Information privacy: measuring individuals' concerns about organizational practices Abstractl Allen Lee was the accepting senior for this paper. This study provides two major contributions to the privacy literature: (1) a framework describing the primary dimensions of individuals' concerns about organizational information privacy practices and (2) a validated instrument for measuring those concerns. The development process included examinations of privacy literature and U.S. laws; experience surveys and focus groups; and the use of expert judges. The result was a parsimonious 15-item instrument with four subscales tapping into dimensions of individuals' concerns about organizational information privacy practices. The instrument was rigorously tested and validated across several heterogenous populations, p.roviding a high degree of confidence in the scales' validity, reliability, and generalizability.. Before considering implications for researchers and managers, two limitations of this study should be noted. First, all scale development processes require a number of "judgment calls" by researchers based on their analysis of the literature; on input from experience surveys, focus groups, and expert judges; and on levels of acceptability for various statistical measures. In particular, based on input from various sources, we concluded that one of the dimensions, Combining Data, was actually represented by two of the other dimensions, Unauthorized Secondary Use (External) and Collection. We also concluded that Reduced Judgment was not a part of the major =individuals' concerns about organiza- Larger means are associated with higher levels of concem (see Table 1 .), tional information privacy practices" construct. Both of these assessments appear to be consistent with the majority views of scholars, consumers, and advocates, and the four-dimension model of the construct seems to reflect current thinking. We acknowledge, however, that this dimensionality is neither absolute nor static, since perceptions of advocates, consumers, and scholars could shift over time. Thus, the instrument should be viewed as measuring the most central dimensions of the construct at this time. Future research endeavors might consider any changes in these dimensions that may occur. The ultimate objective of this research was the development and validation of an instrument to measure individuals' concerns about organizational information privacy practices. While i! is expected that this instrument will be used primarily in positivist studies, the process of instrument development and validation used in this study included steps that addressed not only what Lee (1991) would call reseamher's positivist understanding (e.g., theory taking the form of independent and dependent variables), but also the subjective understanding (i.e., what the research subjects themselves understand their situation to be) as well as a researcher's interpretive understanding (i.e., what the researcher observes and interprets to be the subjective understanding).Z As can be seen in Stage 1 of Figure 1 ,s an iterative process is used to (1) specify the domain and dimensionality of a construct, (2) generate a sample of items, and (3) assess content validity of these items (i.e., the extent to which scale items appear-to be consistent with the theoretical domain/dimensionality of the construct (Churchill, 1979; Cronbach, 1971) ).. Techniques9 used to accomplish these tasks include literature reviews, experience surveys,lo focus groups, expert judges, and pilot tests with relevant samples. During this stage, based on input from individuals, expert judges, and literature, scale items are trimmed and refined and dimensions may be added, deleted, or modified as understanding of the construct improves.. In Stage 2, the items and the conceptualization of the construct are subjected to "field 7 See Lee (1991) for fuller explanations of these terms.. Also, see remarks in our "Discussion" section. 8 Figure 1 represents a synthesis and adaptation of several models of the development and validation process. It is not claimed to be a definitive model; however, it does include the steps that are widely accepted and have been used in past studies. 9 For further discussion of these techniques, see Bearden, et al., 1993 and Chumhill, 1979 . 10 An experience survey is "not a probability sample but a judgment sample of persons who can offer some ideas and insights into the phenomenon" (Churchill, 1979, p. 67 Bearden, et al. (1993) , Churchill (1979) , and Straub (1989) . tests." A preliminary version of the instrument is administered to various samples, and exploratory factor analysis is utilized to assess the items. ?he instrument is "purified" (Churchill, 1979) as researchers find that certain items should again be added, deleted, or modified. Indeed, the researchers may even find that they must modify their understanding of the construct's dimensionality. Stage 2 continues until the loading of the items in the exploratory factor analysis is consistent with the understanding of the construct's dimensions, and the inter-item reliabilities (Cronbach's alpha) are at satisfactory levels for all dimensions. In addition, Stage 2 includes a comparison of alternative models of the construct through confirmatory factor analysis (CFA). (See the Appendix for a discussion of the merits of CFA.). In Stage 3, the internal validity of the instrument is assessed. This includes evaluations of the instrument's construct, concurrent, and nomological validity. Stage 3 also includes an assessment of the instrument's reliability, specifically internal consistency and testretest reliability. Finally, Stage 3 includes an assessment of the instrument's generalizability (i.e., its usefulness for different populations). In all tests, the instrument must perform at statistically adequate levels. These levels have been documented, based on generally accepted criteria, by numerous writers (see Bagozzi and ¥i, 1988; 1991; Bearden, et ai., 1993; Bentler and Bonett, 1980; Fornell and Larcker, 1981) .. The following sections provide further detail regarding our instrument development process.

O B O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O O O O O B O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O


Identification of pathogen genomic variants through an integrated pipeline Background: Whole-genome sequencing represents a powerful experimental tool for pathogen research. We present methods for the analysis of small eukaryotic genomes, including a streamlined system (called Platypus) for finding single nucleotide and copy number variants as well as recombination events. Results: We have validated our pipeline using four sets of Plasmodium falciparum drug resistant data containing 26 clones from 3D7 and Dd2 background strains, identifying an average of 11 single nucleotide variants per clone. We also identify 8 copy number variants with contributions to resistance, and report for the first time that all analyzed amplification events are in tandem.The Platypus pipeline provides malaria researchers with a powerful tool to analyze short read sequencing data. It provides an accurate way to detect SNVs using known software packages, and a novel methodology for detection of CNVs, though it does not currently support detection of small indels. We have validated that the pipeline detects known SNVs in a variety of samples while filtering out spurious data. We bundle the methods into a freely available package. A problem with using WGS is that it may be inaccessible to laboratories that are not strong in bioinformatics. To address this issue we integrated these modules into a program that we call Platypus (Figure 3) . The pipeline integrates a number of other software programs, and these are referenced in full in this manuscript and in the software documentation. Platypus takes as input either unaligned FastA/FastQ sequencing data, or aligned data in the BAM format. SNVs, CNVs, and potential recombination events are output as annotated text files which can be cross-referenced with PlasmoDB or similar databases.. The Platypus pipeline provides malaria researchers with a powerful tool to analyze short read sequencing data. It provides an accurate way to detect SNVs using known software packages, and a novel methodology for detection of CNVs, though it does not currently support detection of small indels. We have validated that the pipeline detects known SNVs in a variety of samples while filtering out spurious data. We have also tested it against both computational samples and actual data with known CNVs (both deletions and amplifications as verified by microarray) and it can detect the size and boundaries of these CNVs with a high degree of accuracy. The success of the Platypus software in both detecting real genetic variants and avoiding the reporting of false positives over a number of parasite lines can be attributed to its basis on first principles. The SNV detection was Figure 6 Recombination events detected in long term culture samples. A. Reassembled sequences from recombination events indicate a splicing of 56,000 base pairs from the left sub-telomeric region of chromosome 1 on to the right sub-telomeric region of chromosome 10. The center sequence is the assembled recombination from the sequencing data, while the top and bottom are the respective reference sequences for each of the indicated chromosomal regions. Note the clear transition between alignments. B. Read pileup for the two regions containing the predicted recombination. Note the deletion (region 1) on chromosome 1 next to the breakpoint (region 2) and subsequent normal coverage (region 3). Similarly, chromosome 10 shows an amplification event (region 4) next to the breakpoint (region 5) and then subsequent normal alignment (region 6). specifically designed only to use filters that accurately segregated true and false positives, and the robustness of this approach is evident, as there is a completely smooth transition between sensitivity/specificity levels when varying over the ideal filter set. The CNV detection was based on the fundamental theorem of digital signal processing, and indeed the assumptions of this field applies directly to the signals coming off a next-generation whole genome sequencer, complete with random and systematic biases. This streamlined package offers an initial starting point for the field to analyze and report these data in a consistent manner. The detection of single nucleotide and copy number variants (SNVs and CNVs) conferring resistance to drug and vaccine candidates provides researchers with a powerful tool to choose the best combination of agents to treat infectious diseases such as malaria in specific regions, to study pathogen population dynamics and transmission, as well as to engineer new treatments that cannot be easily evaded. In addition, in organisms in which genetic complementation or backcrosses may be difficult or time consuming, whole genome sequencing (WGS) offers an opportunity to determine if second-site mutations may have been inadvertently introduced after transfection or transformation, and contribute to an observed phenotype.. With the reduction in price and increased power of current short-read high-throughput WGS methods and the wide dispersal of a variety of sequencing platforms and accompanying support, full genome sequence data is now relatively easy to generate. Recent advances in the algorithmic and programmatic analysis of WGS data have led to a number of standards, especially the use of the Genome Analysis Toolkit (GATK) [1] , being used in the analyses of human genomic data to detect SNVs and CNVs. However, there are opportunities for more comprehensive analyses of the genomes of simpler eukaryotes such as the~23.5 Mb genome of Plasmodium falciparum, the apicomplexan parasite and etiological agent of human malaria, which has also served as a model for eukaryotic pathogen genomics since the completion and full assembly of its genome sequence in 2002 [2] . Full genome sequencing at 30-40X coverage is now readily achieved [3] [4] [5] [6] . Such coverage allows for the identification of recombination events, the description of SNVs in sequences other than in the exomes, and the detection of small structural variants, including short-length insertion or deletion events. P. falciparum is responsible for up to a million deaths annually [7] , and although its haploid genome is worthy of investigation for this reason alone, it also serves as an ideal test system because heterozygous calls generally do not need to be considered in sequence analysis validation (although mixed infections are a real concern) and a fully assembled reference genome is available [2] . Furthermore, the parasite can be sub-cloned and readily cultured in vitro within white-cell depleted, anucleated human erythrocytes [8] , mitigating host DNA contamination.. In this manuscript, we introduce a validated pipeline for the comprehensive analysis of short-read WGS data in Plasmodium spp.. The pipeline, which can be readily adapted to other small eukaryotes, integrates well-known alignment tools and custom filtration options so that SNV or structural variant data can be easily generated and understood. We believe that the pipeline will work well, once adapted, with species of any ploidy (indeed, it has been used already in Arabidopsis analysis) and genomes of size up to 75 Mbp have been tested. As well, we introduce improved algorithms for utilizing depth of coverage to call CNVs, improving on current GC bias normalization methods [9] . This pipeline is implemented in a stand-alone program called "Platypus", for open distribution and collaboration among research groups. We validate the pipeline using data from 26 P. falciparum samples with known SNVs and CNVs (Table 1) , demonstrating both its accuracy and precision. This pipeline should allow those generating WGS data to not only find all SNVs and structural variants detected by other methods (as well as novel ones) but to eliminate all or almost all false positives, reducing ambiguity and potentially allowing WGS to substitute for complementation, Southern blotting, or other genetic methods designed to link phenotype to genotype. Current genotyping programs are generally designed to be conservative and as a consequence, return a large number of false positive variant calls. These programs, including GATK [1] and the sequence/alignment map toolbox (SAMTools) [13] , typically allow the user to set a number of stringency filters such as the quality of the read alignment or bias towards a specific strand, that can theoretically be used to separate false from true positives. However, the actual threshold values for each filter are not pre-determined, and as such, it is left to the researcher to decide how to best utilize each metric, creating barriers for the novice user. Thus, we set out to create a set of empirically-derived filters for Plasmodium WGS data that could be used as a reference point for future SNV analyses.. To identify a robust set of filtering parameters we began with a list of 15,145 known SNVs identified using traditional Sanger resequencing of Dd2 to 7X coverage [14] and deposited in PlasmoDB (http://plasmodb.org) [15] . These distinguish the multidrug-resistant P. falciparum laboratory Indochina strain, Dd2, from the African drug-sensitive reference strain, 3D7. We then compared a P. falciparum Dd2 strain WGS short-read sequence obtained in our lab to the P. falciparum reference (3D7 strain) sequence. Our Dd2 sequence was generated with 70 bp paired-end reads on an Illumina Genome Analyzer II to a mean of 31X coverage with 96.4% of bases being covered by 5 reads or more. We considered the 15,145 curated SNVs to be true positives. All other SNVs detected were considered false positives, although it is likely that some of the novel SNVs are indeed true genetic differences (genetic diversity, especially in the subtelomeric regions, is extremely high approaching 90% diversity in at least one base position between field samples) [16] . We then worked to identify a set of filtering parameters, which would have the sensitivity to detect at least 90% of the known SNVs, while eliminating as many 'novel' SNVs as possible.. Because the entire mathematical domain of all commonly used filtering parameters (17 characteristics of SNVs and their combinations, see Table 2 ) is too large to search Whole genome sequencing data acquisition statistics from each of the experiments used to validate the pipeline. Note that all of the lines with variants to be called were sub-cloned before sequencing and were sequenced as 70 bp paired end reads, except the KAD (imidazolopiperazines resistant) lines, which were sequenced as 60 bp single end reads. Library preparation details for sequences obtained from previous studies are available in their respective manuscripts. Library preparations for sequences obtained for this study (those resistant to cladosporin), are as follows: 200 bp fragments with 70 bp reads were prepared according to the manufacturers instructions using the Illumina NexTera XT sample preparation kit with accompanying primers and sheared using a Covaris E220x machine. n/anot applicable.. exhaustively in efficient computational time, we developed a genetic searching optimization algorithm that searched over the entire domain of the 17 filtering parameters that characterize WGS data. This 'genetic' class of algorithm implements an objective function ('fitness') that is defined by several filters, and tries to minimize the value of the objective function over the entire domain (the lowest and highest possible values) of filters (every possible combination of filter choices) [17] . In our case we forced the sensitivity at various levels (0-100% in increments of 0.5%) and searched for the maximum specificity at each of those levels. Our objective function was a simple linear combination of all possible quality metrics for SNV data generated by GATK [1] and Picard (http://picard.sourceforge.net), with a varying polynomial coefficient matrix.. We chose a population of 10,000 parameter combinations to run through 100 evolutionary iterations. The algorithm we implemented included a low crossover rate (0.5) and high mutation rate (0.1) as well as a tournament pattern parental determination strategy with a tournament size of 100, and with a guaranteed 10 elite children using the MatLab Global Optimization toolbox. These settings were dynamically determined to give consistency and robustness across a variety of sensitivity ranges. Iterating through a forced sensitivity level in 1% increments yielded a smooth progression along a similar combination of filtering parameters.. The list of 10,000 randomly chosen parameter combinations was assessed for both sensitivity and specificity. Each set of filtering parameters sorted the true positives into two categories ("called" or "not called") and similarly sorted the false positives; these calls were then evaluated for accuracy. Filtering sets that provided high specificity for a given level of sensitivity were carried over to the next round. The filtering parameters were then varied slightly within all successful sets, and individual parameters swapped between sets. After 100 iterative cycles, the most successful sets of filters converged on a single resulta theoretical optimal filtering set. We then added a further set of criteria based on the quality of the sequencing reads. The final optimized set excluded all SNV calls that met any of the following criteria listed in Table 2 .. Using the optimal filtering set we detected 95.0% of the known SNVs with a specificity of 75.6% (8,315 total novel calls), and by lowering the total quality threshold we obtained a sensitivity of 90% of known SNVs, with a specificity of 85.1% (5,077 total novel calls). We generated a receiver operating characteristic curve ( Figure 1 ) using optimal parameter sets at each sensitivity level, labeling three sensitivity threshold points of interest. Principal component analysis did not yield any statistically significant common genomic features (e.g. position on chromosome, position within gene, base pair transition) of the false positives detected, but 55% (4,598 calls) were found in the 12% of the genome we define as sub-telomeric (within 100,000 bp of the chromosomal end) and which likely lie in regions that were not adequately covered by the 7X Dd2 Sanger sequencing [14] . We also searched over a space of multi-dimensional filters (those depending on more than one quality metric in a nonlinear relationship). This included all multiplicative combinations of two and three parameters, as well as exponential, power, logarithmic, and quadratic functions of single parameters, but these filters were unable to find results that were as good as a combined one-dimensional approach (that is, better than the optimal specificity and any sensitivity level), possibly due to the computational complexity of searching over multi-dimensional filters. This set of filtering parameters ( Table 2) is thus implemented in our pipeline and was used for all subsequent analyses.. CNVs contribute substantially to drug resistance in Plasmodium and other eukaryotic pathogens [18] [19] [20] [21] . The current methods for calling CNVs in Plasmodium spp. WGS data, like most pathogenic eukaryotes, rely on smoothing the depth of coverage data (e.g. number of reads aligned to the reference) [22] [23] [24] . Smoothing is needed because sequencing depends on multiple stochastic processes and there can be great variability in the actual coverage over a given stretch of genomic DNA. Users are thus required to guess the appropriate smoothing parameters such as the number of base pairs to be averaged, meaning that the user already needs to know the approximate size of the CNV. Furthermore, it is known that there is also a non-stochastic bias in the depth of coverage due to the tendency of areas of high and low GC content to be sequenced less efficiently and this must also be accounted for, especially as P. falciparum is extremely AT-rich (81%). Because we found that the current algorithms produced a large number of false calls when applied to our WGS data, we sought to address this problem by developing our own CNV calling algorithm.. The first improvement we made to the standard method was to improve GC bias correction. GC-content bias describes the dependence between fragment count (read coverage) and GC content found in high-throughput sequencing assays, particularly the Illumina Genome Analyzer technology. This bias can dominate the signal of interest for analyses that focus on measuring fragment abundance within a genome, such as copy number estimation and is not consistent between samples. We therefore analyzed regularities in the GC-bias patterns, and generated a closed-form compact description for this curve family. It is the GC content of the full DNA fragment (generally 100-200 bp), not only the sequenced read (the 50-100 bp sequenced on each end), that most influences this bias [9] . This GC bias distribution is unimodal: both GC rich fragments and AT rich fragments are under-represented in the sequencing results. Based on these findings, we devised a new method to calculate predicted coverage and correct for the bias.. In order to implement the correction we first calculate the GC content of the sequenced fragment (for paired end reads, both reads plus the insert) after aligning the reads to the reference genome (PlasmoDB 7.1 for imidazolopiperazines, 10.1 for the remainder), assuming that the insert matches the reference genome between the reads exactly. While this assumption does not account for potential point mutations, we have tested the effect of this on the bias normalization algorithm, and it is imperceptible, because point mutations occur so infrequently in a long insert size that the total GC content is not affected. After GC normalization CNVs become much more apparent than they were in the raw data (compare Figure 2A and B) .. Secondly, after GC content normalization, the depth of coverage must be 'smoothed' so that true CNVs can be detected and random fluctuations in the data can be identified and discarded. However, smoothing algorithms tend to blur the divisions between otherwise sharp edges. Thus we also developed a simple iterative process of smoothing and edge detection that would identify these boundaries. This step integrates an iterative Weierstrass transform followed by edge detection through convolution with a first-derivative Gaussian kernel [25] . These can be described as follows: Let D n be the smoothed depth of coverage of a chromosome of length l normalized after n iterations. Then, with a Gaussian kernel G with arbitrary coefficient k, we have, for all positions j on the chromosome, χ j :. Which we can expand to:. We can detect the edges of this data by finding all solutions:. Which is expanded to: Figure 1 Receiver operating characteristic for SNV optimization. An ROC for the filtering parameters used in SNV detection optimization. Red points indicate the calculated specificity for certain fixed sensitivity levels. The blue line indicates the calculated specificity and sensitivity in 0.5% increments along the entire range of parameters. The optimal set of parameters for the GATK is given in Table 2 . SNVs were then divided into either a 'called or 'not called' category based on these metrics and the current set of filters being used. The following metrics were obtained from the Unified Genotyper: read depth, strand bias, haplotype score, homopolymer run length, total positional mapping quality, number of null mapping qualities, total positional quality, total quality by depth, and genotype quality (DP, FS, HaplotypeScore, HRun, MQ, MQ0, QUAL, QD, GQ). These SNVs were then hard filtered using the Variant Filtration Walker according to the given set of parameters, as in Table 2 .. An example of the output of this algorithm is demonstrated in Figure 2C .. To save computational time, we applied the convolution theorem to take these operators in the Fourier space and as such, reduce all operations to point-wise multiplication. After each Weierstrass transform, edges are detected by the above formula. The total number of convolution iterations was set to be variable in the first in silico tests, ending only when no new edges had appeared in the last 10 iterations, but was eventually held constant at 5 because in practice no new edges appeared after the 2nd or 3rd iterations of the algorithm. We must treat the mitochondrial and apicoplast genome separately, as the depth of coverage of these is usually very different than the other Plasmodium chromosomes, even by an order of magnitude. The depth of coverage in each region (i.e. between each edge) is then compared to the sample mean, and those that are statistically higher or lower are assigned an amplification number based on their increase (or decrease) relative to the mean.. Recombination contributes substantially to the virulence of many eukaryotic pathogens such as P. falciparum and T. bruceii where genome encoded virulence factors are located in hyper-recombinogenic sections of the genome. In addition, such rearrangements could contribute to a phenotype if no causative SNV or clear dosage effect in a likely target is found. We thus sought to implement a program to find these recombination events.. Our strategy was to identify fragments with mated pairs that had abnormal insert sizes when they were aligned to a reference genome, especially ones with mated pairs that aligned to two different chromosomes or to vastly distant parts of the same chromosome. To find the initial events, all reads which had a mates aligning farther than 10 kb away from each other or on another chromosome were extracted and each region with a group of 10 or more overlapping reads with this property was de novo assembled using PRICE [26] with 20 cycles and otherwise standard settings (−icf $x 1 1 5, -nc 20, -dbmax 100, -maxHp 7, -lenf 2500 20). These contigs were then aligned against the reference genome using ClustalW to discover the origin of each part of the contig. Figure 3A , step IVc outlines the recombination detection process.

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O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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Transitory behaviors in diffusively coupled nonlinear oscillators Abstract We study collective behaviors of diffusively coupled oscillators which exhibit out-of-phase synchrony for the case of weakly interacting two oscillators. In large populations of such oscillators interacting via one-dimensionally nearest neighbor couplings, there appear various collective behaviors depending on the coupling strength, regardless of the number of oscillators. Among others, we focus on an intermittent behavior consisting of the allsynchronized state, a weakly chaotic state and some sorts of metachronal waves. Here, a metachronal wave means a wave with orderly phase shifts of oscillations. Such phase shifts are produced by the dephasing interaction which produces the out-of-phase synchronized states in two coupled oscillators. We also show that the abovementioned intermittent behavior can be interpreted as in-out intermittency where two saddles on an invariant subspace, the all-synchronized state and one of the metachronal waves play an important role.Keywords Diffusively coupled systems of oscillators Á Out-of-phase synchrony Á Metachronal waves Á In-out intermittency Electrically coupled interneurons via gap junctions (GJ) have been widely observed in the mammalian neocortex (Galarreta and Hestrin 1999; Gibson et al. 1999 ). Motivated by this observation, many theoretical studies of collective behaviors of GJ-coupled interneurons have been conducted by the use of neural oscillators interacting via diffusion type couplings.. Although it had been widely believed that the GJ-coupling among interneurons promotes their synchronous firing (Galarreta and Hestrin 1999; Gibson et al. 1999 ), Sherman and Rinzel (1992) first observed that weak GJ-coupling can lead dephasing and phase locking by anti-phase in two coupled neural oscillators. Later, Han et al. (1995 Han et al. ( , 1997 demonstrated how diffusion type weak couplings can lead to dephasing of two oscillators by using the Morris-Lecar model. They also found alternations between synchronization and desynchronization of oscillations in a large population of coupled oscillators. Also in other systems, for instance, in electrochemical dynamical systems, Karantonis and Nakabayashi (2001) found a similar phenomenon in diffusively coupled electrochemical oscillators. The present authors also found that some kinds of neural oscillator, when diffusively coupled, exhibit transitory behaviors, i.e., spontaneously irregular transitions between various dynamical states such as synchronized states and chaotic states .. The earlier studies mentioned above (Sherman and Rinzel 1992; Han et al. 1995 Han et al. , 1997 Karantonis and Nakabayashi 2001) and our previous study show different synchronies in two-oscillator system with weak diffusion coupling. While two oscillators synchronize in anti-phase in the former cases, they synchronize in out-of-phase indicating the phase difference not necessarily equal to p in the latter. Little is known about collective behaviors in large populations of coupled oscillators which have the out-of-phase synchrony in the case of the two oscillator system. In this paper, we show that there appear various transitory behaviors in such diffusively coupled oscillators and one of them can be interpreted as in-out intermittency.. Transitory behaviors with aperiodic changes between dynamic states have been observed as cortical activity, such as fluctuations of local field potentials accompanying with transient synchrony (Gray et al. 1992) and spontaneous cortical activity which encompasses a set of dynamically switching cortical states (Kenet et al. 2003) . Two of the present authors have proposed a hypothesis on the mechanism of the observed chaotic field , that the origin of temporal fluctuations and transient synchrony observed in the neocortical activity stems from chaotic transitions among dynamic states appearing in gap junction (GJ)-coupled interneuron systems. The GJ-coupled interneurons to pyramidal cells can influence in the fluctuations of membrane potentials of the pyramidal cells, which could be experimentally observed.. This paper is organized as follows: In section ''A nonlinear oscillator model, its diffusively coupled system, and dynamics of diffusively coupled two oscillator system'', we describe the nonlinear oscillator and its diffusively coupled system which we treat here. We also discuss the stability of synchronous states in diffusively coupled two oscillators. In section ''Dynamics of diffusively coupled N-oscillator system'', we discuss behaviors appearing in diffusively coupled N-oscillator system in the case of N [ 2. In subsection ''Bifurcation structures of periodic states and system size dependence'', we discuss bifurcation structures of periodic states of coupled N-oscillator systems. And we also show that they, when viewed as functions of rescaled coupling strength g/N 2 , are not depend on N in the case of slightly large N. In subsection ''Transitory behaviors'', we discuss one of typical transitory behaviors appearing in the coupled systems. We also show that it can be interpreted as inout intermittency. In subsection ''Markov chain model'', we calculate the probability distribution of laminar duration of the in-out intermittency and compare it with the one calculated by using a Markov chain model of the in-out-intermittency. In subsection ''Bifurcations along with variation in the coupling strength'', we describe various behaviors appearing through successive bifurcations with variations in the coupling strength. Section ''Summary and discussion'' is devoted to summary and discussion.. A nonlinear oscillator model, its diffusively coupled system, and dynamics of diffusively coupled two oscillator system A nonlinear oscillator model and its diffusively coupled system. The nonlinear oscillator treated here is described by . When it is viewed as a neuron model, the variable V represents the membrane potential of a neuron and the other variable R is a recovery variable representing an activation state, and the parameter I represents an injected current. This model has another parameter l which will be fixed to the value, 1.65 throughout this article. Although this model is essentially the same as the Hindmarsh-Rose model (Hindmarsh and Rose 1984) with two variables, it was derived as a minimal oneparameter family of two-dimensional neural dynamical systems showing both Hopf bifurcation and saddle-node bifurcation . We called it l-model. Figure 1a shows the bifurcation diagram of the model when the injected current I is a bifurcation parameter. The model exhibits saddle-node bifurcation (I = 0) and Hopf bifurcation (I * 0.19), and there appears a limit cycle oscillation between these bifurcation points. Figure 1b shows nullclines for V and R together with a limit cycle for I = 0.004.. The diffusively coupled system of the l-models obeys the following equations:. where N is the number of oscillators and g is the coupling strength. Here the couplings are introduced in variables V i . We treat the case of one-dimensional nearest neighbor coupling with a free boundary condition, which is in accord with the Neumann type of boundary condition in the continuous space limit.. A coupled two oscillator system. Before showing cases of large numbers of oscillators, in this subsection we treat the case of N = 2. In the weak interaction limit, the evolution of the phase difference d/ = / 1 -/ 2 between two oscillators with phases / 1 and / 2 is governed by (Kuramoto 1984) . where C a is the antisymmetric part of the effective coupling defined by. Here V(/ 0 ) denotes the variable V at phase / 0 on the limit cycle. The phase sensitivity function Z(/) gives the change of phase along the limit cycle caused by the change of state vector (V, R) in phase space. Figure 2a shows C a ðd/Þ for I = 0.004. In this figure, it is shown that the system has three types of synchronized states: the unstable in-phase and anti-phase states, and the stable out-of-phase states. The time-series of V 1 and V 2 in one of the out-of-phase synchronized states for I = 0.004 and g = 0.005 is shown in Fig. 2b .. In the case of coexistence of a limit cycle and a stable node with an intervening saddle, it was shown that the saddle causes the deformations of the phase flow and thus the diffusion type of coupling between such oscillators can produce dephasing interaction under a certain condition (Han et al. 1995) . In the case of the l-model, a limit cycle does not coexist with a saddle and a stable node (see Fig. 1 ). Nevertheless, such dephasing interaction can survive even after the saddle disappears via saddle-node bifurcation, because the main features of the phase flow in the vicinity of the limit cycle continue to remain unchanged (Han et al. 1995) . Therefore, it is probable that the dephasing interaction in the case of the l-model is also attributed to this mechanism.. In the case of relatively strong coupling, where the discussion based on the effective coupling cannot be applicable, in-phase and anti-phase synchronization can be stabilized, and either of them appears depending on the initial phase difference of two oscillators. The time-series of V 1 and V 2 in the anti-phase synchronized state for g = 0.02 is shown in Fig. 2c .

O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O B I O O O O B I I I I O B I O B I O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O


The augmented knowledge workshop This paper discusses the theme of augmenting a knowledge workshop. The first part of the paper describes the concept and framework of the knowledge workshop. The second part describes aspects of a prototype knowledge workshop being developed within this framework. First, one can see a definite evolution of new workshop architecture in the trends of computer application systems. An "augmented workshop domain" will probably emerge because many special-purpose application systems are evolving by adding useful features outside their immediate special application area. As a result, many will tend to overlap in their general knowledge work supporting features.. Second, research and development is being directed toward augmenting a "Core" Knowledge Workshop domain. This application system development is aimed expressly at supporting basic functions of knowledge work. An important characteristic of such systems is to interface usefully with specialized systems. This paper is oriented toward this second approach.. Within the framework described above, ARC is developing a prototype workshop system. Our system does not meet all the requirements outlined previously, but it does have a powerful set of core capabilities and experience that leads us to believe that such goals can be achieved.. Within ARC we do as much work as possible using the range of online capabilities offered. We serve not only as researchers, but also as the subjects for the analysis and evaluation of the augmentation system that we have been developing.. Consequently, an important aspect of the augmentation work done within ARC is that the techniques being explored are implemented, studied, and evaluated with the advantage of intensive everyday usage. W 7 e call this research and development strategy "bootstrapping.". In our experience, complex man-machine systems can evolve only in a pragmatic mode, within real-work environments where there is an appropriate commitment to conscious, controlled, exploratory evolution within the general framework outlined earlier. The plans and commitments described later are a consistent extension of this pragmatic bootstrapping strategy.. To give the reader more of a flavor of some of the many dimensions and levels of the ARC workshop, four example areas are discussed below in more detail, following a quick description of our physical environment.. The first area consists of mechanisms for studying and browsing through NLS files as an example of one functional dimension that has been explored in some depth.. The second area consists of mechanisms for collaboration support-a subsystem domain important to many application areas.. The third and fourth areas, support for software engineers and the ARPANET Network Information Center (NIC), show example application domains based on functions in our workshop.. The functions to be described form a set of controls for easily moving one around in an information space and allowing one to adjust the scope, format, and content of the information seen. 26 41 Given the addition of graphical, numerical, and vocal information, which are planned for addition to the workshop, one can visualize many additions to the concepts below. Even for strictly textual material there are yet many useful ideas to be explored.. The approach to collaboration support taken at ARC to date has two main thrusts:. (1) Support for real-time dialogue (teleconferencing) for two or more people at two terminals who want to see and work on a common set of material. The collaborating parties may be further augmented with a voice telephone connection as well. (2) Support for written, recorded dialogue, distributed over time.. These two thrusts give a range of capabilities for support of dialogue distributed over time and space.. As ARC has become more and more involved in the augmentation of teams, serious consideration has been given to improving intra-and inter-team communication with whatever mixture of tools, conventions, and procedures will help. 273639 If a team is solving a problem that extends over a considerable time, the members will begin to need help in remembering some of the important communicationsi.e., some recording and recalling processes must be invoked, and these processes become candidates for augmentation.. If the complexity of the team's problem relative to human working capacity requires partitioning of the problem into many parts-where each part is independently attacked, but where there is considerable interdependence among the parts-the communication between various people may well be too complex for their own accurate recall and coordination without special aids.. Collaborating teams at ARC have been augmented by development of a "Dialogue Support System (DSS)," containing current and thoroughly used working records of the group's plans, designs, notes, etc. The central feature of this system is the ARC Journal, a specially managed and serviced repository for files and messages.. The DSS involves a number of techniques for use by distributed parties to collaborate effectively both using general functions in the workshop and special functions briefly described below and more fully in Reference 39. Further aspects are described in the section on Workshop Utility Service.. One of the important application areas in ARC's work is software engineering. The economics of large computer systems, such as NLS, indicate that software development and maintenance costs exceed hardware costs, and that software costs are rising while hardware costs are rapidly decreasing. The expected lifetime of most large software systems exceeds that of any piece of computer hardware. Large software systems are becoming increasingly complex, difficult to continue evolving and maintain. Costs of additional enhancements made after initial implementation generally exceed the initial cost over the lifetime of the system. It is for these reasons that it is important to develop a powerful application area to aid software engineering. Areas of software engineering in which the ARC workshop offers aids are described below.. The NIC is presently a project embedded within ARC. 39 Workshop support for the NIC is based on the capabilities within the total ARC workshop system.. As useful as is the bootstrapping strategy mentioned earlier, there are limits to the type of feedback it can yield with only ARC as the user population. The NIC is the first of what we expect will be many activities set up to offer services to outside users. The goal is to provide a useful service and to obtain feedback on the needs of a wider class of knowledge workers. Exercised within the NIC are also prototypes of information services expected to be normal parts of the workshop.. The NIC is more than a classical information center, as that term has come to be used, in that it provides a wider range of services than just bibliographic and "library" type services.. The NIC is an experiment in setting up and running a general purpose information service for the ARPANET community with both online and offline services. The services offered and under development by the NIC have as their initial basic objectives:. (1) To help people with problems find the resources (people, systems, and information) available within the network communitv that meet their needs.. (2) To help members of geographically distributed groups collaborate with each other.. Following are the NIC services now provided to meet the above goals in serving the present clientele:. Within a particular professional task area (mission-or discipline-oriented) there are often groups who could be benefited by using special workshop subsystems. These subsystems may be specialized for their specific application or research domain or for support of their more general knowledge work. Our goal is to offer a workshop utility service that contains a range of subsystems and associated methodology particularly aimed at aiding general knowledge work, and that also supports in a coordinated way special application subsystems either by interfacing to subsystems already existing, or by developing new subsystems in selected areas.. In the descriptions to follow are a number of workshop subsystem domains that are fundamental to a wide range of knowledge work in which ARC already has extensive developments or is committed to work. For each subsystem we include some general comments as well as a brief statement of current ARC capabilities in the area. The Network Information Center is an example prototype of a new type of information service that has significant future potential. Even though it is presently in an experimental and developmental phase, it is providing useful online and offline services to the ARPANET community. It is now time for a next stage of application to be established. We want to involve a wider group of people so that we can begin to transfer the fruits of our past work to them and with their assistance, to others, and so that we can obtain feedback needed for further evolution from wider application than is possible in our project alone. 28 We want to find and support selected groups who are willing to take extra trouble to be exploratory, but who:. (1) Are not necessarily oriented to being core-workshop developers (they have their own work to do). (2) Can see enough benefit from the system to be tried and from the experience of trying it so that they can justify the extra risk and expense of being "early birds." (3) Can accept assurance that system reliability and stability, and technical/application help will be available to meet their conditions for risk and cost.. ARC is establishing a Workshop Utility Service, and promoting the type of workshop service described above as part of its long-term commitment to pursue the continued development of augmented knowledge workshops in a pragmatic, evolutionary manner.. It is important to note that the last few years of work have concentrated on the means for delivering support to a distributed community, for providing teleconferencing and other basic processes of collaborative dialogue, etc. ARC has aimed consciously toward developing experience and capabilities especially applicable to support remote and distributed groups of exploratory users for this next stage of wider-application bootstrapping.. One aspect of the service is that it will be an experiment in harnessing the new environment of a modern computer network to increase the feasibility of a wider community of participants cooperating in the evolution of an application system.

O O B B O O O O O O O O B B O O O O O O O O O O O O O B B O O O O O O O O B B O O O O O O O O O O O O O O B O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O B B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O


HandVR: a hand-gesture-based interface to a video retrieval system Using one's hands in human-computer interaction increases both the effectiveness of computer usage and the speed of interaction. One way of accomplishing this goal is to utilize computer vision techniques to develop handgesture-based interfaces. A video database system is one application where a hand-gesture-based interface is useful, because it provides a way to specify certain queries more easily. We present a hand-gesture-based interface for a video database system to specify motion and spatiotemporal object queries. We use a regular, low-cost camera to monitor the movements and configurations of the user's hands and translate them to video queries. We conducted a user study to compare our gesture-based interface with a mouse-based interface on various types of video queries. The users evaluated the two interfaces in terms of different usability parameters, including the ease of learning, ease of use, ease of remembering (memory), naturalness, comfortable use, satisfaction, and enjoyment. The user study showed that querying video databases is a promising application area for hand-gesturebased interfaces, especially for queries involving motion and spatiotemporal relations. Convenience of the interaction device is one of the main criteria for effective human-computer interaction (HCI). There is no one interface suitable for all applications; the one that is the most effective and comfortable for the users is the most appropriate. For example, the human hand provides a very promising interface for certain applications. In fact, hand interfaces are supersets of mouse-based interfaces because the capabilities of a mouse can be easily simulated by a hand. Hand-based systems, however, have poor pixel accuracy, due generally to the low-resolution cameras used to monitor the hands and the image processing involved. Fortunately, not all applications require high pixel accuracies, such as the proposed video query interface.. At first, electromechanical gloves that track the user's palm and fingers were used for hand interaction, but this method was uncomfortable, expensive, and complex. An alternative is a vision-based system, in which one or more cameras monitor the user's hands, and the images acquired from the cameras are processed to determine the command the user performs. This system does not require any wearable or attached electromechanical equipment, that is, it is a passive interface. Furthermore, it only needs an inexpensive camera for image acquisition, and it provides the user with a completely immersive interaction experience. However, there are still some problems with such vision-based systems. First, robust real-time vision systems have not yet been developed; many vision applications work under some constraints, e.g., static background, markers for the users. Second, further research is needed to determine appropriate vision-based hand interface applications and evaluate their performance. This paper contributes to the second problem by investigating whether querying a video database system is an appropriate application for a vision-based hand interface.. Video retrieval systems provide fast access to large video collections, and they are becoming important due to the growing amount of video data [1] . BilVideo-7 [2] is one such system; it supports text, color, texture, shape, location, motion, and spatiotemporal object queries on videos. First, videos are decomposed into their building blocks: shots, keyframes, still, and moving regions. Then, features are extracted and stored in a database, which can be queried via a visual query interface.. The primary goal of the visual query interface is to provide users with a powerful and easy-to-use interface to formulate various queries on a video database and retrieve the most relevant videos or video segments. Some queries are easy to formulate using keywords (query by keyword), for example, "Retrieve video segments that contain an airplane." In this case, the user enters the keyword(s) using the keyboard, presses the enter key to execute the query, and waits for the results. If the query interface has speech recognition capability, the keywords can also be entered with speech. Some queries are easier to formulate using examples (query by example) or sketches, such as retrieving video segments having similar color, texture, motion, etc., to the video segment or sketch that is provided by the user.. We designed our hand-gesture-based query interface to support four different query types: (1) spatial queries, (2) motion trajectory queries, (3) motion trajectory with temporal relation queries, and (4) camera motion queries [2] . In the query interface, the hands represent stationary or moving objects (query types 1, 2, and 3), or a camera in different types of motion (query type 4). Therefore, the hands need to be continuously monitored to keep track of their configurations; this is done by a camera connected to a PC running a low-level visual processing module which processes the video from the camera to track the hands.. Our system employs one webcam to monitor the user's hand movements. To facilitate and speed up the hand monitoring process (robustly detect, recognize, and track the hands in real time), the user wears uniformly colored gloves on her hands. Time-of-flight or projective depth cameras (MS Kinect) [3] can also be used for this purpose within the proposed framework instead of wearing different-colored gloves, but since our focus is to investigate the applicability of a hand-gesture-based interface for query formulation in a video database, our colored glove-based system works well for our purposes.. We conducted a user study to evaluate and compare our gesture-based interface with a mouse-based interface. The users performed predefined test queries for each query type on both interfaces and filled out a questionnaire. We evaluated the results to judge the suitability of a hand-gesture-based interface for different types of queries in a video database. The results showed that the gesture-based interface is better for camera motion and motion trajectory with temporal relation queries. We investigated whether a hand-based interface is appropriate for efficient query formulation on video retrieval systems. This was motivated by the observation that it is very hard to formulate certain queries with a mouse-based interface. Such queries usually require an interaction method/device with a higher degree of freedom; hence, the mouse is insufficient to formulate these queries efficiently. As a solution, we proposed a hand-gesture-based interface, by taking advantage of human hands as the main device for the interaction.. We conducted a user study to compare our hand interface with a mouse interface in terms of attitude and performance criteria on four types of video queries. The results showed that the participants were happy with the mouse interface for the formulation of spatial and motion trajectory queries and that a hand-based interface is more appropriate for motion trajectory with temporal relations and camera motion queries. For the latter queries, human hands are used as an interface device with higher degree of freedom than a mouse, which allowed the participants to prepare such queries efficiently. Although the idea of using hands in HCI is promising, it is not effective in all applications. Appropriate applications for hand interfaces should be determined by considering users' assessments of usability criteria. Some applications focused on low-level visual processing in hand interface systems [4, 5] . However, there exists limited literature on the usability of hand-based systems. To the best of our knowledge, there are no hand-based interfaces for video retrieval systems in the literature; thus, we aim to fill this gap.. Barehand interaction is desirable in hand-based vision systems; however, it is challenging to achieve robust real-time visual processing performance to monitor the hands. Kolsch and Turk [6] developed a vision-based hand gesture interface, HandVu, to detect and track a hand for wearable mobile applications. It tracks hands well but requires high processing power. Segen and Kumar [7] used barehand interaction for their GestureVR system, but it requires a uniform background. Stauffer and Grimson [8] proposed a method that updates the background model adaptively. This method gives good results for gradual background changes, but it fails in indoor environments where sudden changes may occur frequently. Since our focus is on hand-gesture interface, rather than the low-level visual processing for hand monitoring, we decided to use colored gloves to reduce the problems due to low-level visual processing.. Wang and Popovic [9] developed a system that can reconstruct a 3D hand pose from a single image of the hand wearing a specially designed multi-colored glove. Although there are many sensor-based glove hardware systems that can track and reconstruct a hand robustly [10] , Wang and Popovic's system is more comfortable. Since our system does not need 3D model of hand, we sticked to uniformly colored gloves instead of a specially colored or sensor-based gloves.. Numagucci et al. [11] proposed a puppet system to retrieve movie clips that are similar to the motions of a puppet from a motion capture database. They proposed an algorithm to match puppet motions from a movie clip database. Our system enables a user to describe the objects, their motions, and spatiotemporal relations between them by hands. This differs from the study of Numagucci's in two ways. Our system does not use any external objects such as a puppet to define the motion, and the hands describe the objects and their relations, not the motion of one person. In our hand-gesture-based interface, the user formulates queries using her hands (one or both hands, depending on the query) without wearing electromechanical devices. The user's hands are monitored by a camera. The height of the camera determines the available working space of the user. The user wears two different-colored gloves on her hands. The gloves can be in any color provided that they are uniformly colored, and the background does not contain the colors of the gloves. The system is trained once for a pair of gloves (colors), as described in Sect. 5.1. We also assume that severe lighting changes do not occur after training the system for a pair of gloves (colors), in which case, the system needs to be retrained. These constraints are imposed to enable real-time visual processing, which is important for an interactive system.. Our system has two main modules: (1) visual processing module acquires images from the camera and processes them to keep track of the hands' configurations, which are fed to the (2) query interface (Fig. 1 ). The query interface interacts with the user (get inputs, display results, hand properties) and forms the queries according to the query language of the video database system. We conducted a user study to assess the usability of the proposed hand-based interface and a mouse-based interface in terms of performance and attitude criteria [14] . The attitude criteria are usefulness, learning, memory, naturalness, comfort, satisfaction, and enjoyment. The number of trials (or error rate) and the task completion time (elapsed times) are used to measure the performance of the two interfaces.. We evaluated the performance and usability of the two interfaces for each query type (Sect. 4.2), using 10 test queries. The participants were instructed to formulate the given queries using both interfaces and fill out a questionnaire on the attitude criteria. During the experiments, we also measured the error rates and task completion times of the participants. The following hypotheses were determined before building the proposed hand interface.. H1 Spatial queries, where the user defines the object's position, size, and orientation, are easily formed using the mouse-based interface. We do not expect the handbased interface to improve the usability and performance noticeably because the capability of a mouse is sufficient for these operations. The main concern in a motion trajectory query is to draw a path. This can be easily handled by a mouse-based interface. We do not expect the hand-based interface to improve the usability and performance significantly over the mouse-based interface. H3 Motion trajectory with temporal relation queries requires the correct timing of object motions relative to each other. As an example, consider a query to search for two objects colliding, or two cars moving from left to right, one after the other. Each object has its own path, and the paths should be drawn with the appropriate timing (temporal relation between motion trajectories). With a mouse-based interface, it is easy to draw the trajectory of one object, but hard to specify the timing for more trajectories. With a hand-based interface, it is easy to specify both the trajectory and timing of two objects using two hands. Therefore, we expect our hand-based interface to improve both the usability and the performance significantly. H4 Camera motion queries define the parameters of a camera, such as its pan motion, zoom level, and rotation around the z-axis. Usually, when drawing a path for a pan motion, one must specify the zoom level of the camera during the pan motion as well. Since a mouse-based interface has a limited degree of freedom (x-y movement, right button click, etc.), it is not appropriate for specifying multiple camera properties at the same time.. Unlike the mouse-based interface, a hand-based interface is better at providing many properties at once. For instance, the center position of a hand represents the position of a camera, while hand size represents its zoom level, and hand orientation represents its viewing angle. We expect that specifying camera motion queries using a hand-based interface is easier and more efficient.

O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O


The Banzhaf index in complete and incomplete shareholding structures: A new algorithm In this global world many firms present a complex shareholding structure with indirect participation, such that it may become difficult to assess a firm's controllers. Furthermore, if there are numerous dominant shareholders, the control can be shared between them. Determining who has the most influence often is a difficult task. To measure this influence, game theory allows modeling voting game and computing the Banzhaf index. This paper first offers a new algorithm to compute this index in all structures and suggests some modelisations of the floating shareholder. Then, our model is applied to a real case study: The French Group Lafarge. This exemplary case demonstrates how the float's structure and hidden coalition can impact the power relationship between dominant shareholders. Abstract:In this global world many firms present a complex shareholding structure with indirect participation, such that it may become difficult to assess a firm's controllers. Furthermore, if there are numerous dominant shareholders, the control can be shared between them. Determining who has the most influence often is a difficult task. To measure this influence, game theory allows modeling voting game and computing the Banzhaf index. This paper first offers a new algorithm to compute this index in all structures and suggests some modelisations of the floating shareholder. Then, our model is applied to a real case study: The French Group Lafarge. This exemplary case demonstrates how the float's structure and hidden coalition can impact the power relationship between dominant shareholders. JEL Classifications: C63, G32, L22

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Understanding the mechanisms amenable to CRT response: from pre-operative multimodal image data to patient-specific computational models Abstract This manuscript describes our recent developments towards better understanding of the mechanisms amenable to cardiac resynchronization therapy response. We report the results from a full multimodal dataset corresponding to eight patients from the euHeart project. The datasets include echocardiography, MRI and electrophysiological studies. We investigate two aspects. The first one focuses on pre-operative multimodal image data. From 2D echocardiography and 3D tagged MRI images, we compute atlas based dyssynchrony indices. We complement these indices with presence and extent of scar tissue and correlate them with CRT response. The second one focuses on computational models. We use pre-operative imaging to generate a patient-specific computational model. We show results of a fully automatic personalized electromechanical simulation. By case-per-case discussion of the results, we highlight the potential and key issues of this multimodal pipeline for the understanding of the mechanisms of CRT response and a better patient selection. Cardiac resynchronization therapy (CRT) can relieve heart failure (HF) symptoms by reducing heart dyssynchrony through the implantation of a pacemaker. However, nonresponse rates to CRT rise to 30 % (clinical response) or 44 % (volume response) [5] . Thus, patient selection and pacemaker configurations remain open challenges of high concern and focus within the clinical community. Recent updates of the official guidelines for CRT from the European Society of Cardiology now include a number of additional patient subgroups that were previously omitted [32] . Several research groups are also investigating new pacing configurations (number and position of leads) in experimental models under fully controlled conditions [47] as well as the different parameters that are related to response to CRT [4] .. Patient-specific cardiac imaging tools and computational models can help to understand and improve CRT, since they combine anatomical and functional pre-operative data to provide new insights into dyssynchrony mechanics [41] . This has motivated our research under two driving questions: (1) Can pre-operative multimodal image data improve our understanding of the mechanisms of CRT response? (2) Can in silico electromechanical simulations improve our understanding of intra-ventricular mechanical dyssynchrony? This manuscript describes our recent developments towards answering these two questions. These developments have been applied to clinical cases collected for a multi-center study within the euHeart project. Most of the components presented in this work are already integrated into a common software framework, constituting the cardiac resynchronization therapy planning platform, currently implemented in an open-source software, GIMIAS [26] . To understand and improve CRT, we investigated two aspects in this study: pre-operative multimodal image data and patient-specific computational models. From our observations, along with the studies discussed above (Sect. 5), we can conclude the following.. First, image-based criteria can complement the current criteria for selecting CRT candidates. Nonetheless, special care is required for preserving the quantitative information embedded in such mechanical dyssynchrony indices, and not reducing them to the definition of yet another threshold for CRT patient selection. Rather, the likelihood of response should be analyzed based on a deeper understanding of the dyssynchrony patterns of each given patient and the chances of properly delivering the therapy given the patient substrate. By analyzing pre-operative multimodal image data, we can identify the dyssynchrony patterns that will most likely benefit from CRT. In addition, computational models can help to discriminate between non-responders originated from a lack of electrical resynchronization, problems of tissue stimulation (e.g., large scar areas), or mechanical defects.. Second, modeling the electrical defect (LBBB) alone is not enough to capture the mechanisms of intra-ventricular dyssynchrony. From the insights obtained from our preoperative image data, we observed that dyssynchrony mechanisms can vary significantly among CRT candidates. Thus, there is a need for electromechanical simulations that accurately reproduce patient-specific dyssynchrony patterns.. Third, several recent studies suggest the strong potential of electromechanical models to reproduce the effect of CRT on patients. In our study, we observed that with a correct personalization of the eletrophysiological model, abnormal septal motion is retrievable. However, we believe that the whole phenomenon of septal flash, including interventricular pressure differences, lateral pulling and septal stretching, requires further investigation. For instance, parametrization of current electromechanical models should be improved through better electromechanical coupling, inclusion of patient-specific viability information (i.e., scar) and plausible anatomical locations of pacing (i.e., coronary tree), more detailed boundary conditions (e.g., hemodynamics computed by the CircAdapt model), and inclusion of growth models to evaluate the chronic effect of the therapy. Once these issues are tackled, we can further explore the potential of patient-specific electromechanical models to assess whether synchronicity is restored after an in silico CRT device implantation.. Fourth, in this study we present a large amount of multimodal imaging data from CRT candidates. To our knowledge, such an amount of complementary image data had never been used to study CRT candidates, due to the difficulty of acquiring these datasets. This information proved to be highly valuable to understand the complexity of the mechanisms conditioning CRT response. Now that we have a pipeline in place, it is possible to increase the sample size and evaluate multiple pacing sites. Our future work will focus on the evaluation of a larger cohort of patients recruited within the euHeart project. With this we hope to make electromechanical simulations ready to be applied in real clinical scenarios.

O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O


Nondeterministic Algorithm for Breaking Diffie-Hellman Key Exchange using Self-Assembly of DNA Tiles The computation based on DNA tile self-assembly has been demonstrated to be scalable, which is consider as a promising technique for computation. In this work, I first show how the tile self-assembly process can be used for computing the modular multiplication by mainly constructing three small systems including addition system, subtraction system and comparing system which can also be parallely implemented the discrete logarithm problem in the finite field GF (p). Then the nondeterministic algorithm is successfully performed to break Diffie-Hellman key exchange with the computation time complexity of Θ(p), and the probability of finding the successful solutions among many parallel executions is proved to be arbitrarily close to 1. Nature is a rich source for computing devices design. In recent years, computing models and algorithms inspired by biological systems are deeply investigated, e.g., membrane computing inspired by cells and DNA computing inspired by DNA molecules. Most of such computing models inspired by cells (or DNA molecules inside cells) are proved to be universal and computationally efficient [1, 2] . This work focuses on computing systems based on DNA molecules, especially the self-assembly of DNA tiles. Since Adleman demonstrated that the DNA recombination techniques can be used to solve combinational search problem [3] , the field of DNA-based computing has developed very fast. DNA computing potentially provides a degree of parallelism and high density storage far beyond that of conventional silicon-based computers [4] .. DNA tile self-assembly is a crucial process, by which the small objects can autonomously assemble into big complexes [5] . Seeman proposed DNA nanotechnology to make self-assembled nanostructures from DNA molecules [6] . Based on this landmark work, Winfree utilized a kind of DNA nanostructure called DX (double crossover) tile to realize a patterned lattice and the complex algorithmic pattern [7] . Winfree et al. demonstrated that two dimensional DNA selfassembly can be capable of Turing-universal computation [8] . Winfree and Eng proved that self-assembly of linear, hairpin and branched DNA molecules can be generated regular, bilinear and context-free languages respectively [9] . DNA tile algorithmic self-assembly can also be used to create crystals with patterns of binary counters [10, 11] and Sierpinski triangles [12] to implement arbitrary circuit [13] . However, those crystals are deterministic. Mao experimentally implemented the first algorithmic DNA tile self-assembly [14] , where a logical computation (cumulative XOR) is performed. Brun proposed the application of DNA tile self-assembly in arithmetic [15] . DNA self-assembly is also used to cope with combinational NP-complete problems, such as solving the satisfiability problem [16] by using 2D DNA self-assembly tiles, nondeterministically factoring numbers [17] , deciding a system of subset sum problem [18] . DNA self-assembly has potential applications in the cryptography. XOR computation on pairs of bits 618 Z. Cheng can be used to execute a one-time pad cryptosystem, which provides theoretically unbreakable security [19] .. To provide modern security features, the algorithms for public-key cryptosystems such as RSA [20] , Diffie-Hellman key agreement [21] , the digital signature algorithm [22] and systems based on elliptic curve cryptography [23] are widely used. All these algorithms have one thing in common: they all need operate the modular multiplication and exponent multiplication [24, 25] . In 1976, Diffie and Hellman [26] proposed the public-key distribution scheme based on the discrete logarithm problem in a finite field GF (p). Chen [27] gave deterministic algorithm to break Diffie-Hellman key exchange and constructed the basic tiles in which the complex modular multiplication operation in decimal is contained, so it can't be easily executed based on the experiment of simple binary arithmetic and logical operations. Here I mainly propose the nondeterministic algorithm to solve this problem by the addition, subtraction and comparing operations for binary numbers, which can be performed easily in experiments. The computation time complexity of our algorithm is Θ(p), and the probability of finding the successful solutions among the many parallel executions is proved to be arbitrarily close to 1.. The rest of this paper is structured as follows: Section 2 will describe the tile self-assembly model. Section 3 gives the method of computing modular multiplication using DNA tile selfassembly. Section 4 shows the process of breaking Diffie-Hellman key exchange based on modular multiplication by self-assembling. The conclusion will summarize the contribution of our work. DNA tile self-assembly is looked forward to many applications in different fields. In this paper, I show how the DNA self-assembly process can be used for breaking Diffie-Hellman key exchange based on the discrete logarithm problem in the finite field GF (p) by computing the modular multiplication. The advantage of our method is that once the initial strands are constructed, each operation can compute fast parallelly through the process of DNA self-assembly without any participation of manpower, thus the algorithm is proposed which can be successfully solved the modular multiplication, and then can be used to break Diffie-Hellman key exchange with the computation time complexity of Θ(p), and the probability of finding the successful solutions among the many parallel executions is proved to be arbitrarily close to 1.

B O O O B B I O B O B I O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O B O O O O O O B B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O B B I O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B I O O O O O O O O O O O B B I O O B I O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O O B B I O O O B I O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O B I O O O O O O O B B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O


Improving flood forecasting in Bangladesh using an artificial neural network predicted for up to ten days with very high accuracy. Values of R 2 , root mean square and mean absolute error are found ranging from 0.537 to 0.968, 0.607m to 0.206m and 0.475m to 0.154m, respectively, during training and validation of the model. The results of this study can be useful for real-time flood forecasting by reducing computational time, improving water resources

O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O B I O O O O O O O