julilili42/papers huggingface dataset:
Abstract 1938: Increased miR-126 and miR-375 expression in primary ER-positive breast cancer predict longer relapse-free time following treatment with tamoxifen.
2013-04-01

Abstract Adjuvant tamoxifen treatment provides benefit for millions of women with estrogen receptor positive breast cancer; however, up to 50% of patients experience distant or local recurrence or even die. Tamoxifen resistance is contributed to by host and tumor associated factors and the latter has been particularly attributed to adaptive changes of the tumor involving the regulation of cellular pathways associated with growth, proliferation and apoptosis. Recently, microRNA expression signatures have been appreciated as useful tools to improve the classification of tumors into subtypes and the assessment of tumor heterogeneity. However it is not clear to what extend microRNA signatures derived from the primary tumor can predict treatment outcome. Here we test the hypothesis that distinct microRNAs expressed in the primary tumor can predict the onset of local and distant recurrence following adjuvant tamoxifen. We investigated 115 patients diagnosed with ER positive breast cancer at the Robert Bosch Hospital, Stuttgart, Germany, who had received adjuvant tamoxifen, and had a median follow up of 9.23 years (range: 0.21 - 19.96 years). We compared tumor microRNA expression profiles of 6 patients who developed recurrence under tamoxifen with expression profiles of 6 patients who stayed recurrence-free. Matching of patients was based on age at diagnosis, year of surgery and major histopathological parameters. Candidate microRNAs were identified by global microRNA expression profiling using GeneChip miRNA 2.0 arrays (Affymetrix). Different expression of microRNAs was validated using real-time PCR in 103 tumor samples. We identified miR-126 and miR-375 to be expressed at higher levels in tumors of patients with a lower risk of recurrence (p = 0.0003 and p = 0.0081, respectively). Receiver operator characteristics (ROC) were calculated to further validate their values for predicting breast cancer relapse. The area under the curve (AUC) for miR-126 was 0.6838 (p = 0.0006) and 0.6450 (p = 0.0071) for miR-375, respectively. Kaplan-Meier survival analyses showed that a higher expression of miR-126 and/or miRNA-375 in the patients primary tumor was associated with longer relapse-free time (p = 0.0024 and p = 0.0351, respectively). Our data suggest that miR-126 and miR-375 are promising candidates for further evaluation as tamoxifen outcome predictors in ER-positive breast cancer. R.H. and J.A.K. contributed equally to this work Citation Format: Reiner Hoppe, Joanna Achinger-Kawecka, Stefan Winter, Peter Fritz, Wing-Yee Lo, Werner Schroth, Hiltrud Brauch. Increased miR-126 and miR-375 expression in primary ER-positive breast cancer predict longer relapse-free time following treatment with tamoxifen. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1938. doi:10.1158/1538-7445.AM2013-1938
Photoproduction of π+ p-pairs on the 16O nucleus and isobar configurations
2013-04-01

The yield of the O reaction has been measured in the region of the excitation of the isobar at high momentum transfers to the residual nuclear system. The experimental data are interpreted within the model taking into account of isobar configurations in the ground state of the O nucleus. Direct and exchange mechanisms of the production of pions with emission of one and two nucleons, which follow from the structures of the density matrices for these reactions, have been considered. The probability of the production of the isobar in the ground state of the O nucleus has been empirically estimated as .
Configuration splitting of the Gamow-Teller resonance in antimony isotopes: Is this a real or a virtual effect?
2013-04-01

The Gamow-Teller strength functions for a number of antimony isotopes were calculated within a semimicroscopic approach based on the continuum version of the charge-exchange quasiparticle random-phase approximation and on phenomenologically taking into account the fragmentation effect. The structural effect of splitting of the main maximum of the Gamow-Teller resonance in these isotopes was confirmed. Experimental data on the excitation of this resonance in a direct and a resonance reaction for the 118Sn parent nucleus were analyzed with allowance for this effect.
Reimbursement for tissue reconstruction by pedicled and free flaps across five European countries. The importance of autologous breast reconstruction.
2013-04-01

Case payment mechanisms have become the principle means of remunerating hospitals in many countries. We analysed the reimbursement for different types of autologous tissue transfer in five European countries.We looked at common surgical options for breast reconstruction and flaps at other body regions. The principle diagnosis was systematically modified and processed with national grouper software to identify the relevant Diagnosis-Related Groups.The mean difference in payment was 4509 € in breast reconstruction versus only 2599 € in other locations. According to the underlying diagnosis for reconstruction, procedures after resection of malignant breast cancer showed higher reimbursement (mean 8319 €) than of other body parts (mean 6454 €). Sweden had the highest mean reimbursement (9589 €) followed by Austria (8032 €), Germany (7259 €), Italy (6667 €) and the UK (6037 €). Austria, Italy and the UK showed significant differences of reimbursement between pedicled flaps of the breast and other parts of the body.International data for the benchmarking and refinement of a national compensation system can be a useful instrument in identifying ways of improving each system. Across a spectrum of European countries, reimbursement for the reconstruction of the breast and other body parts was analysed and characteristics were identified. As rationalisation of healthcare becomes widespread in European countries, the need for individualised reimbursement which correlates accordingly is becoming ever more important.
Abstract 4714: Vemurafenib reverses immunosuppression by myeloid derived suppressor cells.
2013-04-01

Abstract Purpose: To evaluate the impact of Vemurafenib on myeloid derived suppressor cell (MDSC) populations in patients with advanced melanoma. Experimental Design: Ex vivo MDSCs were obtained from PBMCs of late stage melanoma patients treated with Vemurafenib as well as healthy controls. The frequency and phenotype of MDSCs was determined by flow cytometry. MDSC populations were characterized for their suppressive function on autologous T cells in CFSE proliferation assays. Additionally, conditioned medium of a melanoma cell line treated with Vemurafenib or not was studied for its effect on MDSCs in vitro. Results: In comparison to healthy donors, patient PBMCs showed an increased frequency of CD14+HLA-DR−/low monocytic MDSCs (moMDSCs) and of a previously unrecognized population of CD14−CD66b+Arginase1+ granulocytic MDSCs (grMDSCs). In vitro, both populations suppressed autologous T-cell proliferation. Vemurafenib treatment of melanoma patients reduced the frequency of both moMDSCs and grMDSCs. Accordingly, conditioned medium from Vemurafenib treated melanoma cells was less active in inducing moMDSCs in vitro. Conclusion: Patients with advanced melanoma show increased levels of moMDSCs, as well as a population of CD14−CD66b+Arginase1+ grMDSCs. Both MDSCs are distinct populations capable of suppressing autologous T-cell responses independently of each other. In vitro as well as in vivo, Vemurafenib inhibits the generation of human moMDSCs. Thus, Vemurafenib decreases immunosuppression in patients with advanced melanoma, indicating its potential as a part of future immunotherapies. Citation Format: Bastian Schilling, Antje Sucker, Klaus Griewank, Fang Zhao, Benjamin Weide, Andre Görgens, Bernd Giebel, Dirk Schadendorf, Annette Paschen. Vemurafenib reverses immunosuppression by myeloid derived suppressor cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4714. doi:10.1158/1538-7445.AM2013-4714
Abstract 79: Immunomodulation in response to radiation-induced lung injury.
2013-04-01

Abstract Introduction. Pneumonitis and fibrosis constitute dose-limiting side effects of thorax and whole body irradiation. Although several novel disease biomarkers have been described during recent years, the cellular and molecular factors responsible for disease initiation and progression are still not sufficiently understood. Here, we characterized local and systemic changes in the immune cell compartment in response to radiation-induced lung injury and defined the role of lymphocytes for fibrosis development in a murine model. Material and methods A single dose of hemithorax or whole thorax irradiation (15 Gy) was applied on C57BL/6 wild type mice (WT) or immunodeficient RAG-2-/- mice. Mice were sacrificed at defined time points and lungs were isolated for histological and immunohistochemical analysis as well as immune cell phenotyping. Moreover, immune cells were isolated from spleen, blood and cervical lymph nodes and also characterized by flow cytometry. Bronchioalveolar lavage fluid was collected for determination of cytokine levels. Results and discussion. Whole thorax irradiation triggered time-dependent changes in the composition and activation state of immune cells isolated from the lung tissue. These changes were paralleled by specific alterations in the cytokines present in the bronchoalveolar lavage fluid. In WT mice whole thorax irradiation with 15 Gy led to a time-dependent increase in collagen deposition and lung fibrosis. Irradiated RAG-2-/- mice showed an earlier onset of collagen deposition and an increased number of fibrotic foci in the lung when compared to WT mice. Conclusion. Thorax irradiation triggers local and systemic changes in the composition and the activation state of immune cells. The increased sensitivity of RAG-2-/- mice to radiation-induced fibrosis suggests a role of mature lymphocytes in the suppression of fibrotic changes. An improved understanding of the contribution of specific immune cells to the pathogenic process in the lung may open novel routes to prevent or treat radiation-induced pneumopathy. Citation Format: Federica Cappuccini, Florian Wirsdörfer, Malagorzata Drabczyk, Therese Eldh, Ali Sak, Verena Jendrossek. Immunomodulation in response to radiation-induced lung injury. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 79. doi:10.1158/1538-7445.AM2013-79
An untimely nexus of German biomechanics, evolution and ornithology: Dominik von Kripp and evolutionary functional morphology
2013-04-01

Abstract Failure of research programmes can say something about the historical times in which they appeared. With this in mind, we review the life and career of Dominik von Kripp, an ornithologist and evolutionary biomechanist working principally in the early 1930s. von Kripp's publications and an unpublished manuscript suggest an innovative research programme that combined biomechanical analysis with taxonomy and evolutionary biology in birds, hadrosaurs, ichthyosaurs and pterosaurs. Despite its publication in well-respected journals, this work was summarily ignored and then eclipsed by the evolutionary synthesis and the German response to it. Keywords: Dominik von Krippbiomechanicsfunctional morphologyresearch programmehistory Acknowledgements It is a pleasure and a sorrow that this paper is to be finally published, but it is the last I will ever write with my friend, Wolf Reif. I miss him terribly. We are most grateful to Frau Dorothea Woditschka (daughter of Dominik von Kripp), Prof. Dr R. Pechlaner (Institute of Zoology, University of Innsbruck, Austria), Prof. Dr G. Rabeder (Institute of Paleontology, University of Vienna, Austria), Dr G Krumbiegel [Geiseltalmuseum, University of Halle, Halle (Saale), Federal Republic of Germany] for providing extensive information on Dominik von Kripp. This work was begun while DBW was a visiting professor at the University of Tübingen under the auspices of Sonderforschungs-bereich 230, to which we gratefully extend our thanks.
Judging Deeds, Not Psychopaths
2013-04-01

Click to increase image sizeClick to decrease image size Acknowledgments Writing of this commentary was supported by a grant from the Social Sciences and Humanities Research Council of Canada (ER) and a New Investigator Award from the Canadian Institutes of Health Research (ER).
Variable water transit times under steady-state storm flow conditions in the Gårdsjön G1 catchment
2013-04-01

We report on a series of replicated tracer experiments with deuterium conducted under exceptionally controlled, steady-state storm flow conditions at Gardsjon in SW Sweden. The Gardsjon G1 catchment was covered by a roof underneath which natural throughfall was replaced by artificial irrigation with a pre-defined isotopic composition. For four tracer experiments in a subcatchment of G1, deuterium was applied as a narrow pulse so that probability density functions of water transit times could be directly inferred from the observed tracer breakthrough curves. Significantly different water transit times and hence flow paths under similar experimental conditions were observed. Differences were unrelated to both steady-state irrigation and evapotranspiration rates during the experiments.
Abstract 5237: Systems level modeling following BRAF inhibition reveals an essential role for Ephrin A2 receptor in therapeutic escape.
2013-04-01

Abstract Although initially striking, the therapeutic efficacy of BRAF inhibition is eventually undermined by adaptive cellular signaling that leads to progressive disease. To date, several mechanisms of BRAF inhibitor resistance have been reported focusing primarily on single alterations. To address how global rewiring of melanoma signaling promotes resistance, we utilized mass spectrometry based phosphoproteomic and network analyses to identify signaling changes in tyrosine, threonine and serine that occur prior to and following acquired BRAF inhibitor resistance. This comprehensive bioinformatics approach uncovered a “resistance interactome” consisting of ∼150 nodes that was marked by significant alterations and the emergence of signaling nodes such as ITGB1, EphA2, EphB4, FAK1, STAT3 and PXN. GeneGo pathway enrichment analysis revealed enhanced cytoskeletal rearrangement, adhesion, integrin signaling, cell migration and extracellular matrix remodeling. Consistent with our bioinformatic predictions, melanoma cell lines with acquired vemurafenib resistance were considerably more invasive than their drug naïve counterparts and showed increased trans-endothelial cell migration. Confirmatory Western blot studies showed increased expression and phosphorylation of EphA2 receptor at Ser897, FAK1 at Ser397 and paxillin at Y118. Knockdown of EphA2 in the resistant cultures inhibited ERK signaling and completely prevented cell invasion and trans-endothelial cell migration. Functionally, EphA2 expression appeared to be regulated by an epigenetic mechanism involving promoter methylation and HDAC1. The clinical relevance of these findings was demonstrated in matched pairs of biopsies from patients receiving either BRAF or BRAF+MEK inhibitors, with significant Ephrin A2 receptor expression being observed in a subset of those on therapy. In summary, chronic MAPK pathway inhibition leads to major remodeling of the melanoma signaling network with EphA2 emerging as a key driver of the resistance phenotype. Citation Format: Kim H. T. Paraiso, Bin Fang, Dale Han, Inna Fedorenko, Jobin John, John Koomen, Jennifer Wargo, Keith Flaherty, Friedegund Meier, Kerian S. M. Smalley. Systems level modeling following BRAF inhibition reveals an essential role for Ephrin A2 receptor in therapeutic escape. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5237. doi:10.1158/1538-7445.AM2013-5237
Verlustpartizipation von Vorständen – Eine ökonomische Analyse der Herabsetzungsmöglichkeit von Vorstandsbezügen nach dem VorstAG
2013-04-01

Abstract This paper examines the loss participation of executives following the German law of adequacy of executive directors’ compensation (VorstAG). First I provide an overview and discussion of the relevant law’ contents. To examine the potential economic impact of the loss participation, a modified tournament model is introduced. The model implies that the aspired participation succeds only partially. Hence, the law might probably fail in it’s purpose of lowering executive directors’ compensation.
Spatial and temporal ECM expression pattern during human cardiogenesis ‐ learning from nature's blueprint
2013-04-01

During fetal cardiac development, extracellular matrix (ECM) compounds are recognized to be essential for cell differentiation and maturation processes. Thus, we aimed to identify spatial and temporal ECM expression pattern during human fetal cardiogenesis, in order to learn from these developmental cues for applictions in regenerative medicine. Therefore, we analyzed the temporal expression and the localization of six essential ECM molecules: collagen type I, III, IV and VI (COLI, COLIII, COLIV, COLVI), fibronectin (FN) and elastin (ELN). Here, we used human ventricular heart muscle tissues of different age groups: fetal first (week 4–12) and second (week 14–17) trimester, children (3–9 years), adults (50–70 years). We performed quantitative gene expression analysis of COL I, COL III, COL IV, COL VI, FN and ELN and analyzed temporal and spatial protein expression by immunofluorescence staining. We revealed a spatiotemporal distinct expression of collagen type IV during human cardiac development. Collagen type IV was highly expressed at the early onset of cardiogenesis, decreased during second trimester, where it was primarily detected in the epicardium, and increased postnatal around mature cardiomyocytes and in the epicardium. Collagen type I expression was the highest in first trimester ventricles and decreased during development. Here, we identified distinct spatiotemporal expression patterns of ECM proteins, which will serve as a blueprint for biomaterials that can be used for myocardial regeneration.
JAM‐A –mediated regulation of epithelial barrier function is dependent on a complex with ZO‐2, Afadin and PDZ‐GEF1 that modulates Rap2c activity.
2013-04-01

Intestinal mucosal barrier function is regulated by epithelial tight junctions (TJs), structures that control paracellular permeability. Junctional Adhesion Molecule A (JAM‐A) is a TJ‐associated protein known to regulate epithelial barrier, however mechanisms linking JAM‐A to regulation of permeability are incompletely understood. Proteomic, biochemical and cell‐biological approaches were used to identify candidate proteins involved in JAM‐A regulation of epithelial permeability. Our findings suggest that JAM‐A directly binds to the scaffold molecule ZO‐2 and indirectly associates with Afadin and PDZ‐GEF1 to regulate activation of the small GTPase Rap2c. A link to regulation of barrier was confirmed by siRNA‐mediated downregulation of these regulatory proteins leading to enhanced permeability. Since ZO‐2, Afadin and Rap2c have been implicated in cytoskeletal dynamics, we investigated whether JAM‐A regulation of barrier function is mediated through peri‐junctional actomyosin. While photobleaching experiments suggest that JAM‐A does not regulate actin turnover, JAM‐A deficient cells display enhanced activation of RhoA, a known inducer of actomyosin contraction. These findings suggest that JAM‐A regulates epithelial permeability through association with a multimolecular signaling complex that activates Rap2c, modulating contraction of the peri‐junctional actin cytoskeleton.
The Science Payload of the LOFT Mission
2013-04-01

The scientific payload onboard the Large Observatory For x-ray Timing mission (LOFT, see presentation by P. Ray et al. at this meeting) is composed of two instruments, the Large Area Detector (LAD, 10 m2 effective area in the primary energy range 2-30 keV, 1-deg collimated field of view) and the Wide Field Monitor (WFM, arcmin imaging over a 4-steradian field of view in the primary energy range 2-50 keV). In this paper we present the design solutions for the two experiments, together with their characteristics and anticipated scientific performance.
In Vitro Translocation Experiments with RxLR-Reporter Fusion Proteins of Avr1b from Phytophthora sojae and AVR3a from Phytophthora infestans Fail to Demonstrate Specific Autonomous Uptake in Plant and Animal Cells
2013-04-02

Plant-pathogenic oomycetes have a large set of secreted effectors that can be translocated into their host cells during infection. One group of these effectors are the RxLR effectors for which it has been shown, in a few cases, that the RxLR motif is important for their translocation. It has been suggested that the RxLR-leader sequences alone are enough to translocate the respective effectors into eukaryotic cells through binding to surface-exposed phosphoinositol-3-phosphate. These conclusions were primary based on translocation experiments conducted with recombinant fusion proteins whereby the RxLR leader of RxLR effectors (i.e., Avr1b from Phytophthora sojae) were fused to the green fluorescent protein reporter-protein. However, we failed to observe specific cellular uptake for a comparable fusion protein where the RxLR leader of the P. infestans AVR3a was fused to monomeric red fluorescent protein. Therefore, we reexamined the ability of the reported P. sojae AVR1b RxLR leader to enter eukaryotic cells. Different relevant experiments were performed in three independent laboratories, using fluorescent reporter fusion constructs of AVR3a and Avr1b proteins in a side-by-side comparative study on plant tissue and human and animal cells. We report that we were unable to obtain conclusive evidence for specific RxLR-mediated translocation.
IκBζ Is a Transcriptional Key Regulator of CCL2/MCP-1
2013-04-02

Abstract CCL2, also referred to as MCP-1, is critically involved in directing the migration of blood monocytes to sites of inflammation. Consequently, excessive CCL2 secretion has been linked to many inflammatory diseases, whereas a lack of expression severely impairs immune responsiveness. We demonstrate that IκBζ, an atypical IκB family member and transcriptional coactivator required for the selective expression of a subset of NF-κB target genes, is a key activator of the Ccl2 gene. IκBζ-deficient macrophages exhibited impaired secretion of CCL2 when challenged with diverse inflammatory stimuli, such as LPS or peptidoglycan. These findings were reflected at the level of Ccl2 gene expression, which was tightly coupled to the presence of IκBζ. Moreover, mechanistic insights acquired by chromatin immunoprecipitation demonstrate that IκBζ is directly recruited to the proximal promoter region of the Ccl2 gene and is required for transcription-enhancing histone H3 at lysine-4 trimethylation. Finally, IκBζ-deficient mice showed significantly impaired CCL2 secretion and monocyte infiltration in an experimental model of peritonitis. Together, these findings suggest a distinguished role of IκBζ in mediating the targeted recruitment of monocytes in response to local inflammatory events.