Design, development and characterization of DHA-based emulsion for Nutrilipidomics strategies

The industrial PhD project presented here is part of the R&D strategies of the Lipinutragen company. The innovation brought by the company concerns nutrilipidomics, i.e. the correlation between the lipid composition (in fatty acids) of the cell membrane and lipid-based nutraceuticals, especially starting from the well-known dependence of the lipid composition on the intake of essential fats, omega- 6 and omega-3 polyunsaturated fatty acids. Among the results obtained from the membrane lipidomic profiles, the case of autistic subjects is here highlighted, showing the significant deficiency of docosahexaenoic acid (DHA). The activity during the PhD was devoted to the nutrilipidomic approach. Part of the activities were devoted to scientific research in lipidomics: a) the study of lipidomic profiles in the frame of two collaboration projects: one with the group of Dr. I. Tueros at AZTI, Bilbao, regading obese population, and the other one regarding seed germination with the changes of the fatty acid profiles with the group of prof. A. Balestrazzi of the University of Parma; b) the liposome preparation for protection and lifetime prolongation of the peptide somatostatin, which was an important premise to the formulation of the DHA-containing microemulsion. The activities was also focused on the development of DHA-containing nutraceutical formulations in the form of emulsion, overcoming the difficulty of the capsule ingestion, to be administered orally. The work pointed to study the combination of active ingredients, based on the previous know-how regarding the bioavailability for the cell membrane incorporation. The ingredients of the formulation were studied and tested in vitro for the bioavailability of DHA to be incorporated in the cell membranes of different types of cultured cells. Part of this study is covered by non-disclosure agreement since it belongs to the know-how of Lipinutragen.

Design, realization, and characterization of complex reaction networks in dynamic mechanically interlocked molecules

The experimental projects discussed in this thesis are all related to the field of artificial molecular machines, specifically to systems composed of pseudorotaxane and rotaxane architectures. The characterization of the peculiar properties of these mechano-molecules is frequently associated with the analysis and elucidation of complex reaction networks; this latter aspect represents the main focus and central thread tying my thesis work. In each chapter, a specific project is described as summarized below: the focus of the first chapter is the realization and characterization of a prototype model of a photoactivated molecular transporter based on a pseudorotaxane architecture; in the second chapter is reported the design, synthesis, and characterization of a [2]rotaxane endowed with a dibenzylammonium station and a novel photochromic unit that acts as a recognition site for a DB24C8 crown ether macrocycle; in the last chapter is described the synthesis and characterization of a [3]rotaxane in which the relative number of rings and stations can be changed on command.

Design, development and guidance of the Airborne’s quadrotor

The main goal of the Airborne project is to develop, at technology readiness level 8 (TRL8), a few selected robotic aerial technologies for quick localization of victims by avalanches by equipping drones with two forefront sensors used in SAR operations in case of avalanches, namely the ARVA and RECCO. This thesis focuses on the design, development, and guidance of the TRL8 quadrotor developed during the project. We present and describe the design method that allowed us to obtain an EMI shielded UAV capable of integrating both RECCO and ARVA sensors. Besides, is presented the avionics and power train design and building procedure in order to obtain a modular UAV frame that can be easily carried by rescuers and achieves all the performance benchmarks of the project. Additionally, in addition to the onboard algorithms, a multivariate regressive convolutional neural network whose goal is the localization of the ARVA signal is presented. On guidance, the automatic flight procedure is described, and the onboard waypoint generator algorithm is presented. The goal of this algorithm is the generation and execution of an automatic grid pattern without the need to know the map in advance and without the support of a control ground station (CGS). Moreover, we present an iterative trajectory planner that does not need pre-knowledge of the map and uses Bézier curves to address optimal, dynamically feasible, safe, and re-plannable trajectories. The goal is to develop a method that allows local and fast replannings in case of an obstacle pop up or if some waypoints change. This makes the novel planner suitable to be applied in SAR operations. The introduction of the final version of the quadrotor is supported by internal flight tests and field tests performed in real operative scenarios by the Club Alpino Italiano (CAI).

Design, expression, and characterization of FimH antigen as single recombinant protein or exposed on nanoparticles

Uropathogenic Escherichia coli (UPEC) accounts for approximately 85% of all urinary tract infections (UTIs), causing a global economic burden. E. coli is one of the pathogens mentioned in the ESKAPEE list drafted by OMS, meaning that the increasing antibiotic resistance acquired by UPEC is and will be a serious health problem in the future. Amongst the immunogenic antigens exposed on the surface of UPEC, FimH represent a potential target for vaccine development, since it is involved in the early stages of infection. As already demonstrated, immunizations with FimH elicit functional antibodies that prevent UPEC infections even though the number of doses required to elicit a strong immune response is not optimal. In this work, we aimed to stabilize FimH as a soluble recombinant antigen exploiting the donor strand complementation mechanism by generating different chimeric constructs constituted by FimH and FimG donor strand. To explore the potential of self-assembling nanoparticles to display FimH through genetic fusion, different constructs have been computationally designed and produced. In this work a structure-based design, using available crystal structures of FimH and three different NPs was performed to generate different constructs with optimized properties. Despite the different conditions tested, all the constructs designed (single antigen or chimeric NPs), resulted to be un-soluble proteins in E. coli. To overcome this issue a mammalian expression system has been tested. Soluble antigen expression was achieved for all constructs tested in the culture supernatants. Three novel chimeric NPs have been characterized by transmission electron microscopy (TEM) confirming the presence of correctly assembled NPs displaying UPEC antigen. In vivo study has shown a higher immunogenicity of the E. coli antigen when displayed on NPs surface compared to the single recombinant antigen. The antibodies elicited by chimeric NPs showed a higher functionality in the inhibition of bacterial adhesion.

Design, synthesis and photovoltaic properties of some thiophene-based conjugated polymers for organic solar cells

The current issue of the resource of energy combined with the tendency to give a green footprint to our lifestyle have prompted the research to focus the attention on alternative sources with great strides in the optimization of polymeric photovoltaic devices. The research work described in this dissertation consists in the study of different semiconducting π-conjugated materials based on polythiophenes (Chapter I). In detail, the GRIM polymerization was deepened defining the synthetic conditions to obtain regioregular poly(3-alkylthiophene) (Chapter II). Since the use of symmetrical monomers functionalized with oxygen atom(s) allows to adopt easy synthesis leading to performing materials, disubstituted poly(3,4-dialkoxythiophene)s were successfully prepared, characterized and tested as photoactive materials in solar cells (Chapter III). A “green” resource of energy should be employed through sustainable devices and, for this purpose, the research work was continued on the synthesis of thiophene derivatives soluble in eco-friendly solvents. To make this possible, the photoactive layer was completely tailored starting from the electron-acceptor material. A fullerene derivative soluble in alcohols was successfully synthetized and adopted for the realization of the new devices (Chapter IV). New water/alcohol soluble electron-donor materials with different functional groups were prepared and their properties were compared (Chapter V). Once found the best ionic functional group, a new double-cable material was synthetized optimizing the surface area between the different materials (Chapter VI). Finally, other water/alcohol soluble materials were synthetized, characterized and used as cathode interlayers in eco-friendly devices (Chapter VII). In this work, all prepared materials were characterized by spectroscopy analyses, gel permeation chromatography and thermal analyses. Cyclic voltammetry, X-ray diffraction, atomic force microscopy and external quantum efficiency were used to investigate some peculiar aspects.

Design, synthesis and biological evaluation of dual inhibitors of GSK-3B and Fyn kinases for the study of inflammatory pathways in neurodegenerative diseases

Neuroinflammation represents a key hallmark of neurodegenerative diseases and is the result of a complex network of signaling cascades within microglial cells. A positive feedback loop exists between inflammation, microglia activation and protein misfolding processes, that, together with oxidative stress and excitotoxicity, lead to neuronal degeneration. Therefore, targeting this vicious cycle can be beneficial for mitigating neurodegeneration and cognitive decline in central nervous system disorders. At molecular level, GSK-3B and Fyn kinases play a crucial role in microglia activation and their deregulation has been associated to many neurodegenerative diseases. Thus, we envisioned their combined targeting as an effective approach to disrupt this toxic loop. Specifically in this project, a hit compound, based on a 7-azaindole-3-aminothiazole structure, was first identified in a virtual screening campaign, and displayed a weak dual inhibitory activity on GSK-3B and Fyn, unbalanced towards the former. Then, in a commitment to uncover the structural features required for modulating the activity on the two targets, we systematically manipulated this compound by inserting various substitution patterns in different positions. The most potent compounds obtained were advanced to deeper investigations to test their ability of tackling the inflammatory burden also in cellular systems and to unveil their binding modes within the catalytic pocket. The new class of molecules synthesized emerged as a valuable tool to deepen our understanding of the complex network governing the inflammatory events in neurodegenerative disorders.

Design, fabrication and mechanical characterization of a structural node made using Wire and Arc Additive Manufacturing (WAAM) technology

Additive Manufacturing (AM), also known as “3D printing”, is a recent production technique that allows the creation of three-dimensional elements by depositing multiple layers of material. This technology is widely used in various industrial sectors, such as automotive, aerospace and aviation. With AM, it is possible to produce particularly complex elements for which traditional techniques cannot be used. These technologies are not yet widespread in the civil engineering sector, which is slowly changing thanks to the advantages of AM, such as the possibility of realizing elements without geometric restrictions, with less material usage and a higher efficiency, in particular employing Wire-and-Arc Additive Manufacturing (WAAM) technology. Buildings that benefit most from AM are all those structures designed using form-finding and free-form techniques. These include gridshells, where joints are the most critical and difficult elements to design, as the overall behaviour of the structure depends on them. It must also be considered that, during the design, the engineer must try to minimize the structure's own weight. Self-weight reductions can be achieved by Topological Optimization (TO) of the joint itself, which generates complex geometries that could not be made using traditional techniques. To sum up, weight reductions through TO combined with AM allow for several potential benefits, including economic ones. In this thesis, the roof of the British Museum is considered as a case study, analysing the gridshell structure of which a joint will be chosen to be designed and manufactured, using TO and WAAM techniques. Then, the designed joint will be studied in order to understand its structural behaviour in terms of stiffness and strength. Finally, a printing test will be performed to assess the production feasibility using WAAM technology. The computational design and fabrication stages were carried out at Technische Universität Braunschweig in Germany.

A note on the likelihood and moments of the skew-normal distribution

In this paper an alternative approach to the one in Henze (1986) is proposed for deriving the odd moments of the skew-normal distribution considered in Azzalini (1985). The approach is based on a Pascal type triangle, which seems to greatly simplify moments computation. Moreover, it is shown that the likelihood equation for estimating the asymmetry parameter in such model is generated as orthogonal functions to the sample vector. As a consequence, conditions for a unique solution of the likelihood equation are established, which seem to hold in more general setting.

Effects of Road Construction Intensity and Operations on Rural Freeway Work Zone Capacity, TPF-5(081), 2014

Capacity is affected by construction type and its intensity on adjacent open traffic lanes. The effect on capacity is a function of vehicles moving in and out of the closed lanes of the work zone, and the presence of heavy construction vehicles. Construction activity and its intensity, however, are not commonly considered in estimating capacity of a highway lane. The main purpose of this project was to attempt to quantify the effects of construction type and intensity (e.g. maintenance, rehabilitation, reconstruction, and milling) on work zone capacity. The objective of this project is to quantify the effects of construction type and its intensity on work zone capacity and to develop guidelines for MoDOT to estimate the specific operation type and intensity that will improve the traffic flow by reducing the traffic flow and queue length commonly associated with work zones. Despite the effort put into field data collection, the data collected did not show a full speed-flow chart therefore extracting a reliable capacity value was difficult. A statistical comparison between the capacity values found in this study using either methodologies indicates that there is an effect of construction activity on the values work zone capacity. It was found that the heavy construction activity reduces the capacity. It is very beneficial to conduct similar studies on the capacity of work zone with different lane closure barriers, which is also directly related to the type of work zone being short-term or long-term work zones. Also, the effect of different geometric and environmental characteristics of the roadway should be considered in future studies.

Value added logistics in supply and demand chain. Smile. Part 2. eBusiness in a service business. Case: A maintenance and operations network in forest industry

VVALOSADE is a research project of professor Anita Lukka's VALORE research team in the Lappeenranta University of Technology. The VALOSADE includes the ELO technology program of Tekes. SMILE is one of four subprojects of the VALOSADE. The SMILE study focuses on the case of the company network that is composed of small and micro-sized mechanical maintenance service providers and forest industry as large-scale customers. The basic principle of the SMILE study is the communication and ebusiness in supply and demand networks. The aim of the study is to develop ebusiness strategy, ebusiness model and e-processes among the SME local service providers, and onthe other hand, between the local service provider network and the forest industry customers in a maintenance and operations service business. A literature review, interviews and benchmarking are used as research methods in this qualitative case study. The first SMILE report, 'Ebusiness between Global Company and Its Local SME Supplier Network', concentrated on creating background for the SMILE study by studying general trends of ebusiness in supply chains and networks of different industries. This second phase of the study concentrates on case network background, such as business relationships, information systems and business objectives; core processes in maintenance and operations service network; development needs in communication among the network participants; and ICT solutions to respond needs in changing environment. In the theory part of the report, different ebusiness models and frameworks are introduced. Those models and frameworks are compared to empirical case data. From that analysis of the empirical data, therecommendations for the development of the network information system are derived. In process industry such as the forest industry, it is crucial to achieve a high level of operational efficiency and reliability, which sets up great requirements for maintenance and operations. Therefore, partnerships or strategic alliances are needed between the network participants. In partnerships and alliances, deep communication is important, and therefore the information systems in the network also are critical. Communication, coordination and collaboration will increase in the case network in the future, because network resources must be optimised to improve competitive capability of the forest industry customers and theefficiency of their service providers. At present, ebusiness systems are not usual in this maintenance network. A network information system among the forest industry customers and their local service providers actually is the only genuinenetwork information system in this total network. However, the utilisation of that system has been quite insignificant. The current system does not add value enough either to the customers or to the local service providers. At present, thenetwork information system is the infomediary that share static information forthe network partners. The network information system should be the transaction intermediary, which integrates internal processes of the network companies; the network information system, which provides common standardised processes for thelocal service providers; and the infomediary, which share static and dynamic information on right time, on right partner, on right costs, on right format and on right quality. This study provides recommendations how to develop this system in the future to add value to the network companies. Ebusiness scenarios, vision, objectives, strategies, application architecture, ebusiness model, core processes and development strategy must be considered when the network information system will be developed in the next development step. The core processes in the case network are demand/capacity management, customer/supplier relationship management, service delivery management, knowledge management and cash flow management. Most benefits from ebusiness solutions come from the electrifying of operational level processes, such as service delivery management and cash flow management.

State of Logistics and Operations Management in Finnish and Swedish Companies – Survey Research Findings

In this research we are examining what is the status of logistics and operations management in Finnish and Swedish companies. Empirical data is based on the web based questionnaire, which was completed in the end of 2007 and early 2008. Our examination consists of roughly 30 answers from largest manufacturing (highest representation in our sample), trade and logistics/distribution companies. Generally it could be argued that these companies operate in complex environment, where number of products, raw materials/components and suppliers is high. However, usually companies rely on small amount of suppliers per raw material/component (highest frequency is 2), and this was especially the case among Swedish companies, and among those companies, which favoured overseas sourcing. Sample consisted of companies which mostly are operating in an international environment, and are quite often multinationals. Our survey findings reveal that companies in general have taken logistics and information technology as part of their strategy process; utilization of performance measures as well as system implementations have followed the strategy decisions. In the transportation mode side we identify that road transports dominate all transport flow classes (inbound, internal and outbound), followed by sea and air. Surprisingly small amount of companies use railways, but in general we could argue that Swedish companies prefer this mode over Finnish counterparts. With respect of operations outsourcing, we found that more traditional areas of logistics outsourcing are driving factors in company's performance measurement priority. In contrary to previous research, our results indicate that the scope of outsourcing is not that wide in logistics/operations management area, and companies are not planning to outsource more in the near future. Some support is found for more international operations and increased outsourcing activity. From the increased time pressure of companies, we find evidence that local as well as overseas customers expect deliveries within days or weeks, but suppliers usually supply within weeks or months. So, basically this leads into considerable inventory holding. Interestingly local and overseas sourcing strategy does not have that great influence on lead time performance of these particular sourcing areas - local strategy is anyway considerably better in responding on market changes due to shorter supply lead times. In the end of our research work we have completed correlation analysis concerning items asked with Likert scale. Our analysis shows that seeing logistics more like a process rather than function, applying time based management, favouring partnerships and measuring logistics within different performance dimensions results on preferred features and performance found in logistics literature.

Integration in project business : mechanisms for integrating customers and the project network during the life-cycle of industrial projects

This thesis focuses on integration in project business, i.e. how projectbased companies organize their product and process structures when they deliver industrial solutions to their customers. The customers that invest in these solutions run their businesses in different geographical, political and economical environments, which should be acknowledged by the supplier when providing solutions comprising of larger and more complex scopes than previously supplied to these customers. This means that the suppliers are increasing their supply range by taking over some of the activities in the value chain that have traditionally been handled by the customer. In order to be able to provide the functioning solutions, including more engineering hours, technical equipment and a wider project network, a change is needed in the mindset in order to be able to carry out and take the required responsibility that these new approaches bring. For the supplier it is important to be able to integrate technical products, systems and services, but the supplier also needs to have the capabilities to integrate the cross-functional organizations and departments in the project network, the knowledge and information between and within these organizations and departments, along with inputs from the customer into the product and process structures during the lifecycle of the project under development. Hence, the main objective of this thesis is to explore the challenges of integration that industrial projects meet, and based on that, to suggest a concept of how to manage integration in project business by making use of integration mechanisms. Integration is considered the essential process for accomplishing an industrial project, whereas the accomplishment of the industrial project is considered to be the result of the integration. The thesis consists of an extended summary and four papers, that are based on three studies in which integration mechanisms for value creation in industrial project networks and the management of integration in project business have been explored. The research is based on an inductive approach where in particular the design, commissioning and operations functions of industrial projects have been studied, addressing entire project life-cycles. The studies have been conducted in the shipbuilding and power generation industries where the scopes of supply consist of stand-alone equipment, equipment and engineering, and turnkey solutions. These industrial solutions include demanding efforts in engineering and organization. Addressing the calls for more studies on the evolving value chains of integrated solutions, mechanisms for inter- and intra-organizational integration and subsequent value creation in project networks have been explored. The research results in thirteen integration mechanisms and a typology for integration is proposed. Managing integration consists of integrating the project network (the supplier and the sub-suppliers) and the customer (the customer’s business purpose, operations environment and the end-user) into the project by making use of integration mechanisms. The findings bring new insight into research on industrial project business by proposing integration of technology and engineering related elements with elements related to customer oriented business performance in contemporary project environments. Thirteen mechanisms for combining products and the processes needed to deliver projects are described and categorized according to the impact that they have on the management of knowledge and information. These mechanisms directly relate to the performance of the supplier, and consequently to the functioning of the solution that the project provides. This thesis offers ways to promote integration of knowledge and information during the lifecycle of industrial projects, enhancing the development towards innovative solutions in project business.