PLoS ONE - Category Computer Science

Combination of Real-Value Smell and Metaphor Expression Aids Yeast Detection

2009-11-20T08:00:00Z

Background

Smell provides important information about the quality of food and drink. Most well-known for their expertise in wine tasting, sommeliers sniff out the aroma of wine and describe them using beautiful metaphors. In contrast, electronic noses, devices that mimic our olfactory recognition system, also detect smells using their sensors but describe them using electronic signals. These devices have been used to judge the freshness of food or detect the presence of pathogenic microorganisms. However, unlike information from gas chromatography, it is difficult to compare odour information collected by these devices because they are made for smelling specific smells and their data are relative intensities.

Methodology

Here, we demonstrate the use of an absolute-value description method using known smell metaphors, and early detection of yeast using the method.

Conclusions

This technique may help distinguishing microbial-contamination of food products earlier, or improvement of the food-product qualities.

Distributed Network, Wireless and Cloud Computing Enabled 3-D Ultrasound; a New Medical Technology Paradigm

2009-11-19T08:00:00Z

Medical technologies are indispensable to modern medicine. However, they have become exceedingly expensive and complex and are not available to the economically disadvantaged majority of the world population in underdeveloped as well as developed parts of the world. For example, according to the World Health Organization about two thirds of the world population does not have access to medical imaging. In this paper we introduce a new medical technology paradigm centered on wireless technology and cloud computing that was designed to overcome the problems of increasing health technology costs. We demonstrate the value of the concept with an example; the design of a wireless, distributed network and central (cloud) computing enabled three-dimensional (3-D) ultrasound system. Specifically, we demonstrate the feasibility of producing a 3-D high end ultrasound scan at a central computing facility using the raw data acquired at the remote patient site with an inexpensive low end ultrasound transducer designed for 2-D, through a mobile device and wireless connection link between them. Producing high-end 3D ultrasound images with simple low-end transducers reduces the cost of imaging by orders of magnitude. It also removes the requirement of having a highly trained imaging expert at the patient site, since the need for hand-eye coordination and the ability to reconstruct a 3-D mental image from 2-D scans, which is a necessity for high quality ultrasound imaging, is eliminated. This could enable relatively untrained medical workers in developing nations to administer imaging and a more accurate diagnosis, effectively saving the lives of people.

Novel Protein-Protein Interactions Inferred from Literature Context

2009-11-18T08:00:00Z

We have developed a method that predicts Protein-Protein Interactions (PPIs) based on the similarity of the context in which proteins appear in literature. This method outperforms previously developed PPI prediction algorithms that rely on the conjunction of two protein names in MEDLINE abstracts. We show significant increases in coverage (76% versus 32%) and sensitivity (66% versus 41% at a specificity of 95%) for the prediction of PPIs currently archived in 6 PPI databases. A retrospective analysis shows that PPIs can efficiently be predicted before they enter PPI databases and before their interaction is explicitly described in the literature. The practical value of the method for discovery of novel PPIs is illustrated by the experimental confirmation of the inferred physical interaction between CAPN3 and PARVB, which was based on frequent co-occurrence of both proteins with concepts like Z-disc, dysferlin, and alpha-actinin. The relationships between proteins predicted by our method are broader than PPIs, and include proteins in the same complex or pathway. Dependent on the type of relationships deemed useful, the precision of our method can be as high as 90%. The full set of predicted interactions is available in a downloadable matrix and through the webtool Nermal, which lists the most likely interaction partners for a given protein. Our framework can be used for prioritizing potential interaction partners, hitherto undiscovered, for follow-up studies and to aid the generation of accurate protein interaction maps.

Estimation of Immune Cell Densities in Immune Cell Conglomerates: An Approach for High-Throughput Quantification

2009-11-16T08:00:00Z

Background

Determining the correct number of positive immune cells in immunohistological sections of colorectal cancer and other tumor entities is emerging as an important clinical predictor and therapy selector for an individual patient. This task is usually obstructed by cell conglomerates of various sizes. We here show that at least in colorectal cancer the inclusion of immune cell conglomerates is indispensable for estimating reliable patient cell counts. Integrating virtual microscopy and image processing principally allows the high-throughput evaluation of complete tissue slides.

Methodology/Principal findings

For such large-scale systems we demonstrate a robust quantitative image processing algorithm for the reproducible quantification of cell conglomerates on CD3 positive T cells in colorectal cancer. While isolated cells (28 to 80 µm²) are counted directly, the number of cells contained in a conglomerate is estimated by dividing the area of the conglomerate in thin tissues sections (≤6 µm) by the median area covered by an isolated T cell which we determined as 58 µm². We applied our algorithm to large numbers of CD3 positive T cell conglomerates and compared the results to cell counts obtained manually by two independent observers. While especially for high cell counts, the manual counting showed a deviation of up to 400 cells/mm² (41% variation), algorithm-determined T cell numbers generally lay in between the manually observed cell numbers but with perfect reproducibility.

Conclusion

In summary, we recommend our approach as an objective and robust strategy for quantifying immune cell densities in immunohistological sections which can be directly implemented into automated full slide image processing systems.

BFAST: An Alignment Tool for Large Scale Genome Resequencing

2009-11-11T08:00:00Z

Background

The new generation of massively parallel DNA sequencers, combined with the challenge of whole human genome resequencing, result in the need for rapid and accurate alignment of billions of short DNA sequence reads to a large reference genome. Speed is obviously of great importance, but equally important is maintaining alignment accuracy of short reads, in the 25–100 base range, in the presence of errors and true biological variation.

Methodology

We introduce a new algorithm specifically optimized for this task, as well as a freely available implementation, BFAST, which can align data produced by any of current sequencing platforms, allows for user-customizable levels of speed and accuracy, supports paired end data, and provides for efficient parallel and multi-threaded computation on a computer cluster. The new method is based on creating flexible, efficient whole genome indexes to rapidly map reads to candidate alignment locations, with arbitrary multiple independent indexes allowed to achieve robustness against read errors and sequence variants. The final local alignment uses a Smith-Waterman method, with gaps to support the detection of small indels.

Conclusions

We compare BFAST to a selection of large-scale alignment tools - BLAT, MAQ, SHRiMP, and SOAP - in terms of both speed and accuracy, using simulated and real-world datasets. We show BFAST can achieve substantially greater sensitivity of alignment in the context of errors and true variants, especially insertions and deletions, and minimize false mappings, while maintaining adequate speed compared to other current methods. We show BFAST can align the amount of data needed to fully resequence a human genome, one billion reads, with high sensitivity and accuracy, on a modest computer cluster in less than 24 hours. BFAST is available at http://bfast.sourceforge.net.

A Wireless Lingual Feedback Device to Reduce Overpressures in Seated Posture: A Feasibility Study

2009-10-30T07:00:00Z

Background

Pressure sores are localized injuries to the skin and underlying tissues and are mainly resulting from overpressure. Paraplegic peoples are particularly subjects to pressure sores because of long-time seated postures and sensory deprivation at the lower limbs.

Methodology/Principal Findings

Here we report outcomes of a feasibility trial involving a biofeedback system aimed at reducing buttock overpressure whilst an individual is seated. The system consists of (1) pressure sensors, (2) a laptop coupling sensors and actuator (3) a wireless Tongue Display Unit (TDU) consisting of a circuit embedded in a dental retainer with electrodes put in contact with the tongue. The principle consists in (1) detecting overpressures in people who are seated over long periods of time, (2) estimating a postural change that could reduce these overpressures and (3) communicating this change through directional information transmitted by the TDU.Twenty-four healthy subjects voluntarily participated in this study. Twelve healthy subjects initially formed the experimental group (EG) and were seated on a chair with the wireless TDU inside their mouth. They were asked to follow TDU orders that were randomly spread throughout the session. They were evaluated during two experimental sessions during which 20 electro-stimulations were sent. Twelve other subjects, added retrospectively, formed the control group (CG). These subjects participated in one session of the same experiment without any biofeedback.Three dependent variables were computed: (1) the ability of subjects to reach target posture (EG versus CG), (2) high pressure reductions after a biofeedback (EG versus CG) and (3) the level of these reductions relative to their initial values (EG only). Results show (1) that EG reached target postures in 90.2% of the trials, against 5,3% in the CG, (2) a significant reduction in overpressures in the EG compared to the CG and (3), for the EG, that the higher the initial pressures were, the more they were decreased.

Conclusions/Significance

The findings suggest that, in this trial, subjects were able to use a tongue tactile feedback system to reduce buttock overpressure while seated. Further evaluation of this system on paraplegic subjects remains to be done.

Why Does Public Transport Not Arrive on Time? The Pervasiveness of Equal Headway Instability

2009-10-28T07:00:00Z

Background

The equal headway instability phenomenon is pervasive in public transport systems. This instability is characterized by an aggregation of vehicles that causes inefficient service. While equal headway instability is common, it has not been studied independently of a particular scenario. However, the phenomenon is apparent in many transport systems and can be modeled and rectified in abstraction.

Methodology

We present a multi-agent simulation where a default method with no restrictions always leads to unstable headways. We discuss two methods that attempt to achieve equal headways, called minimum and maximum. Since one parameter of the methods depends on the passenger density, adaptive versions—where the relevant parameter is adjusted automatically—are also put forward. Our results show that the adaptive maximum method improves significantly over the default method. The model and simulation give insights of the interplay between transport design and passenger behavior. Finally, we provide technological and social suggestions for engineers and passengers to help achieve equal headways and thus reduce delays.

Conclusions

The equal headway instability phenomenon can be avoided with the suggested technological and social measures.

Fast and Flexible Selection with a Single Switch

2009-10-22T07:00:00Z

Selection methods that require only a single-switch input, such as a button click or blink, are potentially useful for individuals with motor impairments, mobile technology users, and individuals wishing to transmit information securely. We present a single-switch selection method, “Nomon,” that is general and efficient. Existing single-switch selection methods require selectable options to be arranged in ways that limit potential applications. By contrast, traditional operating systems, web browsers, and free-form applications (such as drawing) place options at arbitrary points on the screen. Nomon, however, has the flexibility to select any point on a screen. Nomon adapts automatically to an individual's clicking ability; it allows a person who clicks precisely to make a selection quickly and allows a person who clicks imprecisely more time to make a selection without error. Nomon reaps gains in information rate by allowing the specification of beliefs (priors) about option selection probabilities and by avoiding tree-based selection schemes in favor of direct (posterior) inference. We have developed both a Nomon-based writing application and a drawing application. To evaluate Nomon's performance, we compared the writing application with a popular existing method for single-switch writing (row-column scanning). Novice users wrote 35% faster with the Nomon interface than with the scanning interface. An experienced user (author TB, with 10 hours practice) wrote at speeds of 9.3 words per minute with Nomon, using 1.2 clicks per character and making no errors in the final text.

Bright Field Microscopy as an Alternative to Whole Cell Fluorescence in Automated Analysis of Macrophage Images

2009-10-22T07:00:00Z

Background

Fluorescence microscopy is the standard tool for detection and analysis of cellular phenomena. This technique, however, has a number of drawbacks such as the limited number of available fluorescent channels in microscopes, overlapping excitation and emission spectra of the stains, and phototoxicity.

Methodology

We here present and validate a method to automatically detect cell population outlines directly from bright field images. By imaging samples with several focus levels forming a bright field -stack, and by measuring the intensity variations of this stack over the -dimension, we construct a new two dimensional projection image of increased contrast. With additional information for locations of each cell, such as stained nuclei, this bright field projection image can be used instead of whole cell fluorescence to locate borders of individual cells, separating touching cells, and enabling single cell analysis. Using the popular CellProfiler freeware cell image analysis software mainly targeted for fluorescence microscopy, we validate our method by automatically segmenting low contrast and rather complex shaped murine macrophage cells.

Significance

The proposed approach frees up a fluorescence channel, which can be used for subcellular studies. It also facilitates cell shape measurement in experiments where whole cell fluorescent staining is either not available, or is dependent on a particular experimental condition. We show that whole cell area detection results using our projected bright field images match closely to the standard approach where cell areas are localized using fluorescence, and conclude that the high contrast bright field projection image can directly replace one fluorescent channel in whole cell quantification. Matlab code for calculating the projections can be downloaded from the supplementary site: http://sites.google.com/site/brightfieldorstaining

Revisiting the Myths of Protein Interior: Studying Proteins with Mass-Fractal Hydrophobicity-Fractal and Polarizability-Fractal Dimensions

2009-10-16T07:00:00Z

A robust marker to describe mass, hydrophobicity and polarizability distribution holds the key to deciphering structural and folding constraints within proteins. Since each of these distributions is inhomogeneous in nature, the construct should be sensitive in describing the patterns therein. We show, for the first time, that the hydrophobicity and polarizability distributions in protein interior follow fractal scaling. It is found that (barring ‘all-α’) all the major structural classes of proteins have an amount of unused hydrophobicity left in them. This amount of untapped hydrophobicity is observed to be greater in thermophilic proteins, than that in their (structurally aligned) mesophilic counterparts. ‘All-β’(thermophilic, mesophilic alike) proteins are found to have maximum amount of unused hydrophobicity, while ‘all-α’ proteins have been found to have minimum polarizability. A non-trivial dependency is observed between dielectric constant and hydrophobicity distributions within (α+β) and ‘all-α’ proteins, whereas absolutely no dependency is found between them in the ‘all-β’ class. This study proves that proteins are not as optimally packed as they are supposed to be. It is also proved that origin of α-helices are possibly not hydrophobic but electrostatic; whereas β-sheets are predominantly hydrophobic in nature. Significance of this study lies in protein engineering studies; because it quantifies the extent of packing that ensures protein functionality. It shows that myths regarding protein interior organization might obfuscate our knowledge of actual reality. However, if the later is studied with a robust marker of strong mathematical basis, unknown correlations can still be unearthed; which help us to understand the nature of hydrophobicity, causality behind protein folding, and the importance of anisotropic electrostatics in stabilizing a highly complex structure named ‘proteins’.

Lacunarity Analysis: A Promising Method for the Automated Assessment of Melanocytic Naevi and Melanoma

2009-10-13T07:00:00Z

The early diagnosis of melanoma is critical to achieving reduced mortality and increased survival. Although clinical examination is currently the method of choice for melanocytic lesion assessment, there is a growing interest among clinicians regarding the potential diagnostic utility of computerised image analysis. Recognising that there exist significant shortcomings in currently available algorithms, we are motivated to investigate the utility of lacunarity, a simple statistical measure previously used in geology and other fields for the analysis of fractal and multi-scaled images, in the automated assessment of melanocytic naevi and melanoma. Digitised dermoscopic images of 111 benign melanocytic naevi, 99 dysplastic naevi and 102 melanomas were obtained over the period 2003 to 2008, and subject to lacunarity analysis. We found the lacunarity algorithm could accurately distinguish melanoma from benign melanocytic naevi or non-melanoma without introducing many of the limitations associated with other previously reported diagnostic algorithms. Lacunarity analysis suggests an ordering of irregularity in melanocytic lesions, and we suggest the clinical application of this ordering may have utility in the naked-eye dermoscopic diagnosis of early melanoma.

Performance of Humans vs. Exploration Algorithms on the Tower of London Test

2009-09-29T07:00:00Z

The Tower of London Test (TOL) used to assess executive functions was inspired in Artificial Intelligence tasks used to test problem-solving algorithms. In this study, we compare the performance of humans and of exploration algorithms. Instead of absolute execution times, we focus on how the execution time varies with the tasks and/or the number of moves. This approach used in Algorithmic Complexity provides a fair comparison between humans and computers, although humans are several orders of magnitude slower. On easy tasks (1 to 5 moves), healthy elderly persons performed like exploration algorithms using bounded memory resources, i.e., the execution time grew exponentially with the number of moves. This result was replicated with a group of healthy young participants. However, for difficult tasks (5 to 8 moves) the execution time of young participants did not increase significantly, whereas for exploration algorithms, the execution time keeps on increasing exponentially. A pre-and post-test control task showed a 25% improvement of visuo-motor skills but this was insufficient to explain this result. The findings suggest that naive participants used systematic exploration to solve the problem but under the effect of practice, they developed markedly more efficient strategies using the information acquired during the test.

Incorporating Existing Network Information into Gene Network Inference

2009-08-27T07:00:00Z

One methodology that has met success to infer gene networks from gene expression data is based upon ordinary differential equations (ODE). However new types of data continue to be produced, so it is worthwhile to investigate how to integrate these new data types into the inference procedure. One such data is physical interactions between transcription factors and the genes they regulate as measured by ChIP-chip or ChIP-seq experiments. These interactions can be incorporated into the gene network inference procedure as a priori network information. In this article, we extend the ODE methodology into a general optimization framework that incorporates existing network information in combination with regularization parameters that encourage network sparsity. We provide theoretical results proving convergence of the estimator for our method and show the corresponding probabilistic interpretation also converges. We demonstrate our method on simulated network data and show that existing network information improves performance, overcomes the lack of observations, and performs well even when some of the existing network information is incorrect. We further apply our method to the core regulatory network of embryonic stem cells utilizing predicted interactions from two studies as existing network information. We show that including the prior network information constructs a more closely representative regulatory network versus when no information is provided.

The Impact of Boundary Spanning Scholarly Publications and Patents

2009-08-18T07:00:00Z

Background

Human knowledge and innovation are recorded in two media: scholarly publication and patents. These records not only document a new scientific insight or new method developed, but they also carefully cite prior work upon which the innovation is built.

Methodology

We quantify the impact of information flow across fields using two large citation dataset: one spanning over a century of scholarly work in the natural sciences, social sciences and humanities, and second spanning a quarter century of United States patents.

Conclusions

We find that a publication's citing across disciplines is tied to its subsequent impact. In the case of patents and natural science publications, those that are cited at least once are cited slightly more when they draw on research outside of their area. In contrast, in the social sciences, citing within one's own field tends to be positively correlated with impact.

Network Analytical Tool for Monitoring Global Food Safety Highlights China

2009-08-18T07:00:00Z

Background

The Beijing Declaration on food safety and security was signed by over fifty countries with the aim of developing comprehensive programs for monitoring food safety and security on behalf of their citizens. Currently, comprehensive systems for food safety and security are absent in many countries, and the systems that are in place have been developed on different principles allowing poor opportunities for integration.

Methodology/Principal Findings

We have developed a user-friendly analytical tool based on network approaches for instant customized analysis of food alert patterns in the European dataset from the Rapid Alert System for Food and Feed. Data taken from alert logs between January 2003 – August 2008 were processed using network analysis to i) capture complexity, ii) analyze trends, and iii) predict possible effects of interventions by identifying patterns of reporting activities between countries. The detector and transgressor relationships are readily identifiable between countries which are ranked using i) Google's PageRank algorithm and ii) the HITS algorithm of Kleinberg. The program identifies Iran, China and Turkey as the transgressors with the largest number of alerts. However, when characterized by impact, counting the transgressor index and the number of countries involved, China predominates as a transgressor country.

Conclusions/Significance

This study reports the first development of a network analysis approach to inform countries on their transgressor and detector profiles as a user-friendly aid for the adoption of the Beijing Declaration. The ability to instantly access the country-specific components of the several thousand annual reports will enable each country to identify the major transgressors and detectors within its trading network. Moreover, the tool can be used to monitor trading countries for improved detector/transgressor ratios.