bluuebunny/crossref_metadata_2025_split huggingface dataset:
Map of the Galaxy in the 6.7-keV emission line
Authors: Revnivtsev M. , Molkov S. , Sazonov S. 
Published: September 2006

Abstract
We study the two-dimensional surface brightness distribution of the Galactic X-ray background emission outside the central degree around Sgr A* in the 6.7-keV line as measured by the Proportional Counter Array spectrometer of the Rossi X-ray Timing Explorer observatory. The use of the emission line instead of continuum (3–20 keV) radiation and application of time-variability filtering to the long data set allows us to strongly suppress the contamination of the Galactic ridge X-ray emission (GRXE) map by bright point-sources. The surface brightness in the 6.7-keV line demonstrates very good correspondence with the near-infrared surface brightness over the whole Galaxy, supporting the notion that the GRXE consists mostly of integrated emission from weak Galactic X-ray sources. We find compatible linear correlations between near-infrared and 6.7-keV surface brightness for the bulge and disc of the Galaxy. This indicates that the populations of weak X-ray sources making up the GRXE in the disc and in the bulge are not significantly different.
A Profit-Based Approach for Gas Turbine Power Plant Outage Planning
Authors: Zhao Yongjun , Volovoi Vitali , Waters Mark , Mavris Dimitri 
Published: September 2006

Abstract
Traditionally, for complicated systems, such as a gas turbine power plant, maintenance cost and online availability are two of the most important concerns to the equipment owner. However, in the deregulated electric power market, cost and reliability are not the only concerns. The ultimate goal is to maximize plant profitability, and this requires the evaluation of many different factors, including system performance, the aging and reliability of equipment, maintenance practices, and market dynamics accounting for the price and availability of fuel as well as the generation of revenues in competing markets. Thus, gas turbine power plant planning optimization is a complex problem, and comprehensive operational modeling and optimization methods are required. In this paper, a profit-based power plant outage planning approach is presented that reflects the new challenges posed by deregulation. Specifically, particular attention is paid to modeling power plant aging, performance degradation, reliability deterioration, and, importantly, the energy market dynamics. A multiple time-scale method is developed for coupled short-term, long-term generation scheduling and outage planning for this profit-based outage planning approach. The procedure is implemented for a base load combined cycle power plant with a single gas turbine, with the results demonstrating the feasibility of the proposed approach.
Influence of Valve Lift and Throttle Angle on Intake Flow in a High-Performance Four-Stroke Motorcycle Engine
Authors: Algieri Angelo , Bova Sergio , De Bartolo Carmine 
Published: September 2006

Abstract
A high-performance four-stroke motorcycle engine was analyzed at a steady flow rig. The aim of the work was to characterize the fluid dynamic behavior of the engine head during the intake phase. To this purpose a twofold approach was adopted: the dimensionless flow coefficient was used to evaluate the global breathability of the intake system, while the laser doppler anemometry (LDA) technique was employed to define the flow structure within the combustion chamber. The analysis gave evidence of two contrarotating vortices with axes parallel to the cylinder axis and showed variations in the flow structure when moving away from the engine head. Furthermore, the study highlighted the great influence of the throttle angle on the head fluid dynamic efficiency and how this influence changes with the valve lift. Experimental data were correlated by a single curve adopting a new dimensionless plot. Moreover, LDA measurements were used to evaluate the angular momentum of the flux and an equivalent swirl coefficient, and to correlate them to a previous global swirl characterization carried out on the same engine head using an impulse swirl meter.
Mapping Essential Domains of
Mycobacterium smegmatis
WhmD: Insights into WhiB Structure and Function
Authors: Raghunand Tirumalai R. , Bishai William R. 
Published: September 2006

ABSTRACT

A growing body of evidence suggests that the WhiB-like proteins exclusive to the GC-rich actinomycete genera play significant roles in pathogenesis and cell division. Each of these proteins contains four invariant cysteine residues and a conserved helix-turn-helix motif.
whmD
, the
Mycobacterium smegmatis
homologue of
Streptomyces coelicolor whiB
, is essential in
M. smegmatis
, and the conditionally complemented mutant
M. smegmatis
628-53 undergoes filamentation under nonpermissive conditions. To identify residues critical to WhmD function, we developed a cotransformation-based assay to screen for alleles that complement the filamentation phenotype of
M. smegmatis
628-53 following inducer withdrawal.
Mycobacterium tuberculosis whiB2
and
S. coelicolor whiB
complemented the defect in
M. smegmatis
628-53, indicating that these genes are true functional orthologues of
whmD
. Deletion analysis suggested that the N-terminal 67 and C-terminal 12 amino acid residues are dispensable for activity. Site-directed mutagenesis indicated that three of the four conserved cysteine residues (C
90
, C
93
, and C
99
) and a conserved aspartate (D
71
) are essential. Mutations in a predicted loop glycine (G
111
) and an unstructured leucine (L
116
) were poorly tolerated. The region essential for WhmD activity encompasses 6 of the 10 residues conserved in all seven
M. tuberculosis
WhiBs, as well as in most members of the WhiB family identified thus far. WhmD structure was found to be sensitive to the presence of a reducing agent, suggesting that the cysteine residues are involved in coordinating a metal ion. Iron-specific staining strongly suggested that WhmD contains a bound iron atom. With this information, we have now begun to comprehend the functional significance of the conserved sequence and structural elements in this novel family of proteins.
Flagella ofPyrococcus furiosus: Multifunctional Organelles, Made for Swimming, Adhesion to Various Surfaces, and Cell-Cell Contacts
Authors: Näther Daniela J. , Rachel Reinhard , Wanner Gerhard , Wirth Reinhard 
Published: September 2006

ABSTRACTPyrococcus furiosus(“rushing fireball”) was named for the ability of this archaeal coccus to rapidly swim at its optimal growth temperature, around 100°C. Early electron microscopic studies identified up to 50 cell surface appendages originating from one pole of the coccus, which have been called flagella. We have analyzed these putative motility organelles and found them to be composed primarily (>95%) of a glycoprotein that is homologous to flagellins from other archaea. Using various electron microscopic techniques, we found that these flagella can aggregate into cable-like structures, forming cell-cell connections between ca. 5% of all cells during stationary growth phase.P. furiosuscells could adhere via their flagella to carbon-coated gold grids used for electron microscopic analyses, to sand grains collected from the original habitat (Porto di Levante, Vulcano, Italy), and to various other surfaces.P. furiosusgrew on surfaces in biofilm-like structures, forming microcolonies with cells interconnected by flagella and adhering to the solid supports. Therefore, we concluded thatP. furiosusprobably uses flagella for swimming but that the cell surface appendages also enable this archaeon to form cable-like cell-cell connections and to adhere to solid surfaces.
DRAWING WITH FAT EDGES
Authors: DUNCAN CHRISTIAN A. , EFRAT ALON , KOBOUROV STEPHEN , WENK CAROLA 
Published: September 2006

Traditionally, graph drawing algorithms represent vertices as circles and edges as curves connecting the vertices. We introduce the problem of drawing with "fat" edges, i.e., with edges of variable thickness. The thickness of an edge is often used as a visualization cue, to indicate importance, or to convey some additional information. We present a model for drawing with fat edges and a corresponding efficient polynomial time algorithm that uses the model. We first focus on a restricted class of graphs that occur in VLSI wire routing and then show how to extend the algorithm to general planar graphs. We show how to convert an arbitrary wire routing into a homotopically equivalent routing that maximizes the distance between any two wires, which is a desired property in VLSI design. Among such, we obtain the routing with minimum total wire length. A homotopically equivalent routing that maximizes the distance between any two wires yields a graph drawing which maximizes edge thickness. Our algorithm does not require unit edge thickness but can be applied as well in the presence of different edge weights.
THE GENERAL STRUCTURE OF G-GRADED CONTRACTIONS OF LIE ALGEBRAS, II: THE CONTRACTED LIE ALGEBRA
Authors: WEIMAR-WOODS EVELYN 
Published: September 2006

We continue our study of G-graded contractions γ of Lie algebras where G is an arbitrary finite Abelian group. We compare them with contractions, especially with respect to their usefulness in physics. (Note that the unfortunate terminology "graded contraction" is confusing since they are, by definition, not contractions.)We give a complete characterization of continuous G-graded contractions and note that they are equivalent to a proper subset of contractions. We study how the structure of the contracted Lie algebra Lγdepends on γ, and show that, for discrete graded contractions, applications in physics seem unlikely.Finally, with respect to applications to representations and invariants of Lie algebras, a comparison of graded contractions with contractions reveals the insurmountable defects of the graded contraction approach. In summary, our detailed analysis shows that graded contractions are clearly not useful in physics.
The Expression of CD30 in Anaplastic Large Cell Lymphoma Is Regulated by Nucleophosmin-Anaplastic Lymphoma Kinase–Mediated JunB Level in a Cell Type–Specific Manner
Authors: Hsu Faye Yuan-Yi , Johnston Patrick B. , Burke Kathleen A. , Zhao Yi 
Published: September 2006

AbstractChromosomal translocation t(2;5) and the resulting fusion protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) are detected in 50% to 70% of anaplastic large cell lymphoma (ALCL), which is a T/null cell non–Hodgkin's lymphoma showing anaplastic morphology with cell surface expression of CD30. Because aberrant CD30 expression was also observed in the T-cell lymphoma derived from lineage-specific NPM-ALK transgenic mice, we tested the hypothesis that there might be a functional relationship between the two neoplastic-related proteins: NPM-ALK and CD30. In this study, we used the RNA interference method to modulate NPM-ALK protein expression in ALCL-derived, t(2;5)-positive Karpas 299 cells. We observed decreased CD30 expression when NPM-ALK was repressed. Further analysis suggested that JunB functioned as the mediator of NPM-ALK-derived CD30 transcriptional regulation. The NPM-ALK-repressed cells, which had low CD30 expression, were characterized with lower cell proliferation compared with cells in the control group, suggesting that altered CD30 expression may correlate to NPM-ALK-mediated tumor cell growth inhibition. Combination of NPM-ALK repression and CD30 ligand leads to significantly increased tumor cell growth inhibition compared with one method alone, suggesting its potential application for ALCL-specific cancer treatment. (Cancer Res 2006; 66(18): 9002-8)
KRN951, a Highly Potent Inhibitor of Vascular Endothelial Growth Factor Receptor Tyrosine Kinases, Has Antitumor Activities and Affects Functional Vascular Properties
Authors: Nakamura Kazuhide , Taguchi Eri , Miura Toru , Yamamoto Atsushi , Takahashi Kazumi , Bichat Francis , Guilbaud Nicolas , Hasegawa Kazumasa , Kubo Kazuo , Fujiwara Yasunari , Suzuki Rika , Kubo Kinya , Shibuya Masabumi , Isae Toshiyuki 
Published: September 2006

Abstract
Vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis by stimulating the proangiogenic signaling of endothelial cells via activation of VEGF receptor (VEGFR) tyrosine kinases. Therefore, VEGFRs are an attractive therapeutic target for cancer treatment. In the present study, we show that a quinoline-urea derivative, KRN951, is a novel tyrosine kinase inhibitor for VEGFRs with antitumor angiogenesis and antigrowth activities. KRN951 potently inhibited VEGF-induced VEGFR-2 phosphorylation in endothelial cells at in vitro subnanomolar IC50 values (IC50 = 0.16 nmol/L). It also inhibited ligand-induced phosphorylation of platelet-derived growth factor receptor-β (PDGFR-β) and c-Kit (IC50 = 1.72 and 1.63 nmol/L, respectively). KRN951 blocked VEGF-dependent, but not VEGF-independent, activation of mitogen-activated protein kinases and proliferation of endothelial cells. In addition, it inhibited VEGF-mediated migration of human umbilical vein endothelial cells. Following p.o. administration to athymic rats, KRN951 decreased the microvessel density within tumor xenografts and attenuated VEGFR-2 phosphorylation levels in tumor endothelium. It also displayed antitumor activity against a wide variety of human tumor xenografts, including lung, breast, colon, ovarian, pancreas, and prostate cancer. Furthermore, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) analysis revealed that a significant reduction in tumor vascular hyperpermeability was closely associated with the antitumor activity of KRN951. These findings suggest that KRN951 is a highly potent, p.o. active antiangiogenesis and antitumor agent and that DCE-MRI would be useful in detecting early responses to KRN951 in a clinical setting. KRN951 is currently in phase I clinical development for the treatment of patients with advanced cancer. (Cancer Res 2006; 66(18): 9134-42)
Hypoxic Stress Induces Dimethylated Histone H3 Lysine 9 through Histone Methyltransferase G9a in Mammalian Cells
Authors: Chen Haobin , Yan Yan , Davidson Todd L. , Shinkai Yoichi , Costa Max 
Published: September 2006

Abstract
Dimethylated histone H3 lysine 9 (H3K9me2) is a critical epigenetic mark for gene repression and silencing and plays an essential role in embryogenesis and carcinogenesis. Here, we investigated the effects of hypoxic stress on H3K9me2 at both global and gene-specific level. We found that hypoxia increased global H3K9me2 in several mammalian cell lines. This hypoxia-induced H3K9me2 was temporally correlated with an increase in histone methyltransferase G9a protein and enzyme activity. The increase in H3K9me2 was significantly mitigated in G9a−/− mouse embryonic stem cells following hypoxia challenge, indicating that G9a was involved in the hypoxia-induced H3K9me2. In addition to the activation of G9a, our results also indicated that hypoxia increased H3K9me2 by inhibiting H3K9 demethylation processes. Hypoxic mimetics, such as deferoxamine and dimethyloxalylglycine, were also found to increase H3K9me2 as well as G9a protein and activity. Finally, hypoxia increased H3K9me2 in the promoter regions of the Mlh1 and Dhfr genes, and these increases temporally correlated with the repression of these genes. Collectively, these results indicate that G9a plays an important role in the hypoxia-induced H3K9me2, which would inhibit the expression of several genes that would likely lead to solid tumor progression. (Cancer Res 2006; 66(18): 9009-16)
Inhibition of the Janus Kinase Family Increases Extracellular Signal-Regulated Kinase 1/2 Phosphorylation and Causes Endoreduplication
Authors: Reiterer Gudrun , Yen Andrew 
Published: September 2006

Abstract
The role of Janus-activated kinase (JAK) signaling in cell cycle transit and maintenance of genomic stability was determined in HL-60 myeloblastic leukemia cells. Inhibition of JAKs, all JAKs (JAK1, JAK2, JAK3, and tyrosine kinase 2), JAK2, or JAK3, caused a significant reduction in cell growth with a major G2-M arrest evident 24 hours after treatment. Targeting all JAKs also caused endoreduplication 48 and 72 hours after treatment. We discovered mitotic cells in both G2 (4N DNA) and G4 (8N DNA) subpopulations of cells treated with an inhibitor of all JAKs as detected by phosphorylated histone H3 expression. Treatment with inhibitors of just JAK2 or JAK3 drastically reduced such mitotic cells. We observed a complete blockage of IFN-γ and interleukin-6-induced signal transducer and activator of transcription (STAT)-1 and STAT-3 response when all JAKs were inhibited. At the same time, we found baseline phosphorylated extracellular signal-regulated kinase (ERK) 1/2 to be elevated by JAK inhibition, particularly when all JAKs were inhibited. The G2-M arrest and endoreduplication induced by JAK inhibitors were reduced in cells pretreated with PD98059 to inhibit ERK. PD98059 also increased back the expression of the MAD2 cell cycle checkpoint protein that was down-regulated during “all JAKs inhibitor”–mediated endoreduplication. These data suggest that JAK signaling is needed for G2-M transit with inhibition of ERK. (Cancer Res 2006; 66(18): 9083-9) (Cancer Res 2006; 66(18): 9083-9)
Daxx Represses Expression of a Subset of Antiapoptotic Genes Regulated by Nuclear Factor-κB
Authors: Croxton Rhonda , Puto Lorena A. , de Belle Ian , Thomas Michael , Torii Seiji , Hanaii Farid , Cuddy Michael , Reed John C. 
Published: September 2006

Abstract
Daxx is a nuclear protein that localizes to PML oncogenic domains, sensitizes cells to apoptosis, and functions as a transcriptional repressor. We found that Daxx represses the expression of several antiapoptotic genes regulated by nuclear factor-κB, including cIAP2, in human tumor cell lines. Daxx interacts with RelB and inhibits RelB-mediated transcriptional activation of the human cIAP2 gene promoter. Daxx also forms complexes with RelB while bound to its target sites in the cIAP2 promoter, as shown by electrophoretic mobility shift assays and chromatin immunoprecipitation experiments. Using cells from daxx−/− mouse embryos, we observed that levels of the corresponding murine c-IAP mRNA and protein are increased in cells lacking Daxx. Conversely, c-IAP mRNA and protein levels were reduced in relB−/− cells. Taken together, these observations provide a mechanism that links two previously ascribed functions of Daxx: transcriptional repression and sensitization to apoptosis. (Cancer Res 2006; 66(18): 9026-35)
Nelfinavir Down-regulates Hypoxia-Inducible Factor 1α and VEGF Expression and Increases Tumor Oxygenation: Implications for Radiotherapy
Authors: Pore Nabendu , Gupta Anjali K. , Cerniglia George J. , Jiang Zibin , Bernhard Eric J. , Evans Sydney M. , Koch Cameron J. , Hahn Stephen M. , Maity Amit 
Published: September 2006

Abstract
The phosphatidylinositol 3-kinase (PI3K)/Akt pathway can increase vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1α (HIF-1α) expression. We examined the effect of nelfinavir, an HIV protease inhibitor that inhibits Akt signaling, on VEGF and HIF-1α expression and on angiogenesis, tumor oxygenation, and radiosensitization. Nelfinavir decreases VEGF expression under normoxia via the transcription factor Sp1, which regulates the proximal core VEGF promoter. Nelfinavir decreased Sp1 phosphorylation and decreased Sp1 binding to a probe corresponding to the proximal VEGF promoter in a gel shift assay. Nelfinavir also decreased the hypoxic induction of HIF-1α, which also regulates the VEGF promoter, most likely by decreasing its translation. The effect of nelfinavir on VEGF expression had the functional consequence of decreasing angiogenesis in an in vivo Matrigel plug assay. To determine the effect this might have on tumor radiosensitization, we did tumor regrowth assays with xenografts in nude mice. The combination of nelfinavir and radiation increased time to regrowth compared with radiation alone whereas nelfinavir alone had little effect on tumor regrowth. This radiosensitizing effect was greater than suggested by in vitro clonogenic survival assays. One possible explanation for the discordance is that nelfinavir has an effect on tumor oxygenation. Therefore, we examined this with the hypoxia marker EF5 and found that nelfinavir leads to increased oxygenation within tumor xenografts. Our results suggest that nelfinavir decreases HIF-1α/VEGF expression and tumor hypoxia, which could play a role in its in vivo radiosensitizing effect. These data support the use of nelfinavir in combination with radiation in future clinical trials. (Cancer Res 2006; 66(18): 9252-9)
A Dimeric Peptide That Binds Selectively to Prostate-Specific Membrane Antigen and Inhibits its Enzymatic Activity
Authors: Aggarwal Saurabh , Singh Pratap , Topaloglu Ozlem , Isaacs John T. , Denmeade Samuel R. 
Published: September 2006

AbstractProstate-specific membrane antigen (PSMA) is highly expressed by both normal and malignant prostate epithelial cells and by the neovasculature of many tumor types; however, it is not expressed by normal endothelial cells or other normal tissues. PSMA, therefore, represents an attractive candidate for selectively targeted therapies for prostate and/or other solid tumors. As an alternative approach to antibody-based anti-PSMA therapies, small peptides that bind selectively to PSMA-producing cells can be used to deliver cytotoxic drugs, protein toxins, and viruses selectively to malignant sites while minimizing systemic toxicity to normal tissues. Small peptides are relatively inexpensive to produce, not immunogenic, and easily coupled to cytotoxic agents. In the present study, a random phage library consisting of linear 12 amino acid peptides was used to identify peptides that bound selectively to PSMA. From a series of monomeric peptides, one with the sequence WQPDTAHHWATL was used to show binding of soluble peptide to PSMA. A dimeric version of this peptide showed markedly enhanced binding to soluble PSMA and an IC50 of 2.2 μmol/L for inhibition of PSMA enzymatic activity. Fluorescently labeled dimeric peptide bound selectively to PSMA-producing prostate cancer cells in vitro with no significant binding to non–PSMA-producing cells. Molecular modeling of the dimeric peptide revealed that histidine residues in close vicinity can efficiently coordinate a divalent ion and hold the peptide in a favorable configuration for binding and subsequent inhibition. These dimeric peptides, therefore, represent putative PSMA-selective targeting agents that are currently being evaluated for selective binding in vivo. (Cancer Res 2006; 66(18): 9171-7)