Hybrid filtering of feed stream noise from oscillating yeast cultures by combined Kalman and neural network configurations

Large continuous flow bioreactors are often under the influence of noise in the feed stream(s). Prior removal of noise is done by filters based either on specific algorithms or on artificial intelligence. Neither method is perfect. Hybrid filters combine both methods and thereby capitalize on their strengths while minimizing their weaknesses. In this study, a number of hybrid models have been compared for their ability to recover nearly noise-free stable oscillations of continuous flow Saccharomyces cerevisiae cultures from aberrant behavior caused by noise in the feed stream. Each hybrid filter had a different neural network in conjunction with an extended Kalman filter (EKF). The choice of the best configuration depended on the performance index. All hybrid filters were superior to both the EKF and purely neural filters. Along with previous studies of monotonic fermentations, the present results establish the suitability of hybrid neural filters for noise-affected bioreactors. IMTECH communication no.045/2006.     

On the performances of noise filters in the restoration of oscillatory behavior in continuous yeast cultures

Continuous flow microbial fermentations under industrial conditions are subject to the influx of noise, mainly through the feed stream. Noise upsets the normal deterministic behavior. For continuous cultures of Saccharomyces cerevisiae exhibiting oscillatory responses, four kinds of commonly used noise filters, three algorithmic and one neural, have been compared for their ability to restore noise-free oscillations. An auto-associative neural filter was the best, similar to earlier observations for other organisms under non-oscillatory conditions. This enhances the general applicability of neural filters for industrial scale fermentations.     

Enhancing oscillations in intracranial electrophysiological recordings with data-driven spatial filters

In invasive electrophysiological recordings, a variety of neural oscillations can be detected across the cortex, with overlap in space and time. This overlap complicates measurement of neural oscillations using standard referencing schemes, like common average or bipolar referencing. Here, we illustrate the effects of spatial mixing on measuring neural oscillations in invasive electrophysiological recordings and demonstrate the benefits of using data-driven referencing schemes in order to improve measurement of neural oscillations. We discuss referencing as the application of a spatial filter. Spatio-spectral decomposition is used to estimate data-driven spatial filters, a computationally fast method which specifically enhances signal-to-noise ratio for oscillations in a frequency band of interest. We show that application of these data-driven spatial filters has benefits for data exploration, investigation of temporal dynamics and assessment of peak frequencies of neural oscillations. We demonstrate multiple use cases, exploring between-participant variability in presence of oscillations, spatial spread and waveform shape of different rhythms as well as narrowband noise removal with the aid of spatial filters. We find high between-participant variability in the presence of neural oscillations, a large variation in spatial spread of individual rhythms and many non-sinusoidal rhythms across the cortex. Improved measurement of cortical rhythms will yield better conditions for establishing links between cortical activity and behavior, as well as bridging scales between the invasive intracranial measurements and noninvasive macroscale scalp measurements.     

一种滤除医学影像噪声的混合滤波算法

目的：医学影像在获取、存储、传输过程中会不同程度地受到噪声污染,这极大影像了其在临床诊疗中的应用。为了有效地滤除医学影像噪声,提出了一种混合滤波算法。方法：该算法首先将含有高斯和椒盐噪声的图像进行形态学开运算,然后对开运算后的图像进行二维小波分解,得到高频和低频小波分解系数。保留低频系数不变,将高频系数经过维纳滤波器进行滤波,最后进行小波系数重构。结果：采用该混合滤波算法、小波阚值去噪、中值滤波、维纳滤波分别对含有混合噪声的医学影像分别进行滤除噪声处理,该滤波算法去噪后影像的PSNR值明显高于其他三种方法。结论：该混合滤波算法是一种较为有效的医学影像噪声滤除方法。     

Selective regulation of cellular processes via protein cascades acting as band-pass filters for time-limited oscillations

We show by mathematical modelling that a two-level protein cascade can act as a band-pass filter for time-limited oscillations. The band-pass filters are then combined into a network of three-level signalling cascades that by filtering the frequency of time-limited oscillations selectively switches cellular processes on and off. The physiological relevance for the selective regulation of cellular processes is demonstrated for the case of regulation by time-limited calcium oscillations.     

Median‐modified Wiener filter provides efficient denoising,preserving spot edge and morphology in 2‐DE image processing

Denoising is a fundamental early stage in 2‐DE image analysis strongly influencing spot detection or pixel‐based methods. A novel nonlinear adaptive spatial filter (median‐modified Wiener filter, MMWF), is here compared with five well‐established denoising techniques (Median, Wiener, Gaussian, and Polynomial‐Savitzky–Golay filters; wavelet denoising) to suggest, by means of fuzzy sets evaluation, the best denoising approach to use in practice. Although median filter and wavelet achieved the best performance in spike and Gaussian denoising respectively, they are unsuitable for contemporary removal of different types of noise, because their best setting is noise‐dependent. Vice versa, MMWF that arrived second in each single denoising category, was evaluated as the best filter for global denoising, being its best setting invariant of the type of noise. In addition, median filter eroded the edge of isolated spots and filled the space between close‐set spots, whereas MMWF because of a novel filter effect (drop‐off‐effect) does not suffer from erosion problem, preserves the morphology of close‐set spots, and avoids spot and spike fuzzyfication, an aberration encountered for Wiener filter. In our tests, MMWF was assessed as the best choice when the goal is to minimize spot edge aberrations while removing spike and Gaussian noise.     

Leveraging mathematical models for optimizing filter utility at manufacturing scale

In the production of biopharmaceuticals depth filters followed by sterile filters are often employed to remove residual cell debris present in the feed stream. In the back drop of a global pandemic, supply chains associated with the production of biopharmaceuticals have been constrained. These constraints have limited the available amount of depth filters for the manufacture of biologics. This has placed manufacturing facilities in a difficult position having to choose between running processes with reduced number of depth filters and risking a failed batch or the prospect of plants going into temporary shutdown until the depth filter resources are replenished. This communication describes a modeling based method that leverages manufacturing scale filtration data to predict the depth filter performance with a reduced number of filters and an increased operational flux. This method can be used to quantify the acceptable level of area reduction before which the filtration process performance is affected. This enables facilities to manage their filter inventory avoiding potential plant shutdowns and reduces the risks of negative depth filter performance.     

Elimination of biological and physical artifacts in abdomen and brain computed tomography procedures using filtering techniques

IntroductionMedical images are usually affected by biological and physical artifacts or noise, which reduces image quality and hence poses difficulties in visual analysis, interpretation and thus requires higher doses and increased radiographs repetition rate.ObjectivesThis study aims at assessing image quality during CT abdomen and brain examinations using filtering techniques as well as estimating the radiogenic risk associated with CT abdomen and brain examinations.Materials and MethodsThe data were collected from the Radiology Department at Royal Care International (RCI) Hospital, Khartoum, Sudan. The study included 100 abdominal CT images and 100 brain CT images selected from adult patients. Filters applied are namely: Mean filter, Gaussian filter, Median filter and Minimum filter. In this study, image quality after denoising is measured based on the Mean Squared Error (MSE), Peak Signal-to-Noise Ratio (PSNR), and the Structural Similarity Index Metric (SSIM).ResultsThe results show that the images quality parameters become higher after applications of filters. Median filter showed improved image quality as interpreted by the measured parameters: PSNR and SSIM, and it is thus considered as a better filter for removing the noise from all other applied filters.DiscussionThe noise removed by the different filters applied to the CT images resulted in enhancing high quality images thereby effectively revealing the important details of the images without increasing the patients’ risks from higher doses.ConclusionsFiltering and image reconstruction techniques not only reduce the dose and thus the radiation risks, but also enhances high quality imaging which allows better diagnosis.     

Design and responses of Butterworth and critically damped digital filters

For many years the Butterworth lowpass filter has been used to smooth many kinds of biomechanical data, despite the fact that it is underdamped and therefore overshoots and/or undershoots data during rapid transitions. A comparison of the conventional Butterworth filter with a critically damped filter shows that the critically damped filter not only removes the undershooting and overshooting, but has a superior rise time during rapid transitions. While analog filters always create phase distortion, both the critically damped and Butterworth filters can be modified to become zero-lag filters when the data are processed in both the forward and reverse directions. In such cases little improvement is realized by applying multiple passes. The Butterworth filter has superior ‘roll-off’ (attenuation of noise above the cutoff frequency) than the critically damped filter, but by increasing the number of passes of the critically damped filter the same ‘roll-off’ can be achieved. In summary, the critically damped filter was shown to have superior performance in the time domain than the Butterworth filter, but for data that need to be double differentiated (e.g. displacement data) the Butterworth filter may still be the better choice.     

Real-time technique for conversion of skin temperature into skin blood flow: human skin as a low-pass filter for thermal waves

Monitoring of skin blood flow oscillations related with mechanical activity of vessels is a very useful modality during diagnosis of peripheral hemodynamic disorders. In this study, we developed a new model and technique for real-time conversion of skin temperature into skin blood flow oscillations, and vice versa. The technique is based on the analogy between the thermal properties of the human skin and electrical properties of the special low-pass filter. Analytical and approximated impulse response functions for the low- and high-pass filters are presented. The general algorithm for the reversible conversion of temperature into blood flow is described. The proposed technique was verified using simulated or experimental data of cold stress, deep inspiratory gasp, and post-occlusive reactive hyperaemia tests. The implementation of the described technique will enable to turn a temperature sensor into a blood flow sensor.     

Fractal characterisation of the effect of noise on biological oscillations: The biosynthesis of ethanol

Summary Biological reactions which interact with their environment are subject to the influx of noise. Noise introduces randomness and imparts fractal character to the deterministic behavior. A methodology is proposed to compute the fractal dimensions of such reactions. It is applied to the continuous culture of Zymomonas mobilis to produce ethanol. Results show that noise can change the nature of oscillations or induce oscillations in a stationary state. The noise-induced oscillations are aperiodic and fractal in nature. The variation of the fractal dimension with dilution rate and the initial ethanol concentration is presented and discussed in terms of the interaction between process kinetics and the incoming noise.     

The affinity of [3H]quinuclidinyl benzilate and some other radioligands for glass microfiber and cellulose filters in some common liquid scintillation solvents

The optimum conditions for measuring radioactivity in the filtration assay of muscarinic cholinoceptors with tritiated quinuclidinyl benzilate are to use Whatman GF/B filters and to add a simple toluene scintillant to them while they are still damp. Practically all the radioactive material is then slowly extracted into the scintillant and high counting efficiencies are obtained after 24 h. Dried filters, or dry filters in control experiments in the absence of receptor, adsorb much of the radioactivity with a 30% reduction in counting efficiency. Other scintillants were able to extract the radioactive material from dry filters, but were generally not preferable to toluene. The GF/B filters performed better than other glass microfiber and cellulose filters in terms of retention of receptor-bound ligand, rapid filtration rates, and low filter blanks. Toluene is unsuitable as a scintillant with GF/B filters for some other radioligands examined.     

Depth filter material process interaction in the harvest of mammalian cells

Upstream advances have led to increased mAb titers above 5 g/L in 14-day fed-batch cultures. This is accompanied by higher cell densities and process-related impurities such as DNA and Host Cell Protein (HCP), which have caused challenges for downstream operations. Depth filtration remains a popular choice for harvesting CHO cell culture, and there is interest in utilizing these to remove process-related impurities at the harvest stage. Operation of the harvest stage has also been shown to affect the performance of the Protein A chromatography step. In addition, manufacturers are looking to move away from natural materials such as cellulose and Diatomaceous Earth (DE) for better filter consistency and security of supply. Therefore, there is an increased need for further understanding and knowledge of depth filtration. This study investigates the effect of depth filter material and loading on the Protein A resin lifetime with an industrially relevant high cell density feed material (40 million cells/ml). It focuses on the retention of process-related impurities such as DNA and HCP through breakthrough studies and a novel confocal microscopy method for imaging foulant in-situ. An increase in loading of the primary-synthetic filter by a third, led to earlier DNA breakthrough in the secondary filter, with DNA concentration at a throughput of 50 L/m² being more than double. Confocal imaging of the depth filters showed that the foulant was pushed forward into the filter structure with higher loading. The additional two layers in the primary-synthetic filter led to better pressure profiles in both primary and secondary filters but did not help to retain HCP or DNA. Reduced filtrate clarity, as measured by OD600, was 1.6 fold lower in the final filtrate where a synthetic filter train was used. This was also associated with precipitation in the Protein A column feed. Confocal imaging of resin after 100 cycles showed that DNA build-up around the outside of the bead was associated with synthetic filter trains, leading to potential mass transfer problems.     

Experimental pitfalls in evaluating vectorial protein secretion in vitro; Sertoli cell secretion of androgen-binding protein and transferrin in two-compartment culture chambers

Summary We examined the influence of various Millipore filter pretreatments on the amounts of androgen-binding protein (ABP) and transferrin (Trf) found in the outer (OC) and inner (IC) compartment of two-compartment Sertoli cell (Sc) cultures. When Sc were cultured on untreated Millipore filters, less than 10% of ABP was found in OC during 3 initial culture days compared to similar cultures on pretreated filters. Most of the glycoprotein was shown to be bound by the filters. Pretreatment of Millipore filters with 5% bovine serum albumin (BSA) or 2% fetal bovine serum (FBS) maximally saturated the nonspecific protein-binding sites resulting in OC:IC ratio of ABP similar to that found in cultures on polycarbonate membranes, which exhibit very low protein-binding capacity. In contrast to ABP, about 40% of Trf was bound by the Millipore filter on Day 1, with only trace amounts bound thereafer. These differences were due to much higher secretion rate of Trf than ABP, resulting in a relatively smaller fraction of Trf bound to the filter. Again, the nonspecific binding of Trf was greatly reduced by filter pretreatment with 5% BSA or 2% FBS. It is concluded that complete saturation of protein-binding sites of cellulose ester supports is necessary for reliable evaluation of vectorial protein secretion by Sc and other polarized epithelial cells maintained in this type of culture. The implications of partial saturation of protein-binding sites of culture support in interpreting experimental results are discussed. This work was supported in part by grant HD-17802 (A.S.) from the National Institutes of Health, Bethesda, MD.     

折流曝气生物滤池中污染物与微生物沿程变化规律

BBAF滤池是一种新型曝气生物滤池,为考察其中污染物与微生物沿程变化规律,分析了不同厚度滤层对有机物、氨氮等污染物的去除效果,MPN法测定了具有代表性滤层厚度处的异养菌和硝化菌数量;通过镜检观察研究了BBAF滤池中微生物种群的沿程分布特点。研究表明:BBAF滤池中COD浓度随滤层厚度增加逐渐降低,前4个单池对COD有很好的去除效果,但对氨氮的去除作用较弱,其中的微生物以异养菌为主;第5、6、7单池中,有机负荷较低,促进了硝化菌增殖,提高了硝化效果。BBAF滤池的各单池之间存在浓度梯度,使不同滤层中形成了微生物优势种属,有利于BBAF滤池达到最佳运行效果。     

Non-linear biological responses to environmental noise affect population extinction risk

Non-linearities are commonly observed in the responses of organisms to environment. They potentially modify the qualitative and quantitative properties of population dynamics. We studied how non-linear responses to environment, or "noise filters", influence population variability and extinction risk by introducing coloured noise to the growth rate in the Hassell single-species model. The consequences of noise filtering were analysed by comparing the model dynamics with linearly filtered and non-linearly filtered noise that have the same mean. Three biologically plausible filters we used: saturating, unimodal optimum type, and sigmoid responses.
Filtering can either decrease or increase population variability when compared to linear noise response. The effect of noise filtering on variability is most pronounced with stable population dynamics and the outcome depends on the filter type, population growth rate, and noise colour.
Non-linear noise filtering predominantly increases extinction risks when population growth rate is low (R<5). As an exception, saturating filter has a window of decreased risk at very low growth rate and reddened environment. In the unstable range of the dynamics (15These results suggest that accounting for the non-linear responses to environment should be considered when estimating extinction risks and population variability. Moreover, the non-linear responses make noise colour a more important factor in these analyses.     

A mathematical model for the leukocyte filtration process

Leukocyte filters are applied clinically to remove leukocytes from blood. In order to optimize leukocyte filters, a mathematical model to describe the leukocyte filtration process was developed by modification of a general theoretical model for depth filtration. The model presented here can be used to predict the time-dependent leukocyte filtration as a function of cell-cell interaction in the filter, filter efficiency, filter capacity, filter dimensions, and leukocyte concentration in the suspension applied to the filter. The results of different leukocyte filtration experiments previously reported in the literature could be well described by the present model. (c) 1995 John Wiley & Sons, Inc.     

Improving wastewater effluent filtration by changing flow regimes—Investigations in two cold climate pilot scale systems

Two pilot-scale experimental filter systems (FSs) filled with light-weight aggregates (LWA) or crushed limestone (CL) and operated under different flow regimes were established during the summer of 2005. The main objective of the study was to compare continuous-flow hybrid CL and LWA filters and batch-operated LWA filters in order to determine optimal loading, design parameters, management schemes and operational regimes for LWA-based FSs in cold climate conditions for the secondary treatment of domestic wastewater. With higher re-circulation rates of treated water, purification efficiency increased in terms of most water quality indicators in both types of filter systems. In the batch-operated FS the highest purification efficiencies of 96% and 51% for BOD₇ and N_tot, respectively, were achieved when the re-circulation rate of 200% was applied. In the continuous-flow FS the highest purification efficiencies of 99% and 81% for BOD₇ and N_tot, respectively, were achieved when the re-circulation rate up to 300% was applied. In order to achieve effective organic matter removal, nitrification/denitrification and TSS removal, the re-circulation rate must be from 100% to 300% of the inflowing wastewater. Both FS designs, the continuous-flow hybrid systems and the batch-operated filters, are suitable for the secondary treatment of domestic wastewater in cold climate conditions.     

WaveletQuant,an improved quantification software based on wavelet signal threshold de-noising for labeled quantitative proteomic analysis

Background  

Quantitative proteomics technologies have been developed to comprehensively identify and quantify proteins in two or more complex samples. Quantitative proteomics based on differential stable isotope labeling is one of the proteomics quantification technologies. Mass spectrometric data generated for peptide quantification are often noisy, and peak detection and definition require various smoothing filters to remove noise in order to achieve accurate peptide quantification. Many traditional smoothing filters, such as the moving average filter, Savitzky-Golay filter and Gaussian filter, have been used to reduce noise in MS peaks. However, limitations of these filtering approaches often result in inaccurate peptide quantification. Here we present the WaveletQuant program, based on wavelet theory, for better or alternative MS-based proteomic quantification.     

Free intracellular amino acid pools during autonomous oscillations in Saccharomyces cerevisiae

In the present work dynamic changes of free intracellular amino acid pools during autonomous oscillations of Saccharomyces cerevisiae were quantified in glucose-limited continuous cultivations. At a dilution rate of D = 0.22 h(-1) cyclic changes with a period of 120 min were found for many variables such as carbon dioxide production rate, dissolved oxygen, pH, biomass content, and various metabolite concentrations. On the basis of the observed dynamic patterns, free intracellular amino acids were classified to show oscillatory, stationary, or chaotic behavior. Amino acid pools such as serine, alanine, valine, leucine, or lysine were subjected to clear oscillations with a frequency of 120 min, identical to that of other described cultivation variables, indicating that there is a direct correlation between the periodic changes of amino acid concentrations and the metabolic oscillations on the cellular level. The oscillations of these amino acids were unequally phase-delayed and had different amplitudes of oscillation. Accordingly, they exhibited different patterns in phase plane plots vs. intracellular trehalose. Despite the complex and marked metabolic changes during oscillation, selected intracellular amino acids such as histidine, threonine, isoleucine, or arginine remained about constant. Concentrations of glutamate and glutamine showed a chaotic behavior. However, the ratio of glutamate to glutamine concentration was found to be oscillatory, with a period of 60 min and a corresponding figure eight-shaped pattern in a plot vs. trehalose concentration. Considering the described diversity, it can be concluded that the observed periodic changes are neither just the consequence of low or high rates of protein biosynthesis/degradation nor correlated to changing cell volumes during oscillation. The ratio between doubling time (189 min) and period of oscillation of intracellular amino acids (120 min) was 1:6. The fact that there is a close relationship between doubling time and period of oscillation underlines that the described autonomous oscillations are cell-cycle-associated.