SALBPGen - A systematic data generator for (simple) assembly line balancing

Assembly line balancing is a well-known and extensively researched decision problem which arises when assembly line production systems are designed and operated. A large variety of real-world problem variations and elaborate solution methods were developed and presented in the academic literature in the past 60 years. Nevertheless, computational experiments examining and comparing the performance of solution procedures were mostly based on very limited data sets unsystematically collected from the literature and from some real-world cases. In particular, the precedence graphs used as the basis of former tests are limited in number and characteristics. As a consequence, former performance analyses suffer from a lack of systematics and statistical evidence. In this article, we propose SALPBGen, a new instance generator for the simple assembly line balancing problem (SALBP) which can be applied to any other assembly line balancing problem, too. It is able to systematically create instances with very diverse structures under full control of the experiment's designer. In particular, based on our analysis of real-world problems from automotive and related industries, typical substructures of the precedence graph like chains, bottlenecks and modules can be generated and combined as required based on a detailed analysis of graph structures and structure measures like the order strength. We also present a collection of new challenging benchmark data sets which are suited for comprehensive statistical tests in comparative studies of solution methods for SALBP and generalized problems as well. Researchers are invited to participate in a challenge to solve these new problem instances.manufacturing, benchmark data set, assembly line balancing, precedence graph, structure analysis, complexity measures

Stakeholder involvement in action plans and/or policies for organic food and farming – ORGAP project recommendations

Stakeholder involvement in action plans and/or policies for organic food and farming are seen as part of good governance. Within the EU project ORGAP (www.orgap.org) recommendations are made how to consider and evaluate the level und degree of stakeholder involvement. Different stakeholder perspectives (organic principles, market, public goods) have to bee taken into account in the different stages of an action plan/policy (the design, decision, implementation and evaluation). Participatory methods can be useful if sufficient resources and time are available

The mapping task and its various applications in next-generation sequencing

The aim of this thesis is the development and benchmarking of computational methods for the analysis of high-throughput data from tiling arrays and next-generation sequencing. Tiling arrays have been a mainstay of genome-wide transcriptomics, e.g., in the identification of functional elements in the human genome. Due to limitations of existing methods for the data analysis of this data, a novel statistical approach is presented that identifies expressed segments as significant differences from the background distribution and thus avoids dataset-specific parameters. This method detects differentially expressed segments in biological data with significantly lower false discovery rates and equivalent sensitivities compared to commonly used methods. In addition, it is also clearly superior in the recovery of exon-intron structures. Moreover, the search for local accumulations of expressed segments in tiling array data has led to the identification of very large expressed regions that may constitute a new class of macroRNAs. This thesis proceeds with next-generation sequencing for which various protocols have been devised to study genomic, transcriptomic, and epigenomic features. One of the first crucial steps in most NGS data analyses is the mapping of sequencing reads to a reference genome. This work introduces algorithmic methods to solve the mapping tasks for three major NGS protocols: DNA-seq, RNA-seq, and MethylC-seq. All methods have been thoroughly benchmarked and integrated into the segemehl mapping suite. First, mapping of DNA-seq data is facilitated by the core mapping algorithm of segemehl. Since the initial publication, it has been continuously updated and expanded. Here, extensive and reproducible benchmarks are presented that compare segemehl to state-of-the-art read aligners on various data sets. The results indicate that it is not only more sensitive in finding the optimal alignment with respect to the unit edit distance but also very specific compared to most commonly used alternative read mappers. These advantages are observable for both real and simulated reads, are largely independent of the read length and sequencing technology, but come at the cost of higher running time and memory consumption. Second, the split-read extension of segemehl, presented by Hoffmann, enables the mapping of RNA-seq data, a computationally more difficult form of the mapping task due to the occurrence of splicing. Here, the novel tool lack is presented, which aims to recover missed RNA-seq read alignments using de novo splice junction information. It performs very well in benchmarks and may thus be a beneficial extension to RNA-seq analysis pipelines. Third, a novel method is introduced that facilitates the mapping of bisulfite-treated sequencing data. This protocol is considered the gold standard in genome-wide studies of DNA methylation, one of the major epigenetic modifications in animals and plants. The treatment of DNA with sodium bisulfite selectively converts unmethylated cytosines to uracils, while methylated ones remain unchanged. The bisulfite extension developed here performs seed searches on a collapsed alphabet followed by bisulfite-sensitive dynamic programming alignments. Thus, it is insensitive to bisulfite-related mismatches and does not rely on post-processing, in contrast to other methods. In comparison to state-of-the-art tools, this method achieves significantly higher sensitivities and performs time-competitive in mapping millions of sequencing reads to vertebrate genomes. Remarkably, the increase in sensitivity does not come at the cost of decreased specificity and thus may finally result in a better performance in calling the methylation rate. Lastly, the potential of mapping strategies for de novo genome assemblies is demonstrated with the introduction of a new guided assembly procedure. It incorporates mapping as major component and uses the additional information (e.g., annotation) as guide. With this method, the complete mitochondrial genome of Eulimnogammarus verrucosus has been successfully assembled even though the sequencing library has been heavily dominated by nuclear DNA. In summary, this thesis introduces algorithmic methods that significantly improve the analysis of tiling array, DNA-seq, RNA-seq, and MethylC-seq data, and proposes standards for benchmarking NGS read aligners. Moreover, it presents a new guided assembly procedure that has been successfully applied in the de novo assembly of a crustacean mitogenome.Diese Arbeit befasst sich mit der Entwicklung und dem Benchmarken von Verfahren zur Analyse von Daten aus Hochdurchsatz-Technologien, wie Tiling Arrays oder Hochdurchsatz-Sequenzierung. Tiling Arrays bildeten lange Zeit die Grundlage für die genomweite Untersuchung des Transkriptoms und kamen beispielsweise bei der Identifizierung funktioneller Elemente im menschlichen Genom zum Einsatz. In dieser Arbeit wird ein neues statistisches Verfahren zur Auswertung von Tiling Array-Daten vorgestellt. Darin werden Segmente als exprimiert klassifiziert, wenn sich deren Signale signifikant von der Hintergrundverteilung unterscheiden. Dadurch werden keine auf den Datensatz abgestimmten Parameterwerte benötigt. Die hier vorgestellte Methode erkennt differentiell exprimierte Segmente in biologischen Daten bei gleicher Sensitivität mit geringerer Falsch-Positiv-Rate im Vergleich zu den derzeit hauptsächlich eingesetzten Verfahren. Zudem ist die Methode bei der Erkennung von Exon-Intron Grenzen präziser. Die Suche nach Anhäufungen exprimierter Segmente hat darüber hinaus zur Entdeckung von sehr langen Regionen geführt, welche möglicherweise eine neue Klasse von macroRNAs darstellen. Nach dem Exkurs zu Tiling Arrays konzentriert sich diese Arbeit nun auf die Hochdurchsatz-Sequenzierung, für die bereits verschiedene Sequenzierungsprotokolle zur Untersuchungen des Genoms, Transkriptoms und Epigenoms etabliert sind. Einer der ersten und entscheidenden Schritte in der Analyse von Sequenzierungsdaten stellt in den meisten Fällen das Mappen dar, bei dem kurze Sequenzen (Reads) auf ein großes Referenzgenom aligniert werden. Die vorliegende Arbeit stellt algorithmische Methoden vor, welche das Mapping-Problem für drei wichtige Sequenzierungsprotokolle (DNA-Seq, RNA-Seq und MethylC-Seq) lösen. Alle Methoden wurden ausführlichen Benchmarks unterzogen und sind in der segemehl-Suite integriert. Als Erstes wird hier der Kern-Algorithmus von segemehl vorgestellt, welcher das Mappen von DNA-Sequenzierungsdaten ermöglicht. Seit der ersten Veröffentlichung wurde dieser kontinuierlich optimiert und erweitert. In dieser Arbeit werden umfangreiche und auf Reproduzierbarkeit bedachte Benchmarks präsentiert, in denen segemehl auf zahlreichen Datensätzen mit bekannten Mapping-Programmen verglichen wird. Die Ergebnisse zeigen, dass segemehl nicht nur sensitiver im Auffinden von optimalen Alignments bezüglich der Editierdistanz sondern auch sehr spezifisch im Vergleich zu anderen Methoden ist. Diese Vorteile sind in realen und simulierten Daten unabhängig von der Sequenzierungstechnologie oder der Länge der Reads erkennbar, gehen aber zu Lasten einer längeren Laufzeit und eines höheren Speicherverbrauchs. Als Zweites wird das Mappen von RNA-Sequenzierungsdaten untersucht, welches bereits von der Split-Read-Erweiterung von segemehl unterstützt wird. Aufgrund von Spleißen ist diese Form des Mapping-Problems rechnerisch aufwendiger. In dieser Arbeit wird das neue Programm lack vorgestellt, welches darauf abzielt, fehlende Read-Alignments mit Hilfe von de novo Spleiß-Information zu finden. Es erzielt hervorragende Ergebnisse und stellt somit eine sinnvolle Ergänzung zu Analyse-Pipelines für RNA-Sequenzierungsdaten dar. Als Drittes wird eine neue Methode zum Mappen von Bisulfit-behandelte Sequenzierungsdaten vorgestellt. Dieses Protokoll gilt als Goldstandard in der genomweiten Untersuchung der DNA-Methylierung, einer der wichtigsten epigenetischen Modifikationen in Tieren und Pflanzen. Dabei wird die DNA vor der Sequenzierung mit Natriumbisulfit behandelt, welches selektiv nicht methylierte Cytosine zu Uracilen konvertiert, während Methylcytosine davon unberührt bleiben. Die hier vorgestellte Bisulfit-Erweiterung führt die Seed-Suche auf einem reduziertem Alphabet durch und verifiziert die erhaltenen Treffer mit einem auf dynamischer Programmierung basierenden Bisulfit-sensitiven Alignment-Algorithmus. Das verwendete Verfahren ist somit unempfindlich gegenüber Bisulfit-Konvertierungen und erfordert im Gegensatz zu anderen Verfahren keine weitere Nachverarbeitung. Im Vergleich zu aktuell eingesetzten Programmen ist die Methode sensitiver und benötigt eine vergleichbare Laufzeit beim Mappen von Millionen von Reads auf große Genome. Bemerkenswerterweise wird die erhöhte Sensitivität bei gleichbleibend guter Spezifizität erreicht. Dadurch könnte diese Methode somit auch bessere Ergebnisse bei der präzisen Bestimmung der Methylierungsraten erreichen. Schließlich wird noch das Potential von Mapping-Strategien für Assemblierungen mit der Einführung eines neuen, Kristallisation-genanntes Verfahren zur unterstützten Assemblierung aufgezeigt. Es enthält Mapping als Hauptbestandteil und nutzt Zusatzinformation (z.B. Annotationen) als Unterstützung. Dieses Verfahren ermöglichte die erfolgreiche Assemblierung des kompletten mitochondrialen Genoms von Eulimnogammarus verrucosus trotz einer vorwiegend aus nukleärer DNA bestehenden genomischen Bibliothek. Zusammenfassend stellt diese Arbeit algorithmische Methoden vor, welche die Analysen von Tiling Array, DNA-Seq, RNA-Seq und MethylC-Seq Daten signifikant verbessern. Es werden zudem Standards für den Vergleich von Programmen zum Mappen von Daten der Hochdurchsatz-Sequenzierung vorgeschlagen. Darüber hinaus wird ein neues Verfahren zur unterstützten Genom-Assemblierung vorgestellt, welches erfolgreich bei der de novo-Assemblierung eines mitochondrialen Krustentier-Genoms eingesetzt wurde

Simultaneous observations of haemolymph flow and ventilation in marine spider crabs at different temperatures: a flow weighted MRI study

In vivo magnetic resonance imaging (MRI) and angiography were applied to the marine spider crab Maja squinado for a study of temperature effects and thermal tolerance. Ventilation and haemolymph circulation were investigated during progressive cooling from 12°C to 2°C. The anatomical resolution of MR images from Maja squinado obtained with a standard spin echo sequence were suitable to resolve the structures of various internal organs. The heart of the animal could be depicted without movement artifacts. The use of a flow compensated gradient echo sequence allowed simultaneous observations of ventilation, reflected by water flow through the gill chambers as well as of haemolymph flow. Simultaneous investigation of various arteries was possible by use of flow weighted MRI. In addition to those accessible by standard invasive flow sensitive doppler sensors, flow changes in gill, leg arteries and the venous return could be observed. Both ventilation and haemolymph flow decreased during progressive cooling and changes in haemolymph flow varied between arteries. Haemolymph flow through the Arteria sternalis, some gill and leg arteries was maintained at low temperatures indicating a reduced thermal sensitivity of flow in selected vessels. In support of previous invasive studies of haemolymph flow as well as heart and ventilation rates, the results demonstrate that the operation of gills and the maintenance of locomotor activity are critical for cold tolerance. A shift in haemolymph flow between arteries likely occurs to ensure the functioning of locomotion and ventilation in the cold

Real-Time Teleguidance of a Non-Surgeon Crew Medical Officer Performing Orthopedic Surgery at the Amundsen-Scott South Pole Station During Winter-Over

The Amundsen-Scott South Pole Research station located at the geographic South Pole, is the most isolated, permanently inhabited human outpost on Earth. Medical care is provided to station personnel by a non-surgeon crew medical officer (CMO). During the winter-over period from February to October, the station is isolated, with no incoming or outgoing flights due to severe weather conditions. In late June, four months after the station had closed for the austral winter, a 31 year old meteorologist suffered a complete rupture of his patellar tendon while sliding done an embankment. An evacuation was deemed to be too risky to aircrews due to the extreme cold and darkness. A panel of physicians from Massachusetts General Hospital, Johns Hopkins University and the University of Texas Medical Branch were able to assess the patient remotely via telemedicine and agreed that surgery was the only means to restore mobility and prevent long term disability. The lack of a surgical facility and a trained surgical team were overcome by conversion of the clinic treatment area, and intensive preparation of medical laypersons as surgical assistants. The non-surgeon CMO and CMO assistant at South Pole, were guided through the administration of spinal anesthetic, and the two-hour operative repair by medical consultants at Massachusetts General Hospital. Real-time video of the operative field, directions from the remote consultants and audio communication were provided by videoconferencing equipment, operative cameras, and high bandwidth satellite communications. In real-time, opening incision/exposure, tendon relocation, hemostatsis, and operative closure by the CMO was closely monitored and guided and by the remote consultants. The patient s subsequent physical rehabilitation over the ensuing months of isolation was also monitored remotely via telemedicine. This was the first time in South Pole s history that remote teleguidance had been used for surgery and represents a model for real-time guidance of CMO s working at remote duty stations

The Stability of Fresh Zero-Slump Concrete

This report focuses upon the effects of cement-substitution in part by two potash feldspar powders, and by silica-fume, on the fresh concrete strength of newly compacted cylinder samples. The water/cement-ratio was kept constant at 0.31. An Intensive Compaction Tester (abbrev: IC-Tester) which exerts a slow kneading action under pressure on the sample in a cylindrical mold, was utilized. It was found that the fresh cylinder compressive strength increased with decreasing water-content and more than doubled with each of the 3 fillers replacing 30 % of the cement-volume. A tradeoff was a loss in 28-day compressive strength for both of the feldspars, while the 28-day strength of the silica-samples remained virtually unaffected

Human papilloma virus vaccination - Paradox of vaccination in cervical cancer and screening

© 2008 BMJ Publishing Group Ltd

Optical measurements on thermal convection processes inside thermal energy storages during stand-by periods

Thermal energy storages (TES) are increasingly important for storing energy from renewable energy sources. TES that work with liquid storage materials are used in their most efficient way by stratifying the storage fluid by its thermal density gradient. Mixing of the stratification layers during stand-by periods decreases the thermal efficiency of the TES. Tank sidewalls, unlike the often poorly heat-conducting storage fluids, promote a heat flux from the hot to the cold layer and lead to thermal convection. In this experimental study planar particle image velocimetry (PIV) measurements and background-oriented schlieren (BOS) temperature measurements are performed in a model experiment of a TES to characterise the influence of the thermal convection on the stratification and thus the storage efficiency. The PIV results show two vertical, counter-directed wall jets that approach in the thermocline between the stratification layers. The wall jet in the hot part of the thermal stratification shows compared to the wall jet in the cold region strong fluctuations in the vertical velocity, that promote mixing of the two layers. The BOS measurements have proven that the technique is capable of measuring temperature fields in thermally stratified storage tanks. The density gradient field as an intermediate result during the evaluation of the temperature field can be used to indicate convective structures that are in good agreement to the measured velocity fields