Oligodeoxynucleotide synthesis using protecting groups and a linker cleavable under non-nucleophilic conditions

Oligodeoxynucleotides (ODNs) containing latent electrophilic groups can be highly useful in antisense drug development and many other applications such as chemical biology and medicine, where covalent cross-linking of ODNs with mRNA, protein and ODN is required. However, such ODN analogues cannot be synthesized using traditional technologies due to the strongly nucleophilic conditions used in traditional deprotection/cleavage process. To solve this long lasting and highly challenging problem in nucleic acid chemistry, I used the 1,3-dithian-2-yl-methoxycarbonyl (Dmoc) function to protect the exo-amino groups on the nucleobases dA, dC and dG, and to design the linker between the nascent ODN and solid support. These protecting groups and linker are completely stable under all ODN synthesis conditions, but can be readily cleaved under non-nucleophilic and nearly neutral conditions. As a result, the new ODN synthesis technology is universally useful for the synthesis of electrophilic ODNs. The dissertation is mainly comprised of two portions. In the first portion, the development of the Dmoc-based linker for ODN synthesis will be described. The construction of the dT-Dmoc-linker required a total of seven steps to synthesize. The linker was then anchored to the solid support―controlled pore glass (CPG). In the second portion, the syntheses of Dmoc-protected phosphoramidites ODN synthesis monomers including Dmoc-dC-amidite, Dmoc-dA-amidite, Dmoc-dG-amidite are described. The protection of dC and dA with 1,3-dithian-2-yl-methyl 4-nitrophenyl carbonate proceeded smoothly giving Dmoc-dC and Dmoc-dA in good yields. However, when the same acylation procedure was applied for the synthesis of Dmoc-dG, very low yield was obtained. This problem was later solved using a highly innovative and environmentally benign procedure, which is expected to be widely useful for the acylation of the exo-amino groups on nucleoside bases. The reactions to convert the Dmoc-protected nucleosides to phosphoramidite monomers proceeded smoothly with high yields. Using the Dmoc phosphoramidite monomers dA, dC, dG and the commercially available dT, and the Dmoc linker, four ODN sequences were synthesized. In all cases, excellent coupling yields were obtained. ODN deprotection/cleavage was achieved by using non-nucleophilic oxidative conditions. The new technology is predicted to be universally useful for the synthesis of ODNs containing one or more electrophilic functionalities.

Understanding the Impact of the Property Tax Appeal Process on Assessment Uniformity: Procedures, Structures, and Outcomes

Property taxes serve as a vital revenue source for local governments. The revenues derived from the property tax function as the primary funding source for a variety of critical local public service systems. Property tax appeal systems serve as quasi-administrative-judicial mechanisms intended to assure the public that property tax assessments are correct, fair, and equitable. Despite these important functions, there is a paucity of empirical research related to property tax appeal systems. This study contributes to property tax literature by identifying who participates in the property tax appeal process and examining their motivations for participation. In addition, the study sought to determine whether patterns of use and success in appeal systems affected the distribution of the tax burden. Data were collected by means of a survey distributed to single-family property owners from two Florida counties. In addition, state and county documents were analyzed to determine appeal patterns and examine the impact on assessment uniformity, over a three-year period. The survey data provided contextual evidence that single-family property owners are not as troubled by property taxes as they are by the conduct of local government officials. The analyses of the decision to appeal indicated that more expensive properties and properties excluded from initial uniformity analyses were more likely to be appealed, while properties with homestead exemptions were less likely to be appealed. The value change analyses indicated that appeals are clustered in certain geographical areas; however, these areas do not always experience a greater percentage of the value changes. Interestingly, professional representation did not increase the probability of obtaining a reduction in value. Other relationships between the variables were discovered, but often with weak predictive ability. Findings from the assessment uniformity analyses were also interesting. The results indicated that the appeals mechanisms in both counties improved assessment uniformity. On average, appealed properties exhibited greater horizontal and vertical inequities, as compared to non-appealed properties, prior to the appeals process. After, the appeal process was completed; the indicators of horizontal and vertical equity were largely improved. However, there were some indications of regressivity in the final year of the study.

Simple approximate MAP inference for Dirichlet processes mixtures

The Dirichlet process mixture model (DPMM) is a ubiquitous, flexible Bayesian nonparametric statistical model. However, full probabilistic inference in this model is analytically intractable, so that computationally intensive techniques such as Gibbs sampling are required. As a result, DPMM-based methods, which have considerable potential, are restricted to applications in which computational resources and time for inference is plentiful. For example, they would not be practical for digital signal processing on embedded hardware, where computational resources are at a serious premium. Here, we develop a simplified yet statistically rigorous approximate maximum a-posteriori (MAP) inference algorithm for DPMMs. This algorithm is as simple as DP-means clustering, solves the MAP problem as well as Gibbs sampling, while requiring only a fraction of the computational effort. (For freely available code that implements the MAP-DP algorithm for Gaussian mixtures see http://www.maxlittle.net/.) Unlike related small variance asymptotics (SVA), our method is non-degenerate and so inherits the “rich get richer” property of the Dirichlet process. It also retains a non-degenerate closed-form likelihood which enables out-of-sample calculations and the use of standard tools such as cross-validation. We illustrate the benefits of our algorithm on a range of examples and contrast it to variational, SVA and sampling approaches from both a computational complexity perspective as well as in terms of clustering performance. We demonstrate the wide applicabiity of our approach by presenting an approximate MAP inference method for the infinite hidden Markov model whose performance contrasts favorably with a recently proposed hybrid SVA approach. Similarly, we show how our algorithm can applied to a semiparametric mixed-effects regression model where the random effects distribution is modelled using an infinite mixture model, as used in longitudinal progression modelling in population health science. Finally, we propose directions for future research on approximate MAP inference in Bayesian nonparametrics.

Non-invasive winding fault detection for induction machines based on stray flux magnetic sensors

Non-intrusive monitoring of health state of induction machines within industrial process and harsh environments poses a technical challenge. In the field, winding failures are a major fault accounting for over 45% of total machine failures. In the literature, many condition monitoring techniques based on different failure mechanisms and fault indicators have been developed where the machine current signature analysis (MCSA) is a very popular and effective method at this stage. However, it is extremely difficult to distinguish different types of failures and hard to obtain local information if a non-intrusive method is adopted. Typically, some sensors need to be installed inside the machines for collecting key information, which leads to disruption to the machine operation and additional costs. This paper presents a new non-invasive monitoring method based on GMRs to measure stray flux leaked from the machines. It is focused on the influence of potential winding failures on the stray magnetic flux in induction machines. Finite element analysis and experimental tests on a 1.5-kW machine are presented to validate the proposed method. With time-frequency spectrogram analysis, it is proven to be effective to detect several winding faults by referencing stray flux information. The novelty lies in the implement of GMR sensing and analysis of machine faults.

Engineering design of an integrated sustainable process system for cassava biobased materials

Cassava contributes significantly to biobased material development. Conventional approaches for its bio-derivative-production and application cause significant wastes, tailored material development challenges, with negative environmental impact and application limitations. Transforming cassava into sustainable value-added resources requires redesigning new approaches. Harnessing unexplored material source, and downstream process innovations can mitigate challenges. The ultimate goal proposed an integrated sustainable process system for cassava biomaterial development and potential application. An improved simultaneous release recovery cyanogenesis (SRRC) methodology, incorporating intact bitter cassava, was developed and standardized. Films were formulated, characterised, their mass transport behaviour, simulating real-distribution-chain conditions quantified, and optimised for desirable properties. Integrated process design system, for sustainable waste-elimination and biomaterial development, was developed. Films and bioderivatives for desired MAP, fast-delivery nutraceutical excipients and antifungal active coating applications were demonstrated. SRRC-processed intact bitter cassava produced significantly higher yield safe bio-derivatives than peeled, guaranteeing 16% waste-elimination. Process standardization transformed entire root into higher yield and clarified colour bio-derivatives and efficient material balance at optimal global desirability. Solvent mass through temperature-humidity-stressed films induced structural changes, and influenced water vapour and oxygen permeability. Sevenunit integrated-process design led to cost-effectiveness, energy-efficient and green cassava processing and biomaterials with zero-environment footprints. Desirable optimised bio-derivatives and films demonstrated application in desirable in-package O2/CO2, mouldgrowth inhibition, faster tablet excipient nutraceutical dissolutions and releases, and thymolencapsulated smooth antifungal coatings. Novel material resources, non-root peeling, zero-waste-elimination, and desirable standardised methodology present promising process integration tools for sustainable cassava biobased system development. Emerging design outcomes have potential applications to mitigate cyanide challenges and provide bio-derivative development pathways. Process system leads to zero-waste, with potential to reshape current style one-way processes into circular designs modelled on nature's effective approaches. Indigenous cassava components as natural material reinforcements, and SRRC processing approach has initiated a process with potential wider deployment in broad product research development. This research contributes to scientific knowledge in material science and engineering process design.

Adopting results based management in the non-profit sector: Trócaire’s experience

The increasing emphasis on aid effectiveness, accountability and impact measurement in international development and humanitarian work has generated a requirement for high quality internal systems for the management of programmes. To help to address this requirement, Trócaire adopted Results Based Management in the 20 countries in which it works. This paper provides an overview of Trócaire’s RBM journey, including the process of embedding the new approach in the organisation, lessons learnt from this process, the subsequent benefits that are emerging at field programme level and the challenges going forward.

Enhancement to the Mortgage Licensing Process

The Consumer Finance Division of the South Carolina State Board of Financial Institutions is responsible for the supervision, licensing and examination of all consumer finance companies, deferred presentment companies, check cashing companies, and non-depository mortgage lenders and their loan originators. This project specifically focuses on the licensing of Mortgage Lender/Servicer ( company), Mortgage Lender/Servicer Branch (branch) and Mortgage Loan Originator (loan originator) licenses. The problem statement is how the Division can handle increasing the number of mortgage loan originators in the state without delaying the time to process applications. The goal of this project is to make the current licensing process more efficient so that the Division can handle the increased workload without having to hire additional personnel.

Commande prédictive non linéaire d’un séchoir à lit fluidisé pour granules pharmaceutiques

Avec la disponibilité de capteurs fiables de teneur en eau exploitant la spectroscopie proche infrarouge (NIR pour near-infrared) et les outils chimiométriques, il est maintenant possible d’appliquer des stratégies de commande en ligne sur plusieurs procédés de séchage dans l’industrie pharmaceutique. Dans cet ouvrage, le séchage de granules pharmaceutiques avec un séchoir à lit fluidisé discontinu (FBD pour fluidized bed dryer) de taille pilote est étudié à l’aide d’un capteur d’humidité spectroscopique. Des modifications électriques sont d’abord effectuées sur le séchoir instrumenté afin d’acheminer les signaux mesurés et manipulés à un périphérique d’acquisition. La conception d’une interface homme-machine permet ensuite de contrôler directement le séchoir à l’aide d’un ordinateur portable. Par la suite, un algorithme de commande prédictive (NMPC pour nonlinear model predictive control), basée sur un modèle phénoménologique consolidé du FBD, est exécuté en boucle sur ce même ordinateur. L’objectif est d’atteindre une consigne précise de teneur en eau en fin de séchage tout en contraignant la température des particules ainsi qu’en diminuant le temps de lot. De plus, la consommation énergétique du FBD est explicitement incluse dans la fonction objectif du NMPC. En comparant à une technique d’opération typique en industrie (principalement en boucle ouverte), il est démontré que le temps de séchage et la consommation énergétique peuvent être efficacement gérés sur le procédé pilote tout en limitant plusieurs problèmes d’opération comme le sous-séchage, le surséchage ou le surchauffage des granules.

The Selection Process of Applications to the Portuguese Innovation Incentive System: Who Gets Financial Support?

Public policies to support entrepreneurship and innovation play a vital role when firms have difficulties in accessing external finance. However, some authors have found evidence of long-term inefficiency in subsidized firms (Bernini and Pelligrini, 2011; Cerqua and Pelligrini, 2014) and ineffectiveness of public funds (Jorge and Suárez, 2011). The aim of the paper is to assess the effectiveness in the selection process of applications to public financial support for stimulating innovation. Using a binary choice model, we investigate which factors influence the probability of obtaining public support for an innovative investment. The explanatory variables are connected to firm profile, the characteristics of the project and the macroeconomic environment. The analysis is based on the case study of the Portuguese Innovation.Incentive System (PIIS) and on the applications managed by the Alentejo Regional Operational Program in the period 2007 – 2013. The results show that the selection process is more focused on the expected impact of the project than on the firm’s past performance. Factors that influence the credit risk and the decision to grant a bank loan do not seem to influence the government evaluator regarding the funding of some projects. Past activities in R&D do not significantly affect the probability of having an application approved under the PIIS, whereas an increase in the number of patents and the number of skilled jobs are both relevant factors. Nevertheless, some evidence of firms’ short-term inefficiency was found, in that receiving public financial support is linked to a smaller increase in productivity compared to non-approved firm applications. At the macroeconomic level, periods with a higher cost of capital in financial markets are linked to a greater probability of getting an application for public support approved, which could be associated with the effectiveness of public support in correcting market failings.

Deposition of thin films by a non-equilibrium atmospheric pressure Plasma Jet: a poly-diagnostic study

The use of atmospheric pressure plasmas for thin film deposition on thermo-sensitive materials is currently one of the main challenges of the plasma scientific community. Despite the growing interest in this field, the existing knowledge gap between gas-phase reaction mechanisms and thin film properties is still one of the most important barriers to overcome for a complete understanding of the process. In this work, thin films surface characterization techniques, combined with passive and active gas-phase diagnostic methods, were used to provide a comprehensive study of the Ar/TEOS deposition process assisted by an atmospheric pressure plasma jet. SiO2-based thin films exhibiting a well-defined chemistry, a good morphological structure and high uniformity were studied in detail by FTIR, XPS, AFM and SEM analysis. Furthermore, non-intrusive spectroscopy techniques (OES, filter imaging) and laser spectroscopic methods (Rayleigh scattering, LIF and TALIF) were employed to shed light on the complexity of gas-phase mechanisms involved in the deposition process and discuss the influence of TEOS admixture on gas temperature, electron density and spatial-temporal behaviours of active species. The poly-diagnostic approach proposed in this work opens interesting perspectives both in terms of process control and optimization of thin film performances.

Non-Equilibrium Atmospheric Plasma As A Novel Route To Nanomaterial Synthesis And Processing For Biomedical Applications

Since last century, the rising interest of value-added and advanced functional materials has spurred a ceaseless development in terms of industrial processes and applications. Among the emerging technologies, thanks to their unique features and versatility in terms of supported processes, non-equilibrium plasma discharges appear as a key solvent-free, high-throughput and cost-efficient technique. Nevertheless, applied research studies are needed with the aim of addressing plasma potentialities optimizing devices and processes for future industrial applications. In this framework, the aim of this dissertation is to report on the activities carried out and the results achieved concerning the development and optimization of plasma techniques for nanomaterial synthesis and processing to be applied in the biomedical field. In the first section, the design and investigation of a plasma assisted process for the production of silver (Ag) nanostructured multilayer coatings exhibiting anti-biofilm and anti-clot properties is described. With the aim on enabling in-situ and on-demand deposition of Ag nanoparticles (NPs), the optimization of a continuous in-flight aerosol process for particle synthesis is reported. The stability and promising biological performances of deposited coatings spurred further investigation through in-vitro and in-vivo tests which results are reported and discussed. With the aim of addressing the unanswered questions and tuning NPs functionalities, the second section concerns the study of silver containing droplet conversion in a flow-through plasma reactor. The presented results, obtained combining different analysis techniques, support a formation mechanism based on droplet to particle conversion driven by plasma induced precursor reduction. Finally, the third section deals with the development of a simulative and experimental approach used to investigate the in-situ droplet evaporation inside the plasma discharge addressing the main contributions to liquid evaporation in the perspective of process industrial scale up.

Development of a thermochemical/biological process to convert waste biomass into new resources

The increasing attention to environmental issues of recent times encourages us to find new methods for the production of energy from renewable sources, and to improve existing ones, increasing their energy yield. Most of the waste and agricultural residues, with a high content of lignin and non-hydrolysable polymers, cannot be effectively transformed into biofuels with existing technology. The purpose of the study was to develop a new thermochemical/ biological process (named Py-AD) for the valorization of scarcely biodegradable substances. A complete continuous prototype was design built and run for 1 year. This consists into a slow pyrolysis system coupled with two sequential digesters and showed to produce a clean pyrobiogas (a biogas with significant amount of C2-C3 hydrocarbons and residual CO/H2), biochar and bio-oil. Py-AD yielded 31.7% w/w biochar 32.5% w/w oil and 24.8% w/w pyrobiogas. The oil condensate obtained was fractionated in its aqueous and organic fraction (87% and 13% respectively). Subsequently, the anaerobic digestion of aqueous fraction was tested in a UASB reactor, for 180 days, in increasing organic loading rate (OLR). The maximum convertible concentration without undergoing instability phenomena and with complete degradation of pyrogenic chemicals was 1.25 gCOD L digester-1 d-1. The final yield of biomethane was equal to 40% of the theoretical yield and with a noticeable additional production equal to 20% of volatile fatty acids. The final results confirm that anaerobic digestion can be used as a useful tool for cleaning of slow pyrolysis products (both gas and condensable fraction) and the obtaining of relatively clean pyrobiogas that could be directly used in internal combustion engine.

Influence of free-radical functionalization on non-woven filtering media for medical application

Nowadays the leukodepletion is one of the most important processes done on the blood in order to reduce the risk of transfusion diseases. It can be performed through different techniques but the most popular one is the filtration due to its simplicity and efficiency. This work aims at improving a current commercial product, by developing a new filter based on Fenton-type reaction to cross-link a hydrogel on to the base material. The filters for leukodepletion are preferably made through the melt flow technique resulting in a non-woven tissue; the functionalization should increase the stability of the filter restricting the extraction of substances to minimum amount when in contact with blood. Through the modification the filters can acquire new properties including wettability, surface charge and good resistance to the extractions. The most important for leukodepletion is the surface charge due to the nature of the filtration process. All the modified samples results have been compared to the commercial product. Three different polymers (A, B and C) have been studied for the filter modifications and every modified filter has been tested in order to determine its properties.

La moltiplicazione relazionale dei non imparentati. Un'etnografia delle attese di genitorialità e filiazione intorno alla categoria giuridica di "minore straniero non accompagnato" in Italia.

Sulla spinta dell’approvazione della legge italiana 47/2017 “Disposizioni in materia di misure di protezione dei minori stranieri non accompagnati”, questo lavoro è teso ad affrontare le complesse aspettative genitoriali e parentali sviluppatesi intorno al processo di categorizzazione MSNA di cui questa legge è diventata approdo giuridico. Le controverse aspettative di accompagnamento legatesi alla denominazione di “non accompagnato”, prese come aspetto scontato e assiomatico in molta parte della letteratura scientifica che utilizza l’acronimo, sono state qui intese come un nodo ambiguo e questionabile. Attraverso una ricerca e una metodologia antropologico-etnografica queste rappresentazioni contradditorie sono esplorate a partire da un “crocevia di campi” da queste interessati in un territorio amministrativo dell’Italia Settentrionale variamente frequentato tra 2018 e 2021. Insieme ad ambienti, metodi e sfide della ricerca locale, una prima sezione situa storicamente e contestualmente la categoria MSNA come fenomeno in sé piuttosto che come efficace espressione descrittiva di soggetti. Le due sezioni successive, dedicate rispettivamente alla neo-realtà di tutela volontaria e a quella di una comunità socio-educativa/di tipo familiare rivolta a persone di minore età, interrogano invece questi ambienti come spazi e tempi di elaborazione prima e negoziazione poi di rappresentazioni e pratiche relazionali e parentali molteplici.

NB-IoT via non terrestrial networks

Massive Internet of Things is expected to play a crucial role in Beyond 5G (B5G) wireless communication systems, offering seamless connectivity among heterogeneous devices without human intervention. However, the exponential proliferation of smart devices and IoT networks, relying solely on terrestrial networks, may not fully meet the demanding IoT requirements in terms of bandwidth and connectivity, especially in areas where terrestrial infrastructures are not economically viable. To unleash the full potential of 5G and B5G networks and enable seamless connectivity everywhere, the 3GPP envisions the integration of Non-Terrestrial Networks (NTNs) into the terrestrial ones starting from Release 17. However, this integration process requires modifications to the 5G standard to ensure reliable communications despite typical satellite channel impairments. In this framework, this thesis aims at proposing techniques at the Physical and Medium Access Control layers that require minimal adaptations in the current NB-IoT standard via NTN. Thus, firstly the satellite impairments are evaluated and, then, a detailed link budget analysis is provided. Following, analyses at the link and the system levels are conducted. In the former case, a novel algorithm leveraging time-frequency analysis is proposed to detect orthogonal preambles and estimate the signals’ arrival time. Besides, the effects of collisions on the detection probability and Bit Error Rate are investigated and Non-Orthogonal Multiple Access approaches are proposed in the random access and data phases. The system analysis evaluates the performance of random access in case of congestion. Various access parameters are tested in different satellite scenarios, and the performance is measured in terms of access probability and time required to complete the procedure. Finally, a heuristic algorithm is proposed to jointly design the access and data phases, determining the number of satellite passages, the Random Access Periodicity, and the number of uplink repetitions that maximize the system's spectral efficiency.