New approaches to working time policy in Germany: The 28,8 hour working week at Volkswagen Company

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Cooperative Cargo Transport by Several Molecular Motors

The transport of cargo particles which are pulled by several molecular motors in a cooperative manner is studied theoretically. The transport properties depend primarily on the maximal number, $N$, of motor molecules that may pull simultaneously on the cargo particle. Since each motor must unbind from the filament after a finite number of steps but can also rebind to it again, the actual number of pulling motors is not constant but varies with time between zero and $N$. An increase in the maximal number $N$ leads to a strong increase of the average walking distance (or run length) of the cargo particle. If the cargo is pulled by up to $N$ kinesin motors, e.g., the walking distance is estimated to be $5^{N-1}/N$ micrometers which implies that seven or eight kinesin molecules are sufficient to attain an average walking distance in the centimeter range. If the cargo particle is pulled against an external load force, this force is shared between the motors which provides a nontrivial motor-motor coupling and a generic mechanism for nonlinear force-velocity relationships. With increasing load force, the probability distribution of the instantenous velocity is shifted towards smaller values, becomes broader, and develops several peaks. Our theory is consistent with available experimental data and makes quantitative predictions that are accessible to systematic in vitro experiments.Comment: 24 pages, latex, 6 figures, includes Supporting Tex

Monte-Carlo simulation with FLUKA for liquid and solid targets

Introduction Monte-Carlo simulations can be used to assess isotope production on small medical cyclotrons. These simulations calculate the particle interactions with electric and magnetic fields, as well as the nuclear reactions. The results can be used to predict both yields and isotopic contaminations and can aid in the optimum design of target material and target geometry [1,2]. FLUKA is a general-purpose tool widely used in many applications from accelerator shielding to target design, calorimetry, activation, dosimetry, detector design, neutrino physics, or radiotherapy [3,4]. In this work, we applied the Monte-Carlo code FLUKA to determine the accuracy of predicting yields of various isotopes as compared to experimental yields. Material and Methods The proton beam collimation system, as well as the liquid and solid target of the TR13 cyclotron at TRIUMF, has been modeled in FLUKA. The proton beam parameters were initially taken from the cyclotron design specifications and were optimized against experimental measurements from the TR13. Data from irradiations of different targets and with different beam currents were collected in order to account for average behavior, see FIG. 1. Yields for a pencil proton beam as well as a beam spread out in direction and energy have been calculated and have been compared to experimental results obtained with the TR13. Results and Conclusion The reactions listed in TABLE 1 were assessed. For most reactions a good agreement was found in the comparison between experimental and simulated saturation yield. TABLE 1 only shows the yields simulated with a proton beam with a spread in both direction and energy. In most cases, the simulated yield is slightly larger or comparable. Only the calculated yield for 55Co was significantly lower by a factor of 4.2. This is still a good agreement considering that FLUKA was originally a high-energy physics code. It may indicate that the FLUKA internal cross-section calculation for this isotope production needs some optimization. In summary, we conclude that FLUKA can be used as a tool for the prediction of isotope production as well as for target design

MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons

Microtubule-dependent transport of vesicles and organelles appears saltatory because particles switch between periods of rest, random Brownian motion, and active transport. The transport can be regulated through motor proteins, cargo adaptors, or microtubule tracks. We report here a mechanism whereby microtubule associated proteins (MAPs) represent obstacles to motors which can be regulated by microtubule affinity regulating kinase (MARK)/Par-1, a family of kinases that is known for its involvement in establishing cell polarity and in phosphorylating tau protein during Alzheimer neurodegeneration. Expression of MARK causes the phosphorylation of MAPs at their KXGS motifs, thereby detaching MAPs from the microtubules and thus facilitating the transport of particles. This occurs without impairing the intrinsic activity of motors because the velocity during active movement remains unchanged. In primary retinal ganglion cells, transfection with tau leads to the inhibition of axonal transport of mitochondria, APP vesicles, and other cell components which leads to starvation of axons and vulnerability against stress. This transport inhibition can be rescued by phosphorylating tau with MARK

Effect of the microtubule-associated protein tau on dynamics of single-headed motor proteins KIF1A

Intracellular transport based on molecular motors and its regulation are crucial to the functioning of cells. Filamentary tracks of the cells are abundantly decorated with nonmotile microtubule-associated proteins, such as tau. Motivated by experiments on kinesin-tau interactions [Dixit et al., Science 319, 1086 (2008)] we developed a stochastic model of interacting single-headed motor proteins KIF1A that also takes into account the interactions between motor proteins and tau molecules. Our model reproduces experimental observations and predicts significant effects of tau on bound time and run length which suggest an important role of tau in regulation of kinesin-based transport.publishedVersionFil: Sparacino, Javier. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Sparacino, Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Farias, María Gimena. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.Fil: Farias, María Gimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.Fil: Farias, María Gimena. Ministerio de Ciencia, Tecnología e Innovación. Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación. Fondo para la Investigación Científica y Tecnológica; Argentina.Fil: Lamberti, Pedro Walter. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Lamberti, Pedro Walter. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Otras Ciencias Física

Stochastic modeling of cargo transport by teams of molecular motors

Many different types of cellular cargos are transported bidirectionally along microtubules by teams of molecular motors. The motion of this cargo-motors system has been experimentally characterized in vivo as processive with rather persistent directionality. Different theoretical approaches have been suggested in order to explore the origin of this kind of motion. An effective theoretical approach, introduced by M\"uller et al., describes the cargo dynamics as a tug-of-war between different kinds of motors. An alternative approach has been suggested recently by Kunwar et al., who considered the coupling between motor and cargo in more detail. Based on this framework we introduce a model considering single motor positions which we propagate in continuous time. Furthermore, we analyze the possible influence of the discrete time update schemes used in previous publications on the system's dynamic.Comment: Cenference proceedings - Traffic and Granular Flow 1