The advanced-maximum-linkage clustering-algorithm

The advanced maximum-linkage-algorithm (AMLA) is a derivative of the maximum-linkage-algorithm (MLA) given by Zerbst (2001). AMLA produces clusterings which have a good separation between the built classes. To reach the separation, centroids were calculated, which are the basis for classification. The separation between the classes is considered large, if this is also true for the so far calculated centroids. The selection of centroids having a large distance to each other is also guaranteed using the MLA. AMLA is improved in this way that the underlying frequency structure of the data can be adapted individually to the problem under consideration. Therefore an additional parameter p∈[0,1] is introduced. The parameter gives the degree to which the frequency structure is regarded

The Concentration centroid Minimum Distance Clustering Criterion

Building homogenous classes is one of the main goals in clustering. Homogeneity can be measured by the intra-class variance (Bock, 1998). Especially in erosion projects but in other applications as well the separation between the built classes is as important as the homogeneity of the classes. Special clustering methods can be used to reach this aim, for instance the Maximum Linkage Algorithm (Zerbst, 2001) or the Advanced Maximum Linkage Algorithm (Tschiersch, 2002). To judge the separation quality of such clusterings, the shortest distances between all centroids is considered. Zerbst (2001) shows that the arithmetic mean over all distances isn’t good enough for judging selectivity. Therefore the concentration centroid minimum distance criterion is proposed in this paper. This criterion is based on the ratio of weighted symmetric mean over the minimal distances and the Gini coefficient over the minimal distances. It also judges the class separation independent of the underlying data situation

Authigenic Greigite as an Indicator of Methane Diffusion in Gas Hydrate-Bearing Sediments of the Hikurangi Margin, New Zealand

Authigenic ferrimagnetic iron sulfides, essentially greigite (Fe$_{3}$S$_{4}$), are commonly found in gas hydrate-bearing marine sediments of active accretionary prisms. Greigite is a by-product, either intracellular or extracellular, of microbial activity, and therefore provides good indication of microbial processes which are closely related to the occurrence of gas hydrate. A high-resolution rock magnetic study was conducted at Site U1518 of International Ocean Discovery Program Expedition 375, located in the frontal accretionary wedge of the Hikurangi Margin, offshore New Zealand. Samples were collected throughout the entire recovered stratigraphic sequence, from the surface to ∼492 m below seafloor (mbsf) which includes the Pāpaku fault zone. This study aims to document the rock magnetic properties and the composition of the magnetic mineral assemblage at Site U1518. Based on downhole magnetic coercivity variations, the studied interval is divided into five consecutive zones. Most of the samples have high remanent coercivity (above 50 mT) and first-order reversal curves (FORC) diagrams typical of single-domain greigite. The top of the hanging wall has intervals that display a lower remanent coercivity, similar to lower coercivities measured on samples from the fault zone and footwall. The widespread distribution of greigite at Site U1518 is linked to methane diffusion and methane hydrate which is mainly disseminated within sediments. In three footwall gas hydrate-bearing intervals, investigated at higher resolution, an improved magnetic signal, especially a stronger FORC signature, is likely related to enhanced microbial activity which favors the formation and preservation of greigite. Our findings at the Hikurangi Margin show a close linkage between greigite, methane hydrate and microbial activity

Non-destructive testing and fracture mechanics: A short discussion

A short discussion is provided on the relationship between non-destructive testing and fracture mechanics. The basic tasks behind this are to guarantee the safety of a component at a potential hazard loading event, to specify inspection intervals or, alternatively, of demands on non-destructive testing for a fixed inspection regime, to plan accompanying actions for cases of temporary continued operation of structures in which cracks have been detected, and, finally, fatigue strength considerations which take into account initial defects

An investigation into the role of autophagy in mediating leukaemic cell location in the bone marrow niche

Leukaemic stem cell (LSC) persistence is the prevailing issue in curing chronic myeloid leukaemia (CML) with the current gold-standard treatment — tyrosine kinase inhibitors (TKIs). To fully comprehend how LSCs evade targeted treatment, it is essential to study LSCs in their natural environment: the bone marrow (BM) niche. In the last few decades, advances have been made to better understand how the niche influences the maintenance and regulation of healthy haematopoietic stem cells (HSCs), as well as the role of the niche in malignancies. LSCs have been shown to be metabolically adapted to survive within the BM niche and outcompete healthy haematopoiesis. Previous research in CML aimed to unravel the role of autophagy in LSC survival. This revealed that autophagy inhibition induced LSCs differentiation and sensitization to TKI treatment. As autophagy is influenced by the environment, such as hypoxia, nutrient availability, and inflammation, our study aimed to investigate the complex interplay of CML cells within the BM niche, with a specific focus on the role of autophagy. Moreover, we aimed to unravel the role of mitophagy, the selective degradation of mitochondria, in TKI resistance in vitro. Through a minimally invasive surgery, high-resolution intravital microscopy (IVM) can be utilised to image cells within the BM in the mouse calvarium. We aimed to assess changes in the niche with leukaemia development and dynamics upon treatment response by developing xenograft and genetically engineered mouse models (GEMM) suitable for confocal IVM. To model CML, we utilised the SCL-tTA/BCR∷ABL1 mouse model — an inducible mouse model resembling human CML-like disease development upon BCR∷ABL1 expression. To study autophagy in primitive leukaemic cells, we used a fluorescent BCR∷ABL1 mouse expressing the autophagy marker GFP-LC3. While we could observe autophagic flux in vitro, we faced challenges in detecting the GFP signal within the BM niche. Various strategies, including injectable fluorescent antibodies and ex vivo dyes for long-term tracking, were explored to overcome these challenges. Lastly, we generated a fluorescent version of the SCL-tTA/BCR∷ABL1 model by crossing it with the mTmG mouse, which expresses membrane-targeted tdTomato (tdTom). Encouragingly, transplantation of BCR∷ABL1tdTom+ haematopoietic cells allowed us to visualise leukaemic cells within the BM niche in WT recipient mice, providing a solid foundation for future studies. The investigation extends to xenograft mouse models, aiming to understand the in vivo localisation and interactions of human leukaemic cells in the BM microenvironment. We observed highly variable BM engraftment of different cell lines, particularly concerning localisation within the calvarial BM compared to localisation within the long bones. This posed challenges for attempts to unravel the role of autophagy in BM engraftment and in vivo localisation. Furthermore, we noted different migration patterns of transplanted cells, with extramedullary tumour formation dependent on the mouse’s sex occurring in female mice but not males. Finally, we investigated the role of mitophagy in response to TKI treatment. High-resolution confocal live-cell microscopy was used with KCL22 and K562 cell lines expressing the reporter gene mCherry-GFP-Fis1, referred to as MitoQC. This fluorescent tandem-dye allows distinction of healthy mitochondria and those undergoing mitophagy due to the pH-sensitivity of GFP. We observed an increase in mitophagy upon TKI treatment, mediated by the autophagy machinery, which, to our knowledge, has not been demonstrated previously. To validate our results, we inhibited autophagy by blocking ULK1 activity and by using ATG7 knockout (KO) cells. We explored different canonical mitophagy pathways, focusing on Nix and BNIP3, key proteins in hypoxia-mediated mitophagy. Our results provide initial insights that Nix and, in a broader sense, BNIP3 may be involved in this process, although further investigation is required to unravel their specific roles in TKI-induced mitophagy

Biblical theism enhanced or transformed? An evaluation of Paul Tillich's concept of God

BIBLICAL THEISM ENHANCED OR TRANSFORMED? AN EVALUATION OF PAUL TILLICH'S CONCEPT OF GOD. This dissertation seeks to establish whether Paul Tillich s God-concept is theistic or not. Has Tillich transformed theism into something else? To answer this question requires a detailed examination of Tillich's concept of "being-itself" as a translation of the term "God". It can be established that the concept has a place within Christian tradition, and may be seriously considered as an alternative description to the supranaturalistic idea of God. In this latter conception, which still has broad acceptance today, God is seen as a being, an object located somewhere in space. The primitive and anthropomorphic nature of such a description of God is criticised in this dissertation; such a conception must give way to a more sophisticated one. The concept of "being-itself" though, must be tested against the nominalist objection that there are only existing beings and that there is no category of "existence" or "being". This dissertation shows how an idealist model for being-itself can be defended against the objections of nominalism. However, Tillich is not an idealist (as is amply shown) and because of this the concept of being itself loses much of its forcefulness. For if, as Tillich insists, creator and creation are distinct and separate from each other, then what can the terms "being-itself" and "ground of being" mean? The term "ground" could only mean "source", not "underlying substance". It is argued, though, that Tillich wants the term (and, by extension, "being-itself") to imply both meanings at once, so as to give force to an immanentist theology without surrendering the notion of God's transcendence. In other words, Tillich's theology is accused of a certain ambiguity and imprecision. Yet even if the terra "beirtg-itself" seems unsatisfactory, Tillich s idea that God is forcefully present within the world of men is defensible without an insistence on the term. It is argued that the idea of Spirit can convey such nearness and, further, it is contended that this term is the only satisfactory one to describe God. In the dissertation it is pointed out that "Spirit can imply a "surrounding" omnipresence as easily as it can imply an inhabiting" omnipresence. If God is perceived as "Surrounding Spirit", then an immanentist theism, which has a strong emphasis on religious experience as the factor which establishes the existence of God, can be formulated. Idealism (the model in which Spirit "inhabits" matter) is then avoided; it is argued that this is necessary if God's transcendence is to be maintained. The second half of the dissertation examines the extent of Tillich's appeal outside the boundaries of traditional theism. Does Tillich's concept of God broaden, and thus enhance, the appeal of theism? The answer, in the mainj is affirmative. To be sure, Tillich's description of the awareness of the Ultimate cannot convince the atheist of the existence of God. Yet such a description certainly points the wav to an understanding of what such a conviction entails. Outside of his appeal to the atheist, it is argued that Tillich s theology has been important in establishing Christian dialogue with other faiths and in contributing to the debate on religious secularity. Even if Tillich has expressed serious reservations about the "Radical Theology" he is said to have inspired, one could also claim a success for Tillich in this field in that he has helped to spawn a religious school of thought which is at least vigorous and adventurous, Radical theologians clearly state that Tillich provided them with a mandate to explore the God-concept in an unrestricted way, and even if the arguments of this school go beyond what Tillich felt was acceptable, one must at least concede that these theologians have revitalised religious thought, This revitalisation owes much to Tillich, whose stress oil God s immanence and our experience of him in this secular realm, has done much to re-emphasise the immediacy of the divine presence in the life of man. The conclusion arrived at in this dissertation is that, despite certain terminological imprecisions, Tillich's theology enhances theism without transforming it. Paul Tillich, it is held, must be seen as a theologian of the greatest consequence

Strain partitioning across a subduction thrust fault near the deformation front of the Hikurangi subduction margin, New Zealand: A magnetic fabric study on IODP Expedition 375 Site U1518

Understanding the distribution of strain along thrust and splay faults in active accretionary systems is crucial to understand the mechanical properties of the sediments and the strength of the fault zone and its slip behavior. This paper investigates the distribution of strain through sediment compaction and texture development across the Pāpaku fault, a major splay fault near the deformation front of the Hikurangi subduction margin, New Zealand using the anisotropy of magnetic susceptibility technique (AMS). International Ocean Discovery Program Site U1518 penetrated hanging wall, fault zone and footwall sequences to a maximum depth of 484.9 meters below seafloor. A total of 330 discrete samples was subjected to AMS measurements and magnetic remanence data used to reconstruct the axial orientation of each sample in a geographic reference frame. The AMS display distinct fabric differences between hanging wall, through the fault zone and footwall domains, demonstrating that strain is partitioned across the fault zone. Hanging wall sequences show a strike-parallel northeasterly lineation of K$_{max}$ and weakly prolate shapes, typical for a component of northeast-southwest lateral shortening. In contrast, footwall sequences are more oblate and show a clustering of K$_{max}$ in northerly direction. This demonstrates that strain in the footwall is dominated by gravitational loading, however a component of sub-horizontal east-westerly strain, parallel to the convergence direction of the Pacific Plate exists. Strain decoupling between hanging- and footwall sequences occurs near the top of the Pāpaku fault zone. Differences in the degree of magnetic susceptibility between footwall sediments incorporated into the fault zone, and the underlying undeformed footwall sequences are indicative for the progressive dewatering of the underconsolidated footwall sequences