Liver genomic responses to ciguatoxin: evidence for activation of Phase I and Phase II detoxification pathways following an acute hypothermic response in mice

Ciguatoxins (CTX) are polyether neurotoxins that target voltage-gated sodium channels and are responsible for ciguatera, the most common fish-borne food poisoning in humans. This study characterizes the global transcriptional response of mouse liver to a symptomatic dose (0.26 ng/g) of the highly potent Pacific ciguatoxin-1 (P-CTX-1). At 1 h post-exposure 2.4% of features on a 44K whole genome array were differentially expressed (p ≤ 0.0001), increasing to 5.2% at 4 h and decreasing to 1.4% by 24 h post-CTX exposure. Data were filtered (|fold change| ≥ 1.5 and p ≤ 0.0001 in at least one time point) and a trend set of 1550 genes were used for further analysis. Early gene expression was likely influenced prominently by an acute 4°C decline in core body temperature by 1 h, which resolved by 8 h following exposure. An initial downregulation of 32 different solute carriers, many involved in sodium transport, was observed. Differential gene expression in pathways involving eicosanoid biosynthesis and cholesterol homeostasis was also noted. Cytochrome P450s (Cyps) were of particular interest due to their role in xenobiotic metabolism. Twenty-seven genes, mostly members of Cyp2 and Cyp4 families, showed significant changes in expression. Many Cyps underwent an initial downregulation at 1 h but were quickly and strongly upregulated at 4 and 24 h post-exposure. In addition to Cyps, increases in several glutathione S-transferases were observed, an indication that both phase I and phase II metabolic reactions are involved in the hepatic response to CTX in mice.

Analysis of case histories on deep excavations in marine clay

Two case histories on deep excavation of marine clay are used to study the use of a decision-making tool based on a new deign method called the Mobilized Strength Design (MSD) method which allows the designer to use a simple method of predicting ground displacements during deep excavation. This application can approximately satisfy both safety and serviceability requirements by predicting stresses and displacements under working conditions by introducing the concept of "Mobilizable soil strength". The new method accommodates a number of features which are important to design of underground construction between retaining walls, including different deformation mechanism in different stages of excavation. The influence of wall depth, wall flexibility and stratified ground are the major focus of this paper. These developments should make it possible for a design engineer to take informed decisions on the influence of wall stiffness, or on the need for a jet-grouted base slab, for example, without having to conduct project-specific Finite Element Analysis.

Robust pairwise matching of interest points with complex wavelets

We present a matching framework to find robust correspondences between image features by considering the spatial information between them. To achieve this, we define spatial constraints on the relative orientation and change in scale between pairs of features. A pairwise similarity score, which measures the similarity of features based on these spatial constraints, is considered. The pairwise similarity scores for all pairs of candidate correspondences are then accumulated in a 2-D similarity space. Robust correspondences can be found by searching for clusters in the similarity space, since actual correspondences are expected to form clusters that satisfy similar spatial constraints in this space. As it is difficult to achieve reliable and consistent estimates of scale and orientation, an additional contribution is that these parameters do not need to be determined at the interest point detection stage, which differs from conventional methods. Polar matching of dual-tree complex wavelet transform features is used, since it fits naturally into the framework with the defined spatial constraints. Our tests show that the proposed framework is capable of producing robust correspondences with higher correspondence ratios and reasonable computational efficiency, compared to other well-known algorithms. © 1992-2012 IEEE.

Structural and optical properties of GaAsSb/GaAs heterostructure quantum wells

The structural and optical properties of MBE-grown GaAsSb/GaAs multiple quantum wells (MQWs) as well as strain-compensated GaAsSb/GaAs/GaAsP MQWs are investigated. The results of double crystal X-ray diffraction and reciprocal space mapping show that when strain-compensated layers are introduced, the interface quality of QW structure is remarkably improved, and the MQW structure containing GaAsSb layers with a high Sb composition can be coherently grown. Due to the influence of inserted GaAsP layers on the energy band and carrier distribution of QWs, the optical properties of GaAsSb/GaAs/GaAsP MQWs display a lot of features mainly characteristic of type-I QWs despite the type-II GaAsSb/GaAs interfaces exist in the structure. (C) 2004 Elsevier B.V. All rights reserved.

Structural and optical properties of GaAsSb/GaAs heterostructure quantum wells

The structural and optical properties of MBE-grown GaAsSb/GaAs multiple quantum wells (MQWs) as well as strain-compensated GaAsSb/GaAs/GaAsP MQWs are investigated. The results of double crystal X-ray diffraction and reciprocal space mapping show that when strain-compensated layers are introduced, the interface quality of QW structure is remarkably improved, and the MQW structure containing GaAsSb layers with a high Sb composition can be coherently grown. Due to the influence of inserted GaAsP layers on the energy band and carrier distribution of QWs, the optical properties of GaAsSb/GaAs/GaAsP MQWs display a lot of features mainly characteristic of type-I QWs despite the type-II GaAsSb/GaAs interfaces exist in the structure. (C) 2004 Elsevier B.V. All rights reserved.

图像不变局部特征研究及应用

图像不变局部特征是新近兴起的一类图像特征，基于不变局部特征的图像表示是计算机视觉的热点研究问题，在理论研究和实际应用上都具有重要意义。本论文针对图像不变局部特征的原理特性及应用展开研究：（1）当今流行的不变局部特征检测和描述方法；（2）局部特征组织方式；（3）基于局部不变特征的摄像机运动检测方法；（4）基于局部特征组合的目标模型及识别方法。 深入研究了当今流行的不变局部特征检测子，重点分析了其提取原理、特征结构、不变性阶次、精确度等特性，在此基础上对多种检测子进行比较分析，得出各自的适用范围，并总结出在具体应用环境下的特征选择原则。 针对视频分析中摄像机运动检测的具体应用，提出一种基于尺度不变局部特征的摄像机运动检测方法。该方法选取尺度不变局部特征，采用无序特征集合的方式表示图像帧，通过帧间局部特征的匹配，提出归一化软投票的方法鲁棒地估计特征匹配对的位置、尺度的变化，并根据各变化值和投票数的特点识别出摄像机的运动类型。该方法简单、鲁棒，满足了摄像机运动检测的处理速度和准确性需求。 针对基于局部特征的目标表示和识别问题，研究分析现有两种模型bag-of-words和part-based的优缺点，将二者结合，提出一种局部特征组合的目标表示模型和相应的识别算法。该方法在半局部区域内的特征同时进行外观描述和空间位置编码，并用数据挖掘中的频繁项挖掘技术自动提取出表征目标的特征组合，作为子模型。目标模型由一系列子模型构成，子模型的数量及每个子模型中包含的部件数目均自动从训练集中发现，是完全目标自适应的。所提方法克服了bag-of-words方法表达的精确性不足、part-based方法训练速度过慢的缺点，在识别问题上得到了较好的总体性能。

Laurencia nanhaiense sp nov., a new species of the genus Laurencia(Rhodomelaceae, Rhodophyta) from China

Laurencia nanhaiense sp. nov. (Rhodomelaceae, Rhodophyta) is described from Hainan and Guangdong Provinces, China. The new species clearly displays one of the defining features of the genus, viz. four periaxial cells per vegetative axial segment. It differs from other closely related species in having a combination of features such as terete axes from a basal system composed of a primary, discoid holdfast and a secondary attachment to give rise to many short rhizoids, branching oppositely and alternately, irregularly tristichous or subverticillately polystichous, having more curve branches with very sparse, adventitious ultimate branchlets, non-projecting superficial cortical cells at the apices of ultimate branchlets, presence of longitudinally oriented secondary pit-connections between contiguous superficial cortical cells, absence of lenticular thickenings in the walls of medullary cells, parallel arrangement of tetrasporangia along the axis of stichidia, and presence of intercellular spaces between medullary cells.

Feature Matching for Object Localization in the Presence of Uncertainty

We consider the problem of matching model and sensory data features in the presence of geometric uncertainty, for the purpose of object localization and identification. The problem is to construct sets of model feature and sensory data feature pairs that are geometrically consistent given that there is uncertainty in the geometry of the sensory data features. If there is no geometric uncertainty, polynomial-time algorithms are possible for feature matching, yet these approaches can fail when there is uncertainty in the geometry of data features. Existing matching and recognition techniques which account for the geometric uncertainty in features either cannot guarantee finding a correct solution, or can construct geometrically consistent sets of feature pairs yet have worst case exponential complexity in terms of the number of features. The major new contribution of this work is to demonstrate a polynomial-time algorithm for constructing sets of geometrically consistent feature pairs given uncertainty in the geometry of the data features. We show that under a certain model of geometric uncertainty the feature matching problem in the presence of uncertainty is of polynomial complexity. This has important theoretical implications by demonstrating an upper bound on the complexity of the matching problem, an by offering insight into the nature of the matching problem itself. These insights prove useful in the solution to the matching problem in higher dimensional cases as well, such as matching three-dimensional models to either two or three-dimensional sensory data. The approach is based on an analysis of the space of feasible transformation parameters. This paper outlines the mathematical basis for the method, and describes the implementation of an algorithm for the procedure. Experiments demonstrating the method are reported.

Sharing visual features for multiclass and multiview object detection

We consider the problem of detecting a large number of different classes of objects in cluttered scenes. Traditional approaches require applying a battery of different classifiers to the image, at multiple locations and scales. This can be slow and can require a lot of training data, since each classifier requires the computation of many different image features. In particular, for independently trained detectors, the (run-time) computational complexity, and the (training-time) sample complexity, scales linearly with the number of classes to be detected. It seems unlikely that such an approach will scale up to allow recognition of hundreds or thousands of objects. We present a multi-class boosting procedure (joint boosting) that reduces the computational and sample complexity, by finding common features that can be shared across the classes (and/or views). The detectors for each class are trained jointly, rather than independently. For a given performance level, the total number of features required, and therefore the computational cost, is observed to scale approximately logarithmically with the number of classes. The features selected jointly are closer to edges and generic features typical of many natural structures instead of finding specific object parts. Those generic features generalize better and reduce considerably the computational cost of an algorithm for multi-class object detection.

Aiding classification of gene expression data with feature selection: a comparative study

C. Shang and Q. Shen. Aiding classification of gene expression data with feature selection: a comparative study. Computational Intelligence Research, 1(1):68-76.

A Customizable Camera-based Human Computer Interaction System Allowing People With Disabilities Autonomous Hands Free Navigation of Multiple Computing Task

Many people suffer from conditions that lead to deterioration of motor control and makes access to the computer using traditional input devices difficult. In particular, they may loose control of hand movement to the extent that the standard mouse cannot be used as a pointing device. Most current alternatives use markers or specialized hardware to track and translate a user's movement to pointer movement. These approaches may be perceived as intrusive, for example, wearable devices. Camera-based assistive systems that use visual tracking of features on the user's body often require cumbersome manual adjustment. This paper introduces an enhanced computer vision based strategy where features, for example on a user's face, viewed through an inexpensive USB camera, are tracked and translated to pointer movement. The main contributions of this paper are (1) enhancing a video based interface with a mechanism for mapping feature movement to pointer movement, which allows users to navigate to all areas of the screen even with very limited physical movement, and (2) providing a customizable, hierarchical navigation framework for human computer interaction (HCI). This framework provides effective use of the vision-based interface system for accessing multiple applications in an autonomous setting. Experiments with several users show the effectiveness of the mapping strategy and its usage within the application framework as a practical tool for desktop users with disabilities.

Cortical Learning of Recognition Categories: A Resolution of the Exemplar Vs. Prototype Debate

Do humans and animals learn exemplars or prototypes when they categorize objects and events in the world? How are different degrees of abstraction realized through learning by neurons in inferotemporal and prefrontal cortex? How do top-down expectations influence the course of learning? Thirty related human cognitive experiments (the 5-4 category structure) have been used to test competing views in the prototype-exemplar debate. In these experiments, during the test phase, subjects unlearn in a characteristic way items that they had learned to categorize perfectly in the training phase. Many cognitive models do not describe how an individual learns or forgets such categories through time. Adaptive Resonance Theory (ART) neural models provide such a description, and also clarify both psychological and neurobiological data. Matching of bottom-up signals with learned top-down expectations plays a key role in ART model learning. Here, an ART model is used to learn incrementally in response to 5-4 category structure stimuli. Simulation results agree with experimental data, achieving perfect categorization in training and a good match to the pattern of errors exhibited by human subjects in the testing phase. These results show how the model learns both prototypes and certain exemplars in the training phase. ART prototypes are, however, unlike the ones posited in the traditional prototype-exemplar debate. Rather, they are critical patterns of features to which a subject learns to pay attention based on past predictive success and the order in which exemplars are experienced. Perturbations of old memories by newly arriving test items generate a performance curve that closely matches the performance pattern of human subjects. The model also clarifies exemplar-based accounts of data concerning amnesia.

Micro-Anatomical Quantitative Imaging Towards Enabling Automated Diagnosis of Thick Tissues at the Point of Care

Histopathology is the clinical standard for tissue diagnosis. However, histopathology has several limitations including that it requires tissue processing, which can take 30 minutes or more, and requires a highly trained pathologist to diagnose the tissue. Additionally, the diagnosis is qualitative, and the lack of quantitation leads to possible observer-specific diagnosis. Taken together, it is difficult to diagnose tissue at the point of care using histopathology.

Several clinical situations could benefit from more rapid and automated histological processing, which could reduce the time and the number of steps required between obtaining a fresh tissue specimen and rendering a diagnosis. For example, there is need for rapid detection of residual cancer on the surface of tumor resection specimens during excisional surgeries, which is known as intraoperative tumor margin assessment. Additionally, rapid assessment of biopsy specimens at the point-of-care could enable clinicians to confirm that a suspicious lesion is successfully sampled, thus preventing an unnecessary repeat biopsy procedure. Rapid and low cost histological processing could also be potentially useful in settings lacking the human resources and equipment necessary to perform standard histologic assessment. Lastly, automated interpretation of tissue samples could potentially reduce inter-observer error, particularly in the diagnosis of borderline lesions.

To address these needs, high quality microscopic images of the tissue must be obtained in rapid timeframes, in order for a pathologic assessment to be useful for guiding the intervention. Optical microscopy is a powerful technique to obtain high-resolution images of tissue morphology in real-time at the point of care, without the need for tissue processing. In particular, a number of groups have combined fluorescence microscopy with vital fluorescent stains to visualize micro-anatomical features of thick (i.e. unsectioned or unprocessed) tissue. However, robust methods for segmentation and quantitative analysis of heterogeneous images are essential to enable automated diagnosis. Thus, the goal of this work was to obtain high resolution imaging of tissue morphology through employing fluorescence microscopy and vital fluorescent stains and to develop a quantitative strategy to segment and quantify tissue features in heterogeneous images, such as nuclei and the surrounding stroma, which will enable automated diagnosis of thick tissues.

To achieve these goals, three specific aims were proposed. The first aim was to develop an image processing method that can differentiate nuclei from background tissue heterogeneity and enable automated diagnosis of thick tissue at the point of care. A computational technique called sparse component analysis (SCA) was adapted to isolate features of interest, such as nuclei, from the background. SCA has been used previously in the image processing community for image compression, enhancement, and restoration, but has never been applied to separate distinct tissue types in a heterogeneous image. In combination with a high resolution fluorescence microendoscope (HRME) and a contrast agent acriflavine, the utility of this technique was demonstrated through imaging preclinical sarcoma tumor margins. Acriflavine localizes to the nuclei of cells where it reversibly associates with RNA and DNA. Additionally, acriflavine shows some affinity for collagen and muscle. SCA was adapted to isolate acriflavine positive features or APFs (which correspond to RNA and DNA) from background tissue heterogeneity. The circle transform (CT) was applied to the SCA output to quantify the size and density of overlapping APFs. The sensitivity of the SCA+CT approach to variations in APF size, density and background heterogeneity was demonstrated through simulations. Specifically, SCA+CT achieved the lowest errors for higher contrast ratios and larger APF sizes. When applied to tissue images of excised sarcoma margins, SCA+CT correctly isolated APFs and showed consistently increased density in tumor and tumor + muscle images compared to images containing muscle. Next, variables were quantified from images of resected primary sarcomas and used to optimize a multivariate model. The sensitivity and specificity for differentiating positive from negative ex vivo resected tumor margins was 82% and 75%. The utility of this approach was further tested by imaging the in vivo tumor cavities from 34 mice after resection of a sarcoma with local recurrence as a bench mark. When applied prospectively to images from the tumor cavity, the sensitivity and specificity for differentiating local recurrence was 78% and 82%. The results indicate that SCA+CT can accurately delineate APFs in heterogeneous tissue, which is essential to enable automated and rapid surveillance of tissue pathology.

Two primary challenges were identified in the work in aim 1. First, while SCA can be used to isolate features, such as APFs, from heterogeneous images, its performance is limited by the contrast between APFs and the background. Second, while it is feasible to create mosaics by scanning a sarcoma tumor bed in a mouse, which is on the order of 3-7 mm in any one dimension, it is not feasible to evaluate an entire human surgical margin. Thus, improvements to the microscopic imaging system were made to (1) improve image contrast through rejecting out-of-focus background fluorescence and to (2) increase the field of view (FOV) while maintaining the sub-cellular resolution needed for delineation of nuclei. To address these challenges, a technique called structured illumination microscopy (SIM) was employed in which the entire FOV is illuminated with a defined spatial pattern rather than scanning a focal spot, such as in confocal microscopy.

Thus, the second aim was to improve image contrast and increase the FOV through employing wide-field, non-contact structured illumination microscopy and optimize the segmentation algorithm for new imaging modality. Both image contrast and FOV were increased through the development of a wide-field fluorescence SIM system. Clear improvement in image contrast was seen in structured illumination images compared to uniform illumination images. Additionally, the FOV is over 13X larger than the fluorescence microendoscope used in aim 1. Initial segmentation results of SIM images revealed that SCA is unable to segment large numbers of APFs in the tumor images. Because the FOV of the SIM system is over 13X larger than the FOV of the fluorescence microendoscope, dense collections of APFs commonly seen in tumor images could no longer be sparsely represented, and the fundamental sparsity assumption associated with SCA was no longer met. Thus, an algorithm called maximally stable extremal regions (MSER) was investigated as an alternative approach for APF segmentation in SIM images. MSER was able to accurately segment large numbers of APFs in SIM images of tumor tissue. In addition to optimizing MSER for SIM image segmentation, an optimal frequency of the illumination pattern used in SIM was carefully selected because the image signal to noise ratio (SNR) is dependent on the grid frequency. A grid frequency of 31.7 mm-1 led to the highest SNR and lowest percent error associated with MSER segmentation.

Once MSER was optimized for SIM image segmentation and the optimal grid frequency was selected, a quantitative model was developed to diagnose mouse sarcoma tumor margins that were imaged ex vivo with SIM. Tumor margins were stained with acridine orange (AO) in aim 2 because AO was found to stain the sarcoma tissue more brightly than acriflavine. Both acriflavine and AO are intravital dyes, which have been shown to stain nuclei, skeletal muscle, and collagenous stroma. A tissue-type classification model was developed to differentiate localized regions (75x75 µm) of tumor from skeletal muscle and adipose tissue based on the MSER segmentation output. Specifically, a logistic regression model was used to classify each localized region. The logistic regression model yielded an output in terms of probability (0-100%) that tumor was located within each 75x75 µm region. The model performance was tested using a receiver operator characteristic (ROC) curve analysis that revealed 77% sensitivity and 81% specificity. For margin classification, the whole margin image was divided into localized regions and this tissue-type classification model was applied. In a subset of 6 margins (3 negative, 3 positive), it was shown that with a tumor probability threshold of 50%, 8% of all regions from negative margins exceeded this threshold, while over 17% of all regions exceeded the threshold in the positive margins. Thus, 8% of regions in negative margins were considered false positives. These false positive regions are likely due to the high density of APFs present in normal tissues, which clearly demonstrates a challenge in implementing this automatic algorithm based on AO staining alone.

Thus, the third aim was to improve the specificity of the diagnostic model through leveraging other sources of contrast. Modifications were made to the SIM system to enable fluorescence imaging at a variety of wavelengths. Specifically, the SIM system was modified to enabling imaging of red fluorescent protein (RFP) expressing sarcomas, which were used to delineate the location of tumor cells within each image. Initial analysis of AO stained panels confirmed that there was room for improvement in tumor detection, particularly in regards to false positive regions that were negative for RFP. One approach for improving the specificity of the diagnostic model was to investigate using a fluorophore that was more specific to staining tumor. Specifically, tetracycline was selected because it appeared to specifically stain freshly excised tumor tissue in a matter of minutes, and was non-toxic and stable in solution. Results indicated that tetracycline staining has promise for increasing the specificity of tumor detection in SIM images of a preclinical sarcoma model and further investigation is warranted.

In conclusion, this work presents the development of a combination of tools that is capable of automated segmentation and quantification of micro-anatomical images of thick tissue. When compared to the fluorescence microendoscope, wide-field multispectral fluorescence SIM imaging provided improved image contrast, a larger FOV with comparable resolution, and the ability to image a variety of fluorophores. MSER was an appropriate and rapid approach to segment dense collections of APFs from wide-field SIM images. Variables that reflect the morphology of the tissue, such as the density, size, and shape of nuclei and nucleoli, can be used to automatically diagnose SIM images. The clinical utility of SIM imaging and MSER segmentation to detect microscopic residual disease has been demonstrated by imaging excised preclinical sarcoma margins. Ultimately, this work demonstrates that fluorescence imaging of tissue micro-anatomy combined with a specialized algorithm for delineation and quantification of features is a means for rapid, non-destructive and automated detection of microscopic disease, which could improve cancer management in a variety of clinical scenarios.

Predictive Modeling of Loss-of-Heterozygosity Events in Yeast

During mitotic cell cycles, DNA experiences many types of endogenous and exogenous damaging agents that could potentially cause double strand breaks (DSB). In S. cerevisiae, DSBs are primarily repaired by mitotic recombination and as a result, could lead to loss-of-heterozygosity (LOH). Genetic recombination can happen in both meiosis and mitosis. While genome-wide distribution of meiotic recombination events has been intensively studied, mitotic recombination events have not been mapped unbiasedly throughout the genome until recently. Methods for selecting mitotic crossovers and mapping the positions of crossovers have recently been developed in our lab. Our current approach uses a diploid yeast strain that is heterozygous for about 55,000 SNPs, and employs SNP-Microarrays to map LOH events throughout the genome. These methods allow us to examine selected crossovers and unselected mitotic recombination events (crossover, noncrossover and BIR) at about 1 kb resolution across the genome. Using this method, we generated maps of spontaneous and UV-induced LOH events. In this study, we explore machine learning and variable selection techniques to build a predictive model for where the LOH events occur in the genome.

Randomly from the yeast genome, we simulated control tracts resembling the LOH tracts in terms of tract lengths and locations with respect to single-nucleotide-polymorphism positions. We then extracted roughly 1,100 features such as base compositions, histone modifications, presence of tandem repeats etc. and train classifiers to distinguish control tracts and LOH tracts. We found interesting features of good predictive values. We also found that with the current repertoire of features, the prediction is generally better for spontaneous LOH events than UV-induced LOH events.

Modeling of ingot development during the start-up phase of direct chill casting

Direct chill (DC) casting is a core primary process in the production of aluminum ingots. However, its operational optimization is still under investigation with regard to a number of features, one of which is the issue of curvature at the base of the ingot. Analysis of these features requires a computational model of the process that accounts for the fluid flow, heat transfer, solidification phase change, and thermomechanical analysis. This article describes an integrated approach to the modeling of all the preceding phenomena and their interactions.