julilili42/papers huggingface dataset:
The Application of <i>In Situ</i> 3D X-Ray Diffraction in Annealing Experiments: First Interpretation of Substructure Development in Deformed NaCl
2012-04-01

n-situ 3D X-ray diffraction (3DXRD) annealing experiments were conducted at the ID-11 beamline at the European Synchrotron Radiation Facility in Grenoble. This allowed us to non-destructively document and subsequently analyse the development of substructures during heating, without the influence of surface effects. A sample of deformed single crystal halite was heated to between 260-400 °C. Before and after heating a volume of 500 by 500 by 300 μm was mapped using a planar beam, which was translated over the sample volume at intervals of 5-10 μm in the vertical dimension. In the following we present partially reconstructed orientation maps over one layer before and after heating for 240min at 260 °C. Additional small syn-heating maps over a constrained sample rotation of 12-30o. The purpose of this was to illuminate a few reflections from 1 or 2 subgrains and follow their evolution during heating. Preliminary results show that significant changes occurred within the sample volume, for which, surface effects can be excluded. Results show a number of processes, including: i) change in subgrain boundary misorientation angle and ii) subgrain subdivision into areas of similar lattice orientation with new subgrain boundary formation. These results demonstrate that 3DXRD coupled with in-situ heating is a successful non-destructive technique for examining real-time post-deformational annealing in strongly deformed crystalline materials with complicated microstructures.
VEGF Receptors Identify a Multipotent Cardiovascular Progenitor Cell in Developing Hearts and Induced Pluripotent Stem Cells
2012-04-01

Cardiovascular progenitor cells (CPCs) were identified within developing mouse hearts by expression of Nkx2.5 and Islet 1 (Isl1). Detailed study of endogenous CPCs has been limited due to the lack of specific cell surface markers. Here, we identified cell surface markers of Isl1+ CPCs. We functionally validated these CPC markers in induced pluripotent stem cell (iPSC)‐derived CPCs. Microarray analysis of Isl1+/Flk1+ mouse CPCs identified a panel of surface markers expressed on Isl1+ CPCs. The combination of Flt1+/Flt4+ best identified and facilitated purification of Isl1+ CPCs from embryonic hearts as well as differentiating iPSCs. Selective inhibition of p300‐dependent Î 2 ‐catenin signals using the small molecule IQ‐1 allowed in vitro CPC clonal expansion while maintaining their phenotype and multipotency. Endogenous mouse and iPSC‐derived Flt1+/Flt4+ CPCs differentiated into all cells of the cardiovascular lineage in vitro, and demonstrated robust engraftment and differentiation into mature adult cardiomyocytes in vivo. In conclusion, we have demonstrated that the combination of Flt1 and Flt4 can specifically identify endogenous and iPSC‐derived Isl1+ CPCs with trilineage cardiovascular potential. We showed robust differentiation into cardiomyocytes, smooth muscle and endothelial cells in vitro as well as post transplantation in vivo.
Abstract 5365: Prolonged survival of patients with advanced renal cancer responding to multi-peptide vaccine IMA901 after single-dose cyclophosphamide
2012-04-01

Abstract Translational research and the clinical development of therapeutic cancer vaccines requires stronger scientific rationalization. Here we demonstrate how immune response markers as well as biomarkers defining the immune regulatory environment were utilized as guiding tools from discovery to advanced clinical trials of IMA901, a novel therapeutic vaccine for the treatment of renal cell carcinoma (RCC). IMA901 consists of multiple tumor-associated peptides (TUMAPs) confirmed to be naturally presented in human RCC tissue by mass spectrometry, selected using differential transcriptomics and preclinically validated by systematic analysis of immunogenicity with artificial antigen-presenting cells. Two consecutive independent clinical studies in a total of 96 HLA-A*02+ advanced/metastatic RCC patients were conducted. The phase I study revealed that T-cell responses to multiple IMA901 antigens were significantly associated with disease control and negatively associated with the presence of FoxP3+ regulatory T cells (Tregs). The subsequent randomized phase II study demonstrated that pre-treatment with a single low dose of cyclophosphamide (Cy) reduced Treg frequencies and prolonged overall survival (OS) in patients who mounted an immune response to the IMA901 vaccine. Additionally, T-cell responses to multiple IMA901 antigens were again associated with clinical benefit. Furthermore, a comprehensive prognostic and predictive biomarker program was conducted. Among cellular biomarkers, highly significantly elevated levels of myeloid-derived suppressor cells (MDSC), IL-17-/IL-10-secreting T cells and dysfunctional T cells in RCC patients vs. healthy individuals were found. Two MDSC populations (CD14+ HLA-DR- and CD14- CD11b+ CD15+) were significantly negatively associated with survival in vaccinated RCC patients. Interestingly, both MDSC populations were also found to be negatively associated with OS in an independent trial in colorectal cancer patients (N=79) implying a broader role for these MDSC species. Additionally, among over 300 serum biomarkers tested, apolipoprotein A-I (ApoA1) and the chemokine CCL17 were found to be predictive for both immune responses to IMA901 and survival of the RCC patients. The knowledge acquired in these trials was used to design a randomized phase III study. In this ongoing study, IMA901 is combined with the tyrosine kinase inhibitor sunitinib based on the findings that sunitinib downmodulates the two MDSC populations described above. Furthermore, in this phase III study, the relevance of ApoA1/CCL17 will be explored by prospectively defined subgroup analyses. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5365. doi:1538-7445.AM2012-5365
Abstract 4658: Delta9-Tetrahydrocannabinol induces apoptosis via Cannabinol Receptor 1 and modulates methylation of oncogenes and tumorsuppressors in blasts derived from patients with acute lympoblastic or myeloid leukemia
2012-04-01

Abstract Some cannabinol derivatives are said to possess antitumor efficacy. We have evidence that the CB1/2 cannabinoid receptor agonist Delta9-Tetrahydrocannabinol (THC), the major psychoactive component of marijuana, may have contributed to disease control in a patient with acute myeloid leukemia. We speculated that THC may induce apoptosis in native leukemic blasts and thus treated various leukemia cell lines and ex vivo blasts derived from patients with either acute lymphoblastic or myeloid leukemia in dilution series with THC. The antiproliferative effect was measured using an XTT-based assay. Induction of apoptosis was assessed by annexinV-based immunofluorescence analysis. The CB1 antagonist LY320135 or JTE-907, a selective CB2 inverse ligand agonist, were used to confirm involvement of CB1 (mainly expressed in brain tissue) or CB2 (expression in hematologic/lymphoid cells). THC was obtained with permission of the Bundesopiumstelle, Germany. Indeed, we demonstrate potent antiproliferative and proapoptotic efficacy of Delta9-THC in a dose dependent manner in leukemia cell lines of lymphoid and myeloid origin. Pretreatment with LY320135, but not with JTE-907, resulted in a dramatic abrogation of the antileukemic effect seen with THC monotherapy, arguing that THC-induced apoptosis is mediated via the cannabinoid receptor CB1. Besides a proapoptotic effect, THC was able to abrogate cellular differentiation blockage as observed in a change of morphology. Of note, THC was able to induce apoptosis in a subset of leukemia samples derived from patients with acute myeloid (mainly undifferentited AML) or lymphoblastic leukemia. Due to the patient cohort responsive to THC therapy, we speculated that epigenetic modifications might be associated with MLL (mixed lineage leukemia) methyltransferase function. In a global DNA methylation gene array, we could demonstrate that THC leads to modulation of methylation status of histone deacetylases, oncogenes and tumorsuppressors, some reported to be regulated by MLL. Ongoing work is focussing on validation whether THC treatment can be linked to MLL activity using an siRNA approach. In conclusion, while not being able to directly correlate the disease course of the above described patient to marijuana abuse, our in vitro results nevertheless demonstrate that THC mediates antileukemic activity in blasts of some patients ex vivo including that of our patient. Clinical evaluation of cannabinol receptor agonists as low-toxic agents could thus be considered in selected cases of patients with acute leukemia and this approach should further be followed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4658. doi:1538-7445.AM2012-4658
Abstract 455: Phospho-ERK as a predictor for different ways of metastasis and / or survival in patients with metastasized colon cancer
2012-04-01

Abstract Background: Not much is known about different signalling pathways and its influence on metastasis in colon cancer. Phospho-ERK (pERK) is a downstream-target of K-Ras within the EGFR-Pathway. The goal of our investigations was the evaluation of the MAP-Kinase-cascade in regard to different ways of metastasis. Methods: 98 patients with adenocarcinom of the colon and a postoperative pT2/3-status, who underwent surgical resection between 2006 and 2008 at the University of Tübingen had been included within the study collective. 53 patients had no metastasis (control group), while 45 patients revealed primary metastasis: lymphogenetic metastasis (n=20), hepatic spread (n=20) and multiple metastasize (n=5). On a tissue-micro-Array pERK was stained by immunohistochemistry, the analysis was done semiquantitatively. Results: The graduation in immunohistochemistry was done as followed: negative staining (n=31), weak positive staining (n=36), moderate staining (n=20) and strong staining (n=11). 19 out of 31 negative patients (61%) revealed metastasis, while this had been 17 out of 36 weak positive (47%), 6 out of 20 (30%) moderate and 4 out of 11 (36%) strongly positive stained patients (p=0.229). No significant correlation was observed for lypmhogenetic (p=0.683) or multiple metastatic localization (p=0.666) and the pERK-expression. A significant correlation between the pERK-expression and the number of hepatic metastasis was observed (p=0.049). Additionally pERK-negative patients (31/98 = 32%) revealed a significant worse survival compared to those with positive pERK-staining (p=0.003). Conclusion: Our first results show, that a weak pERK-expression is correlated with a higher incidence in patients with liver metastasis. Patients without a pERK-expression revealed a worse survival compared to patients with pERK-expression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 455. doi:1538-7445.AM2012-455
Effect of Natural Abiotic Colloids on the Transport of Lindane (gamma-hexachlorocyclohexane) through Saturated Porous Media: Laboratory Experiments and Model-Based Analysis
2012-04-01

In many developing countries, the hygienic situation has improved by changing from surface-water bodies to groundwater as drinking water resource. However, failures have frequently been reported, presumably caused by wrong design of groundwater extraction (e.g., wells too close to open-water bodies, landfill leachates or agricultural areas). Moreover threat to groundwater pollution is enhanced when colloidal particles in the subsurface can act as carriers for adsorbing contaminants such as hydrophobic chlorinated organic contaminants. In this study, the main objective was to investigate the influence of particles in the size range of colloids on the subsurface transport of pesticides which are known to cause severe health problems. The model pesticide was gamma-hexachlorocyclohexane, a representative hydrophobic insecticide which is still used mainly in tropical countries. Colloid-facilitated transport was carried out by considering a first case where the adsorption of the contaminant to the particles is at equilibrium before getting simultaneously transported, and a second case where this equilibrium was not reached before their transport. Another focus besides colloid-facilitated transport was placed on the release of the contaminant from trapped colloids. Data analysis was done with the help of numerical modeling and the minimum model complexity needed to simulate such transports was examined.
Exhumation of the northwestern Fairweather Range, southeast Alaska
2012-04-01

The study investigates spatial and temporal patterns in exhumation along the transpressive plate boundary Fairweather Fault, Alaska, USA. The Fairweather transform fault forms the eastern boundary between the obliquely colliding Yakutat Terrane and the North American plate. Deformation on the Fairweather Fault initiated around 30 Ma and has been suggested to be a transpressive dextral strike-slip fault zone that formed the Fairweather Range. This 300 km long and 50 km wide mountain range is characterized by > 4000 m high peaks and deep glacial valleys that drain into the North Pacific. Previously published low-temperature thermochronometer data suggest that deformation and exhumation is not restricted to one side of the fault. Maximum estimated exhumation rates of up to 2 mm/yr occur within 10 km of the fault and extend about 300 km along strike. We collected 15 sand samples from modern glacial drainages spanning 80 km along strike of the northwestern part of the Fairweather Range to quantify spatial variations in deformation and exhumation of this range. Zircon fission track age distributions are measured to quantify the long-term exhumation patterns along this fault. The aim of this study is to gain better special coverage for the cooling age signals in this glaciated and remote region. We concentrate on the northern part of the Fairweather Range because it comprises the partitioning of strain as the strike-slip motion of the Fairweather Fault changes to convergence and thrust tectonics when it merges into the St. Elias Range. Calculation of final grain-age distributions from these samples is in progress. We will present detrital zircon fission track ages along the northwestern ca. 80 km of the Fairweather Fault and including the transition into the St. Elias Range. Based on existing bedrock samples we anticipate the youngest age populations to be 15 Ma in catchments that are located farther away from the fault. Additionally, we expect to see changes in the amount of exhumation and its distribution with respect to the fault zone along the strike. Deviations in the new detrital samples compared to existing bedrock samples could be due a) localized areas of enhanced or retarded exhumation due to temporal variations on Fairweather Fault slip, b) deformation and exhumation of rocks on previously unrecognized structures, and/or c) spatial variations in the intensity of glacial erosion along strike of the Fairweather Fault.
Stepwise magnetic-geochemical approach for efficient assessment of heavy metal polluted sites
2012-04-01

Previous studies have shown that magnetometry can outline the distribution of fly ash deposition in the surroundings of coal-burning power plants and steel industries. Especially the easy-to-measure magnetic susceptibility (MS) is capable to act as a proxy for heavy metal (HM) pollution caused by such kind of point source pollution. Here we present a demonstration project around the coal-burning power plant complex “Schwarze Pumpe” in eastern Germany. Before reunification of West and East Germany huge amounts of HM pollutants were emitted from the “Schwarze Pumpe” into the environment by both fly ash emission and dumped clinker. The project has been conducted as part of the TASK Centre of Competence which aims at bringing new innovative techniques closer to the market. Our project combines in situ and laboratory MS measurements and HM analyses in order to demonstrate the efficiency of a stepwise approach for site assessment of HM pollution around point sources of fly-ash emission and deposition into soil. The following scenario is played through: We assume that the “true” spatial distribution of HM pollution (given by the pollution load index PLI comprising Fe, Zn, Pb, and Cu) is represented by our entire set of 85 measured samples (XRF analyses) from forest sites around the “Schwarze Pumpe”. Surface MS data (collected with a Bartington MS2D) and in situ vertical MS sections (logged by an SM400 instrument) are used to determine a qualitative overview of potentially higher and lower polluted areas. A suite of spatial HM distribution maps obtained by random selections of 30 out of the 85 analysed sites is compared to the HM map obtained from a targeted 30-sites-selection based on pre-information from the MS results. The PLI distribution map obtained from the targeted 30-sites-selection shows all essential details of the “true” pollution map, while the different random 30-sites-selections miss important features. This comparison shows that, for the same cost investment, a stepwise combined magnetic-geochemical site assessment leads to a clearly more significant characterization of soil pollution than by a common approach with exclusively random sampling for geochemical analysis, or alternatively to an equal quality result for lower costs.
Marjorie Wheeler‐Barclay . The Science of Religion in Britain, 1860–1915 . (Victorian Literature and Culture Series.) Charlottesville: University of Virginia Press. 2010. Pp. x, 311. $45.00.
2012-04-01

In this book, Marjorie Wheeler‐Barclay starts from the assumption that some early British classics within the academic discipline now commonly known as the comparative study of religions have frequently been analyzed to ascertain their contribution to the present state of knowledge in the field, but without a sufficient view to elucidating their role in Victorian discourse on religion. To remedy this, she discusses in detail six writers who justifiably can be taken to exemplify the full scope of non‐theological Victorian writing on religion and the religions. In her introduction, the author argues “that their work is best regarded not as a cause of, but as a response to, the sense of cultural disorientation that was engendered by religious turmoil” (p. 2), claiming that the “widespread interest in the ‘utility’ and human ‘meaning’ of all forms of religious belief and practice offered a favourable atmosphere for the creation of a comparative study of religions” (p. 7). Chapter one consequently details some major influences that had shaped the perception of religion and religions by the early decades of the Victorian period, most notably the evolutionary ideas propagated by Auguste Comte and Herbert Spencer. Following this setting of the stage, the author discusses in the following six chapters the lives and works of Friedrich Max Müller, Edward Burnett Tylor, Andrew Lang, William Robertson Smith, James George Frazer, and Jane Ellen Harrison; each of the chapters moves from vital biographical information via key themes and concepts to an outline of the contemporary reception. In her conclusion, Wheeler‐Barclay reaffirms her conviction that the “Victorian ‘science of religion’ was a reaction to and a reflection of the sense of crisis that had troubled the educated classes of British society as the traditional Anglican cultural elite came under increasingly successful attack, a process that had reached its most intense phase in the years between 1850 and 1890” (p. 247). Summarizing the individual positions taken by the authors discussed in her book, she notes that “while the science of religion was not able to create a new cultural consensus, it had contributed in ways not always easy to trace to a new and more wide‐ranging conception of religion” (p. 252).
Abstract 2002: OCT-3/4 expression is associated with high levels of the pro-apoptotic BH3 only protein NOXA in testicular germ cell tumors (TGCTs)
2012-04-01

Abstract Embryonal carcinoma (EC) cells are the pluripotent precursors of differentiated structures of testicular germ cell tumors (TGCT) characterized by expression of the embryonal transcription factor OCT-3/4. Loss of OCT-3/4 during differentiation abrogates the extraordinary high sensitivity to cisplatin in these cells. We previously observed a constitutively high expression level of NOXA and a major role of this pro-apoptotic BH3-only protein for cisplatin hypersensitivity in the EC cell lines NTERA-2D1 and 2102EP. We now investigated if these high NOXA protein levels may be directly linked to the OCT-3/4 status in TGCT cells. Therefore, we analyzed NOXA protein expression in an extended TGCT cell line panel of 5 OCT-3/4 negative and 5 OCT-3/4 positive cell lines. Importantly, NOXA protein was highly correlated with OCT-3/4 levels and also with cisplatin sensitivity. These data indicate that constitutively high NOXA levels might be responsible for the low threshold for cisplatin-induced apoptosis in OCT-3/4 positive pluripotent cells. A direct link between OCT-3/4 and NOXA could also be demonstrated by RNAi mediated silencing experiments performed in NTERA-2D1 and 2102EP cells. Silencing of OCT-3/4 resulted in a significant downregulation of NOXA transcript and an almost complete loss of NOXA protein accompanied by a loss of cisplatin sensitivity. This was observed in both differentiation competent NTERA-2D1 cells as well as in differentiation incompetent 2102EP cells pointing to a direct OCT-3/4 dependent NOXA regulation rather than a bystander effect of differentiation upon loss of OCT-3/4. We further validated our in vitro data by comparing OCT-3/4 and NOXA expression levels in patient samples derived from ECs with other non-seminomatous GCTs, seminomas, and tumor entities from lung, breast, and ovary. In agreement with our in vitro observations, OCT-3/4 and NOXA were found to be highly expressed selectively in seminomas and ECs. This could also be confirmed on protein level in primary tissue samples derived from 5 ECs and 8 seminomas by western blot analysis. In conclusion, our data for the first time demonstrate a close correlation between OCT-3/4 and NOXA protein levels and strengthen the previously hypothesized role of constitutively high NOXA levels for the exquisite sensitivity of TGCTs to cisplatin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2002. doi:1538-7445.AM2012-2002