Understanding ten-eleven translocation-2 in hematological and nervous systems

I proposed the study of two distinct aspects of Ten-Eleven Translocation 2 (TET2) protein for understanding specific functions in different body systems. ^ In Part I, I characterized the molecular mechanisms of Tet2 in the hematological system. As the second member of Ten-Eleven Translocation protein family, TET2 is frequently mutated in leukemic patients. Previous studies have shown that the TET2 mutations frequently occur in 20% myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 10% T-cell lymphoma leukemia and 2% B-cell lymphoma leukemia. Genetic mouse models also display distinct phenotypes of various types of hematological malignancies. I performed 5-hydroxymethylcytosine (5hmC) chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA sequencing (RNA-Seq) of hematopoietic stem/progenitor cells to determine whether the deletion of Tet2 can affect the abundance of 5hmC at myeloid, T-cell and B-cell specific gene transcription start sites, which ultimately result in various hematological malignancies. Subsequent Exome sequencing (Exome-Seq) showed that disease-specific genes are mutated in different types of tumors, which suggests that TET2 may protect the genome from being mutated. The direct interaction between TET2 and Mutator S Homolog 6 (MSH6) protein suggests TET2 is involved in DNA mismatch repair. Finally, in vivo mismatch repair studies show that the loss of Tet2 causes a mutator phenotype. Taken together, my data indicate that TET2 binds to MSH6 to protect genome integrity. ^ In Part II, I intended to better understand the role of Tet2 in the nervous system. 5-hydroxymethylcytosine regulates epigenetic modification during neurodevelopment and aging. Thus, Tet2 may play a critical role in regulating adult neurogenesis. To examine the physiological significance of Tet2 in the nervous system, I first showed that the deletion of Tet2 reduces the 5hmC levels in neural stem cells. Mice lacking Tet2 show abnormal hippocampal neurogenesis along with 5hmC alternations at different gene promoters and corresponding gene expression downregulation. Through the luciferase reporter assay, two neural factors Neurogenic differentiation 1 (NeuroD1) and Glial fibrillary acidic protein (Gfap) were down-regulated in Tet2 knockout cells. My results suggest that Tet2 regulates neural stem/progenitor cell proliferation and differentiation in adult brain.^

Multivariate orthogonal polynomials and integrable systems

Multivariate orthogonal polynomials in D real dimensions are considered from the perspective of the Cholesky factorization of a moment matrix. The approach allows for the construction of corresponding multivariate orthogonal polynomials, associated second kind functions, Jacobi type matrices and associated three term relations and also Christoffel-Darboux formulae. The multivariate orthogonal polynomials, their second kind functions and the corresponding Christoffel-Darboux kernels are shown to be quasi-determinants as well as Schur complements of bordered truncations of the moment matrix; quasi-tau functions are introduced. It is proven that the second kind functions are multivariate Cauchy transforms of the multivariate orthogonal polynomials. Discrete and continuous deformations of the measure lead to Toda type integrable hierarchy, being the corresponding flows described through Lax and Zakharov-Shabat equations; bilinear equations are found. Varying size matrix nonlinear partial difference and differential equations of the 2D Toda lattice type are shown to be solved by matrix coefficients of the multivariate orthogonal polynomials. The discrete flows, which are shown to be connected with a Gauss-Borel factorization of the Jacobi type matrices and its quasi-determinants, lead to expressions for the multivariate orthogonal polynomials and their second kind functions in terms of shifted quasi-tau matrices, which generalize to the multidimensional realm, those that relate the Baker and adjoint Baker functions to ratios of Miwa shifted tau-functions in the 1D scenario. In this context, the multivariate extension of the elementary Darboux transformation is given in terms of quasi-determinants of matrices built up by the evaluation, at a poised set of nodes lying in an appropriate hyperplane in R^D, of the multivariate orthogonal polynomials. The multivariate Christoffel formula for the iteration of m elementary Darboux transformations is given as a quasi-determinant. It is shown, using congruences in the space of semi-infinite matrices, that the discrete and continuous flows are intimately connected and determine nonlinear partial difference-differential equations that involve only one site in the integrable lattice behaving as a Kadomstev-Petviashvili type system. Finally, a brief discussion of measures with a particular linear isometry invariance and some of its consequences for the corresponding multivariate polynomials is given. In particular, it is shown that the Toda times that preserve the invariance condition lay in a secant variety of the Veronese variety of the fixed point set of the linear isometry.

Talking about quality: exploring how ‘quality’ is conceptualized in European hospitals and healthcare systems

BACKGROUND: Conceptualization of quality of care - in terms of what individuals, groups and organizations include in their meaning of quality, is an unexplored research area. It is important to understand how quality is conceptualised as a means to successfully implement improvement efforts and bridge potential disconnect in language about quality between system levels, professions, and clinical services. The aim is therefore to explore and compare conceptualization of quality among national bodies (macro level), senior hospital managers (meso level), and professional groups within clinical micro systems (micro level) in a cross-national study. METHODS: This cross-national multi-level case study combines analysis of national policy documents and regulations at the macro level with semi-structured interviews (383) and non-participant observation (803 hours) of key meetings and shadowing of staff at the meso and micro levels in ten purposively sampled European hospitals (England, the Netherlands, Portugal, Sweden, and Norway). Fieldwork at the meso and micro levels was undertaken over a 12-month period (2011-2012) and different types of micro systems were included (maternity, oncology, orthopaedics, elderly care, intensive care, and geriatrics). RESULTS: The three quality dimensions clinical effectiveness, patient safety, and patient experience were incorporated in macro level policies in all countries. Senior hospital managers adopted a similar conceptualization, but also included efficiency and costs in their conceptualization of quality. 'Quality' in the forms of measuring indicators and performance management were dominant among senior hospital managers (with clinical and non-clinical background). The differential emphasis on the three quality dimensions was strongly linked to professional roles, personal ideas, and beliefs at the micro level. Clinical effectiveness was dominant among physicians (evidence-based approach), while patient experience was dominant among nurses (patient-centered care, enough time to talk with patients). Conceptualization varied between micro systems depending on the type of services provided. CONCLUSION: The quality conceptualization differed across system levels (macro-meso-micro), among professional groups (nurses, doctors, managers), and between the studied micro systems in our ten sampled European hospitals. This entails a managerial alignment challenge translating macro level quality definitions into different local contexts.

Investigating the Roles and Requirements, Manifestations and Management of Metadata in the Creation of Reliable and Preservation of Authentic Electronic Entities Created by Dynamic, Interactive and Experiential Systems: Report on the Work and Findings of the Interpares 2 Description Cross Domain Group

Metadata that is associated with either an information system or an information object for purposes of description, administration, legal requirements, technical functionality, use and usage, and preservation, plays a critical role in ensuring the creation, management, preservation and use and re-use of trustworthymaterials, including records. Recordkeeping1 metadata, of which one key type is archival description, plays a particularly important role in documenting the reliability and authenticity of records and recordkeeping systemsas well as the various contexts (legal-administrative, provenancial, procedural, documentary, and technical) within which records are created and kept as they move across space and time. In the digital environment, metadata is also the means by which it is possible to identify how record components – those constituent aspects of a digital record that may be managed, stored and used separately by the creator or the preserver – can be reassembled to generate an authentic copy of a record or reformulated per a user’s request as a customized output package.Issues relating to the creation, capture, management and preservation of adequate metadata are, therefore, integral to any research study addressing the reliability and authenticity of digital entities, regardless of the community, sector or institution within which they are being created. The InterPARES 2 Description Cross-Domain Group (DCD) examined the conceptualization, definitions, roles, and current functionality of metadata and archival description in terms of requirements generated by InterPARES 12. Because of the needs to communicate the work of InterPARES in a meaningful way across not only other disciplines, but also different archival traditions; to interface with, evaluate and inform existing standards, practices and other research projects; and to ensure interoperability across the three focus areas of InterPARES2, the Description Cross-Domain also addressed its research goals with reference to wider thinking about and developments in recordkeeping and metadata. InterPARES2 addressed not only records, however, but a range of digital information objects (referred to as “entities” by InterPARES 2, but not to be confused with the term “entities” as used in metadata and database applications) that are the products and by-products of government, scientific and artistic activities that are carried out using dynamic, interactive or experiential digital systems. The nature of these entities was determined through a diplomatic analysis undertaken as part of extensive case studies of digital systems that were conducted by the InterPARES 2 Focus Groups. This diplomatic analysis established whether the entities identified during the case studies were records, non-records that nevertheless raised important concerns relating to reliability and authenticity, or “potential records.” To be determined to be records, the entities had to meet the criteria outlined by archival theory – they had to have a fixed documentary format and stable content. It was not sufficient that they be considered to be or treated as records by the creator. “Potential records” is a new construct that indicates that a digital system has the potential to create records upon demand, but does not actually fix and set aside records in the normal course of business. The work of the Description Cross-Domain Group, therefore, addresses the metadata needs for all three categories of entities.Finally, since “metadata” as a term is used today so ubiquitously and in so many different ways by different communities, that it is in peril of losing any specificity, part of the work of the DCD sought to name and type categories of metadata. It also addressed incentives for creators to generate appropriate metadata, as well as issues associated with the retention, maintenance and eventual disposition of the metadata that aggregates around digital entities over time.

Integrated soil fertility management in eastern and western Africa: The role of knowledge and innovation systems, its adoption and impact

The rise in population growth, as well as nutrient mining, has contributed to low agricultural productivity in Sub-Saharan Africa (SSA). A plethora of technologies to boost agricultural production have been developed but the dissemination of these agricultural innovations and subsequent uptake by smallholder farmers has remained a challenge. Scientists and philanthropists have adopted the Integrated Soil Fertility Management (ISFM) paradigm as a means to promote sustainable intensification of African farming systems. This comparative study aimed: 1) To assess the efficacy of Agricultural Knowledge and Innovation Systems (AKIS) in East (Kenya) and West (Ghana) Africa in the communication and dissemination of ISFM (Study I); 2) To investigate how specifically soil quality, and more broadly socio-economic status and institutional factors, influence farmer adoption of ISFM (Study II); and 3) To assess the effect of ISFM on maize yield and total household income of smallholder farmers (Study III). To address these aims, a mixed methodology approach was employed for study I. AKIS actors were subjected to social network analysis methods and in-depth interviews. Structured questionnaires were administered to 285 farming households in Tamale and 300 households in Kakamega selected using a stratified random sampling approach. There was a positive relationship between complete ISFM awareness among farmers and weak knowledge ties to both formal and informal actors at both research locations. The Kakamega AKIS revealed a relationship between complete ISFM awareness among farmers and them having strong knowledge ties to formal actors implying that further integration of formal actors with farmers’ local knowledge is crucial for the agricultural development progress. The structured questionnaire was also utilized to answer the query pertaining to study II. Soil samples (0-20 cm depth) were drawn from 322 (Tamale, Ghana) and 459 (Kakamega, Kenya) maize plots and analysed non-destructively for various soil fertility indicators. Ordinal regression modeling was applied to assess the cumulative adoption of ISFM. According to model estimates, soil carbon seemed to preclude farmers from intensifying input use in Tamale, whereas in Kakamega it spurred complete adoption. This varied response by farmers to soil quality conditions is multifaceted. From the Tamale perspective, it is consistent with farmers’ tendency to judiciously allocate scarce resources. Viewed from the Kakamega perspective, it points to a need for farmers here to intensify agricultural production in order to foster food security. In Kakamega, farmers with more acidic soils were more likely to adopt ISFM. Other household and farm-level factors necessary for ISFM adoption included off-farm income, livestock ownership, farmer associations, and market inter-linkages. Finally, in study III a counterfactual model was used to calculate the difference in outcomes (yield and household income) of the treatment (ISFM adoption) in order to estimate causal effects of ISFM adoption. Adoption of ISFM contributed to a yield increase of 16% in both Tamale and Kakamega. The innovation affected total household income only in Tamale, where ISFM adopters had an income gain of 20%. This may be attributable to the different policy contexts under which the two sets of farmers operate. The main recommendations underscored the need to: (1) improve the functioning of AKIS, (2) enhance farmer access to hybrid maize seed and credit, (3) and conduct additional multi-locational studies as farmers operate under varying contexts.

Identification of endophytic bactéria from micropropagated yacon (Smallanthus sonchifolius) crowing under autotrophic and Heterotrophic systems.

Yacon, Smallanthus sonchifolius, an Andean species. is a rich source of dictetíc oligofructans with low glucose content. proteins and phenolic compounds. These constituents have shown efficacy in the prevention of diet-related ehronic diseases, including gastroin-testinal disorders and diabetes |1,2|. Yacon is part of a research program at the National Center for Natural Products Research (NCNPR) and University of Mississippi Field Station to develop new alternative root crops for Mississippi while attempting to im-prove the diet of low incorne families. Yacon can be easily propa-gated by cultings. Virus and nematode infections have been re-ported on plants propagated by cuttings in Brazil. a country that hás adopted Yacon as specialty crop [3|. We have developed two culture systems. autotrophic and heterotrophic, to produce healthy plants. Herem we describe the presence of endophytic bactéria m micropropagated Yacon. In auxin free media, new roots were induced. Overa 15day period. the average root mduction per expiam was 5.45 to 8.75 under autotrophic and heterotrophic cul-tures, respectively. Root lenglh vaned between 3 and 60mrn. The presence of root hairs and lateral roots was noticed only in auto-trophic condilions. These beneficiai bactéria were identified and chemically ctiaracterized. Acknowledgement: This research work was partially supported by the USDA/ARS Cooperative Research Agreement No. 58-6408-2-009. Referentes; |1) Terada S. et ai. (2006] Yakugaku Zasshi 126(8): 665-669. (2| Valentová K. Ulri-chová j. (2003) Biomedical Papers 147: 119-130. [3| Mogor C. et ai, (2003) Acta Horticulturea 597: 311 -313.

Enabling Human Centric Smart Campuses via Edge Computing and Connected Objects

Early definitions of Smart Building focused almost entirely on the technology aspect and did not suggest user interaction at all. Indeed, today we would attribute it more to the concept of the automated building. In this sense, control of comfort conditions inside buildings is a problem that is being well investigated, since it has a direct effect on users’ productivity and an indirect effect on energy saving. Therefore, from the users’ perspective, a typical environment can be considered comfortable, if it’s capable of providing adequate thermal comfort, visual comfort and indoor air quality conditions and acoustic comfort. In the last years, the scientific community has dealt with many challenges, especially from a technological point of view. For instance, smart sensing devices, the internet, and communication technologies have enabled a new paradigm called Edge computing that brings computation and data storage closer to the location where it is needed, to improve response times and save bandwidth. This has allowed us to improve services, sustainability and decision making. Many solutions have been implemented such as smart classrooms, controlling the thermal condition of the building, monitoring HVAC data for energy-efficient of the campus and so forth. Though these projects provide to the realization of smart campus, a framework for smart campus is yet to be determined. These new technologies have also introduced new research challenges: within this thesis work, some of the principal open challenges will be faced, proposing a new conceptual framework, technologies and tools to move forward the actual implementation of smart campuses. Keeping in mind, several problems known in the literature have been investigated: the occupancy detection, noise monitoring for acoustic comfort, context awareness inside the building, wayfinding indoor, strategic deployment for air quality and books preserving.

Appropriate technologies and natural systems for wastewater treatment in low- and middle-income countries

Wastewater management is an environmental and social burden that primarily affects populations in Low- and Middle-Income Countries and the global environment. Wastewater collection, treatment, and reuse have become urgent, especially considering that 80% of the world's wastewater is untreated or improperly treated and discharged directly into water bodies. In recent years, the role of wastewater treatment plants in a sustainable water cycle has become even more critical, as they are the final destination of the collected wastewater. Indeed, the management of wastewater treatment plants should play an essential role in achieving SDG target 6.3 of the United Nations 2030 Agenda for SD. In this context, water reuse, especially wastewater reuse, plays a key role. This research focuses on investigating the valorization of wastewater resources applying Appropriate Technologies and Natural Systems for wastewater treatment in two different Low- and Middle-Income Countries, the Palestinian Territories and Sub-Saharan Africa. The research objectives are: (1) Determine the characteristics and quality of wastewater in the two case studies analysed. (2) Identify Appropriate Technology to be used in the Palestinian Territories to treat wastewater for reuse in agriculture. (3) Assess the environmental, economic, and social impacts of this project. (4) Assess the feasibility of using natural wetlands for household wastewater treatment in Sub-Saharan region. The first study, conducted in Rafah, Gaza Strip, showed that implementing existing primary treatment plant with a natural secondary treatment plant properly optimized the wastewater quality for reuse in agriculture and was suitable for the study area. The second case study was conducted in Cape Coast, Ghana. It shows that the natural wetland studied is currently overly polluted and threatened by various anthropogenic factors that cannot remove pollutants from the incoming domestic wastewater. Therefore, some recommendations were made in order to improve the efficiency of this natural wetland.

Interference mitigation techniques for cloud-RAN deployments in 5G and beyond systems

The deployment of ultra-dense networks is one of the most promising solutions to manage the phenomenon of co-channel interference that affects the latest wireless communication systems, especially in hotspots. To meet the requirements of the use-cases and the immense amount of traffic generated in these scenarios, 5G ultra-dense networks are being deployed using various technologies, such as distributed antenna system (DAS) and cloud-radio access network (C-RAN). Through these centralized densification schemes, virtualized baseband processing units coordinate the distributed access points and manage the available network resources. In particular, link adaptation techniques are shown to be fundamental to overall system operation and performance enhancement. The core of this dissertation is the result of an analysis and a comparison of dynamic and adaptive methods for modulation and coding scheme (MCS) selection applied to the latest mobile telecommunications standards. A novel algorithm based on the proportional-integral-derivative (PID) controller principles and block error rate (BLER) target has been proposed. Tests were conducted in a 4G and 5G system level laboratory and, by means of a channel emulator, the performance was evaluated for different channel models and target BLERs. Furthermore, due to the intrinsic sectorization of the end-users distribution in the investigated scenario, a preliminary analysis on the joint application of users grouping algorithms with multi-antenna and multi-user techniques has been performed. In conclusion, the importance and impact of other fundamental physical layer operations, such as channel estimation and power control, on the overall end-to-end system behavior and performance were highlighted.

Hybrid ground-aerial mesh networks for IoT monitoring applications: network design and software platform development

The Internet of Things (IoT) has grown rapidly in recent years, leading to an increased need for efficient and secure communication between connected devices. Wireless Sensor Networks (WSNs) are composed of small, low-power devices that are capable of sensing and exchanging data, and are often used in IoT applications. In addition, Mesh WSNs involve intermediate nodes forwarding data to ensure more robust communication. The integration of Unmanned Aerial Vehicles (UAVs) in Mesh WSNs has emerged as a promising solution for increasing the effectiveness of data collection, as UAVs can act as mobile relays, providing extended communication range and reducing energy consumption. However, the integration of UAVs and Mesh WSNs still poses new challenges, such as the design of efficient control and communication strategies. This thesis explores the networking capabilities of WSNs and investigates how the integration of UAVs can enhance their performance. The research focuses on three main objectives: (1) Ground Wireless Mesh Sensor Networks, (2) Aerial Wireless Mesh Sensor Networks, and (3) Ground/Aerial WMSN integration. For the first objective, we investigate the use of the Bluetooth Mesh standard for IoT monitoring in different environments. The second objective focuses on deploying aerial nodes to maximize data collection effectiveness and QoS of UAV-to-UAV links while maintaining the aerial mesh connectivity. The third objective investigates hybrid WMSN scenarios with air-to-ground communication links. One of the main contribution of the thesis consists in the design and implementation of a software framework called "Uhura", which enables the creation of Hybrid Wireless Mesh Sensor Networks and abstracts and handles multiple M2M communication stacks on both ground and aerial links. The operations of Uhura have been validated through simulations and small-scale testbeds involving ground and aerial devices.

Molecular and hybrid systems for solar-to-chemical energy conversion

My Ph.D. thesis was dedicated to the exploration of different paths to convert sunlight into the shape of chemical bonds, by the formation of solar fuels. During the past three years, I have focused my research on two of these, namely molecular hydrogen H2 and the reduced nicotinamide adenine dinucleotide enzyme cofactor NAD(P)H. The first could become the ideal energy carrier for a truly clean energy system; it currently represents the best chance to liberate humanity from its dependence on fossil fuels. To address this, I studied different systems which can achieve proton reduction upon light absorption. More specifically, part of my work was aimed to the development of a cost-effective and stable catalyst in combination with a well-known photochemical cycle. To this extent, I worked on transition metal oxides which, as demonstrated in this work, have been identified as promising H2 evolution catalysts, showing excellent activity, stability, and previously unreported versatility. Another branch of my work on hydrogen production dealt with the use of a new class of polymeric semiconductor materials to absorb light and convert it into H2. The second solar fuel mentioned above is a key component of the most powerful methods for chemical synthesis: enzyme catalysis. The high cost of the reduced forms prohibits large-scale utilization, so artificial photosynthetic approaches for regenerating it are being intensively studied. The first system I developed exploits the tremendous reducing properties of a scarcely known ruthenium complex which is able to reduce NAD+. Lastly, I sought to revert the classical role of the sacrificial electron donor to an active component of the system and, to boost the process, I build up an autonomous microfluidic system able to generate highly reproducible NAD(P)H amount, demonstrating the superior performance of microfluidic reactors over batch and representing another successful photochemical NAD(P)H regeneration system.

Quantum computing and post-quantum cryptography

One of the main practical implications of quantum mechanical theory is quantum computing, and therefore the quantum computer. Quantum computing (for example, with Shor’s algorithm) challenges the computational hardness assumptions, such as the factoring problem and the discrete logarithm problem, that anchor the safety of cryptosystems. So the scientific community is studying how to defend cryptography; there are two defense strategies: the quantum cryptography (which involves the use of quantum cryptographic algorithms on quantum computers) and the post-quantum cryptography (based on classical cryptographic algorithms, but resistant to quantum computers). For example, National Institute of Standards and Technology (NIST) is collecting and standardizing the post-quantum ciphers, as it established DES and AES as symmetric cipher standards, in the past. In this thesis an introduction on quantum mechanics was given, in order to be able to talk about quantum computing and to analyze Shor’s algorithm. The differences between quantum and post-quantum cryptography were then analyzed. Subsequently the focus was given to the mathematical problems assumed to be resistant to quantum computers. To conclude, post-quantum digital signature cryptographic algorithms selected by NIST were studied and compared in order to apply them in today’s life.

Satellite IoT: a Study and Performance Analysis of GEO and LEO Systems

The study is divided into two main part: one focused on the GEO Satellite IoT and the other on the LEO Satellite IoT. Concerning the GEO Satellite IoT, the activity has been developed in the context of EUMETSAT Data Collection Service (DCS) by investigating the performance at the receiver within challenging scenarios. DCS are provided by several GEO Satellite operators, giving almost total coverage around the world. In this study firstly an overview of the DCS end-to-end architecture is given followed by a detailed description of both the tools used for the simulations: the DCP-TST (message generator and transmitter) and the DCP-RX (receiver). After generating several test messages, the performances have been evaluated with the addition of impairments (CW and sweeping interferences) and considerations in terms of BER and Good Messages are produced. Furthermore, a study on the PLL System is also conducted together with evaluations on the effectiveness of tuning the PLL Bw on the overall performance. Concerning the LEO Satellite IoT, the activity was carried out in the framework of the ASI Bidirectional IoT Satellite Service (BISS) Project. The elaborate covers a survey about the possible services that the project can accomplish and a technical analysis on the uplink MA. In particular, the LR-FHSS is proved to be a valid alternative for the uplink through an extensive analysis on its Network capacity and through the study of an analytic model for Success Probability with its Matlab implementation.

Proposta de normalização da gestão de sinistros, na relação entre hospitais e fornecedores de seguros de saúde

Trabalho de projeto apresentado à Escola Superior de Comunicação Social como parte dos requisitos para obtenção de grau de mestre em Audiovisual e Multimédia.

Hybrid hypervisor partially deployed on FPGA

Tese de Doutoramento em Engenharia Eletrónica e Computadores.