Cooperative transport by small teams of molecular motors

Molecular motors power directed transport of cargoes within cells. Even if a single motor is sufficient to transport a cargo, motors often cooperate in small teams. We discuss the cooperative cargo transport by several motors theoretically and explore some of its properties. In particular we emphasize how motor teams can drag cargoes through a viscous environment.Comment: 9 pages, 1 figure, uses ws-brl.cls, presented at Bio-Systems conference, Berlin, June 200

Stability and magnetic properties of Fe double-layers on Ir (111)

We investigate the interplay between the structural reconstruction and the magnetic properties of Fe doublelayers on Ir (111)-substrate using first-principles calculations based on density functional theory and mapping of the total energies on an atomistic spin model. We show that, if a second Fe monolayer is deposited on Fe/Ir (111), the stacking may change from hexagonal close-packed to bcc (110)-like accompanied by a reduction of symmetry from trigonal to centered rectangular. Although the bcc-like surface has a lower coordination, we find that this is the structural ground state. This reconstruction has a major impact on the magnetic structure. We investigate in detail the changes in the magnetic exchange interaction, the magnetocrystalline anisotropy, and the Dzyaloshinskii Moriya interaction depending on the stacking sequence of the Fe double-layer. Based on our findings, we suggest a new technique to engineer Dzyaloshinskii Moriya interactions in multilayer systems employing symmetry considerations. The resulting anisotropic Dzyaloshinskii-Moriya interactions may stabilize higher-order skyrmions or antiskyrmions

Tug-of-war as a cooperative mechanism for bidirectional cargo transport by molecular motors

Intracellular transport is based on molecular motors that pull cargos along cytoskeletal filaments. One motor species always moves in one direction, e.g. conventional kinesin moves to the microtubule plus end, while cytoplasmic dynein moves to the microtubule minus end. However, many cellular cargos are observed to move bidirectionally, involving both plus-end and minus-end directed motors. The presumably simplest mechanism for such bidirectional transport is provided by a tug-of-war between the two motor species. This mechanism is studied theoretically using the load-dependent transport properties of individual motors as measured in single-molecule experiments. In contrast to previous expectations, such a tug-of-war is found to be highly cooperative and to exhibit seven different motility regimes depending on the precise values of the single motor parameters. The sensitivity of the transport process to small parameter changes can be used by the cell to regulate its cargo traffic.Comment: 17 pages, latex, 11 figures, 4 tables, includes Supporting Informatio

Gaussian entanglement distribution with gigahertz bandwidth

The distribution of entanglement with Gaussian statistic can be used to generate a mathematically-proven secure key for quantum cryptography. The distributed secret key rate is limited by the {entanglement strength, the entanglement bandwidth and the bandwidth of the photo-electric detectors}. The development of a source for strongly, bi-partite entangled light with high bandwidth promises an increased measurement speed and a linear boost in the secure data rate. Here, we present the experimental realization of a Gaussian entanglement source with a bandwidth of more than 1.25\,GHz. The entanglement spectrum was measured with balanced homodyne detectors and was quantified via the inseparability criterion introduced by Duan and coworkers with a critical value of 4 below which entanglement is certified. Our measurements yielded an inseparability value of about 1.8 at a frequency of 300\,MHz to about 2.8 at 1.2\,GHz extending further to about 3.1 at 1.48\,GHz. In the experiment we used two 2.6\,mm long monolithic periodically poled potassium titanyl phosphate (PPKTP) resonators to generate two squeezed fields at the telecommunication wavelength of 1550\,nm. Our result proves the possibility of generating and detecting strong continuous-variable entanglement with high speed.Comment: 5 pages, 3 figures, published in Optics Letter

Structural Analysis and Stochastic Modelling Suggest a Mechanism for Calmodulin Trapping by CaMKII

Activation of CaMKII by calmodulin and the subsequent maintenance of constitutive activity through autophosphorylation at threonine residue 286 (Thr286) are thought to play a major role in synaptic plasticity. One of the effects of autophosphorylation at Thr286 is to increase the apparent affinity of CaMKII for calmodulin, a phenomenon known as “calmodulin trapping”. It has previously been suggested that two binding sites for calmodulin exist on CaMKII, with high and low affinities, respectively. We built structural models of calmodulin bound to both of these sites. Molecular dynamics simulation showed that while binding of calmodulin to the supposed low-affinity binding site on CaMKII is compatible with closing (and hence, inactivation) of the kinase, and could even favour it, binding to the high-affinity site is not. Stochastic simulations of a biochemical model showed that the existence of two such binding sites, one of them accessible only in the active, open conformation, would be sufficient to explain calmodulin trapping by CaMKII. We can explain the effect of CaMKII autophosphorylation at Thr286 on calmodulin trapping: It stabilises the active state and therefore makes the high-affinity binding site accessible. Crucially, a model with only one binding site where calmodulin binding and CaMKII inactivation are strictly mutually exclusive cannot reproduce calmodulin trapping. One of the predictions of our study is that calmodulin binding in itself is not sufficient for CaMKII activation, although high-affinity binding of calmodulin is

Analysing welfare reform in a microsimulation-AGE model: the value of disaggregation

We present a combined, consistent microsimulation-AGE model that uses the labour market model PACE-L, data from the German Socio-Economic Panel and a discrete choice labour supply estimation. The model is used to analyse a reform that cuts the social assistance minimum income and lowers the transfer withdrawal rate in order to encourage labour force participation at the lower end of the wage distribution. We compare a disaggregated and an aggregated version of the model as well as a partial and a general equilibrium variant. It turns out that both disaggregation and general equilibrium feedback tend to mitigate the labour supply response to the reform proposal. While some labour supply indicators react quite sensitively to the level of aggregation, most macroeconomic variables are considerably more robust. --applied general equilibrium,discrete working time choice,labour market,wage bargaining,labour market reform,logit model,microsimulation

Multi-Stage Modeling of the Kinetics of Activation of CaMKII

Ca 2+ /calmodulin-dependent protein kinase 2 (CaMKII) plays an important role in induction of long-term potentiation and formation of memory. It is abundant in dendritic spines, and is activated when Ca 2+ flows into the postsynaptic cytosol through open NMDA-type glutamate receptors. Its function is fine-tuned through interaction with other proteins as well as through subunit interactions and regulatory autophosphorylation. We have undertaken a multi-stage project to study the critical kinetics of activation of CaMKII in the spine by combining modeling and experimental studies. We are using computational modeling and simulations on various platforms, coupled with biochemical experiments in vitro, and eventually in vivo, to understand CaMKII regulation. The project includes the following steps: 1. Determining the parameters governing activation of a monomeric subunit. The CaMKII holoenzyme is a large dodecamer of similar, homologous subunits held together by interactions between the association domains located at the carboxyl end of each subunit. Individual, monomeric subunits can be expressed recombinantly by removing the association domain. Computer simulations of activation of monomeric CaMKII by Ca 2+ /calmodulin at both saturating and non-saturating concentrations in a test tube have helped to identify the binding parameters that are most crucial for modeling of regulation of CaMKII and thus have indicated the most useful biochemical assays to measure those parameters (Pepke et al., 2010). We are using these measurements to fine-tune our model of activation of individual catalytic subunits. 2. Building a model of the holoenzyme. Because a CaMKII holoenzyme contains 12 similar subunits, each of which can exist in several states, the holoenzyme can have a large number of state combinations. Thus, modeling the entire holoenzyme requires a computational framework that avoids the ensuing combinatorial complexity. The stochastic simulator MCell provides an elegant, rule-based way of modeling state changes in the CaMKII holoenzyme. 3. Modeling cooperativity that arises from the dodecameric structure of CaMKII. Autophosphorylation at threonine-286, which activates CaMKII subunits, is an inter-subunit event. Thus, it is greatly facilitated by the close proximity of subunits in the holoenzyme. In addition, the subunits within the holoenzyme are arranged as dimers which appears to result in cooperativity in the binding of Ca 2+ /CaM to individual subunits of the dimer (Chao et al., 2010). An accurate model of activation of subunits in the holoenzyme and their autophosphorylation will allow us to explore the effects of cooperativity on CaMKII activation on various time scales. 4. Modeling CaMKII within the context of a postsynaptic spine CaMKII interacts with a variety of other proteins, both in the postsynaptic density (PSD), close to major sources of Ca 2+ influx, and in other parts of the spine. In the fourth stage of this project we plan to implement kinetic models of activation of CaMKII in the context of an MCell model of Ca 2+ influx into a spine upon activation of NMDA-type glutamate receptors (Keller et al., 2008; Keller et al., 2011, submitted). We will explore the effects of different localization and numbers of CaMKII holoenzymes in the spine on CaMKII activation. References: Pepke, S., Kinzer-Ursem, T., Mihalas, S., and Kennedy, M.B. (2010). A dynamic model of interactions of Ca 2+ , calmodulin, and catalytic subunits of Ca 2+ /calmodulin-dependent protein kinase II. PLoS Comput Biol 6, e1000675. Chao, L.H., Pellicena, P., Deindl, S., Barclay, L.A., Schulman, H., and Kuriyan, J. (2010). Intersubunit capture of regulatory segments is a component of cooperative CaMKII activation. Nat Struct Mol Biol 17, 264-272. Keller, D.X., Franks, K.M., Bartol, T.M., Jr., and Sejnowski, T.J. (2008). Calmodulin activation by calcium transients in the postsynaptic density of dendritic spines. PLoS ONE 3, e2045. Keller, D.X., Bartol, T.M., Kinney, J.P, Kennedy, M.B., Bajaj, C., Harris, K.M., and Sejnowski, T.J. Regulation of synaptic calcium transients in reconstructed dendritic spines of hippocampal CA1 pyramidal neurons, submitted

Aktienrecht zwischen börsen- und kapitalmarktorientiertem Ansatz

Auf dem 67. Deutschen Juristentag (DJT) in Erfurt wurde über eine Grundfrage des deutschen Aktienrechts diskutiert. Gefordert wurde eine stärkere Differenzierung zwischen börsennotierten und nichtbörsennotierten Aktiengesellschaften. Einzelne Deregulierungsvorschläge bezogen sich in diesem Zusammenhang auf die Reichweite des Prinzips der Satzungsstrenge, die Vinkulierung von Aktien und das Mehrstimmrecht. Die folgende Ausarbeitung beschäftigt sich mit der Frage, ob eine Differenzierung zwischen börsennotierten und nichtbörsennotierten Aktiengesellschaften insbesondere vor dem Hintergrund einer rechtsvergleichenden und empirischen Betrachtung überzeugt. Im Einzelnen wird zunächst kurz der Vorschlag Bayer an dem 67. DJT dargestellt (II.). Weiter wird die Bedeutung des außerbörslichen Handels in Deutschland untersucht (III.). Im Anschluss werden das deutsche, englische und – kursorisch – das US-amerikanische Aktien- und Kapitalmarktrecht rechtsvergleichend betrachtet (IV.). Dem folgt eine Stellungnahme zum Reformvorschlag Bayer (V.). Ein Fazit schließt die Untersuchung ab (VI.)

Abmahnung von GmbH-Geschäftsführern in befristeten Anstellungsverhältnissen

Befristete Anstellungsverhältnisse enden, sofern keine andere vertragliche Vereinbarung getroffen wurde, mit Ende der Laufzeit nach § 620 Abs. 1 BGB oder durch außerordentliche Kündigung gemäß § 626 BGB. Liegt kein wichtiger Grund im Sinne des § 626 BGB vor, kann allenfalls die erfolglose Abmahnung eine vorzeitige Beendigung des Anstellungsverhältnisses ermöglichen. Es sprechen keine zwingenden Gründe dafür, die Abmahnung nicht auch auf einen Geschäftsführer anzuwenden. Etwas anderes ergibt sich auch nicht aus § 14 Abs. 1 Nr. 1 KSchG und der mittlerweile gefestigten Rechtsprechung des Bundesgerichtshofes. Diese Rechtsprechung bezieht sich nicht auf den hier erörterten Fall der Pflichtverletzung unterhalb der Schwelle des § 626 BGB. Bei der Frage nach der konkreten Anwendung müssen grundsätzlich zwei Fallkonstellationen unterschieden werden: Im ersten Fall, in dem der Geschäftsführer zunächst nach § 38 GmbHG abberufen wurde, sein Anstellungsverhältnis jedoch weiterhin fortbesteht, kann der Geschäftsführer nur dann abgemahnt werden, wenn dieser nach seiner Abberufung gegen eine nachwirkende Pflicht verstößt und diese Pflichtverletzung nicht ausreicht, um ihn gemäß § 626 BGB fristlos zu kündigen. Wird der Geschäftsführer im Zusammenhang mit der Beendigung seines Organverhältnisses auf eine Stelle unterhalb der Geschäftsführerebene versetzt, findet die Abmahnung nach den allgemeinen Grundsätzen auf zukünftige Pflichtverstöße Anwendung. Wird ein Geschäftsführer trotz einer Pflichtverletzung im Organverhältnis belassen, steht einer Abmahnung ebenfalls kein Hinderungsgrund entgegen. Bei der durch die Abwägung nach § 314 Abs. 2 Satz 2 i. V. m. § 323 Abs. 2 Nr. 3 BGB vorgeschriebenen Berücksichtigung der beiderseitigen Interessen zeigt sich, dass das Rechtsinstitut der Abmahnung in der angesprochenen Konstellation ein geeignetes Instrument des Interessenausgleichs darstellt, auf das im Interesse beider Parteien zunächst zurückgegriffen werden sollte

Analysing Welfare Reform in a Microsimulation-AGE Model

We present a fully integrated microsimulation-AGE model that uses the labour market model PACE-L and data from the German Socio-Economic Panel. We use the model to analyse reform proposals designed to encourage labour force participation at the lower end of the wage distribution. A special focus of this paper is on comparing the fully disaggregated version of the model with more aggregated ones in order to pin down in which respects disaggregation can actually further our insights, and in which respects aggregation can be justifiedapplied general equilibrium, discrete working time choice, labour market, wage bargaining, labour market reform, logit model