1731 research outputs found
Sort by
Beyond the Nuclear Pore Complex, Nup358 Clusters at the Axon Initial Segment of Cultured Neurons
Get PDFNup358 is the largest nucleoporin of around 358 kDa molecular weight that localizes on the cytoplasmic face of the nuclear pore complex (NPC). It takes part in the overall activity of the NPC mediating the transport of nucleic acids and proteins between the nucleus and the cytoplasm. However, due to its multi-domain configuration, Nup358 has a more pleiotropic function in several cellular mechanisms such as mediating the stability of microtubules and axon specification. Since little is known about the non-conventional role of Nup358 in neuronal polarity, my PhD thesis was focused on characterizing the subcellular distribution and expression pattern of Nup358 protein in cultured neurons. My results show Nup358 present at the nuclear rim of neuronal cells, associated with NPCs, also in the cytoplasm having a spotted pattern along the neuronal processes. Interestingly, Nup358 was remarkably clustered at the axon initial segment (AIS) of mature neurons and dependent on a prior recruitment of the master AIS scaffold, Ankyrin-G (AnkG), to this specific region. Of the distinct domains present in Nup358 protein, the N-terminal region was found to be crucial for its localization at the AIS. Further, changes in Nup358 protein expression were monitored during neuronal development. Indeed, I detected the presence of a shorter isoform of Nup358 that was increasing as neurons develop whereas the full-length protein had an opposite decreasing trend. To gain knowledge about the functional role of Nup358 in neurons, I investigated its protein expression/distribution in response to an increasing or decreasing neuronal activity with specific drug treatments. Surprisingly, Nup358 protein expression was reduced following the stimulation or the depolarization of neurons, mediated by calcium influx and NMDA receptors. Overall, my results show that Nup358 has a unique subcellular distribution in neurons, being enriched at the AIS at advanced stages of development, therefore, suggest an involvement of Nup358 protein in maintaining and modulating neuronal polarity and activity
The Connective Power of Reminiscence: Designing a Reminiscence-based Tool to Increase Social Interactions in Residential Care
Get PDFReminiscence powers therapeutic interventions such as Life review and Reminiscence therapy, with well known positive outcomes on the wellbeing of older adults. In particular, reminiscence therapy supported by technology can increase self-esteem, facilitate social interactions and increase opportunities for conversation. Much research on reminiscence technology has in fact focused on improving interactions and conversation, mainly for people with dementia. Nonetheless, the potential for reminiscence to discover common life points among residents in residential care facilities and especially to use this information to foster bonding between residents has been little explored. The focus of this thesis is to design a reminiscence-based tool, to be used in nursing homes to stimulate interactions among older adults, family members, and nursing home staff.
We start by describing early work that reinforces the potential of ICT interventions on improving the wellbeing of older adults. These studies highlight the importance of social interactions on social wellbeing and of doing activities together in engagement and motivation. Through review works and exploratory studies we confirm the positive effects of social interaction on the wellbeing of older adults, the benefits associated to contributing, and the opportunities to improve social interactions, not only from distance but also in co-located settings.
In nursing homes we find a context that requires improving social interactions, and in reminiscence we find an ideal activity to make contributors out of older adults, stimulate conversation, and possibly increase connectedness between older adults and their networks. A series of studies were conducted with nursing homes stakeholders to define and design a tool suitable to their current practices, that could be used and adopted in nursing homes to stimulate co-located interactions.
In this thesis, we present the work carried out to define and validate and concept of a reminiscence-based tool, and describe how input from nursing home stakeholders has been integrated into the design of a tool to improve social interactions in residential care facilities
Contributions regarding the research of the sustainable development in agro-tourism from a circular economy perspective
Get PDFThe research background and motivation of this paper is related with the role of agro-tourism impact on environment. Agro-tourism activities impact on the development of rural area represent the reasons for it is strategic support at microeconomic and macroeconomic context. In the process of developing agro-tourism, significant attention is necessary to the environment, representing the raw material of agro-tourism activity. So, the relation among agro-tourism and environment shows a particular significance. A sustainable development and protection of the environment being the required circumstances for its practice. It is necessary realizing vital changes regarding the production and consumption of goods and services. In order to preserve our One Planet while taking into consideration economic and
social aspects. Research suggests that agro-tourism sector it is a growing sector. Therefore, the link from
agro-tourism and sustainable development are claiming the identification of new models by making the development more sustainable. So, this thesis proposes the approach of the
influence of circular economy on the sustainable development of agro-tourism. To introduce the notion of circular economy in agro-tourism it necessary to establish and apply
a sustainable development for agro-tourism structures activities. Adopting a new exemplary of management starts up with promoting new intentions related to production, consumption, ethics, etc. Circular economy in agro-tourism can lead to a sustainable use of resources for the present
and future generations and accomplish sustainable development in this domain. The present research is a contribution, by questioning present issues and future potentialities, suggest ways in which agro-tourism can embrace a sustainable development with the influence of circular economy. Highlighting to focus agro-tourism structures concerning optimizing the environment by delivering major benefits for local communities and for the
economy of Europe
Characterization of Retinal Defects in Engrailed-2 Knockout (En2-/-) Mice, a Model for Autism Spectrum Disorders (ASD)
Get PDFMice lacking the homeobox-containing transcription factor En2 (En2-/- mice) are considered as a reliable animal model for investigating the neurodevelopmental basis of autism spectrum disorders, as they display some ASD-related anatomical deficits, including cerebellar hypoplasia (Joyner A L, et al., 1991), reduced Purkinje neurons numbers (Kuemerle B, et al., 1997), altered anatomy of the amygdala (Kuemerle B, et al., 2007), and a significant loss of forebrain GABAergic interneurons (Sgadò P et al., 2013). En2-/- mice also display autistic-like behavioral defects, including decreased sociability (Brielmaier J, et al., 2012), enhanced seizure susceptibility (Tripathi P P, et al., 2009) and impaired spatial learning and memory (Provenzano G, et al., 2014) (Cheh M A, et al., 2006). A recently published study from our laboratory revealed that En2-/- mice displayed an altered disposition of GABAergic circuits in the visual cortex, that might contribute to alter binocularity and plasticity of the visual system, while leaving other visual functional properties (acuity, response latency, receptive field size) unaffected (Allegra M, et al., 2014). Moreover, preliminary experiments performed in our laboratory suggested that, at cellular level, the retina of En2-/- mice showed alterations in the number of specific cell subtypes compared with the retina of WT littermates. More importantly, an increasing number of studies published in the past years indicated that difficulties in sensory processing might somehow contribute to the pathogenesis of autism (Robertson C E, Simon B C, 2017). Therefore, we decided to investigate the possible retinal defects in the En2-/- mice. We showed for the first time that the En2 gene is expressed in all nuclear layers of the adult mouse retina. We also found that En2-/- adult mice showed a significantly decreased number of Calbindin (Calbindin+) positive horizontal cells, and a significantly increased number of Calbindin+ amacrine/ganglion cells. The number of Brn-3a (Brn-3a+) positive ganglion cells displayed no difference with respect to wild-type littermates. In addition, En2-/- adult mice showed a significantly reduced expression of the rod photoreceptor marker rhodopsin at both mRNA and protein levels, and a significant reduction of the S-cone photoreceptor S opsin, the bipolar cells marker pcp2, and the GABAergic interneurons marker parvalbumin. Electroretinogram (ERG) analysis revealed that the amplitude of b-wave in En2-/- mice scotoptic ERG was significantly reduced as compared with controls. Together, all these data indicate that En2-/- mice exhibit retinal defects at molecular, cellular and functional level, whose significance needs to be further investigated
Agon: a Gamification-Based Framework for Acceptance Requirements
Get PDFWe live in the days of social software where social interactions, from simple notifications to complex business processes, are supported by software platforms such as Facebook and Twitter. But for any social software to be successful, it must be used by a sizeable portion of its intended user community. This is fundamental for social software, but also a crucial point for most of the software systems in general, and the fulfillment of such (Usage) Acceptance Requirements critically depends on psychological, behavioral and social factors which may influence intrinsic and extrinsic motivations of the user. Operationalization techniques for Acceptance Requirements largely consist of making a game out of software usage where users are rewarded depending on the degree of their participation. The game, for instance, may be competitive or non-competitive, depending on the anticipated personality traits of intended users. Making a game out of usage is often referred to Gamification. It has attracted significant attention in the literature for the past few years because it offers a novel approach to software usage. Gamification is a powerful paradigm and a set of best practices used to motivate people carrying out a variety of ICT-mediated tasks. Designing gamification solutions and applying them to a ICT system is a complex and expensive process (in time, competences and money) as software engineers have to cope with heterogeneous stakeholder requirements on one hand, and Acceptance Requirements on the other, that together ensure effective user participation and a high level of system utilization. As such, gamification solutions require significant analysis and design as well as suitable supporting tools and techniques. In this thesis, we describe Agon, an Acceptance Requirements Framework based on Gamification, for supporting the requirements engineer in the analysis and design of engaging software systems. The framework adopts concepts and design techniques from Requirements Engineering, Human Behavior and Gamification. Agon encompasses both a method and a meta-model capturing acceptance and gamification knowledge. In particular, the framework consists of a generic acceptance goal meta-model that characterizes the problem space by capturing possible refinements for acceptance requirements, and a generic gamification meta-model that captures possible gamified operationalizations for acceptance requirements. The framework is illustrated with the Meeting Scheduler Exemplar and different heterogeneous case studies. In particular, we describe Agon through a real case study concerning the gamification of a system for collaborative decision-making, within the Participatory Architectural Change MAnagement in ATM Systems (PACAS) European Project. We describe also the Agon-Tool, a tool for enabling the requirements engineer in carrying out the systematic acceptance requirements analysis of the Agon framework in a semi-automatic supported way
Design, analysis, application and experimental assessment of algorithms for the synthesis of maximally sparse, planar, non-superdirective and steerable arrays
Get PDFThis thesis deals with the problem of synthesizing planar, maximally sparse, steerable and non-superdirective array antennas by means of convex optimization algorithms and testing their performances on an existing array to assess its far field performances in terms of requirements ful-
filment. The reason behind the choice of such topic is related to those applications wherein the power supply/consumption, the weight and the hardware/software complexity of the whole radiating system have a strong impact on the overall cost. On the other hand, the reduction of the number of elements has of course drawbacks as well (loss in directivity, which means a smaller radar coverage in radar applications, loss in robustness, etc.), however the developed algorithms can be utilized for finding acceptable trade-offs that arise, inevitably, when placing advantages and disadvantages of sparsification on the balance: it is only a matter of appropriately
translating requirements in a convex way. The synthesis scheme will be described in detail in its generality at the beginning, showing how the proposed synthesis techniques outperform several results existing in literature and setting the bar for new benchmarks. In particular, an important, innovative constraint has been considered in the synthesis problem that prevents selection of elements at distances below half-wavelength: the non-superdirectivity. Moreover, an interesting result will be derived and discussed: the trend of the reduction of the number of elements Versus the (maximum) antenna size is decreasing as the latter increases. Afterwards the discussion will
be focused on an existing antenna for radar applications, showing how the proposed algorithms intrinsically return a single layout that works jointly for transmitting and receiving (two-way synthesis). The results for the specific case chosen (mainly the set of weights and relative posi-
tions) are first numerically validated by a full-wave software (Ansys HFSS) and then experimentally assessed in anechoic chamber through measurements
Optimal choices: mean field games with controlled jumps and optimality in a stochastic volatility model
Get PDFDecision making in continuous time under random influences is the leitmotif of this work.
In the first part a family of mean field games with a state variable evolving as a jump-diffusion process is studied. Under fairly general conditions, the existence of a solution in a relaxed version of these games is established and conditions under which the optimal strategies are in fact Markovian are given. The proofs rely upon the notions of relaxed controls and martingale problems. Mean field games represent the limit, as the number of players tends to infinity, of nonzero-sum stochastic differential games. Under the assumption that the former admit a regular Markovian solution, an approximate Nash equilibrium for the corresponding n-player games is constructed, and the rate of convergence is provided. Finally, the general theory is applied to a simple illiquid inter-bank market model, where the banks can adjust their reserves only at the jump times of some given Poisson processes with a common constant intensity, and some numerical results are provided.
In the second part a stochastic optimization problem is presented. Here the evolution of the state is modeled as in the Heston model, but with a further multiplicative control input in the volatility term. The main objective is to consider the possible role of an external actor, whose exogenous contribution is summarised in the control itself. The solvability of the Hamilton-Jacobi-Bellman equation associated to this optimal control problem is discussed
Inhibition of mitochondrial translation as a novel strategy to eradicate glioblastoma stem cells
Get PDFGlioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults. The search for new effective chemotherapeutic agents to treat GBM has proven challenging throughout the last few decades. As a result, very limited pharmacological treatment is currently available. GBM aggressiveness is associated with its glioblastoma stem cells (GSCs) component, which is responsible for resistance to therapy. Therefore, new specific pharmacological approaches directed to eradicate GSCs are endowed with a great therapeutic potential.
GSCs have been shown to rely on mitochondrial respiration for their high energy demand. In order to have a functional mitochondrial respiration process, the five complexes forming the oxidative phosphorylation (OXPHOS) chain have to be built by the coordinate assembly of proteins translated by either the cytosolic or the mitochondrial ribosomes.
Given their endosymbiotic origin and despite the evolutionary changes occurred the mitochondrial ribosomes (mitoribosomes) still share structural and functional similarities with the bacterial ones, particularly considering the functional ribosomal core. In the light of these similarities, we hypothesized that antibiotics targeting bacterial ribosomes could be exploited to inhibit mitoribosomes, affecting mitochondrial translation and OXPHOS assembly, and hence leading to detrimental effect on GSCs viability. We performed a high-content imaging driven screening of several bacterial ribosome targeting antibiotics and identified Drug A as the most promising compound due to its cytotoxic and mitotoxic effects on GSCs.
We demonstrated that Drug A effectively prevents GSCs expansion, resulting to be over an order of magnitude more effective in GSCs growth inhibition than temozolomide, the only drug used in first line GBM therapy. We then investigated the mechanism of action of Drug A, proving that it inhibits mitochondrial translation and, as a consequence, it decreases the functionality of the OXPHOS complexes reducing mitochondrial respiration capacity. Moreover, we obtained the structure of this compound bound to the human mitoribosome using cryo-electron microscopy, which provides the basis for further development of more potent analogs.
Finally we proved the efficacy of Drug A in vivo using a xenograft mouse model of GBM.
Our results suggest that mitochondrial translation represents a therapeutic target for GBM and show that Drug A, acting via inhibition of mitochondrial translation, is extremely effective against GSCs. Given the urgent medical need for novel therapeutic approaches in GBM treatment, Drug A represents a promising therapeutic solution that is worth further preclinical and clinical investigations
Three essays on the drivers of employee motivation
Get PDFIn the last decade several surveys have suggested that monetary motivation is just one face of the diverse set of motivational drivers of employees' behavior, and sometimes it is not even the most powerful: indeed, they seem to be moved by different psychological motivations, such as peer motivation, the intrinsic desire to do a good job, recognition, and so on. Behavioral and experimental economics incorporate these psychological elements into the standard agency theory, and provide experimental evidence to support their relevance.
The aim of this dissertation is to explore the effects on employees' behavior of two of these psychological forces: intrinsic motivation and solidarity towards peers. Chapter 1 is a review of the effects of the interaction between intrinsic motivation and other motivational forces, both external (such as external interventions, social context, and externally set goals) and internal (such as subject's identity and achievement motives). The laboratory experiment presented in Chapter 2 investigates the relation between intrinsic motivation, wage delegation, and performance, with a twofold aim: 1) testing whether subjects who are delegated their wage choice become more intrinsically motivated 2) exploring the different reactions to wage delegation of differently motivated workers. Chapter 3 reproduces the cash posters framework à la Homans (1953, 1954) in the laboratory, and it examines whether employees are moved also by solidarity concerns towards their coworkers
Hydrothermal Processes Applied to Sludge Reduction
Get PDFConventional Activated Sludge (CAS) systems have been widely implemented to treat wastewater. CAS systems produce huge amounts of waste sludge and its subsequent treatment represents up to 65 % of the operational costs of Waste Water Treatment Plants. The final disposal of sludge is usually performed by landfilling or incineration, involving severe environmental issues. In order to reduce sludge amount, many studies have been conducted, developing new technologies. One of these technologies is HydroThermal Carbonisation (HTC), where sludge is heated up to 180-250 °C at water vapour pressure producing a solid product enriched in carbon for different possible exploitations. The aim of this work is to apply HTC to different kinds of sludge such as thickened sludge, digested sludge and dewatered sludge and compare the behaviour of the solid and liquid phases produced by the process. For the purpose, experimental tests were performed at different operating conditions in a lab
batch reactor capable to withstand high pressure (140 bar) and temperature (300 °C). In order to compare the HTC products of the different kinds of sludge, the hydrochars from HTC at different operative conditions were characterized in order to explore possible application of hydrochar and HTC process water