Fault-tolerant formation driving mechanism designed for heterogeneous MAVs-UGVs groups

A fault-tolerant method for stabilization and navigation of 3D heterogeneous formations is proposed in this paper. The presented Model Predictive Control (MPC) based approach enables to deploy compact formations of closely cooperating autonomous aerial and ground robots in surveillance scenarios without the necessity of a precise external localization. Instead, the proposed method relies on a top-view visual relative localization provided by the micro aerial vehicles flying above the ground robots and on a simple yet stable visual based navigation using images from an onboard monocular camera. The MPC based schema together with a fault detection and recovery mechanism provide a robust solution applicable in complex environments with static and dynamic obstacles. The core of the proposed leader-follower based formation driving method consists in a representation of the entire 3D formation as a convex hull projected along a desired path that has to be followed by the group. Such an approach provides non-collision solution and respects requirements of the direct visibility between the team members. The uninterrupted visibility is crucial for the employed top-view localization and therefore for the stabilization of the group. The proposed formation driving method and the fault recovery mechanisms are verified by simulations and hardware experiments presented in the paper

Chemokine and chemikine receptor expression by human brain endothelium :an in vitro and in situ study

The infiltration of leukocytes across the BBB is thought to be mediated by chemokines released in the CNS. This study investigated the production of chemokines and expression of chemokine receptors by human brain endothelial cells (HBEC) as well as the consequences of CXCL10 stimulation on brain endothelial function in terms of leukocyte migration and endothelial permeability. Purified primary HBEC as well as a novel human brain endothelial cell line, called hCEMC/D3 and generated in collaboration with the Institute Cochin, were used in the present study. Characterisation of hCMEC/D3 cells was effected by determining the expression and localisation of HBEC markers such as tight junction and adherens junction proteins. Both primary and immortalized HBEC were tested for the production of four chemokines (CCL2, CCL5, CXCL8 and CXCL10) considered to play a role in multiple sclerosis. CXCL8 and CCL2 were constitutively released, whereas CXCL10 and CCL5 could not be detected at basal levels. By contrast, all these chemokines were up-regulated in response to either TNF-a or IFN-y or a combination of both. TNF-a had the most striking effect, up-regulating the production of CCL2, CCL5 and CXCL8, while IFN-y up-regulated CXCL10 exclusively. The chemokine receptors CXCR1 and CXCR3, whose ligands include CXCL8 and CXCL10, were expressed constitutively by HBEC both in vitro and in vivo, and only CXCR3 was up-regulated in response to cytokine stimulation in vitro. Furthermore, CXCR3 on endothelial cells is functional as CXCL10 induces phosphorylation of p42/44 MAP kinase, p38 MAP kinase and JNK/SAPK. However, activation of HBEC by CXCL10 did not induce any permeability change nor did it modulate leukocyte adhesion. These results demonstrate that endothelial cells could play an important role in chemokine production and hence leukocyte infiltration during inflammatory pathologies such as MS. The role of chemokine receptors requires further investigation

Investigating the biological importance of Dipeptidyl Peptidase 9 enzymatic activity using a mouse model

Dipeptidyl peptidase 9 (DPP9) is an atypical post-proline serine protease of the DPP4 enzyme family which has ubiquitous expression and DPP4-like enzymatic activity. It is localised intracellularly and has roles in antigen processing and epidermal growth factor signalling. It interacts with H-Ras and small ubiquitin-like modifier-1 and influences cellular interactions with extracellular matrix. Our lab made the first DDP9 gene knock-in (gki) mouse with a DPP9 active site (S729A) mutation which results in a lack of DPP9 enzymatic activity. This thesis investigated the biological properties of DPP9 using this genetically modified mouse model. Mice lacking DPP9 proteolytic activity die in the early neonatal stage. This study validated that the DPP9 protein, while present in the gki mouse, is enzyme-inactive and the DPP9-S729A protein and wild-type DPP9 have similar subcellular localisation. A range of investigations were undertaken to determine if obvious histological and/or physiological differences exist between early neonate DPP9S729A/S729A homozygotes from their heterozygous and wild-type littermates and involved analysis of organ morphology, histology and function and investigation of autophagy. The novel findings of this study show that DPP9 enzymatic activity is essential for early neonatal survival in mice and suggest that there is dysregulated autophagy in the DPP9-enzyme-activity-deficient neonatal mice that may contribute to the lethal phenotype. Other members of the DPP4 protein family are implicated in wound healing with fibroblast activation protein expressed in the granulation tissue of healing wounds and DPP4-positive T cells involved in regulation of granulation tissue formation. As there is a heterozygous effect on survival to weaning and DPP9 immunoreactivity was shown in the skin of both WT and DPP9S729A/S729A neonates, the skin of adult mice was studied using a model of cutaneous wound healing. This involved analysis of wound closure rates, tensile strength and collagen levels of both wounded and steady state tissue in adult DPP9wt/S729A mice and their wild-type littermates. It was found that adult heterozygous DPP9-GKI mice display reduced skin collagen levels compared to their WT littermates, but that the rate of skin wound healing appeared unaffected. DPP9 has in vivo expression in normal immunological tissues and major lymphocyte populations that alters with chronic liver injury, suggesting a role in immune function. To investigate the importance of DPP9 in immune regeneration and function, primary and secondary mixed chimeric mice were created using DPP9S729A/S729A and WT fetal liver cells and adult bone marrow, respectively, injected into irradiated recipients. The process of regeneration of the immune system in these mice was assessed at several time-points and the immune cells present in the regenerated immune systems were compared between DPP9S729A/S729A-origin and WT-origin chimeras. These chimeric mice were then subjected to an immune challenge by influenza virus infection. The novel findings of this study suggest that DPP9-enzyme-activity-deficient secondary chimeric mice may have an enhanced ability to recover from an immune challenge with influenza virus. Therefore, DPP9 appears to influence immune function in that viral infection. Together, these studies underline the biological significance of DPP9 in vivo in both neonatal and adult mice. These data contribute to the expanding knowledge of the role of DPP9, building upon recent discoveries in vitro of its involvement in multiple biological processes. By providing physiologically relevant results, this study has enhanced the knowledge of DPP9 enzyme function and the overall biological roles of DPP9

Structure, function and genetic diversity of glucosyltransferase IV (GtrIV) of Shigella flexneri

There are 15 known S. flexneri serotypes, which differ in their virulence, prevalence, distribution and the nature of their O-antigens. The three bacteriophage genes gtrA, gtrB and gtr(type) are responsible for O-antigen glucosylation in Shigella flexneri. Both gtrA and gtrB have been demonstrated to be highly conserved and interchangeable among serotypes while gtr(type) was found to be specific to each serotype, leading to the hypothesis that the Gtr(type) proteins are responsible for attaching glucosyl groups to the O-antigen in a site- and serotype- specific manner. Such interaction and attachment of the glucosyl groups to the O-antigen has been postulated to occur in the periplasm. In this study, the topology of GtrIV, a S. flexneri glucosyltransferase responsible for converting serotype Y to serotype 4a, was experimentally determined by creating different fusions between GtrIV and a dual-reporter protein, PhoA/LacZ. This study shows that GtrIV consists of 8 transmembrane helices, 2 large periplasmic loops, 2 small cytoplasmic N- and C- terminal ends and a re-entrant loop that occurs between transmembrane helices III and IV. This topology is similar to that of GtrIc. Based on the newly elucidated topology of GtrIV, the roles of the N-terminal and C-terminal periplasmic loops of GtrIV (loop No. 2 and loop No. 6) were investigated through loop deletions. By sequentially deleting loop segments in loop No. 6, the presence of a potential catalytic site located between resides D260 to W269 was hypothesised. The roles of conserved or specific functions of the two periplasmic loops of GtrIV was also investigated by creating loop swap chimeras between GtrIV and its closest structural homologue, GtrIc. The resulting hybrids lost their native function and were unable to substitute function to the other protein thus, signifying the importance of both loops in GtrIV function. A total of 20 negatively charged amino acids that occur throughout GtrIV were mutated to alanine to investigate their role in GtrIV function. Three of these acidic residues located in the periplasmic loop No. 6, D261, E262 and D267, when mutated in tandem, were found to abolish function of GtrIV. They are thought to be involved in the interaction with the donor and acceptor substrates that help confer serotype specificity in O-antigen glucosylation. 28 wildtype strains isolated from Japan, Bangladesh and Vietnam that were originally typed as serotype 4a, 4b or just 4 were subjected to a series of slide agglutination experiments to confirm their serotype. A number of strains had atypical agglutination patterns, highlighting the possibility that they are potentially new serotypes or subserotypes. The GtrIV sequences obtained from these strains revealed the presence of point mutations within several strains. Southern blots carried out using DIG-labelled gtrIV suggested that two different serotype 4a strains, with the possibility of one of them being originally a 4b strain, have been circulating within these populations. Taken together, this study has provided valuable insight into the possibly unique mode of action of GtrIV and has provided grounds for further investigation into the evolution of one of the most important human pathogens

The synthesis and characterisation of new macrocyclic complexing agent for use in tumour targeting

Macrocyclic complexing agents have been synthesised for the binding of indiumdil(III), gallium(III), yttrium(III), gold(I), silver(I) and rhenium(V) and a comparative study has been made between the macrocyclic complexing agents, 18N(_4)S(_2), 18N(_4)S(_2)Me(_4), 18N(_4)O(_2) and 18N(_4)0(_2)Me(_4) and their ability to bind silver (I). The gallium(III) and indium(III) complexes of 9N(_3)C(_3)Me(_3) and 9N(_3)C(_3)Ph(_3) have been investigated extensively both in vitro and in vivo. The stability of the complexes have been characterised using 71Ga NMR, 1H NMR, U.V. spectral analysis, ligand protonation constants, and complex binding constants. A full X-ray crystallographic structural determination has been obtained for the indium-9N(_3)C(_3)Me(_3) complex. Following confirmation of the excellent binding characteristics of the 9N(_3)C(_3)Me(_3) and 9N(_3)C(_3)Ph(_3) complexing agents, the in vivo kinetic stability of the indium and gallium complexes has been investigated. The 9N(_3)C(_3)Me(_3) complexes were exceptionally stable and cleared rapidly (99% within 24 hrs) via the renal excretion pathway. The complexes of the 9N(_3)C(_3)Ph(_3) were less stable and also showed a preference for clearance via the kidneys. Further to this, the tumour localising properties in a human melanotic melanoma has been investigated for the 67Ga- 9N(_3)C(_3)Ph(_3) complex. The complex has shown a preference for. tumour localisation, although a low tumour: blood ratio (1:1) may prohibit its application for tumour targeting. The stability constants of the silver(I) complexes of 18N(_4)S(_2), 18N(_4)S(_2)Me(_4), 18N(_4)O(_2) and 18N(_4)0(_2)Me(_4) have been measured both in methanolic and aqueous media. The [Ag-18N(_4)S(_2)Me(_4)]+ complex stability (log KmL= 14.6) is the highest stability constant recorded in methanol. In aqueous media, of the four complexes, the [Ag-18N(_4)S(_2)]+ is the most stable (log KmL=10-4) a reversal of the observed order of complex stability in methanol. The stability of the new yttrium(III) complexing agent has been ascertained using 1H NMR and HPLC radiometry and proved to be insufficiently stable for in vivo use, and was easily displaced by DTPA in a trial experiment

Étude du mécanisme moléculaire d'incorporation de la molécule de l'hôte ICAM-1 par le VIH-1

Le virus de l’immunodéficience humaine de type-1 (VIH-1) a été identifié comme étant l’agent responsable de la pandémie qui frappe actuellement notre civilisation. En une trentaine d’années le virus à causé la mort de plus de 35 millions de personnes. Une telle épidémie dans l’histoire de l’humanité n’est pas une première; rappelons-nous dans le passé, la peste noire ou encore la grippe espagnole qui ont fait elles aussi des millions de morts. Cependant, pour la première fois dans l’ère moderne, nous avons la possibilité de lutter contre ce fléau grâce à l’étude approfondie de la biologie du virus qui a permis, entre autres, l’avènement de la trithérapie. Le VIH-1 acquiert un nombre impressionnant de molécules cellulaires tout au long de son cycle réplicatif. En dépit de tous les efforts consacrés à l’étude des molécules de l’hôte, le(s) mécanisme(s) exact par lequel toutes ces molécules sont acquises n'est toujours pas connu. Néanmoins, dans le cas d'ICAM-1, une des molécules transmembranaires les plus étudié il apparaît que le précurseur viral Pr55Gag est un candidat potentiel d'interaction avec ICAM-1. Par conséquent, nous avons étudié et caractérisé au niveau moléculaire le processus d'incorporation d'ICAM-1 en utilisant dans un premier temps un modèle de pseudo particules virales (VLPs) dérivé de Pr55Gag. La substitution de plusieurs domaines de Pr55Gag tels que la nucléocapside, SP2 et p6 n'ont pas eu d'effet sur son acquisition. Par la suite, nous avons démontré que la protéine de matrice (MA) est nécessaire à son incorporation. Nous avons confirmé ces résultats préliminaires en générant le mutant de matrice dans un clone moléculaire couramment utilisé en laboratoire (NL4.3). Des études complémentaires suggèrent que les deux tiers C-terminal de la MA sont importants et en particulier treize acides aminés présents dans l'hélice-α 5. De plus, en se basant sur la modélisation 3D des interactions protéines-protéines et en validant par la suite ces prédictions par immunocapture, nous avons trouvé qu'une série d'acides aminés acides de la MA interagit avec des acides aminés basiques présents sur le domaine cytoplasmique d'ICAM-1 et sont responsables de son incorporation. En résumé, nos résultats apportent de nouvelles connaissances dans le mécanisme moléculaire régissant l'acquisition d'ICAM-1, une molécule de l'hôte connu pour renforcer l'infectiosité virale et moduler la pathogénèse du VIH-1

Enabling self organisation for future cellular networks.

The rapid growth in mobile communications due to the exponential demand for wireless access is causing the distribution and maintenance of cellular networks to become more complex, expensive and time consuming. Lately, extensive research and standardisation work has been focused on the novel paradigm of self-organising network (SON). SON is an automated technology that allows the planning, deployment, operation, optimisation and healing of the network to become faster and easier by reducing the human involvement in network operational tasks, while optimising the network coverage, capacity and quality of service. However, these SON autonomous features cannot be achieved with the current drive test coverage assessment approach due to its lack of automaticity which results in huge delays and cost. Minimization of drive test (MDT) has recently been standardized by 3GPP as a key self- organising network (SON) feature. MDT allows coverage to be estimated at the base station using user equipment (UE) measurement reports with the objective to eliminate the need for drive tests. However, most MDT based coverage estimation methods recently proposed in literature assume that UE position is known at the base station with 100% accuracy, an assumption that does not hold in reality. In this work, we develop a novel and accurate analytical model that allows the quantification of error in MDT based autonomous coverage estimation (ACE) as a function of error in UE as well as base station (user deployed cell) positioning. We first consider a circular cell with an omnidirectional antenna and then we use a three-sectored cell and see how the system is going to be affected by the UE and the base station (user deployed cell) geographical location information errors. Our model also allows characterization of error in ACE as function of standard deviation of shadowing in addition to the path-loss

Developing a person guidance module for hospital robots

This dissertation describes the design and implementation of the Person Guidance Module (PGM) that enables the IWARD (Intelligent Robot Swarm for attendance, Recognition, Cleaning and delivery) base robot to offer route guidance service to the patients or visitors inside the hospital arena. One of the common problems encountered in huge hospital buildings today is foreigners not being able to find their way around in the hospital. Although there are a variety of guide robots currently existing on the market and offering a wide range of guidance and related activities, they do not fit into the modular concept of the IWARD project. The PGM features a robust and foolproof non-hierarchical sensor fusion approach of an active RFID, stereovision and cricket mote sensor for guiding a patient to the X-ray room, or a visitor to a patient’s ward in every possible scenario in a complex, dynamic and crowded hospital environment. Moreover, the speed of the robot can be adjusted automatically according to the pace of the follower for physical comfort using this system. Furthermore, the module performs these tasks in any unconstructed environment solely from a robot’s onboard perceptual resources in order to limit the hardware installation costs and therefore the indoor setting support. Similar comprehensive solution in one single platform has remained elusive in existing literature. The finished module can be connected to any IWARD base robot using quick-change mechanical connections and standard electrical connections. The PGM module box is equipped with a Gumstix embedded computer for all module computing which is powered up automatically once the module box is inserted into the robot. In line with the general software architecture of the IWARD project, all software modules are developed as Orca2 components and cross-complied for Gumstix’s XScale processor. To support standardized communication between different software components, Internet Communications Engine (Ice) has been used as middleware. Additionally, plug-and-play capabilities have been developed and incorporated so that swarm system is aware at all times of which robot is equipped with PGM. Finally, in several field trials in hospital environments, the person guidance module has shown its suitability for a challenging real-world application as well as the necessary user acceptance