Fuzzy clustering with spatial-temporal information

Clustering geographical units based on a set of quantitative features observed at several time occasions requires to deal with the complexity of both space and time information. In particular, one should consider (1) the spatial nature of the units to be clustered, (2) the characteristics of the space of multivariate time trajectories, and (3) the uncertainty related to the assignment of a geographical unit to a given cluster on the basis of the above com- plex features. This paper discusses a novel spatially constrained multivariate time series clustering for units characterised by different levels of spatial proximity. In particular, the Fuzzy Partitioning Around Medoids algorithm with Dynamic Time Warping dissimilarity measure and spatial penalization terms is applied to classify multivariate Spatial-Temporal series. The clustering method has been theoretically presented and discussed using both simulated and real data, highlighting its main features. In particular, the capability of embedding different levels of proximity among units, and the ability of considering time series with different length

Fuzzy clustering of spatial interval-valued data

In this paper, two fuzzy clustering methods for spatial intervalvalued data are proposed, i.e. the fuzzy C-Medoids clustering of spatial interval-valued data with and without entropy regularization. Both methods are based on the Partitioning Around Medoids (PAM) algorithm, inheriting the great advantage of obtaining non-fictitious representative units for each cluster. In both methods, the units are endowed with a relation of contiguity, represented by a symmetric binary matrix. This can be intended both as contiguity in a physical space and as a more abstract notion of contiguity. The performances of the methods are proved by simulation, testing the methods with different contiguity matrices associated to natural clusters of units. In order to show the effectiveness of the methods in empirical studies, three applications are presented: the clustering of municipalities based on interval-valued pollutants levels, the clustering of European fact-checkers based on interval-valued data on the average number of impressions received by their tweets and the clustering of the residential zones of the city of Rome based on the interval of price values

Fuzzy clustering of spatial interval-valued data

In this paper, two fuzzy clustering methods for spatial interval-valued data are proposed, i.e. the fuzzy C-Medoids clustering of spatial interval-valued data with and without entropy regularization. Both methods are based on the Partitioning Around Medoids (PAM) algorithm, inheriting the great advantage of obtaining non-fictitious representative units for each cluster. In both methods, the units are endowed with a relation of contiguity, represented by a symmetric binary matrix. This can be intended both as contiguity in a physical space and as a more abstract notion of contiguity. The performances of the methods are proved by simulation, testing the methods with different contiguity matrices associated to natural clusters of units. In order to show the effectiveness of the methods in empirical studies, three applications are presented: the clustering of municipalities based on interval-valued pollutants levels, the clustering of European fact-checkers based on interval-valued data on the average number of impressions received by their tweets and the clustering of the residential zones of the city of Rome based on the interval of price values

Integrated hydrogeological and geochemical processes in swelling clay-sulfate rocks

Quellende Ton-Sulfatgesteine führen immer wieder zu unvorhergesehenen Problemen im Tunnelbau oder bei oberflächennahen Geothermiebohrungen und machen dort langwierige Sanierungsmaßnahmen erforderlich. Die Prozesse, die dem Quellen zugrunde liegen, sind komplex. Im Allgemeinen wird davon ausgegangen, dass der Quellvorgang hauptsächlich auf die Umwandlung von Anhydrit zu Gips zurückzuführen ist. Auslöser ist in der Regel eine Änderung der hydraulischen Bedingungen, gefolgt von einem Wasserzutritt in die quellfähigen Gesteinsschichten, was wiederum die vorherrschenden geochemischen Bedingungen verändert. In der Folge kommt es zu einer Zunahme des Gesteinsvolumens im Untergrund. Dies führte in der süddeutschen Stadt Staufen, dem Untersuchungsstandort dieser Arbeit, zu großräumigen Hebungen an der Geländeoberfläche und, damit verbunden, zu großen Schäden an Häusern und Infrastruktur. Gerade diese hydrogeologischen und geochemischen Prozesse, sowie der Einfluss menschlicher Aktivitäten (z.B. Geothermiebohrungen), lassen sich jedoch nur sehr schwer nachvollziehen oder gar vorhersagen, da die genauen Zusammenhänge bisher unzureichend erforscht sind. Im ersten Teil dieser Arbeit wird zunächst ein 3D geologisches Modell entwickelt, um die komplexen geologischen Verhältnisse im Untersuchungsgebiet zu rekonstruieren. Dieses Modell stellt die geometrische Grundlage für die im weiteren Verlauf durchgeführten numerischen Untersuchungen der hydrogeologischen und geochemischen Prozesse des Quellphänomens dar. In diesem Zusammenhang wird außerdem eine Unsicherheitenanalyse der 3D geologischen Modellierung basierend auf der Theorie der Informationsentropie durchgeführt. Die Analyse veranschaulicht wie sich verschiedene geologische Erkundungsdaten unterschiedlich auf die vorhandenen Modellunsicherheiten und die Modellgeometrie auswirken. Der erstmals auf ein komplexes Standortmodell angewendete Ansatz ermöglicht dabei eine detaillierte, Voxel-basierte Visualisierung und Quantifizierung der Unterschiede und Änderungen der Unsicherheit zwischen mehreren Modellinterpretationen. Zusätzlich können mit Hilfe der verwendeten Jaccard- und der City-block-Distanzen Unähnlichkeiten zwischen den Modellen direkt identifiziert werden. Damit ermöglicht die Methodik unter anderem eine effizientere Durchführung von geologischen Erkundungskampagnen und bietet außerdem eine fundierte Grundlage für Kosten-Nutzen-Analysen. Für die komplexen geologischen Verhältnisse des Untersuchungsstandorts Staufen zeigt sich, dass mit zunehmender Datendichte mehr geologische Strukturen identifiziert werden, gleichzeitig aber auch vermehrt lokal hohe strukturelle Unsicherheiten auftreten. Im zweiten Teil der Arbeit wird ein neuartiger Modellansatz entwickelt und numerisch als radialsymmetrisches, reaktives Transportmodell umgesetzt. Das Model kann genutzt werden, um den Quellprozess abzubilden und berücksichtigt folgende Einflüsse: 1) die veränderten hydraulischen Randbedingungen auf Grund menschlicher Aktivitäten (Geothermiebohrungen), 2) die Wasserverfügbarkeit in der Quellzone, und 3) die Geochemie. Dazu wird die Quellhebung an der Geländeoberfläche in Abhängigkeit der geochemischen Umwandlung von Anhydrit in Gips und einer daraus abgeleiteten Volumenzunahme im Untergrund simuliert und quantifiziert. Der Modellansatz trennt dabei zwischen advektivem Stofftransport entlang von Klüften im Gestein und der Umwandlung von Anhydrit zu Gips in der Gesteinsmatrix. Um den beiden Wirkungsbereichen (Domänen) spezifische Porositäten zuordnen zu können, wird ein Zwei-Domänen Modellierungsansatz (``dual domain approach\u27\u27) verwendet, der diese gleichzeitig über eine Transferrate für den diffusiven Wassertransport koppelt. Mit diesem Modellansatz können prozessspezifische hydraulische, geochemische und mechanische Modellparameter basierend auf geodätischen Hebungsdaten in einer inversen Modellierung abgeschätzt werden. Die hierbei ermittelten Reaktionskonstanten für Anhydritlösung (\SI{2.4e-5}{\mole\per\square\metre\per\second}) und Gipsfällung (\SI{3.2e-6}{\mole\per\square\metre\per\second}) sind vergleichbar mit Literaturwerten aus Laborversuchen. Es zeigt sich jedoch, dass der diffuse Stofftransport in die Gesteinsmatrix wesentlich die Geschwindigkeit des Quellprozesses beeinflusst, was insbesondere bei niedrigen Gesteinsporositäten (z. B. kompakte Anhydritlagen) ein limitierender Faktor sein kann. Insgesamt ist das Modell in der Lage, den am Untersuchungsstandort beobachteten Hebungsverlauf abzubilden. Im dritten Teil der Arbeit wird das zuvor entwickelte Quellhebungsmodell auf die komplexe geologische Situation am Untersuchungsstandort Staufen angewendet. Dadurch können, im Vergleich zum radialsymmetrischen Ansatz, sowohl lokale Grundwasserströmungen, als auch die örtlichen geologischen Gegebenheiten explizit und umfassend bei der Simulation des Quellprozesses berücksichtigt werden. Das Modell kann genutzt werden, um eine Prognose über die weitere Entwicklung der Hebungsprozesse in Abhängigkeit der Sanierungsmaßnahmen vorzunehmen und bietet damit die wissenschaftliche Grundlage für eine Bewertung verschiedener Strategien, um den Quellprozess zu stoppen. Die Methode ermöglicht eine Bilanzierung der Wasserzuflüsse in die Quellzone, sowie eine Abschätzung des zukünftige Quellpotentials für individuelle Sanierungsszenarien. Für den Untersuchungsstandort Staufen zeigen die Ergebnisse, dass auch bei einer unvollständigen, nachträglichen Abdichtung der Erdwärmesonden der Wasserfluss in die Quellzone und damit der Quellprozess durch entsprechende hydraulische Gegenmaßnahmen gestoppt werden kann. Außerdem wird ersichtlich, dass umfassende geologische, hydraulische und geochemische Informationen für eine stichhaltige Simulation der Quellprozesse und eine Beurteilung geeigneter standortspezifischer Sanierungsmaßnahmen erforderlich sind

Some further studies on improving QFD methodology and analysis

Quality Function Deployment (QFD) starts and ends with the customer. In other words, how it ends may depend largely on how it starts. Any QFD practitioners will start with collecting the voice of the customer that reflects customer’s needs as to make sure that the products will eventually sell or the service may satisfy the customer. On the basis of those needs, a product or service creation process is initiated. It always takes a certain period of time for the product or service to be ready for the customer. The question here is whether those customer-needs may remain exactly the same during the product or service creation process. The answer would be very likely to be a ‘no’, especially in today’s rapidly changing environment due to increased competition and globalization. The focus of this thesis is placed on dealing with the change of relative importance of the customer’s needs during product or service creation process. In other words, the assumption is that there is no new need discovered along the time or an old one becomes outdated; only the relative importance change of the existing needs is dealt with. Considering the latest development of QFD research, especially the increasingly extensive use of Analytic Hierarchy Process (AHP) in QFD, this thesis aims to enhance the current QFD methodology and analysis, with respect to the change during product or service creation process, as to continually meet or exceed the needs of the customer. The entire research works are divided into three main parts, namely, the further use of AHP in QFD, the incorporation of AHP-based priorities’ dynamics in QFD, and decision making analysis with respect to the dynamics. The first part focuses on the question "In what ways does AHP, considering its strength and weakness, contribute to an improved QFD analysis?" The usefulness of AHP in QFD is demonstrated through a case study in improving higher education quality of an education institution. Furthermore, a generalized model of using AHP in QFD is also proposed. The generalized model not only provides an alternative way to construct the house of quality (HoQ), but also creates the possibility to include other relevant factors into QFD analysis, such as new product development risks. The second part addresses the question "How to use the AHP in QFD in dealing with the dynamics of priorities?" A novel quantitative method to model the dynamics of AHP-based priorities in the HoQ is proposed. The method is simple and time-efficient. It is especially useful when the historical data is limited, which is the case in a highly dynamic environment. As to further improve QFD analysis, the modeling method is applied into two areas. The first area is to enhance the use of Kano’s model in QFD by considering its dynamics. It not only extends the use of Kano’s model in QFD, but also advances the academic literature on modeling the life cycle of quality attributes quantitatively. The second area is to enhance the benchmarking part of QFD by including the dynamics of competitors’ performance in addition to the dynamics of customer’s needs. The third part deals with the question "How to make decision in a QFD analysis with respect to the dynamics in the house of quality?" Two decision making approaches are proposed to prioritize and/or optimize the technical attributes with respect to the modeling results. Considering the fact that almost all QFD translation process employs the relationship matrix, a guideline for QFD practitioners to decide whether the relationship matrix should be normalized is developed. Furthermore, a practical implication of the research work towards the possible use of QFD in helping a company develop more innovative products is also discussed. In brief, the main contribution of this thesis is in providing some novel methods and/or approaches to enhance the QFD’s use with respect to the change during product or service creation process. For scientific community, this means that the existing QFD research has been considerably improved, especially with the use of AHP in QFD. For engineering practice, a better way of doing QFD analysis, as a customer-driven engineering design tool, has been proposed. It is hoped that the research work may provide a first step into a better customer-driven product or service design process, and eventually increase the possibility to create more innovative and competitive products or services over time

Dynamics of the Intrinsically Disordered Inhibitor IF7 of Glutamine Synthetase in Isolation and in Complex with its Partner

Glutamine synthetase (GS) catalyzes the ATP-dependent formation of glutamine from glutamate and ammonia. The activity of Synechocystis sp. PCC 6803 GS is regulated, among other mechanisms, by protein-protein interactions with a 65-residue-long, intrinsically disordered protein (IDP), named IF7. IDPs explore diverse conformations in their free states and, in some cases, in their molecular complexes. We used both nuclear magnetic resonance (NMR) at 11.7 T and small angle X-ray scattering (SAXS) to study the size and the dynamics in the picoseconds-to-nanosecond (ps-ns) timescale of: (i) isolated IF7; and (ii) the IF7/GS complex. Our SAXS findings, together with MD results, show: (i) some of the possible IF7 structures in solution; and, (ii) that the presence of IF7 affected the structure of GS in solution. The joint use of SAXS and NMR shows that movements of each amino acid of IF7 were uncorrelated with those of its neighbors. Residues of IF7 with the largest values of the relaxation rates (R1, R2 and ηxy), in the free and bound species, were mainly clustered around: (i) the C terminus of the protein; and (ii) Ala30. These residues, together with Arg8 (which is a hot-spot residue in the interaction with GS), had a restricted mobility in the presence of GS. The C-terminal region, which appeared more compact in our MD simulations of isolated IF7, seemed to be involved in non-native contacts with GS that help in the binding between the two macromolecules.Ministerio de Economía y Competitividad RTI 2018-097991- BI0

Intrinsically Disordered Proteins and Chronic Diseases

This book is an embodiment of a series of articles that were published as part of a Special Issue of Biomolecules. It is dedicated to exploring the role of intrinsically disordered proteins (IDPs) in various chronic diseases. The main goal of the articles is to describe recent progress in elucidating the mechanisms by which IDPs cause various human diseases, such as cancer, cardiovascular disease, amyloidosis, neurodegenerative diseases, diabetes, and genetic diseases, to name a few. Contributed by leading investigators in the field, this compendium serves as a valuable resource for researchers, clinicians as well as postdoctoral fellows and graduate student

The Semantic Shadow : Combining User Interaction with Context Information for Semantic Web-Site Annotation

This thesis develops the concept of the Semantic Shadow (SemS), a model for managing contentual and structural annotations on web page elements and their values. The model supports a contextual weighting of the annotated information, allowing to specify the annotation values in relation to the evaluation context. A procedure is presented, which allows to manage and process this context-dependent meta information on web page elements using a dedicated programming interface. Two distinct implementations for the model have been developed: One based on Java objects, the other using the Resource Description Framework (RDF) as modeling backend. This RDF-based storage allows to integrate the annotations of the Semantic Shadow with other information of the Semantic Web. To demonstrate the application of the Semantic Shadow concept, a procedure to optimize web based user interfaces based on the structural semantics has been developed: Assuming a mobile client, a requested web page is dynamically adapted by a proxy prototype, where the context-awareness of the adaptation can be directly modeled alongside with the structural annotations. To overcome the drawback of missing annotations for existing web pages, this thesis introduces a concept to derive context-dependent meta-information on the web pages from their usage: From the observation of the users' interaction with a web page, certain context-dependent structural information about the concerned web page elements can be derived and stored in the annotation model of the Semantic Shadow concept.In dieser Arbeit wird das Konzept des Semantic Shadow (dt. Semantischer Schatten) entwickelt, ein Programmier-Modell um Webseiten-Elemente mit inhaltsbezogenen und strukturellen Anmerkungen zu versehen. Das Modell unterstützt dabei eine kontextabhängige Gewichtung der Anmerkungen, so dass eine Anmerkung in Bezug zum Auswertungs-Kontext gesetzt werden kann. Zur Verwaltung und Verarbeitung dieser kontextbezogenen Meta-Informationen für Webseiten-Elemente wurde im Rahmen der Arbeit eine Programmierschnittstelle definiert. Dazu wurden zwei Implementierungen der Schnittstelle entwickelt: Eine basiert ausschließlich auf Java-Objekten, die andere baut auf einem RDF-Modell auf. Die RDF-basierte Persistierung erlaubt eine Integration der Semantic-Shadow-Anmerkungen mit anderen Anwendungen des Semantic Webs. Um die Anwendungsmöglichkeiten des Semantic-Shadow-Konzepts darzustellen, wurde eine Vorgehensweise zur Optimierung von webbasierten Benutzerschnittstellen auf Grundlage von semantischen Strukturinformationen entwickelt: Wenn ein mobiler Benutzer eine Webseite anfordert, wird diese dynamisch durch einen Proxy angepasst. Die Kontextabhängigkeit dieser Anpassung wird dabei bereits direkt mit den Struktur-Anmerkungen modelliert. Für bestehende Webseiten liegen zumeist keine Annotationen vor. Daher wird in dieser Arbeit ein Konzept vorgestellt, kontextabhängige Meta-Informationen aus der Benutzung der Webseiten zu bestimmen: Durch Beobachtung der Benutzer-Interaktionen mit den Webseiten-Elementen ist es möglich bestimmte kontextabhängige Strukturinformationen abzuleiten und als Anmerkungen im Modell des Semantic-Shadow-Konzepts zu persistieren

Thermodynamic characterization of DNA Triple-Helical three-way junctions

Watson-Crick CWC) and Hoogsteen (HG) triple-helical three-way junctions were constructed from three 33-mer oligonucleotides. The same sub-set of sequences have been used in the arms of the junctions. The junctions differ primary in the arrangement of the branch point and the ends of the arms. In the case of the HG triple-helical three-way junction, the three 33-mer oligonucleotides can fold into hairpin structures, linked by a four membered cytosine loop. Each of the hairpins contain a homo-pyrimidine 10-mer single strand extension which interacts with a neighboring hairpin to form a triple-helix on lowering the pH (between 6 and 4), via Hoogsteen (HG) hydrogen bonding. Collectively this process results in the formation of the branch point and the triple-helical arms. In the case of the WC triple-helical three-way junction, the three 33-mer oligonucleotides interact with a neighboring oligonucleotide to form a duplex. Collectively this process leads to the formation of a double-helical three-way junction with each arm containing a 9-mer homo-pyrimidine extension connected by four cytosines. Each of the single strand extensions can mutually fold back onto the duplex arms converting each arm into a triplex. The WC and HG triple-helical three-way junctions were characterized by gel electrophoresis, temperature gradient gel electrophoresis, circular dichroism (CD), uv melting, and differential scanning calorimetry (DSC). In both structures; arm A contained exclusively TAT triad bases, while arms B and C contained an increasing number of CGC+ triads, respectively. To counteract possible crowding at the branch point the 5' sequence was shortened by one base. The assembly of the completely folded structure was found to be spontaneous if an appropriate ionic strength and pH range was chosen. A separate set of isolated arms has been investigated to elucidate the role each arm plays in the complete structure. Comparing the summed-up properties of these arms with the data obtained for the integral three-way junctions, it is obvious that the we three-way junction is partly distorted at the branch point, in line with observation obtained from double-helical three-way junctions, while the HG threeway junction is completely ordered. A set of mathematical models has been developed to describe the thermal unfolding of the multi-strand DNA structure and to identify the intermediate states. Presented is a formalism, starting from the grand partition function, that describes the effects of pH on the thermal stability of triple-helices. The formalism can be used over a wide pH range. It covers nearest neighbor electrostatic effects of closely spaced cytosines in the Hoogsteen and Watson & Crick strands. A procedure is employed to predict enthalpy and entropy changes for triplex formation. The obtained values are in good agreement with the results obtained by differential scanning calorimetry. It is the first time that multistrand, branched DNA structures of this complexity were constructed, completely described, and characterized thermodynamically