Understanding Influenza

Influenza, a serious illness of humans and domesticated animals, has been studied intensively for many years. It therefore provides an example of how much we can learn from detailed studies of an infectious disease and of how even the most intensive scientific research leaves further questions to answer. This introduction is written for researchers who have become interested in one of these unanswered questions, but who may not have previously worked on influenza. To investigate these questions, researchers must not only have a firm grasp of relevant methods and protocols; they must also be familiar with the basic details of our current understanding of influenza. This article therefore briefly covers the burden of disease that has driven influenza research, summarizes how our thinking about influenza has evolved over time, and sets out key features of influenza viruses by discussing how we classify them and what we understand of their replication. It does not aim to be comprehensive, as any researcher will read deeply into the specific areas that have grasped their interest. Instead, it aims to provide a general summary of how we came to think about influenza in the way we do now, in the hope that the reader’s own research will help us to understand it better

Qualification of AM parts: Extreme value statistics applied to tomographic measurements

reserved5siThe progressive improvement of additive manufacturing (AM) techniques enables the production of geometrically complex and lightweight parts, which explains the incredibly fast growth of AM for space and aerospace applications. The first standards require the production of witness specimens manufactured together with the components for assessment and qualification for the material control. However, one of the most critical issues is determining the âfitness-for-purposeâ of fatigue loaded parts, which is strictly related to the microstructure and defects generated during the manufacturing process. One of the most suitable techniques for detecting defects even near the surface or in thin, complex geometries is micro-computed tomography (μ-CT). This paper deals with the application of statistics of extremes for analysing X-ray CT scan measurements in view of component assessment by discussing its advantages and requirements.mixedRomano, S; Brandã£o, A.; Gumpinger, J.; Gschweitl, M.; Beretta, S.Romano, Simone; Brandã£o, A.; Gumpinger, J.; Gschweitl, M.; Beretta, Stefan

Design and realization of an additive manufactured multifunctional spacecraft structure through a systems and concurrent engineering approach

The use of AM technologies within the space systems of the present but especially of the near future is increasingly pervasive as it is considered a key enabling technology for both commercial and exploration missions, bringing humans on Moon and on Mars. To reach these goals present and future designers must adopt a new Additive-thinking, where Design for Additive Manufacturing (DFAM) must be adopted within a rigorous systemic and systematic approach from the very early design phases. The intended contribution of this research work is to demonstrate that to really maximize the AM benefits for space systems it is necessary to adopt an holistic approach both for the space system and for its development workflow. This permits to leverage the usual AM-improvements twofold, on the equipment itself on one side and for the entire system on the other. By starting from a simple component re-design is possible to obtain only marginal improvements, while re-thinking the traditional design methodology within the innovative DFAM logics with a Systems Engineering (SE) approach is the only way to reach really disruptive advantages, in terms of merging functions and innovative configurations, strongly affecting the traditional spacecraft architectures. To reach the optimal level of integration with concurrent engineering processes the Through-life Integrated Concurrent Engineering approach has been selected for the development of the case-study. In order to demonstrate the effectiveness of the method, a multifunctional integrated spacecraft lateral panel has been chosen as a representative benchmark of a spacecraft system. Thanks to this case-study it has been possible to completely address two main goals within the established time frame: to rethink, introduce and validate the design methodology and to realize an innovative system with increased technical and programmatics performances

Systems Engineering and Systems Architecting approaches for innovative Additive Manufactured Spacecraft Structures

Additive Manufacturing (AM) for space applications is no more only a very impressive and promising production technology, permitting high-speed and low-cost development and delivering, but a real product/process/business game-changer offering opportunities that any space actor cannot lose. At the same time, it represents a very new complex design and development environment which introduction and regular adoption within space industry represents a great challenge. Sapienza University of Rome and RUAG Space share a common understanding about what is necessary to fully leverage the benefits of AM for space systems in terms of different spacecraft architectures design methodologies. A strong mind-set change is requested for the effective introduction of the disruptive Design For Additive Manufacturing (DFAM) logics and rules into the traditional design workflows. In this paper a novel design approach based on the integration of Systems Engineering (SE) and Systems Architecting (SA) methodologies for the development of innovative additive manufactured spacecraft platforms is presented. In particular a smart AM-suited design tool is described and used for the AM re-design of a multifunctional integrated spacecraft lateral panel, as a representative case-study

The Endosomal Network: Mediators and Regulators of Endosome Maturation

Endocytosis is a means for the cell to sample its environment for nutrients and regulate plasma membrane (PM) composition and area. Whereas the majority of internalized cargo is recycled back to the cell surface, select material is sent to the lysosome for degradation. Endosomes further play major roles in central cell activities as diverse as establishment of cell polarity and signaling, lysosomal storage and immunity. The complexity of endosomal functions is reflected by the extensive changes to endosome properties as they mature. The identity of individual endosomes is influenced by the presence of specific Rab GTPases and phosphoinositides (PIPs), which coordinate membrane traffic and facilitate endosomal functions. Motors and tethers direct the endosomes to the required locations and moderate fusion with other organelles. The maintenance of the elaborate endosomal network is supported by the ER and the trans-Golgi network (TGN), which promote the exchange of membrane components, provide enzymes, and assist with signaling. Additionally, V-ATPase is emerging as an underappreciated coordinator of endosome maturation and cell signaling. The inputs of the various mediators of endosome maturation are tightly regulated and coordinated to ensure appropriate maintenance and functioning of endosomes at each stage of the maturation process. Perturbations in endosome maturation are implicated in devastating diseases, such as neurodegeneration and cancer, and the endosome maturation processes are manipulated and exploited by intracellular pathogens to meet their own needs. A greater understanding of coordination and fine-tuning of endosome maturation will help us address various pathologies more effectively

EGFR Trafficking in Physiology and Cancer

Signaling from the epidermal growth factor receptor (EGFR) elicits multiple biological responses, including cell proliferation, migration, and survival. Receptor endocytosis and trafficking are critical physiological processes that control the strength, duration, diversification, and spatial restriction of EGFR signaling through multiple mechanisms, which we review in this chapter. These mechanisms include: (i) regulation of receptor density and activation at the cell surface; (ii) concentration of receptors into distinct nascent endocytic structures; (iii) commitment of the receptor to different endocytic routes; (iv) endosomal sorting and postendocytic trafficking of the receptor through distinct pathways, and (v) recycling to restricted regions of the cell surface. We also highlight how communication between organelles controls EGFR activity along the endocytic route. Finally, we illustrate how abnormal trafficking of EGFR oncogenic mutants, as well as alterations of the endocytic machinery, contributes to aberrant EGFR signaling in cancer