bluuebunny/crossref_metadata_2025_split huggingface dataset:
Static and dynamic connectivity in bed-scale models of faulted and unfaulted turbidites
Authors: Manzocchi T. , Walsh J. J. , Tomasso M. , Strand J. , Childs C. , Haughton P. D. W. 
Published: December 2007

Abstract

A range of unfaulted and faulted bed-scale models with sheet-like or lobate bed geometries and faults of comparable sizes to beds have been built and analysed in terms of bed connectivity and fractional permeability assuming permeable sands and impermeable shales and shale smears. A new method has been devised allowing amalgamation ratio to be included explicitly as model input and this property, rather than net:gross ratio, is found to be the dominant control on the connectivity of unfaulted sequences. At the geometrically representative scales considered (horizontal distances of >1 km for beds up to
c
. 1 m thick and faults up to
c
. 5 m throw), faulted sequences rarely have lower connectivities than their unfaulted sedimentological equivalents irrespective of whether fault rock properties are included. Models containing stochastically placed shale smears associated with each faulted shale horizon are generally better connected than if deterministic Shale Gouge Ratio cut-offs are applied. Despite the complex interactions between geological input and connectivity of the faulted sequences, the flow properties at representative scales are controlled by three geometrical variables describing connectivity, anisotropy and resolution. If two different faulted or unfaulted systems have identical values of these three variables they will have the same equivalent flow properties.
Three-dimensional upscaling of fault damage zones for reservoir simulation
Authors: Harris S. D. , Vaszi A. Z. , Knipe R. J. 
Published: December 2007

Abstract
Major faults are surrounded by damage zones of minor faults that, in siliclastic rocks, can form barriers to flow in their own right. Reservoir flow simulation, now a routine part of reservoir management, requires equivalent hydraulic parameters on the scale of the whole fault. Geological models of structurally complex reservoirs, from which flow simulator grids are generated, require information on the 3D characteristics of fault populations. Here, 3D stochastic models of fault damage zone (FDZ) architecture are generated based on fault population statistics (offset, orientation, length, thickness, spatial distribution) measured from seismic, outcrop and core data. These FDZ models provide input to a 3D discrete fault flow model (DFFM) and we consider the case when the minor faults have permeabilities (isotropic) that are several orders of magnitude lower than the host rock, and thus form partial barriers to flow. The DFFM is used to determine and characterize the impact of the parameters defining the FDZ on the predicted bulk FDZ permeability, connectivity, ‘efficiency’ as a barrier or retarder to flow, and the ‘effective’ fault rock throw to thickness relationship for the FDZ. The latter of the summary results presented provides a means for incorporating FDZs into conventional production simulation package models of structurally complex reservoirs.
The modelling of fractured reservoirs: constraints and potential for fracture network geometry and hydraulics analysis
Authors: Mäkel G. H. 
Published: December 2007

Abstract
The interconnectedness of a subsurface fracture system depends on five fracture and fracture set geometry characteristics: density, orientation, dimensions (height and length), connectivity and aperture. Orientation and density can be determined with some degree of accuracy but the uncertainty ranges associated with the other characteristics will be large. Calibration with dynamic indicators will bring out the hydraulic properties of the network and can help to reduce uncertainty in the geometric characteristics. The fracture network geometry in the inter-well space can be described through geostatistical analysis but more commonly it is derived from seismic data, through edge detection or the analysis and calibration of seismic velocity anisotropy attributes or curvature analysis. Geomechanical analysis is necessary to evaluate the impact on network conductivity of the changing stress state in the reservoir. Using percolation theory, a qualitative assessment can be made of how the conductivity and interconnectedness of the fracture network is developed in terms of network clusters. This integrated analysis of static and dynamic fracture data leads to the formulation of conceptual models and a set of modelling rules. A Digital (Discrete) Fracture Network model, based on these concept(s), rules and inter-well interpolation data, can then be analysed in terms of expected network cluster size, distribution and hydraulics. This provides a control on the expectations embedded in the concepts prior to dynamic modelling. The uncertainties are normally quite large and very seldom will they allow construction of the definitive fracture model. The systematic and integrated analysis of fracture network geometry, constrained with dynamic indicators and subsequent network cluster analysis, are necessary preparatory steps for construction and analysis of dynamic models.
Numerical simulation of multi-phase fluid flow in structurally complex reservoirs
Authors: Matthäi S. K. , Geiger S. , Roberts S. G. , Paluszny A. , Belayneh M. , Burri A. , Mezentsev A. , Lu H. , Coumou D. , Driesner T. , Heinrich C. A. 
Published: December 2007

Abstract
Realistic simulation of structurally complex reservoirs (SCR) is challenging in at least three ways: (1) geological structures must be represented and discretized accurately on vastly different length scales; (2) extreme ranges and discontinuous variations of material properties have to be associated with the discretized structures and accounted for in the computations; and (3) episodic, highly transient and often localized events such as well shut-in have to be resolved adequately within the overall production history, necessitating a highly adaptive resolution of time. To facilitate numerical experiments that elucidate the emergent properties, typical states and state transitions of SCRs, an application programmer interface (API) called complex systems modelling platform (CSMP++) has been engineered in ANSI/ISO C++. It implements a geometry and process-based SCR decomposition in space and time, and uses an algebraic multigrid solver (SAMG) for the spatio-temporal integration of the governing partial differential equations. This paper describes a new SCR simulation workflow including a two-phase fluid flow model that is compared with ECLIPSE in a single-fracture flow simulation. Geologically realistic application examples are presented for incompressible 2-phase flow, compressible 3-phase flow, and pressure-diffusion in a sector-scale model of a structurally complex reservoir.
Evidence for Microtubule Target Engagement in Tumors of Patients Receiving Ixabepilone
Authors: Zhuang Sen H. , Hung Y. Elizabeth , Hung Laura , Robey Robert W. , Sackett Dan L. , Linehan W. Marston , Bates Susan E. , Fojo Tito , Poruchynsky Marianne S. 
Published: December 2007

Abstract
Purpose: Microtubule-stabilizing agents, such as taxanes, have been shown to be effective anticancer drugs. α-Tubulin, a basic unit of microtubules, can undergo several posttranslational modifications after assembly into stabilized microtubules, including acetylation and detyrosination. These modifications have been observed in cell cultures after exposure to microtubule stabilizers. Our objective was to develop a straightforward and dependable assay to show tubulin target engagement in tumor tissue after treatment of patients with ixabepilone(BMS-247550; Ixempra).
Experimental Design: Levels of posttranslationally modified α-tubulin were assessed in lysates of cultured malignant cell lines, as well as in both tumor tissue and peripheral blood mononuclear cells derived from patients before and after treatment with ixabepilone. Modification-specific antibodies permitted quantitative Western blot analysis.
Results: In cultured cell lines, the levels of detyrosinated (glu-terminated) and acetylated α-tubulin increased after microtubule stabilization induced by ixabepilone. ixabepilone treatment also induced a 2-fold to 25-fold increase in detyrosinated α-tubulin levels in 11 of 13 serial biopsies and a 2-fold to 100-fold increase in acetylated α-tubulin in 11 of 12 serial biopsies obtained from patients receiving ixabepilone. Overall, little or no difference in tubulin modifications were observed between the before and after ixabepilone treatment in lysates from their peripheral blood mononuclear cells at the time point examined.
Conclusion: Assessing the levels of detyrosinated and/or acetylated α-tubulin seems to provide a simple and reliable assay to show target engagement by the microtubule-stabilizing agent ixabepilone. Such analyses may provide further understanding of therapeutic success or failure of microtubule-stabilizing agents in cancer therapy.
Angiogenesis-Promoting Gene Patterns in Alveolar Soft Part Sarcoma
Authors: Lazar Alexander J.F. , Das Parimal , Tuvin Daniel , Korchin Borys , Zhu Quansheng , Jin Zeming , Warneke Carla L. , Zhang Peter S. , Hernandez Vivian , Lopez-Terrada Dolores , Pisters Peter W. , Pollock Raphael E. , Lev Dina 
Published: December 2007

Abstract
Purpose: We examined a cohort of patients with alveolar soft part sarcoma (ASPS) treated at our institution and showed the characteristic ASPSCR1-TFE3 fusion transcript in their tumors. Investigation of potential angiogenesis-modulating molecular determinants provided mechanistic and potentially therapeutically relevant insight into the enhanced vascularity characteristic of this unusual tumor.
Experimental Design: Medical records of 71 patients with ASPS presenting at the University of Texas M.D. Anderson Cancer Center (1986-2005) were reviewed to isolate 33 patients with formalin-fixed paraffin-embedded material available for study. RNA extracted from available fresh-frozen and formalin-fixed paraffin-embedded human ASPS tumors were analyzed for ASPSCR1-TFE3 fusion transcript expression using reverse transcription-PCR and by angiogenesis oligomicroarrays with immunohistochemical confirmation.
Results: Similar to previous studies, actuarial 5- and 10-year survival rates were 74% and 51%, respectively, despite frequent metastasis. ASPSCR1-TFE3 fusion transcripts were identified in 16 of 18 ASPS samples. In the three frozen samples subjected to an angiogenesis oligoarray, 18 angiogenesis-related genes were up-regulated in tumor over adjacent normal tissue. Immunohistochemistry for jag-1, midkine, and angiogenin in 33 human ASPS samples confirmed these results. Comparison with other sarcomas indicates that the ASPS angiogenic signature is unique.
Conclusion: ASPS is a highly vascular and metastatic tumor with a surprisingly favorable outcome; therapeutically resistant metastases drive mortality. Future molecular therapies targeting overexpressed angiogenesis-promoting proteins (such as those identified here) could benefit patients with ASPS.
Influence of CYP3A4 Inhibition on the Steady-State Pharmacokinetics of Imatinib
Authors: van Erp Nielka P. , Gelderblom Hans , Karlsson Mats O. , Li Jing , Zhao Ming , Ouwerkerk Jan , Nortier Johan W. , Guchelaar Henk-Jan , Baker Sharyn D. , Sparreboom Alex 
Published: December 2007

Abstract
Purpose: To evaluate the effects of ritonavir, a potent inhibitor of CYP3A4, on the steady-state pharmacokinetics of imatinib.
Experimental Design: Imatinib pharmacokinetics were evaluated in cancer patients receiving the drug for at least 2 months, after which ritonavir (600 mg) was administered daily for 3 days. Samples were obtained on the day before ritonavir (day 1) and on the third day (day 4). The in vitro metabolism of imatinib with or without ritonavir and the effect of imatinib on 1-OH-midazolam formation rate, a probe for CYP3A4 activity, were evaluated with human CYP3A4 and pooled liver microsomes.
Results: In 11 evaluable patients, the geometric mean (95% confidence interval) area under the curve of imatinib on days 1 and 4 were 42.6 (33.0-54.9) μg·h/mL and 41.2 (32.1-53.1) μg·h/mL, respectively (P = 0.65). A population analysis done in NONMEM with a time-dependent covariate confirmed that ritonavir did not influence the clearance or bioavailability of imatinib. In vitro, imatinib was metabolized to the active metabolite CGP74588 by CYP3A4 and CYP3A5 and, to a lesser extent, by CYP2D6. Ritonavir (1 μmol/L) completely inhibited CYP3A4-mediated metabolism of imatinib to CGP74588 but inhibited metabolism in microsomes by only 50%. Imatinib significantly inhibited CYP3A4 activity in vitro.
Conclusion: At steady state, imatinib is insensitive to potent CYP3A4 inhibition and relies on alternate elimination pathways. For agents with complex elimination pathways that involve autoinhibition, interaction studies that are done after a single dose may not be applicable when drugs are administered chronically.
Hypoxia-Inducible Factor 1α in Clear Cell Renal Cell Carcinoma
Authors: Klatte Tobias , Seligson David B. , Riggs Stephen B. , Leppert John T. , Berkman Maria K. , Kleid Mark D. , Yu Hong , Kabbinavar Fairooz F. , Pantuck Allan J. , Belldegrun Arie S. 
Published: December 2007

AbstractPurpose: Hypoxia-inducible factor-1α (HIF-1α) plays an important role in tumoral adaptation to hypoxic conditions by serving as a transcription factor for several crucial proteins, including vascular endothelial growth factor and carbonic anhydrase IX (CAIX). Here, we evaluated the significance of HIF-1α in renal cell carcinoma (RCC).Experimental Design: Immunohistochemical analysis was done on a tissue microarray constructed from paraffin-embedded primary tumor specimens from 357 patients treated by nephrectomy for RCC. Nuclear expression was evaluated by a single pathologist who was blinded to outcome. The expression levels were associated with pathologic variables and survival.Results: HIF-1α expression was greater in RCC than in benign tissue. Clear cell RCC showed the highest expression levels. In clear cell RCC, HIF-1α was significantly correlated with markers of apoptosis (p21, p53), the mammalian target of rapamycin pathway (pAkt, p27), CXCR3, and proteins of the vascular endothelial growth factor family. HIF-1α was correlated with CAIX and CAXII in localized, but not in metastatic RCC. HIF-1α expression predicted outcome in metastatic patients: patients with high HIF-1α expression (&gt;35%) had significantly worse survival than patients with low expression (≤35%); median survival, 13.5 versus 24.4 months, respectively (P = 0.005). Multivariate analysis retained HIF-1α and CAIX expression as the strongest independent prognostic factors for patients with metastatic clear cell RCC.Conclusions: HIF-1α is an important independent prognostic factor for patients with metastatic clear cell RCC. Because HIF-1α and CAIX are independently and differentially regulated in metastatic clear cell RCC, both tumor markers can be complementary in predicting prognosis.
Loss of Heterozygosity at D8S298 Is a Predictor for Long-term Survival of Patients with Tumor-Node-Metastasis Stage I of Hepatocellular Carcinoma
Authors: Pang Jin-Zhong , Qin Lun-Xiu , Ren Ning , Hei Zhen-Yu , Ye Qing-Hai , Jia Wei-Dong , Sun Bing-Sheng , Lin Guo-Ling , Liu Dao-Yong , Liu Yin-Kun , Tang Zhao-You 
Published: December 2007

Abstract
Purpose: Our previous studies have shown that chromosome 8p deletion correlates with metastasis of hepatocellular carcinoma (HCC). This study was to determine whether 8p deletion could be used in predicting the prognosis of patients with HCC, particularly in those with early stage of HCC.
Experimental Design: A total of 131 patients with tumor-node-metastasis (TNM) stage I of HCC who underwent curative liver resection were enrolled. Loss of heterozygosity (LOH) was examined using 10 microsatellite markers at chromosome 8p, as well as 14 microsatellites at chromosome 1p, 17p, 4q, 13q, and 16q, and their association with 5-year overall survival (OS) and disease-free survival (DFS) of patients was analyzed.
Results: In the entire cohort of patients, the mean LOH frequency at these 24 loci was 43.2%; LOH frequencies at D8S298 and D1S199 were 31.5% and 33.7%, respectively. LOH at D8S298 was associated with a worse 5-year OS (P = 0.008) and DFS (P = 0.038) in patients with TNM stage I of HCC. Likewise, the patients with LOH at D1S199 had a worse 5-year OS (P &lt; 0.001) and DFS (P = 0.014) compared with those without LOH at D1S199. In multivariate analyses, LOH at D8S298 was an independent predictor of decreased DFS (hazard ratio, 0.372; 95% 95% confidence interval, 0.146-0.948; P = 0.038), whereas LOH at D1S199 was an independent predictor of decreased OS (hazard ratio, 0.281; 95% confidence interval, 0.123-0.643; P = 0.003).
Conclusions: LOH at D8S298 and D1S199 is independently associated with a worse survival in patients with TNM stage I of HCC after curative resection and could serve as novel prognostic predictors for this subgroup of patients.
l-Arginine Reduces Cell Proliferation and Ornithine Decarboxylase Activity in Patients with Colorectal Adenoma and Adenocarcinoma
Authors: Ma Qingyong , Wang Yunjian , Gao Xiaopeng , Ma Zhenhua , Song Zhengjun 
Published: December 2007

Abstract
Purpose: Evidence suggests that the majority of colorectal carcinomas arise from adenomas, and l-arginine suppresses colorectal tumorigenesis. We suppose that l-arginine may inhibit the process of carcinogenesis from colorectal adenoma to adenocarcinoma. The aim of this study was to investigate the effects of l-arginine on the formation and development of colorectal tumors.
Experimental Design: We selected 60 patients with colorectal cancer and 60 patients with colorectal adenoma (CRA) and divided them into four groups of 30 patients each. We gave 30 g (120 mL) of l-arginine everyday for 3 days to the test groups, whereas l-arginine was substituted by 5% glucose in the control groups. The expression of the proliferating cell nuclear antigen, survivin, and nitric oxide synthase was examined immunohistochemically, and ornithine decarboxylase (ODC) activity was examined spectrophotometrically. Serum nitric oxide (NO) was detected by the Griess assay.
Results: In patients with CRA, the proliferating cell nuclear antigen and survivin labeling indexes and ODC activity of the tumor and paratumor mucosa in the l-arginine–treated group after l-arginine treatment were significantly lower as compared with the corresponding pretreatment values (P &lt; 0.01). Moreover, inducible nitric oxide synthase expression in the tumor markedly increased after l-arginine treatment (P &lt; 0.05). Serum NO levels in the patients with colorectal cancer were markedly higher than those in the patients with CRA, and l-arginine treatment was responsible for this increase (P &lt; 0.05).
Conclusions: Our results show that l-arginine can restrain crypt cell hyperproliferation and the expression of survivin, an inhibitor of apoptosis protein. This suggests that l-arginine can block the formation and development of colorectal tumors, and this effect might be related to the increased serum NO concentration and decreased ODC activity.
PAM4-Reactive MUC1 Is a Biomarker for Early Pancreatic Adenocarcinoma
Authors: Gold David V. , Karanjawala Zarir , Modrak David E. , Goldenberg David M. , Hruban Ralph H. 
Published: December 2007

Abstract
Purpose: The anti-MUC1 monoclonal antibody (MAb), PAM4, has a high specificity for pancreatic adenocarcinoma compared with other cancers, normal tissues, or pancreatitis. In order to assess its role in early pancreatic cancer development, we examined the expression of the PAM4-reactive MUC1 in the noninvasive precursor lesions, pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasia (IPMN).
Experimental Design: Tissue microarrays prepared from formalin-fixed, paraffin-embedded specimens were assessed by immunohistology for expression of the PAM4-reactive, non–variable number of tandem repeats (VNTR), MUC1 epitope, and the VNTR epitope bound by the MA5 MAb.
Results: The PAM4-reactive MUC1 epitope was not detected in normal pancreas but was expressed in 87% (48 of 55) of invasive pancreatic adenocarcinomas, including early stage 1 disease: PAM4 labeled 94% (44 of 47) of the earliest PanIN lesions, PanIN-1A and 1B, along with 91% (10 of 11) of PanIN-2, 40% (2 of 5) of PanIN-3, and 86% (31 of 36) of intraductal papillary mucinous neoplasia lesions. A mostly diffuse pattern of labeling was observed. A second, unrelated, anti-MUC1 MAb, MA5, showed considerably less sensitivity with early PanIN-1 lesions; only 61% (25 of 41) were positive and the labeling did not differentiate normal pancreas from PanINs.
Conclusions: The results suggest that expression of the PAM4-reactive antigen may represent an early event in the development of invasive pancreatic adenocarcinoma, and is unrelated to the VNTR peptide core epitopes of MUC1. Detection of this biomarker using immunohistology, in vitro immunoassays, and in vivo antibody–based imaging may provide new opportunities for the early detection and improved diagnosis of pancreatic cancer.
When Memory Challenges History: Public Contestation of the Past in Post-Suharto Indonesia
Authors:   Budiawan
Published: December 2007

AbstractServing to legitimate the power of a political regime, official history is usually radically questioned as the regime collapses. Such is the case in Indonesia since the fall of Suharto in May 1998. Yet, unlike many other countries which have experienced transitions from authoritarian or totalitarian rule to democracy, post-Suharto Indonesia is witnessing an ambivalent critique of the official history, especially regarding the "September 30, 1965 affair" (the killing of six top Army officers by a regiment of Presidential guards which brought about Suharto's rise to power). On one hand, there is a public query over who masterminded the killings; on the other hand, there are reactionary responses towards the claims of victimization among ex-political prisoners associated with the September 30,1965 movement, as they articulate their experiences of the past tragedy. This paper attempts to explore the current controversy surrounding the official history of the September 30, 1965 affair through discussions of the paradox of memory, and the relationship between memory and history.
Johannes Kuchlinus, the 'Faithful Teacher': His Role in the Arminian Controversy and His Impact as a Theological Interpreter and Educator
Authors: Stanglin Keith 
Published: December 2007

AbstractJohannes Kuchlinus (1546-1606) was a Reformed pastor in Amsterdam and the founding regent of the theological college at Leiden University. Modern scholarship has overlooked the impact he had during his tenure at the university. Part of his impact has to do with his ability to keep relative peace in the midst of a boiling faculty controversy between Jacobus Arminius and Franciscus Gomarus. His greatest influence, though, is seen in his work as an interpreter and teacher of the Heidelberg Catechism. His first-hand knowledge of the Catechism and one of its authors, Zacharias Ursinus, combined with his prominent position of training pastors, uniquely qualified him as a proponent of the Catechism in the low countries. The disputations on the catechetical topics that he composed for student defenses, a list of which appears at the conclusion of this article, not only comprise a vast wealth of material for further study of this figure who influenced a generation, but also represent another source for the "Leiden theology" during this controversial period.