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281 results on '"Mielke T"'

1. Handlungsfelder des Produktionsmanagements

Author

Anders, S., Biedermann, H., Dix, Y., Dombrowski, U., Franz, K., Gemeiner, A., Gerkens, U., Hoffmann, T., Huke, P., Intra, C., Knake, H., Krenkel, P., Meeser, M., Mielke, T., Nottbohm, H., Nyhuis, F., Opritescu, D., Patzelt, K., Rennemann, T., Richter, T., Wullbrandt, J., Zahn, T., Dombrowski, Uwe, editor, and Krenkel, Philipp, editor

Published
2021
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2. Identification and characterization of a synaptic active zone assembly protein

Author

Lützkendorf, J., primary, Matkovic-Rachid, T., additional, Götz, T., additional, Liu, S., additional, Ghelani, T., additional, Maglione, M., additional, Grieger, M., additional, Putignano, S., additional, Gao, L., additional, Gimber, N., additional, Schmoranzer, J., additional, Stawrakakis, A., additional, Walter, A.M., additional, Heine, M., additional, Wahl, M.C., additional, Mielke, T., additional, Liu, F., additional, and Sigrist, S.J., additional

Published
2024
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4. MO-0054 Quality of life results of the APROVE trial after proton beam therapy for gynecological cancer

Author

Meixner, E., primary, Wark, A., additional, Forster, T., additional, Weykamp, F., additional, Lang, K., additional, König, L., additional, Lindel, K., additional, Oelmann-Avendano, J.T., additional, Krisam, J., additional, Schneeweiss, A., additional, Ellerbrock, M., additional, Mielke, T., additional, Hörner-Rieber, J., additional, Herfarth, K., additional, Debus, J., additional, and Arians, N., additional

Published
2023
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8. SIMPLE—A modular tool for simulating complex platform trials

Author

Meyer, E.L., Mielke, T., Parke, T., Jacko, P., Koenig, F., Meyer, E.L., Mielke, T., Parke, T., Jacko, P., and Koenig, F.

Abstract

Platform trials are becoming increasingly popular within drug development, attracting interest by patients, clinicians, regulatory agencies and statisticians. More often than not, these platform trial designs are highly complex and involve many weakly predictable events (e.g. number of investigational treatments that will enter over time) to determine the impact of relevant design parameters (e.g. decision rules, sharing of information across cohorts and allocation ratios) on the operating characteristics with high confidence. Simulations may address these uncertainties at the design stage. However, the number and combination of design elements for potential implementation in real platform trials is immense. As a result, simulation software which is developed based on specific project needs is typically limited in the variety of available design options for comparison, as such software is developed for a particular need, not for researching all potential new approaches to clinical research and statistical science. On the other hand, software solutions which allow for a wide range of design options may easily overload the user with requirements for design specifications. We have developed an R software package (“SIMPLE”), which is modular in the sense that if users want to simulate the most common platform designs, minimal effort and understanding of the package is needed, but it allows the users to take control of different parts of the simulation (e.g. patient accrual, outcome simulation, etc.) step-by-step, thereby facilitating the simulation of arbitrarily complex platform trials. We will give an overview of this software package alongside some examples on how to simulate common platform trial designs and derive their operating characteristics.

Published
2023

9. T-REX17 is a transiently expressed non-coding RNA essential for human endoderm formation

Author

Landshammer, A., https://orcid.org/0000-0001-5367-3303, Bolondi, A., https://orcid.org/0000-0002-1096-9435, Kretzmer, H., https://orcid.org/0000-0002-0723-4980, Much, C., Buschow, R., https://orcid.org/0000-0002-9800-2578, Rose, A., Wu, H., Mackowiak, S., Braendl, B., Gießelmann, P., https://orcid.org/0000-0002-1227-897X, Tornisiello, R., https://orcid.org/0000-0002-6358-4934, Mohan Parsi, K., Huey, J., Mielke, T., https://orcid.org/0000-0001-9275-3146, Meierhofer, D., https://orcid.org/0000-0002-0170-868X, Maehr, R., Hnisz, D., https://orcid.org/0000-0002-6256-1693, Michor, F., Rinn, J., Meissner, A., and https://orcid.org/0000-0001-8646-7469

Abstract

Long non-coding RNAs (lncRNAs) have emerged as fundamental regulators in various biological processes, including embryonic development and cellular differentiation. Despite much progress over the past decade, the genome-wide annotation of lncRNAs remains incomplete and many known non-coding loci are still poorly characterized. Here, we report the discovery of a previously unannotated lncRNA that is transcribed 230 kb upstream of the SOX17 gene and located within the same topologically associating domain. We termed it T-REX17 (Transcript Regulating Endoderm and activated by soX17) and show that it is induced following SOX17 activation but its expression is more tightly restricted to early definitive endoderm. Loss of T-REX17 affects crucial functions independent of SOX17 and leads to an aberrant endodermal transcriptome, signaling pathway deregulation and epithelial to mesenchymal transition defects. Consequently, cells lacking the lncRNA cannot further differentiate into more mature endodermal cell types. Taken together, our study identified and characterized T-REX17 as a transiently expressed and essential non-coding regulator in early human endoderm differentiation.

Published
2023

14. Timed global reorganization of protein synthesis during neocortex neurogenesis at codon resolution

Author

Harnett, D., Ambrozkiewicz, M.C., Zinnall, U., Borisova, E., Rusanova, A., Dannenberg, R., Imami, K., Münster-Wandowski, A., Fauler, B., Mielke, T., Selbach, M., Landthaler, M., Spahn, C.M.T., Tarabykin, V., Ohler, U., and Kraushar, M.L.

Subjects
Cancer Research, nervous system, Cardiovascular and Metabolic Diseases, Function and Dysfunction of the Nervous System
Abstract

Translation modulates the timing and amplification of gene expression after transcription. Development of the brain’s neocortex requires precisely timed and spatially targeted gene expression, but the relationship between mRNA vs. protein synthesis throughout the genome is unknown. We perform a comprehensive analysis of the reactants, synthesis, and products of mRNA translation spanning mouse neocortex neurogenesis. Ribosome number in the cortical plate decreases sharply at mid-neurogenesis during a transition in neuronal subtype specification, shifting the fundamental kinetics of protein synthesis, with mRNA and protein levels frequently divergent. Satb2, which drives an essential neuronal subtype-specific program, is a highly dynamically translated mRNA with surprisingly broad transcription across diverse neuronal lineages. Satb2 protein achieves its neuronal subtype expression through timed regulation by the RNA-binding protein Pumilio2. Thus, the refinement of transcriptional programs by protein synthesis is a widespread feature of neuronal specification. Developmental neocortex translatome data are provided in an open-source resource: https://shiny.mdc-berlin.de/cortexomics/.

Published
2021

26. An experiment on the threshold effect in the coherent wave instability

Author

Mielke, T. A and Helliwell, R. A

Subjects
Geophysics
Abstract

Results are reported from an experimental study of the threshold effect in the coherent wave instability in which a combination of simulated VLF noise 200 Hz wide, superimposed on a variable amplitude constant frequency test signal (about 3 kHz) is transmitted from Siple Station, Antarctica, and received at Lake Mistissini, Quebec. As the test signal is slowly ramped up in power a 'threshold' level at which growth and triggering of emissions begin (coherent wave instability) is reached. It is shown that sufficiently strong simulated noise supresses the coherent wave instability, which corresponds to increasing the threshold level. This experiment is repeated at progressively lower levels of the simulated noise, until the threshold level for growth and triggering on the test signal no longer changes. At this point the simulated noise power is estimated to equal typical background noise levels due to magnetospheric hiss in the interaction region. It is suggested that unducted magnetospheric hiss is responsible for the threshold effect.

Published
1992

34. Current limits of structural biology: The transient interaction between cytochrome c6and photosystem I

Author

Kölsch, A., Radon, C., Golub, M., Baumert, A., Bürger, J., Mielke, T., Lisdat, F., Feoktystov, A., Pieper, J., Zouni, A., and Wendler, P.

Abstract

Trimeric photosystem I from the cyanobacterium Thermosynechococcus elongatus(TePSI) is an intrinsic membrane protein, which converts solar energy into electrical energy by oxidizing the soluble redox mediator cytochrome c6(Cyt c6) and reducing ferredoxin. Here, we use cryo-electron microscopy and small angle neutron scattering (SANS) to characterize the transient binding of Cyt c6to TePSI. The structure of TePSI cross-linked to Cyt c6was solved at a resolution of 2.9 Å and shows additional cofactors as well as side chain density for 84% of the peptide chain of subunit PsaK, revealing a hydrophobic, membrane intrinsic loop that enables binding of associated proteins. Due to the poor binding specificity, Cyt c6could not be localized with certainty in our cryo-EM analysis. SANS measurements confirm that Cyt c6does not bind to TePSI at protein concentrations comparable to those for cross-linking. However, SANS data indicate a complex formation between TePSI and the non-native mitochondrial cytochrome from horse heart (Cyt cHH). Our study pinpoints the difficulty of identifying very small binding partners (less than 5% of the overall size) in EM structures when binding affinities are poor. We relate our results to well resolved co-structures with known binding affinities and recommend confirmatory methods for complexes with KMvalues higher than 20 μM.

Published
2020
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35. Cryo-Electron Microscopic Structure of SecA Bound to the 70S Ribosome

Author

Singh, R., Kraft, C., Jaiswal, R., Sejwal, K., Kasaragod, V.B., Kuper, J., Berger, J., Mielke, T., Luirink, J., Bhushan, S., Molecular Microbiology, AIMMS, and LaserLaB - Analytical Chemistry and Spectroscopy

Subjects
bacteria, environment and public health
Abstract

Background: SecA targets preproteins to the protein-conducting channel in bacteria. Results: Both the single and double copies of SecA bind to the 70S ribosome. Conclusion: Two copies of SecA completely surround the polypeptide tunnel exit. Significance: The structures suggest a function of the dimeric form of SecA on the ribosome. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Published
2014
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38. Mammalian 40S HCV-IRES complex

Author

Yamamoto, H., primary, Collier, M., additional, Loerke, J., additional, Ismer, J., additional, Schmidt, A., additional, Hilal, T., additional, Sprink, T., additional, Yamamoto, K., additional, Mielke, T., additional, Burger, J., additional, Shaikh, T.R., additional, Dabrowski, M., additional, Hildebrand, P.W., additional, Scheerer, P., additional, and Spahn, C.M.T., additional

Published
2015
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42. Structure of the ribosome-bound cricket paralysis virus IRES RNA

Author

Schüler, M., Connell, S., Lescoute, A., Giesebrecht, J., Dabrowski, M., Schroeer, B., Mielke, T., Penczek, P., Westhof, E., and Spahn, C.

Subjects
fungi
Abstract

Internal ribosome entry sites (IRESs) facilitate an alternative, end-independent pathway of translation initiation. A particular family of dicistroviral IRESs can assemble elongation-competent 80S ribosomal complexes in the absence of canonical initiation factors and initiator transfer RNA. We present here a cryo-EM reconstruction of a dicistroviral IRES bound to the 80S ribosome. The resolution of the cryo-EM reconstruction, in the subnanometer range, allowed the molecular structure of the complete IRES in its active, ribosome-bound state to be solved. The structure, harboring three pseudoknot-containing domains, each with a specific functional role, shows how defined elements of the IRES emerge from a compactly folded core and interact with the key ribosomal components that form the A, P and E sites, where tRNAs normally bind. Our results exemplify the molecular strategy for recruitment of an IRES and reveal the dynamic features necessary for internal initiation.

Published
2006

46. Model of the small subunit RNA based on a 5.5 A cryo-EM map of Triticum aestivum translating 80S ribosome

Author

Barrio-Garcia, C., primary, Armache, J.-P., additional, Jarasch, A., additional, Anger, A.M., additional, Villa, E., additional, Becker, T., additional, Bhushan, S., additional, Jossinet, F., additional, Habeck, M., additional, Dindar, G., additional, Franckenberg, S., additional, Marquez, V., additional, Mielke, T., additional, Thomm, M., additional, Berninghausen, O., additional, Beatrix, B., additional, Soeding, J., additional, Westhof, E., additional, Wilson, D.N., additional, and Beckmann, R., additional

Published
2014
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47. tRNA tranlocation on the 70S ribosome: the pre-translocational translocation intermediate TI(PRE)

Author

Ratje, A.H., primary, Loerke, J., additional, Mikolajka, A., additional, Bruenner, M., additional, Hildebrand, P.W., additional, Starosta, A.L., additional, Doenhoefer, A., additional, Connell, S.R., additional, Fucini, P., additional, Mielke, T., additional, Whitford, P.C., additional, Onuchic, J.N., additional, Yu, Y., additional, Sanbonmatsu, K.Y., additional, Hartmann, R.K., additional, Penczek, P.A., additional, Wilson, D.N., additional, and Spahn, C.M.T., additional

Published
2014
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49. Localization of the small subunit ribosomal proteins into a 6.1 A cryo-EM map of Saccharomyces cerevisiae translating 80S ribosome

Author

Armache, J.-P., primary, Jarasch, A., additional, Anger, A.M., additional, Villa, E., additional, Becker, T., additional, Bhushan, S., additional, Jossinet, F., additional, Habeck, M., additional, Dindar, G., additional, Franckenberg, S., additional, Marquez, V., additional, Mielke, T., additional, Thomm, M., additional, Berninghausen, O., additional, Beatrix, B., additional, Soeding, J., additional, Westhof, E., additional, Wilson, D.N., additional, and Beckmann, R., additional

Published
2014
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