Statistical mechanics of prion diseases

We present a two-dimensional, lattice based, protein-level statistical mechanical model for prion diseases (e.g., mad cow disease) with concomitant prion protein misfolding and aggregation. Our studies lead us to the hypothesis that the observed broad incubation time distribution in epidemiological data reflect fluctuation dominated growth seeded by a few nanometer scale aggregates, while much narrower incubation time distributions for innoculated lab animals arise from statistical self-averaging. We model "species barriers" to prion infection and assess a related treatment protocol.     

Solid-state NMR structural studies of the fibril form of a mutant mouse prion peptide PrP89-143(P101L)

The peptide fragment 89-143 of the prion protein (carrying a P101L mutation) is biologically active in transgenic mice when in a fibrillar form. Injection of these fibrils into transgenic mice (expressing full length PrP with the P101L mutation) induces a neurodegenerative prion disease (Kaneko et al., J. Mol. Biol. 295 (2000) 997). Here we present solid-state NMR studies of PrP(89-143)(P101L) fibrils, probing the conformation of residues in the hydrophobic segment 112-124 with chemical shifts. The conformations of glycine residues were analyzed using doubly (13)C=O labeled peptides by two-dimensional (2D) double-quantum correlation, and double-quantum filtered dephasing distance measurements. MQ-NMR experiments were carried out to probe the relative alignment of the individual peptides fibrils. These NMR studies indicate that the 112-124 segment adopts an extended beta-sheet conformation, though not in a parallel, in register alignment. There is evidence for conformational variability at Gly 113. DQ correlation experiments provide useful information in regions with conformational heterogeneity.     

Scaling in the bombay stock exchange index

In this paper we study Bombay stock exchange (BSE) index financial time series for fractal and multifractal behaviour. We show that BSE index time series is monofractal and can be represented by a fractional Brownian motion.     

Modeling,validation and performance evaluation of body shadowing effect in ultra-wideband networks

Ultra-Wideband (UWB) is an emerging wireless technology with high data rates and low transmission power, which is very suitable for high-speed, short-range multimedia applications such as the Internet Protocol Television (IPTV) indoor distribution. However, human body shadowing is very common in any office or household environment, and can dramatically affect the UWB link performance when the significant propagation paths are blocked. In this paper, we build an analytical model for the Body Shadowing Effect (BSE) on indoor UWB channels based on the IEEE 802.15.3a standard and the channel reciprocity property. The BSE model and the reciprocity property of UWB channels in both the baseband and the radio frequency band are validated with extensive measurement. We further apply the extended BSE model in the analysis of application-layer Quality-of-Service (QoS) metrics for IPTV services, and derive the packet loss rate of the IPTV streams analytically and obtain the admission region to ensure the QoS. The work is of particular importance for the performance evaluation of UWB networks and the service provisioning for IPTV indoor distribution.     

Analysis and localization of metal‐ and metalloid‐containing proteins by synchrotron radiation x‐ray fluorescence spectrometry

Synchrotron radiation x‐ray fluorescence (SRXRF) spectrometry has been applied for the determination of metals and metalloids in electrophoretically separated proteins and histological samples. The method was tested by the analysis of trace element‐containing proteins in rat testis homogenate and the determination of the spatial distribution of some metals in brain sections of scrapie‐infected hamsters. After sodium dodecyl sulfate—polyacrylamide gel electrophoresis (SDS‐PAGE) and transfer on to a blotting membrane, the distribution of selenium among the proteins of testis homogenate was determined. The comparison with the autoradiogram of ⁷⁵Se‐labeled testicular proteins separated in the same way showed that of nine selenium‐containing proteins found by autoradiography, four could be detected by SRXRF. The distribution of several metals and metalloids in cryo‐sections of 10 µm thin brain sections of three Syrian hamsters intracerebrally infected with the scrapie strain ME7‐H and of three control animals was investigated at the HASYLAB beamline L by scanning with a synchrotron radiation beam focused by a polycapillary lens. The copper‐binding prion protein (PrP) in its pathological form PrP^Sc, determined by immunohistochemistry on cryo‐sections, was found to be diffusely dispersed in the scrapie‐infected brains, and the copper distribution differed from that in the control animals. The question whether, and to what extent, PrP^Sc and copper hot‐spots are related, remains to be investigated. The method was shown to be suitable for the determination of trace element distribution patterns in electrophoretically separated proteins and histological tissue preparations. Copyright © 2004 John Wiley & Sons, Ltd.     

Determination of chemical shift anisotropies of unresolved carbonyl sites by C-alpha detection under magic-angle spinning

We demonstrate that the static powder pattern line shape of chemical shift anisotropy (CSA) can be obtained for unresolved carbonyl sites of polypeptides under magic-angle spinning. The CSA interaction is first recoupled at the carbonyl site. The phase factors associated with the CSA recoupling are then transferred to the adjacent alpha carbon by an isotropic polarization transfer based on scalar spin-spin coupling. Because alpha carbons of polypeptides are usually better resolved, we can then obtain the CSA static powder pattern line shapes of the carbonyl sites after Fourier transformation in the second dimension. We validate our approach experimentally by measurements on [U-(13)C, (15)N]-l-alanine, [U-(13)C, (15)N]-l-valine and prion fibrils with uniform (13)C and (15)N labels on selected residues.     

Characterization of water mobility and distribution in low- and intermediate-moisture food systems

The mechanism of water uptake in low moisture cereals and cookies has been studied by NMR relaxometry and solid imaging technology implemented on a low-resolution benchtop NMR spectrometer. A comparison between classical MRI and SPRITE imaging are also presented to highlight the benefits of each technology. The spin lattice (T(1)) and spin spin (T(2)) relaxation times, the 1D and 2D SPRITE imaging, were determined on Smacks, corn flakes, chocolate chips cookies, soft caramel candies with a chocolate crème filler, and corn starch/water systems. The Smacks and corn flakes were studied based on the soaking time in milk, and the results showed that T(1) and T(2) decreased in the first 20 sec of soaking and then increased with the soaking time. For Smacks stored at different relative humidity, T(1) decreased during the first day of storage and then was relatively constant over storage time indicating that the system reached an equilibrium. 1D SPRITE profiles indicated an increase in signal intensity over storage time for cookies in 58% RH. However, the moisture uptake was insignificant indicating that the water mobility (and not the amount of water) changed due to various chemical interactions in the system (hydrogen bonding, starch retrogradation, glassy/rubbery equilibrium). The T(1) and T(2) of corn starch/water systems decreased as the concentration in starch increased and temperature increased from 30 degrees C to 60 degrees C. However, for temperatures higher than 60 degrees C, the relaxation times increased showing more mobility and flexibility of the polymer chains during gelatinization.     

Experimental observation of multicritical behaviors in pressure-temperature diagrams of pure compounds with twist grain boundary phases

In order to study critical behaviors of pure compounds anticipated by Renn and Lubensky's theoretical calculations, high-pressure experiments have been performed on six tolan series homologous to the 3-fluoro-4-[(R) or (S)-methylheptyloxy]-4'-(4"-alkoxy-2",3"-difluorobenzoyloxy), which exhibit the twist grain boundary (TGB(A) and TGB(C)) mesophases. Measurements were carried out by thermobarometric analysis. Six pressure-temperature phase diagrams are determined. The studies establish the existence of multicritical points twisted-smectic-C (S*(C))-TGB(C)-TGB(A), TGB(C)-TGB(A)-cholesteric nematic (N*) and S*(C)-TGB(C)-N* for single component systems in pressure-temperature (P-T) phase diagrams. Our results also show that a pressure increase has the same effect on the (P-T) phase diagrams as a decreasing number of carbon atoms in the aliphatic chain; then pressure change can have the same effects on intermolecular interactions as those observed when shortening the molecular length. The existence of transition lines with negative slope values was also found. The experimental results are in qualitative agreement with the model proposed by Renn and Lubensky.     

Squalestatin alters the intracellular trafficking of a neurotoxic prion peptide

Background  

Neurotoxic peptides derived from the protease-resistant core of the prion protein are used to model the pathogenesis of prion diseases. The current study characterised the ingestion, internalization and intracellular trafficking of a neurotoxic peptide containing amino acids 105–132 of the murine prion protein (MoPrP105-132) in neuroblastoma cells and primary cortical neurons.     

红外导引头高速流场及其对光线传输影响的数值模拟

研究红外光线经过高速流场时由于折射产生的瞄视误差(BSE),对于红外末制导拦截弹的命中精度有重要意义。考虑高温真实气体效应,求解热化学非平衡Navier-Stokes(N-S)方程得到导引头的流场,采用光线追迹的方法,对红外光线经过流场后到达导引头光学窗口的瞄视误差进行了计算分析,研究了光线入射角、飞行马赫数、攻角、高度及红外导引头外形对瞄视误差的影响。     

Lingering Random Walks in Random Environment on a Strip

We consider a recurrent random walk (RW) in random environment (RE) on a strip. We prove that if the RE is i. i. d. and its distribution is not supported by an algebraic subsurface in the space of parameters defining the RE then the RW exhibits the (log t)² asymptotic behaviour. The exceptional algebraic subsurface is described by an explicit system of algebraic equations. One-dimensional walks with bounded jumps in a RE are treated as a particular case of the strip model. If the one dimensional RE is i. i. d., then our approach leads to a complete and constructive classification of possible types of asymptotic behaviour of recurrent random walks. Namely, the RW exhibits the (log t)² asymptotic behaviour if the distribution of the RE is not supported by a hyperplane in the space of parameters which shall be explicitly described. And if the support of the RE belongs to this hyperplane then the corresponding RW is a martingale and its asymptotic behaviour is governed by the Central Limit Theorem.     

反刍动物精料补充料中肉骨粉快速检测近红外光谱法

为探讨利用近红外漫反射光谱技术快速定量分析反刍动物精料补充料中肉骨粉含量的可行性,收集了我国常用的、具有代表性的精料补充料225个和肉骨粉75个,按照不同的肉骨粉含量（0.5%～ 35%）制备样品225个,其中135个为定标集,90个作为独立的验证集。用光栅型近红外光谱仪进行光谱扫描,选择合适的光谱预处理方法和光谱范围,采用改善的偏最小二乘法（MPLS）建立了定量分析 模型,相关系数为0.979,标准差为1.522%,交互验证标准差为1.582%。用90个独立的验证样品对所建立的定量分析模型进行验证,相关系数为0.972,预测标准差为1.764%,RPD值为5.99。结果表明 利用近红外反射光谱法可以分析精补料中肉骨粉的含量,对于丰富我国动物源性饲料的快速检测手段,具有实际应用意义。     

CPMG relaxation by diffusion with constant magnetic field gradient in a restricted geometry: numerical simulation and application

Carr-Purcell-Meiboom-Gill (CPMG) measurements are the primary nuclear magnetic resonance (NMR) technique used for evaluating formation properties and reservoir fluid properties in the well logging industry and laboratory sample analysis. The estimation of bulk volume irreducible (BVI), permeability, and fluid type relies on the accurate interpretation of the spin-spin relaxation time (T(2)) distribution. The interpretation is complicated when spin's self-diffusion in an inhomogeneous field and restricted geometry becomes dominant. The combined effects of field gradient, diffusion, and a restricted geometry are not easily evaluated analytically. We used a numerical method to evaluate the dependence of the free and restricted diffusion on the system parameters in the absence of surface relaxation, which usually can be neglected for the non-wetting fluids (e.g., oil or gas). The parameter space that defines the relaxation process is reduced to two dimensionless groups: D* and tau*. Three relaxation regimes: free diffusion, localization, and motionally averaging regimes are identified in the (log(10)D*, log(10)tau*) domain. The hypothesis that the normalized magnetization, M*, relaxes as a single exponential with a constant dimensionless relaxation time T*(2) is justified for most regions of the parameter space. The numerical simulation results are compared with the analytical solutions from the contour plots of T*(2). The locations of the boundaries between different relaxation regimes, derived from equalizing length scales, are challenged by observed discrepancies between numerical and analytical solutions. After adjustment of boundaries by equalizing T*(2), numerical simulation result and analytical solution match each other for every relaxation regime. The parameters, fluid diffusivity and pore length, can be estimated from analytical solutions in the free diffusion and motionally averaging regimes, respectively. Estimation of the parameters near the boundaries of the regimes may require numerical simulation.     

Grüneisen ratio divergence at the quantum critical point in CeCu(6-x)Agx

The heavy-fermion system CeCu6-xAgx is studied at its antiferromagnetic quantum critical point, xc=0.2, by low-temperature (T> or =50 mK) specific heat, C(T), and volume thermal expansion, beta(T), measurements. Whereas C/T proportional to log((T0/T) would be compatible with the predictions of the itinerant spin-density-wave (SDW) theory for two-dimensional critical spin fluctuations, beta(T)/T and the Grüneisen ratio, Gamma(T) proportional to beta/C, diverge much weaker than expected, in strong contrast to this model. Both C and beta, plotted as a function of the reduced temperature t=T/T0 with T0=4.6 K, are similar to what was observed for YbRh2(Si(0.95)Ge(0.05))2 (T0=23.3 K), indicating a striking discrepancy to the SDW prediction in both systems.     

Simple off-lattice model to study the folding and aggregation of peptides

We present a numerical study of a new protein model. This off-lattice model takes into account both the hydrogen bonds and the amino-acid interactions. It reproduces the folding of a small protein (peptide): morphological analysis of the conformations at low temperature shows two well-known substructures α-helix and β-sheet depending on the chosen sequence. The folding pathway in the scope of this model is studied through a free-energy analysis. We then study the aggregation of proteins. Proteins in the aggregate are mainly bound via hydrogen bonds. Performing a free-energy analysis we show that the addition of a peptide to such an aggregate is not favourable. We qualitatively reproduce the abnormal aggregation of proteins in prion diseases.     

Weak mixing and anomalous kinetics along filamented surfaces

We consider chaotic properties of a particle in a square billiard with a horizontal bar in the middle. Such a system can model field-line windings of the merged surfaces. The system has weak-mixing properties with zero Lyapunov exponent and entropy, and it can be also interesting as an example of a system with intermediate chaotic properties, between the integrability and strong mixing. We show that the transport is anomalous and that its properties can be linked to the ergodic properties of continued fractions. The distribution of Poincare recurrences, distribution of the displacements, and the moments of the truncated distribution of the displacements are obtained. Connections between different exponents are found. It is shown that the distribution function of displacements and its truncated moments as a function of time exhibit log-periodic oscillations (modulations) with a universal period T(log)=pi(2)/12 ln 2. We note that similar results are valid for a family of billiard, particularly for billiards with square-in-square geometry. (c) 2001 American Institute of Physics.     

NMR-Based amide hydrogen-deuterium exchange measurements for complex membrane proteins: development and critical evaluation

A method for measuring site-specific amide hydrogen-deuterium exchange rates for membrane proteins in bilayers is reported and evaluated. This method represents an adaptation and extension of the approach of Dempsey and co-workers (Biophys. J. 70, 1777-1788 (1996)) and is based on reconstituting (15)N-labeled membrane proteins into phospholipid bilayers, followed by lyophilization and rehydration with D(2)O or H(2)O (control). Following incubation for a time t under hydrated conditions, samples are again lyophilized and then solubilized in an organic solvent system, where (1)H-(15)N HSQC spectra are recorded. Comparison of spectra from D(2)O-exposed samples to spectra from control samples yields the extent of the H-D exchange which occurred in the bilayers during time t. Measurements are site specific if specific (15)N labeling is used. The first part of this paper deals with the search for a suitable solvent system in which to solubilize complex membrane proteins in an amide "exchange-trapped" form for NMR quantitation of amide peak intensities. The second portion of the paper documents application of the overall procedure to measuring site-specific amide exchange rates in diacylglycerol kinase, a representative integral membrane protein. Both the potential usefulness and the significant limitations of the new method are documented.     

镜像核13N-13C 和15N-15O中的激发态晕或皮(英文)

用非线性相对论平均场对两对镜像核13N-13C 和15N-15O进行了研究. 发现无论在基态还是激发态， 用两套参数所得的结合能都跟实验值很接近. 计算结果显示13N的第一激发态（2s1/2）和第三激发态（1d5/2）各存在一个非束缚的质子晕， 而13C的第三激发态（1d5/2）存在一个弱束缚的中子皮. 另外研究表明, 在另一对镜像核15N-15O的第二激发态（2s1/2）和第一激发态（2s1/2）分别存在一个中子晕和质子皮. Properties of two pairs of mirror nuclei 13N-13C and15N-15O are investigated by using the nonlinear relativistic mean field theory. It is found that all the calculated binding energies with two different parameter sets are very close to the experimental ones for both the ground states and the excited states. The calculations show that the first excited state (2s1/2) and the third excited state (1d5/2) in 13N are both unbound resonances with proton halo structure, whereas the third excited state (1d5/2) in 13C is weakly bound with a neutron skin. It is also predicted that there has a proton halo in the second excited state (2s1/2) of 15N as well as a neutron skin in the first excited state (2s1/2) of 15O.     

Magnetization process of single molecule magnets at low temperatures

We show that correlations established before quenching to very low temperatures later drive the magnetization process of systems of single molecule magnets, after a magnetic field is applied at t=0. We also show that in simple cubic lattices m proportional, variant sqrt[t], as observed in Fe8, but only for 1+2log((10)(h(d)/h(w)) time decades, where h(d) is a nearest neighbor dipolar magnetic field and a spin reversal can occur only if the field on it is within (-h(w),h(w)). However, the sqrt[t] behavior is not universal. For bcc and fcc lattices, m proportional, variant t(p), but p approximately 0.7. The value to which m finally levels off is also given.     

Monte Carlo方法计算低能电子作用下固体背散射电子发射及空间分布

应用Monte Carlo方法,对能量E₀≤5keV低能电子作用下固体Al、Cu、Ag、Au的背散射电子发射及表面空间分布作了计算.模型应用Mott散射截面及修正的Bethe方程分别描述低能电子在固体中的弹性和非弹性散射.计算了背散射电子能量分布、表面空间分布、深度分布和角分布规律及特征,还计算分析了背散射电子角分布与深度分布、表面空间分布及能量分布之间的关系,系统地描述了背散射电子的发射及分布规律.