The role of annexin II in vesicle traffic

The annexins are a family of proteins that bind acidic phospholipids in the presence of Ca2+. The association of these proteins with the membranes of secretory granules and endosomes indicates these proteins may play a role in membrane trafficking. One member of the family, annexin II, can exist either as a monomer, heterodimer or heterotetramer in conjunction with the S100 protein p11. The ability of annexin II tetramer to bind both membranes and actin in a Ca2+-dependent manner has led to the hypothesis that annexin II may mediate between vesicle and/or plasma membranes and the cortical cytoskeleton. However, despite intensive biochemical characterisation in vitro, the function of this protein in vivo remains a mystery. In this study annexin II function in living cells was analysed in several different ways using green fluorescent protein (GFP) in full length annexin II-GFP chimeras and chimeras consisting of fragments of annexin II fused to GFP. Transfection of different cell lines with these annexin II-GFP constructs and fluorescence assisted cell sorting (FACS) allowed the generation of multiclonal cell populations expressing annexin II-GFP fusion proteins. These cell populations were analysed for effects on physiological functions - such as secretion (in the RBL cell line) or differentiation (of the PC12 cell line). This line of investigation did not yield evidence to support a role for annexin II in either of these processes. Using novel forms of microscopy the localisation of a full length annexin II- GFP chimera (NAII-GFP) was followed in single cells under physiological conditions. Under conditions of stress NAII-GFP was found to become incorporated into novel actin based structures, reminiscent of Listeria rockets, which propelled pinosomes through the cell interior. This form of vesicle locomotion is dependent on actin polymerisation and may represent a hitherto unrecognised form of vesicle transport

An Investigation Of Mathematical Models For Animal Group Movement, Using Classical And Statistical Approaches

Collective actions of large animal groups result in elaborate behaviour, whose nature can be breathtaking in their complexity. Social organisation is the key to the origin of this behaviour and the mechanisms by which this organisation occurs are of particular interest. In this thesis, these mechanisms of social interactions and their consequences for group-level behaviour are explored. Social interactions amongst individuals are based on simple rules of attraction, alignment and orientation amongst neighbouring individuals. As part of this study, we will be interested in data that takes the form of a set of directions in space. In Chapter 2, we discuss relevant statistical measure and theory which will allow us to analyse directional data. These statistical tools will be employed on the results of the simulations of the mathematical models formulated in the course of the thesis. The first mathematical model for collective group behaviour is a Lagrangian self-organising model, which is formulated in Chapter 3. This model is based on basic social interactions between group members. Resulting collective behaviours and other related issues are examined during this chapter. Once we have an understanding of the model in Chapter 3, we use this model in Chapter 4 to investigate the idea of guidance of large groups by a select number of individuals. These individuals are privy to information regarding the location of a specific goal. This is used to explore a mechanism proposed for honeybee (Apis mellifera) swarm migrations. The spherical theory introduced in Chapter 2 will prove to be particularly useful in analysing the results of the modelling. In Chapter 5, we introduce a second mathematical model for aggregative behaviour. The model uses ideas from electromagnetic forces and particle physics, reinterpreting them in the context of social forces. While attraction and repulsion terms have been included in similar models in past literature, we introduce an orientation force to our model and show the requirement of a dissipative force to prevent individuals from escaping from the confines of the group

Towards Demisable Fiber Reinforced Plastics

For avoiding the Kessler syndrome, satellites in low Earth orbits must be removed in due time after the end of their service life by re-entering into the Earth's atmosphere. Active, controlled re-entry requires availability of thrusters and propellant at the end of the mission. Thus, the active re-entry comes at a high cost and reduces the available payload mass of a mission. It is accordingly desirable to leave the satellite to itself at the end of its life and allow it to re-enter in an uncontrolled way. Unfortunately, parts of such satellites can survive the destructive re-entry flight and may impact on the ground. These debris pose a risk to public safety if they go down over an inhabited area. Rules that limit the acceptable ground risk per mission to a specific threshold are therefore in place in many countries. The typical accepted risk is one incident in ten thousand missions (1:10 000). Fiber reinforced plastics (FRPs) have been considered easily demisable because of their organic matrices and the fact that they would be able to burn at ground conditions. However, wind tunnel tests have revealed that FRPs have a very high demise resistance and can act as an ablative heat shield. This results in FRPs generally being a problematic material in the ground risk assessment. The good news is that there have been material level tests that showed a desirable demise behavior, which resulted in higher demise rates. The goal of the COMP2DEM project is identifying the microscopic and macroscopic parameters that determine the demise process and phenomena and explaining the differences in the observed behavior. Based on this knowledge, new fiber-reinforced plastics with increased demisability shall be formulated. The presentation covers the first phase of the COMP2DEM project: the screening of different FRP variants by thermophysical material characterization and demise simulation in the arc heated wind tunnels of DLR. New FRPs with increased demisability are currently under development and an outlook on the developments in the project is given

Quadruple-peaked spectral line profiles as a tool to constrain gravitational potential of shell galaxies

Stellar shells observed in many giant elliptical and lenticular as well as a few spiral and dwarf galaxies, presumably result from galaxy mergers. Line-of-sight velocity distributions of the shells could, in principle, if measured with a sufficiently high S/N, constitute one of methods to constrain the gravitational potential of the host galaxy. Merrifield & Kuijken (1998) predicted a double-peaked line profile for stationary shells resulting from a nearly radial minor merger. In this paper, we aim at extending their analysis to a more realistic case of expanding shells, inherent to the merging process, whereas we assume the same type of merger and the same orbital geometry. We use analytical approach as well as test particle simulations to predict the line-of-sight velocity profile across the shell structure. Simulated line profiles are convolved with spectral PSFs to estimate the peak detectability. The resulting line-of-sight velocity distributions are more complex than previously predicted due to non-zero phase velocity of the shells. In principle, each of the Merrifield & Kuijken (1998) peaks splits into two, giving a quadruple-peaked line profile, which allows more precise determination of the potential of the host galaxy and, moreover, contains additional information. We find simple analytical expressions that connect the positions of the four peaks of the line profile and the mass distribution of the galaxy, namely the circular velocity at the given shell radius and the propagation velocity of the shell. The analytical expressions were applied to a test-particle simulation of a radial minor merger and the potential of the simulated host galaxy was successfully recovered. The shell kinematics can thus become an independent tool to determine the content and distribution of the dark matter in shell galaxies, up to ~100 kpc from the center of the host galaxy.Comment: 15 pages, 16 figures | v2: accepted for publication in A&A, minor language correction

DEVELOPING A FLEXIBLE THERMAL PROTECTION SYSTEM FOR MARS ENTRY: SYSTEMS ENGINEERING, MECHANICAL DESIGN AND MANUFACTURING PROCESSES

A flexible thermal protection system (FTPS) is needed to enable the use of deployable and inflatable hypersonic decelerators. These decelerators could increase entry vehicle drag area beyond that of a conventional rigid heatshield, enabling Mars missions with greater landed masses and higher-elevation landing sites than can be currently achieved. An FTPS is essential to protect the hypersonic decelerator and payload from atmospheric entry aerothermal loads; conventional rigid heatshields are constrained by the available space within the launcher fairing. An ESA technology development is ongoing to raise the European FTPS technology readiness level from 2 to 3 and to define an FTPS that may be integrated with a Mars-entry inflatable hypersonic decelerator. This paper presents the FTPS requirements, material selection, mechanical characterisation and manufacturing technique development

International cancer microbiome consortium consensus statement on the role of the human microbiome in carcinogenesis

Objective In this consensus statement, an international panel of experts deliver their opinions on key questions regarding the contribution of the human microbiome to carcinogenesis.Design International experts in oncology and/or microbiome research were approached by personal communication to form a panel. A structured, iterative, methodology based around a 1-day roundtable discussion was employed to derive expert consensus on key questions in microbiome-oncology research.Results Some 18 experts convened for the roundtable discussion and five key questions were identified regarding: (1) the relevance of dysbiosis/an altered gut microbiome to carcinogenesis; (2) potential mechanisms of microbiota-induced carcinogenesis; (3) conceptual frameworks describing how the human microbiome may drive carcinogenesis; (4) causation versus association; and (5) future directions for research in the field.The panel considered that, despite mechanistic and supporting evidence from animal and human studies, there is currently no direct evidence that the human commensal microbiome is a key determinant in the aetiopathogenesis of cancer. The panel cited the lack of large longitudinal, cohort studies as a principal deciding factor and agreed that this should be a future research priority. However, while acknowledging gaps in the evidence, expert opinion was that the microbiome, alongside environmental factors and an epigenetically/genetically vulnerable host, represents one apex of a tripartite, multidirectional interactome that drives carcinogenesis.Conclusion Data from longitudinal cohort studies are needed to confirm the role of the human microbiome as a key driver in the aetiopathogenesis of cancer

DEVELOPING A FLEXIBLE THERMAL PROTECTION SYSTEM FOR MARS ENTRY: THERMAL DESIGN AND TESTING

Flexible Thermal Protection Systems (FTPS) are a key technology needed to enable novel inflatable and deployable aerodynamic decelerators. A development campaign is underway to raise the European FTPS technology readiness level from 2 to 3, advancing design and test capability. An FTPS suitable for a reference Mars landing mission is being designed. The FTPS has three functional layers: outer layers of Nextel 440 BF-20 fabric; insulation layers of SIGRATHERM GFA5 graphite felt and Pyrogel XTE aerogel; and a silicone-coated Kevlar fabric gas barrier. The density, specific heat capacity and thermal diffusivity of candidate materials was measured. Results were then used in thermal simulations to define a baseline layup. The layup thermal conductance was assessed in thermocouple-instrumented layup tests. Layups including joints were also tested and found not to have significantly different conductance. Layup test thermal simulations showed good agreement with the experimental data. Future work will include arc-jet tests and thermal model optimisation