Spatial Organization of the Cytoskeleton enhances Cargo Delivery to Specific Target Areas on the Plasma Membrane of Spherical Cells

Intracellular transport is vital for the proper functioning and survival of a cell. Cargo (proteins, vesicles, organelles, etc.) is transferred from its place of creation to its target locations via molecular motor assisted transport along cytoskeletal filaments. The transport efficiency is strongly affected by the spatial organization of the cytoskeleton, which constitutes an inhomogeneous, complex network. In cells with a centrosome microtubules grow radially from the central microtubule organizing center towards the cell periphery whereas actin filaments form a dense meshwork, the actin cortex, underneath the cell membrane with a broad range of orientations. The emerging ballistic motion along filaments is frequently interrupted due to constricting intersection nodes or cycles of detachment and reattachment processes in the crowded cytoplasm. In order to investigate the efficiency of search strategies established by the cell's specific spatial organization of the cytoskeleton we formulate a random velocity model with intermittent arrest states. With extensive computer simulations we analyze the dependence of the mean first passage times for narrow escape problems on the structural characteristics of the cytoskeleton, the motor properties and the fraction of time spent in each state. We find that an inhomogeneous architecture with a small width of the actin cortex constitutes an efficient intracellular search strategy.Comment: 14 pages, 9 figure

Discovery of a ~5 day characteristic timescale in the Kepler power spectrum of Zw 229-15

We present time series analyses of the full Kepler dataset of Zw 229-15. This Kepler light curve --- with a baseline greater than three years, composed of virtually continuous, evenly sampled 30-minute measurements --- is unprecedented in its quality and precision. We utilize two methods of power spectral analysis to investigate the optical variability and search for evidence of a bend frequency associated with a characteristic optical variability timescale. Each method yields similar results. The first interpolates across data gaps to use the standard Fourier periodogram. The second, using the CARMA-based time-domain modeling technique of Kelly et al. (2014), does not need evenly-sampled data. Both methods find excess power at high frequencies that may be due to Kepler instrumental effects. More importantly both also show strong bends ({\Delta}{\alpha} ~ 2) at timescales of ~5 days, a feature similar to those seen in the X-ray PSDs of AGN but never before in the optical. This observed ~5 day timescale may be associated with one of several physical processes potentially responsible for the variability. A plausible association could be made with light-crossing, dynamical or thermal timescales, depending on the assumed value of the accretion disk size and on unobserved disk parameters such as {\alpha} and H/R. This timescale is not consistent with the viscous timescale, which would be years in a ~10^7 Solar mass AGN such as Zw 229-15. However there must be a second bend on long (>~1 year) timescales, and that feature could be associated with the viscous timescale.Comment: 10 pages, 5 figures, 1 table. To appear in the Astrophysical Journal, Part

Alteration of cerebrovascular haemodynamic patterns due to atrial fibrillation: an in silico investigation

There has recently been growing evidence that atrial fibrillation (AF), the most common cardiac arrhythmia, is independently associated with the risk of dementia. This represents a very recent frontier with high social impact for the number of individuals involved and for the expected increase in AF incidence in the next 40 years. Although a number of potential haemodynamic processes, such as microembolisms, altered cerebral blood flow, hypoperfusion and microbleeds, arise as connecting links between the two pathologies, the causal mechanisms are far from clear. An in silico approach is proposed that combines in sequence two lumped-parameter schemes, for the cardiovascular system and the cerebral circulation. The systemic arterial pressure is obtained from the cardiovascular system and used as the input for the cerebral circulation, with the aim of studying the role of AF on the cerebral haemodynamics with respect to normal sinus rhythm (NSR), over a 5000 beat recording. In particular, the alteration of the haemodynamic (pressure and flowrate) patterns in the microcirculation during AF is analysed by means of different statistical tools, from correlation coefficients to autocorrelation functions, crossing times, extreme values analysis and multivariate linear regression models. A remarkable signal alteration, such as a reduction in signal correlation (NSR, about 3 s; AF, less than 1 s) and increased probability (up to three to four times higher in AF than in NSR) of extreme value events, emerges for the peripheral brain circulation. The described scenario offers a number of plausible cause-effect mechanisms that might explain the occurrence of critical events and the haemodynamic links relating to AF and dementia.Comment: 13 pages, 9 Figures, 3 Table

Search for domain wall dark matter with atomic clocks on board global positioning system satellites

Cosmological observations indicate that 85% of all matter in the Universe is dark matter (DM), yet its microscopic composition remains a mystery. One hypothesis is that DM arises from ultralight quantum fields that form macroscopic objects such as topological defects. Here we use GPS as a ~ 50,000 km aperture DM detector to search for such defects in the form of domain walls. GPS navigation relies on precision timing signals furnished by atomic clocks hosted on board GPS satellites. As the Earth moves through the galactic DM halo, interactions with topological defects could cause atomic clock glitches that propagate through the GPS satellite constellation at galactic velocities ~ 300 km/s. Mining 16 years of archival GPS data, we find no evidence for DM in the form of domain walls at our current sensitivity level. This allows us to improve the limits on certain quadratic scalar couplings of domain wall DM to standard model particles by several orders of magnitude.Comment: 7 pages (main text), and 12 pages for Supplementary Information. v3: Update titl

Safety Margins for Flight Through Stochastic Gusts

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140648/1/1.g000299.pd