Step-wise assembly, maturation and dynamic behavior of the human CENP-P/O/R/Q/U kinetochore sub-complex

Kinetochores are multi-protein megadalton assemblies that are required for attachment of microtubules to centromeres and, in turn, the segregation of chromosomes in mitosis. Kinetochore assembly is a cell cycle regulated multi-step process. The initial step occurs during interphase and involves loading of the 15-subunit constitutive centromere associated complex (CCAN), which contains a 5-subunit (CENP-P/O/R/Q/U) sub-complex. Here we show using a fluorescent three-hybrid (F3H) assay and fluorescence resonance energy transfer (FRET) in living mammalian cells that CENP-P/O/R/Q/U subunits exist in a tightly packed arrangement that involves multifold protein-protein interactions. This sub-complex is, however, not pre-assembled in the cytoplasm, but rather assembled on kinetochores through the step-wise recruitment of CENP-O/P heterodimers and the CENP-P, -O, -R, -Q and -U single protein units. SNAP-tag experiments and immuno-staining indicate that these loading events occur during S-phase in a manner similar to the nucleosome binding components of the CCAN, CENP-T/W/N. Furthermore, CENP-P/O/R/Q/U binding to the CCAN is largely mediated through interactions with the CENP-N binding protein CENP-L as well as CENP-K. Once assembled, CENP-P/O/R/Q/U exchanges slowly with the free nucleoplasmic pool indicating a low off-rate for individual CENP-P/O/R/Q/U subunits. Surprisingly, we then find that during late S-phase, following the kinetochore-binding step, both CENP-Q and -U but not -R undergo oligomerization. We propose that CENP-P/O/R/Q/U self-assembles on kinetochores with varying stoichiometry and undergoes a pre-mitotic maturation step that could be important for kinetochores switching into the correct conformation necessary for microtubule-attachment

Digitalisierung beruflicher Lern- und Arbeitsprozesse. Impulse aus der Bauwirtschaft und anderen gewerblich-technischen Sektoren

Der Sammelband stellt aktuelle Ansätze zum digital unterstützten beruflichen Lernen dar. Die Beiträge geben Einblicke in die dynamische Entwicklung der Schnittstellen von Erwerbsarbeit und beruflicher Aus-, Fort- und Weiterbildung im Kontext der Digitalisierung Arbeits- und Lernmitteln. Der Band schließt damit an die 2019 ebenfalls im Universitätsverlag der Technischen Universität Berlin erschienene Publikation „Berufsbildung am Bau digital“ (hrsg. von Bernd Mahrin und Johannes Meyser) an. Das erste Kapitel erörtert grundsätzliche didaktische Fragen zu digital unterstütztem Lernen und Arbeiten einschließlich der Rahmenbedingungen. Im zweiten Kapitel schließen sich Beiträge zur Kapazitätsentwicklung, zu Standards und zu digitalen Werkzeugen an. Das dritte Kapitel widmet sich konkreten Einzellösungen mit starkem Praxisbezug und hohem Transferpotenzial zum digitalisierten Arbeiten und Lernen im Bausektor und im Metallbereich. Das abschließende vierte Kapitel präsentiert übergreifend nutzbare und frei zugängliche Online-Angebote wie einen Medienpool für Bildungszwecke, eine Lernmedien-Datenbank und ein hybrides Lernsystem mit virtuellem 3D-Gebäudemodell. Das Buch ist entstanden im Rahmen des durch das Bundesministerium für Bildung und Forschung und den Europäischen Sozialfonds geförderten Projektes DigiBAU – Digitales Bauberufliches Lernen und Arbeiten. (DIPF/Orig.)The anthology presents current approaches to digitally supported professional learning. The articles provide insights into the dynamic development of the interfaces between gainful employment and vocational training and further education in the context of digitization of work and learning aids. The volume is thus connected to the publication “Berufsbildung am Bau digital” (edited by Bernd Mahrin and Johannes Meyser), which was published in 2019 by the University Press of the Technische Universität Berlin. The first chapter discusses fundamental didactic questions about digitally supported learning and working, including the framework conditions. The second chapter picks contributions on capacity development, standards, and digital tools out as central themes. The third chapter is dedicated to concrete specific solutions with strong practical relevance and high transfer potential for digitized work and learning in the construction sector and in the metal sector. The final fourth chapter presents comprehensive and freely accessible online offers such as a media pool for educational purposes, a learning media database and a hybrid learning system with a virtual 3D building model. The book was created as part of the DigiBAU project - digital vocational learning and working in the field of construction - funded by the German Federal Ministry of Education and Research and the European Social Fund. (DIPF/Orig.

Moral mid-level principles in modeling

Modelers, especially in operational research, are becoming increasingly aware that their role in decision-making raises moral problems. This paper discusses two questions: How do moral issues in modeling arise? How can these moral issues be addressed? I propose a framework that (1) provides tools for discovering moral issues raised by models, and (2) provides practical guidance for solving moral problems in modeling. As regards (1), I discuss three moral perspectives on modeling: a perspective that focuses on the beneficial or harmful consequences of using a model; a perspective that focuses on the intentions of using a model; and a perspective that focuses on whether a model promotes virtuous behavior. In order to achieve practical action guidance, (2), four moral mid-level principles are introduced: (i) The principle of transparency expresses the obligations to explain the structure, assumptions and further properties of the model; (ii) the principle of integrity demands for the application of professional standards; (iii) the principle of comprehensiveness stresses that all moral concerns should be acknowledged thoroughly; and finally, (iv) the principle of efficacy states that models should evaluate moral issues explicitly

On Common Intervals with Errors

Chauve C, Diekmann Y, Heber S, Mixtacki J, Rahmann S, Stoye J. On Common Intervals with Errors. Forschungsberichte. Bielefeld: Technische Fakultät der Universität Bielefeld; 2006.The information that groups of genes co-occur in several genomes provides a basis for further comparative genomic analysis. The task of finding such constellations, mostly referred to as gene clusters, has led to various models of increasing generality. A central feature to enhance the biological relevance of their definition when applied to real genomic data is to allow for slight differences in the gene content within a cluster, thus not only considering groups of exact equality. We contribute a model defining gene clusters as common intervals with errors and discuss different representations and the corresponding problems resulting for the search procedure

Influence of Substrate Electronic Properties on the Integrity and Functionality of an Adsorbed Fe(II) Spin-Crossover Compound

The bistability of spin-crossover complexes on surfaces is of great interest for potential applications. Using X-ray absorption spectroscopy, we investigated the properties of [Fe(pypyr(CF$_3$)$_2$)$_2$(phen)] (pypyr = 2-(2′-pyridyl)pyrrolide, phen = 1,10-phenanthroline), a vacuum-evaporable Fe(II) complex, in direct contact to a set of substrates. The electronic properties of these substrates range from metallic to semiconducting. While dissociation is observed on metal surfaces, efficient light-induced switching is realized on semimetallic and semiconducting surfaces. This indicates that the density of states of the substrate at the Fermi level plays a role for the integrity and functionality of the adsorbed compound. In an intermediate case, namely, [Fe(pypyr(CF$_3$)$_2$)$_2$(phen)] on graphene/Ni(111), functional and dissociated species are found to coexist. This result indicates that some previous studies may deserve to be reconsidered because the possibility of coexisting intact and fragmented spin-crossover complexes was neglected

Fractionation of 230Th, 231Pa, and 10Be induced by particle size and composition within an opal-rich sediment of the Atlantic Southern Ocean

This study centers on the question: How sensitive are 231Pa/230Th and 10Be/230Th to sediment composition and redistribution? The natural radionuclides 231Pa, 230Th and 10Be recorded in deep sea sediments are tracers for water mass advection and particle fluxes. We investigate the influence of oceanic particle composition on the element adsorption in order to improve our understanding of sedimentary isotope records. We present new data on particle size specific 231Pa and 10Be concentrations. An additional separation step, based on settling velocities, led to the isolation of a very opal-rich phase. We find that opal-rich particles contain the highest 231Pa and 10Be concentrations, and higher 231Pa/230Th and 10Be/230Th isotope ratios than opal-poor particles. The fractionation relative to 230Th induced by the adsorption to opal-rich particles is more pronounced for 231Pa than for 10Be. We conclude that bulk 231Pa/230Th in Southern Ocean sediments is most suitable as a proxy for past opal fluxes. The comparison between two neighboring cores with rapid and slow accumulation rates reveals that these isotope ratios are not influenced significantly by the intensity of sediment focusing at these two study sites. However, a simulation shows that particle sorting by selective removal of sediment (winnowing) could change the isotope ratios. Consequently, 231Pa/230Th should not be used as paleocirculation proxy in cases where a strong loss of opal-rich material due to bottom currents occurred