Dynamic random testing of web services: a methodology and evaluation

In recent years, Service Oriented Architecture (SOA) has been increasingly adopted to develop distributed applications in the context of the Internet. To develop reliable SOA-based applications, an important issue is how to ensure the quality of web services. In this paper, we propose a dynamic random testing (DRT) technique for web services, which is an improvement over the widely-practiced random testing (RT) and partition testing (PT). We examine key issues when adapting DRT to the context of SOA, including a framework, guidelines for parameter settings, and a prototype for such an adaptation. Empirical studies are reported where DRT is used to test three real-life web services, and mutation analysis is employed to measure the effectiveness. Our experimental results show that, compared with the three baseline techniques, RT, Adaptive Testing (AT) and Random Partition Testing (RPT), DRT demonstrates higher fault-detection effectiveness with a lower test case selection overhead. Furthermore, the theoretical guidelines of parameter setting for DRT are confirmed to be effective. The proposed DRT and the prototype provide an effective and efficient approach for testing web services. IEE

An integrated analysis tool for analyzing hybridization intensities and genotypes using new-generation population-optimized human arrays

The cross-sample plot of the multipoint LOH/LCSH analyses of the three samples used in Fig. 5. The plot comprises four panels: (a) The top-left panel is a cross-sample and cross-chromosome plot. The vertical axis is the index of study samples, and the horizontal axis is the physical position (Mb) on each of the 23 chromosomes. The blue and red bars represent SNPs without and with LOH/LSCH, respectively. (b) The top-right panel is a histogram of cross-chromosome aberration frequency. The vertical axis is the index of study samples, and the horizontal axis is the cross-chromosome aberration frequency of the corresponding samples. The pink (skyblue) background represents that the genetic gender of a sample is female (male). The histogram represents the aberration frequency of LOH/LCSH SNPs across the chromosomes of the corresponding samples. (c) The bottom-left panel is a histogram of the cross-sample aberration frequency. The vertical axis is the cross-sample aberration frequency of a SNP, and the horizontal axis is the physical position (Mb) on each of the 23 chromosomes. The purple line represents the aberration proportion of samples carrying the SNPs with LOH/LCSH. (d) The bottom-right panel is the legend of the genetic gender that is used in panel (b), where the pink (skyblue) background represents that the genetic gender of a sample is female (male). (TIFF 1656 kb

Langerhans cell hyperplasia in the tumor stage of mycosis fungoides: a mimic of Langerhans cell histiocytosis

AbstractMycosis fungoides is a form of cutaneous T-cell lymphoma (CTCL). Malignant CD4+ T cells have been found to adopt the T-regulatory (Treg) cell phenotype and function. We present the case of a 66-year-old man diagnosed with mycosis fungoides that was progressing from the plaque to the tumor stage. The histopathological examinations showed that the Langerhans cell (LC) infiltration in the skin lesion of the tumor stage was greater than that in the patch/plaque stage; the tumor stage lesions resembled LC histiocytosis pathologically. The associations among LCs, apoptotic tumor cells, Treg CTCL cells, and relevant cytokines are complex. Treg CTCL cells produce the immunosuppressive cytokines interleukin-10 and transforming growth factor beta, which facilitate continuous recruitment of LCs and maintenance of long-term dendritic cell immaturity, thereby explaining the remarkable LC infiltration in the tumor stage samples from our patient. This phenomenon indicates that LCs accompanied by Treg CTCL cells may play an important synergistic role in the tumor progression. The development of immunotherapy directed against Treg CTCL cells and LCs overproduction and other immunosuppressive cytokines may be a potent useful adjuvant and worthy of further investigation

Functional analysis of novel SNPs and mutations in human and mouse genomes

<p>Abstract</p> <p>Background</p> <p>With the flood of information generated by the new generation of sequencing technologies, more efficient bioinformatics tools are needed for in-depth impact analysis of novel genomic variations. FANS (Functional Analysis of Novel SNPs) was developed to streamline comprehensive but tedious functional analysis steps into a few clicks and to offer a carefully designed presentation of results so researchers can focus more on thinking instead of typing and calculating.</p> <p>Results</p> <p>FANS <url>http://fans.ngc.sinica.edu.tw/</url> harnesses the power of public information databases and powerful tools from six well established websites to enhance the efficiency of analysis of novel variations. FANS can process any point change in any coding region or GT-AG splice site to provide a clear picture of the disease risk of a prioritized variation by classifying splicing and functional alterations into one of nine risk subtypes with five risk levels.</p> <p>Conclusion</p> <p>FANS significantly simplifies the analysis operations to a four-step procedure while still covering all major areas of interest to researchers. FANS offers a convenient way to prioritize the variations and select the ones with most functional impact for validation. Additionally, the program offers a distinct improvement in efficiency over manual operations in our benchmark test.</p

Cyclic Alopecia and Abnormal Epidermal Cornification in Zdhhc13-Deficient Mice Reveal the Importance of Palmitoylation in Hair and Skin Differentiation

Many biochemical pathways involved in hair and skin development have not been investigated. Here, we reported on the lesions and investigated the mechanism underlying hair and skin abnormalities in Zdhhc13skc4 mice with a deficiency in DHHC13, a palmitoyl-acyl transferase encoded by Zdhhc13. Homozygous affected mice showed ragged and dilapidated cuticle of the hair shaft (CUH, a hair anchoring structure), poor hair anchoring ability, and premature hair loss at early telogen phase of the hair cycle, resulting in cyclic alopecia. Furthermore, the homozygous affected mice exhibited hyperproliferation of the epidermis, disturbed cornification, fragile cornified envelope (CE, a skin barrier structure), and impaired skin barrier function. Biochemical investigations revealed that cornifelin, which contains five palmitoylation sites at cysteine residues (C58, C59, C60, C95, and C101), was a specific substrate of DHHC13 and that it was absent in the CUH and CE structures of the affected mice. Furthermore, cornifelin levels were markedly reduced when two palmitoylated cysteines were replaced with serine (C95S and C101S). Taken together, our results suggest that DHHC13 is important for hair anchoring and skin barrier function and that cornifelin deficiency contributes to cyclic alopecia and skin abnormalities in Zdhhc13skc4 mice

A new analysis tool for individual-level allele frequency for genomic studies

<p>Abstract</p> <p>Background</p> <p>Allele frequency is one of the most important population indices and has been broadly applied to genetic/genomic studies. Estimation of allele frequency using genotypes is convenient but may lose data information and be sensitive to genotyping errors.</p> <p>Results</p> <p>This study utilizes a unified intensity-measuring approach to estimating individual-level allele frequencies for 1,104 and 1,270 samples genotyped with the single-nucleotide-polymorphism arrays of the Affymetrix Human Mapping 100K and 500K Sets, respectively. Allele frequencies of all samples are estimated and adjusted by coefficients of preferential amplification/hybridization (CPA), and large ethnicity-specific and cross-ethnicity databases of CPA and allele frequency are established. The results show that using the CPA significantly improves the accuracy of allele frequency estimates; moreover, this paramount factor is insensitive to the time of data acquisition, effect of laboratory site, type of gene chip, and phenotypic status. Based on accurate allele frequency estimates, analytic methods based on individual-level allele frequencies are developed and successfully applied to discover genomic patterns of allele frequencies, detect chromosomal abnormalities, classify sample groups, identify outlier samples, and estimate the purity of tumor samples. The methods are packaged into a new analysis tool, ALOHA (<b>A</b>llele-frequency/<b>L</b>oss-<b>o</b>f-<b>h</b>eterozygosity/<b>A</b>llele-imbalance).</p> <p>Conclusions</p> <p>This is the first time that these important genetic/genomic applications have been simultaneously conducted by the analyses of individual-level allele frequencies estimated by a unified intensity-measuring approach. We expect that additional practical applications for allele frequency analysis will be found. The developed databases and tools provide useful resources for human genome analysis via high-throughput single-nucleotide-polymorphism arrays. The ALOHA software was written in R and R GUI and can be downloaded at <url>http://www.stat.sinica.edu.tw/hsinchou/genetics/aloha/ALOHA.htm</url>.</p

A large-scale survey of genetic copy number variations among Han Chinese residing in Taiwan

<p>Abstract</p> <p>Background</p> <p>Copy number variations (CNVs) have recently been recognized as important structural variations in the human genome. CNVs can affect gene expression and thus may contribute to phenotypic differences. The copy number inferring tool (CNIT) is an effective hidden Markov model-based algorithm for estimating allele-specific copy number and predicting chromosomal alterations from single nucleotide polymorphism microarrays. The CNIT algorithm, which was constructed using data from 270 HapMap multi-ethnic individuals, was applied to identify CNVs from 300 unrelated Han Chinese individuals in Taiwan.</p> <p>Results</p> <p>Using stringent selection criteria, 230 regions with variable copy numbers were identified in the Han Chinese population; 133 (57.83%) had been reported previously, 64 displayed greater than 1% CNV allele frequency. The average size of the CNV regions was 322 kb (ranging from 1.48 kb to 5.68 Mb) and covered a total of 2.47% of the human genome. A total of 196 of the CNV regions were simple deletions and 27 were simple amplifications. There were 449 genes and 5 microRNAs within these CNV regions; some of these genes are known to be associated with diseases.</p> <p>Conclusion</p> <p>The identified CNVs are characteristic of the Han Chinese population and should be considered when genetic studies are conducted. The CNV distribution in the human genome is still poorly characterized, and there is much diversity among different ethnic populations.</p

FASTSNP: an always up-to-date and extendable service for SNP function analysis and prioritization

Single nucleotide polymorphism (SNP) prioritization based on the phenotypic risk is essential for association studies. Assessment of the risk requires access to a variety of heterogeneous biological databases and analytical tools. FASTSNP (function analysis and selection tool for single nucleotide polymorphisms) is a web server that allows users to efficiently identify and prioritize high-risk SNPs according to their phenotypic risks and putative functional effects. A unique feature of FASTSNP is that the functional effect information used for SNP prioritization is always up-to-date, because FASTSNP extracts the information from 11 external web servers at query time using a team of web wrapper agents. Moreover, FASTSNP is extendable by simply deploying more Web wrapper agents. To validate the results of our prioritization, we analyzed 1569 SNPs from the SNP500Cancer database. The results show that SNPs with a high predicted risk exhibit low allele frequencies for the minor alleles, consistent with a well-known finding that a strong selective pressure exists for functional polymorphisms. We have been using FASTSNP for 2 years and FASTSNP enables us to discover a novel promoter polymorphism. FASTSNP is available at