Διευρύνοντας το Μεθοδολογικό πλάισιο των Ολοκληρωμένων Μοντέλων Χρήσεων-Γης και Μεταφορών: Χωρικά Οικονομετρικά Μοντέλα και Αξιολόγηση Πολιτικών

323 σ.Στην παρούσα εργασία εξετάζεται η διεύρυνση του μεθοδολογικού πλαισίου των Όλοκληρωμένων Μοντέλων Χρήσεων-Γης και Μεταφορών σε κάθε επίπεδο. Οι προτεινόμενες βελτιώσεις αποσκοπούν στην αύξηση των ικανοτήτων πρόβλεψης, αξιοποιώντας τα οφέλη της μικροπροσομοίωσης σε τρείς διαστάσεις, άτομο, χώρο και χρόνο, με σκοπό να καταστόύν τα μοντέλα αυτά ευέλικτα εργαλεία αξιολοόγησης πολιτικών.In this research, the methodological framework of the Integrated Land-Use and Transport (LUTI) models is extended at every level. The objective of developing and implementing LUTI models is to predict the direct and indirect impacts of –transport and land-use– policies, on the environment, the society and the economy. The proposed improvements aim to increase the predicting capabilities of the current LUTI models, exploiting the strengths of microsimulation in three dimensions, agents, space and time, in order to render them flexible platforms for policy evaluation. The effects of the current economic crisis are discussed and explored throughout the doctoral dissertation. Aiming to decrease the required budget for a LUTI model development, public on-line data are used to a large part of the analysis. Moreover, a graph-theoretic solution for associations generation in synthetic simulation is suggested. Different types of spatial econometric models are used for the development of real estate price models, which form fundamental component of every LUTI model. Urban quality indicators (i.e. accessibility, population segregation, economic viability, available open space, housing affordability, land-use and social mix, and building density) are effectively employed manifesting the benefits of trans-disciplinary collaboration in urban planning. In this research, a policy evaluation methodology based on distributions rather than single aggregate measures of quality indicators is proposed. The results indicate that spatial econometrics effectively remove the spatial autocorrelation and achieve higher accuracy than the traditional linear regression, in predicting the dwelling prices. The impact of transportation infrastructure locations on real estate purchase prices and rents differs, depending on the type of the transit system. Qualitative transit infrastructure has preserved the real estate prices at higher levels during the crisis. Synthetic populations and real, on-line, crowdsourced data can efficiently be used for the development of LUTI models. Finally, agent-based LUTI models provide an opportunity for the development of an improved, flexible policy evaluation platform.Δημήτριος Β. Ευθυμίο

A Review of Copy Number Variants in Inherited Neuropathies

The rapid development in the last 10-15 years of microarray technologies, such as oligonucleotide array Comparative Genomic Hybridization (CGH) and Single Nucleotide Polymorphisms (SNP) genotyping array, has improved the identification of fine chromosomal structural variants, ranging in length from kilobases (kb) to megabases (Mb), as an important cause of genetic differences among healthy individuals and also as disease-susceptibility and/or disease-causing factors. Structural genomic variations due to unbalanced chromosomal rearrangements are known as Copy-Number Variants (CNVs) and these include variably sized deletions, duplications, triplications and translocations. CNVs can significantly contribute to human diseases and rearrangements in several dosagesensitive genes have been identified as an important causative mechanism in the molecular aetiology of Charcot-Marie-Tooth (CMT) disease and of several CMT-related disorders, a group of inherited neuropathies with a broad range of clinical phenotypes, inheritance patterns and causative genes. Duplications or deletions of the dosage-sensitive gene PMP22 mapped to chromosome 17p12 represent the most frequent causes of CMT type 1A and Hereditary Neuropathy with liability to Pressure Palsies (HNPP), respectively. Additionally, CNVs have been identified in patients with other CMT types (e.g., CMT1X, CMT1B, CMT4D) and different hereditary poly- (e.g., giant axonal neuropathy) and focal- (e.g., hereditary neuralgic amyotrophy) neuropathies, supporting the notion of hereditary peripheral nerve diseases as possible genomic disorders and making crucial the identification of fine chromosomal rearrangements in the molecular assessment of such patients. Notably, the application of advanced computational tools in the analysis of Next-Generation Sequencing (NGS) data has emerged in recent years as a powerful technique for identifying a genome-wide scale complex structural variants (e.g., as the ones resulted from balanced rearrangements) and also smaller pathogenic (intragenic) CNVs that often remain beyond the detection limit of most conventional genomic microarray analyses; in the context of inherited neuropathies where more than 70 disease-causing genes have been identified to date, NGS and particularly Whole-Genome Sequencing (WGS) hold the potential to reduce the number of genomic assays required per patient to reach a diagnosis, analyzing with a single test all the Single Nucleotide Variants (SNVs) and CNVs in the genes possibly implicated in this heterogeneous group of disorders

Tough Tables: Carefully Evaluating Entity Linking for Tabular Data

Table annotation is a key task to improve querying the Web and support the Knowledge Graph population from legacy sources (tables). Last year, the SemTab challenge was introduced to unify different efforts to evaluate table annotation algorithms by providing a common interface and several general-purpose datasets as a ground truth. The SemTab dataset is useful to have a general understanding of how these algorithms work, and the organizers of the challenge included some artificial noise to the data to make the annotation trickier. However, it is hard to analyze specific aspects in an automatic way. For example, the ambiguity of names at the entity-level can largely affect the quality of the annotation. In this paper, we propose a novel dataset to complement the datasets proposed by SemTab. The dataset consists of a set of high-quality manually-curated tables with non-obviously linkable cells, i.e., where values are ambiguous names, typos, and misspelled entity names not appearing in the current version of the SemTab dataset. These challenges are particularly relevant for the ingestion of structured legacy sources into existing knowledge graphs. Evaluations run on this dataset show that ambiguity is a key problem for entity linking algorithms and encourage a promising direction for future work in the field

SemTab 2019: Resources to Benchmark Tabular Data to Knowledge Graph Matching Systems

Tabular data to Knowledge Graph matching is the process of assigning semantic tags from knowledge graphs (e.g., Wikidata or DBpedia) to the elements of a table. This task is a challenging problem for various reasons, including the lack of metadata (e.g., table and column names), the noisiness, heterogeneity, incompleteness and ambiguity in the data. The results of this task provide significant insights about potentially highly valuable tabular data, as recent works have shown, enabling a new family of data analytics and data science applications. Despite significant amount of work on various flavors of this problem, there is a lack of a common framework to conduct a systematic evaluation of state-of-the-art systems. The creation of the Semantic Web Challenge on Tabular Data to Knowledge Graph Matching (SemTab) aims at filling this gap. In this paper, we report about the datasets, infrastructure and lessons learned from the first edition of the SemTab challenge

Life after care: psychological adjustment to bereavement in family carers of people with dementia

BACKGROUND: Despite well-documented evidence of the psychological effects of caring for a relative with dementia, little is known about the bereavement experiences of family carers. The aim of this study was to explore the key psychological changes associated with carers' adjustment to bereavement and "life after care." METHODS: All carers taking part were recruited from a day care center, providing specialist services to people with dementia. We asked carers to describe the key changes associated with psychological adjustment to bereavement through semi-structured qualitative in-depth interviews. Strategies carers used to cope with and adapt to their new role were also explored. All data were thematically analysed. RESULTS: Thirty-one carers were interviewed. The most frequent emotional reactions to bereavement were feelings of loneliness, loss, void, sadness, anger, and relief. Most carers were able to adapt to their new role, and engaging in pleasant activities was the most frequent strategy used to cope with loss and "life after care." CONCLUSIONS: Feelings of loneliness and loss are amongst the key emotional reactions shaping carers' adjustment to bereavement. Most carers are able to adapt to loss; however, a minority experience increased psychological distress after the death of their loved one. A small percentage of carers continues caring for other dependants. Further research is required to identify how carers of people with dementia adapt to bereavement and how this increasing number of individuals can be best supported

Allelic and phenotypic heterogeneity in Junctophillin-3 related neurodevelopmental and movement disorders.

Junctophilin-3 belongs to a triprotein junctional complex implicated in the regulation of neuronal excitability and involved in the formation of junctional membrane structures between voltage-gated ion channels and endoplasmic (ryanodine) reticular receptors. A monoallelic trinucleotide repeat expansion located within the junctophilin-3 gene (JPH3) has been implicated in a rare autosomal dominant (AD) late-onset (and progressive) disorder clinically resembling Huntington disease (HD), and known as HD-like 2 (HDL2; MIM# 606438). Although the exact molecular mechanisms underlying HDL2 has not yet been fully elucidated, toxic gain-of-function of the aberrant transcript (containing the trinucleotide repeat) and loss of expression of (full-length) junctophilin-3 have both been implicated in HDL2 pathophysiology. In this study, we identified by whole exome sequencing (WES) a JPH3 homozygous truncating variant [NM_020655.4: c.17405dup; p.(Val581Argfs*137)]. in a female individual affected with genetically undetermined neurodevelopmental anomalies (including delayed motor milestones, abnormal social communication, language difficulties and borderline cognitive impairment) and paroxysmal attacks of dystonia since her early infancy. Our study expands the JPH3-associated mutational spectrum and clinical phenotypes, implicating the loss of Junctophilin-3 in heterogeneous neurodevelopmental phenotypes and early-onset paroxysmal movement disorders

Novel variants underlying autosomal recessive intellectual disability in Pakistani consanguineous families

Background: Intellectual disability (ID) is both a clinically diverse and genetically heterogeneous group of disorder, with an onset of cognitive impairment before the age of 18 years. ID is characterized by significant limitations in intellectual functioning and adaptive behaviour. The identification of genetic variants causing ID and neurodevelopmental disorders using whole-exome sequencing (WES) has proven to be successful. So far more than 1222 primary and 1127 candidate genes are associated with ID. Methods: To determine pathogenic variants causative of ID in three unrelated consanguineous Pakistani families, we used a combination of WES, homozygosity-by-descent mapping, de-deoxy sequencing and bioinformatics analysis. Results: Rare pathogenic single nucleotide variants identified by WES which passed our filtering strategy were confirmed by traditional Sanger sequencing and segregation analysis. Novel and deleterious variants in VPS53, GLB1, and MLC1, genes previously associated with variable neurodevelopmental anomalies, were found to segregate with the disease in the three families. Conclusions: This study expands our knowledge on the molecular basis of ID as well as the clinical heterogeneity associated to different rare genetic causes of neurodevelopmental disorders. This genetic study could also provide additional knowledge to help genetic assessment as well as clinical and social management of ID in Pakistani familie

Analysis of the prion protein gene in multiple system atrophy

Neurodegenerative diseases are a very diverse group of disorders but they share some common mechanisms such as abnormally misfolded proteins with prion-like propagation and aggregation. Creutzfeldt-Jakob disease (CJD) is the most prevalent prion disease in humans. In the sporadic form of CJD the only known risk factor is the codon 129 polymorphism. Recent reports suggested that α-synuclein in multiple system atrophy (MSA) has similar pathogenic mechanisms as the prion protein. Here we present 1 Italian family with MSA and prion disease. Also, cases of concurrent MSA and prion pathology in the same individual or family suggest the possibility of molecular interaction between prion protein and α-synuclein in the process of protein accumulation and neurodegeneration, warranting further investigations. We assessed the PRNP gene by whole-exome sequencing in 264 pathologically confirmed MSA cases and 462 healthy controls to determine whether the 2 diseases share similar risk factors. We then analyzed codon 129 polymorphism by Sanger sequencing and compared with previously published results in sporadic CJD. Homozygosity at codon 129 was present in 50% of pathologically confirmed MSA cases and in 58% of normal controls (odds ratio, 0.7 (95% confidence interval of 0.5-0.9)) compared with 88.2% in sporadic CJD. Our data show that the homozygous state of position 129 in the PRNP is not a risk factor for MSA. No other variants in the PRNP gene were associated with increased risk for MSA