The Territorial Dimension: The Component of Business Strategy that Prevents the Generation of Social Conflicts

Taking advantage of economic opportunities has led to numerous conflicts between society and business in various geographies of the world. Companies have developed social responsibility programs to prevent and manage these types of problems. However, some authors comment that these programs lack a strategic vision. Starting with the Working with People model, created for the field of rural development planning, this paper proposes a methodology to prevent the generation of social conflicts from business strategy: the territorial dimension. The proposal emphasizes that local development support prevents the generation of social conflicts. Finally, an experience in Peru, a country that has been characterized in recent years by high economic growth and also by the presence of social conflicts that have stopped entrepreneurship is analyzed.

DYNAMIC MODEL BASED STATE ESTIMATION IN A HEAVY DUTY DIESEL AFTERTREATMENT SYSTEM FOR ONBOARD DIAGNOSTICS AND CONTROLS

Estimating un-measurable states is an important component for onboard diagnostics (OBD) and control strategy development in diesel exhaust aftertreatment systems. This research focuses on the development of an Extended Kalman Filter (EKF) based state estimator for two of the main components in a diesel engine aftertreatment system: the Diesel Oxidation Catalyst (DOC) and the Selective Catalytic Reduction (SCR) catalyst. One of the key areas of interest is the performance of these estimators when the catalyzed particulate filter (CPF) is being actively regenerated. In this study, model reduction techniques were developed and used to develop reduced order models from the 1D models used to simulate the DOC and SCR. As a result of order reduction, the number of states in the estimator is reduced from 12 to 1 per element for the DOC and 12 to 2 per element for the SCR. The reduced order models were simulated on the experimental data and compared to the high fidelity model and the experimental data. The results show that the effect of eliminating the heat transfer and mass transfer coefficients are not significant on the performance of the reduced order models. This is shown by an insignificant change in the kinetic parameters between the reduced order and 1D model for simulating the experimental data. An EKF based estimator to estimate the internal states of the DOC and SCR was developed. The DOC and SCR estimators were simulated on the experimental data to show that the estimator provides improved estimation of states compared to a reduced order model. The results showed that using the temperature measurement at the DOC outlet improved the estimates of the CO , NO , NO2 and HC concentrations from the DOC. The SCR estimator was used to evaluate the effect of NH3 and NOX sensors on state estimation quality. Three sensor combinations of NOX sensor only, NH3 sensor only and both NOX and NH3 sensors were evaluated. The NOX only configuration had the worst performance, the NH3 sensor only configuration was in the middle and both the NOX and NH3 sensor combination provided the best performance.

Development of an innovative non rule-based energy management strategy for a Hybrid Electric Vehicle, structured for predictive driving controls based on external information knowledge

Recently, the interest of the automotive market for hybrid vehicles has increased due to the more restrictive pollutants emissions legislation and to the necessity of decreasing the fossil fuel consumption, since such solution allows a consistent improvement of the vehicle global efficiency. The term hybridization regards the energy flow in the powertrain of a vehicle: a standard vehicle has, usually, only one energy source and one energy tank; instead, a hybrid vehicle has at least two energy sources. In most cases, the prime mover is an internal combustion engine (ICE) while the auxiliary energy source can be mechanical, electrical, pneumatic or hydraulic. It is expected from the control unit of a hybrid vehicle the use of the ICE in high efficiency working zones and to shut it down when it is more convenient, while using the EMG at partial loads and as a fast torque response during transients. However, the battery state of charge may represent a limitation for such a strategy. That’s the reason why, in most cases, energy management strategies are based on the State Of Charge, or SOC, control. Several studies have been conducted on this topic and many different approaches have been illustrated. The purpose of this dissertation is to develop an online (usable on-board) control strategy in which the operating modes are defined using an instantaneous optimization method that minimizes the equivalent fuel consumption of a hybrid electric vehicle. The equivalent fuel consumption is calculated by taking into account the total energy used by the hybrid powertrain during the propulsion phases. The first section presents the hybrid vehicles characteristics. The second chapter describes the global model, with a particular focus on the energy management strategies usable for the supervisory control of such a powertrain. The third chapter shows the performance of the implemented controller on a NEDC cycle compared with the one obtained with the original control strategy.

Iowa Nutrient Reduction Strategy : a science and technology-based framework to assess and reduce nutrients to Iowa waters and the Gulf of Mexico (2016)

On November 19, 2012, Iowa Gov. Terry Branstad, Iowa Secretary of Agriculture Bill Northey, Director Chuck Gipp from the Iowa Department of Natural Resources and Dr. John Lawrence of Iowa State University announced the release of the Iowa Nutrient Reduction Strategy for public comment. A two-month public comment period and several informational meetings allowed the public to provide feedback on the draft strategy. Updates and improvements were made to the draft based on the public comments. The final version of the strategy was released May 29, 2013. The Iowa Nutrient Reduction Strategy is a science and technology-based approach to assess and reduce nutrients delivered to Iowa waterways and the Gulf of Mexico. The strategy outlines voluntary efforts to reduce nutrients in surface water from both point sources, such as wastewater treatment plants and industrial facilities, and nonpoint sources, including farm fields and urban areas, in a scientific, reasonable and cost effective manner. The development of the strategy reflects more than two years of work led by the Iowa Department of Agriculture and Land Stewardship, Iowa Department of Natural Resources and Iowa State University. The scientific assessment to evaluate and model the effects of practices was developed through the efforts of 23 individuals representing five agencies or organizations, including scientists from ISU, IDALS, DNR, USDA Agricultural Research Service and USDA Natural Resources Conservation Service. The strategy was developed in response to the 2008 Gulf Hypoxia Action Plan that calls for the 12 states along the Mississippi River to develop strategies to reduce nutrient loading to the Gulf of Mexico. The Iowa strategy follows the recommended framework provided by EPA in 2011 and is only the second state to complete a statewide nutrient reduction strategy. This strategy is the beginning. Operational plans are being developed and work is underway. This is a dynamic document that will evolve over time, and is a key step towards improving Iowa’s water quality. The impetus for this report comes from the Water Resources Coordination Council (WRCC) which states in its 2014‐15 Annual Report “Efforts are underway to improve understanding of the multiple nutrient monitoring efforts that may be available and can be compared to the nutrient WQ monitoring framework to identify opportunities and potential data gaps to better coordinate and prioritize future nutrient monitoring efforts.” This report is the culmination of those efforts.

Iowa Nutrient Reduction Strategy : a science and technology-based framework to assess and reduce nutrients to Iowa waters and the Gulf of Mexico (2013)

On November 19, 2012, Iowa Gov. Terry Branstad, Iowa Secretary of Agriculture Bill Northey, Director Chuck Gipp from the Iowa Department of Natural Resources and Dr. John Lawrence of Iowa State University announced the release of the Iowa Nutrient Reduction Strategy for public comment. A two-month public comment period and several informational meetings allowed the public to provide feedback on the draft strategy. Updates and improvements were made to the draft based on the public comments. The final version of the strategy was released May 29, 2013. The Iowa Nutrient Reduction Strategy is a science and technology-based approach to assess and reduce nutrients delivered to Iowa waterways and the Gulf of Mexico. The strategy outlines voluntary efforts to reduce nutrients in surface water from both point sources, such as wastewater treatment plants and industrial facilities, and nonpoint sources, including farm fields and urban areas, in a scientific, reasonable and cost effective manner. The development of the strategy reflects more than two years of work led by the Iowa Department of Agriculture and Land Stewardship, Iowa Department of Natural Resources and Iowa State University. The scientific assessment to evaluate and model the effects of practices was developed through the efforts of 23 individuals representing five agencies or organizations, including scientists from ISU, IDALS, DNR, USDA Agricultural Research Service and USDA Natural Resources Conservation Service. The strategy was developed in response to the 2008 Gulf Hypoxia Action Plan that calls for the 12 states along the Mississippi River to develop strategies to reduce nutrient loading to the Gulf of Mexico. The Iowa strategy follows the recommended framework provided by EPA in 2011 and is only the second state to complete a statewide nutrient reduction strategy. This strategy is the beginning. Operational plans are being developed and work is underway. This is a dynamic document that will evolve over time, and is a key step towards improving Iowa’s water quality. The impetus for this report comes from the Water Resources Coordination Council (WRCC) which states in its 2014‐15 Annual Report “Efforts are underway to improve understanding of the multiple nutrient monitoring efforts that may be available and can be compared to the nutrient WQ monitoring framework to identify opportunities and potential data gaps to better coordinate and prioritize future nutrient monitoring efforts.” This report is the culmination of those efforts.

Iowa Nutrient Reduction Strategy : a science and technology-based framework to assess and reduce nutrients to Iowa waters and the Gulf of Mexico (2012)

On November 19, 2012, Iowa Gov. Terry Branstad, Iowa Secretary of Agriculture Bill Northey, Director Chuck Gipp from the Iowa Department of Natural Resources and Dr. John Lawrence of Iowa State University announced the release of the Iowa Nutrient Reduction Strategy for public comment. A two-month public comment period and several informational meetings allowed the public to provide feedback on the draft strategy. Updates and improvements were made to the draft based on the public comments. The final version of the strategy was released May 29, 2013. The Iowa Nutrient Reduction Strategy is a science and technology-based approach to assess and reduce nutrients delivered to Iowa waterways and the Gulf of Mexico. The strategy outlines voluntary efforts to reduce nutrients in surface water from both point sources, such as wastewater treatment plants and industrial facilities, and nonpoint sources, including farm fields and urban areas, in a scientific, reasonable and cost effective manner. The development of the strategy reflects more than two years of work led by the Iowa Department of Agriculture and Land Stewardship, Iowa Department of Natural Resources and Iowa State University. The scientific assessment to evaluate and model the effects of practices was developed through the efforts of 23 individuals representing five agencies or organizations, including scientists from ISU, IDALS, DNR, USDA Agricultural Research Service and USDA Natural Resources Conservation Service. The strategy was developed in response to the 2008 Gulf Hypoxia Action Plan that calls for the 12 states along the Mississippi River to develop strategies to reduce nutrient loading to the Gulf of Mexico. The Iowa strategy follows the recommended framework provided by EPA in 2011 and is only the second state to complete a statewide nutrient reduction strategy. This strategy is the beginning. Operational plans are being developed and work is underway. This is a dynamic document that will evolve over time, and is a key step towards improving Iowa’s water quality. The impetus for this report comes from the Water Resources Coordination Council (WRCC) which states in its 2014‐15 Annual Report “Efforts are underway to improve understanding of the multiple nutrient monitoring efforts that may be available and can be compared to the nutrient WQ monitoring framework to identify opportunities and potential data gaps to better coordinate and prioritize future nutrient monitoring efforts.” This report is the culmination of those efforts.

The Analogy as a Cognitive Strategy that Encourages Reading Comprehension in Expository Texts

This research arises from the current state of reading in Mexico, because the contextual situation to local and national level has become critical on this issue. Results on standardized tests such as ENLACE (National Assessment of Academic Achievement in Schools) and PISA (Program for International Student Assessment) have shown that Mexican basic level students have text comprehension problems. Given this reality, this is a qualitative descriptive study on the use of analogies in reading as a strategy for reading comprehension, through application of an ethnographic survey, a questionnaire and the application of a pedagogical model for the use of analogies in reading. The study incorporates the theoretical tenets of Constructivism, referring to Piaget (1969), Vygotsky (1997) and Ausubel (2002). The results show that the use of analogies promotes reading comprehension in 4th grade students, from an expository text that compares the evolution of man and the metamorphosis of a butterfly.

Development and experimental validation of a knock induced damage model and real-time implementation of model-based strategies to control knock intensity in boosted gasoline engines

This PhD thesis reports the main activities carried out during the 3 years long “Mechanics and advanced engineering sciences” course, at the Department of Industrial Engineering of the University of Bologna. The research project title is “Development and analysis of high efficiency combustion systems for internal combustion engines” and the main topic is knock, one of the main challenges for boosted gasoline engines. Through experimental campaigns, modelling activity and test bench validation, 4 different aspects have been addressed to tackle the issue. The main path goes towards the definition and calibration of a knock-induced damage model, to be implemented in the on-board control strategy, but also usable for the engine calibration and potentially during the engine design. Ionization current signal capabilities have been investigated to fully replace the pressure sensor, to develop a robust on-board close-loop combustion control strategy, both in knock-free and knock-limited conditions. Water injection is a powerful solution to mitigate knock intensity and exhaust temperature, improving fuel consumption; its capabilities have been modelled and validated at the test bench. Finally, an empiric model is proposed to predict the engine knock response, depending on several operating condition and control parameters, including injected water quantity.

Development and Validation of a Model-Based Combustion Controller for Water Injection Management

This manuscript reports the overall development of a Ph.D. research project during the “Mechanics and advanced engineering sciences” course at the Department of Industrial Engineering of the University of Bologna. The project is focused on the development of a combustion control system for an innovative Spark Ignited engine layout. In details, the controller is oriented to manage a prototypal engine equipped with a Port Water Injection system. The water injection technology allows an increment of combustion efficiency due to the knock mitigation effect that permits to keep the combustion phasing closer to the optimal position with respect to the traditional layout. At the beginning of the project, the effects and the possible benefits achievable by water injection have been investigated by a focused experimental campaign. Then the data obtained by combustion analysis have been processed to design a control-oriented combustion model. The model identifies the correlation between Spark Advance, combustion phasing and injected water mass, and two different strategies are presented, both based on an analytic and semi-empirical approach and therefore compatible with a real-time application. The model has been implemented in a combustion controller that manages water injection to reach the best achievable combustion efficiency while keeping knock levels under a pre-established threshold. Three different versions of the algorithm are described in detail. This controller has been designed and pre-calibrated in a software-in-the-loop environment and later an experimental validation has been performed with a rapid control prototyping approach to highlight the performance of the system on real set-up. To further make the strategy implementable on an onboard application, an estimation algorithm of combustion phasing, necessary for the controller, has been developed during the last phase of the PhD Course, based on accelerometric signals.

Novel dual D3R/GSK-3β modulators: an innovative multitarget strategy for bipolar disorder

Among the psychiatric diseases, bipolar disorder (BD) is the sixth leading cause of disability with a prevalence up to 4 % worldwide. BD is a complex neuropsychiatric condition which alternates episodes of mania with symptoms of depression. Although the neurobiological pathways are not completely clarified, the dopamine (DA) hypothesis, recognized as the leading theory explaining the pathophysiology of the malady, states that the dramatically compromised homeostatic regulation of dopaminergic circuits leads to alternated changes in DA neurotransmission. Modulation of D2 and D3 receptors (D2/3R) through partial agonists represents the first-line therapeutic strategy for psychiatric diseases. Moreover, a deregulation of the enzyme glycogen synthase kinase-3β (GSK-3β) has been reported as peculiar feature of BD. In this scenario, the concomitant modulation of D3R and GSK-3β, by employing multitarget compounds, could offer promises to achieve an effective cure of this illness. In the light of these findings, we rationally envisaged the pharmacophoric model at the basis of the design of several D3R partial agonists, suitable to be exploited for the dual D3R/GSK-3β ligand design. Thus, synthetic efforts were addressed to develop a first set of hybrid molecules able to concurrently modulate the selected targets. For a chemical structure point of view, we employed different spacers to combine a substituted aryl-piperazine moiety, reported in previously discovered D3R modulators, with a pyrazole-based fragment, already identified in GSK-3β inhibitors. A fluorescent and a cellular functional assays were carried out to assess the activity of all synthetized compounds against GSK-3β and on D3R, respectively. Most of the derivatives proved to effectively modulate both GSK-3β and D3R with potencies in the low-µM and low-nM range, respectively. The consistent biological data allowed us to identify some lead candidates worth to be further modified with the aim to optimize their biological profile and to perform a structure-activity relationship (SAR) study.

Development of 3D Cancer Cell Models to Test Metabolic Interventions as an Anticancer Strategy

In recent years, it has become evident that the role of mitochondria in the metabolic rewiring is essential for cancer development and progression. The metabolic profile during tumorigenesis has been performed mainly in traditional 2D cell models, including cell lines of various lineages and phenotypes. Although useful in many ways, their relevance can be often debatable, as they lack the interactions between different cells of the tumour microenvironment and/or interaction with the extracellular matrix 1,2. Improved models are now being developed using 3D cell culture technology, contributing with increased physiological relevance 3,4. In this work, we improved a method for the generation of 3D models from healthy and tumour colon tissue, based on organoid technology, and performed their molecular and biochemical characterization and validation. Further, in-plate cryopreservation was applied to these models, and optimal results were obtained in terms of cell viability and functionality of the cryopreserved models. We also cryopreserved colon fibroblasts with the aim to introduce them in a co-culture cryopreserved model with organoids. This technology allows the conversion of cell models into “plug and play” formats. Therefore, cryopreservation in-plate facilitates the accessibility of specialized cell models to cell-based research and application, in cases where otherwise such specialized models would be out of reach. Finally, we briefly explored the field of bioprinting, by testing a new matrix to support the growth of colon tumour organoids, which revealed promising preliminary results. To facilitate the reader, we organized this thesis into chapters, divided by the main points of work which include development, characterization and validation of the model, commercial output, and associated applications. Each chapter has a brief introduction, followed by results and discussion and a final conclusion. The thesis has also a general discussion and conclusion section in the end, which covers the main results obtained during this work.

Development of an innovative strategy to enhance the efficacy of gene therapy for CDKL5 deficiency disorder

CDKL5 (cyclin-dependent kinase-like 5) deficiency disorder (CDD) is a severe X-linked neurodevelopmental disease caused by mutations in the CDKL5 gene, characterized by early-onset epileptic seizures, intellectual disability, motor and visual impairment and respiratory dysregulation. Although pharmacological treatments are used to control seizures, there is currently no cure to ameliorate symptoms for CDD. Albeit delivery of a wild-type copy of the mutated gene to cells represents the most curative approach for a monogenic disease, proof-of-concept studies highlight significant efficacy caveats for brain gene therapy. The major one regards the low efficiency of gene delivery to the CNS by viral vectors. We used a secretable Igk-TATk-CDKL5 protein to enhance the efficiency of a gene therapy for CDD. In view of the properties of the Igk-chain leader sequence, the TATk-CDKL5 protein produced by infected cells is secreted via constitutive secretory pathways. Importantly, due to the transduction property of the TATk peptide, the secreted CDKL5 protein is internalized by cells. We compared the effects of a CDKL5 gene therapy with an IgK-TATk-CDKL5 gene therapy in a Cdkl5 KO mouse model to validate whether the Igk-TATk-CDKL5 approach significantly improve the therapeutic efficacy. We found that, although AAVPHP.B_Igk-TATk-CDKL5 and AAVPHP.B_CDKL5 vectors had similar brain infection efficiency, the AAVPHP.B_Igk-TATk-CDKL5 vector led to a higher CDKL5 protein replacement and Cdkl5 KO mice treated with the AAVPHP.B_Igk-TATk-CDKL5 vector showed a behavioral and neuroanatomical improvement in comparison with Cdkl5 KO mice treated with the AAVPHP.B_CDKL5 vector.

Study of Bone Biomineralization in 2D and 3D Cultures of a Human Osteosarcoma Cell Line As Osteoblast-like Model

This PhD project focuses on the study of the early stages of bone biomineralization in 2D and 3D cultures of osteoblast-like SaOS-2 osteosarcoma cells, exposed to an osteogenic cocktail. The efficacy of osteogenic treatment was assessed on 2D cell cultures after 7 days. A large calcium minerals production, an overexpression of osteogenic markers and of alkaline phosphatase activity occurred in treated samples. TEM microscopy and cryo-XANES micro-spectroscopy were performed for localizing and characterizing Ca-depositions. These techniques revealed a different localization and chemical composition of Ca-minerals over time and after treatment. Nevertheless, the Mito stress test showed in treated samples a significant increase in maximal respiration levels associated to an upregulation of mitochondrial biogenesis indicative of an ongoing differentiation process. The 3D cell cultures were realized using two different hydrogels: a commercial collagen type I and a mixture of agarose and lactose-modified chitosan (CTL). Both biomaterials showed good biocompatibility with SaOS-2 cells. The gene expression analysis of SaOS-2 cells on collagen scaffolds indicated an osteogenic commitment after treatment. and Alizarin red staining highlighted the presence of Ca-spots in the differentiated samples. In addition, the intracellular magnesium quantification, and the X-ray microscopy on mineral depositions, suggested the incorporation of Mg during the early stages of bone formation process., SaOS-2 cells treated with osteogenic cocktail produced Ca mineral deposits also on CTL/agarose scaffolds, as confirmed by alizarin red staining. Further studies are underway to evaluate the differentiation also at the genetic level. Thanks to the combination of conventional laboratory methods and synchrotron-based techniques, it has been demonstrated that SaOS-2 is a suitable model for the study of biomineralization in vitro. These results have contributed to a deeper knowledge of biomineralization process in osteosarcoma cells and could provide new evidences about a therapeutic strategy acting on the reversibility of tumorigenicity by osteogenic induction.

Waste prevention: policy instruments and business model innovation

Waste prevention (WP) is a strategy which helps societies and individuals to strive for sufficiency in resource consumption within planetary boundaries alongside sustainable and equitable well-being and to decouple the concepts of well-being and life satisfaction from materialism. Within this dissertation, some instruments to promote WP are analysed, by adopting two perspectives: firstly, the one of policymakers, at different governance levels, and secondly, the one of business in the electrical and electronic equipment (EEE) sector. At a national level, the role of WP programmes and market-based instruments (extended producer responsibility, pay-as-you-throw schemes, deposit-refund systems, environmental taxes) in boosting prevention of municipal solid waste is investigated. Then, focusing on the Emilia-Romagna Region (Italy), the performances of the waste management system are assessed over a long period, including some years before and after an institutional reform of the waste management governance regime. The impact of a centralisation (at a regional level) of both planning and economic regulation of the waste services on waste generation and WP is analysed. Finally, to support the regional decision-makers in the prioritisation of publicly funded projects for WP, a framework for the sustainability assessment, the evaluation of success, and the prioritisation of WP measures was applied to some projects implemented by Municipalities in the Region. Trying to close the research gap between engineering and business, WP strategies are discussed as drivers for business model (BM) innovation in EEE sector. Firstly, an innovative approach to a digital tracking solution for professional EEE management is analysed. New BMs which facilitate repair, reuse, remanufacturing, and recycling are created and discussed. Secondly, the impact of BMs based on servitisation and on producer ownership on the extension of equipment lifetime is analysed, by performing a review of real cases of organizations in the EEE sector applying result- and use-oriented BMs.

Orchestration of multiscale model for computational oncology

Cancer is a challenging disease that involves multiple types of biological interactions in different time and space scales. Often computational modelling has been facing problems that, in the current technology level, is impracticable to represent in a single space-time continuum. To handle this sort of problems, complex orchestrations of multiscale models is frequently done. PRIMAGE is a large EU project that aims to support personalized childhood cancer diagnosis and prognosis. The goal is to do so predicting the growth of the solid tumour using multiscale in-silico technologies. The project proposes an open cloud-based platform to support decision making in the clinical management of paediatric cancers. The orchestration of predictive models is in general complex and would require a software framework that support and facilitate such task. The present work, proposes the development of an updated framework, referred herein as the VPH-HFv3, as a part of the PRIMAGE project. This framework, a complete re-writing with respect to the previous versions, aims to orchestrate several models, which are in concurrent development, using an architecture as simple as possible, easy to maintain and with high reusability. This sort of problem generally requires unfeasible execution times. To overcome this problem was developed a strategy of particularisation, which maps the upper-scale model results into a smaller number and homogenisation which does the inverse way and analysed the accuracy of this approach.