The Alignment of Objects With Smooth Surfaces: Error Analysis of the Curvature Method

The recognition of objects with smooth bounding surfaces from their contour images is considerably more complicated than that of objects with sharp edges, since in the former case the set of object points that generates the silhouette contours changes from one view to another. The "curvature method", developed by Basri and Ullman [1988], provides a method to approximate the appearance of such objects from different viewpoints. In this paper we analyze the curvature method. We apply the method to ellipsoidal objects and compute analytically the error obtained for different rotations of the objects. The error depends on the exact shape of the ellipsoid (namely, the relative lengths of its axes), and it increases a sthe ellipsoid becomes "deep" (elongated in the Z-direction). We show that the errors are usually small, and that, in general, a small number of models is required to predict the appearance of an ellipsoid from all possible views. Finally, we show experimentally that the curvature method applies as well to objects with hyperbolic surface patches.

On the Relationship Between Generalization Error, Hypothesis Complexity, and Sample Complexity for Radial Basis Functions

In this paper, we bound the generalization error of a class of Radial Basis Function networks, for certain well defined function learning tasks, in terms of the number of parameters and number of examples. We show that the total generalization error is partly due to the insufficient representational capacity of the network (because of its finite size) and partly due to insufficient information about the target function (because of finite number of samples). We make several observations about generalization error which are valid irrespective of the approximation scheme. Our result also sheds light on ways to choose an appropriate network architecture for a particular problem.

Quantitative Analysis of Single Nucleotide Polymorphisms within Copy Number Variation

Background Single nucleotide polymorphisms (SNPs) have been used extensively in genetics and epidemiology studies. Traditionally, SNPs that did not pass the Hardy-Weinberg equilibrium (HWE) test were excluded from these analyses. Many investigators have addressed possible causes for departure from HWE, including genotyping errors, population admixture and segmental duplication. Recent large-scale surveys have revealed abundant structural variations in the human genome, including copy number variations (CNVs). This suggests that a significant number of SNPs must be within these regions, which may cause deviation from HWE. Results We performed a Bayesian analysis on the potential effect of copy number variation, segmental duplication and genotyping errors on the behavior of SNPs. Our results suggest that copy number variation is a major factor of HWE violation for SNPs with a small minor allele frequency, when the sample size is large and the genotyping error rate is 0~1%. Conclusions Our study provides the posterior probability that a SNP falls in a CNV or a segmental duplication, given the observed allele frequency of the SNP, sample size and the significance level of HWE testing.

On the Geographic Location of Internet Resources

One relatively unexplored question about the Internet's physical structure concerns the geographical location of its components: routers, links and autonomous systems (ASes). We study this question using two large inventories of Internet routers and links, collected by different methods and about two years apart. We first map each router to its geographical location using two different state-of-the-art tools. We then study the relationship between router location and population density; between geographic distance and link density; and between the size and geographic extent of ASes. Our findings are consistent across the two datasets and both mapping methods. First, as expected, router density per person varies widely over different economic regions; however, in economically homogeneous regions, router density shows a strong superlinear relationship to population density. Second, the probability that two routers are directly connected is strongly dependent on distance; our data is consistent with a model in which a majority (up to 75-95%) of link formation is based on geographical distance (as in the Waxman topology generation method). Finally, we find that ASes show high variability in geographic size, which is correlated with other measures of AS size (degree and number of interfaces). Among small to medium ASes, ASes show wide variability in their geographic dispersal; however, all ASes exceeding a certain threshold in size are maximally dispersed geographically. These findings have many implications for the next generation of topology generators, which we envisage as producing router-level graphs annotated with attributes such as link latencies, AS identifiers and geographical locations.

Extracting Location from Contact Traces

Localization is essential feature for many mobile wireless applications. Data collected from applications such as environmental monitoring, package tracking or position tracking has no meaning without knowing the location of this data. Other applications have location information as a building block for example, geographic routing protocols, data dissemination protocols and location-based services such as sensing coverage. Many of the techniques have the trade-off among many features such as deployment of special hardware, level of accuracy and computation power. In this paper, we present an algorithm that extracts location constraints from the connectivity information. Our solution, which does not require any special hardware and a small number of landmark nodes, uses two types of location constraints. The spatial constraints derive the estimated locations observing which nodes are within communication range of each other. The temporal constraints refine the areas, computed by the spatial constraints, using properties of time and space extracted from a contact trace. The intuition of the temporal constraints is to limit the possible locations that a node can be using its previous and future locations. To quantify this intuitive improvement in refine the nodes estimated areas adding temporal information, we performed simulations using synthetic and real contact traces. The results show this improvement and also the difficulties of using real traces.

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.

Modeling energy consumption in error-prone IEEE 802.11-based wireless ad-hoc networks

In the IEEE 802.11 MAC layer protocol, there are different trade-off points between the number of nodes competing for the medium and the network capacity provided to them. There is also a trade-off between the wireless channel condition during the transmission period and the energy consumption of the nodes. Current approaches at modeling energy consumption in 802.11 based networks do not consider the influence of the channel condition on all types of frames (control and data) in the WLAN. Nor do they consider the effect on the different MAC and PHY schemes that can occur in 802.11 networks. In this paper, we investigate energy consumption corresponding to the number of competing nodes in IEEE 802.11's MAC and PHY layers in error-prone wireless channel conditions, and present a new energy consumption model. Analysis of the power consumed by each type of MAC and PHY over different bit error rates shows that the parameters in these layers play a critical role in determining the overall energy consumption of the ad-hoc network. The goal of this research is not only to compare the energy consumption using exact formulae in saturated IEEE 802.11-based DCF networks under varying numbers of competing nodes, but also, as the results show, to demonstrate that channel errors have a significant impact on the energy consumption.

Bit error rate performance enhancement of a retrodirective array over a conventional fixed beam array in a dynamic multipath environment

In this paper, we provide experimental evidence to show that enhanced bit error rate (BER) performance is possible using a retrodirective array operating in a dynamically varying multipath environment. The operation of such a system will be compared to that obtained by a conventional nonretrodirective array. The ability of the array to recover amplitude shift keyed encoded data transmitted from a remote location whose position is not known a priori is described. In addition, its ability to retransmit data inserted at the retrodirective array back to a spatially remote beacon location whose position is also not known beforehand is also demonstrated. Comparison with an equivalent conventional fixed beam antenna array utilizing an identical radiating aperture arrangement to that of the retrodirective array are given. These show that the retrodirective array can effectively exploit the presence of time varying multipath in order to give significant reductions in BER over what can be otherwise achieved. Additionally, the retrodirective system is shown to be able to deliver low BER regardless of whether line of sight is present or absent.

Microsatellite standardization and evaluation of genotyping error in a large multi-partner research programme for conservation of Atlantic salmon (Salmo salar L.).

Microsatellite genotyping is a common DNA characterization technique in population, ecological and evolutionary genetics research. Since different alleles are sized relative to internal size-standards, different laboratories must calibrate and standardize allelic designations when exchanging data. This interchange of microsatellite data can often prove problematic. Here, 16 microsatellite loci were calibrated and standardized for the Atlantic salmon, Salmo salar, across 12 laboratories. Although inconsistencies were observed, particularly due to differences between migration of DNA fragments and actual allelic size ('size shifts'), inter-laboratory calibration was successful. Standardization also allowed an assessment of the degree and partitioning of genotyping error. Notably, the global allelic error rate was reduced from 0.05 ± 0.01 prior to calibration to 0.01 ± 0.002 post-calibration. Most errors were found to occur during analysis (i.e. when size-calling alleles; the mean proportion of all errors that were analytical errors across loci was 0.58 after calibration). No evidence was found of an association between the degree of error and allelic size range of a locus, number of alleles, nor repeat type, nor was there evidence that genotyping errors were more prevalent when a laboratory analyzed samples outside of the usual geographic area they encounter. The microsatellite calibration between laboratories presented here will be especially important for genetic assignment of marine-caught Atlantic salmon, enabling analysis of marine mortality, a major factor in the observed declines of this highly valued species.

Numerical Investigation of Optimal Pin Actuator Location on a Supersonic Projectile

The flowfield around a supersonic projectile using a pin actuator control method has been predicted using computational fluid dynamics. It has been predicted using both viscous and inviscid methods for a number of positions. Both methods showed that an optimal longitudinal position exists. However, the inviscid model over-predicted the lateral acceleration due to the difference in shock formation around the pin between the two approaches. The optimal location was predicted independent of solver, however the higher-fidelity solver predicted lower achievable lateral accelerations. This is due to the viscous interactions caused by the pin. The effect of projectile orientation has shown that shielding the pin leads to reduced effectiveness due to the wake of the fin enveloping the pin. When the pin is exposed to onset flow, the forces achieved are increased. There is also an increase in the achievable forces and moments with increasing Mach number.

Effects of Charge Location on the Absorptions and Lifetimes of Protonated Tyrosine Peptides in Vacuo

Nearby charges affect the electronic energy levels of chromophores, with the extent of the effect being determined by the magnitude of the charge and degree of charge-chromophore separation. The molecular configuration dictates the charge chromophore distance. Hence, in this study, we aim to assess how the location of the charge influences the absorption of a set of model protonated and diprotonated peptide ions, and whether spectral differences are large enough to be identified. The studied ions were the dipeptide YK, the tripeptide KYK (Y = tyrosine; K = lysine) and their complexes with 18-crown-6-ether (CE). The CE targets the ammonium group by forming internal ionic hydrogen bonds and limits the folding of the peptide. In the tripeptide, the distance between the chromophore and the backbone ammonium is enlarged relative to that in the dipeptide. Experiments were performed in an electrostatic ion storage ring using a tunable laser system, and action spectra based on lifetime measurements were obtained in the range from 210 to 310 nm. The spectra are all quite similar though there seems to be some changes in the absorption band between 210 and 250 nm, while in the lower energy band all ions had a maximum absorption at similar to 275 nm. Lifetimes after photoexcitation were found to shorten upon protonation and lengthen upon CE complexation, in accordance with the increased number of degrees of freedom and an increase in activation energies for dissociation as the mobile proton model is no longer operative.

Detecting sequence dependent transcriptional pauses from RNA and protein number time series

Background: Evidence suggests that in prokaryotes sequence-dependent transcriptional pauses a?ect the dynamics of transcription and translation, as well as of small genetic circuits. So far, a few pause-prone sequences have been identi?ed from in vitro measurements of transcription elongation kinetics.

Results: Using a stochastic model of gene expression at the nucleotide and codon levels with realistic parameter values, we investigate three di?erent but related questions and present statistical methods for their analysis. First, we show that information from in vivo RNA and protein temporal numbers is su?cient to discriminate between models with and without a pause site in their coding sequence. Second, we demonstrate that it is possible to separate a large variety of models from each other with pauses of various durations and locations in the template by means of a hierarchical clustering and a random forest classi?er. Third, we introduce an approximate likelihood function that allows to estimate the location of a pause site.

Conclusions: This method can aid in detecting unknown pause-prone sequences from temporal measurements of RNA and protein numbers at a genome-wide scale and thus elucidate possible roles that these sequences play in the dynamics of genetic networks and phenotype.

Making geography mobile: using location aware technology to improve student performance in physical geography

With the increased availability of new technologies, geography educators are revisiting their pedagogical approaches to teaching and calling for opportunities to share local and international practices which will enhance the learning experience and improve students’ performance. This paper reports on the use of handheld mobile devices, fitted with GPS, by secondary (high) school pupils in geography. Two location-aware activities were completed over one academic year (one per semester) and pre-test and post-test scores for both topics revealed a statistically significant increase in pupils’ performance as measured by the standard national assessments. A learner centred educational approach was adopted with the first mobile learning activity being created by the teacher as an exemplar of effective mobile learning design. Pupils built on their experiences of using mobile learning when they were required to created their own location aware learning task for peer use. An analysis of the qualitative data from the pupils’ journals, group diaries and focus group interviews revealed the five pillars of learner centred education are addressed when using location aware technologies and the use of handheld mobile devices offered greater flexibility and autonomy to the pupils thus altering the level of power and control away from the teacher. Due to the relatively small number of participants in the study, the results are more informative than generalisable however in light of the growing interest in geo-spatial technologies in geography education, this paper offers encouragement and insight into the use of location aware technology in a compulsory school context

Offshore wind power forecasting error and electricity market implications

Wind energy has been identified as key to the European Union’s 2050 low carbon economy. However, as wind is a variable resource and stochastic by nature, it is difficult to plan and schedule the power system under varying wind power generation. This paper investigates the impacts of offshore wind power forecast error on the operation and management of a pool-based electricity market in 2050. The impact of the magnitude and variance of the offshore wind power forecast error on system generation costs, emission costs, dispatch-down of wind, number of start-ups and system marginal price is analysed. The main findings of this research are that the magnitude of the offshore wind power forecast error has the largest impact on system generation costs and dispatch-down of wind, but the variance of the offshore wind power forecast error has the biggest impact on emissions costs and system marginal price. Overall offshore wind power forecast error variance results in a system marginal price increase of 9.6% in 2050.

A Tight Upper Bound on Bit Error Rate of Joint OFDM and Multi-Carrier Index Keying

This letter investigates performance enhancement by the concept of multi-carrier index keying in orthogonal frequency division multiplexing (OFDM) systems. For the performance evaluation, a tight closed-form approximation of the bit error rate (BER) is derived introducing the expression for the number of bit errors occurring in both the index domain and the complex domain, in the presence of both imperfect and perfect detection of active multi-carrier indices. The accuracy of the derived BER results for various cases are validated using simulations, which can provide accuracy within 1 dB at favorable channels.