Powerful Exact Unconditional Tests for Agreement between Two Raters with Binary Endpoints

Asymptotic and exact conditional approaches have often been used for testing agreement between two raters with binary outcomes. The exact conditional approach is guaranteed to respect the test size as compared to the traditionally used asymptotic approach based on the standardized Cohen''s kappa coefficient. An alternative to the conditional approach is an unconditional strategy which relaxes the restriction of fixed marginal totals as in the conditional approach. Three exact unconditional hypothesis testing procedures are considered in this article: an approach based on maximization, an approach based on the conditional p-value and maximization, and an approach based on estimation and maximization. We compared these testing procedures based on the commonly used Cohen''s kappa with regards to test size and power. We recommend the following two exact approaches for use in practice due to power advantages: the approach based on conditional p-value and maximization and the approach based on estimation and maximization.     

Local fractal dimension based ECG arrhythmia classification

We propose a local fractal dimension based nearest neighbor classifier for ECG based classification of arrhythmia. Local fractal dimension (LFD) at each sample point of the ECG waveform is taken as the feature. A nearest neighbor algorithm in the feature space is used to find the class of the test ECG beat. The nearest neighbor is found based on the RR-interval-information-biased Euclidean distance, proposed in the current work. Based on the two algorithms used for estimating the LFD, two classification algorithms are validated in the current work, viz. variance based fractal dimension estimation based nearest neighbor classifier and power spectral density based fractal dimension estimation based nearest neighbor classifier. Their performances are evaluated based on various figures of merit. MIT-BIH (Massachusetts Institute of Technology - Boston’s Beth Israel Hospital) Arrhythmia dataset has been used to validate the algorithms. Along with showing good performance against all the figures of merit, the proposed algorithms also proved to be patient independent in the sense that the performance is good even when the test ECG signal is from a patient whose ECG is not present in the training ECG dataset.     

群落结构复杂性的测度方法研究进展

该文对群落结构复杂性的测度方法的研究进展状况进行了综述。根据测度方法建立的方法基础,将现有的方法分成3类:基于多样性的复杂性测度、基于计算复杂性的测度和基于几何学特征的复杂性测度。对每类测度方法进行了介绍,对其优缺点进行了评述。同时提出了未来研究中应给予重视的问题。结果表明,现有群落结构复杂性的测度方法普遍存在区分能力差的问题,对于基于多样性的结构复杂性测度,目前还缺乏确定各测度属性权重的客观方法;现有的一些基于计算复杂性的结构测度与多样性指标关系过于密切,还不完善,同时其生态学的意义还不明确,而另一些计算复杂性指标还缺乏实际检验。今后,如何建立既具有区分力、又与多样性在概念和数值上都有一定区别的群落结构的计算复杂性的测度方法、如何科学合理地确定复杂性测度中的属性权重以及如何建立结构复杂性的测度和功能过程之间的联系等都是需要深入和系统研究的。由于方法的相似性,有关群落结构复杂性的测度方法也可以应用到其它尺度上的结构复杂性的研究中。     

Development and testing of an Index of Stream Condition for waterway management in Australia

1. An Index of Stream Condition (ISC) has been developed to assist broad scale management of waterways by providing an integrated measure of their environmental condition. 2. The ISC provides scores for five components of stream condition: (i) hydrology (based on change in volume and seasonality of flow from natural conditions); (ii) physical form (based on bank stability, bed erosion or aggradation, influence of artificial barriers, and abundance and origin of coarse woody debris); (iii) streamside zone (based on types of plants; spatial extent, width, and intactness of riparian vegetation; regeneration of overstorey species, and condition of wetlands and billabongs); (iv) water quality (based on an assessment of phosphorus, turbidity, electrical conductivity and pH); and (v) aquatic life (based on number of families of macroinvertebrates). 3. The ISC is intended for use by managers at state and regional levels and can be used to report on stream condition, assist with priority setting, judge the long-term effectiveness of rehabilitation programs and assist with adaptive management. The best available scientific information was used by a multidisciplinary group of scientists and managers to create a stream assessment procedure that can be used routinely by people with limited scientific training. 4. ISC development included trials in four catchments in Victoria, Australia. Over 80 stream reaches were assessed and the results were used to refine the ISC to improve the ease of measurement and ensure that outcomes met the expectations of users. The ISC is now available to be used more widely for reporting on stream condition.     

A portable generic DNA bioassay system based on in situ oligonucleotide synthesis and hybridization detection

In this study, we present a portable and generic DNA bioassay system based on in situ oligonucleotide synthesis followed by hybridization based detection. The system include two main parts, an oligonucleotide synthesizer and a fluorescence detection system. The oligonucleotide synthesizer is based on microfluidic technology and capable of synthesizing any desired oligonucleotide which can be either used as a primer for PCR based detection (external) or a probe for hybridization based detection (integrated) of a target DNA analyte. The oligonucleotide sequence can be remotely sent to the system. The integrated fluorescence detection system is based on a photodiode to detect Texas Red fluorophore as low as 0.5 fmol. The complete system, integrating the oligonucleotide synthesizer and fluorescence detection system, was successfully used to distinguish DNA from two different bacteria strains. The presented generic portable instrument has the potential to detect any desired DNA target sequence in the field. Potential applications are for homeland security and fast responses to emerging bio-threats.     

Cryptography with DNA binary strands

Biotechnological methods can be used for cryptography. Here two different cryptographic approaches based on DNA binary strands are shown. The first approach shows how DNA binary strands can be used for steganography, a technique of encryption by information hiding, to provide rapid encryption and decryption. It is shown that DNA steganography based on DNA binary strands is secure under the assumption that an interceptor has the same technological capabilities as sender and receiver of encrypted messages. The second approach shown here is based on steganography and a method of graphical subtraction of binary gel-images. It can be used to constitute a molecular checksum and can be combined with the first approach to support encryption. DNA cryptography might become of practical relevance in the context of labelling organic and inorganic materials with DNA 'barcodes'.     

Genetic algorithm-based optimization of hydrophobicity tables

SUMMARY: The genomic abundance and pharmacological importance of membrane proteins have fueled efforts to identify them based solely on sequence information. Previous methods based on the physicochemical principle of a sliding window of hydrophobicity (hydropathy analysis) have been replaced by approaches based on hidden Markov models or neural networks which prevail due to their probabilistic orientation. In the current study, an optimization of the hydrophobicity tables used in hydropathy analysis is performed using a genetic algorithm. As such, the approach can be viewed as a synthesis between the physicochemically and statistically based methods. The resulting hydrophobicity tables lead to significant improvement in the prediction accuracy of hydropathy analysis. Furthermore, since hydropathy analysis is less dependent on the basis set of membrane proteins is used to hone the statistically based methods, as well as being faster, it may be valuable in the analysis of new genomes. Finally, the values obtained for each of the amino acids in the new hydrophobicity tables are discussed.     

Evolution of the silver and gold stains in neurohistology

Scientific investigations depend on the reliability of the observations that can be made. This reliability is determined in part by the understanding of the techniques and technology used to make the observations. The limitations and the strengths of the methodology and the equipment used must be evaluated thoroughly. The extent to which this is and has been the case for the use of the metal based stains in neuroscience is the subject of this paper. I evaluate the metallic stains used for neuroscience from several perspectives. I review briefly the state of neurohistology prior to its “golden years,” 1870-1910. Then I trace the development of the silver based stains used for neurohistology. I wanted to discuss the reasoning used by the originators of the silver based techniques in developing their specific procedures, but discovered that while procedures may be published, the methods and ideas used to arrive at the final procedures are not usually described in published work.     

Evolution of the silver and gold stains in neurohistology

Scientific investigations depend on the reliability of the observations that can be made. This reliability is determined in part by the understanding of the techniques and technology used to make the observations. The limitations and the strengths of the methodology and the equipment used must be evaluated thoroughly. The extent to which this is and has been the case for the use of the metal based stains in neuroscience is the subject of this paper. I evaluate the metallic stains used for neuroscience from several perspectives. I review briefly the state of neurohistology prior to its “golden years,” 1870–1910. Then I trace the development of the silver based stains used for neurohistology. I wanted to discuss the reasoning used by the originators of the silver based techniques in developing their specific procedures, but discovered that while procedures may be published, the methods and ideas used to arrive at the final procedures are not usually described in published work.     

Estimation of Monod model parameters by hybrid differential evolution

A hybrid method based on evolutionary algorithms is developed in this study. Two additional operations, an acceleration operation and a migration operation, are embedded into the original version of differential evolution. These two operations are used for the improvement of the convergence speed without decreasing the diversity among the individuals. The acceleration operation is used to speed up convergence. However, the migration operation is used to increase the diversity among the individuals. The hybrid method is applied to estimate the parameters of the Monod model of a recombinant fermentation process. The model profiles based on ᇆ% variations of the initial concentrations of glucose can fit the experimental observations satisfactorily.     

Fibrinolysis standards: A review of the current status

Biological standards are used to calibrate measurements of components of the fibrinolytic system, either for assigning potency values to therapeutic products, or to determine levels in human plasma as an indicator of thrombotic risk. Traditionally WHO International Standards are calibrated in International Units based on consensus values from collaborative studies. The International Unit is defined by the response activity of a given amount of the standard in a bioassay, independent of the method used. Assay validity is based on the assumption that both standard and test preparation contain the same analyte, and the response in an assay is a true function of this analyte. This principle is reflected in the diversity of source materials used to prepare fibrinolysis standards, which has depended on the contemporary preparations they were employed to measure. With advancing recombinant technology, and improved analytical techniques, a reference system based on reference materials and associated reference methods has been recommended for future fibrinolysis standards. Careful consideration and scientific judgement must however be applied when deciding on an approach to develop a new standard, with decisions based on the suitability of a standard to serve its purpose, and not just to satisfy a metrological ideal.     

Effects of pH probe lag on bioreactor mixing time estimation

Mixing time is one of the most important characteristics of bioreactors used to validate computational fluid dynamics (CFD) models in bioprocess. The pH tracer based method is commonly used to estimate mixing time by monitoring the pH change after perturbation to the system. However, pH probe lag is known to introduce errors in the test results. To determine the impact of probe lag on the measurement, pH probe response times were investigated. A second order mathematical model was established to describe the probe response profile and calculate the probe transfer function which was used to correct the empirical results. The corrected mixing time was used to validate the CFD models and also showed that the impact of pH probe response time on mixing time measurement is significant even in larger (pilot and manufacturing) scales. In addition, comparison with a conductance based tracer method is also discussed in this paper.     

Feature selection in validating mass spectrometry database search results

Tandem mass spectrometry (MS/MS) combined with protein database searching has been widely used in protein identification. A validation procedure is generally required to reduce the number of false positives. Advanced tools using statistical and machine learning approaches may provide faster and more accurate validation than manual inspection and empirical filtering criteria. In this study, we use two feature selection algorithms based on random forest and support vector machine to identify peptide properties that can be used to improve validation models. We demonstrate that an improved model based on an optimized set of features reduces the number of false positives by 58% relative to the model which used only search engine scores, at the same sensitivity score of 0.8. In addition, we develop classification models based on the physicochemical properties and protein sequence environment of these peptides without using search engine scores. The performance of the best model based on the support vector machine algorithm is at 0.8 AUC, 0.78 accuracy, and 0.7 specificity, suggesting a reasonably accurate classification. The identified properties important to fragmentation and ionization can be either used in independent validation tools or incorporated into peptide sequencing and database search algorithms to improve existing software programs.     

Evolution of the silver and gold stains in neurohistology.

Scientific investigations depend on the reliability of the observations that can be made. This reliability is determined in part by the understanding of the techniques and technology used to make the observations. The limitations and the strengths of the methodology and the equipment used must be evaluated thoroughly. The extent to which this is and has been the case for the use of the metal based stains in neuroscience is the subject of this paper. I evaluate the metallic stains used for neuroscience from several perspectives. I review briefly the state of neurohistology prior to its "golden years," 1870-1910. Then I trace the development of the silver based stains used for neurohistology. I wanted to discuss the reasoning used by the originators of the silver based techniques in developing their specific procedures, but discovered that while procedures may be published, the methods and ideas used to arrive at the final procedures are not usually described in published work.     

DNA启动子的计算机识别

本文介绍了两种预测DNA顺序上的启动子位置的计算机识别方法,方法1是基于启动子部位单核苷酸的分布不均一性,方法2是基于启动子部位二核苷酸的分布不均一性。分别用这两种方法推测了质粒pBR322DNA上启动子的位置,从而验证了化学实验的结果。     

Use of pseudorandom noise in studies of frequency selectivity: The periphery of the auditory system

Frequency selectivity of single auditory nerve fibers in the rat was studied using pseudorandom noise based on ternary m-sequences as the stimulus, and the results were compared to those of earlier studies in which noise based on binary m-sequences was used. Pseudorandom noise based on ternary m-sequences has fewer anomalies than noise based on binary m-sequences. Detailed tests using linear and nonlinear filters showed that the present method provides accurate measures of bandwidth and center frequency. Period histograms of the response, locked to the periodicity of the noise, were cross-correlated with one period of the noise to obtain estimates of the impulse response function of the peripheral auditory system. Fourier transforms of these cross-correlograms were used as estimates of the filter function of single auditory nerve fibers. The results obtained using ternary noise were not different from previous results showing a downward shift in center frequency and increase in bandwidth with increasing stimulus intensity for fibers with center frequencies between 1000 and 5000 Hz. The difference between spectral selectivity based on phase-locked responses and that based on discharge rate is discussed.     

Surface plasmon resonance based pesticide assay on a renewable biosensing surface using the reversible concanavalin A monosaccharide interaction

A competitive immunoassay based on surface plasmon resonance (SPR) for the detection of the pesticide 2,4-dichlorophenoxyacetic acid (2,4-D) is reported. The novelty of the assay is based on the regeneration of the chip surface by the reversible interaction between monosaccharide (D-glucose) and lectin (Concanavalin A). Concanavalin A-2,4-D conjugate was chemically synthesized, purified and used for binding to the SPR chip modified with covalently bound alpha-D-glucose. The interaction between anti-2,4-D antibody and the surface-bound concanavalin A-2,4-D conjugate was monitored by surface plasmon resonance and the response was used for the quantification of 2,4-D. The dynamic range of the calibration curve was between 3 and 100 ng/ml. The demonstrated principle of surface regeneration based on the reversible sugar-lectin interaction may be of more general applicability in immunoassays.     

基于形态特征和ITS序列对7个鹅膏菌属菌株的分类鉴定

以采自浙江省丽水地区的7个鹅膏菌属菌株作为研究材料,在基于形态特征进行初步鉴定的基础上,对7种鹅膏菌的rDNAITS区段进行克隆测序和序列特征比较分析。进一步对ITS序列进行核酸序列数据库GenBank同源性检索比对,将从GenBank检索获得的9个最相似物种的ITS序列连同7种鹅膏菌的ITS序列一起作系统发育分析。结果表明:基于ITS序列对f6、f9和f493个菌株的分子鉴定支持了基于形态特征的鉴定结果,对f5的分子鉴定不支持形态鉴定的结果,f8为鹅膏菌属内某种,f66为鹅膏菌属内某种,并与Amanitafulva,A.atrofusca,A.orientifulva3种鹅膏菌的亲缘关系较近,f7与另外6种鹅膏菌的亲缘关系相差甚远。研究结果提示基于分子水平上的ITS序列分析不能单方面作为大型真菌分类鉴定的可靠依据,可以作为基于传统形态学分类鉴定的辅助参考依据。