Calpain 2 Controls Turnover of LFA-1 Adhesions on Migrating T Lymphocytes

The immune cells named T lymphocytes circulate around the body fulfilling their role in immunosurveillance by monitoring the tissues for injury or infection. To migrate from the blood into the tissues, they make use of the integrin LFA-1 which is exclusively expressed by immune cells. These highly motile cells attach and migrate on substrates expressing the LFA-1 ligand ICAM-1. The molecular events signaling LFA-1 activation and adhesion are now reasonably well identified, but the process of detaching LFA-1 adhesions is less understood. The cysteine protease calpain is involved in turnover of integrin-mediated adhesions in less motile cell types. In this study we have explored the involvement of calpain in turnover of LFA-1-mediated adhesions of T lymphocytes. Using live cell imaging and immunohistochemistry, we demonstrate that turnover of adhesions depends on the Ca2+-dependent enzyme, calpain 2. Inhibition of calpain activity by means of siRNA silencing or pharmacological inhibition results in inefficient disassembly of LFA-1 adhesions causing T lymphocyte elongation and shedding of LFA-1 clusters behind the migrating T lymphocytes. We show that calpain 2 is distributed throughout the T lymphocyte, but is most active at the trailing edge as detected by expression of its fluorescent substrate CMAC,t-BOC-Leu-Met. Extracellular Ca2+ entry is essential for the activity of calpain 2 that is constantly maintained as the T lymphocytes migrate. Use of T cells from a patient with mutation in ORAI1 revealed that the major calcium-release-activated-calcium channel is not the ion channel delivering the Ca2+. We propose a model whereby Ca2+ influx, potentially through stretch activated channels, is sufficient to activate calpain 2 at the trailing edge of a migrating T cell and this activity is essential for the turnover of LFA-1 adhesions

Extremal Optimization at the Phase Transition of the 3-Coloring Problem

We investigate the phase transition of the 3-coloring problem on random graphs, using the extremal optimization heuristic. 3-coloring is among the hardest combinatorial optimization problems and is closely related to a 3-state anti-ferromagnetic Potts model. Like many other such optimization problems, it has been shown to exhibit a phase transition in its ground state behavior under variation of a system parameter: the graph's mean vertex degree. This phase transition is often associated with the instances of highest complexity. We use extremal optimization to measure the ground state cost and the ``backbone'', an order parameter related to ground state overlap, averaged over a large number of instances near the transition for random graphs of size $n$ up to 512. For graphs up to this size, benchmarks show that extremal optimization reaches ground states and explores a sufficient number of them to give the correct backbone value after about $O(n^{3.5})$ update steps. Finite size scaling gives a critical mean degree value $\alpha_{\rm c}=4.703(28)$. Furthermore, the exploration of the degenerate ground states indicates that the backbone order parameter, measuring the constrainedness of the problem, exhibits a first-order phase transition.Comment: RevTex4, 8 pages, 4 postscript figures, related information available at http://www.physics.emory.edu/faculty/boettcher

The Extragalactic Distance Scale without Cepheids IV

The Cepheid period-luminosity relation is the primary distance indicator used in most determinations of the Hubble constant. The tip of the red giant branch (TRGB) is an alternative basis. Using the new ANU SkyMapper Telescope, we calibrate the Tully Fisher relation in the I band. We find that the TRGB and Cepheid distance scales are consistent.Comment: ApJ in press 201

Building in China - Study trip of the faculty of Civil Engineering of the HTWG Konstanz 2008

Im März 2008 führte die Fakultät Bauingenieurwesen der HTWG Konstanz eine studentische Exkursion nach China durch. Auf dem Programm standen interessante Baustellen Shanghai, Nanjing, Zhenjiang und Beijing sowie der Besuch von Hochschulen. Der Exkursionsbericht beschreibt die besuchten Bauvorhaben und gibt persönliche Eindrücke der Exkursionsteilnehmer wieder.In March 2008 the faculty of civil engineering of the University of Applied Sciences Konstanz, Germany, conducted a study trip for students of civil engineering to China. Construction sites and universities in Shanghai, Nanjing, Zhenjiang and Beijing have been visited. The report describes the places seen and reflects the personal impressions of the participants

Climate and surface mass balance of coastal West Antarctica resolved by regional climate modelling

West Antarctic climate and surface mass balance (SMB) records are sparse. To fill this gap, regional atmospheric climate modelling is useful, providing that such models are employed at sufficiently high horizontal resolution and coupled with a snow model. Here we present the results of a high-resolution (5.5 km) regional atmospheric climate model (RACMO2) simulation of coastal West Antarctica for the period 1979–2015. We evaluate the results with available in situ weather observations, remote-sensing estimates of surface melt, and SMB estimates derived from radar and firn cores. Moreover, results are compared with those from a lower-resolution version, to assess the added value of the resolution. The high-resolution model resolves small-scale climate variability invoked by topography, such as the relatively warm conditions over ice-shelf grounding zones, and local wind speed accelerations. Surface melt and SMB are well reproduced by RACMO2. This dataset will prove useful for picking ice core locations, converting elevation changes to mass changes, for driving ocean, ice-sheet and coupled models, and for attributing changes in the West Antarctic Ice Sheet and shelves to changes in atmospheric forcing

Robust abandoned object detection integrating wide area visual surveillance and social context

This paper presents a video surveillance framework that robustly and efficiently detects abandoned objects in surveillance scenes. The framework is based on a novel threat assessment algorithm which combines the concept of ownership with automatic understanding of social relations in order to infer abandonment of objects. Implementation is achieved through development of a logic-based inference engine based on Prolog. Threat detection performance is conducted by testing against a range of datasets describing realistic situations and demonstrates a reduction in the number of false alarms generated. The proposed system represents the approach employed in the EU SUBITO project (Surveillance of Unattended Baggage and the Identification and Tracking of the Owner)

Channelized melting drives thinning under a rapidly melting Antarctic ice shelf

Ice shelves play a vital role in regulating loss of grounded ice and in supplying freshwater to coastal seas. However, melt variability within ice shelves is poorly constrained and may be instrumental in driving ice shelf imbalance and collapse. High-resolution altimetry measurements from 2010 to 2016 show that Dotson Ice Shelf (DIS), West Antarctica, thins in response to basal melting focused along a single 5 km-wide and 60 km-long channel extending from the ice shelf's grounding zone to its calving front. If focused thinning continues at present rates, the channel will melt through, and the ice shelf collapse, within 40–50 years, almost two centuries before collapse is projected from the average thinning rate. Our findings provide evidence of basal melt-driven sub-ice shelf channel formation and its potential for accelerating the weakening of ice shelves

Interior pathways of the North Atlantic meridional overturning circulation

To understand how our global climate will change in response to natural and anthropogenic forcing, it is essential to determine how quickly and by what pathways climate change signals are transported throughout the global ocean, a vast reservoir for heat and carbon dioxide. Labrador Sea Water (LSW), formed by open ocean convection in the subpolar North Atlantic, is a particularly sensitive indicator of climate change on interannual to decadal timescales. Hydrographic observations made anywhere along the western boundary of the North Atlantic reveal a core of LSW at intermediate depths advected southward within the Deep Western Boundary Current (DWBC). These observations have led to the widely held view that the DWBC is the dominant pathway for the export of LSW from its formation site in the northern North Atlantic towards the Equator. Here we show that most of the recently ventilated LSW entering the subtropics follows interior, not DWBC, pathways. The interior pathways are revealed by trajectories of subsurface RAFOS floats released during the period 2003-2005 that recorded once-daily temperature, pressure and acoustically determined position for two years, and by model-simulated 'e-floats' released in the subpolar DWBC. The evidence points to a few specific locations around the Grand Banks where LSW is most often injected into the interior. These results have implications for deep ocean ventilation and suggest that the interior subtropical gyre should not be ignored when considering the Atlantic meridional overturning circulation.Dissertatio