Evidence of Presence of the Eltville Tuff Layer in Dutsch and Belgian Limbourg and the Consequences for the Loess Stratigraphy

Anfang 1979 ist zum ersten Male in den Niederlanden ein vulkanischer Tuff in den Lößablagerungen von Süd-Limburg gefunden worden (Meijs 1980a). Auf Grund der stratigraphischen Lage, des makroskopischen Aussehens und der mineralogischen Zusammensetzung wurde dieser Tuff mit dem Eltviller Tuff korreliert. In dieser Veröffentlichung werden die Korrelierungsbeweisgründe eingehend behandelt und mit den Ergebnissen mikromorphologischer und röntgenologischer Untersuchungen ergänzt. Die Entdeckung des Eltviller Tuffs in dieser Region gerade unter dem Kesselt-Paläoboden (= Nagelbeek Horizont) bedeutet, daß dieser Paläoboden ein stratigraphisches Äquivalent des E4-Naßbodens ist. Dieses steht im Widerspruch mit der in Belgien und den Niederlanden herrschenden Ansicht, laut der der Kesselt-Paläoboden mit dem im Denekamp Interstadial geformten Stillfried-B Paläoboden korreliert wird (z. B. Zagwijn & Paepe 1968). Der letztgenannte Paläoboden liegt aber stratigraphisch unter dem Eltviller Tuff und ist ungefähr 10.000 Jahr älter als der E4-Naßboden (Semmel 1967, Vogel & van der Hammen 1967).researc

Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump

Imatinib mesylate (STI571), a potent tyrosine kinase inhibitor, is successfully used in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors. However, the intended chronic oral administration of imatinib may lead to development of cellular resistance and subsequent treatment failure. Indeed, several molecular mechanisms leading to imatinib resistance have already been reported, including overexpression of the MDR1/ABCB1 drug pump. We examined whether imatinib is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump that is frequently overexpressed in human tumors. Using a panel of well-defined BCRP-overexpressing cell lines, we provide the first evidence that imatinib is a substrate for BCRP, that it competes with mitoxantrone for drug export, and that BCRP-mediated efflux can be reversed by the fumitremorgin C analog Ko-143. Since BCRP is highly expressed in the gastrointestinal tract, BCRP might not only play a role in cellular resistance of tumor cells but also influence the gastrointestinal absorption of imatinib

N=8 superconformal gauge theories and M2 branes

Based on recent developments, in this letter we find 2+1 dimensional gauge theories with scale invariance and N=8 supersymmetry. The gauge theories are defined by a Lagrangian and are based on an infinite set of 3-algebras, constructed as an extension of ordinary Lie algebras. Recent no-go theorems on the existence of 3-algebras are circumvented by relaxing the assumption that the invariant metric is positive definite. The gauge group is non compact, and its maximally compact subgroup can be chosen to be any ordinary Lie group, under which the matter fields are adjoints or singlets. The theories are parity invariant and do not admit any tunable coupling constant. In the case of SU(N) the moduli space of vacua contains a branch of the form (R^8)^N/S_N. These properties are expected for the field theory living on a stack of M2 branes.Comment: 14 pages, no figure

Neutrophil-Mediated Experimental Metastasis Is Enhanced by VEGFR Inhibition in a Zebrafish Xenograft Model

Inhibition of VEGF signalling effectively suppresses localized tumour growth but accelerates tumour invasiveness and micrometastasis by unknown mechanisms. To study the dynamic and reciprocal interactions between tumour cells and their microenvironment during these processes, we established a xenograft model by injecting tumour cells into the blood circulation of transparent zebrafish embryos. This reproducibly results in rapid simultaneous formation of a localized tumour and experimental micrometastasis, allowing time-resolved imaging of both processes at single-cell resolution within 1 week. The tumour vasculature was initiated de novo by remodelling of primitive endothelial cells into a functional network. Roles of myeloid cells in critical tumourigenesis steps such as vascularization and invasion were revealed by genetic and pharmaceutical approaches. We discovered that the physiological migration of neutrophils controlled tumour invasion by conditioning the collagen matrix and forming the metastatic niche, as detected by two-photon confocal microscopy and second harmonic generation. Administration of VEGFR inhibitors blocked tumour vascularization and a localized tumour growth but enhanced migration of neutrophils, which in turn promoted tumour invasion and formation of micrometastasis. This demonstrates the in vivo cooperation between VEGF signalling and myeloid cells in metastasis and provides a new mechanism underlying the recent findings that VEGFR targeting can promote tumour invasiveness

Quantum Black Hole Evaporation

We investigate a recently proposed model for a full quantum description of two-dimensional black hole evaporation, in which a reflecting boundary condition is imposed in the strong coupling region. It is shown that in this model each initial state is mapped to a well-defined asymptotic out-state, provided one performs a certain projection in the gravitational zero mode sector. We find that for an incoming localized energy pulse, the corresponding out-going state contains approximately thermal radiation, in accordance with semi-classical predictions. In addition, our model allows for certain acausal strong coupling effects near the singularity, that give rise to corrections to the Hawking spectrum and restore the coherence of the out-state. To an asymptotic observer these corrections appear to originate from behind the receding apparent horizon and start to influence the out-going state long before the black hole has emitted most of its mass. Finally, by putting the system in a finite box, we are able to derive some algebraic properties of the scattering matrix and prove that the final state contains all initial information.Comment: 37 pages (figs 2 and 3 included as uuencoded compressed tar file), Latex, needs epsf.tex, PUPT-1395, IASSNS-HEP-93/25 (revised version has minor corrections, one reference added

Comparison of Short-Term Estrogenicity Tests for Identification of Hormone-Disrupting Chemicals

The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, estrogenic antagonists, and a known cytotoxic agent. Also included in the test panel were 17β-estradiol as a positive control and ethanol as solvent control. The test compounds were coded before distribution. Test methods included direct binding to the estrogen receptor (ER), proliferation of MCF-7 cells, transient reporter gene expression in MCF-7 cells, reporter gene expression in yeast strains stably transfected with the human ER and an estrogen-responsive reporter gene, and vitellogenin production in juvenile rainbow trout. 17β-Estradiol, 17α-ethynyl estradiol, and diethylstilbestrol induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds—tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol dodecylethoxylate, butylbenzylphthalate, dibutylphthalate, methoxychlor, o,p′-DDT, p,p′-DDE, endosulfan, chlomequat chloride, and ethanol—varied among the assays. The results demonstrate that careful standardization is necessary to obtain a reasonable degree of reproducibility. Also, similar methods vary in their sensitivity to estrogenic compounds. Thus, short-term tests are useful for screening purposes, but the methods must be further validated by additional interlaboratory and interassay comparisons to document the reliability of the methods

Deep RNA Sequencing of the Skeletal Muscle Transcriptome in Swimming Fish

Deep RNA sequencing (RNA-seq) was performed to provide an in-depth view of the transcriptome of red and white skeletal muscle of exercised and non-exercised rainbow trout (Oncorhynchus mykiss) with the specific objective to identify expressed genes and quantify the transcriptomic effects of swimming-induced exercise. Pubertal autumn-spawning seawater-raised female rainbow trout were rested (n = 10) or swum (n = 10) for 1176 km at 0.75 body-lengths per second in a 6,000-L swimflume under reproductive conditions for 40 days. Red and white muscle RNA of exercised and non-exercised fish (4 lanes) was sequenced and resulted in 15–17 million reads per lane that, after de novo assembly, yielded 149,159 red and 118,572 white muscle contigs. Most contigs were annotated using an iterative homology search strategy against salmonid ESTs, the zebrafish Danio rerio genome and general Metazoan genes. When selecting for large contigs (.500 nucleotides), a number of novel rainbow trout gene sequences were identified in this study: 1,085 and 1,228 novel gene sequences for red and white muscle, respectively, which included a number of important molecules for skeletal muscle function. Transcriptomic analysis revealed that sustained swimming increased transcriptional activity in skeletal muscle and specifically an upregulation of genes involved in muscle growth and developmental processes in white muscle. The unique collection of transcripts will contribute to our understanding of red and white muscle physiology, specifically during the long-term reproductive migration of salmonids.Fil: Palstra, Arjan P.. Universidad de Barcelona. Facultad de Biología; España;Fil: Beltran, Sergi. Universitat de Barcelona. Centres Cientifics i Tecnològics. Unitat de Bioinformàtica; España;Fil: Burgerhout, Erik. Leiden University. Institute of Biology. Molecular Cell Biology; Países Bajos; ZF-screens; Países Bajos;Fil: Brittijn, Sebastiaan A.. Leiden University. Institute of Biology. Molecular Cell Biology; Países Bajos; ZF-screens; Países Bajos;Fil: Magnoni, Leonardo Julián. Universidad de Barcelona. Facultad de Biología; España; Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); Argentina;Fil: Henkel, Christiaan V.. ZF-screens; Países Bajos;Fil: Jansen, Hans J.. ZF-screens; Países Bajos;Fil: Van Den Thillart, Guido E. E. J. M.. Leiden University. Institute of Biology. Molecular Cell Biology; Países Bajos; ZF-screens; Países Bajos;Fil: Spaink, Herman P.. Leiden University. Institute of Biology. Molecular Cell Biology; Países Bajos; ZF-screens; Países Bajos;Fil: Planas, Josep V.. Universidad de Barcelona. Facultad de Biologia; España

Back to the future:re-establishing guinea pig in vivo asthma models

Research using animal models of asthma is currently dominated by mouse models. This has been driven by the comprehensive knowledge on inflammatory and immune reactions in mice, as well as tools to produce genetically modified mice. Many of the identified therapeutic targets influencing airway hyper-responsiveness and inflammation in mouse models, have however been disappointing when tested clinically in asthma. It is therefore a great need for new animal models that more closely resemble human asthma. The guinea pig has for decades been used in asthma research and a comprehensive table of different protocols for asthma models is presented. The studies have primarily been focused on the pharmacological aspects of the disease, where the guinea pig undoubtedly is superior to mice. Further reasons are the anatomical and physiological similarities between human and guinea pig airways compared with that of the mouse, especially with respect to airway branching, neurophysiology, pulmonary circulation and smooth muscle distribution, as well as mast cell localization and mediator secretion. Lack of reagents and specific molecular tools to study inflammatory and immunological reactions in the guinea pig has however greatly diminished its use in asthma research. The aim in this position paper is to review and summarize what we know about different aspects of the use of guinea pig in vivo models for asthma research. The associated aim is to highlight the unmet needs that have to be addressed in the future

Whole breast proton irradiation for maximal reduction of heart dose in breast cancer patients

PURPOSE: In left-sided breast cancer radiotherapy, tangential intensity modulated radiotherapy combined with breath-hold enables a dose reduction to the heart and left anterior descending (LAD) coronary artery. Aim of this study was to investigate the added value of intensity modulated proton therapy (IMPT) with regard to decreasing the radiation dose to these structures. METHODS: In this comparative planning study, four treatment plans were generated in 20 patients: an IMPT plan and a tangential IMRT plan, both with breath-hold and free-breathing. At least 97 % of the target volume had to be covered by at least 95 % of the prescribed dose in all cases. Specifically with respect to the heart, the LAD, and the target volumes, we analyzed the maximum doses, the mean doses, and the volumes receiving 5-30 Gy. RESULTS: As compared to IMRT, IMPT resulted in significant dose reductions to the heart and LAD-region even without breath-hold. In the majority of the IMPT cases, a reduction to almost zero to the heart and LAD-region was obtained. IMPT treatment plans yielded the lowest dose to the lungs. CONCLUSIONS: With IMPT the dose to the heart and LAD-region could be significantly decreased compared to tangential IMRT with breath-hold. The clinical relevance should be assessed individually based on the baseline risk of cardiac complications in combination with the dose to organs at risk. However, as IMPT for breast cancer is currently not widely available, IMPT should be reserved for patients remaining at high risk for major coronary events