Mining gene–sample–time microarray data: a coherent gene cluster discovery approach

Extensive studies have shown that mining microarray data sets is important in bioinformatics research and biomedical applications. In this paper, we explore a novel type of gene–sample–time microarray data sets that records the expression levels of various genes under a set of samples during a series of time points. In particular, we propose the mining of coherent gene clusters from such data sets. Each cluster contains a subset of genes and a subset of samples such that the genes are coherent on the samples along the time series. The coherent gene clusters may identify the samples corresponding to some phenotypes (e.g., diseases), and suggest the candidate genes correlated to the phenotypes. We present two efficient algorithms, namely the Sample-Gene Search and the Gene–Sample Search, to mine the complete set of coherent gene clusters. We empirically evaluate the performance of our approaches on both a real microarray data set and synthetic data sets. The test results have shown that our approaches are both efficient and effective to find meaningful coherent gene clusters. Daxin Jiang received the Ph.D. degree in computer science and engineering from the State University of New York at Buffalo in 2005. He received the B.S. degree in computer science from the University of Science and Technology of China. From 1998 to 2000, he was a M.S. student in Software Institute, Chinese Academy of Sciences. He is currently an assistant professor at the School of Computer Engineering, Nanyang Technology University, Singapore. His research interests include data mining, bioinformatics, machine learning, and information retrieval. Jian Pei received the Ph.D. degree in computing science from Simon Fraser University, Canada, in 2002, under Dr. Jiawei Han's supervision. He also received the B.Eng. and the M.Eng. degrees from Shanghai Jiao Tong University, China, in 1991 and 1993, respectively, both in Computer Science. He is currently an assistant professor of computing science at Simon Fraser University. His research interests include developing effective and efficient data analysis techniques for novel data intensive applications. He is currently interested in various techniques of data mining, data warehousing, online analytical processing, and database systems, as well as their applications in bioinformatics. His current research is supported in part by the Natural Sciences and Engineering Research Council of Canada (NSERC) and the National Science Foundation (NSF) of the United States. Since 2000, he has published over 70 research papers in refereed journals, conferences, and workshops, has served in the organization committees and the program committees of over 60 international conferences and workshops, and has been a reviewer for some leading academic journals. He is a member of the ACM, the ACM SIGMOD, and the ACM SIGKDD. Murali Ramanathan is an associate professor of pharmaceutical sciences and neurology. He received the B.Tech. (Honors) in chemical engineering from the Indian Institute of Technology, India, in 1983. After a 4-year stint in the chemical industry, he obtained the M.S. degree in chemical engineering from Iowa State University, Ames, IA, in 1987, and the Ph.D. degree in bioengineering from the University of California-San Francisco and University of California-Berkeley Joint Program in Bioengineering in 1994. Dr. Ramanathan research interests are primarily focused on the treatment of multiple sclerosis (MS), an inflammatory-demyelinating disease of the central nervous system that affects over 1 million patients worldwide. MS is a complex, variable disease that causes physical and cognitive disability and nearly 50% of patients diagnosed with MS are unable to walk after 15 years. The etiology and pathogenesis of MS remains poorly understood. Dr. Ramanathan's research interests include stochastic modeling of pharmaceutical systems and novel approaches to analyzing and using genetic and genomic data for improving patient care and optimizing therapy. Chuan Lin is currently a Ph.D. student in the Department of Computer Science and Engineering, State University of New York at Buffalo. She received the B.E. and the M.S. degrees in computer science and technology from Tsinghua University in China. Her research interests include bioinformatics, data mining, and machine learning. Chun Tang received the B.S. and M.S. degrees from Peking University, China, in 1996 and 1999, respectively, and the Ph.D. degree from State University of New York at Buffalo, USA, in 2005, all in computer science. Currently, she is a postdoctoral associate of Center for Medical Informatics, Yale University. Her research interests include bioinformatics, data mining, machine learning, database, and information retrieval. Aidong Zhang received the Ph.D. degree in computer science from Purdue University, West Lafayette, Indiana, in 1994. She was an assistant professor from 1994 to 1999, an associate professor from 1999 to 2002, and has been a professor since 2002 in the Department of Computer Science and Engineering at State University of New York at Buffalo. Her research interests include multimedia systems, content-based image retrieval, bioinformatics, and data mining. She is an author of over 140 research publications in these areas. Dr. Zhang's research has been funded by NSF, NIH, NIMA, and Xerox. Zhang serves on the editorial boards of International Journal of Bioinformatics Research and Applications (IJBRA), ACM Multimedia Systems, International Journal of Multimedia Tools and Applications, and International Journal of Distributed and Parallel Databases. She was the editor for ACM SIGMOD DiSC (Digital Symposium Collection) from 2001 to 2003. She was co-chair of the technical program committee for ACM Multimedia in 2001. She has also served on various conference program committees. Dr. Zhang is a recipient of the National Science Foundation CAREER award and SUNY Chancellor's Research Recognition award.     

Failures after operation for skeletal metastatic lesions of long bones

This study was based on 192 patients treated surgically for 228 metastatic lesions of the long bones from 1986 through 1995. The survival rate was 0.3 at 1 year after surgery. The surgical treatment consisted of resection and reconstruction of the involved bone (18), intralesional curettage (133), or stabilization only (77). Reconstruction was achieved by an endoprosthesis in 54 cases, by an osteosynthetic device in 162, by cement only in 10. In two cases no reconstruction was performed. The local failure rate was 11% and the median time to failure was 8 months. Local failure was most frequent in patients with kidney cancer (24%) and in diaphyseal and distal femoral lesions (20%). Among 162 operations involving osteosynthetic devices, 22 (14%) were failures as compared with one of 54 (2%) endoprostheses. Sixty percent of the patients received preoperative or postoperative radiotherapy. Five of the six patients who had surgery for local tumor progression had not received radiotherapy. Eight of 10 nonunions and all five patients who developed a stress fracture had been treated with radiotherapy. It is concluded that endoprosthetic reconstructions are preferable to osteosynthetic devices. The skeletal complications associated with radiotherapy may be circumvented by the use of endoprostheses.     

Structural studies on an inhibitory antibody against Thermus aquaticus DNA polymerase suggest mode of inhibition

TP7, an antibody against Thermus aquaticus DNA polymerase I (TaqP), is used as a thermolabile switch in 'hot start' variations of PCR to minimize non-specific amplification events. Earlier studies have established that TP7 binds to the polymerase domain of TaqP, competes with primer template complex for binding and is a potent inhibitor of the polymerase activity of TaqP. We report crystallographic determination of the structure of an Fab fragment of TP7 and computational docking of the structure with the known three-dimensional structure of the enzyme. Our observations strongly suggest that the origin of inhibitory ability of TP7 is its binding to enzyme residues involved in DNA binding and polymerization mechanism. Although criteria unbiased by extant biochemical data have been used in identification of a putative solution, the resulting complex offers an eminently plausible structural explanation of biochemical observations. The results presented are of general significance for interpretation of docking experiments and in design of small molecular inhibitors of TaqP, that are not structurally similar to substrates, for use in PCR. Structural and functional similarities noted among DNA polymerases, and the fact that several DNA polymerases are pharmacological targets, make discovery of non-substrate based inhibitors of additional importance.      

Gate bias polarity dependence of charge trapping and time-dependentdielectric breakdown in nitrided and reoxidized nitrided oxides

The gate bias polarity dependence of charge trapping and time-dependent dielectric breakdown (TDDB) in nitrided and reoxidized nitrided silicon dioxides prepared by rapid thermal processing (RTP) is reported. Charge trapping during high-field injection can be reduced by rapid thermal nitridation for both substrate and gate injection. While reoxidation of nitrided oxides shows further reduction in charge trapping for substrate injection, degradation is observed for gate injection. Similar effects are observed for TDDB: reoxidized nitrided oxides show charge-to-breakdown in excess of 300 C/cm² for substrate injection, but less than 30 C/cm² for gate injection. These effects are related to the nitrogen and hydrogen profiles in the oxides. By tailoring the process conditions, a symmetric behavior of NO and RONO films with low charge trappings and Q _BD in excess of 50 C/cm² is possible, making them attractive as long-lifetime dielectrics from EEPROM (electrically erasable programmable ROM) and flash EEPROM technologies     

Severe gastrointestinal hemorrhage due to Mycobacterium avium complex in a patient receiving immunosuppressive therapy

Intense immunosuppressive therapy is used frequently for treatment of systemic vasculitides, collagenoses, rapidly progressive glomerulonephritis, and after organ transplantation. Numerous serious treatment-related side effects include localized or disseminated opportunistic infections, and require careful monitoring of immunosuppressed patients. Gastrointestinal infections with Mycobacterium avium complex (MAC) or other nontuberculous mycobacteria have been previously identified in HIV seropositive patients only. We now report the first case of an HIV seronegative patient who received immunosuppressive therapy for rapidly progressive glomerulonephritis. The patient presented with severe lower gastrointestinal bleeding and was diagnosed to have ulcerative colitis due to infection with MAC. The patient recovered promptly after administration of antimycobacterial therapy. MAC infection should be included in the differential diagnosis of gastrointestinal bleeding in all immunodeficient patients. The significance of repeated colonoscopy to obtain multiple biopsy specimens with histological examination for foam cells and specific staining for acid-fast organisms is emphasized.     

The Potential Role of Kallistatin in the Development of Abdominal Aortic Aneurysm

Abdominal aortic aneurysm (AAA) is a vascular condition that causes permanent dilation of the abdominal aorta, which can lead to death due to aortic rupture. The only treatment for AAA is surgical repair, and there is no current drug treatment for AAA. Aortic inflammation, vascular smooth muscle cell apoptosis, angiogenesis, oxidative stress and vascular remodeling are implicated in AAA pathogenesis. Kallistatin is a serine proteinase inhibitor, which has been shown to have a variety of functions, potentially relevant in AAA pathogenesis. Kallistatin has been reported to have inhibitory effects on tumor necrosis factor alpha (TNF-α) signaling induced oxidative stress and apoptosis. Kallistatin also inhibits vascular endothelial growth factor (VEGF) and Wnt canonical signaling, which promote inflammation, angiogenesis, and vascular remodeling in various pre-clinical experimental models. This review explores the potential protective role of kallistatin in AAA pathogenesis.     

Characteristics of slurry coated CdSeTe films

CdSe_xTe_1?x films were deposited by the slurry coating technique using CdSe_xTe_1?x powders synthesized in the laboratory. X-ray diffraction studies indicated the formation of a hexagonal phase. From EDAX compositional analysis, the individual concentrations of Se and Te in the films were estimated. Analysis of the optical data indicate the band gap to vary from 1.44 to 1.68 eV as the value of ‘x’ changes from 0 to 1. XPS analysis was also carried out on the films. The films were used as photoanodes in polysulphide electrolyte and it was observed that the films with composition CdSe_0.6Te_0.4 exhibited the maximum photoactivity. The Mott–Schottky plot indicated an n-type behaviour. Spectral response measurements were made and the electrodes exhibited a quantum efficiency of 0.6.