bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Potential‐Based Inversion of Unconfined Steady‐State Hydraulic Tomography
Authors: Cardiff M. , Barrash W. , Kitanidis P.K. , Malama B. , Revil A. , Straface S. , Rizzo E. 
Published: January 2009

AbstractThe importance of estimating spatially variable aquifer parameters such as transmissivity is widely recognized for studies in resource evaluation and contaminant transport. A useful approach for mapping such parameters is inverse modeling of data from series of pumping tests, that is, via hydraulic tomography. This inversion of field hydraulic tomographic data requires development of numerical forward models that can accurately represent test conditions while maintaining computational efficiency. One issue this presents is specification of boundary and initial conditions, whose location, type, and value may be poorly constrained. To circumvent this issue when modeling unconfined steady‐state pumping tests, we present a strategy that analyzes field data using a potential difference method and that uses dipole pumping tests as the aquifer stimulation. By using our potential difference approach, which is similar to modeling drawdown in confined settings, we remove the need for specifying poorly known boundary condition values and natural source/sink terms within the problem domain. Dipole pumping tests are complementary to this strategy in that they can be more realistically modeled than single‐well tests due to their conservative nature, quick achievement of steady state, and the insensitivity of near‐field response to far‐field boundary conditions. After developing the mathematical theory, our approach is first validated through a synthetic example. We then apply our method to the inversion of data from a field campaign at the Boise Hydrogeophysical Research Site. Results from inversion of nine pumping tests show expected geologic features, and uncertainty bounds indicate that hydraulic conductivity is well constrained within the central site area.
Travel Time Distributions Derived from Particle Tracking in Models Containing Weak Sinks
Authors: Visser A. , Heerdink R. , Broers H. P. , Bierkens M.F.P. 
Published: January 2009

AbstractA travel time distribution based on a particle‐tracking analysis in a ground water model containing weak sinks is often uncertain because whether a particle is discharged or allowed to pass through a weak sink is unresolved by particle‐tracking theory. We present a probability‐based method to derive an objective travel time distribution in models containing weak sinks. The method discharges a fraction of the particle at the weak sink and allows the remaining fraction to pass through the weak sink. The weight of the discharged fraction depends on the ratio of the sink flux to the influx into the weak sink cell. We tested this approach on a coarse (100 × 100 m) and a fine (25 × 25 m) horizontal resolution regional scale ground water model (34.5 × 24 km). We compared the travel time distributions in a small subcatchment derived from particle‐tracking analysis with one derived from a transport model. We found that the particle‐tracking analysis with the coarse model underestimated the travel time distribution of the catchment compared to the transport solution or a particle‐tracking analysis with the fine model. The underestimation of travel times with the coarse model was a result of a large area covered by sink cells in this model and the more accurate flow patterns simulated by the fine model. The probability‐based method presented here compares favorably with a solute transport solution and provides an accurate travel time distribution when used with a fine‐resolution ground water model.
Plastic Collapse Load for Vessel With External Flaw Simultaneously Subjected to Internal Pressure and External Bending Moment: Experimental and FEA Results
Authors: Konosu Shinji , Kano Masato , Mukaimachi Norihiko , Komura Hiroyuki , Takada Hiroyuki 
Published: January 2009

Abstract
This paper is based on work done to establish the validity of a simple engineering approach to assess plastic collapse for a vessel with a local thin area (LTA). The approach is based on a recently developed p-M (internal pressure ratio and external bending moment ratio) diagram, which is an easy way to visualize the status of a vessel with a LTA simultaneously subjected to internal pressure, p and external bending moment, M due to earthquake, etc. If the assessment point (Mr,pr) lies inside the p-M line, the vessel with the LTA is judged to be safe. Numerous experiments and finite element analyses for a cylinder with an external flaw were conducted under (1) pure internal pressure, (2) pure external bending moment, and (3) subjected simultaneously to both internal pressure and external bending moment, in order to determine the plastic initiation load and plastic collapse load by applying the twice-elastic slope (TES) as recommended by ASME. It has been clarified that the collapse (TES) loads are similar to those calculated under the proposed p-M line based on the measured yield stress. The p-M line adopted in the Ibaraki fitness for service (FFS) rule based on the specified minimum yield stress with a safety factor of 1.5 indicates that the safety margin for the plastic initiation loads at LTA is about 1.0–3.0, about 1.5–4.0 for the TES loads at LTA, and 2.5–6.5 for the plastic instability (break) loads.
Effect of task familiarisation on distribution of energy during a 2000 m cycling time trial
Authors: Corbett J , Barwood M J , Parkhouse K 
Published: January 2009

Aim:To investigate the effect of task familiarisation on the spontaneous pattern of energy expenditure during a series of 2000 m cycling time trials (TTs).Method:Nine trained males completed three 2000 m TTs on a Velotron cycling ergometer. To examine pacing strategy, the data were assigned to 250 m “bins,” with the pattern of aerobic and anaerobic energy expenditure calculated from total work accomplished and gas-exchange data.Results:There were no significant differences between trials in performance times (191.4 (SD 4.3), 189.4 (4.6), 190.1 (5.6) s), total aerobic (58.3 (2.7), 58.4 (3.1), 58.0 (3.4) kJ) and total anaerobic energy expenditure (16.4 (3.3), 17.3 (2.8), 16.5 (3.1) kJ). Pacing strategy in the second and third TT differed from the first TT in that a lower power output was adopted during the first 500 m, enabling a higher power output during the final 750 m of the TT. This adjustment in the pattern of energy expenditure was mediated by an alteration in the pattern of anaerobic energy expenditure, which paralleled changes in total energy expenditure. Furthermore, participants retained an anaerobic energy “reserve” enabling an end-spurt during the second and third trials.Conclusion:Small modifications to the pacing strategy are made following a single bout of exercise, primarily by altering the rate of anaerobic energy expenditure. This may have served to prevent critical metabolic disturbances. The alteration in pacing strategy following the first exercise bout is compatible with a complex intelligent regulatory system.
Multiple work-related accidents: tracing the role of hearing status and noise exposure
Authors: Girard S A , Picard M , Davis A C , Simard M , Larocque R , Leroux T , Turcotte F 
Published: January 2009

Objectives:Our main purpose was to investigate any relationship between noise exposure levels in the workplace, degree of hearing loss (HL), and the relative risk of accident (OR of single or multiple events).Methods:We conducted a retrospective study of 52 982 male workers aged 16–64 years with long-standing exposures to occupational noise over a 5-year period, using “hearing status” and “noise exposure” from the registry held by the Quebec National Institute of Public Health. Information on work-related accidents was obtained from the Quebec Workers’ Compensation Board. Hearing threshold level measurements and noise exposures were regressed on the numbers of accidents after adjusting for age.Results:Exposure to extremely noisy environments (Leq8h(equivalent noise level for 8 h exposure) ⩾90 dBA) is associated with a higher relative risk of accident. The severity of hearing impairment (average bilateral hearing threshold levels at 3, 4 and 6 kHz) increases the relative risk of single and multiple events when threshold levels exceed 15 dB of hearing loss. The relative risk of multiple events (four or more) is approximately three times higher among severely hearing-impaired workers who are exposed to Leq8h⩾90 dBA.Conclusion:Single and multiple events are associated with high noise exposure and hearing status. This suggests that reducing noise exposure contributes to increased safety in noisy industries and prevents hearing loss. Hearing-impaired workers assigned to noisy workstations should be provided with assistive listening devices and efficient communication strategies should be implemented.
Prediction of Clinical Outcome in Multiple Lung Cancer Cohorts by Integrative Genomics: Implications for Chemotherapy Selection
Authors: Broët Philippe , Camilleri-Broët Sophie , Zhang Shenli , Alifano Marco , Bangarusamy Dhinoth , Battistella Maxime , Wu Yonghui , Tuefferd Marianne , Régnard Jean-François , Lim Elaine , Tan Patrick , Miller Lance D. 
Published: January 2009

Abstract
The role of adjuvant chemotherapy in patients with stage IB non–small-cell lung cancer (NSCLC) is controversial. Identifying patient subgroups with the greatest risk of relapse and, consequently, most likely to benefit from adjuvant treatment thus remains an important clinical challenge. Here, we hypothesized that recurrent patterns of genomic amplifications and deletions in lung tumors could be integrated with gene expression information to establish a robust predictor of clinical outcome in stage IB NSCLC. Using high-resolution microarrays, we generated tandem DNA copy number and gene expression profiles for 85 stage IB lung adenocarcinomas/large cell carcinomas. We identified specific copy number alterations linked to relapse-free survival and selected genes within these regions exhibiting copy number–driven expression to construct a novel integrated signature (IS) capable of predicting clinical outcome in this series (P = 0.02). Importantly, the IS also significantly predicted clinical outcome in two other independent stage I NSCLC cohorts (P = 0.003 and P = 0.025), showing its robustness. In contrast, a more conventional molecular predictor based solely on gene expression, while capable of predicting outcome in the initial series, failed to significantly predict outcome in the two independent data sets. Our results suggest that recurrent copy number alterations, when combined with gene expression information, can be successfully used to create robust predictors of clinical outcome in early-stage NSCLC. The utility of the IS in identifying early-stage NSCLC patients as candidates for adjuvant treatment should be further evaluated in a clinical trial. [Cancer Res 2009;69(3):1055–62]
Vasculostatin Inhibits Intracranial Glioma Growth and Negatively RegulatesIn vivoAngiogenesis through a CD36-Dependent Mechanism
Authors: Kaur Balveen , Cork Sarah M. , Sandberg Eric M. , Devi Narra S. , Zhang Zhaobin , Klenotic Philip A. , Febbraio Maria , Shim Hyunsuk , Mao Hui , Tucker-Burden Carol , Silverstein Roy L. , Brat Daniel J. , Olson Jeffrey J. , Van Meir Erwin G. 
Published: January 2009

AbstractAngiogenesis is a critical physiologic process that is appropriated during tumorigenesis. Little is known about how this process is specifically regulated in the brain. Brain angiogenesis inhibitor-1 (BAI1) is a brain-predominant seven-transmembrane protein that contains five antiangiogenic thrombospondin type-1 repeats (TSR). We recently showed that BAI1 is cleaved at a conserved proteolytic cleavage site releasing a soluble, 120 kDa antiangiogenic factor called vasculostatin (Vstat120). Vstat120 has been shown to inhibit in vitro angiogenesis and suppress subcutaneous tumor growth. Here, we examine its effect on the intracranial growth of malignant gliomas and further study its antitumor mechanism. First, we show that expression of Vstat120 strongly suppresses the intracranial growth of malignant gliomas, even in the presence of the strong proangiogenic stimulus mediated by the oncoprotein epidermal growth factor receptor variant III (EGFRvIII). This tumor-suppressive effect is accompanied by a decrease in tumor vascular density, suggesting a potent antiangiogenic effect in the brain. Second, and consistent with this interpretation, we find that treatment with Vstat120 reduces the migration of cultured microvascular endothelial cells in vitro and inhibits corneal angiogenesis in vivo. Third, we show that these antivascular effects critically depend on the presence of the cell surface receptor CD36 on endothelial cells in vitro and in vivo, supporting the role of Vstat120 TSRs in mediating these effects. These results advance the understanding of brain-specific angiogenic regulation, and suggest that Vstat120 has therapeutic potential in the treatment of brain tumors and other intracerebral vasculopathies. [Cancer Res 2009;69(3):1212–20]
A Gonadotropin-Releasing Hormone-II Antagonist Induces Autophagy of Prostate Cancer Cells
Authors: Kim Dong-Ki , Yang Ji Sook , Maiti Kaushik , Hwang Jong-Ik , Kim Kyungjin , Seen Dongseung , Ahn Younghee , Lee Cheolju , Kang Byeong-Cheol , Kwon Hyuk Bang , Cheon Jun , Seong Jae Young 
Published: January 2009

AbstractGonadotropin-releasing hormone-I (GnRH-I) is known to directly regulate prostate cancer cell proliferation. However, the role of GnRH-II in prostate cancer is unclear. Here, we investigated the effect of the GnRH-II antagonist trptorelix-1 (Trp-1) on growth of PC3 prostate cancer cells. Trp-1 induced growth inhibition of PC3 cells in vitro and inhibited growth of PC3 cells xenografted into nude mice. FITC-N3, an FITC-conjugated Trp-1 analogue, was largely present in the mitochondria of prostate cancer cells, but not in other cells that are not derived from the prostate. Trp-1–induced PC3 growth inhibition was associated with decreased mitochondrial membrane potential and increased levels of mitochondrial and cytosolic reactive oxygen species (ROS). Growth inhibition was partially prevented by cotreating cells with N-acetyl cysteine, an antioxidant. Cytochrome c release and caspase-3 activation were not detected in Trp-1–treated cells. However, Trp-1 induced autophagosome formation, as seen by increased LysoTracker staining and recruitment of microtubule-associated protein 1 light chain 3 to these new lysosomal compartments. Trp-1–induced autophagy was accompanied by decreased AKT phosphorylation and increased c-Jun NH2 terminal kinase phosphorylation, two events known to be linked to autophagy. Taken together, these data suggest that Trp-1 directly induces mitochondrial dysfunction and ROS increase, leading to autophagy of prostate cancer cells. GnRH-II antagonists may hold promise in the treatment of prostate cancer. [Cancer Res 2009;69(3):923–31]
Distinct Roles of BARD1 Isoforms in Mitosis: Full-Length BARD1 Mediates Aurora B Degradation, Cancer-Associated BARD1β Scaffolds Aurora B and BRCA2
Authors: Ryser Stephan , Dizin Eva , Jefford Charles Edward , Delaval Bénédicte , Gagos Sarantis , Christodoulidou Agni , Krause Karl-Heinz , Birnbaum Daniel , Irminger-Finger Irmgard 
Published: January 2009

AbstractThe BRCA1-associated ring domain protein 1 (BARD1) interacts with BRCA1 via its RING finger domain. The BARD1-BRCA1 complex participates in DNA repair, cell cycle control, genomic stability, and mitotic spindle formation through its E3 ubiquitin ligase activity. Cancer cells express several BARD1 protein isoforms, including the RING finger–deficient variant BARD1β. Here, we show that BARD1 has BRCA1-dependent and BRCA1-independent functions in mitosis. BARD1, but not BRCA1, localizes to the midbody at telophase and cytokinesis, where it colocalizes with Aurora B. The 97-kDa full-length (FL) BARD1 coimmunoprecipates with BRCA1, but the 82-kDa BARD1β coimmunoprecipitates with Aurora B and BRCA2. We used selective small interfering RNAs to distinguish the functions of FL BARD1 and BARD1β. Depletion of FL BARD1 had only minor effects on cell growth and did not abolish midbody localization of BARD1 staining, but resulted in massive up-regulation of Aurora B. In contrast, suppression of FL BARD1 and BARD1β led to growth arrest and correlated with various mitotic defects and disappearance of midbody localization of BARD1 staining. Our data suggest a novel function of FL BARD1 in Aurora B ubiquitination and degradation, opposing a proproliferative function of BARD1β in scaffolding Aurora B and BRCA2. Thus, loss of FL BARD1 and up-regulation of Aurora B, as observed in cancer cells, can be explained by an imbalance of FL BARD1 and BARD1β. [Cancer Res 2009;69(3):1125–34]
A Destructive Cascade Mediated by CCL2 Facilitates Prostate Cancer Growth in Bone
Authors: Li Xin , Loberg Robert , Liao Jinhui , Ying Chi , Snyder Linda A. , Pienta Kenneth J. , McCauley Laurie K. 
Published: January 2009

Abstract
Monocyte chemoattractant protein 1 (CCL2) is a recently identified prominent regulator of prostate cancer growth and metastasis. The purpose of this study was to investigate the mechanistic role of CCL2 in prostate cancer growth in bone. The present study found that CCL2 was up-regulated in osteoblasts (3-fold by PC-3 and 2-fold by VCaP conditioned medium) and endothelial cells (2-fold by PC-3 and VCaP conditioned medium). Parathyroid hormone-related protein (PTHrP) treatment of osteoblastic cells up-regulated CCL2 and was blocked by a PTHrP antagonist, suggesting that prostate cancer–derived PTHrP plays an important role in elevation of osteoblast-derived CCL2. CCL2 indirectly increased blood vessel formation in endothelial cells through vascular endothelial growth factor-A, which was up-regulated 2-fold with administration of CCL2 in prostate cancer cells. In vivo, anti-CCL2 treatment suppressed tumor growth in bone. The decreased tumor burden was associated with decreased bone resorption (serum TRAP5b levels were decreased by 50–60% in anti–CCL2-treated animals from VCaP or PC-3 cell osseous lesions) and microvessel density was decreased by 70% in anti–CCL2-treated animals with bone lesions from VCaP cells. These data suggest that a destructive cascade is driven by tumor cell–derived, PTHrP-mediated induction of CCL2, which facilitates tumor growth via enhanced osteoclastic and endothelial cell activity in bone marrow. Taken together, CCL2 mediates the interaction between tumor-derived factors and host-derived chemokines acting in cooperation to promote skeletal metastasis. [Cancer Res 2009;69(4):1685–92]
Histone Deacetylases Are Required for Androgen Receptor Function in Hormone-Sensitive and Castrate-Resistant Prostate Cancer
Authors: Welsbie Derek S. , Xu Jin , Chen Yu , Borsu Laetitia , Scher Howard I. , Rosen Neal , Sawyers Charles L. 
Published: January 2009

Abstract
Transcriptional activity of the androgen receptor (AR) is crucial for growth and survival of prostate cancer even upon development of resistance to androgen ablation and antiandrogen therapies. Therefore, novel therapies that can suppress AR transcriptional activity when conventional hormone therapies fail are needed. Here, we show that histone deacetylase (HDAC) inhibitors, including SAHA (vorinostat) and LBH589, which are currently being tested in clinic, could be such a therapy. HDAC inhibitors block the AR-mediated transcriptional activation of many genes, including the TMPRSS2 gene involved in fusion with ETS family members in a majority of prostate cancers. Genetic knockdown of either HDAC1 or HDAC3 can also suppress expression of AR-regulated genes, recapitulating the effect of HDAC inhibitor treatment. Whereas HDAC inhibitor treatment can lower androgen receptor protein levels in prostate cancer cells, we show that independent of AR protein levels, HDAC inhibitors block AR activity through inhibiting the assembly of coactivator/RNA polymerase II complex after AR binds to the enhancers of target genes. Failed complex assembly is associated with a phase shift in the cyclical wave of AR recruitment that typically occurs in response to ligand treatment. HDAC inhibitors retain the ability to block AR activity in castration-resistant prostate cancer models and, therefore, merit clinical investigation in this setting. The HDAC-regulated AR target genes defined here can serve as biomarkers to ensure sufficient levels of HDAC inhibition. [Cancer Res 2009;69(3):958–66]
Cyclic AMP Signaling as a Mediator of Vasculogenic Mimicry in Aggressive Human Melanoma Cells In vitro
Authors: Lissitzky Jean-Claude , Parriaux Danielle , Ristorcelli Elodie , Vérine Alain , Lombardo Dominique , Verrando Patrick 
Published: January 2009

Abstract
Aggressive melanoma cells can engage in a process termed vasculogenic mimicry (VM) that reflects the ability of tumor cells to express a multipotent, stem cell–like phenotype. Melanoma cell plasticity contributes to the lack of efficient therapeutic strategies targeting metastatic tumors. This study reveals cyclic AMP as a mediator of VM in vitro. In uveal and cutaneous metastatic aggressive human melanoma cells, an increase in cyclic AMP by forskolin, dibutyryl cyclic AMP, or G protein–coupled receptor (GPCR) ligands such as adrenaline and vasoactive intestinal peptide inhibited VM to different extents. Although chemical modulators of protein kinase A (PKA) had no effect, a specific pharmacologic activator of Exchange protein directly activated by cyclic AMP (Epac) impaired VM. Ras-associated protein-1 (Rap1) activation assays revealed that cyclic AMP–elevating agents induce a PKA-independent activation of Epac/Rap1. Pharmacologic inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) activity abolished VM. Phosphorylation of ERK1/2 was PKA-independently inhibited by forskolin but not inhibited by Epac/Rap1 signaling, PKA modulation, or GPCR ligands. Furthermore, the forskolin also inhibited phosphatidyl inositol-3-kinase (PI3K)-mediated activation of protein kinase Akt, as monitored by Ser473 phosphorylation. The pharmacologic activation of Epac and GPCR ligands slightly stimulated Akt, a likely concomitant process of VM modulation. Collectively, these data show that forskolin strongly inhibits VM through PKA-independent activation of Epac/Rap1, PKA-, and Epac-independent inactivation of ERK1/2 and inhibition of PI3K/Akt. The data also show that VM inhibition by GPCR ligands involves mainly the Epac/Rap1-activated signal. Thus cyclic AMP inhibits VM through multiple signaling pathways. [Cancer Res 2009;69(3):802–9]