Verkehr in Zahlen 2020/2021

Verkehr in Zahlen (ViZ) ist seit mehr als vierzig Jahren das Standardwerk zur Verkehrsstatistik in Deutschland. Das Kompendium enthält auf über 300 Seiten aktuelle Zahlen und Zeitreihen zu allen Themen aus den Bereichen Mobilität und Verkehr

International Consensus Conference for Advanced Breast Cancer, Lisbon 2019: ABC5 Consensus – Assessment by a German Group of Experts

The 5th International Consensus Conference for Advanced Breast Cancer (ABC5) took place on November 14–16, 2019, in Lisbon, Portugal. Its aim is to standardize the treatment of advanced breast cancer based on the available evidence and to ensure that all breast cancer patients worldwide receive adequate treatment and access to new therapies. This year, the conference focused on developments and study results in the treatment of patients with hormone receptor-positive/HER2-negative breast cancer as well as precision medicine. As in previous years, patient advocates from around the world were integrated into the ABC conference and had seats on the ABC consensus panel. In the present paper, a working group of German breast cancer experts comments on the results of the on-site ABC5 consensus votes by ABC panelists regarding their applicability for routine treatment in Germany. These comments take the recommendations of the Breast Committee of the Gynecological Oncology Working Group (Arbeitsgemeinschaft Gynäkologische Onkologie; AGO) into account. The report and assessment presented here pertain to the preliminary results of the ABC5 consensus. The final version of the statements will be published in Annals of Oncology and The Breast

Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin

Epigenetic memory in induced pluripotent stem cells, which is related to the somatic cell type of origin of the stem cells, might lead to variations in the differentiation capacities of the pluripotent stem cells. In this context, induced pluripotent stem cells from human CD34(+) hematopoietic stem cells might be more suitable for hematopoietic differentiation than the commonly used fibroblast-derived induced pluripotent stem cells. To investigate the influence of an epigenetic memory on the ex vivo expansion of induced pluripotent stem cells into erythroid cells, we compared induced pluripotent stem cells from human neural stem cells and human cord blood-derived CD34(+) hematopoietic stem cells and evaluated their potential for differentiation into hematopoietic progenitor and mature red blood cells. Although genome-wide DNA methylation profiling at all promoter regions demonstrates that the epigenetic memory of induced pluripotent stem cells is influenced by the somatic cell type of origin of the stem cells, we found a similar hematopoietic induction potential and erythroid differentiation pattern of induced pluripotent stem cells of different somatic cell origin. All human induced pluripotent stem cell lines showed terminal maturation into normoblasts and enucleated reticulocytes, producing predominantly fetal hemoglobin. Differences were only observed in the growth rate of erythroid cells, which was slightly higher in the induced pluripotent stem cells derived from CD34(+) hematopoietic stem cells. More detailed methylation analysis of the hematopoietic and erythroid promoters identified similar CpG methylation levels in the induced pluripotent stem cell lines derived from CD34(+) cells and those derived from neural stem cells, which confirms their comparable erythroid differentiation potential.close1

An expression signature of syndecan-1 (CD138), E-cadherin and c-met is associated with factors of angiogenesis and lymphangiogenesis in ductal breast carcinoma in situ

INTRODUCTION: Heparan sulphate proteoglycan syndecan-1 modulates cell proliferation, adhesion, migration and angiogenesis. It is a coreceptor for the hepatocyte growth factor receptor c-met, and its coexpression with E-cadherin is synchronously regulated during epithelial-mesenchymal transition. In breast cancer, changes in the expression of syndecan-1, E-cadherin and c-met correlate with poor prognosis. In this study we evaluated whether coexpression of these functionally linked prognostic markers constitutes an expression signature in ductal carcinoma in situ (DCIS) of the breast that may promote cell proliferation and (lymph)angiogenesis. METHODS: Expression of syndecan-1, E-cadherin and c-met was detected immunohistochemically using a tissue microarray in tumour specimens from 200 DCIS patients. Results were correlated with the expression patterns of angiogenic and lymphangiogenic markers. Coexpression of the three prognostic markers was evaluated in human breast cancer cells by confocal immunofluorescence microscopy and RT-PCR. RESULTS: Coexpression and membrane colocalization of the three markers was confirmed in MCF-7 cells. E-cadherin expression decreased, and c-met expression increased progressively in more aggressive cell lines. Tissue microarray analysis revealed strong positive staining of tumour cells for syndecan-1 in 72%, E-cadherin in 67.8% and c-met in 48.6% of DCIS. E-cadherin expression was significantly associated with c-met and syndecan-1. Expression of c-met and syndecan-1 was significantly more frequent in the subgroup of patients with pure DCIS than in those with DCIS and a coexisting invasive carcinoma. Levels of c-met and syndecan-1 expression were associated with HER2 expression. Expression of c-met significantly correlated with expression of endothelin A and B receptors, vascular endothelial growth factor (VEGF)-A and fibroblast growth factor receptor-1, whereas E-cadherin expression correlated significantly with endothelin A receptor, VEGF-A and VEGF-C staining. CONCLUSION: Syndecan-1, E-cadherin and c-met constitute a marker signature associated with angiogenic and lymphangiogenic factors in DCIS. This coexpression may reflect a state of parallel activation of different signal transduction pathways, promoting tumour cell proliferation and angiogenesis. Our findings have implications for future therapeutic approaches in terms of a multiple target approach, which may be useful early in breast cancer progression

Middle East - North Africa and the millennium development goals : implications for German development cooperation

          Closed-loop controlled combustion is a promising technique to improve the overall performance of internal combustion engines and Diesel engines in particular. In order for this technique to be implemented some form of feedback from the combustion process is required. The feedback signal is processed and from it combustionrelated parameters are computed. These parameters are then fed to a control process which drives a series of outputs (e.g. injection timing in Diesel engines) to control their values. This paper’s focus lies on the processing and computation that is needed on the feedback signal before this is ready to be fed to the control process as well as on the electronics necessary to support it. A number of feedback alternatives are briefly discussed and for one of them, the in-cylinder pressure sensor, the CA50 (crank angle in which the integrated heat release curve reaches its 50% value) and the IMEP (Indicated Mean Effective Pressure) are identified as two potential control variables. The hardware architecture of a system capable of calculating both of them on-line is proposed and necessary feasibility size and speed considerations are made by implementing critical blocks in VHDL targeting a flash-based Actel ProASIC3 automotive-grade FPGA

Genomic and epigenomic BRCA alterations predict adaptive resistance and response to platinum-based therapy in patients with triple-negative breast and ovarian carcinomas

Triple-negative breast cancer (TNBC) and ovarian carcinomas (OvCas) with BRCA1 promoter methylation (BRCA1meth) respond more poorly to alkylating agents compared to those bearing mutations in BRCA1 and BRCA2 (BRCAmut). This is a conundrum given the biologically equivalent homologous recombination deficiency (HRD) induced by these genetic and epigenetic BRCA perturbations. We dissected this problem through detailed genomic analyses of TNBC and OvCa cohorts and experimentation with patient-derived xenografts and genetically engineered cell lines. We found that despite identical downstream genomic mutational signatures associated with BRCA1meth and BRCAmut states, BRCA1meth uniformly associates with poor outcomes. Exposure of BRCA1meth TNBCs to platinum chemotherapy, either as clinical treatment of a patient or as experimental in vivo exposure of preclinical patient derived xenografts, resulted in allelic loss of BRCA1 methylation and increased BRCA1 expression and platinum resistance. These data suggest that, unlike BRCAmut cancers, where BRCA loss is a genetically fixed deficiency state, BRCA1meth cancers are highly adaptive to genotoxin exposure and, through reversal of promoter methylation, recover BRCA1 expression and become resistant to therapy. We further found a specific augmented immune transcriptional signal associated with enhanced response to platinum chemotherapy but only in patients with BRCA-proficient cancers. We showed how integrating both this cancer immune signature and the presence of BRCA mutations results in more accurate predictions of patient response when compared to either HRD status or BRCA status alone. This underscores the importance of defining BRCA heterogeneity in optimizing the predictive precision of assigning response probabilities in TNBC and OvCa

Shallow burial dolomitisation of Middle–Upper Permian paleosols in an extensional tectonic context (SE Iberian Basin, Spain): Controls on temperature of precipitation and source of fluids

This work is focused on carbonate paleosols developed in three stratigraphic sections (Landete, Talayuelas and Henarejos) of theMiddle–Late Permian Alcotas Formation in the SE Iberian Basin. The Alcotas Formation, of alluvial origin, was deposited in semi-connected half-grabens developed during the early stages of the Permian–Triassic rifting stage that affected the Iberian Basin. The studied sections were located in two of these half-grabens, the Henarejos section being much closer to the basin boundary fault than the other two sections. The mineralogy and texture of the carbonate precursor of paleosols in the three studied sections are not preserved because original carbonate is replaced by coarse crystals of dolomite and/or magnesite. Dolomite crystals are typically euhedral, displaying rhombohedral shapes and reddish luminescence, although in the Henarejos section dolomite displays non-planar boundaries and frequently saddle habit. Micas are deformed and adapted to dolomite crystals, which, in turn, are affected by stylolites, suggesting that dolomite precipitated before mechanical and chemical compaction. Carbon and oxygen isotopic compositions of dolomite fromthe three sections showdifferent values (δ13CVPDB mean values=−6.7‰,−5.5‰ and −7.5‰; δ18OVPDB mean values=−4.0‰; –5.6‰and−8.2‰, at Landete, Talayuelas and Henarejos sections, respectively). The 87Sr/86Sr ratios are similar in the three sections yielding values between 0.71391 and 0.72213. The petrographic and geochemical features of dolomite in the three studied sections suggest precipitation fromsimilar fluids and during shallow burial diagenesis. Assuming that theminimum temperature for dolomite precipitation in the Henarejos sectionwas 60 °C (as suggested by the presence of non-planar saddle habit), and that the dolomitizing fluid had similar δ18O values at the three localities, then dolomite in the Talayuelas and Landete sections precipitated at temperatures around 16 and 25 °C cooler, respectively. In addition, the δ18OVSMOW values of the water from which dolomite precipitated would have ranged between −0.3 and −2.9‰. Dolomite is partially or totally replaced by non- to dark dull luminescent magnesite in the Landete and Talayuelas sections. Magnesite crystals are affected by stylolites, indicating that it precipitated before chemical compaction. The δ13C mean values are −6.5 and −6.0‰ and the δ18OVPDB mean values are −6.7 and −7.8‰, in the Landete and Talayuelas sections, respectively. The 87Sr/86Sr ratios of magnesite are similar in both sections yielding values between 0.71258 and 0.72508. This suggests that they probably precipitated from similar fluids during progressive burial and at higher temperatures than dolomites at the same sections. Assuming thatmagnesite precipitated froma fluid with similar δ18O values in both sections, then it had to precipitate at a temperature around 8 °C higher in Talayuelas than in the Landete section. Dolomitisation and magnesite precipitation probably occurred via reflux of saline to hypersaline brines from the overlying Mid-Late Triassic Muschelkalk and/or Keuper facies. The temperatures inferred for dolomite precipitation, however, are too high for shallow burial if a normal geothermal gradient is applied. Thus, it can be inferred that salinefluidswere heated as theyflowed through the syn-sedimentary extensional faults that controlledMiddle Permian to Middle Triassic sedimentation; consequently fluidswould have been at higher temperatures near the Henarejos area, which was closer to the basin boundary fault than at the Talayuelas and Landete areas, whichwere situated further away. This contention is in agreement with recent studies which demonstrate that an important thermal event took place during Late Triassic–Early Jurassic times in the Iberian Peninsula