The development of new cancer treatments has significantly improved life expectancy of patients. However, these advances increase the risk of suffering from secondary tumours (metastases). Particularly, breast cancer brain metastases are a major cause of morbidity, with meagre life expectancy (3-18 months). These facts highlight the urgent need to find better treatment against this disease. Immunotherapy has recently gained great momentum in the clinic to treat different type of cancers. However, its therapeutic use for metastatic spread to the central nervous system (CNS) remains scarce. The immune response within the CNS during metastasis progression greatly depends on microglial cells (resident CNS macrophages). Their roles in neuroinflammatory and neurodegenerative processes have been intensely investigated, whereas their function in metastasis has received minor attention. During brain metastasis, microglia show impaired immune defence, secreting a variety of anti-inflammatory cytokines (e.g. IL-10 and TGF-B) and growth factors which may contribute to metastasis progression. A key molecule which might alter such adverse behaviour is beta-galactoside-specific animal lectin galectin-3 (Gal-3). Studies of this promiscuous protein has shown a pivotal role during tumour progression and metastasis to non-CNS sites. Importantly, recent studies from Prof Venero’s group have shown how inhibition of microglial Gal-3 shifted the phenotype of these cells into a more pro-inflammatory state. Therefore, since pro-inflammatory state in microglial cells has been described to exert anti-metastatic effects, Gal-3 inhibition may provide a powerful and novel brain metastasis immunotherapeutic approach. Moreover, the fact of the existence of Gal-3 drugs in current clinical trials enhance the possibility of using this strategy as neo-adjuvant therapy to treat breast cancer patients at risk of brain metastasis.
The goal of GRIFFIN is the derivation of a unified framework with methods, tools and technologies for the development of flying robots with dexterous manipulation capabilities. The robots will be able to fly minimizing energy consumption, to perch on curved surfaces and to perform dexterous manipulation. Flying will be based on foldable wings with flapping capabilities. They will be able to safely operate in sites where rotorcrafts cannot do it and physically interact with people. Dexterous manipulation will be performed maintaining fixed contact with a surface, such as a pole or a pipe, by means of one or more limbs and manipulating with others overcoming the limitations of dexterous manipulation in free flying of existing aerial manipulators. Compliance will play an important role in these robots and in their flight and manipulation control methods. The control systems will be based on appropriate kinematic, dynamic and aerodynamic models. The GRIFFIN robots will have autonomous perception, reactivity and planning based on these models. They will be also able to associate with others to perform cooperative manipulation tasks. New software tools will be developed to facilitate the design and implementation of these complex robotic systems. Thus, configurations with different complexity could be derived depending on the requirements of flight endurance and manipulation tasks from simple grasping to more complex dexterous manipulation. The implementation will be based on additive and shape deposition manufacturing to fabricate multi-material parts and parts with embedded electronics and sensors. In GRIFFIN we will develop a small flapping wings proof of concept prototype which will be able to land autonomously on a small surface by using computer vision, a manipulation system with the body attached to a pole, and finally full size prototypes which will demonstrate flying, landing and manipulation, including cooperative manipulation, by maintaining the equilibrium.
The overarching goal of the THOR research project is to augment space operations autonomy and robustness through uncertainty management and quantification. This involves a bottom up process where novel uncertainty estimation and propagation techniques will be employed to be subsequently embedded within a stochastic robust controller. The main outcome will be a robust non-linear non-gaussian integrated guidance, navigation and control strategy with both model-based and exogenous disturbance estimation. Since both uncertainty sources are quantified, a more reliable and efficient space operation management and planning will be obtained. The THOR scenario relates to asteroid exploration which is one of the most challenging and uncertain space operations nowadays. This is due to the limited asteroid data known prior to the arrival if the body is visited for the first time. Two mission phases can be clearly distinguished: on-orbit data collection where most of the uncertainty will be removed by estimation; then, an entry descent and landing critical phase where the stochastic robust controller will use the previous uncertainty knowledge, is envisioned. The THOR project methodology and results are expected to advance current state-of-the-art in autonomous spacecraft guidance, navigation and control, thus enabling more advanced space exploration mission concepts with a higher scientific return, without loss of generality.