Applications of a signal averager for neurophysiological investigations in clinical function laboratories using a general signal-processing unit

A general 'coherent signal averager' software package which can be run on a small laboratory computer is presented as an application of a new approach to medical instrumentation. The combination of the minicomputer, preprocessing hardware and the above-mentioned software yields a flexible multipurpose averaging system for electrophysiological signals. The possibilities of the system are discussed with reference to visual evoked potential measurements in a clinical function laboratory.     

EEG data acquisition and preprocessing by microcomputer satellite system

Recent development in computer technology allows already medium scale EEG data processing to be performed within the clinical neurophysiology department, if a fast minicomputer with adequate mass storage and graphical output facilities is used. Data acquisition, however, should be delegated to a microcomputer which also should take over as much preprocessing as possible. A system is presented, where one or several microcomputer-based satellite units perform analog-digital conversion, Fourier transformation (FFT), calculation of power spectra and crossproducts, as well as event related averaging or other preprocessing procedures. The units are connected to a fast central minicomputer, where a supervisor program loads the microprocessors with their programs, supervises their activity, receives preprocessed data and activates appropriate postprocessing programs to produce the final results.     

Evoked potential measurement and analysis on a small laboratory computer

A program is described for the collection and subsequent analysis of somatosensory evoked potentials using a LINC-8 computer. The program allows simple evoked-potentials analysis in centers where a small laboratory computer may be available but sophisticated instrumentation such as a computer of average transients is not available. This program provides an efficient method of easily obtaining information concerning the conduction pathways of the nervous system as well as the cerebral function; the program can be implemented on small laboratory computers which most hospitals currently own, without the associated cost or complexity of additional hardware in the laboratory. Combining utilization of a small laboratory computer with an easily programmable method provides an approach for evoked potential analysis which is well within the financial and technical scope of most neurophysiology laboratories.     

A lava rock-based biofilter for the treatment of alpha-pinene

Biofiltration is an emerging technology in the United States that utilizes microorganisms to biodegrade harmful contaminants in air to carbon dioxide and water. Biofiltration is not only more cost effective, but also more environmentally friendly than traditional technologies such as thermal oxidation and chemical scrubbing. The primary objectives of the study were to operate a lava rock-based laboratory biofiltration system for the removal of alpha-pinene. A consortium of microorganisms to be used as an inoculum was recovered that was able to use alpha-pinene as a sole source of carbon and energy. The removal of alpha-pinene from the laboratory system was monitored with a total hydrocarbon analyzer (THA). Based on THA analysis, elimination capacities as high as 100+g/m(3)/h were obtained in the laboratory biofilters. Removal efficiencies averaged 99% over a two year period. The solid support maintained a neutral pH with no buffer addition throughout the two year study and microbial levels were maintained between 10(6) and 10(7) colony forming units (CFU)/g of solid support. Bacillus and Rhodococcus species were found to be the majority of the microorganisms in the biofilters over a two year period. This is the first time an organism from either of these genera has been reported to utilize alpha-pinene as a sole source of carbon and energy. Overall, a preselected consortium of microorganisms coupled with lava rock as a biofilter solid support achieved extended alpha-pinene treatment levels that far exceed previously published values.     

基于基因表达变异性的通路富集方法研究

当前的通路富集方法主要是基于基因的表达差异,很少有方法从通路变异性(方差)角度对其富集分析．我们注意到用合适的统计量描述通路的变异性时,在疾病表型下一些通路的变异性有明显的上升或者下降．因此本研究假设：通路变异性程度在不同表型中存在差异．本文设计了14种描述通路变异性的统计量与检验方法,检测不同表型下变异性有差异的通路即富集通路,并将富集结果与文献检索结果进行比较,同时,分析不同芯片预处理方法对数据和结果的影响．研究结果表明：5种预处理方法中,多阵列对数健壮算法(RMA)是数据预处理的最优方法;不同表型下通路的变异性程度存在差异;根据文献检索的通路结果,14种基于变异性的通路富集方法中,以通路中各基因欧氏距离的方差做统计量进行permutation检验(方法11)能有效识别显著通路,其富集结果优于基因集富集分析(GSEA)．综上所述,基于通路变异性的通路富集策略具有可行性,不仅对通路富集分析有一定的理论指导意义,而且为人类疾病研究提供新的视角．     

A computer system for neurosurgical patient monitoring.

The variables monitored in intensive care units are generally late indicators of neurologic deterioration. A system based on a LINC-8 computer was therefore developed for on-line monitoring of evoked potentials, electroencephalography (EEG), and transcranial and transthoracic impedances as well as conventional parameters. Somatosensory evoked potentials are recorded at either 30 min or 1 h intervals. One minute epochs of EEG are analyzed every 10 min using a peak-detection algorithm. Impedances and conventional parameters are also monitored at 10 min intervals. In a study of 50 patients, the technical feasibility of this type of monitoring with a small laboratory computer has been demonstrated. In some instances, evoked potentials and EEG show changes prior to detectable neurologic changes. The study suggests that this type of monitoring can provide a valuable adjunct for evaluation of physiologic function in neurosurgical intensive care.     

Differences in acquired knowledge and attitudes achieved with traditional,computer-supported and virtual laboratory biology laboratory exercises

This paper reports on the contribution to biological knowledge of three different laboratory technologies and also endeavours to discover which technology students prefer the most. To examine differences in knowledge gained and learners’ preferences for different technologies in biology laboratory work, we prepared three variants (triplets) of three laboratory exercises. Each laboratory variant in a triplet was prepared as a classical laboratory work, a computer-supported laboratory and an interactive virtual simulation. A group of 670 learners at a school for all genders, aged between 11 and 15 (6th to 9th grade) of lower secondary Slovenia schools performed three well-known and easy to perform laboratory exercises that are included in their curriculum (‘Gas Exchange’, ‘Activity of Yeast’ and ‘Heart Rate’) as a traditional, computer-supported laboratory and computer simulation. The data indicated that there were no statistical differences pertaining to students’ knowledge gain between these laboratory technologies with regard to grade, gender or school score. In this study, students preferred a computer-supported laboratory mostly followed by a classic laboratory with a computer simulation in last place, regardless of students’ grade, gender or academic scores.     

Sexual behaviour of Anastrepha obliqua (Macquart) (Diptera: Tephritidae): Do laboratory domestication conditions influence male courtship behaviour?

We analysed the influence of laboratory domestication, under relaxed conditions, on the courtship behaviour of the fruit fly species Anastrepha obliqua, an important agricultural pest. We compared the temporal patterns of pheromone emission (Calling behaviour) and the frequencies and sequences of the courtship behavioural units of males of a laboratory lineage and a wild lineage. Our results indicated similarities in the temporal behavioural patterns of calling, the durations of their behavioural sequences, the final sequences of courtships resulting in copulation, of wild and laboratory males. Differences, however, were observed between the two populations in terms of the frequencies of the behavioural units executed and the initial sequence of courtship. Differences were noted in the presence or absence of some behavioural units within the courtship behavioural repertoires of the laboratory-reared and wild. The wild males did not show units such as Alignment, Contact, Fighting and Marking Leaf that were observed in the laboratory males' courtship behaviour under laboratory conditions; on the other hand, laboratory males did not show the Abdominal movements and Oscillation observed in the courtship behaviour of wild males. The rearing of A. obliqua males under relaxed conditions in the laboratory provides an environment adequate for the preservation of behavioural characteristics relevant to the successful mating, such as Movement, Arrowhead 1, and Attempt, and in temporal patterns of pheromone emission.     

Performance of a membrane-dialysis bioreactor with a radial-flow fixed bed for the cultivation of a hybridoma cell line

A bioreactor system for the continuous cultivation of animal cells with a high potential for scale-up is presented. This reactor system consists of radial-flow fixed-bed units coupled with a dialysis module. The dialysis membrane enables the supply of low-molecular-weight nutrients and removal of toxic metabolites, while high-molecular-weight nutrients and products (e.g. monoclonal antibodies) are retained and accumulated. This concept was investigated on the laboratory scale in a bioreactor with an integrated dialysis membrane. The efficiency of the reactor system and the reproducibility of the cell activity (hybridoma cells) under certain process conditions could be demonstrated in fermentations up to 77 days. Based on model calculations, an optimized fermentation strategy was formulated and experimentally confirmed. Compared to chemostat cultures with suspended cells, a ten-times higher mAb concentration (383 mgl⁻¹) could be obtained. The highest volumetric specific mAb production rate determined was 6.1 mg mAb (1 fixed bed)⁻¹ h⁻¹.     

Rapid affinity chromatographic purification of human lung and kidney angiotensin-converting enzyme with the novel N-carboxyalkyl dipeptide inhibitor N-[1(S)-carboxy-5-aminopentyl]glycylglycine

Human angiotensin-converting enzyme has been purified, in a single chromatographic step, using a novel N-carboxyalkyl dipeptide CA-GlyGly (N-[1(S)-carboxy-5-aminopentyl]glycylglycine) synthesised in our laboratory. CA-GlyGly is a weak competitive inhibitor, Ki = 0.18 mM, and its inhibitory profile is markedly pH-dependent. Human lung and kidney angiotensin-converting enzyme were solubilised with Triton X-100 and after ammonium sulphate fractionation the crude extract was applied to a column containing CA-GlyGly coupled to agarose via a 2.8 nm spacer group. Electrophoretically pure human angiotensin-converting enzyme could be eluted by raising the pH of the chromatography buffer from 7.50 to 9.50. The specific activity of human angiotensin-converting enzyme purified from lung was 104 units/mg, while that from kidney was 88 units/mg. Molecular weight for both enzymes was estimated to be 160,000. The Km with respect to hippuryl-L-histidyl-L-leucine was 1.9 mM in the case of lung angiotensin-converting enzyme and 1.7 mM in that of kidney angiotensin-converting enzyme, while for the substrate angiotensin I Km values were 62 microM and 76 microM, respectively. Hydrolysis of either substrate was chloride-dependent and both enzymes were strongly inhibited by captopril.     

Role of modern radiological investigations in obstructive uropathy.

Obstructive uropathy in its various forms accounts for much of the work load in urological units and general hospitals. Until recently, laboratory tests and excretion urography were the only procedures available for its assessment. The past few years have seen the development and refinement of ultrasound, examination by computer tomography, nuclear medicine, antegrade pyelography, and perfusion pressure flow studies. This paper examines the particular qualities of these modern procedures and their role in the clinical assessment of the obstructed urinary tract.     

Interaction of coupled nonlinear oscillators having different intrinsic resting levels

The interaction among coupled oscillators is governed by oscillator properties (intrinsic frequency and amplitude) and coupling mechanisms. This study considers another oscillator property, the intrinsic resting level, and evaluates its role in governing oscillator interactions. The results of computer experiments on a chain of either three or five bidirectionally coupled nonlinear oscillators, suggest that an intrinsic resting level gradient, if present, is one of the factors governing the interaction between coupled oscillators. If there is no intrinsic frequency gradient, then an intrinsic resting level gradient is sufficient to produce many features of interaction among coupled oscillators. If both intrinsic frequency and intrinsic resting level gradients are present, then both of them determine the manner in which the coupled oscillators interact with each other.     

An introduction to hybrid computers and their application to optimization problems

The author, who is Secretary of the Analog Section of the British Computer Society, describes the way in which some of the logic components of a parallel logic analog computer function, and goes on to discuss the use of such a computer in optimization problems, as for instance in finding the best estimates of the parameters on compartmentation analysis of isotopic tracer experiments. The increased power which is gained when an analog computer is coupled to (hybridized with) a general purpose digital computer is then discussed, as shown for example in the increased speed of random-search optimization techniques when an analog computer is used to integrate the differential equations, or the improvement in steepest ascent methods when the parallel logic can be used to keep the hill-climb path continuously on the line of steepest ascent. Finally, the use of a hybrid computer in solving partial differential equations is briefly outlined.     

Fourier analysis of the nuclear and cytoplasmic shapes of living two-cell murine embryos

Living two-cell mouse embryos were flushed out from the oviduct 17, 24 and 36 hours after fertilization in order to obtain cells in the G1S, early G2 and late G2 phases of the second cell cycle. The nuclei of the living cells were stained with Hoechst 33342. The coordinates of the contour shapes of the entire cells (cellular contours) were registered by contour image processing with a TV camera coupled with a computer; the contours of the nuclei were computed by means of a digitizer coupled with the computer. Fourier analysis of the cellular and nuclear contours revealed systematic modifications in the folding of the cells and nuclei in the course of the murine second cell cycle. The progression of cells through the second cell cycle was correlated with an increasing diversification of cellular and nuclear shape, with the diversification being much more pronounced in the nuclear shapes.     

Computer simulation of the phosphorylation cascade controlling bacterial chemotaxis.

We have developed a computer program that simulates the intracellular reactions mediating the rapid (nonadaptive) chemotactic response of Escherichia coli bacteria to the attractant aspartate and the repellent Ni2+ ions. The model is built from modular units representing the molecular components involved, which are each assigned a known value of intracellular concentration and enzymatic rate constant wherever possible. The components are linked into a network of coupled biochemical reactions based on a compilation of widely accepted mechanisms but incorporating several novel features. The computer motor shows the same pattern of runs, tumbles and pauses seen in actual bacteria and responds in the same way as living bacteria to sudden changes in concentration of aspartate or Ni2+. The simulated network accurately reproduces the phenotype of more than 30 mutants in which components of the chemotactic pathway are deleted and/or expressed in excess amounts and shows a rapidity of response to a step change in aspartate concentration similar to living bacteria. Discrepancies between the simulation and real bacteria in the phenotype of certain mutants and in the gain of the chemotactic response to aspartate suggest the existence of additional as yet unidentified interactions in the in vivo signal processing pathway.     

Optimizing preprocessing and analysis pipelines for single-subject fMRI: 2. Interactions with ICA, PCA, task contrast and inter-subject heterogeneity

A variety of preprocessing techniques are available to correct subject-dependant artifacts in fMRI, caused by head motion and physiological noise. Although it has been established that the chosen preprocessing steps (or "pipeline") may significantly affect fMRI results, it is not well understood how preprocessing choices interact with other parts of the fMRI experimental design. In this study, we examine how two experimental factors interact with preprocessing: between-subject heterogeneity, and strength of task contrast. Two levels of cognitive contrast were examined in an fMRI adaptation of the Trail-Making Test, with data from young, healthy adults. The importance of standard preprocessing with motion correction, physiological noise correction, motion parameter regression and temporal detrending were examined for the two task contrasts. We also tested subspace estimation using Principal Component Analysis (PCA), and Independent Component Analysis (ICA). Results were obtained for Penalized Discriminant Analysis, and model performance quantified with reproducibility (R) and prediction metrics (P). Simulation methods were also used to test for potential biases from individual-subject optimization. Our results demonstrate that (1) individual pipeline optimization is not significantly more biased than fixed preprocessing. In addition, (2) when applying a fixed pipeline across all subjects, the task contrast significantly affects pipeline performance; in particular, the effects of PCA and ICA models vary with contrast, and are not by themselves optimal preprocessing steps. Also, (3) selecting the optimal pipeline for each subject improves within-subject (P,R) and between-subject overlap, with the weaker cognitive contrast being more sensitive to pipeline optimization. These results demonstrate that sensitivity of fMRI results is influenced not only by preprocessing choices, but also by interactions with other experimental design factors. This paper outlines a quantitative procedure to denoise data that would otherwise be discarded due to artifact; this is particularly relevant for weak signal contrasts in single-subject, small-sample and clinical datasets.     

Time-locked and phase-locked features of P300 event-related potentials (ERPs) for brain–computer interface speller

The brain–computer interface P300 speller is aimed to help those patients unable to activate muscles to spell words by utilizing their brain activity. However, a problem associated with the use of this brain–computer interface paradigm is the generation mechanics of P300 related to responses to visual stimuli. Herein, we investigated the event-related potential (ERP) response for the P300-based brain–computer interface speller. A signal preprocessing method integrated coherent average, principal component analysis (PCA) and independent component analysis (ICA) to reduce the dimensions and noise in the raw data. The time–frequency analysis was based on wavelet and two characteristic parameters of event-related spectral perturbation (ERSP) and inter-trial coherence (ITC) were computed to indicate the evoked response (time-locked) and phase reset (phase-locked) activity, respectively. Results demonstrated that the proposed method was valid for the time-locked and phase-locked feature extraction and both the evoked response and phase reset contributed to the genesis of the P300 signal. These electrophysiological responses characteristics of ERPs would be used for BCI P300 speller design and its signal processing strategies.     

Computer-assisted method for multi-exponential curve fitting for determining cerebral blood flow.

A computer program has been developed for use in determining cerebral blood flow using an inert radioactive gas. The basic algorithm involves the determination of multiple exponential coefficients from the complex concentration-time function. The exponential coefficients are determined by 'peeling' away slower exponentials complex function one at a time. The procedure involves the use of a small laboratory computer in the interactive graphics mode. The method is currently in use analyzing data in a cerebral vascular research laboratory.     

An Automated,Adaptive Framework for Optimizing Preprocessing Pipelines in Task-Based Functional MRI

BOLD fMRI is sensitive to blood-oxygenation changes correlated with brain function; however, it is limited by relatively weak signal and significant noise confounds. Many preprocessing algorithms have been developed to control noise and improve signal detection in fMRI. Although the chosen set of preprocessing and analysis steps (the “pipeline”) significantly affects signal detection, pipelines are rarely quantitatively validated in the neuroimaging literature, due to complex preprocessing interactions. This paper outlines and validates an adaptive resampling framework for evaluating and optimizing preprocessing choices by optimizing data-driven metrics of task prediction and spatial reproducibility. Compared to standard “fixed” preprocessing pipelines, this optimization approach significantly improves independent validation measures of within-subject test-retest, and between-subject activation overlap, and behavioural prediction accuracy. We demonstrate that preprocessing choices function as implicit model regularizers, and that improvements due to pipeline optimization generalize across a range of simple to complex experimental tasks and analysis models. Results are shown for brief scanning sessions (<3 minutes each), demonstrating that with pipeline optimization, it is possible to obtain reliable results and brain-behaviour correlations in relatively small datasets.