bluuebunny/crossref_metadata_2025_split huggingface dataset:
From the chair
Authors: Sipior Janice C. , Lending Diane , Amoroso Donald L. , Shayo Conrad , Vowels Susan A. 
Published: November 2007

A warm invitation to attend... "
The Seventh Annual ACM-SIGMIS Reception
," will be held as an ACM-SIGMIS event prior to the International Conference on Information Systems (ICIS2007) in Montréal, Québec, Canada, December 9 -- 12, 2007. Light refreshments will be served.

Where: International Conference on Information Systems (ICIS2007) Montréal, Québec, Canada Fairmont Queen Elizabeth Hotel Room not yet assigned

When: Saturday, December 9, 2007, 5:30 to 7:00 pm

Who: All ACM-SIGMIS members and their invited guests are welcome

.

Please plan to attend the SIGMIS CPR'08 Conference to be held April 3--5, 2008 at the Omni Charlottesville Hotel in Charlottesville, Virginia, USA. The theme of this year's conference is "Refilling the Pipeline: Meeting the Renewed Demand for Information Technology Workers." Additionally, the 2008 conference will include a doctoral student consortium on April 3, 2007 that will host a competition for best doctoral consortium paper. More information can be found at: http://www.sigmis.org/Call_for_Papers_2008.pd.
Please consider volunteering to serve on the Program Committee for the 2008 conference. Members of the Program Committee serve as reviewers and assist in identifying session chairs and discussants. If you would like to serve on the Program Committee, please contact Program Co-Chair Deb Armstrong at djarmstrong@fsu.edu. Let's make the SIGMIS CPR Conference a continuing success!

Also, please continue to consider
Data Base
as an outlet for your research. The new online submission system is available at the Data Base website at: http://the-database.org.
Federal aviation administration and ada
Authors: O'Leary Jeff 
Published: November 2007

The US Federal Aviation Administration (FAA) depends upon large, complex and highly available software systems to manage the vast commercial and civil aviation network and to carry out the agency's mission of ensuring high capacity, efficient and extremely safe air travel for the flying public. The FAA's Tower domain provides air traffic control services in the airport environment. There are more than 500 FAA managed Towers. The Terminal Radar Approach Control (TRACON) domain provides air traffic control services in the terminal environment where aircraft are climbing or descending. There are 197 TRACONs. The En Route domain provides air traffic control services typically above 10,000 feet between departure and arrival domains where aircraft achieve their optimal cruise altitude. There are only 21 En Route centers, so each must provide coverage to very large areas.
Ada has become a strategic technology in developing and sustaining systems that require high availability and high reliability. The FAA Air Traffic Organization's (ATO) major recent initiative, the En-Route Automation Modernization (ERAM) program goes a long way to reintegrating many disparate system components into a modern composite architecture. This program leverages and significantly expands upon previous Ada based systems, so the FAA has a vital interest in Ada language technology now and for the foreseeable future.
Mr. O'Leary will present a federal customer's perspective on systems development and quality, with emphasis on higher reliability, security, and safety. Ada is exceptionally well positioned to support these characteristics, and that is why many current large FAA ATC systems are largely or significantly Ada based. He will touch on past Ada based systems that FAA fielded, the current major ERAM effort, and also where FAA is going in the future with the Next Generation Air Transportation System (NextGen). He will give some insights on what the language and development technologies can contribute towards facilitating the vision of our future.
FAA accepts use of DO-278 as a means of assuring systems integrity for Communications, Navigation, Surveillance, and Air Traffic Management (CNS/ATM) software. Ada has also performed well in DO-278.
Chemosensitization of B-Cell Lymphomas by Methylseleninic Acid Involves Nuclear Factor-κB Inhibition and the Rapid Generation of Other Selenium Species
Authors: Jüliger Simone , Goenaga-Infante Heidi , Lister T. Andrew , Fitzgibbon Jude , Joel Simon P. 
Published: November 2007

AbstractAlthough recent reports suggest that selenium can modulate the activity of cytotoxic drugs, the mechanism underlying this activity remains unclear. This has been investigated using a panel of human B-cell lymphoma cell lines. The cytotoxic effects of chemotherapeutic agents (e.g., doxorubicin, etoposide, 4-hydroperoxycyclophosphamide, melphalan, and 1-β-d-arabinofuranosylcytosine) were increased by up to 2.5-fold when combined with minimally toxic concentrations (EC5-10) of the organic selenium compound, methylseleninic acid (MSA). DNA strand breaks were identified using comet assays, but the measured genotoxic activity of the combinations did not explain the observed synergistic effects in cell death. However, minimally toxic (EC10) concentrations of MSA induced a 50% decrease in nuclear factor-κB (NF-κB) activity after an exposure of 5 h, similar to that obtained with the specific NF-κB inhibitor, BAY 11-7082. Combinations of BAY 11-7082 with these cytotoxic drugs also resulted in synergism, suggesting that the chemosensitizing activity of MSA is mediated, at least in part, by its effects on NF-κB. Basal intracellular selenium concentration was higher in a MSA-sensitive cell line. After exposure to MSA, methylselenocysteine and selenomethionine were identified as the main intracellular species generated. Volatile selenium species, trapped using solid-phase microextraction fibers, were identified as dimethylselenide and dimethyldiselenide. These volatile species are thought to be the most biologically active forms of selenium. Taken together, these results show that the NF-κB pathway is one target for MSA underlying the interaction between MSA and chemotherapy. These data encourage the further clinical development of selenium as a potential modulator of cytotoxic drug activity in B-cell lymphomas. [Cancer Res 2007;67(22):10984–92]
High Expression of Lymphocyte-Associated Genes in Node-Negative HER2+ Breast Cancers Correlates with Lower Recurrence Rates
Authors: Alexe Gabriela , Dalgin Gul S. , Scanfeld Daniel , Tamayo Pablo , Mesirov Jill P. , DeLisi Charles , Harris Lyndsay , Barnard Nicola , Martel Maritza , Levine Arnold J. , Ganesan Shridar , Bhanot Gyan 
Published: November 2007

Abstract
Gene expression analysis has identified biologically relevant subclasses of breast cancer. However, most classification schemes do not robustly cluster all HER2+ breast cancers, in part due to limitations and bias of clustering techniques used. In this article, we propose an alternative approach that first separates the HER2+ tumors using a gene amplification signal for Her2/neu amplicon genes and then applies consensus ensemble clustering separately to the HER2+ and HER2− clusters to look for further substructure. We applied this procedure to a microarray data set of 286 early-stage breast cancers treated only with surgery and radiation and identified two basal and four luminal subtypes in the HER2− tumors, as well as two novel and robust HER2+ subtypes. HER2+ subtypes had median distant metastasis-free survival of 99 months [95% confidence interval (95% CI), 83–118 months] and 33 months (95% CI, 11–54 months), respectively, and recurrence rates of 11% and 58%, respectively. The low recurrence subtype had a strong relative overexpression of lymphocyte-associated genes and was also associated with a prominent lymphocytic infiltration on histologic analysis. These data suggest that early-stage HER2+ cancers associated with lymphocytic infiltration are a biologically distinct subtype with an improved natural history. [Cancer Res 2007;67(22):10669–76]
HIV-1 Protease Inhibitors Nelfinavir and Atazanavir Induce Malignant Glioma Death by Triggering Endoplasmic Reticulum Stress
Authors: Pyrko Peter , Kardosh Adel , Wang Weijun , Xiong Wenyong , Schönthal Axel H. , Chen Thomas C. 
Published: November 2007

Abstract
HIV type 1 (HIV-1) protease inhibitors (PI) have been shown to have anticancer activity in non–HIV-associated human cancer cells. The underlying mechanism of this effect is unclear. Here, we show that the PIs nelfinavir and atazanavir cause cell death in various malignant glioma cell lines in vitro. The underlying mechanism of this antitumor effect involves the potent stimulation of the endoplasmic reticulum (ER) stress response (ESR), as indicated by increased expression of two ESR markers, GRP78 and CHOP, and activation of ESR-associated caspase-4. Induction of ESR seems to play a central role in PI-induced cell death because small interfering RNA–mediated knockdown of the protective ER chaperone GRP78 sensitizes cells; whereas knockdown of proapoptotic caspase-4 protects cells from PI-induced cell death. Furthermore, the treatment of cells with PIs leads to aggresome formation and accumulation of polyubiquitinated proteins, implying proteasome inhibition. Thus, our results support a model whereby PIs cause tumor cell death via triggering of the ESR, inhibition of proteasome activity, and subsequent accumulation of misfolded proteins. Inhibition of glioma growth via ESR takes place in the in vivo setting as well, as nelfinavir inhibits the growth of xenografted human malignant glioma, with concomitant induction of the proapoptotic ER stress marker CHOP. Because ER stress has also been reported as the mechanism for insulin resistance and diabetes, our ER stress model of PI function may also explain why these drugs may induce insulin resistance as one of their most common side effects. [Cancer Res 2007;67(22):10920–8]
The Lysine 831 of Vascular Endothelial Growth Factor Receptor 1 Is a Novel Target of Methylation by SMYD3
Authors: Kunizaki Masaki , Hamamoto Ryuji , Silva Fabio Pittella , Yamaguchi Kiyoshi , Nagayasu Takeshi , Shibuya Masabumi , Nakamura Yusuke , Furukawa Yoichi 
Published: November 2007

Abstract
We previously identified SMYD3 as a histone methyltransferase and showed that its expression was elevated in colorectal, hepatocellular, and breast carcinomas. In the investigation of methyltransferase activity of SMYD3, we have found that vascular endothelial growth factor receptor 1 (VEGFR1) was also methylated by SMYD3. We further identified the methylated residue at VEGFR1 lysine 831, which is located in the kinase domain and is conserved among VEGFR1 orthologues. We also found that the lysine is followed by serine, which is conserved among some of the methylation targets of histone methyltransferases. Furthermore, methylation of VEGFR1 enhanced its kinase activity in cells. These data should be helpful for the profound understanding of the biological role of SMYD3 and regulatory mechanisms of VEGFR1. Additionally our finding may facilitate the development of strategies that may inhibit the progression of cancer cells. [Cancer Res 2007;67(22):10759–65]
ΔDNMT3B Variants Regulate DNA Methylation in a Promoter-Specific Manner
Authors: Wang Jie , Bhutani Manisha , Pathak Ashutosh K. , Lang Wenhua , Ren Hening , Jelinek Jaroslav , He Rong , Shen Lanlan , Issa Jean-Pierre , Mao Li 
Published: November 2007

Abstract
DNA methyltransferase 3B (DNMT3B) is critical in de novo DNA methylation during development and tumorigenesis. We recently reported the identification of a DNMT3B subfamily, ΔDNMT3B, which contains at least seven variants, resulting from alternative pre-mRNA splicing. ΔDNMT3Bs are the predominant expression forms of DNMT3B in human lung cancer. A strong correlation was observed between the promoter methylation of RASSF1A gene but not p16 gene (both frequently inactivated by promoter methylation in lung cancer) and expression of ΔDNMT3B4 in primary lung cancer, suggesting a role of ΔDNMT3B in regulating promoter-specific methylation of common tumor suppressor genes in tumorigenesis. In this report, we provide first experimental evidence showing a direct involvement of ΔDNMT3B4 in regulating RASSF1A promoter methylation in human lung cancer cells. Knockdown of ΔDNMT3B4 expression by small interfering RNA resulted in a rapid demethylation of RASSF1A promoter and reexpression of RASSF1A mRNA but had no effect on p16 promoter in the lung cancer cells. Conversely, normal bronchial epithelial cells with stably transfected ΔDNMT3B4 gained an increased DNA methylation in RASSF1A promoter but not p16 promoter. We conclude that promoter DNA methylation can be differentially regulated and ΔDNMT3Bs are involved in regulation of such promoter-specific de novo DNA methylation. [Cancer Res 2007;67(22):10647–52]
Prolonged Chronic Inflammation Progresses to Dysplasia in a Novel Rat Model of Colitis-Associated Colon Cancer
Authors: Santiago Cariluz , Pagán Beatriz , Isidro Angel A. , Appleyard Caroline B. 
Published: November 2007

Abstract
Inflammatory bowel disease (IBD) is a gastrointestinal disorder of unknown etiology or cure. One complication of IBD is an increased risk for development of colon cancer. The aims of this study were to use a previously established rat model of colitis to develop a new model of colitis-associated colon cancer and ascertain the involvement of three cancer-related genes: K-ras, adenomatous polyposis coli (APC), and p53. Four groups of rats were used: reactivated 1,2-dimethylhydrazine [DMH; trinitrobenzene sulfonic acid (TNBS) was used to induce colitis followed by a weekly s.c. dose of DMH], prolonged reactivation (inflammation was induced with TNBS, then maintained twice a week), saline-DMH (animals received saline instead of TNBS followed by a weekly dose of DMH), and normal (received no treatment). Animals were sacrificed at 5, 10, or 15 weeks, and colon samples were taken for pathologic analysis and gene mutation detection. No dysplasia was found in the normal group. The highest incidences of dysplasia were as follows: prolonged reactivation group at 5 weeks (60%), reactivated DMH group at 10 weeks (83%), and saline-DMH group at 15 weeks (67%). Carcinoma was found in both the prolonged reactivation and saline-DMH groups. No mutations were found in the K-ras oncogene; however 62% of the APC samples (exon 15 at nucleotide 2778) and 76% of p53 (exon 6 at nucleotide 1327) showed substitutions. The prolonged reactivation group may be considered a new model of colitis-associated colon cancer, offering the potential to study cancer prevention strategies for patients with IBD. [Cancer Res 2007;67(22):10766–73]
The Extra-domain A of Fibronectin Is a Vascular Marker of Solid Tumors and Metastases
Authors: Rybak Jascha-N. , Roesli Christoph , Kaspar Manuela , Villa Alessandra , Neri Dario 
Published: November 2007

Abstract
One of the most promising new avenues for the development of more selective and efficacious cancer therapies relies on the antibody-mediated targeted delivery of bioactive agents (e.g., cytokines) to the tumor environment. The identification of quantitative differences in the expression of accessible vascular proteins in metastatic lesions and host organs facilitate the development of antibody-based strategies, which should be highly efficient and selective, considering the fact that an over-exuberant neovasculature is a characteristic feature of aggressive cancers, and that tumor blood vessels are readily accessible for i.v. administered therapeutic agents. Metastasis is the main cause of death in cancer. The availability of metastasis-specific antigens accessible from the bloodstream will allow a selective delivery of therapeutic agents to metastatic lesions using antibodies as vehicles. Using a combination of vascular biotinylation of 129Sv mice bearing F9 liver metastases and mass spectrometry, we have identified 435 accessible proteins in metastasis and host organ specimens, of which 117 were exclusively detected in metastases. In particular, we found that the alternatively spliced extra-domain A (EDA) of fibronectin is strongly expressed in the neovasculature of liver metastases, while being undetectable in most normal organs. A human antibody to EDA was used to show EDA expression in the neovasculature of metastases and primary tumors of human cancer patients and to target mouse liver metastases and subcutaneous tumors in vivo. Human antibody fragments specific to the EDA domain of fibronectin promise to serve as general vehicles for the efficient and selective delivery of imaging agents or therapeutic molecules to metastatic sites. [Cancer Res 2007;67(22):10948–57]
Genome-Scale MicroRNA and Small Interfering RNA Screens Identify Small RNA Modulators of TRAIL-Induced Apoptosis Pathway
Authors: Ovcharenko Dmitriy , Kelnar Kevin , Johnson Charles , Leng Nan , Brown David 
Published: November 2007

Abstract
Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) binds to death receptors 4/5 and selectively induces caspase-dependent apoptosis. The RNA interference screening approach has led to the discovery and characterization of several TRAIL pathway components in human cells. Here, libraries of synthetic small interfering RNA (siRNA) and microRNAs (miRNA) were used to probe the TRAIL pathway. In addition to known genes, siRNAs targeting CDK4, PTGS1, ALG2, CLCN3, IRAK4, and MAP3K8 altered TRAIL-induced caspase-3 activation responses. Introduction of the miRNAs let-7c, mir-10a, mir-144, mir-150, mir-155, and mir-193 also affected the activation of the caspase cascade. Putative targets of these endogenous miRNAs included genes encoding death receptors, caspases, and other apoptosis-related genes. Among the novel genes revealed in the screen, CDK4 was selected for further characterization. CDK4 was the only member of the cyclin-dependent kinase gene family that bore a unique function in apoptotic signal transduction. [Cancer Res 2007;67(22):10782–8]
Cyclooxygenase-2 Is a Target Gene of Rho GDP Dissociation Inhibitor β in Breast Cancer Cells
Authors: Schunke Dario , Span Paul , Ronneburg Henrike , Dittmer Angela , Vetter Martina , Holzhausen Hans-Jürgen , Kantelhardt Eva , Krenkel Sylke , Müller Volkmar , Sweep Fred C.G.J. , Thomssen Christoph , Dittmer Jürgen 
Published: November 2007

Abstract
Rho GDP dissociation inhibitor β (Rho-GDIβ), an inhibitor of Rho GTPases, is primarily expressed by hematopoietic cells but is also found in epithelial cancer cells. Recently, we have identified Rho-GDIβ as a target of the transcription factor Ets1. Here, we show that, in breast cancer cells, Ets1 regulates Rho-GDIβ expression and binds to the upstream region of the Rho-GDIβ gene. Furthermore, in primary breast cancer, Rho-GDIβ is coexpressed with Ets1. Studying the function of Rho-GDIβ in breast cancer, we found that a Rho-GDIβ–specific small interfering RNA increased cellular migration but also decreased the expression of cyclooxygenase-2 (Cox-2) oncogene as shown by microarray, quantitative reverse transcription-PCR, and Western blot analyses. Further studies revealed that Rho-GDIβ regulates Cox-2 gene at least partly on the transcriptional level, most likely by activating nuclear factor of activated T cells 1 (NFAT-1). Vav-1, an interaction partner of Rho-GDIβ, was also found to interfere with Cox-2 expression and NFAT-1 cellular distribution, suggesting a cooperative action of Rho-GDIβ and Vav-1 on Cox-2 expression. To explore the importance of Rho-GDIβ for the survival of breast cancer patients, two cohorts, including 263 and 117 patients, were analyzed for clinical outcome in relation to Rho-GDIβ RNA and protein levels, respectively. Expression of Rho-GDIβ was not associated with either disease-free or overall survival in the two patient population. Our data suggest that the expression of Rho-GDIβ in breast cancer is neither beneficial nor disadvantageous to the patient. This may be the net effect of two opposing activities of Rho-GDIβ, one that suppresses tumor progression by inhibiting migration and the other that stimulates it by enhancing Cox-2 expression. [Cancer Res 2007;67(22):10694–702]
Pirh2 Promotes Ubiquitin-Dependent Degradation of the Cyclin-Dependent Kinase Inhibitor p27Kip1
Authors: Hattori Takayuki , Isobe Tomoyasu , Abe Kenji , Kikuchi Hirotoshi , Kitagawa Kyoko , Oda Toshiaki , Uchida Chiharu , Kitagawa Masatoshi 
Published: November 2007

Abstract
The cyclin-dependent kinase inhibitor p27Kip1 is degraded in late G1 phase by the ubiquitin-proteasome pathway, allowing cells to enter S phase. Due to accelerated degradation of p27Kip1, various human cancers express low levels of p27Kip1 associated with poor prognosis. S-phase kinase–associated protein 2, the F-box protein component of an SCF ubiquitin ligase complex, is implicated in degradation of p27Kip1 during S-G2 phases. Recently, Kip1 ubiquitination–promoting complex has been reported as another ubiquitin ligase that targets cytoplasmic p27Kip1 exported from the nucleus in G0-G1 phases. Here, we identified a RING-H2–type ubiquitin ligase, Pirh2, as a p27Kip1-interacting protein. Endogenous Pirh2 physically interacted with endogenous p27Kip1 in mammalian cells. Pirh2 directly ubiquitinated p27Kip1 in an intact RING finger domain-dependent manner in vivo, as well as in vitro. Ablation of endogenous Pirh2 by small interfering RNA increased the steady-state level of p27Kip1 and decelerated p27Kip1 turnover. Depletion of Pirh2 induced accumulation of p27Kip1 in both the nucleus and cytoplasm. Pirh2 expression was induced from late G1-S phase, whereas p27Kip1 was decreased in synchronization with accumulation of Pirh2. Furthermore, reduction of Pirh2 resulted in an impairment of p27Kip1 degradation and an inhibition of cell cycle progression at G1-S transition in a p53-independent manner. Overall, the results indicate that Pirh2 acts as a negative regulator of p27Kip1 function by promoting ubiquitin-dependent proteasomal degradation. [Cancer Res 2007;67(22):10789–95]
Cathepsin E Prevents Tumor Growth and Metastasis by Catalyzing the Proteolytic Release of Soluble TRAIL from Tumor Cell Surface
Authors: Kawakubo Tomoyo , Okamoto Kuniaki , Iwata Jun-ichi , Shin Masashi , Okamoto Yoshiko , Yasukochi Atsushi , Nakayama Keiichi I. , Kadowaki Tomoko , Tsukuba Takayuki , Yamamoto Kenji 
Published: November 2007

AbstractThe aspartic proteinase cathepsin E is expressed predominantly in cells of the immune system and highly secreted by activated phagocytes, and deficiency of cathepsin E in mice results in a phenotype affecting immune responses. However, because physiologic substrates for cathepsin E have not yet been identified, the relevance of these observations to the physiologic functions of this protein remains speculative. Here, we show that cathepsin E specifically induces growth arrest and apoptosis in human prostate carcinoma tumor cell lines without affecting normal cells by catalyzing the proteolytic release of soluble tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) from the cell surface. The antitumor activity of cathepsin E was corroborated by in vivo studies with mice bearing human and mouse tumor transplants. Administration of purified cathepsin E into human tumor xenografts in nude mice dose-dependently induced apoptosis in the tumor cells to inhibit tumor growth. The growth, viability, and metastasis of mouse B16 melanoma cells were also more profound in cathepsin E–deficient mice compared with those in the syngeneic wild-type and transgenic mice overexpressing cathepsin E. Taken together, the number of apoptotic tumor cells, as well as tumor-infiltrating activated macrophages, was apparently reduced in cathepsin E–deficient mice compared with those in the other two groups, implying the positive correlation of endogenous cathepsin E levels with the extent of tumor suppression in vivo. These results thus indicate that cathepsin E plays a substantial role in host defense against tumor cells through TRAIL-dependent apoptosis and/or tumor-associated macrophage-mediated cytotoxicity. [Cancer Res 2007;67(22):10869–78]