bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive Value of Aurora-A/STK15 Expression for Late Stage Epithelial Ovarian Cancer Patients Treated by Adjuvant Chemotherapy
Authors: Lassmann Silke , Shen Yi , Jütting Uta , Wiehle Philipp , Walch Axel , Gitsch Gerald , Hasenburg Annette , Werner Martin 
Published: July 2007

Abstract
Purpose: To investigate the expression and regulation of the centrosomal kinase Aurora-A/STK15 (AURKA) in epithelial ovarian cancers and to determine the prognostic and predictive value of this marker for patients with late stage epithelial ovarian cancer treated by distinct adjuvant chemotherapies.
Experimental Design: Archival resection specimens of epithelial ovarian cancers (n = 115) and nonneoplastic ovaries (n = 28) were analyzed for AURKA mRNA and protein expression by microdissection and quantitative reverse transcriptase-PCR and immunohistochemistry. AURKA DNA copy numbers were measured by fluorescence in situ hybridization in 37 cases. Statistical evaluation was done with respect to clinicopathologic variables, disease-free survival, and overall survival.
Results: AURKA mRNA expression was significantly elevated in cancers (P &lt; 0.001) and correlated with AURKA protein expression (P = 0.0134). Overexpression of AURKA protein was detected in 68 of 107 (63.5%) cases and was linked with increased AURKA DNA copy numbers (P = 0.0141) and centromere 20 aneusomy (P = 0.0137). Moreover, AURKA overexpression was associated with improved overall survival in optimal debulked patients receiving taxol/carboplatin therapy (n = 43, P = 0.018). Finally, in an exploratory approach, patients receiving non–taxane-based therapy, AURKA overexpression was predictive for worse overall survival (n = 30, P = 0.049).
Conclusions: AURKA overexpression is seen in the majority of late stage epithelial ovarian cancers, most likely due to increased AURKA DNA copy numbers and/or chromosome 20 aneusomy. Importantly, AURKA overexpression may differentially affect taxane and non–taxane-based adjuvant therapy responses. The study sheds new light on AURKA expression and regulation in epithelial cancers in vivo and specifically shows its value as a clinically relevant marker and as a potential therapeutic target per se.
Low Expression of Bax Predicts Poor Prognosis in Patients with Locally Advanced Esophageal Cancer Treated with Definitive Chemoradiotherapy
Authors: Kang Seok Yun , Han Jae Ho , Lee Kwang Jae , Choi Jin-Hyuk , Park Jung Il , Kim Hyoung Il , Lee Hyun-Woo , Jang Jun Ho , Park Joon Seong , Kim Hugh Chul , Kang Seunghee , Oh Young Taek , Chun Mison , Kim Jang Hee , Sheen Seung Soo , Lim Ho-Yeong 
Published: July 2007

Abstract
Purpose: The present study evaluated the prognostic significance of apoptosis-related proteins, p53, Bcl-2, Bax, and galectin-3 in patients with locally advanced esophageal cancer treated with definitive chemoradiotherapy.
Experimental Design: A total of 63 patients with locally advanced esophageal cancer (squamous cell carcinoma: 62; adenocarcinoma: 1; stages II-IV) were treated with definitive chemoradiotherapy using 5-fluorouracil and cisplatin combined with radiotherapy. Pretreatment tumor biopsy specimens were analyzed for p53, Bcl-2, Bax, and galectin-3 expression by immunohistochemistry.
Results: High expression of Bax, p53, Bcl-2, and galectin-3 was observed in 67%, 47%, 24%, and 29% of patients, respectively. The median overall survival (OS) of total patients was 14 months with 16% of 3-year OS. High expression of p53, Bcl-2, and galectin-3 did not show correlation with clinicopathologic characteristics, including patient outcome. Low expression of Bax was significantly correlated with lack of clinical complete response (P = 0.023). Low expression of Bax was also associated with poor OS (median, 8 months versus 16 months; P = 0.0008) in univariate analysis. In multivariate analysis, low expression of Bax was the most significant independent predictor of poor OS (P = 0.009), followed by low dose intensity of cisplatin and lack of clinical complete response.
Conclusions: Low expression of Bax was significantly associated with the poor survival of patients with locally advanced esophageal cancer treated with chemoradiotherapy using 5-fluorouracil and cisplatin. Immunohistochemical staining for Bax with a pretreatment biopsy specimen might be useful to select the optimal treatment options for these patients.
Humanized Anti-CD26 Monoclonal Antibody as a Treatment for Malignant Mesothelioma Tumors
Authors: Inamoto Teruo , Yamada Taketo , Ohnuma Kei , Kina Shinichiro , Takahashi Nozomu , Yamochi Tadanori , Inamoto Sakiko , Katsuoka Yoji , Hosono Osamu , Tanaka Hirotoshi , Dang Nam H. , Morimoto Chikao 
Published: July 2007

AbstractPurpose: CD26 is a 110-kDa cell surface antigen with a role in tumor development. In this report, we show that CD26 is highly expressed on the cell surface of malignant mesothelioma and that a newly developed humanized anti-CD26 monoclonal antibody (mAb) has an inhibitory effect on malignant mesothelioma cells in both in vitro and in vivo experiments.Experimental Design: Using immunohistochemistry, 12 patients' surgical specimens consisting of seven malignant mesothelioma, three reactive mesothelial cells, and two adenomatoid tumors were evaluated for expression of CD26. The effects of CD26 on malignant mesothelioma cells were assessed in the presence of transfection of CD26-expressing plasmid, humanized anti-CD26 mAb, or small interfering RNA against CD26. The in vivo growth inhibitory effect of humanized anti-CD26 mAb was assessed in human malignant mesothelioma cell mouse xenograft models.Results: In surgical specimens, CD26 is highly expressed in malignant mesothelioma but not in benign mesothelial tissues. Depletion of CD26 by small interfering RNA results in the loss of adhesive property, suggesting that CD26 is a binding protein to the extracellular matrix. Moreover, our in vitro data indicate that humanized anti-CD26 mAb induces cell lysis of malignant mesothelioma cells via antibody-dependent cell-mediated cytotoxicity in addition to its direct anti-tumor effect via p27kip1 accumulation. In vivo experiments with mouse xenograft models involving human malignant mesothelioma cells show that humanized anti-CD26 mAb treatment drastically inhibits tumor growth in tumor-bearing mice, resulting in enhanced survival.Conclusions: Our data strongly suggest that humanized anti-CD26 mAb treatment may have potential clinical use as a novel cancer therapeutic agent in CD26-positive malignant mesothelioma.
Predicting Human Tumor Drug Concentrations from a Preclinical Pharmacokinetic Model of Temozolomide Brain Disposition
Authors: Zhou Qingyu , Guo Ping , Kruh Gary D. , Vicini Paolo , Wang Xiaomin , Gallo James M. 
Published: July 2007

AbstractPurpose: Knowledge of drug concentrations in tumors is critical for understanding the determinants of drug accumulation in tumors. Because significant obstacles prevent making these measurements in humans, development of a predictive pharmacokinetic model would be of great value to the translation of preclinical data to the clinic. Our goal was to show how the latter could be achieved for temozolomide, an agent used in the treatment of brain tumors, using an orthotopic brain tumor model in rats.Experimental Design: Rats bearing i.c. tumors received 20 mg/kg i.v. of temozolomide followed by the subsequent measurement of serial plasma, cerebrospinal fluid (CSF), normal brain, and brain tumor temozolomide concentrations. The resultant data provided the framework to develop a hybrid physiologically based pharmacokinetic model for temozolomide in brain. The preclinical pharmacokinetic model was scaled to predict temozolomide concentrations in human CSF, normal brain, and brain tumor, and through a series of Monte Carlo simulations, the accumulation of temozolomide in brain tumors under conditions of altered blood-brain barrier permeability, fractional blood volume, and clinical dosing schedules was evaluated.Results: The developed physiologically based pharmacokinetic model afforded a mechanistic and accurate prediction of temozolomide brain disposition in rats, which through model scale-up procedures accurately predicted the CSF/plasma area under the drug concentration-time curve ratios of 0.2 reported in patients. Through a series of model simulations, it was shown that the brain tumor accumulation of temozolomide varied substantially based on changes in blood-brain barrier permeability and fractional tumor blood volume but minimally based on clinical dosing regimens.Conclusions: A physiologically based pharmacokinetic modeling approach offers a means to translate preclinical to clinical characteristics of drug disposition in target tissues and, thus, a means to select appropriate drug dosing regimens for achieving optimal target tissue drug concentrations.
The International Criminal Court and the Lord's Resistance Army Leaders: Prosecution or Amnesty?
Authors: Ssenyonjo Manisuli 
Published: July 2007

AbstractOn 13 October 2005, the International Criminal Court (ICC) Pre-Trial Chamber II unsealed the warrants of arrest for five senior leaders of the Lord's Resistance Army/Movement (LRA/M) for crimes against humanity and war crimes committed in Uganda since July 2002. While these warrants were yet to be executed, the Ugandan government entered negotiations with the LRA/M rebels. As a result Uganda's President Yoweri Museveni, disregarding the ICC arrest warrants, announced a 'total amnesty' for the LRA combatants in July 2006 on the condition that the rebels renounced terrorism and accepted peace. Following the amnesty offer, an agreement on cessation of hostilities between the Ugandan government and the LRA/M was concluded with effect from 29 August 2006. This article considers the question whether a 'total amnesty' to individuals indicted by the ICC may be binding upon the ICC.
Justice pénale internationale pour la paix et la réconciliation
Authors: Ayat Mohammed 
Published: July 2007

AbstractInternational criminal justice has made a tremendous leap forward since the mid-1990s. Gradually, it tends to reacting more and more to situations of armed conflict with declared objectives aiming at restoring peace and bringing about reconciliation among people. To what extent have these objectives been achieved?This article is revolves around this important question. The analysis is particularly focused on the case of the International Criminal Tribunal for Rwanda, where the author has been working for the past ten years. Ad hoc international tribunals have helped formalizing the judicial recognition by the international community of crimes that go against the conscience of the entire mankind. They consecrate their disapproval of the commission of such offences. In so doing, they contribute towards fighting impunity, which has for long been associated with those offences. They function in an environment where conventional national jurisdictions would have found it difficult to operate with efficiency. The author is neither overestimating nor underestimating their contribution. It is presented as one of the components in a reply that is inescapably of a multiple nature, to some complex situations where a remedy is as difficult as the illness to be cured. It is in this perspective that such contribution is indeed appreciated.
Monthly Forecast of the Madden–Julian Oscillation Using a Coupled GCM
Authors: Vitart Frédéric , Woolnough Steve , Balmaseda M. A. , Tompkins A. M. 
Published: July 2007

Abstract
A set of five-member ensemble forecasts initialized daily for 48 days during the Tropical Ocean Global Atmosphere Coupled Ocean–Atmosphere Response Experiment period are performed with the ECMWF monthly forecasting system in order to assess its skill in predicting a Madden–Julian oscillation (MJO) event. Results show that the model is skillful in predicting the evolution of the MJO up to about 14 days, but the amplitude of the MJO is damped after a few days of integration. In addition, the model has some deficiencies in propagating the MJO through the Maritime Continent. The same experiment framework is used to quantify the impacts of changing the model physics, the ocean model, the atmospheric horizontal resolution, and the initial conditions on the skill of the monthly forecasting system. Results show that there is a scope for extending the skillful range of the operational monthly forecasting system to predict the evolution of the MJO by at least a week. This is achieved by using an improved cloud parameterization together with a better representation of the mixing of the upper ocean. An additional set of experiments suggests that degrading the quality of the initial conditions (by using the 15-yr ECMWF Re-Analysis instead of the 40-yr ECMWF Re-Analysis) significantly degrades the skill of the model to predict an MJO event and that increasing the horizontal resolution of the atmospheric mode had only a minor impact on the MJO forecasts. In addition, results show that there is a significant sensitivity to the initial perturbations of the ensemble members, and therefore, targeting perturbations on the MJO could improve the skill of the monthly forecasting system. While the propagation of the MJO was sensitive to most of the changes described in this paper, only the change in cloud parameterization improved the strength of the MJO. The propagation of the MJO over the Maritime Continent remains an issue.
Mountain-Wave-Like Spurious Waves Associated with Simulated Cold Fronts due to Inconsistencies between Horizontal and Vertical Resolutions
Authors: Iga Shin-ichi , Tomita Hirofumi , Satoh Masaki , Goto Koji 
Published: July 2007

Abstract
A newly developed global nonhydrostatic model is used for life cycle experiments (LCEs) of baroclinic waves, and the resolution dependency of frontal structures is examined. LCEs are integrated for 12 days with horizontal grid intervals ranging from 223 to 3.5 km in a global domain. In general, fronts become sharper and corresponding vertical flow strengthens as horizontal resolution increases. However, if the ratio of vertical and horizontal grid intervals is sufficiently small compared to the frontal slope s, the overall frontal structure remains unchanged. In contrast, when the ratio of horizontal and vertical grid intervals exceeds 2s − 4s, spurious gravity waves are generated at the cold front. A linear model for mountain waves quantitatively explains the mechanism of the spurious waves. The distribution of the basic wind is the major factor that determines wave amplitude and propagation. The spurious waves propagate up to a critical level at which the basic wind speed normal to the front is equal to the propagation speed of the front. Results from the linear model suggest that an effective way to eliminate spurious waves is to choose a stretched grid with a smaller vertical grid interval in lower layers where strong horizontal winds exist.
A Stability Analysis of Finite-Volume Advection Schemes Permitting Long Time Steps
Authors: Lauritzen Peter Hjort 
Published: July 2007

Abstract
Finite-volume schemes developed in the meteorological community that permit long time steps are considered. These include Eulerian flux-form schemes as well as fully two-dimensional and cascade cell-integrated semi-Lagrangian (CISL) schemes. A one- and two-dimensional Von Neumann stability analysis of these finite-volume advection schemes is given. Contrary to previous analysis, no simplifications in terms of reducing the formal order of the schemes, which makes the analysis mathematically less complex, have been applied. An interscheme comparison of both dissipation and dispersion properties is given. The main finding is that the dissipation and dispersion properties of Eulerian flux-form schemes are sensitive to the choice of inner and outer operators applied in the scheme that can lead to increased numerical damping for large Courant numbers. This spurious dependence on the integer value of the Courant number disappears if the inner and outer operators are identical, in which case, under the assumptions used in the stability analysis, the Eulerian flux-form scheme becomes identical to the cascade scheme. To explain these properties a conceptual interpretation of the flux-based Eulerian schemes is provided. Of the two CISL schemes, the cascade scheme has superior stability properties.
Immunoglobulin gene rearrangements and the pathogenesis of multiple myeloma
Authors: González David , van der Burg Mirjam , García-Sanz Ramón , Fenton James A. , Langerak Anton W. , González Marcos , van Dongen Jacques J. M. , San Miguel Jesus F. , Morgan Gareth J. 
Published: July 2007

AbstractThe ability to rearrange the germ-line DNA to generate antibody diversity is an essential prerequisite for the production of a functional repertoire. While this is essential to prevent infections, it also represents the “Achilles heal” of the B-cell lineage, occasionally leading to malignant transformation of these cells by translocation of protooncogenes into the immunoglobulin (Ig) loci. However, in evolutionary terms this is a small price to pay for a functional immune system. The study of the configuration and rearrangements of the Ig gene loci has contributed extensively to our understanding of the natural history of development of myeloma. In addition to this, the analysis of Ig gene rearrangements in B-cell neoplasms provides information about the clonal origin of the disease, prognosis, as well as providing a clinical useful tool for clonality detection and minimal residual disease monitoring. Herein, we review the data currently available on both Ig gene rearrangements and protein patterns seen in myeloma with the aim of illustrating how this knowledge has contributed to our understanding of the pathobiology of myeloma.
The BH3-only protein Puma plays an essential role in cytokine deprivation–induced apoptosis of mast cells
Authors: Ekoff Maria , Kaufmann Thomas , Engström Maria , Motoyama Noboru , Villunger Andreas , Jönsson Jan-Ingvar , Strasser Andreas , Nilsson Gunnar 
Published: July 2007

AbstractMast cells play critical roles in the regulation of inflammation. One characteristic feature of mast cells is their relatively long lifespan in vivo. Members of the Bcl-2 protein family are regulators of cell survival and apoptosis, where the BH3-only proteins are critical proapoptotic proteins. In this study we investigated the role of the BH3-only proteins Noxa, Bad, Bim, Bmf, Bid, and Puma in apoptosis of mucosal-like mast cells (MLMCs) and connective tissue–like mast cells (CTLMCs). We demonstrate that Puma is critical for the induction of mast-cell death following cytokine deprivation and treatment with the DNA-damaging agent etoposide in MLMCs and CTLMCs. Using p53−/− mast cells, we found that cytokine deprivation–induced apoptosis, in contrast to that elicited by etoposide, is p53-independent. Interestingly, mast cells deficient in FOXO3a, previously proposed as a transcription factor for Puma induction in response to growth factor deprivation, were markedly resistant to cytokine withdrawal compared with wild-type cells. Moreover, overexpression of phosphorylation-deficient, constitutively active FOXO3a caused an up-regulation of Puma. In conclusion, our data demonstrate a pivotal role for Puma in the regulation of cytokine deprivation–induced mast-cell apoptosis and suggest a plausible role for Puma in the regulation of mast cell numbers in vivo.
Lymphocyte contributions to altered endometrial angiogenesis during early and midgestation fetal loss
Authors: Tayade Chandrakant , Fang Yuan , Hilchie David , Croy B Anne 
Published: July 2007

AbstractPeri-implantation and midgestational fetal losses reduce potential litter sizes up to 40% in commercial swine. Peri-implantation studies [gestation days (gd)15–23] of porcine RNA from laser capture microdissected uterine lymphocytes and biopsies of mesometrial endometrium and trophoblast previously linked gd21–23 fetal arrest with transcriptional deficits in vascular endothelial growth factor (VEGF) and its regulatory factor, hypoxia inducible factor (HIF)-1α, and with elevations in IFN-γ and TNF-α and suggested endometrial lymphocytes played a pivotal, proangiogenic role in fetal survival. Here, we address more comprehensively porcine endometrial angiogenesis by comparing transcription between endometrial endothelium and lymphocytes during early (gd20) and midgestation (gd50) losses and by incorporation of histopathology and protein immunolocalization of VEGF, placenta growth factor (PlGF), VEGF receptor I (VEGFRI), and VEGFRII. In healthy sites, endometrial lymphocytes transcribed more VEGF at gd50 than gd20, and transcripts were more abundant in lymphocytes than in endothelium or trophoblast. Arterial endothelial cells showed the most abundant transcription of PlGF. With fetal arrest, maternal transcripts for VEGF but not PlGF dropped, and fetal transcripts remained relatively stable. Maternal and fetal HIF-1α transcription declined. Lymphocytes preferentially transcribed VEGFRI over VEGFRII, and endometrial arterial endothelium and trophoblast preferentially transcribed VEGFRII. IFN-γ and TNF-α transcripts were present in gd20 and gd50 healthy- and arresting-implantation sites. gd20 arrest was associated with greater transcription of IFN-γ than TNF-α in maternal and fetal tissues. At gd50, this was reversed. Endometrial, vascular pathology was evident only at gd50. These data suggest the critical importance for lymphocyte-driven endometrial angiogenesis, which extends to midgestation.
Selection of a Water‐Extractable Phosphorus Test for Manures and Biosolids as an Indicator of Runoff Loss Potential
Authors: Kleinman Peter , Sullivan Dan , Wolf Ann , Brandt Robin , Dou Zhengxia , Elliott Herschel , Kovar John , Leytem April , Maguire Rory , Moore Philip , Saporito Lou , Sharpley Andrew , Shober Amy , Sims Tom , Toth John , Toor Gurpal , Zhang Hailin , Zhang Tiequan 
Published: July 2007

AbstractThe correlation of runoff phosphorus (P) with water‐extractable phosphorus (WEP) in land‐applied manures and biosolids has spurred wide use of WEP as a water quality indicator. Land managers, planners, and researchers need a common WEP protocol to consistently use WEP in nutrient management. Our objectives were to (i) identify a common WEP protocol with sufficient accuracy and precision to be adopted by commercial testing laboratories and (ii) confirm that the common protocol is a reliable index of runoff P. Ten laboratories across North America evaluated alternative protocols with an array of manure and biosolids samples. A single laboratory analyzed all samples and conducted a separate runoff study with the manures and biosolids. Extraction ratio (solution:solids) was the most important factor affecting WEP, with WEP increasing from 10:1 to 100:1 and increasing from 100:1 to 200:1. When WEP was measured by a single laboratory, correlations with runoff P from packed soil boxes amended with manure and biosolids ranged from 0.79 to 0.92 across all protocol combinations (extraction ratio, filtration method, and P determination method). Correlations with P in runoff were slightly lower but significant when WEP was measured by the 10 labs (r = 0.56–0.86). Based on laboratory repeatability and water quality evaluation criteria, we recommend the following common protocol: 100:1 extraction ratio; 1‐h shaking and centrifuge 10 min at 1500 × g (filter with Whatman #1 paper if necessary); and determining P by inductively coupled plasma–atomic emission spectrometry or colorimetric methods.