Combined hyperlipidemia in transgenic mice overexpressing human apolipoprotein Cl

We have generated transgenic mice over-expressing human apolipoprotein CI (apo CI) using the native gene joined to the downstream 154-bp liver-specific enhancer that we defined for apo E. Human apo CI (HuCI)-transgenic mice showed elevation of plasma triglycerides (mg/dl) compared to controls in both the fasted (211 +/- 81 vs 123 +/- 52, P = 0.0001) and fed (265 +/- 105 vs 146 +/- 68, P < 0.0001) states. Unlike the human apo CII (HuCII)- and apo CIII (HuCIII)-transgenic mouse models of hypertriglyceridemia, plasma cholesterol was disproportionately elevated (95 +/- 23 vs 73 +/- 23, P = 0.002, fasted and 90 +/- 24 vs 61 +/- 14, P < 0.0001, fed). Lipoprotein fractionation showed increased VLDL and IDL + LDL with an increased cholesterol/triglyceride ratio (0.114 vs 0.065, P = 0.02, in VLDL). The VLDL apo E/apo B ratio was decreased 3.4-fold (P = 0.05) and apo CII and apo CIII decreased in proportion to apo E. Triglyceride and apo B production rates were normal, but clearance rates of VLDL triglycerides and postlipolysis lipoprotein "remnants" were significantly slowed. Plasma apo B was significantly elevated. Unlike HuCII- and HuCIII-transgenic mice, VLDL from HuCI transgenic mice bound heparin-Sepharose, a model for cell-surface glycosaminoglycans, normally. In summary, apo CI overexpression is associated with decreased particulate uptake of apo B-containing lipoproteins, leading to increased levels of several potentially atherogenic species, including cholesterol-enriched VLDL, IDL, and LDL.     

Sleep-induced breathing instability. University of Wisconsin-Madison Sleep and respiration Research Group

We present a view of the neuromechanical regulation of breathing and causes of breathing instability during sleep. First, we would expect transient increases in upper airway resistance to be a major cause of transient hypopnea. This occurs in sleep because a hypotonic upper airway is more susceptible to narrowing and because the immediate excitatory increase in respiratory motor output in response to increased loads is absent in non-REM sleep. Secondly, sleep predisposes to an increased occurrence of ventilatory "overshoots", in part because abruptly changing sleep states cause transient changes in upper airway resistance and in the gain of the respiratory controller. Following these ventilatory overshoots, breathing stability will be maintained if excitatory short-term potentiation is the prevailing influence. On the other hand, apnea and hypopnea will occur if inhibitory mechanisms dominate following the ventilatory overshoot. These inhibitory mechanisms include: a) hypocapnia-if transient, will inhibit carotid chemoreceptors and cause hypopnea, but if prolonged will inhibit medullary chemoreceptors and cause apnea; b) a persistent inhibitory effect from lung stretch; c) baroreceptor stimulation, from a transient rise in systemic blood pressure immediately following termination of apnea or hypopnea may partially suppress the accompanying hyperpnea; d) depression of central respiratory motor output via prolonged brain hypoxia. Once apneas are initiated, reinitiation of inspiration is delayed even though excitatory stimuli have risen well above their apneic thresholds, and these prolonged apneas are commonly accompanied by tonic EMG activation of expiratory muscles of the chest wall and upper airway.     

Visual comparability of 3D regular sampling and reconstruction

The Body-Centered Cubic (BCC) and Face-Centered Cubic (FCC) lattices have been analytically shown to be more efficient sampling lattices than the traditional Cartesian Cubic (CC) lattice, but there has been no estimate of their visual comparability. Two perceptual studies (each with N = 12 participants) compared the visual quality of images rendered from BCC and FCC lattices to images rendered from the CC lattice. Images were generated from two signals: the commonly used Marschner-Lobb synthetic function and a computed tomography scan of a fish tail. Observers found that BCC and FCC could produce images of comparable visual quality to CC, using 30-35 percent fewer samples. For the images used in our studies, the L(2) error metric shows high correlation with the judgement of human observers. Using the L(2) metric as a proxy, the results of the experiments appear to extend across a wide range of images and parameter choices.     

A rapid computational filter for predicting the rate of human renal clearance

In silico models that predict the rate of human renal clearance for a diverse set of drugs, that exhibit both active secretion and net re-absorption, have been produced using three statistical approaches. Partial Least Squares (PLS) and Random Forests (RF) have been used to produce continuous models whereas Classification And Regression Trees (CART) has only been used for a classification model. The best models generated from either PLS or RF produce significant models that can predict acids/zwitterions, bases and neutrals with approximate average fold errors of 3, 3 and 4, respectively, for an independent test set that covers oral drug-like property space. These models contain additional information on top of any influence arising from plasma protein binding on the rate of renal clearance. Classification And Regression Trees (CART) has been used to generate a classification tree leading to a simple set of Renal Clearance Rules (RCR) that can be applied to man. The rules are influenced by lipophilicity and ion class and can correctly predict 60% of an independent test set. These percentages increase to 71% and 79% for drugs with renal clearances of < 0.1 ml/min/kg and > 1 ml/min/kg, respectively. As far as the authors are aware these are the first set of models to appear in the literature that predict the rate of human renal clearance and can be used to manipulate molecular properties leading to new drugs that are less likely to fail due to renal clearance.     

中国传统符号的演变——门

人类学会构筑房屋并为自己的进出留下一个进出方便的口,门就产生了。门是一个极为抽象的形态,一个变化万千的符号,这个古老的符号——门的形态变化一直在随着科技的发展而演变,无论是古人还是后人都在其中精心地演绎着中国的传统民族文化。     

Properties and performance modelling of finite buffer M/G/1/K networks

Finite buffer, single-server queueing systems and networks are difficult to analyze since the length of time a customer spends in the system does not follow the Markovian property. A two-moment approximation schema is developed for the probability distribution of M/G/1/K systems and extended to the analysis of M/G/1/K   queueing networks. The general purpose of this paper is to develop a flexible and practical transform-free approach for computing the probability distribution and performance measures of the system as well as identify the underlying properties of these systems. It is shown that for most performance measures, a sigmoid or S-shaped curve with an inflection point at ρ=1$\rho =1$ appears as K→∞$K\to \infty$. This has direct implications for the analysis and optimization of such systems. The performance modelling of the M/G/1/K queueing networks of general topologies along with extensive numerical results accompany the paper along with the linear concave performance measures for these systems.     

我国GNP的单位根不确定性研究

对于一个实际的时间序列数据,我们并不知道其真正的数据生成过程,只能通过假设和基于假设的统计推断来确定。本文利用蒙特卡罗模拟进行有限样本的ADF检验。结果表明,当原假设是存在单位根,备择假设是趋势稳定时,ADF检验的势很低。这意味着,我国GNP存在单位根是不确定的。