TY - JOUR TI - STP Achievement Award—Dr. William W. Carlton AU - Rebar, Alan H. AU - Van Vleet, John F. T2 - Toxicologic Pathology DA - 2006/1// PY - 2006/1// DO - 10.1080/01926230600570123 VL - 34 IS - 1 SP - 1-2 J2 - Toxicol Pathol LA - en OP - SN - 0192-6233 1533-1601 UR - http://dx.doi.org/10.1080/01926230600570123 DB - Crossref ER - TY - CHAP TI - Locally Invertible Multivariate Polynomial Matrices AU - Lobo, Ruben G. AU - Bitzer, Donald L. AU - Vouk, Mladen A. T2 - Coding and Cryptography AB - A new class of rectangular zero prime multivariate polynomial matrices are introduced and their inverses are computed. These matrices are ideal for use in multidimensional systems involving input-output transformations. We show that certain multivariate polynomial matrices, when transformed to the sequence space domain, have an invertible subsequence map between their input and output sequences. This invertible subsequence map can be used to derive the polynomial inverse matrix together with a set of pseudo-inverses. All computations are performed using elementary operations on the ground field without using any polynomial operations. PY - 2006/// DO - 10.1007/11779360_33 SP - 427-441 OP - PB - Springer Berlin Heidelberg SN - 9783540354819 9783540354826 UR - http://dx.doi.org/10.1007/11779360_33 DB - Crossref ER - TY - JOUR TI - Reliability AU - Keller-McNulty, S. AU - Wilson, A. AU - Anderson-Cook, C. T2 - Statistical Science DA - 2006/// PY - 2006/// DO - 10.1214/088342306000000664 VL - 21 IS - 4 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-34249333066&partnerID=MN8TOARS ER - TY - BOOK TI - Statistical methods in counterterrorism: Game theory, modeling, syndromic surveillance, and biometric authentication AU - Wilson, A.G. AU - Wilson, G.D. AU - Olwell, D.H. DA - 2006/// PY - 2006/// DO - 10.1007/0-387-35209-0 SE - 1-292 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84889962244&partnerID=MN8TOARS ER - TY - JOUR TI - Advances in data combination, analysis and collection for system reliability assessment AU - Wilson, A.G. AU - Graves, T.L. AU - Hamada, M.S. AU - Reese, C.S. T2 - Statistical Science AB - The systems that statisticians are asked to assess, such as nuclear weapons, infrastructure networks, supercomputer codes and munitions, have become increasingly complex. It is often costly to conduct full system tests. As such, we present a review of methodology that has been proposed for addressing system reliability with limited full system testing. The first approaches presented in this paper are concerned with the combination of multiple sources of information to assess the reliability of a single component. The second general set of methodology addresses the combination of multiple levels of data to determine system reliability. We then present developments for complex systems beyond traditional series/parallel representations through the use of Bayesian networks and flowgraph models. We also include methodological contributions to resource allocation considerations for system relability assessment. We illustrate each method with applications primarily encountered at Los Alamos National Laboratory. DA - 2006/// PY - 2006/// DO - 10.1214/088342306000000439 VL - 21 IS - 4 SP - 514-531 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-34249308477&partnerID=MN8TOARS KW - Bayesian KW - Bayesian network KW - biased data KW - complex system KW - count data KW - degradation data KW - fault tree KW - flowgraph KW - genetic algorithm KW - lifetime data KW - logistic regression KW - Markov chain Monte Carlo KW - Metropolis algorithm KW - multilevel data KW - nonhomogeneous Poisson process KW - prior elicitation KW - reliability block diagram KW - repairable system KW - resource allocation ER - TY - CONF TI - The relationship between high school mathematics and career choices among high achieving young women AU - Berenson, S. B. AU - Michael, J. J. AU - Vouk, M. C2 - 2006/// C3 - Pme 30: proceedings of the 30th conference of the international group for the psychology of mathematics education, vol 1, DA - 2006/// SP - 220-220 ER - TY - JOUR TI - Predicting Shine-Dalgarno sequence locations exposes genome annotation errors AU - Starmer, J. AU - Stomp, A. AU - Vouk, M. AU - Bitzer, D. T2 - PLOS COMPUTATIONAL BIOLOGY AB - In prokaryotes, Shine-Dalgarno (SD) sequences, nucleotides upstream from start codons on messenger RNAs (mRNAs) that are complementary to ribosomal RNA (rRNA), facilitate the initiation of protein synthesis. The location of SD sequences relative to start codons and the stability of the hybridization between the mRNA and the rRNA correlate with the rate of synthesis. Thus, accurate characterization of SD sequences enhances our understanding of how an organism's transcriptome relates to its cellular proteome. We implemented the Individual Nearest Neighbor Hydrogen Bond model for oligo-oligo hybridization and created a new metric, relative spacing (RS), to identify both the location and the hybridization potential of SD sequences by simulating the binding between mRNAs and single-stranded 16S rRNA 3' tails. In 18 prokaryote genomes, we identified 2,420 genes out of 58,550 where the strongest binding in the translation initiation region included the start codon, deviating from the expected location for the SD sequence of five to ten bases upstream. We designated these as RS+1 genes. Additional analysis uncovered an unusual bias of the start codon in that the majority of the RS+1 genes used GUG, not AUG. Furthermore, of the 624 RS+1 genes whose SD sequence was associated with a free energy release of less than -8.4 kcal/mol (strong RS+1 genes), 384 were within 12 nucleotides upstream of in-frame initiation codons. The most likely explanation for the unexpected location of the SD sequence for these 384 genes is mis-annotation of the start codon. In this way, the new RS metric provides an improved method for gene sequence annotation. The remaining strong RS+1 genes appear to have their SD sequences in an unexpected location that includes the start codon. Thus, our RS metric provides a new way to explore the role of rRNA-mRNA nucleotide hybridization in translation initiation. DA - 2006/5// PY - 2006/5// DO - 10.1371/journal.pcbi.0020057 VL - 2 IS - 5 SP - 454-466 SN - 1553-7358 ER - TY - JOUR TI - Locally invertible multivariate polynomial matrices AU - Lobo, R. G. AU - Bitzer, D. L. AU - Vouk, M. A. T2 - Lecture Notes in Computer Science DA - 2006/// PY - 2006/// IS - 3969 SP - 427-441 ER - TY - JOUR TI - On the value of static analysis for fault detection in software AU - Zheng, J AU - Williams, L AU - Nagappan, N AU - Snipes, W AU - Hudepohl, JP AU - Vouk, MA T2 - IEEE TRANSACTIONS ON SOFTWARE ENGINEERING AB - No single software fault-detection technique is capable of addressing all fault-detection concerns. Similarly to software reviews and testing, static analysis tools (or automated static analysis) can be used to remove defects prior to release of a software product. To determine to what extent automated static analysis can help in the economic production of a high-quality product, we have analyzed static analysis faults and test and customer-reported failures for three large-scale industrial software systems developed at Nortel Networks. The data indicate that automated static analysis is an affordable means of software fault detection. Using the orthogonal defect classification scheme, we found that automated static analysis is effective at identifying assignment and checking faults, allowing the later software production phases to focus on more complex, functional, and algorithmic faults. A majority of the defects found by automated static analysis appear to be produced by a few key types of programmer errors and some of these types have the potential to cause security vulnerabilities. Statistical analysis results indicate the number of automated static analysis faults can be effective for identifying problem modules. Our results indicate static analysis tools are complementary to other fault-detection techniques for the economic production of a high-quality software product. DA - 2006/4// PY - 2006/4// DO - 10.1109/TSE.2006.38 VL - 32 IS - 4 SP - 240-253 SN - 1939-3520 KW - code inspections KW - walkthroughs ER - TY - JOUR TI - Early growth response gene-1 regulates hypoxia-induced expression of tissue factor in glioblastoma multiforme through hypoxia-inducible factor-1-independent mechanisms AU - Rong, Yuan AU - Hu, Fang AU - Huang, RuoPan AU - Mackman, Nigel AU - Horowitz, Jonathan M. AU - Jensen, Randy L. AU - Durden, Donald L. AU - Van Meir, Erwin G. AU - Brat, Daniel J. T2 - CANCER RESEARCH AB - Hypoxia strongly up-regulates tissue factor and promotes plasma clotting by glioblastoma multiforme, but transcriptional mechanisms remain undefined. Here, we investigated the potential roles of early growth response gene-1 (Egr-1), Sp1, nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1), and hypoxia-inducible factor-1 (HIF-1) in the hypoxic regulation of tissue factor by glioblastoma multiforme cells in vitro. Hypoxia (1% O2) strongly induced Egr-1 mRNA within 1 hour and led to nuclear localization of Egr-1 protein. Using luciferase reporter plasmids in glioma cells, we found that hypoxia dramatically increased luciferase activity in cells with constructs containing Egr-1-binding sites but not in cells with constructs containing AP-1- or NF-kappaB-binding sites. Electrophoretic mobility shift assays revealed hypoxia-induced Egr-1, but not Sp1, binding to oligonucleotides containing the Egr-1/Sp1 motif of tissue factor gene promoter. Using an expression vector containing the minimal tissue factor promoter (-111 to +14 bp) and small interfering RNA (siRNA) directed at Egr-1 and Sp1 mRNAs, we found that Egr-1 was required for maximal hypoxic induction of promoter activity. Forced overexpression of Egr-1 but not Sp1 by cDNA transfection caused up-regulation of tissue factor in glioma cells under normoxia (21% O2), whereas siRNA directed at Egr-1 strongly attenuated hypoxia-induced tissue factor expression. To examine the effects of HIF-1alpha on tissue factor expression, we used glioma cells stably transfected with a HIF-1alpha siRNA expression vector and found that HIF-1alpha mRNA silencing did not affect tissue factor expression under hypoxia. We conclude that hypoxic up-regulation of tissue factor in glioblastoma multiforme cells depends largely on Egr-1 and is independent of HIF-1. DA - 2006/7/15/ PY - 2006/7/15/ DO - 10.1158/0008-5472.CAN-06-0346 VL - 66 IS - 14 SP - 7067-7074 SN - 1538-7445 ER - TY - JOUR TI - Nkx3.1 binds and negatively regulates the transcriptional activity of Sp-family members in prostate-derived cells AU - Simmons, SO AU - Horowitz, JM T2 - BIOCHEMICAL JOURNAL AB - Nkx3.1 is a homeodomain-containing transcription factor that is expressed early in the development of the prostate gland and is believed to play an important role in the differentiation of prostatic epithelia. Loss of Nkx3.1 protein expression is often an early event in prostate tumorigenesis, and the abundance of Nkx3.1-negative epithelial cells increases with disease progression. In a number of systems, homeodomain proteins collaborate with zinc-finger-containing transcription factors to bind and regulate target genes. In the present paper, we report that Nkx3.1 collaborates with Sp-family members in the regulation of PSA (prostate-specific antigen) in prostate-derived cells. Nkx3.1 forms protein complexes with Sp proteins that are dependent on their respective DNA-binding domains and an N-terminal segment of Nkx3.1, and Nkx3.1 negatively regulates Sp-mediated transcription via Trichostatin A-sensitive and -insensitive mechanisms. A distal 1000 bp portion of the PSA promoter is required for transrepression by Nkx3.1, although Nkx3.1 DNA-binding activity is itself not required. We conclude that Nkx3.1 negatively regulates Sp-mediated transcription via the tethering of histone deacetylases and/or by inhibiting the association of Sp proteins with co-activators. DA - 2006/1/1/ PY - 2006/1/1/ DO - 10.1042/bj20051030 VL - 393 SP - 397-409 SN - 1470-8728 KW - histone deacetylase KW - Nkx3.1 KW - prostate KW - prostate-specific antigen KW - Sp protein KW - transrepression ER - TY - JOUR TI - Classification of Escherichia coli K-12 ribosome binding sites AU - May, EE AU - Vouk, MA AU - Bitzer, DL T2 - IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE AB - Drawing on parallels between genetic information processing in living organisms and the processing of communications data, we develop an error-control coding-based translation initiation classification system that uses an eleven base classification window. An overview of channel codes and a summary of the translation initiation process are presented. Parallels between the two are drawn and a brief review of a channel code model for translation initiation is shown. A block-code Bayesian classifier is presented and the results of applying the system to the translation start site location problem for Escherichia coli K-12 is discussed. DA - 2006/// PY - 2006/// DO - 10.1109/memb.2006.1578668 VL - 25 IS - 1 SP - 90-97 SN - 0739-5175 ER - TY - JOUR TI - Sp2 localizes to subnuclear foci associated with the nuclear matrix AU - Moorefield, KS AU - Yin, HF AU - Nichols, TD AU - Cathcart, C AU - Simmons, SO AU - Horowitz, JM T2 - MOLECULAR BIOLOGY OF THE CELL AB - We have reported that extracts prepared from many human and mouse cell lines show little or no Sp2 DNA-binding activity and that Sp2 has little or no capacity to stimulate transcription of promoters that are activated by Sp1, Sp3, and Sp4. Using an array of chimeric Sp1/Sp2 proteins we showed further that Sp2 DNA-binding activity and trans-activation are each negatively regulated in mammalian cells. As part of an ongoing effort to study Sp2 function and regulation we characterized its subcellular localization in comparison with other Sp-family members in fixed and live cells. We report that 1) Sp2 localizes largely within subnuclear foci associated with the nuclear matrix, and 2) these foci are distinct from promyelocytic oncogenic domains and appear to be stable during an 18-h time course of observation. Deletion analyses identified a 37 amino acid sequence spanning the first zinc-"finger" that is sufficient to direct nuclear matrix association, and this region also encodes a bipartite nuclear localization sequence. A second nuclear matrix targeting sequence is encoded within the Sp2 trans-activation domain. We conclude that Sp2 preferentially associates with the nuclear matrix and speculate that this subcellular localization plays an important role in the regulation of Sp2 function. DA - 2006/4// PY - 2006/4// DO - 10.1091/mbc.E05-11-1063 VL - 17 IS - 4 SP - 1711-1722 SN - 1939-4586 ER - TY - JOUR TI - Theoretical analysis of the SABUL congestion control algorithm AU - Oothongsap, P AU - Viniotis, Y AU - Vouk, M T2 - TELECOMMUNICATION SYSTEMS DA - 2006/3// PY - 2006/3// DO - 10.1007/s11235-006-6516-8 VL - 31 IS - 2-3 SP - 115-139 SN - 1572-9451 ER -