bluuebunny/crossref_metadata_2025 huggingface dataset:
Large Eddy Simulation of Autoignition in a Turbulent Hydrogen Jet Flame Using a Progress Variable Approach
Authors: Kulkarni Rohit , Polifke Wolfgang
Published: March 2012

The potential of a progress variable formulation for predicting autoignition and subsequent kernel development in a nonpremixed jet flame is explored in the LES (Large Eddy Simulation) context. The chemistry is tabulated as a function of mixture fraction and a composite progress variable, which is defined as a combination of an intermediate and a product species. Transport equations are solved for mixture fraction and progress variable. The filtered mean source term for the progress variable is closed using a probability density function of presumed shape for the mixture fraction. Subgrid fluctuations of the progress variable conditioned on the mixture fraction are neglected. A diluted hydrogen jet issuing into a turbulent coflow of preheated air is chosen as a test case. The model predicts ignition lengths and subsequent kernel growth in good agreement with experiment without any adjustment of model parameters. The autoignition length predicted by the model depends noticeably on the chemical mechanism which the tabulated chemistry is based on. Compared to models using detailed chemistry, significant reduction in computational costs can be realized with the progress variable formulation.
Risk-Adjusted Mortality: Problems and Possibilities
Authors: Shine Daniel
Published: March 2012

The ratio of observed-to-expected deaths is considered a measure of hospital quality and for this reason will soon become a basis for payment. However, there are drivers of that metric more potent than quality: most important are medical documentation and patient acuity. If hositals underdocument and therefore do not capture the full “expected mortality” they may be tempted to lower their observed/expected ratio by reducing “observed mortality” through limiting access to the very ill. Underdocumentation occurs because hospitals do not recognize, and therefore cannot seek to confirm, specific comorbidities conferring high mortality risk. To help hospitals identify these comorbidities, this paper describes an easily implemented spread-sheet for evaluating comorbid conditions associated, in any particular hospital, with each discharge. This method identifies comorbidities that increase in frequency as mortality risk increases within each diagnostic grouping. The method is inductive and therefore independent of any particular risk-adjustment technique.
Structural Health Monitoring Using Wireless Technologies: An Ambient Vibration Test on the Adolphe Bridge, Luxembourg City
Authors: Oth Adrien , Picozzi Matteo
Published: March 2012

Major threats to bridges primarily consist of the aging of the structural elements, earthquake-induced shaking and standing waves generated by windstorms. The necessity of information on the state of health of structures in real-time, allowing for timely warnings in the case of damaging events, requires structural health monitoring (SHM) systems that allow the risks of these threats to be mitigated. Here we present the results of a short-duration experiment carried out with low-cost wireless instruments for monitoring the vibration characteristics and dynamic properties of a strategic civil infrastructure, the Adolphe Bridge in Luxembourg City. The Adolphe Bridge is a masonry arch construction dating from 1903 and will undergo major renovation works in the upcoming years. Our experiment shows that a network of these wireless sensing units is well suited to monitor the vibration characteristics of such a historical arch bridge and hence represents a low-cost and efficient solution for SHM.
Comparison and Optimization of Different Methods for theIn VitroProduction ofPlasmodium falciparumGametocytes
Authors: Roncalés María , Vidal-Mas Jaume , Leroy Didier , Herreros Esperanza
Published: March 2012

The generation of sexually committed parasites (gametocytogenesis) is poorly understood in malaria. If the mechanisms regulating this process were elucidated, new opportunities for blocking malaria transmission could be revealed. Here we compare several methods described previously for thein vitroproduction ofPlasmodium falciparumgametocytes. Our approach relies on the combination of several factors that we demonstrated as impacting on or being critical to gametocytogenesis. An improved method has been developed for thein vitroproduction ofP. falciparumgametocytes as the first step toward obtaining adequate numbers of pure gametocytes forin vitrostudies, such as, for example, the identification of transmission blocking drugs.
Toll-Like Receptors inLeishmaniaInfections: Guardians or Promoters?
Authors: Faria Marilia S. , Reis Flavia C. G. , Lima Ana Paula C. A.
Published: March 2012

Protozoa of the genusLeishmaniacause a wide variety of pathologies ranging from self-healing skin lesions to visceral damage, depending on the parasite species. The outcome of infection depends on the quality of the adaptive immune response, which is determined by parasite factors and the host genetic background. Innate responses, resulting in the generation of mediators with anti-leishmanial activity, contribute to parasite control and help the development of efficient adaptive responses. Among those, the potential contribution of members of the Toll-like receptors (TLRs) family in the control ofLeishmaniainfections started to be investigated about a decade ago. Although most studies appoint a protective role for TLRs, there is growing evidence that in some cases, TLRs facilitate infection. This review highlights recent advances in TLR function duringLeishmaniainfections and discusses their potential role in restraining parasite growth versus yielding disease.
Consistency ofMycobacterium tuberculosis-Specific Interferon-Gamma Responses in HIV-1-Infected Women during Pregnancy and Postpartum
Authors: Jonnalagadda Sasi R. , Brown Elizabeth , Lohman-Payne Barbara , Wamalwa Dalton , Farquhar Carey , Tapia Kenneth , Cranmer Lisa M. , John-Stewart Grace C.
Published: March 2012

Background. We determined the consistency of positive interferon-gamma (IFN-γ) release assays (IGRAs) to detect latent TB infection (LTBI) over one-year postpartum in HIV-1-infected women.Methods. Women with positive IGRAs during pregnancy had four 3-monthly postpartum IGRAs. Postpartum change in magnitude of IFN-γ response was determined using linear mixed models.Results. Among 18 women with positive pregnancy IGRA, 15 (83%) had a subsequent positive IGRA; 9 (50%) were always positive, 3 (17%) were always negative, and 6 (33%) fluctuated between positive and negative IGRAs. Women with pregnancy IGRA IFN-γ>8spot forming cells (SFCs)/well were more likely to have consistent postpartum IGRA response (odds ratio: 10.0; 95% confidence interval (CI): 0.9–117.0). Change in IFN-γ response over postpartum was 10.2 SFCs/well (95% CI: −1.5–21.8 SFCs/well).Conclusion. Pregnancy positive IGRAs were often maintained postpartum with increased consistency in women with higher baseline responses. There were modest increases in magnitude of IGRA responses postpartum.
Conjunctival Lymphatic Response to Corneal Inflammation in Mice
Authors: Ecoiffier Tatiana , Sadovnikova Anna , Yuen Don , Chen Lu
Published: March 2012

Due to its unique characteristics, the cornea has been widely used for vascular research. However, it has never been studied whether lymphatic vessels in the conjunctiva, its neighboring tissue, are affected by corneal lymphangiogenesis (LG). The purpose of this study was to investigate whether the distribution pattern of conjunctival lymphatic vessels changes during LG using a standardized two-suture placement model. Our data from immunofluorescent microscopic studies demonstrate, for the first time, that conjunctival lymphatic vessels were more distributed in the nasal side under both normal and inflamed conditions. Additionally, under the inflamed condition, conjunctival lymphatic vessels showed a higher density and more branching points, indicating that LG occurs in the conjunctiva in response to corneal inflammation. This study not only provides novel insights into lymphatic events in the ocular surface but also offers new guidelines for developing therapeutic strategies to treat lymphatic diseases at related sites.
A Pilot Study on Dietary Approaches in Multiethnicity: Two Methods Compared
Authors: Valentini Romina , Dalfrà Maria Grazia , Masin Michela , Barison Antonella , Marialisa Marcon , Pegoraro Eva , Lapolla Annunziata
Published: March 2012

Background. Medical nutritional therapy is the most important method for normalizing glucose levels in pregnancy. In this setting, there is a new problem to consider relating to migrants, their personal food preferences, and ethnic, cultural, and religious aspects of their diet. We compared maternal and fetal outcomes between two multiethnic groups of pregnant women, one adopting a food plan that included dishes typical of the foreign women's original countries (the “ethnic meal plan” group), while the other group adopted a standard meal plan.Findings. To develop the meal plan, each dish chosen by the women was broken down into its principal ingredients. The quantity of each food was given in tablespoons, teaspoons, slices, and cups, and there were photographs of the complete dish. The group treated with the ethnic meal plan achieved a better metabolic control at the end of the pregnancy and a lower weight gain (though the difference was not statistically significant). As for fetal outcome, the group on the ethnic meal plan had babies with a lower birth weight and there were no cases of macrosomia or LGA babies.Conclusions. This preliminary study indicates the positive effect of an ethnic approach to diet on the outcome of pregnancy.
Systems Biology of Tumor Dormancy: Linking Biology and Mathematics on Multiple Scales to Improve Cancer Therapy
Authors: Enderling Heiko , Hahnfeldt Philip , Hlatky Lynn , Almog Nava
Published: March 2012

For many decades, it has been appreciated that tumor progression is not monotonic, and development of a cancer cell does not equate to inevitable cancer presentation in the clinic. Tumor progression is challenged by numerous intrinsic and extrinsic bottlenecks that can hold the tumor in dormant stages for prolonged periods. Given the complex, multiscale nature of these bottlenecks, the Center of Cancer Systems Biology organized a workshop on critical issues of systems biology of tumor dormancy. The program for the meeting this past July, chaired by N. Almog and H. Enderling, included discussions and interactive breakout sessions on regulation of tumor dormancy by angiogenesis, tumor–immune system interactions, cancer stem cell kinetics, and cell signaling pathways. Three important conclusions emerged from the meeting. The first was the urgent need to differentiate between tumor cell and tumor population dormancy of the primary tumor and metastatic deposits, the second was the continued need for interdisciplinary dialogs, and the third was the need to bring cross-scale mechanistic thinking to the field to achieve a more robust understanding of tumor dormancy and its clinical implications. Cancer Res; 72(9); 2172–5. ©2012 AACR.
Hepatocyte–Stellate Cell Cross-Talk in the Liver Engenders a Permissive Inflammatory Microenvironment That Drives Progression in Hepatocellular Carcinoma
Authors: Coulouarn Cédric , Corlu Anne , Glaise Denise , Guénon Isabelle , Thorgeirsson Snorri S. , Clément Bruno
Published: March 2012

Many solid malignant tumors arise on a background of inflamed and/or fibrotic tissues, features that are found in more than 80% hepatocellular carcinomas (HCC). Activated hepatic stellate cells (HSC) play a critical role in fibrogenesis associated with HCC onset and progression, yet their functional impact on hepatocyte fate remains largely unexplored. Here, we used a coculture model to investigate the cross-talk between hepatocytes (human hepatoma cells) and activated human HSCs. Unsupervised genome-wide expression profiling showed that hepatocyte–HSC cross-talk is bidirectional and results in the deregulation of functionally relevant gene networks. Notably, coculturing increased the expression of proinflammatory cytokines and modified the phenotype of hepatocytes toward motile cells. Hepatocyte–HSC cross-talk also generated a permissive proangiogenic microenvironment, particularly by inducing VEGFA and matrix metalloproteinase (MMP)9 expression in HSCs. An integrative genomic analysis revealed that the expression of genes associated with hepatocyte–HSC cross-talk correlated with HCC progression in mice and was predictive of a poor prognosis and metastasis propensity in human HCCs. Interestingly, the effects of cross-talk on migration and angiogenesis were reversed by the histone deacetylase inhibitor trichostatin A. Our findings, therefore, indicate that the cross-talk between hepatoma cells and activated HSCs is an important feature of HCC progression, which may be targeted by epigenetic modulation. Cancer Res; 72(10); 2533–42. ©2012 AACR.
Hypoxia-Inducible Factor-2α Activation Promotes Colorectal Cancer Progression by Dysregulating Iron Homeostasis
Authors: Xue Xiang , Taylor Matthew , Anderson Erik , Hao Cathy , Qu Aijuan , Greenson Joel K. , Zimmermann Ellen M. , Gonzalez Frank J. , Shah Yatrik M.
Published: March 2012

Hypoxia-inducible factor (HIF), a key modulator of the transcriptional response to hypoxia, is increased in colon cancer. However, the role of HIF in colon carcinogenesis in vivo remains unclear. In this study, we found that intestinal epithelium-specific disruption of the von Hippel–Lindau tumor suppressor protein (VHL) resulted in constitutive HIF signaling, and increased HIF expression augmented colon tumorigenesis in the Apcmin/+ intestinal tumor model. Intestine-specific disruption of Vhl increased colon tumor multiplicity and progression from adenomas to carcinomas. These effects were ameliorated in mice with double disruption of Vhl and HIF-2α. Activation of HIF signaling resulted in increased cell survival in normal colon tissue; however, tumor apoptosis was not affected. Interestingly, a robust activation of cyclin D1 was observed in tumors of Apcmin/+ mice in which HIF-2α was activated in the intestine. Consistent with this result, bromodeoxyuridine incorporation indicated that cellular proliferation was increased in colon tumors following HIF activation. Further analysis showed that dysregulation of the intestinal iron absorption transporter divalent metal transporter-1 (DMT-1) was a critical event in HIF-2α–mediated colon carcinogenesis. These data provide a mechanistic basis for the widely reported link between iron accumulation and colon cancer risk. Together, our findings show that a chronic increase in HIF-2α in the colon initiates protumorigenic signaling, which may have important implications in developing preventive and therapeutic strategies for colon cancer. Cancer Res; 72(9); 2285–93. ©2012 AACR.
Biomarker Discovery, Development, and Implementation in France: A Report from the French National Cancer Institute and Cooperative Groups
Authors: Andre Fabrice , Nowak Frederique , Arnedos Monica , Lacroix Ludovic , Viens Patrice , Calvo Fabien
Published: March 2012

Biomarkers are increasingly changing the medical practice in oncology. One of the major challenges in the field of personalized medicine or biologically adapted therapies is to ensure a rapid and extensive implementation of emerging biomarkers as soon as proof of their medical usefulness is obtained. A special program has been developed in France to facilitate the assessment and use of biomarkers. The French National Cancer Institute has set up a total of 28 laboratories in public hospitals to perform biomarker testing for clinical use. This program is enabling all patients who present with cancer to receive free testing for biomarkers, such as K-Ras, epidermal growth factor receptor, c-Kit, and Braf mutations. Funding for these laboratories comes from the French Ministry of Health. The future of these laboratories includes the development of DNA arrays and multiplex technologies for clinical use. Toward that end, the French National Cancer Institute is financing several large clinical trials that several large clinical trials are currently evaluating the feasibility and medical utility of DNA arrays and next-generation sequencing in the context of academic centers. The programs are being run by cooperative groups. Clin Cancer Res; 18(6); 1555–60. ©2012 AACR.
Development and Use of Integral Assays in Clinical Trials
Authors: Schilsky Richard L. , Doroshow James H. , LeBlanc Michael , Conley Barbara A.
Published: March 2012

Clinical trials that include integral biomarkers to determine eligibility, assign treatment, or assess outcome must employ robust assays to measure the molecular analyte of interest. The decision to develop a biomarker assay into a test suitable for use in humans should be driven by clinical need, that is, there should be a clear clinical purpose for undertaking the test development. Supporting in vitro or in vivo research on the ability of the marker to distinguish subgroups of patients with a given characteristic is necessary. The magnitude of the difference in treatment effect expected with use of the marker should be sufficient to support differential treatment prescription for marker-positive and -negative patients. Analytical and clinical validation of the marker assay should be completed before the clinical trial is initiated to ensure that the assay is stable enough for clinical use throughout the trial. Clinical use of the assay requires that it be performed in a Clinical Laboratory Improvement Amendments–accredited laboratory, and the need to apply for an Investigational Device Exemption from the U.S. Food and Drug Administration should be considered. In this article we elaborate on the steps required to get a biomarker assay ready for use as an integral component of a clinical trial and give an example of the use of an integral assay in a phase III trial. Clin Cancer Res; 18(6); 1540–6. ©2012 AACR.
Impact of Preanalytic Factors on the Design and Application of Integral Biomarkers for Directing Patient Therapy
Authors: Hewitt Stephen M. , Badve Sunil S. , True Lawrence D.
Published: March 2012

Molecular assays have been routinely applied to improve diagnosis for the last 25 years. Assays that guide therapy have a similar history; however, their evolution has lacked the focus on analytic integrity that is required for the molecularly targeted therapies of today. New molecularly targeted agents require assays of greater precision/quantitation to predict the likelihood of response, i.e., to identify patients whose tumors will respond, while at the same time excluding and protecting those patients whose tumors will not respond or in whom treatment will cause unacceptable toxicity. The handling of tissue has followed a fit-for-purpose approach focused on appropriateness for diagnostic needs, which is less rigorous than the demands of new molecular assays that interrogate DNA, RNA, and proteins in a quantitative, multiplex manner. There is a new appreciation of the importance and fragility of tissue specimens as the source of analytes to direct therapy. By applying a total test paradigm and defining and measuring sources of variability in specimens, we can develop a set of specifications that can be incorporated into the clinical-care environment to ensure that a specimen is appropriate for analysis and will return a true result. Clin Cancer Res; 18(6); 1524–30. ©2012 AACR.
Lessons Learned from the Investigational Device Exemption Review of Children's Oncology Group Trial AAML1031
Authors: Meshinchi Soheil , Hunger Stephen P. , Aplenc Richard , Adamson Peter C. , Jessup J. Milburn
Published: March 2012

The U.S. Food and Drug Administration is now exerting its regulatory authority over the use of molecular diagnostics and related assays for medical decision making in clinical trials, by performing pre–Investigational Device Exemption reviews in all phases of clinical trials. In this review, we assess the analytical performance of the assay for the diagnostic, and consider how that performance affects the diagnostic and the patient and their risks and benefits from treatment. We also discuss the process involved in the first review of a new Children's Oncology Group phase III trial in acute myelogenous leukemia. The lessons learned and recommendations for how to prepare for and incorporate this new level of regulatory review into the protocol development process are presented. Clin Cancer Res; 18(6); 1547–54. ©2012 AACR.
IDH Mutation and Neuroglial Developmental Features Define Clinically Distinct Subclasses of Lower Grade Diffuse Astrocytic Glioma
Authors: Gorovets Daniel , Kannan Kasthuri , Shen Ronglai , Kastenhuber Edward R. , Islamdoust Nasrin , Campos Carl , Pentsova Elena , Heguy Adriana , Jhanwar Suresh C. , Mellinghoff Ingo K. , Chan Timothy A. , Huse Jason T.
Published: March 2012

Purpose: Diffuse gliomas represent the most prevalent class of primary brain tumor. Despite significant recent advances in the understanding of glioblastoma [World Health Organization (WHO) IV], its most malignant subtype, lower grade (WHO II and III) glioma variants remain comparatively understudied, especially in light of their notable clinical heterogeneity. Accordingly, we sought to identify and characterize clinically relevant molecular subclasses of lower grade diffuse astrocytic gliomas.

Experimental Design: We conducted multidimensional molecular profiling, including global transcriptional analysis, on 101 lower grade diffuse astrocytic gliomas collected at our own institution and validated our findings using publically available gene expression and copy number data from large independent patient cohorts.

Results: We found that IDH mutational status delineated molecularly and clinically distinct glioma subsets, with IDH mutant (IDH mt) tumors exhibiting TP53 mutations, platelet—derived growth factor receptor (PDGFR)A overexpression, and prolonged survival, and IDH wild-type (IDH wt) tumors exhibiting EGFR amplification, PTEN loss, and unfavorable disease outcome. Furthermore, global expression profiling revealed three robust molecular subclasses within lower grade diffuse astrocytic gliomas, two of which were predominantly IDH mt and one almost entirely IDH wt. IDH mt subclasses were distinguished from each other on the basis of TP53 mutations, DNA copy number abnormalities, and links to distinct stages of neurogenesis in the subventricular zone. This latter finding implicates discrete pools of neuroglial progenitors as cells of origin for the different subclasses of IDH mt tumors.

Conclusion: We have elucidated molecularly distinct subclasses of lower grade diffuse astrocytic glioma that dictate clinical behavior and show fundamental associations with both IDH mutational status and neuroglial developmental stage. Clin Cancer Res; 18(9); 2490–501. ©2012 AACR.
Spleen Cells from Young but Not Old Immunized Mice Eradicate Large Established Cancers
Authors: Schreiber Karin , Arina Ainhoa , Engels Boris , Spiotto Michael T. , Sidney John , Sette Alessandro , Karrison Theodore G. , Weichselbaum Ralph R. , Rowley Donald A. , Schreiber Hans
Published: March 2012

Purpose: Solid tumors that have grown two weeks or longer in mice and have diameters larger than 1 cm are histologically indistinguishable from autochthonous human cancers. When experimental tumors reach this clinically relevant size, they are usually refractory to most immunotherapies but may be destroyed by adoptive T-cell transfer. However, TCR-transgenic T cells and/or tumor cells overexpressing antigens are frequently used in these experiments. Here we studied the requirements for destroying clinical size, unmanipulated 8101 tumors by adoptive cell therapy.

Experimental Design: 8101 arose in an old mouse after chronic exposure to UV light. A cancer line was established, which was never serially transplanted. The immunodominant CD8+ T cell-recognized antigen of this tumor is caused by a somatic tumor–specific mutation in the RNA helicase p68. 8101 tumors were treated with spleen cells from young naive, or young and old immunized mice to ascertain the characteristics of immune cells that lead to rejection.

Results: Here we show that the mutant p68 peptide has an exceptionally high affinity to the presenting MHC class I molecule Kb and that spleen cells from immunized young syngeneic mice adoptively transferred to Rag−/− or cancer-suppressed euthymic mice eradicate 8101 tumors larger than 1 cm in average diameter and established for several weeks. Spleen cells from naive young mice or from old and boosted (reimmunized) mice were ineffective.

Conclusions: Relapse-free destruction of large and long-established tumors expressing a genuine very high-affinity tumor-specific antigen can be achieved by using adoptive transfer of lymphocytes from immunized young individuals. Clin Cancer Res; 18(9); 2526–33. ©2012 AACR.
Restoring Nitric Oxide Cytosolic Calcium Regulation by Cyclic Guanosine Monophosphate Protein Kinase I Alpha Transfection in Coronary Endothelial Cells of Spontaneously Hypertensive Rats
Authors: Nistri Silvia , Di Cesare Mannelli Lorenzo , Mazzetti Luca , Feil Robert , Bani Daniele , Failli Paola
Published: March 2012

In microcoronary endothelial cells (RCEs) from spontaneously hypertensive rats (SHR), the nitric oxide (NO)/cyclic guanosine monophosphate (GMP)-dependent proteinkinase I (cGKI) pathway cannot regulate the cytosolic calcium ([Ca2+]i) dynamic as in RCEs from Wistar Kyoto rats (WKY). We investigated the altered downstream NO target in SHR cells and, since cGKI expression was low, whether the re-expression of cGKIα in SHR RCEs could restore NO calcium responsiveness. We measured [Ca2+]i dynamic by fura-2 imaging analysis and the cGKI level by RT-PCR and Western blot in SHR and WKY RCEs. Plasmids encoding for enhanced green fluorescence protein or cGKIα-enhanced green fluorescence protein were transiently transfected in SHR RCEs, and [Ca2+]i was evaluated. Angiotensin-II (AT-II) increased [Ca2+]i in a concentration-dependent way in both strains. Whereas in WKY, endogenously produced NO and cyclic GMP analog decreased the AT-II-induced [Ca2+]i transient, they were ineffective in SHR RCEs. The cGKI level was low in SHR cells. However, after cGKIα re-expression, endogenous NO decreased the AT-II-induced [Ca2+]i transient, while endothelial NO synthase and cGKI inhibition prevented it. The low expression of cGKI in SHR accounts for the absent regulation of the agonist-induced [Ca2+]i transient by the NO/cyclic GMP pathway. Studies on cGKI in humans could contribute to a better understanding of cardiovascular pathologies.
Related Transcriptional Enhancer Factor 1 Increases Endothelial-Dependent Microvascular Relaxation and Proliferation
Authors: Messmer-Blust Angela F. , Zhang Cuili , Shie Jue-Lon , Song Qinhui , He Ping , Lubenec Isabel , Liu Yuhong , Sellke Frank , Li Jian
Published: March 2012

Objective: Related transcriptional enhancer factor 1 (RTEF-1) is a key transcriptional regulator in endothelial function. In this study, we investigated a possible role for RTEF-1 in the regulation of microvascular relaxation and the underlying mechanism involved. Activation of fibroblast growth factor receptor 1 (FGFR1) by FGFs increases vasodilation, although transcriptional control of the molecular mechanisms underlying FGFR1 is still unclear. Materials and Methods: We demonstrated that RTEF-1 stimulated FGFR1 expression at the transcriptional level, specifically an area including Sp1 elements, as evidenced by promoter assays. Additionally, RTEF-1 increased FGFR1 mRNA and protein expression in vitro and in VE-cadherin-promoted RTEF-1 (VE-Cad/RTEF-1) transgenic mice, whereas RTEF-1 siRNA blocked the upregulation of FGFR1 expression. Furthermore, increased endothelial-dependent microvessel relaxation was observed in the coronary arteries of VE-Cad/RTEF-1 mice, and increased proliferation was observed in RTEF-1-overexpressing cells, both of which correlated to increased FGF/FGFR1 signaling and endothelial nitric oxide synthase (eNOS) upregulation. Our results indicate that RTEF-1 acts as a transcriptional stimulator of FGFR1 and is involved in FGF pathways by increasing microvessel dilatation via eNOS. Conclusions: These findings suggest that RTEF-1 plays an important role in FGFR1- stimulated vasodilatation. Understanding the effect of RTEF-1 in microvessel relaxation may provide beneficial knowledge in improving treatments in regards to ischemic vascular disorders.
H-ras Mutation Detection in Bladder Cancer by COLD-PCR Analysis and Direct Sequencing
Authors: Wang Ai-Xiang , Chang Ji-Wu , Li Chang-Ying , Liu Kun , Lin Ying-Li
Published: March 2012

Objective: A sensitive mutation detection method called co-amplification at lower denaturation temperature-polymerase chain reaction (COLD-PCR) was applied to improve the detection frequencies of expressive mutations in the H-ras gene, including exons 1 and 2, in a group of Chinese patients diagnosed with bladder cancer. Materials and Methods: The expressive mutations in the H-ras gene in 86 fresh tissues of human bladder cancer were identified by COLD-PCR or conventional PCR, followed by direct sequencing. Results: A high frequency of silent mutations of 29.1% (25 of 86) in exon 1 (c.81T>C, H27H) and activating mutations of 8.1% (7 of 86) were detected by COLD-PCR, yielding a 36% improvement in mutation detection compared with conventional PCR. No significant association was shown between activating mutations and clinicopathologic parameters, but the frequencies of silent mutations in recurrent tumors were higher than those in primary tumors (p = 0.034). Conclusions: COLD-PCR is a highly sensitive, reliable, and convenient clinical assay for mutation detection. The adoption of the method is straightforward and requires no additional reagents or instruments. Silent mutations might be important genomic alterations in bladder cancer, and play a role in bladder cancer recurrence.
An Image-Based Model of Atrial Muscular Architecture
Authors: Zhao Jichao , Butters Timothy D. , Zhang Henggui , Pullan Andrew J. , LeGrice Ian J. , Sands Gregory B. , Smaill Bruce H.
Published: March 2012

Background—

Computer models that capture key features of the heterogeneous myofiber architecture of right and left atria and interatrial septum provide a means of investigating the mechanisms responsible for atrial arrhythmia. The data necessary to implement such models have not previously been available. The aims of this study were to characterize surface geometry and myofiber architecture throughout the atrial chambers and to investigate the effects of this structure on atrial activation.

Methods and Results—

Atrial surface geometry and myofiber orientations were reconstructed in 3D at 50×50×50-μm
3
resolution from serial images acquired throughout the sheep atrial chambers. Myofiber orientations were determined by Eigen-analysis of the structure tensor. These data have been incorporated into an anatomic model that provides the first quantitative representation of myofiber architecture throughout the atrial chambers. By simulating activation on this 3D structure, we have confirmed the roles of specialized myofiber tracts such as the crista terminalis, pectinate muscles, and the Bachman bundle on the spread of activation from the sinus node. We also demonstrate how the complex myocyte arrangement in the posterior left atrium contributes to activation time dispersion adjacent to the pulmonary veins and increased vulnerability to rhythm disturbance generated by ectopic stimuli originating in the pulmonary vein sleeves.

Conclusions—

We have developed a structurally detailed, image-based model of atrial anatomy that provides deeper understanding of the role that myocyte architecture plays in normal and abnormal atrial electric function.
Zebrafish in the Study of Early Cardiac Development
Authors: Liu Jiandong , Stainier Didier Y.R.
Published: March 2012

Heart development is a complex process that involves cell specification and differentiation, as well as elaborate tissue morphogenesis and remodeling, to generate a functional organ. The zebrafish has emerged as a powerful model system to unravel the basic genetic, molecular, and cellular mechanisms of cardiac development and function. We summarize and discuss recent discoveries on early cardiac specification and the identification of the second heart field in zebrafish. In addition to the inductive signals regulating cardiac specification, these studies have shown that heart development also requires a repressive mechanism imposed by retinoic acid signaling to select cardiac progenitors from a multipotent population. Another recent advance in the study of early zebrafish cardiac development is the identification of the second heart field. These studies suggest that the molecular mechanisms that regulate the second heart field development are conserved between zebrafish and other vertebrates including mammals and provide insight into the evolution of the second heart field and its derivatives.
Association of Bleeding and In-Hospital Mortality in Black and White Patients With ST-Segment–Elevation Myocardial Infarction Receiving Reperfusion
Authors: Mehta Rajendra H. , Parsons Lori , Rao Sunil V. , Peterson Eric D.
Published: March 2012

Background—

Prior studies have suggested that blacks with acute ST-segment–elevation myocardial infarction have increased bleeding risks with fibrinolysis relative to whites, yet these data were quite limited. Additionally, it is unknown whether there are racial differences in bleeding risks among patients with ST-segment–elevation myocardial infarction receiving primary percutaneous coronary intervention.

Methods and Results—

We evaluated data on blacks and whites with ST-segment–elevation myocardial infarction treated with either fibrinolysis or primary percutaneous coronary intervention from the National Registry of Myocardial Infarction (NRMI)-4 and 5 participating centers between July 2000 and December 2006. We compared differences between the 2 groups in rates of in-hospital major bleeding and mortality, adjusted with logistic regression analyses. In fibrinolytic-treated patients with ST-segment–elevation myocardial infarction, the bleeding rates were higher among blacks (n=2283) than whites (n=42 243; 10.9% versus 10.3%; adjusted odds ratio, 1.21; 95% confidence interval, 1.02–1.43). Similarly, in patients receiving primary percutaneous coronary intervention, the bleeding rates were higher in blacks (n=2826) than in whites (n=46 332; 10.3% versus 7.8%; adjusted odds ratio, 1.33; 95% confidence interval, 1.13–1.56). Bleeding was associated with higher risk of death in both ethnic groups. However, there was no overall racial difference in in-hospital mortality among those with bleeding or without bleeding treated with either fibrinolysis or primary percutaneous coronary intervention.

Conclusions—

Blacks with ST-segment–elevation myocardial infarction treated with either fibrinolysis or primary percutaneous coronary intervention had a higher risk of bleeding events than their white counterparts. Bleeding was associated with a similar increased risk of death in both ethnic groups treated by either reperfusion strategy.
Person to Person: Vivarana of Abhinavagupta on Parātrimśikāverses 3–4
Authors: Dupuche
Published: March 2012

No Abstract
Franco, Eli, Dharmakīrti on Compassion and Rebirth [Wiener Studien zur Tibetologie und Buddhismuskunde Heft 38]
Authors: Namai
Published: March 2012

No Abstract
Les Aśvin Dans Les Énumérations Divines Du Neuvième Mandala De La Rgvedasamhitā
Authors: Pirart É.
Published: March 2012

Although they are soma-drinkers like Indra or Vāyu, the Aśvins, in the ninth mandala of the Rgvedasamhitā do not appear more than four times, probably because their cult has lost importance. Nevertheless, the few stanzas mentioning them among other vedic deities in order to compose a minimal pantheon do not contain very interesting data except the fact that those twins seem to be somehow more closely associated with the ambiguous Vāyu. Having analysed the stanzas, I propose some new solutions to the grammatical and semantical problems they present (9.7.7 rána, dhármabhih;9.7.8 vidānah;9.8.1 abhí priyám;9.81.4 suyámā;9.88.3 istáyāmā, viśvávārah)
Remarks on the Text of the Kubjikāmatatantra
Authors: Sanderson
Published: March 2012

No Abstract
The Purification of the Body in Tantric Ritual Representation
Authors: Flood
Published: March 2012

No Abstract
Water and ocean
Authors: Bronkhorst
Published: March 2012

No Abstract
Dravid, Raja Ram, The Problem of Universals in Indian Philosophy
Authors: Flood
Published: March 2012

No Abstract
Cahill, Timothy C., An Annotated Bibliography of the Alamkāraśāstra
Authors: Hinüber
Published: March 2012

No Abstract
Jens Braarvig (ed.), Buddhist Manuscripts, Volume I by Mark Allon, Jens Braarvig, Torkel Brekke, Paul Harrison, Jens-Uwe Hartmann, Seishi Karashima, Kazunobu Matsuda, Richard Salomon, Lore Sander, Nicholas Sims-Williams, Klaus Wille
Authors: Boucher
Published: March 2012

No Abstract
Jaini, Padmanabh Shrivarma, Collected Papers on Buddhist Studies with a Foreword by Paul Dundas
Authors: Mette
Published: March 2012

No Abstract
Hiltebeitel, Alf, Rethinking the Mahābhārata. A Reader's Guide to the Education of the Dharma King
Authors: Brockington
Published: March 2012

No Abstract
Yama und Yami (V X 10)
Authors: Schneider Ulrich
Published: March 2012

Zu den leider nicht wenigen Texten des V, deren Interpretation noch nicht als gelungen bezeichnet werden kann, gehört auch der Dialog zwischen Yama und Yamī (X 10). Zwar ist es klar, dass es sich bei den Sprechern um ein Zwillings-Geschwisterpaar handelt und dass die Schwester ihren Bruder mit immer neuen Argumenten, aber ohne jeden Erfolg zum Inzest überreden will, doch warum sie das tut und warum der Bruder sich so hartnäckig weigert, ja, was man überhaupt mit dem Savāda bezweckte, bleibt weitgehend dunkel.
The assimilation of Dravidian loans to Konkani phonological and morphological patterns
Authors: Miranda Rocky V.
Published: March 2012

After briefly reviewing the status of Konkani in the Dravidian area, and the extent of Dravidian influence on this Indo-Aryan language, the assimilation of Dravidian loan words to Konkani phonological and morphological patterns is examined in detail. In the process of accommodation, Dravidian loanwords have undergone various phonological modifications (such as syncope, apocope, vowel rounding, vowel raising, vowel lowering, palatalization, depalatalization, gemination, and degemination). They have undergone also various morphological modifications in order to adjust to a considerably different system of morphological classes and inflectional patterns. Finally, certain sociolinguistic factors are pointed out which might have enabled Konkani phonological and morphological patterns to withstand the pressures of the massive influx of Dravidian loans.
Notes on the Ahraurā version of Aśoka's first minor rock edict
Authors: Norman K. R.
Published: March 2012

I therefore conclude that the sentence amaca budhasa salīle ālohe at the end of the Ahraurā version of Aśoka's MRE I arises from the misreading by the scribe83 of a carelessly written exemplar,84 and from his subsequent conjecture of words to make sense of the apparent nonsense which he had received. Although this may perhaps seem unlikely to some readers, the examples of miswritten akaras and the attempts of scribes to make sense of them which I have discussed elsewhere85 make it quite clear that may suggestion is well within the range of possibility.
Sur le terme yóga, le verbe yuj- et quelques-uns de leurs dérivés dans les hymnes védiques
Authors: Oguibenine Boris
Published: March 2012

The term yóga must have designed an essential part of the sacrificial cult as known in the Rgveda: the putting in motion (“Intätigkeitsetzen”, following Geldner), the launching of a specific activity with the ultimate goal to yoke, to join together or to pair the objects and the entities which match or can match each other or which can be viewed as comparable and even identical according to Vedic archaic speculative thought. Vedic sacrifice is in fact a powerful explicatory device, a set of gestures and of designs condensing a speculative experience. The verb yuj- and its derivates translate thus one of the central themes of the Vedic religion where the poet officiating in the sacrifice has to proclaim the connections and the identifications between the phenomena to be correlated (“yoked, harnessed”). The hippological vocabulary in the Rgveda as applied to the representation of the speculative practice is less an accidental metaphor than a true and meaningful translation of one of the basic principles this practice.
Nala et Damayantī, héros épiques
Authors: Biardeau M.
Published: March 2012

When regarded separately, the story of Nala and Damayantī does not amount to much more than a tale. Therefore it has been inserted in book III of the Mahābhārata as a “sub-story”, according to the usual practice of the Epic. The aim of this article is to show that this insertion is not without importance for an understanding of the story itself. The Epic provides a context for it and thereby helps in distinguishing the levels of significance which would otherwise pass unnoticed. Reciprocally, the ‘sub-story’ brings to the Epic an outlook which is in part new and more profound by taking up the Epic plot in its own way and at its proper level. In this way, the role of the Avatāra in the Nalopākhyāna is taken up by the wife of the exiled king. This leads one to ask oneself about the link connecting the Avatāra Ka and the princess Kā Draupadī, wife of the five Pāava king, in the Epic ideology.At the background of all of this, there are an active concept of the entire Epic, and also the aspects of the method which results from this.
Worum handelt es sich beim Soma?
Authors: Stuhrmann Rainer
Published: March 2012

The present article was given as a lecture at the XXII. Deutscher Orientalistentag in Tübingen (March, 1983) and deals with the problem of Soma. G. Wasson proposed a hallicunogenic mushroom, viz. the fly-agaric. It is shown that the severe criticism he met with on behalf of Indo-Iranian philology is justified in so far as it is impossible to classify Soma botanically, whereas it went too far in excluding the mushroom absolutly. Actually the solution cannot be found in the physical descriptions of the plant, but in the hitherto neglected type of the intoxication it produces. In this regard the information of the Vedic poets can be relied on. They furnish evidence of the alcaloidic nature of the active substance of Soma, because it produces especially optical and accustical delusions with changes in the dimensions of the objects perceived. This can be shown by a careful examination of many stanzas. These effects are the clue to most of the ‘mysterious’ Soma poems.
Zum Gebrauch der samāsopamā bei aśvaghosa
Authors: Bock-Raming Andreas
Published: March 2012

The use of the samāsopamā in the S. and the B. shows some striking peculiarities: In a large number of occurrences they are connected with the śabdālamkāras anuprāsa and lātānuprāsa. Furthermore, they are often found in close vicinity to each other or occur together with the similes yathā and iva which leads to a certain cumulative effect. Although in many instances the use of the s. in both kāvyas can be described as rather conventional and stereotyped, there are some striking differences between the S. and the Sanskrit text of the B. In the latter kāvya the number of s. of each category is twice or even thrice as large as in the respective categories in the S. Moreover, it can be shown that in the B. Aśvaghosa strives to make use of more ornate and elaborate forms of samāsopamā. Examples are a ślesa-upamā in B. 5,37a, and two compounds in B. 5,26b and d which are at the same time yathāsamkhyas.
The "Virtually Unknown" Benedictive Middle in Classical Sanskrit: Two Occurences in the Buddhist ABHISAMAYĀLANKĀRA
Authors: Reigle
Published: March 2012

No Abstract
Atharvavedic recitation and the Śaunaka Prātiśākhya
Authors: Howard
Published: March 2012

No Abstract
Reviews; Jyotish Nath: The Dāsas, Dasyus and Raksases in the R. gvedic Literature
Authors: Mylius
Published: March 2012

No Abstract
The Distribution of the Variant Endings -U, -Aü and -ā in the Apabhramśa Verses in HEMACANDRA's PRĀKRIT GRAMMAR
Authors: Tieken
Published: March 2012

No Abstract
Marion Meisig, König Śibi und die Taube. Wandlung und Wanderung eines Erzäahlstoffes von Indien nach China
Authors: de Jong
Published: March 2012

No Abstract
Catalogue of Palm Leaf Manuscripts Kept in the Otani University Library Edited by Otani University Library
Authors: Pecenko
Published: March 2012

No Abstract
K.R. Norman (tr.), The Word of the Doctrine (Dhammapada)
Authors:   de Jong
Published: March 2012

No Abstract
Mauro Maggi: The Khotanese Karmavibhanga
Authors: von Hinüber
Published: March 2012

No Abstract
W. Sundermann (ed.), Iranian Manichaean Turfan Texts in Early Publications (1904–1934), Photo Edition
Authors: Lieu
Published: March 2012

No Abstract
Vasudha Dalmia, The Nationalization of Hindu Traditions. Bhāratendu Hariśchandra and Nineteenth-Century Banaras
Authors: Damsteegt
Published: March 2012

No Abstract
Avestisch Apāuuaiia-
Authors: Schmitt
Published: March 2012

No Abstract
Langue, style et structure dans le monde indien. Centenaire de Louis Renou
Authors: de Jong
Published: March 2012

No Abstract
Twentieth Annual Roland H. Bainton Presidential Lecture: Intertextual Play: Erasmus' Use of Adages in the Colloquies
Authors: Wesseling Ari
Published: March 2012

A copious use of ancient adages is a prominent feature of the Praise of Folly. Focusing on the Colloquies, this essay discusses passages where a source or subtext has previously not been recognized. In the Ciceronianus, his plea for eclectic imitation, Erasmus declares that the basic principle of art is concealing the technique. This rule is taken as a point of departure for analyzing the ways in which he handles adages. Rather than concealing a borrowing, Erasmus adapts it, using paraphrase, parody, inversion of the sense, and by combining it with other materials. Angelo Poliziano's writing was an important model for him.
Indigenous Education and Human Rights
Authors: Schimmel Noam
Published: March 2012

The right to an education that is consonant with and draws upon the culture and language of indigenous peoples is a human right which is too often overlooked by governments when they develop and implement programmes whose purported goals are to improve the social, economic and political status of these peoples. Educational programmes for indigenous peoples must fully respect and integrate human rights protections, particularly rights to cultural continuity and integrity. Racist attitudes dominate many government development programmes aimed at indigenous peoples. Educational programmes for indigenous peoples are often designed to forcibly assimilate them and destroy the uniqueness of their language, values, culture and relationship with their native lands. Until indigenous peoples are empowered to develop educational programmes for their own communities that reflect and promote their values and culture, their human rights are likely to remain threatened by governments that use education as a political mechanism for coercing indigenous peoples to adapt to a majority culture that does not recognize their rights, and that seeks to destroy their ability to sustain and pass on to future generations their language and culture.