltransferase in vascular endothelial cells in rat brain

Furchgott and Zawadski have shown that acetylcholine (ACh) does not act directly on the smooth muscle of blood vessel walls, but rather via receptors on the endothelial cells lining the lumen, to release an endothelium-derived relaxing factor (EDRF). As it is very unlikely that neurotransmitter released from the periarterial nerves, which are confined to the adventitial-medial border, diffuses all the way through the medial muscle coat before acting on endothelial cells to release EDRF to produce vasodilatation, this discovery has been regarded as an indication of a pathophysiological mechanism, rather than a physiological one (see refs 2, 3). ACh is rapidly degraded in the blood by acetylcholinesterase, so that ACh must be released locally to be effective on endothelial cells. Here we demonstrate the immunocytochemical localization of choline acetyltransferase in endothelial cells of small brain vessels, which is consistent with the view that the ACh originates from endothelial cells that can synthesize and store it. We suggest that release of ACh following damage to endothelial cells during ischaemia contributes to a pathophysiological mechanism of vasodilation which protects that segment of vessel from further damage as well as brain cells from hypoxia.     

Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide

Studies of cultured bovine aortic endothelial cells using quantitative chemiluminescence techniques have shown that the amount of nitric oxide released under basal conditions, or in response to either bradykinin or the calcium ionophore A23187 is insufficient to account for the vasorelaxant activities of the endothelium-derived relaxing factor (EDRF) derived from the same source. This observation contradicts previous suggestions that nitric oxide and EDRF are the same compound, but may be explained if EDRF is a compound that contains nitric oxide within its structure but is a much more potent vasodilator than nitric oxide. Such a molecule could be one of several nitrosothiols which may yield nitric oxide after a one-electron reduction. The present experiments were carried out to test the possibility that the biological activities of the endothelium-derived relaxing factor might more closely resemble those of one of these compounds, S-nitrosocysteine, than nitric oxide. Nitric oxide release from cultured bovine aortic endothelial cells was detected by chemiluminescence and bioassay experiments compared the vasodilator potencies of nitric oxide, S-nitrosocysteine, and EDRF. The results suggest that EDRF is much more likely to be a nitrosylated compound such as a nitrosothiol than authentic nitric oxide.     

Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor

Endothelium-derived relaxing factor (EDRF) is a labile humoral agent which mediates the action of some vasodilators. Nitrovasodilators, which may act by releasing nitric oxide (NO), mimic the effect of EDRF and it has recently been suggested by Furchgott that EDRF may be NO. We have examined this suggestion by studying the release of EDRF and NO from endothelial cells in culture. No was determined as the chemiluminescent product of its reaction with ozone. The biological activity of EDRF and of NO was measured by bioassay. The relaxation of the bioassay tissues induced by EDRF was indistinguishable from that induced by NO. Both substances were equally unstable. Bradykinin caused concentration-dependent release of NO from the cells in amounts sufficient to account for the biological activity of EDRF. The relaxations induced by EDRF and NO were inhibited by haemoglobin and enhanced by superoxide dismutase to a similar degree. Thus NO released from endothelial cells is indistinguishable from EDRF in terms of biological activity, stability, and susceptibility to an inhibitor and to a potentiator. We suggest that EDRF and NO are identical.     

Ice-sheet acceleration driven by melt supply variability

Increased ice velocities in Greenland are contributing significantly to eustatic sea level rise. Faster ice flow has been associated with ice-ocean interactions in water-terminating outlet glaciers and with increased surface meltwater supply to the ice-sheet bed inland. Observed correlations between surface melt and ice acceleration have raised the possibility of a positive feedback in which surface melting and accelerated dynamic thinning reinforce one another, suggesting that overall warming could lead to accelerated mass loss. Here I show that it is not simply mean surface melt but an increase in water input variability that drives faster ice flow. Glacier sliding responds to melt indirectly through changes in basal water pressure, with observations showing that water under glaciers drains through channels at low pressure or through interconnected cavities at high pressure. Using a model that captures the dynamic switching between channel and cavity drainage modes, I show that channelization and glacier deceleration rather than acceleration occur above a critical rate of water flow. Higher rates of steady water supply can therefore suppress rather than enhance dynamic thinning, indicating that the melt/dynamic thinning feedback is not universally operational. Short-term increases in water input are, however, accommodated by the drainage system through temporary spikes in water pressure. It is these spikes that lead to ice acceleration, which is therefore driven by strong diurnal melt cycles and an increase in rain and surface lake drainage events rather than an increase in mean melt supply.     

Acclimatization of soil respiration to warming in a tall grass prairie.

The latest report by the Intergovernmental Panel on Climate Change (IPCC) predicts a 1.4-5.8 degrees C average increase in the global surface temperature over the period 1990 to 2100 (ref. 1). These estimates of future warming are greater than earlier projections, which is partly due to incorporation of a positive feedback. This feedback results from further release of greenhouse gases from terrestrial ecosystems in response to climatic warming. The feedback mechanism is usually based on the assumption that observed sensitivity of soil respiration to temperature under current climate conditions would hold in a warmer climate. However, this assumption has not been carefully examined. We have therefore conducted an experiment in a tall grass prairie ecosystem in the US Great Plains to study the response of soil respiration (the sum of root and heterotrophic respiration) to artificial warming of about 2 degrees C. Our observations indicate that the temperature sensitivity of soil respiration decreases--or acclimatizes--under warming and that the acclimatization is greater at high temperatures. This acclimatization of soil respiration to warming may therefore weaken the positive feedback between the terrestrial carbon cycle and climate.     

密度核反馈条件下低压自然循环两相流动稳定性实验

为了研究核供热反应堆主回路自然循环两相流动稳定性，考证了具有密度－核反馈耦合条件下两相流动的热工水力学行为。在热工实验回路ＨＲＴＬ－５中引入了反应堆中子动力学模拟系统。以实测冷却剂密度作为其输入参数，以中子动力学模拟系统的功率输出通过ＨＰ－３８５２５控制器对系统电加热功率进行实时控制，实验研究了不同工况条件下自然循环两相流动的稳定性。研究结果表明，核反馈耦合条件下系统中出现很低欠热度不稳定性区，反馈系数大小、测量系统和元件动态响应特性对自然循环两相流动稳定性有重要影响。     

输沙量对海岸沙丘表面风沙流中不同粒径沙粒垂向分布的影响

 在我国海岸沙丘的典型分布区河北昌黎黄金海 岸,对不同输沙量下海岸沙丘表面风沙流中不同粒径组沙粒垂向分布的变化进行了野外观测。结果表明,在风速相近、物质组成一 致和下垫面性质相同情况下,随着风沙流总输沙量的增加,在非均匀沙床面上不同粒径组沙粒的垂向分布呈现出了不同的变化特点 。其中,随总输沙量增加粗沙输沙量总量并无增加,其输沙量下层减少、中层增加、上层减少,垂向分布转变为典型负幂函数模式 ;中沙在不同高度的绝对输沙量均有增加,相对输沙量下层（0~4 cm）减少、上层（4~60 cm）增加或基本持平,其垂向分布基本 符合指数递减规律,尤其是在0~60 cm高度内的分布随总输沙量的增加由负幂函数转变为指数函数;细沙输沙量总量和不同高度的 输沙量均有不同程度的增加,相对输沙量下层（0~6 cm）减少、上层（6~60 cm）基本持平或增加,垂向分布符合典型的指数函数 布模式。究其原因,主要应与不同风速气流的携沙极限以及不同粒径组沙粒的运动方式密切相关。     

基于神经网络的ATM网络ABR业务流量控制

提出了异步转移模式ATM网络可用位速率ABR业务一种基于神经网络的流量控制方法。采用基于径向基神经网络的流量控制算法可以实现在线学习,自适应根据流量大小的变化和网络的拥塞状况调整神经网络的模型参数。仿真结果表明与传统的静态反馈方法相比,文中所用的算法可有效地提高信道的利用率和降低信元丢失率。     

Nitric oxide release from a single cell measured in situ by a porphyrinic-based microsensor.

Nitric oxide is an important bioregulatory molecule, being responsible, for example, for activity of endothelium-derived relaxing factor (EDRF). Acute hypertension, diabetes, ischaemia and atherosclerosis are associated with abnormalities of EDRF. Nitric oxide is thought to be a retrograde messenger in the central nervous system. The technology is not yet available for rapid detection of NO released by a single cell in the presence of oxygen and/or nitrite, so the release, distribution and reactivity of endogenous NO in biological systems cannot be analysed. Here we describe a porphyrinic microsensor that we have developed and applied to monitoring NO release in a microsystem. We selectively measured in situ the NO released from a single cell with a response time of less than 10 ms. The microsensor consists of p-type semiconducting polymeric porphyrin and a cationic exchanger (Nafion) deposited on a thermally sharpened carbon fibre with a tip diameter of approximately 0.5 microns. The microsensor, which can be operated in either the amperometric or voltammetric mode, is characterized by a linear response up to 300 microM and a detection limit of 10 nM. Nitric oxide at the level of 10(-20) mols can be detected in a single cell.     

最小相位系统的自适应鲁棒镇定

对一类ＭＩＭＯ最小相位系统，提出了一种适应鲁棒镇定的新策略，控制目的是通过一具固定结构的反馈控制器和一反馈增益自适应调节器而实现的，论文证明了，闭环的自适应控制系统的状态向量渐近趋于零，反馈增益趋近于某一常数。     

Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain

In the vascular system, endothelium-derived relaxing factor (EDRF) is the name of the local hormone released from endothelial cells in response to vasodilators such as acetylcholine, bradykinin and histamine. It diffuses into underlying smooth muscle where it causes relaxation by activating guanylate cyclase, so producing a rise in cyclic GMP levels. It has been known for many years that in the central nervous system (CNS) the excitatory neurotransmitter glutamate can elicit large increases in cGMP levels, particularly in the cerebellum where the turnover rate of cGMP is low. Recent evidence indicates that cell-cell interactions are involved in this response. We report here that by acting on NMDA (N-methyl-D-aspartate) receptors on cerebellar cells, glutamate induces the release of a diffusible messenger with strikingly similar properties to EDRF. This messenger is released in a Ca2+-dependent manner and its activity accounts for the cGMP responses that take place following NMDA receptor activation. In the CNS, EDRF may link activation of postsynaptic NMDA receptors to functional modifications in neighbouring presynaptic terminals and glial cells.     

工程车全液压制动系统性能试验台设计

为了对全液压制动系统的动态响应特性及制动压力输出特性进行精确检测,设计了一套由供油、主体、制动器及测控4个模块组成的全液压制动系统性能试验台,为满足充液阀和制动阀高低温试验空间的要求,主体模块的结构布置力求紧凑.另外,基于LabVIEW平台构建了制动系统参数检测与控制模块,并开发了一套制动踏板驱动机构及其反馈控制算法,实现了制动踏板运动过程的编程控制以及相关测试数据的自动化采集处理等功能.实验表明,该试验台可对不同温度和不同工况条件下的制动系统动态响应特性及制动压力输出特性等关键性能进行自动化精确检测.     

Sarcolemma-localized nNOS is required to maintain activity after mild exercise

Many neuromuscular conditions are characterized by an exaggerated exercise-induced fatigue response that is disproportionate to activity level. This fatigue is not necessarily correlated with greater central or peripheral fatigue in patients, and some patients experience severe fatigue without any demonstrable somatic disease. Except in myopathies that are due to specific metabolic defects, the mechanism underlying this type of fatigue remains unknown. With no treatment available, this form of inactivity is a major determinant of disability. Here we show, using mouse models, that this exaggerated fatigue response is distinct from a loss in specific force production by muscle, and that sarcolemma-localized signalling by neuronal nitric oxide synthase (nNOS) in skeletal muscle is required to maintain activity after mild exercise. We show that nNOS-null mice do not have muscle pathology and have no loss of muscle-specific force after exercise but do display this exaggerated fatigue response to mild exercise. In mouse models of nNOS mislocalization from the sarcolemma, prolonged inactivity was only relieved by pharmacologically enhancing the cGMP signal that results from muscle nNOS activation during the nitric oxide signalling response to mild exercise. Our findings suggest that the mechanism underlying the exaggerated fatigue response to mild exercise is a lack of contraction-induced signalling from sarcolemma-localized nNOS, which decreases cGMP-mediated vasomodulation in the vessels that supply active muscle after mild exercise. Sarcolemmal nNOS staining was decreased in patient biopsies from a large number of distinct myopathies, suggesting a common mechanism of fatigue. Our results suggest that patients with an exaggerated fatigue response to mild exercise would show clinical improvement in response to treatment strategies aimed at improving exercise-induced signalling.     

Bidirectional control of CNS capillary diameter by pericytes

Neural activity increases local blood flow in the central nervous system (CNS), which is the basis of BOLD (blood oxygen level dependent) and PET (positron emission tomography) functional imaging techniques. Blood flow is assumed to be regulated by precapillary arterioles, because capillaries lack smooth muscle. However, most (65%) noradrenergic innervation of CNS blood vessels terminates near capillaries rather than arterioles, and in muscle and brain a dilatory signal propagates from vessels near metabolically active cells to precapillary arterioles, suggesting that blood flow control is initiated in capillaries. Pericytes, which are apposed to CNS capillaries and contain contractile proteins, could initiate such signalling. Here we show that pericytes can control capillary diameter in whole retina and cerebellar slices. Electrical stimulation of retinal pericytes evoked a localized capillary constriction, which propagated at approximately 2 microm s(-1) to constrict distant pericytes. Superfused ATP in retina or noradrenaline in cerebellum resulted in constriction of capillaries by pericytes, and glutamate reversed the constriction produced by noradrenaline. Electrical stimulation or puffing GABA (gamma-amino butyric acid) receptor blockers in the inner retina also evoked pericyte constriction. In simulated ischaemia, some pericytes constricted capillaries. Pericytes are probably modulators of blood flow in response to changes in neural activity, which may contribute to functional imaging signals and to CNS vascular disease.     

Housing Pricesand General Economic Conditions： An Analysis of Chinese New Dwelling Market

This paper presents an investigation of the interaction between housing prices and general economic conditions in China for the period of 1986-2002, The empirical results indicate that housing prices in China are predictable by market fundamentals, which could explain most of the variations in housing prices. The results of Granger causality tests confirm that unemployment rate, total population, changes in construction costs, changes in the consumer price index (CPI) are all Granger causalities of housing prices, with feedback effects observed to affect the vacancy rate of new dwellings, changes in CPI, and changes in per capita disposable income of urban households, Studies with impulse response functions further illustrate these relationships in terms of the degree of the impact on housing prices from the determinants and the feedbacks, The findings indicate that there is a long-term equilibrium relationship between housing prices and market fundamentals in China and it is the identified fundamentals that drive housing prices up, rather than a bubble,     

Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor

Endothelium-derived vascular relaxing factor (EDRF) is a humoral agent that is released by vascular endothelium and mediates vasodilator responses induced by various substances including acetylcholine and bradykinin. EDRF is very unstable, with a half-life of between 6 and 50 s, and is clearly distinguishable from prostacyclin. The chemical structure of EDRF is unknown but it has been suggested that it is either a hydroperoxy- or free radical-derivative of arachidonic acid or an unstable aldehyde, ketone or lactone. We have examined the role of superoxide anion (O-2) in the inactivation of EDRF released from vascular endothelial cells cultured on microcarrier beads and bioassayed using a cascade of superfused aortic smooth muscle strips. With this system, we have now demonstrated that EDRF is protected from breakdown by superoxide dismutase (SOD) and Cu2+, but not by catalase, and is inactivated by Fe2+. These findings indicate that O-2 contributes significantly to the instability of EDRF.     

微通信元系统构架下拥塞控制服务元的设计

提出了把拥塞控制机制做成独立且又易扩展的拥塞控制类服务元．它结合了模糊随即早期检测算法和模糊漏桶算法的优点，加入了站到站抑制信号的反馈，使网络中数据流量抖动平缓，并能及时响应和缓解拥塞情况．     

基于RTCP反馈的TCP友好的实时流媒体拥塞控制机制

提出了一种端到端的、基于RTCP反馈的、改进了的TFRC拥塞控制机制,即a-TFRC(amelioratedTFRC);主要针对实时流媒体要求低延迟和低抖动的特点,修改了TFRC的慢启动阶段,使得TFRC流开始的发送速率不至于太低而使得接收端在开始有较大的延迟和抖动·仿真结果验证了此机制在实现对TCP流友好性的同时提高了实时流媒体的QoS