Matching-based preprocessing algorithms to the solution of saddle-point problems in large-scale nonconvex interior-point optimization

Interior-point methods are among the most efficient approaches for solving large-scale nonlinear programming problems. At the core of these methods, highly ill-conditioned symmetric saddle-point problems have to be solved. We present combinatorial methods to preprocess these matrices in order to establish more favorable numerical properties for the subsequent factorization. Our approach is based on symmetric weighted matchings and is used in a sparse direct LDL T factorization method where the pivoting is restricted to static supernode data structures. In addition, we will dynamically expand the supernode data structure in cases where additional fill-in helps to select better numerical pivot elements. This technique can be seen as an alternative to the more traditional threshold pivoting techniques. We demonstrate the competitiveness of this approach within an interior-point method on a large set of test problems from the CUTE and COPS sets, as well as large optimal control problems based on partial differential equations. The largest nonlinear optimization problem solved has more than 12 million variables and 6 million constraint

Which Leadership Principles Currently Have The Most Appeal: Leadership in the Light of Contemporary Popular Leadership Literature

Purpose: This study aims to identify principles and critical elements of leadership reflected in contemporary popular leadership literature. Study design/methodology/approach: In a quantitative-qualitative study, the main topics of leadership are extracted from business bestseller lists to infer the issues in leadership that have the most significant popular resonance. Findings: Current popular business literature focuses on the leader as a person, respectively, on the personality of the leader, and in particular on transformational leadership, including elements of transactional leadership. Originality/value: Examining contemporary popular leadership literature and interrogating it for underlying leadership principles and models breaks new ground in scholarly research

Does Current Popular Leadership Literature Show a Preference for Transformational Leadership?

Over the past few years, numerous Leadership models, theories, and methodologies have emerged so that the question arises as to which of the models is most effective, or even which has prevailed. One approach to this question is to compare different models in terms of their overlaps or similarities. This study researches the topic with a reverse approach: can one derive a preference for a particular leadership style or even a leadership direction or leadership ‘school' from the popular leadership literature? The guiding question is which leadership books sell the most and which leadership style or elements of leadership they represent. For this purpose, Amazon's bestseller lists in leadership and management in a specific period and local market are examined in a quantitative-qualitative study both to elicit the distribution of a model and to find common styles and elements of leadership among different authors. The result shows that current popular leadership literature primarily reflects transformational leadership models with elements of transactional management. A particular leadership mindset and special leadership activities such as goal orientation or inspirational motivation can be found in almost all of the most widespread models

Shadows, faces and echoes of an African war: The Rhodesian bush war through the eyes of Chas Lotter – soldier poet

Philosophiae Doctor - PhDPoetry that is rooted in that most extreme of human experiences, war, continues to grip the public imagination. When the poetry under scrutiny comes from the "losing side" in a colonial war of liberation, important moral and ethical questions arise. In this thesis, I examine the published and unpublished works of Chas Lotter, a soldier who fought in the Rhodesian Army during the Zimbabwean liberation war (1965- 1980). In investigating Lotter's artistic record of this war, I propose that a powerful, socially embedded Rhodesian national mythology was a catalyst for acceptance of, and participation in, the Rhodesian regime's ideological and military aims. A variety of postcolonial theoretical approaches will be used to explore the range of thematic concerns that emerge and to unpack the dilemmas experienced by a soldier-poet who took part in that conflict. Trauma theory, too, will be drawn upon to critically respond to the personal impact that participation in organized violence has upon combatants and non-combatants alike. The production and marketing of this cultural record will also be examined and in the conclusion, I speculate on the changes modern technology and evolving social mores may have on future developments in war literature. Finally, I conclude my case for installing the challenging work of this often conflicted and contradictory soldier-poet as a necessary adjunct to the established canon of Zimbabwean Chimurenga writing

Breathe (in the air) : pulmonary immunology in multiple sclerosis

Multiple Sclerosis (MS) is a demyelinating disease of the central nervous system, with etiology still unknown. MS is thought to arise from a complex interplay between genetic and environmental factors. One of the most well established environmental risk factor is smoking, which confers a striking increase in risk of developing MS and especially in interaction with the risk allele HLA-DRB1*15 and absence of the protective allele HLA-A*02. The major part of this thesis is focused on investigating the involvement of the pulmonary immune system in MS, and further to uncover underlying smoking associated changes that could elucidate on the role of smoking as a risk factor in MS. To characterize the lung immune cells, bronchoalveolar lavage (BAL) cells were obtained by bronchoscopy, from healthy volunteers and MS-patients, smokers and non-smokers. In project I we provide an initial characterization of our study cohort. We could observe that smokers carrying the MS specific risk allele HLA-DRB1*15 did not show a smoking-associated increase in macrophages defined in non-carriers. Smokers showed higher frequency of proliferating T-cells, while non-smoking MS-patients had increased levels of preformed CD40L in CD4+ T-cells. We could further provide a more in-depth characterization of pulmonary T-cells in MS-patients and smokers, in Project III. The majority of CD4+T-cells in both healthy and MS patients showed a tissue resident memory phenotype, characterized by expression of CD69 and CD44, while also expressing both CXCR3 and CCR6. Cells from healthy smokers showed an increased proliferative capacity and we also observed a significantly higher frequency of regulatory Tcells in the lungs of both healthy smokers and MS-patients compared to healthy non-smokers. When investigating the migratory profile of lung T-cells based on integrins VLA-4 and LFA- 1, both implicated in MS pathogenesis, we found no upregulation of these in MS patients compared to healthy. In recent years, it has been suggested that dysbiosis of the commensal microbiome in the gut is involved in the pathogenies of MS. The lungs also host a unique commensal microbiota, which recently was shown to be dysregulated in the autoimmune disease Rheumatoid Arthritis and pulmonary Sarcoidosis. In Project IV we investigated if the microbiota in the lungs of MS patients also show dysbiosis. We found that the microbial composition in the lungs of MS patients differed considerably compared to healthy controls, with increased richness and diversity. We could further report that MS patients also had altered expression and presence of the antimicrobial peptide human beta defensin-1 (hBD1) in the lungs. In Project II we developed a novel method, called Small-seq, to study small RNAs, such as microRNAs (miRNA) from a scarce source of starting material; a single cell. Previously methods required large quantities of sample material in order to investigate small RNAs, which often can be a limitation to obtain in clinical samples, as well as average out biological variability and heterogeneity within populations. With Small-seq we are were able to capture different types of small RNAs from single cells, such as miRNA, snoRNA and tsRNA. Captured miRNAs revealed cellular heterogeneity in primed hESC, as well as being able to cluster and separate different cell types. The method implemented a masking strategy to efficiently limit capture of the highly abundant 5.8S rRNA, and incorporation of a unique molecular identifier allowed for molecular quantification of the detected small RNAs. The work provided in this thesis concludes that the pulmonary immune milieu is altered in MS patients, thereby presenting the lungs as an organ of interest for further investigation into the pathology and potential therapeutic opportunities in MS. The described changes in immune cell composition between smokers carrying the MS risk allele HLA-DRB1*15 and noncarriers, could further shed light upon the mechanisms behind the impact of smoking as a risk factor for disease and in exacerbating MS. Herein we further provide the development of a novel technique to capture and investigate small RNA, such as miRNAs in single cell

Physiological and molecular mechanisms of fruitlet abscission in mango

Compared to the typical high initial fruit set of mango (Mangifera indica L.), only a small share of those fruits reach harvest-maturity. This extensive fruitlet drop is a major yield-limiting factor, leading to substantial economic losses for mango growers world-wide. The numerous causes of fruitlet drop include infections with pests or diseases and unsuitable environmental or crop management conditions. Due to the high impact of fruitlet drop for mango production, the overall objective of this study was to further the understanding of the underlying mechanisms and to develop strategies for reducing fruitlet drop in mango. Different experimental approaches have been applied to reduce mango fruitlet drop, however, almost as numerous methods have been used for data interpretation, which makes the comparison of data between studies difficult. Therefore a model was developed for defining the timely pattern of fruitlet drop more generally, thus allowing inter-study comparisons of results. The model was tested and validated by monitoring the fruitlet drop in different management systems: traditional monocropping orchard versus 1) intercropping; 2) irrigation; and 3) plant growth regulator applications, respectively. The timely pattern of fruitlet drop was best described with a sigmoid function, which also formed the basis for defining the post-bloom, the midseason and the pre-harvest fruitlet drop stage. Results of the crop management evaluation show that intercropping of maize with mango has no detrimental effect on fruitlet drop. Irrigation resulted in approximately three times higher fruit retention compared with the non-irrigated control. A single application of 40 ppm 1 naphthaleneacetic acid at the end of the post-bloom drop stage resulted consistently in the highest fruit retention. The developed model permits for example the evaluation the treatment efficacies during midseason drop or yield forecasting at the beginning of the pre-harvest stage. It was suggested that especially during the midseason drop stage tree resources are limited, which results in inter-organ concurrence and subsequently induces fruitlet drop. This is supported by the current findings that during midseason drop mango trees show low rates of photosynthesis, which indicates drought stress. Such stress can induce ethylene-dependent fruitlet abscission. Therefore the ethylene releasing substance ethephon was used in order to study the onset and time-dependent course of fruitlet abscission. The results show that ethephon at a concentration of 7200 ppm (ET7200) is a reliable abscission inducer. The experiment was extended using ethephon at an additional concentration of 600 ppm (ET600). Both ethephon treatments reduced significantly the capacity of polar auxin transport (PAT) in the pedicel at 1 day after treatment (DAT) and thereafter compared to untreated pedicels. The transcript levels of the ethylene receptor genes MiETR1 and MiERS1 were significantly upregulated already at 1 DAT in the ET7200 while only at 2 DAT in the ET600 when compared to the control fruitlets. Specifically, a significant increase of MiETR1 in the pericarp at 2 DAT and of MiERS1 in the pedicel at 2 and 3 DAT was induced by ET600. In contrast, both genes were significantly upregulated in both tissues, except MiETR1 in the pedicel, at 1 DAT and thereafter by ET7200. The last parameter that significantly changed in response to the ethephon treatments was the concentration of sucrose in fruitlet pericarps, which was reduced at 2 DAT compared to control fruitlets. Based on these results, it is postulated that the ethephon-induced abscission process commences with a reduction of the PAT capacity in the pedicel, followed by an upregulation of ethylene receptors and finally a decrease of the sucrose concentration in the fruitlets. Ethylene receptors are key elements of abscission and other processes of the plants life cycle. Therefore the ethylene receptors were further studied at the molecular level in mango. Additionally to the previously known receptors MiETR1 and MiERS, two novel versions of the MiERS1 were identified in mango. These receptor genes, MiERS1m and MiERS1s, translate into truncated proteins with deletions of functional domains and show different expression patterns compared to MiERS1. The receptors were further studied through transient expression of fluorescent fusion proteins in the leaves of the model plant tobacco. All receptors are localized at the endoplasmic reticulum. Specific dimerization assays via bi-molecular fluorescence complementation indicate, that MiERS1m can dimerize with itself and with MiERS1, but not with MiETR1. In contrast, no dimerization of MiERS1s with the other receptors could be detected.Im Vergleich zum typischerweise hohen Fruchtansatz bei Mango (Mangifera indica L.) erreicht oft nur ein geringer Teil der Früchte die Erntereife. Dieser extensive Fruchtfall ist ein Hauptgrund für Ertragseinbußen und führt somit weltweit zu substantiellen ökonomischen Verlusten für Mangoanbauer. Die zahlreichen Ursachen des Fruchtfalls umfassen Schädlings und Krankheitsbefall, ungeeignete Umweltbedingungen oder Kulturführungsmaßnahmen. Aufgrund der negativen Auswirkung des Fruchtfalls auf die Mangoproduktion ist das Ziel dieser Arbeit das Verständnis der zugrundeliegenden Mechanismen zu erweitern und Gegenmaßnahmen zu entwickeln. Zur Verminderung des Fruchtfalls sind bereits verschiedene Ansätze getestet worden, jedoch wurden auch ebenso viele Auswertungsmethoden genutzt, was den Vergleich verschiedener Studien erschwert. Daher wurde ein Modell entwickelt das den Zeitverlauf des Fruchtfalls allgemeingültig definiert und somit den Vergleich verschiedener Studien untereinander ermöglicht. Das Model wurde anhand des Fruchtfalls im Kontext verschiedener Kulturführungsmaßnahmen getestet und validiert, wobei traditionelle Monokulturplantagen jeweils mit 1) Mischkultur; 2) Bewässerung; und 3) Applikation von Wachstumsregulatoren verglichen wurde. Der zeitliche Verlauf des Fruchtfalls konnte am besten mit einer Sigmoidfunktion angenähert werden, worauf basierend der Nachblüte-, der mittelsaisonale und der Vorerntefruchtfall unterschieden wurde. Die Ergebnisse der Evaluation der Kulturführungsmaßnahmen zeigte, dass der Anbau von Mais und Mango als Mischkultur keine negativen Effekte auf den Fruchtfall bei Mango hat. Die Bewässerung führte zu einem dreimal höheren Fruchtbehang im Vergleich zur unbewässerten Kontrolle. Die Einzelbehandlung mit 40 ppm 1 Naphthylessigsäure am Ende des Nachblütefruchtfalls führte zu durchgängig höherem Behang. Das entwickelte Model erlaubt unter anderem eine frühe Abschätzung der Behandlungswirksamkeit oder fundierte Ernteprognosen. Die Ressourcen eines Baumes sind im Besonderen während des mittelsaisonalen Fruchtfalls limitiert, welches zur Konkurrenz zwischen den Pflanzenorganen führt und somit Fruchtfall induziert. Das Mangobäume während des mittelsaisonalen Fruchtfalls geringe Photosyntheseraten aufweisen die auf Trockenstress hindeuten, unterstützt diese Theorie. Da das Stresshormon Ethylen am Abszissionsprozess beteiligt ist, wurde die ethylenemittierende Substanz Ethephon genutzt um den zeitlichen Verlauf der Abszission zu studieren. Dabei zeigte sich, dass eine Behandlung mit 7200 ppm Ethephon (ET7200) zuverlässig die Fruchtabszission bei Mango induziert. Das Experiment wurde um eine zusätzliche Ethephonkonzentration von 600 ppm (ET600) erweitert. Im Vergleich zur unbehandelten Kontrolle war die polare Auxin-transportkapazität (PAT) des Pedizels infolge beider Ethephonbehandlungen bereits am Tag 1 nach Behandlung und an den Folgetagen signifikant reduziert. ET7200 führte im Vergleich zur Kontrolle bereits am Tag 1 nach Behandlung zur Hochregulierung der Transkriptlevel der Ethylenrezeptorgene MiETR1 und MiERS1, wobei dies durch ET600 erst am Tag 2 nach Behandlung erreicht wurde. ET600 induzierte einen signifikanten Anstieg der Rezeptoren MiETR1 im Perikarp am Tag 2 nach Behandlung und MiERS1 im Pedizel am Tag 2 und 3 nach Behandlung. Im Gegensatz dazu waren, abgesehen von MiETR1 im Pedizel, in Folge von ET7200 ab Tag 1 nach Behandlung beide Gene in beiden Geweben signifikant hochreguliert. Der Effekt von Ethephon war als letztes anhand der Saccharosekonzentration im Perikarp messbar, welche im Vergleich zur Kontrolle am Tag 2 nach Behandlung signifikant reduziert war. Basierend auf diesen Ergebnissen wurde postuliert, dass eine durch Ethephon induzierte Abszission mit der Reduzierung des PAT im Pedizel beginnt, gefolgt von der Hochregulierung der Ethylenrezeptoren und letztlich der Reduktion von Saccharose in den Früchten. Ethylenrezeptoren sind Schlüsselelemente der Abszission und anderer Prozessen des Lebenszyklus der Pflanzen. Daher wurden diese Rezeptoren bei Mango tiefgehender auf molekularer Ebene untersucht. Zusätzlich zu den zuvor bekannten Rezeptoren MiETR1 und MiERS, konnten zwei neue Versionen des MiERS1 bei Mango identifiziert werden. Im Vergleich zu MiERS1, weisen diese Gene, MiERS1m und MiERS1s, andere Expressionsmuster auf und kodieren für Proteine denen bestimmte funktionale Domänen des MiERS1 fehlen. Die Rezeptoren wurden mittels transienter Expression von Fluoreszenzfusionsproteinen in der Modellpflanze Tabak untersucht. Alle Rezeptoren konnten am endoplasmatischen Retikulum lokalisiert werden. Experimente mit bi-molekularer Fluoreszenzkomplementierung zeigten, dass der MiERS1 mit sich selbst und mit dem MiERS1, aber nicht mit dem MiETR1 dimerisieren kann. Beim MiERS1s hingegen, wurde keine Dimerisation mit anderen Rezeptoren detektiert

Absence of GAPDH regulation in tumor-cells of different origin under hypoxic conditions in – vitro

<p>Abstract</p> <p>Background</p> <p>Gene expression studies related to cancer diagnosis and treatment are important. In order to conduct such experiment accurately, absolutely reliable housekeeping genes are essential to normalize cancer related gene expression. The most important characteristics of such genes are their presence in all cells and their expression levels remain relatively constant under different experimental conditions. However, no single gene of this group of genes manifests always stable expression levels under all experimental conditions. Incorrect choice of housekeeping genes leads to interpretation errors of experimental results including evaluation and quantification of pathological gene expression. Here, we examined (a) the degree of GAPDH expression regulation in Hep-1-6 mouse hepatoma and Hep-3-B and HepG2 human hepatocellular carcinoma cell lines as well as in human lung adenocarcinoma epithelial cell line (A-549) in addition to both HT-29, and HCT-116 colon cancer cell lines, under hypoxic conditions <it>in vitro </it>in comparison to other housekeeping genes like β-actin, serving as experimental loading controls, (b) the potential use of GAPDH as a target for tumor therapeutic approaches was comparatively examined <it>in vitro </it>on both protein and mRNA level, by western blot and semi quantitative RT-PCR, respectively.</p> <p>Findings</p> <p>No hypoxia-induced regulatory effect on GAPDH expression was observed in the cell lines studied <it>in vitro </it>that were; Hep-1-6 mouse hepatoma and Hep-3-B and HepG2 human hepatocellular carcinoma cell lines, Human lung adenocarcinoma epithelial cell line (A-549), both colon cancer cell lines HT-29, and HCT-116.</p> <p>Conclusion</p> <p>As it is the case for human hepatocellular carcinoma, mouse hepatoma, human colon cancer, and human lung adenocarcinoma, GAPDH represents an optimal choice of a housekeeping gene and/(or) loading control to determine the expression of hypoxia induced genes in tumors of different origin. The results confirm our previous findings in human glioblastoma that this gene is not an attractive target for tumor therapeutic approaches because of the lack of GAPDH regulation under hypoxia.</p

Entwicklung neuer Studiengänge - Curricula kooperativ und kompetenzorientiert gestalten

Mit einer "kooperativen Curriculumsentwicklung" soll ein Beitrag zur Öffnung von Hochschulen geleistet werden: Neue Studiengänge werden nicht mehr nur von der Hochschule, sondern gemeinsam mit Unternehmen und Einrichtungen der beruflichen Bildung entwickelt. Die Fachhochschule der Diakonie in Bielefeld hat dazu ein Modell entwickelt und setzt dieses in einem Forschungsprojekt im Rahmen der BMBF-Initiative "Aufstieg durch Bildung – Offene Hochschulen" um. Der Werkstattbericht gibt einen Einblick in die konkreten Entwicklungsschritte und diskutiert Chancen und Hürden des Modells. 21.03.2014 | Miriam Schäfer, Michael Kriegel & Tim Hagemann (Bielefeld