Challenges and Opportunities in Transforming Laser System Industry to Deliver Integrated Product and Service Offers

Part 4: Transition Towards Product-Service Systems

Literary reading is a team game: exercices with Carroll and Carle.

This paper will focus on the issue of training future literary reading mediators or promoters. It will propose a practical exercise on playing with intertextuality with the aid of two children literature classics and masterpieces—The Adventures of Alice in Wonderland by Lewis Carroll (1865) and The Very Hungry Caterpillar by Eric Carle (1969). This exercise is not designed to be a pedagogical or didactic tool used with children (that could alternatively be done with the same corpora), but it is designed to focus on issues of literary studies and contemporary culture. The aim of this practical exercise with future reading promoters is to enable graduate students or trainees to be able to recognize that literary reading can be a team game. However, before arriving at the agan stage, where the rules get simplified and attainable by young readers, hard and solitary work of the mediator is required. The rules of this solitary game of preparing the reading of classical texts are not always evident. On the other hand, the reason why literary reading could be (and perhaps should be) defined as a new team game in our contemporary and globalized world derives directly from the fact that we now live in a world where mass culture is definitely installed. We should be pragmatic on evaluating the conditions of communication between people (not only young adults or children) and we should look the way people read the signs on everyday life and consequently behave in contemporary society, and then apply the same rules or procedures to introduce old players such as the classical books in the game. We are talking about adult mediators and native digital readers. In the contemporary democratic social context, cultural producers and consumers are two very important elements (as the book itself) of the literary polissystem. So, teaching literature is more than ever to be aware that the literary reader meaning of a text does not reside only in the text and in its solitary relationship with the quiet and comfortably installed reader. Meaning is produced by the reader in relation both to the text in question and to the complex network of texts invoked in the reading process and plural connections provided by the world of a new media environment.

"Portuguese Observatory of Taeniasis and Cysticercosis": A "One Health" example for epidemiological surveillance of one neglected disease in a European country

Cysticercosis results from the ingestion Taenia solium eggs directly by faecal-oral route or contaminated food or water. Human tapeworm carriers who have become infected after ingesting pork meat contaminated with cysticerci release these eggs. Cysticercosis occurs after tapeworm eggs are ingested by an intermediate host (pig or human) and then hatch, migrate, and lodge in the host's tissues, where they develop onto larval cysticerci. When they lodged in the central nervous system of humans, results in the disease condition called Neurocysticercosis (NCC), with a heterogeneous manifestations depending of the locations of cysts, number, size and their stage of evolution (1). Consequently the prognostic ranges from asymptomatic to situations leading to death in 2% to 9.8%. of cases (7) In swine’s there are few studies, but recent works have proved that animals, for the same reasons, also have neurological abnormalities, expressed by seizures, stereotypic walk in circles, chewing motions with foamy salivation included tonic muscle contractions followed by a sudden diminution in all muscle tone leading to collapse (2). Conventional domestic wastewater treatment processes may not be totally effective in inactivating parasites eggs from Taenia solium, allowing some contamination of soils and agricultural products (11). In Portugal there are some evidence of aggregation of human cysticercosis cases in specific regions, bases in ecological design studies (6). There are few information about human tapeworm carriers and social and economic factors associated with them. Success in knowledge and consequently in lowering transmission is limited by the complex network of biological and social factors that maintain the spread. Effective control of mostly zoonosis require One Health approach, after a real knowledge and transparency in the information provided by the institutions responsible for both animal and human health, allowing sustained interventions targeted at the transmission cycle's crucial nodes. In general, the model used to control, reflects a rural reality, where pigs are raised freely, poor sanitation conditions and incipient sanitary inspection. In cysticercosis, pigs are obligate intermediate hosts and so considered as first targets for control and used as sentinels to monitor environmental T. solium contamination (3). Usually environmental contamination with Taenia spp. eggs is a key issue in most of studies with landscape factors influencing presence of Taenia spp. antigens in both pigs and humans (5). Soil-related factors as well as socio-economic and behavioural factors are associated with the emergence of significant clustering human cysticercosis (4,5). However scarce studies has been produced in urban environmental and in developed countries with the finality to characterize the spatial pattern. There are still few data available regarding its prevalence and spatial distribution; Transmission patterns are likely to exhibit correlations as housing conditions, water supply, basic sanitation, schooling and birthplace of the individual or relatives, more than pigs rearing free, soil conditions (9). As a matter of fact, tapeworm carriers from endemic zones can auto-infect or transmit infection to other people or arrive already suffering NCC (as a result of travelling to or being a citizen from an endemic cysticercosis country) to a free cysticercosis country. Transmission is fecal-oral; this includes transmission through person-to-person contact, through autoinfection, or through contaminated food This has been happening in different continents as North America (5.4–18% been autochthonous), Europe and Australia (7). Recently, case reports of NCC have also emerged from Muslim countries. (10). Actually, different papers relate an epidemic situation in Spain and Portugal (7, 8). However the kind of study done does not authorize such conclusion. There are no evidence that infections were acquired in Portugal and there are not characterized the mode of transmission. Papers with these kind of information will be allow to have economic consequences resulted from artificial trade barriers with serious consequences for pig producers and pig meat trade. We need transparency in information’s that allow provide the basis to support the development and targeting of future effective control programmes (and prove we need that). So, to have a real picture of the disease, it is necessary integrate data from human, animal and environmental factors surrounding human and pig cases to characterize the pattern of the transmission. The design needs to be able to capture unexpected, and not common outcomes (routine data). We need to think “One Health” to get a genuine image of the situation.

Synthesis, Characterization, and Applications of a Novel Cu(II)-MOF Based on a Propargylcarbamate-Functionalized Isophthalate Ligand

This work describes the synthesis of a propargylcarbamate-functionalized isophthalate ligand and its use in the solvothermal preparation of a new copper(II)-based metal organic framework named [Cu(1,3-YBDC)]ˑxH2O (also abbreviated as Cu-MOF. The characterization of this compound was performed using several complementary techniques such as infrared (ATR-FTIR) and Raman spectroscopy, X-ray powder diffraction spectroscopy (PXRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), atomic absorption spectroscopy (AAS) as well as thermal and surface area measurements. Synchrotron X-ray diffraction analysis revealed that this MOF contains a complex network of 5-substituted isophthalate anions bound to Cu(II) centers, arranged in pairs within paddlewheel (or “Chinese lantern”) structure with a short Cu…Cu distance of 2.633 Å. Quite unexpectedly, the apical atom in the paddlewheel structure belongs to the carbamate carbonyl oxygen atom. Such extra coordination by the propargylcarbamate groups drastically reduces the MOF porosity, a feature that was also confirmed by BET measurements. Indeed, its surface area was determined to be low (14.5 ± 0.8 m2/g) as its total pore volume (46 mm3/g). Successively the Cu-MOF was treated with HAuCl4 with the aim of studying the ability of the propargylcarbamate functionality to capture the Au(III) ion and reduce it to Au(0) to give gold nanoparticles (AuNPs). The overall amount of gold retained by the Cu-MOF/Au was determined by AAS while the amount of gold and its oxidation state on the surface of the MOF was studied by XPS. A glassy carbon (GC) electrode was drop-casted with a Cu-MOF suspension to electrochemically characterize the material through cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The performance of the modified electrodes towards nitrite oxidation was tested by CV and chronoamperometry.

Development of new chemical entities to target neuroinflammatory pathways.

Neuroinflammatory pathways are main culprits of neurodegenerative diseases' onset and progression, including Alzheimer’s disease (AD). On this basis, several anti-inflammatory drugs were repurposed in clinical trials. However, they have failed, probably because neuroinflammation is a complex network, still not fully understood. From these evidences, this thesis focused on the design and synthesis of new chemical entities as potential neuroinflammatory drugs or chemical probes. Projects 1 and 2 aimed to multi-target-directed ligand (MTDL) development to target neuroinflammation in AD. Polypharmacology by MTDLs is considered one of the most promising strategies to face the multifactorial nature of neurodegenerative diseases. Particularly, Project 1 took inspiration from a cromolyn-ibuprofen drug combination polypharmacological approach, which was recently investigated in AD clinical trials. Based on that, two cromolyn-(S)-ibuprofen codrug series were designed and synthesized. Parent drugs were combined via linking or fusing strategies in 1:2 or 1:1 ratio, by means of hydrolyzable bonds. Project 2 started from a still ongoing AD clinical trial on investigational drug neflamapimod. It is a selective inhibitor of p38α-MAPK, a kinase strictly involved in neuroinflammatory pathways. On the other side, rasagiline, an anti-Parkinson drug, was also repurposed as AD treatment. Indeed, rasagiline’s propargylamine fragment demonstrated to be responsible not only for the MAO-B selective inhibition, but also for the neuroprotective activity. Thus, to synergistically combine these two effects into single-molecules, a small set of neflamapimod-rasagiline hybrids was developed. In the end BMX, a poorly investigated kinase, which seems to be involved in pro-inflammatory mediator production, was explored for the development of new chemical probes. High-quality chemical probes are a powerful tool in target validation and starting points for the development of new drug candidates. Thus, Project 3 focused on the design and synthesis of two series of optimized BMX covalent inhibitors as selective chemical probes.

Aquivion-based spray freeze-dried composite catalysts for the cascade conversion of furfural to γ-valerolactone

Furfural is one of the most promising biomass derived platform molecules. It is to this day produced in volumes above 300 ktons per year from the hydrolysis and dehydration of hemicellulose, one of the main components of lignocellulosic biomass. While the majority of the yearly production is destined to selective reduction to furfuryl alcohol for the production of furan resins, these molecules hold great potential for the production of more valuable chemicals, fuels, fuel additives and solvents. Among these products are alkyl levulinates and γ-valerolactone. To convert furfural to these target products, a cascade process involving Lewis acidity-catalysed reduction steps and Brønsted acidity-catalysed steps. In order to develop catalysts capable of promoting the one-pot domino reaction from furfural to γ-valerolactone, the two kinds of acidity must both be present. To this end, in this work, the spray freeze-drying technique is employed to combine the high activity and strong Brønsted acidity of Aquivion with the structural properties and Lewis acidity of different supporting metal oxide, forming composite catalysts. The flexibility of the spray freeze-drying technique and the modulable composition of the catalysts allowed a thorough study of the complex network of equilibria underlying the cascade reaction, while achieving high selectivities towards the final product.

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.

Models for the assessment of resilience in water distribution networks

The following thesis work focuses on the use and implementation of advanced models for measuring the resilience of water distribution networks. In particular, the functions implemented in GRA Tool, a software developed by the University of Exeter (UK), and the functions of the Toolkit of Epanet 2.2 were investigated. The study of the resilience and failure, obtained through GRA Tool and the development of the methodology based on the combined use of EPANET 2.2 and MATLAB software, was tested in a first phase, on a small-sized literature water distribution network, so that the variability of the results could be perceived more clearly and with greater immediacy, and then, on a more complex network, that of Modena. In the specific, it has been decided to go to recreate a mode of failure deferred in time, one proposed by the software GRA Tool, that is failure to the pipes, to make a comparison between the two methodologies. The analysis of hydraulic efficiency was conducted using a synthetic and global network performance index, i.e., Resilience index, introduced by Todini in the years 2000-2016. In fact, this index, being one of the parameters with which to evaluate the overall state of "hydraulic well-being" of a network, has the advantage of being able to act as a criterion for selecting any improvements to be made on the network itself. Furthermore, during these analyzes, was shown the analytical development undergone over time by the formula of the Resilience Index. The final intent of this thesis work was to understand by what means to improve the resilience of the system in question, as the introduction of the scenario linked to the rupture of the pipelines was designed to be able to identify the most problematic branches, i.e., those that in the event of a failure it would entail greater damage to the network, including lowering the Resilience Index.

MODELING THE EVOLUTION OF COMPLEX NETWORKS THROUGH THE PATH-STAR TRANSFORMATION AND OPTIMAL MULTIVARIATE METHODS

The topology of real-world complex networks, such as in transportation and communication, is always changing with time. Such changes can arise not only as a natural consequence of their growth, but also due to major modi. cations in their intrinsic organization. For instance, the network of transportation routes between cities and towns ( hence locations) of a given country undergo a major change with the progressive implementation of commercial air transportation. While the locations could be originally interconnected through highways ( paths, giving rise to geographical networks), transportation between those sites progressively shifted or was complemented by air transportation, with scale free characteristics. In the present work we introduce the path-star transformation ( in its uniform and preferential versions) as a means to model such network transformations where paths give rise to stars of connectivity. It is also shown, through optimal multivariate statistical methods (i.e. canonical projections and maximum likelihood classification) that while the US highways network adheres closely to a geographical network model, its path-star transformation yields a network whose topological properties closely resembles those of the respective airport transportation network.

Optimal Path Searching through Specified Routes using different Algorithms

To connect different electrical, network and data devices with the minimum cost and shortest path, is a complex job. In huge buildings, where the devices are placed at different locations on different floors and only some specific routes are available to pass the cables and buses, the shortest path search becomes more complex. The aim of this thesis project is, to develop an application which indentifies the best path to connect all objects or devices by following the specific routes.To address the above issue we adopted three algorithms Greedy Algorithm, Simulated Annealing and Exhaustive search and analyzed their results. The given problem is similar to Travelling Salesman Problem. Exhaustive search is a best algorithm to solve this problem as it checks each and every possibility and give the accurate result but it is an impractical solution because of huge time consumption. If no. of objects increased from 12 it takes hours to search the shortest path. Simulated annealing is emerged with some promising results with lower time cost. As of probabilistic nature, Simulated annealing could be non optimal but it gives a near optimal solution in a reasonable duration. Greedy algorithm is not a good choice for this problem. So, simulated annealing is proved best algorithm for this problem. The project has been implemented in C-language which takes input and store output in an Excel Workbook

An Optimal Distributed Algorithm for All-Pairs Shortest-Path

In this paper the network problem of determining all-pairs shortest-path is examined. A distributed algorithm which runs in O(n) time on a network of n nodes is presented. The number of messages of the algorithm is O(e+n log n) where e is the number of communication links of the network. We prove that this algorithm is time optimal.

Solving complex optimal control problems at no cost with PSOPT

This paper introduces PSOPT, an open source optimal control solver written in C++. PSOPT uses pseudospectral and local discretizations, sparse nonlinear programming, automatic differentiation, and it incorporates automatic scaling and mesh refinement facilities. The software is able to solve complex optimal control problems including multiple phases, delayed differential equations, nonlinear path constraints, interior point constraints, integral constraints, and free initial and/or final times. The software does not require any non-free platform to run, not even the operating system, as it is able to run under Linux. Additionally, the software generates plots as well as LATEX code so that its results can easily be included in publications. An illustrative example is provided.

A roughly smooth optimal consumption path: smoothing the rough annuity puzzle

A inconsistência entre a teoria e o comportamento empírico dos agentes no que tange ao mercado privado de pensões tem se mostrado um dos mais resistentes puzzles presentes na literatura econômica. Em modelos de otimização intertemporal de consumo e poupança sob incerteza em relação ao tempo de vida dos agentes, anuidades são ativos dominantes, anulando ou restringindo fortemente a demanda por ativos cujos retornos não estão relacionados à probabilidade de sobrevivência. Na prática, entretanto, consumidores são extremamente céticos em relação às anuidades. Em oposição ao seguro contra longevidade oferecido pelas anuidades, direitos sobre esses ativos - essencialmente ilíquidos - cessam no caso de morte do titular. Nesse sentido, choques não seguráveis de liquidez e a presença de bequest motives foram consideravelmente explorados como possíveis determinantes da baixa demanda verificada. Apesar dos esforços, o puzzle persiste. Este trabalho amplia a dominância teórica das anuidades sobre ativos não contingentes em mercados incompletos; total na ausência de bequest motives, e parcial, quando os agentes se preocupam com possíveis herdeiros. Em linha com a literatura, simulações numéricas atestam que uma parcela considerável do portfolio ótimo dos agentes seria constituída de anuidades mesmo diante de choques de liquidez, bequest motives, e preços não atuarialmente justos. Em relação a um aspecto relativamente negligenciado pela academia, mostramos que o tempo ótimo de conversão de poupança em anuidades está diretamente relacionado à curva salarial dos agentes. Finalmente, indicamos que, caso as preferências dos agentes sejam tais que o nível de consumo ótimo decaia com a idade, a demanda por anuidades torna-se bastante sensível ao sobrepreço (em relação àquele atuarialmente justo) praticado pela indústria, chegando a níveis bem mais compatíveis com a realidade empírica.

Evolutionary multi-move path-relinking for transmission network expansion planning

This paper presents the application of a new metaheuristic algorithm to solve the transmission expansion planning problem. A simple heuristic, using a relaxed network model associated with cost perturbation, is applied to generate a set of high quality initial solutions with different topologies. The population is evolved using a multi-move path-relinking with the objective of finding minimum investment cost for the transmission expansion planning problem employing the DC representation. The algorithm is tested on the southern Brazilian system, obtaining the optimal solution for the system with better performance than similar metaheuristics algorithms applied to the same problem. ©2010 IEEE.

Finding Quasi-Optimal Network Topologies for Information Transmission in Active Networks

This work clarifies the relation between network circuit (topology) and behaviour (information transmission and synchronization) in active networks, e.g. neural networks. As an application, we show how one can find network topologies that are able to transmit a large amount of information, possess a large number of communication channels, and are robust under large variations of the network coupling configuration. This theoretical approach is general and does not depend on the particular dynamic of the elements forming the network, since the network topology can be determined by finding a Laplacian matrix (the matrix that describes the connections and the coupling strengths among the elements) whose eigenvalues satisfy some special conditions. To illustrate our ideas and theoretical approaches, we use neural networks of electrically connected chaotic Hindmarsh-Rose neurons.