Wiener analysis of nonlinear feedback in sensory systems

Experimental studies of certain sensory systems (e.g., vertebrate retinal cells and auditory fibers) have yielded qualitative evidence of the presence of nonlinear feedback. However, no methods have been available to provide the tools for quantitative analysis of this nonlinear feedback mechanism and subsequent modeling of the overall dynamics of these sensory systems. Recent results offer the analytical means to relate Wiener kernel measurements with corresponding nonlinear feedback models and, thus, the ability to model the overall dynamics of such sensory systems. Furthermore, our analytical results offer an explanation for experimentally observed changes in the waveform of Wiener kernel estimates obtained for different white-noise input mean and/or power levels.     

The identification of nonlinear biological systems: Wiener kernel approaches

Detection, representation, and identification of nonlinearities in biological systems are considered. We begin by briefly but critically examining a well-known test of system nonlinearity, and point out that this test cannot be used to prove that a system is linear. We then concentrate on the representation of nonlinear systems by Wiener's orthogonal functional series, discussing its advantages, limitations, and biological applications. System identification through estimating the kernels in the functional series is considered in detail. An efficient time-domain method of correcting for coloring in inputs is examined and shown to result in significantly improved kernel estimates in a biologically realistic system.     

Asymptotic approach of generalized orthogonal functional expansions to Wiener kernels

Wiener-like orthogonal functional expansions may be constructed with respect to test ensembles that are non-Gaussian, nonwhite, or both. Although the original Wiener expansion has particularly advantageous analytical properties, orthogonal expansions constructed with respect to other ensembles have practical advantages for laboratory implementation. We show how functional expansions based on two classes of input ensembles — white but non-Gaussian discrete noises and the sum of sinusoids-converge to the standard Wiener kernels. For discrete noises, the disparity between the standard and nonstandard kernels of a linear-static nonlinear transducer is proportional to the kurtosis of the input signal and inversely proportional to the ratio of the integration time of the linear filter to the time discretization. For the sum of sinusoids, the disparity is inversely proportional to the effective number of sinusoids passed by the initial linear stage.     

Identifying nonlinear difference equation and functional expansion representations: The fast orthogonal algorithm

A method is presented for identifying functional expansion and difference equation representations for nonlinear systems. The method relies on an orthogonal approach which does not require explicit creation of orthogonal functions. This greatly reduces computing time, so that 15-fold increases in speed of estimating kernels or difference equation coefficients are readily obtainable, compared with a previous orthogonal technique. In addition, storage requirements are considerably diminished. A wide variety of input excitation, both random and deterministic, can be used, and the method is not limited to inputs which are Gaussian, white or lengthy. A model of the peripheral auditory system is simulated to show kernel measurement is free of artifacts using the present method, in contrast to the crosscorrelation approach.     

Parallel cascade identification and kernel estimation for nonlinear systems

We consider the representation and identification of nonlinear systems through the use of parallel cascades of alternating dynamic linear and static nonlinear elements. Building on the work of Palm and others, we show that any discrete-time finite-memory nonlinear system having a finite-order Volterra series representation can be exactly represented by a finite number of parallel LN cascade paths. Each LN path consists of a dynamic linear system followed by a static nonlinearity (which can be a polynomial). In particular, we provide an upper bound for the number of parallel LN paths required to represent exactly a discrete-time finite-memory Volterra functional of a given order. Next, we show how to obtain a parallel cascade representation of a nonlinear system from a single input-output record. The input is not required to be Gaussian or white, nor to have special autocorrelation properties. Next, our parallel cascade identification is applied to measure accurately the kernels of nonlinear systems (even those with lengthy memory), and to discover the significant terms to include in a nonlinear difference equation model for a system. In addition, the kernel estimation is used as a means of studying individual signals to distinguish deterministic from random behaviour, in an alternative to the use of chaotic dynamics. Finally, an alternate kernel estimation scheme is presented.     

Exact orthogonal kernel estimation from finite data records: Extending Weiner's identification of nonlinear systems

A technique is described for exact estimation of kernels in functional expansions for nonlinear systems. The technique operates by orthogonalizing over the data record and in so doing permits a wide variety of input excitation. In particular, the excitation is not limited to inputs that are white, Gaussian, or lengthy. Diagonal kernel values can be estimated, without modification, as accurately as off-diagonal values. Simulations are provided to demonstrate that the technique is more accurate than the Lee-Schetzen method with a white Gaussian input of limited duration, retaining its superiority when the system output is corrupted by noise.     

Adaptive Wiener Filtering for Improved Acquisition of Distortion Product Otoacoustic Emissions

An innovative acoustic noise canceling method using adaptive Wiener filtering (AWF) was developed for improved acquisition of distortion product otoacoustic emissions (DPOAEs). The system used one microphone placed in the test ear for the primary signal. Noise reference signals were obtained from three different sources: (a) pre-stimulus response from the test ear microphone, (b) post-stimulus response from a microphone placed near the head of the subject and (c) post-stimulus response obtained from a microphone placed in the subjects nontest ear. In order to improve spectral estimation, block averaging of a different number of single sweep responses was used. DPOAE data were obtained from 11 ears of healthy newborns in a well-baby nursery of a hospital under typical noise conditions. Simultaneously obtained recordings from all three microphones were digitized, stored and processed off-line to evaluate the effects of AWF with respect to DPOAE detection and signal-to-noise ratio (SNR) improvement. Results show that compared to standard DPOAE processing, AWF improved signal detection and improved SNR. © 1998 Biomedical Engineering Society. PAC98: 4364Jb, 4360-c, 8790+y     

Parallel Cascade Recognition of Exon and Intron DNA Sequences

Many of the current procedures for detecting coding regions on human DNA sequences combine a number of individual techniques such as discriminant analysis and neural net methods. Recent papers have used techniques from nonlinear systems identification, in particular, parallel cascade identification (PCI), as one means for classifying protein sequences into their structure/function groups. In the present paper, PCI is used in a pilot study to distinguish exon (coding) from intron (noncoding; interspersed within genes) human DNA sequences. Only the first exon and first intron sequences with known boundaries in genomic DNA from the T-cell receptor locus were used for training. Then, the parallel cascade classifiers were able to achieve classification rates of about 89% on novel sequences in a test set, and averaged about 82% when results of a blind test were included. In testing over a much wider range of human nucleotide sequences, PCI classifiers averaged 83.6% correct classifications. These results indicate that parallel cascade classifiers may be useful components in future coding region detection programs. © 2002 Biomedical Engineering Society. PAC2002: 8715Cc, 8714Gg, 8715Aa     

一种恢复高刺激率下听觉诱发电位的迭代维纳滤波方法

研究分离高刺激率诱发的听觉诱发电位(AEP)暂态成分的方法。根据前期提出的维纳滤波技术,结合高阶反应的数学模型,提出一种长期记忆的迭代计算方案,在无需信号先验知识的条件下逼近一个稳定的AEP估计。将该方法应用于仿真数据和真实数据进行检验,其效果接近理想条件下维纳滤波的理论解。结果表明该方法可在缺乏信号先验知识的条件下,得到一个接近于理论真实值的AEP估计,为在高刺激率下还原AEP提供了一定的启示。     

Identification of time-varying Hammerstein systems from ensemble data

In this paper, we describe a new technique to identify rapidly time-varying Hammerstein systems from ensembles of input–output realizations. The technique involves two steps. A correlation approach is first used to obtain initial estimates of the linear subsystem parameters for every sampling time. An iterative optimization algorithm is then employed to produce final estimates of the system parameters. The input does not need to be white. The technique was tested on simulated data and was found to produce excellent results under realistic conditions. © 2001 Biomedical Engineering Society. PAC01: 8710+e, 0545Tp     

Dissection of a nonlinear cascade model for sensory encoding

Action potential encoding in the cockroach tactile spine neuron may be treated as a single-input, single-output dynamic nonlinear process, where the input is the electric current flowing across the neuronal membrane and the output is the resultant train of action potentials. The nonlinear behavior of the system may be characterized by a functional expansion method which efficiently and accurately yields similar kernels to the Wiener method. A simple nonlinear cascade consisting of sequential dynamic linear, static nonlinear, and dynamic linear components was identified and gives a good approximation to the response of the neuron to random stimulation. Next, we attempted to study the components of the cascade by the use of a drug, phentolamine, which selectively modifies the dynamic behavior of the encoder. Application of phentolamine to the neuron caused a significant change in the first dynamic linear component of the cascade without affecting the other components. The change was much larger than the variability between results obtained from individual animals. This finding has implications for the biophysical processes which are involved in the components of the cascade.     

Nonlinear model predictive control for dosing daily anticancer agents using a novel saturating-rate cell-cycle model

A nonlinear model predictive control (NMPC) algorithm was developed to dose the chemotherapeutic agent tamoxifen based on a novel saturating-rate, cell-cycle model (SCM). Using daily tumor measurements, the algorithm decreased tumor volume along a specified reference trajectory in simulated animals over 4 months. In mismatch case studies, controllers based on the Gompertz model (GM) yielded equivalent total drug delivered and elapsed time to t(99%) reference step convergence to those obtained using the SCM, though this performance was dependent on the cell-cycle phase of drug effect. Overall, the NMPC algorithm is suitable for dosing chemotherapeutics with regular administration schedules and may be adapted for regularly administered chemotherapeutics other than tamoxifen.     

A New Titanium Complex Having Two Phenoxy‐Imine Chelate Ligands for Ethylene Polymerization

A new titanium complex having two phenoxy‐imine chelate ligands, bis[N‐(3‐tert‐butylsalicylidene)anilinato]titanium(IV)dichloride 1 , was synthesized and its structure determined by X‐ray analysis. Density functional theory (DFT) calculations and X‐ray analysis suggest that complex 1 , when activated, possesses two available cis‐located sites needed for ethylene polymerization. Complex 1 /methylaluminoxane (MAO) in toluene or heptane solvent displayed very high ethylene polymerization activities (2 280–4 150 (kg PE)·(mol cat)^–1·h^–1) with high molecular weight values (M̄_v = 288 000–881 000) at 25–75°C under atmospheric pressure. The activity values displayed by complex 1 /MAO are some of the highest values exhibited by any titanium complex with no cyclopentadienyl (Cp) ligand(s). Alternatively, complex 1 /ⁱBu₃Al/Ph₃CB(C₆F₅)₄ in toluene solvent displayed high ethylene polymerization activities (190–670 (kg PE)· (mol cat)^–1·h^–1) with exceptionally high molecular weight values (M̄_v = 3 920 000–5 860 000) at 25–75°C under atmospheric pressure. The molecular weight values displayed by complex 1 /ⁱBu₃Al/Ph₃CB(C₆F₅)₄ are some of the largest values displayed by homogeneous olefin polymerization catalysts including the group 4 metallocenes. The high potential of complex 1 for ethylene polymerization has therefore been demonstrated.     

A Comparison between Two Methods for Assessing Heartbeat Perception

In this study two methods assessing heartbeat perception ability were compared. Subjects (N = 64) completed Schandry's (1981) mental tracking task and Störmer's (1988) heartbeat discrimination procedure (based on Whitehead, Drescher, Heiman, & Blackwell, 1977). In addition, subjects were tested on their ability to estimate the duration of time intervals. A high degree of correspondence was found between the two heartbeat perception tasks for the extreme groups of very good and very poor perceivers, but a low degree of correspondence emerged for the middle range of performance (overall r= .59, p<.001). Time estimation did not correlate significantly with either heartbeat detection procedure. Blood pressure measurements taken after the Schandry task and between Störmer test blocks showed that blood pressure amplitude was elevated among good perceivers on both heartbeat detection tasks.     

两种尿微量白蛋白测定方法的临床评价

对化学发光免疫测定法(CLIA)测定尿微量白蛋白的方法进行临床评估, 旨在为尿微量白蛋白测定选择一种简便快速, 准确和特异的方法.85例糖尿病患者及80名对照均留取8h尿样本, 用CLIA和RIA法测定, 并进行比较和分析精密度, 准确性、特异性及干扰因素.结果显示CLIA和RIA两种方法均具有很好的精密度, 批内CV小于4%, 批间CV小于6%,回收率在95.1%-105.9%,且测定不受样本中γ球蛋白的影响.CLIA的最低检测浓度为2.5μmol/L.两种方法测定的尿微量白蛋白值相关较好(Y=0.9974X-0.0291),r=0.9902.结论: CLIA和RIA尿微量白蛋白测定方法均具有高精密度, 高特异性, 两种方法的结果明显相关.然而, 与RIA比较CLIA简便、快速, 没有放射性污染, 且自动化程度高, 比较适合临床常规实验室应用.     

人血清布鲁氏菌病两种检测方法比较

目的 对比分析虎红平板凝集实验（RBPT）和试管凝集实验（SAT）两种检测方法的实验结果,为提高布鲁菌病实验室检测水平提供依据。方法 同时采用RBPT和SAT两种方法对2016年1月~2017年12月到锦州市疾控中心布病免疫门诊就诊的高危人群2873份人血清进行布鲁菌病实验室检测,对检测结果进行对比分析。结果 RBPT的阳性率为53.11%（1526/2873）,SAT的阳性率为52.41%（1506/2873）。RBPT与SAT总体阳性进行比较:敏感度为98.47%（1483/1506）,特异性为96.85%（1324/1367）,符合率为97.70%（2807/2873）,两种检测方法符合率很高;RBPT与SAT 1:100++及以上阳性者比较,符合率为72.96%（2096/2873）,两种检测方法符合率不高。结论 RBPT不能代替SAT用于布鲁菌病的临床诊断,对SAT凝集低滴度者应跟踪调查。     

两种方法检测促甲状腺受体抗体的比对研究

目的 探讨不同免疫分析系统检测促甲状腺受体抗体(TRAb)结果的可比性,以评估国产新产业化学发光法检测TRAb能否满足临床需求.方法 分别用新产业化学发光免疫分析(CLIA)仪和罗氏电化学发光免疫分析(ECLIA)仪测定TRAb,依据美国国家临床实验室标准化协会(NCCLS)EP9-A2文件,将ECLIA法作为参比方法,以CLIA法为试验方法,进行方法学比对试验.并应用Bland-Altman分析法评估其一致性.结果 定性判断CLIA法检测假阳性率、假阴性率和总符合率分别为0、11.8%和95%,Kappa值为0.896;两种方法定量检测TRAb结果差异无统计学意义,P=0.55,并在0~30IU/L具有较好的线性相关性, 其相关系数r=0.98, Passing-Bablock回归方程为Y=-0.04+1.06 X,截距A的系统差异95% CI为-0.16~0.09 ,斜率B的比例差异95% CI为0.97~1.12,线性度无明显偏差 (P=0.38),且Bland-Altman差异图显示,配对数据差值的平均值为-0.3IU/L,95%一致性界限为-3.9IU/L、4.5IU/L,在临床上可以接受.结论 国产新产业化学发光免疫分析(CLIA)仪TRAb检测结果可以满足临床需求.