Kinesin-1 is a molecular transporter that trafficks along microtubules. There is some evidence that kinesin-1 targets specific cellular sites, but it is unclear how this spatial regulation is achieved. To investigate this process, we used a combination of in vivo imaging of kinesin heavy-chain Kif5c (an isoform of kinesin-1) fused to GFP, in vitro analyses and mathematical modelling. GFP-Kif5c fluorescent puncta localised to a subset of microtubules in live cells. These puncta moved at speeds of up to 1 m second -1 and exchanged into cortically labelled clusters at microtubule ends. This behaviour depended on the presence of a functional motor domain, because a rigor-mutant GFP-Kif5c bound to microtubules but did not move along them. Further analysis indicated that the microtubule subset decorated by GFP-Kif5c was highly stable and primarily composed of detyrosinated tubulin. In vitro motility assays showed that the motor domain of Kif5c moved detyrosinated microtubules at significantly lower velocities than tyrosinated (unmodified) microtubules. Mathematical modelling predicted that a small increase in detyrosination would bias kinesin-1 occupancy towards detyrosinated microtubules. These data suggest that kinesin-1 preferentially binds to and trafficks on detyrosinated microtubules in vivo, providing a potential basis for the spatial targeting of kinesin-1-based cargo transport. Supplementary material available online at
Acoustic spacetimes", in which techniques of differential geometry are used to investigate sound propagation in moving fluids, have attracted considerable attention over the last few decades. Most of the models currently considered in the literature are based on non-relativistic barotropic irrotational fluids, defined in a flat Newtonian background. The extension, first to special relativistic barotropic fluid flow, and then to general relativistic barotropic fluid flow in an arbitrary background, is less straightforward than it might at first appear. In this article we provide a pedagogical and simple derivation of the general relativistic "acoustic spacetime" in an arbitrary (d+1) dimensional curved-space background.
We consider the lifetime of a T cell clonotype, the set of T cells with the same T cell receptor, from its thymic origin to its extinction in a multiclonal repertoire. Using published estimates of total cell numbers and thymic production rates, we calculate the mean number of cells per TCR clonotype, and the total number of clonotypes, in mice and humans. When there is little peripheral division, as in a mouse, the number of cells per clonotype is small and governed by the number of cells with identical TCR that exit the thymus. In humans, peripheral division is important and a clonotype may survive for decades, during which it expands to comprise many cells. We therefore devise and analyse a computational model of homeostasis of a multiclonal population. Each T cell in the model competes for self pMHC stimuli, cells of any one clonotype only recognising a small fraction of the many subsets of stimuli. A constant mean total number of cells is maintained by a balance between cell division and death, and a stable number of clonotypes by a balance between thymic production of new clonotypes and extinction of existing ones. The number of distinct clonotypes in a human body may be smaller than the total number of naive T cells by only one order of magnitude.
In this Letter we investigate the minimal conditions under which the creation of our universe might arise due to a "bounce" from a previous collapse, rather than an explosion from a big-bang singularity. Such a bounce is sometimes referred to as a Tolman wormhole. We subject the bounce to a general model-independent analysis along the lines of that applied to the Morris-Thorne traversable wormholes, and show that there is always an open temporal region surrounding the bounce over which the strong energy condition (SEC) must be violated. On the other hand, all the other energy conditions can easily be satisfied. In particular, we exhibit an inflation-inspired model in which a big bounce is "natural".Oscillating universes [1,2] are alternatives to standard big bang cosmology [3][4][5][6]. They avoid the big-bang singularity and replace it with a cyclical evolution from a previous incarnation of our present universe. Unfortunately, many of the older discussions of oscillating universes leave the nature of the turnaround quite ambiguous (cusp? angular-momentum barrier?). Interest in oscillating universes largely declined after the development of the first cosmological singularity theorem [3,4], but we feel that the time is ripe for a reassessment of the situation. In this Letter, we model the turnaround by a Friedman-Robertson-Walker (FRW) universe undergoing a "bounce" and ask what the absolute minimum requirements are for such a bounce to occur. Not too surprisingly, the strong energy condition (SEC) of classical gravity must be violated [7][8][9]. (SEC-violation is a necessary but not sufficient condition.) More surprisingly, for universes with positive spatial curvature, none of the other energy conditions need be violated. We shall present a model-independent analysis of the bounce similar to the model-independent analysis applied to the Morris-Thorne traversable wormholes [10][11][12][13][14][15], and also show with specific examples how the various cosmological singularity theorems [3,4] and their modern extensions [16][17][18][19][20] can be evaded. Finally we discuss the extent to which SEC violations are compatible with known physics, and exhibit an inflation-inspired model for which a big-bounce is "natural".A bouncing baby universe, or Tolman wormhole, is simply a FRW universe that undergoes a collapse, instant of maximum compression, and subsequent expansion (as opposed to undergoing a big crunch singularity or exhibiting a big-bang singularity). In a model-independent analysis, the key idea is to extract as much information as possible from the energy conditions without making any particular commitment to the equation of state for the matter content of the universe [10][11][12][13][14][15]. The utility of such an approach has recently been demonstrated in a different context: applying the energy conditions to the epoch of galaxy formation [21][22][23].The FRW cosmology is described by the metric [3-6]with k = +1, 0, or −1 for hyperspherical, flat, or hyperbolic spatial sections, respectively....
Motivated by the prospect of testing inflation from precision cosmic microwave background observations, we present analytic results for scalar and tensor perturbations in single-field inflation models based on the application of uniform approximations. This technique is systematically improvable, possesses controlled error bounds, and does not rely on assuming the slow-roll parameters to be constant. We provide closed-form expressions for the power spectra and the corresponding scalar and tensor spectral indices.
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