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Current diagnostic methods for evaluating the functionality of the lymphatic vascular system usually do not provide quantitative data and suffer from many limitations including high costs, complexity, and the need to perform them in hospital settings. In this work, we present a quantitative, simple outpatient technology named LymphMonitor to quantitatively assess lymphatic function. This method is based on the painless injection of the lymphatic-specific near-infrared fluorescent tracer indocyanine green complexed with human serum albumin, using MicronJet600™ microneedles, and monitoring the disappearance of the fluorescence signal at the injection site over time using a portable detection device named LymphMeter. This technology was investigated in 10 patients with unilateral leg or arm lymphedema. After injection of a tracer solution into each limb, the signal was measured over 3 h and the area under the normalized clearance curve was calculated to quantify the lymphatic function. A statistically significant difference in lymphatic clearance in the healthy versus the lymphedema extremities was found, based on the obtained area under curves of the normalized clearance curves. This study provides the first evidence that the LymphMonitor technology has the potential to diagnose and monitor the lymphatic function in patients., Diagnostics, 11 (10)

Preliminary studies have shown the superiority of convolutional neural networks (CNNs) compared to other network architectures for determining the surface quality of friction stir welds. In this paper, CNNs were employed to detect cavities inside friction stir welds by evaluating inline measured process data. The aim was to determine whether CNNs are suitable for identifying surface defects exclusively, or if the approach is transferable to internal weld defects. For this purpose, 120 welds were produced and examined by ultrasonic testing, which was the basis for labeling the data as “good” or “defective.” Different types of artificial neural network were tested for predicting the placement of the welds into the defined classes. It was found that the way of labeling the data is significant for the accuracy achievable. When the complete welds were uniformly labeled as “good” or “defective,” an accuracy of 98.5% was achieved by a CNN, which was a significant improvement compared to the state of the art. When the welds were labeled segment-wise, an accuracy of 79.2% was obtained by using a CNN, showing that a segment-wise prediction of the cavities is also possible. The results confirm that CNNs are well suited for process monitoring in friction stir welding and their application enables the identification of various defect types.

Die Schweißtemperatur spielt beim Rührreibschweißen (FSW) eine wichtige Rolle, da sie die Nahteigenschaften maßgeblich beeinflusst. Deshalb wurde im Rahmen dieser Dissertation eine Schweißtemperaturregelung für das FSW entwickelt und experimentell getestet. Im Anschluss wurde der Mehrwert der Schweißtemperaturregelung beim FSW an einer hochfesten Aluminiumlegierung demonstriert. Abschließend wurde gezeigt, dass beim FSW eine indirekte Schweißtemperaturregelung über das Prozessmoment möglich ist. The welding temperature plays an important role in friction stir welding (FSW), because it significantly influences the weld properties. In this thesis, a welding temperature control system for FSW was developed and experimentally tested. Subsequently, the benefit of the welding temperature control system for FSW was demonstrated at a high strength aluminum alloy. Finally, it was shown that for FSW an indirect welding temperature control via the process torque is feasible.

Laser-based Powder Bed Fusion (LPBF) has become a key Additive Manufacturing (AM) technology for the production of complex metallic components within a short lead-time. Contaminated powder feedstock is a major challenge in LPBF due to the uncertain influence of contaminations on part quality. This study investigates the effects of different contaminants inside the feedstock on material density and metallurgical structure in order to evaluate their implications for serial production. Pieces of rubber gloves, human, and recoater brush hair as well as five more substances were applied manually at a defined layer during the manufacturing process of Hastelloy® X (HX) specimens. The part densities were 99.9% for all contaminated specimens. Cross-sections did not show increased porosity. For some contaminants, inclusions of foreign material residue were observed. The results for HX were evaluated and implications for comparable materials were derived. Lastly, the criticality of the investigated contaminants on part quality was analyzed.

Dynamic regulation of chromatin, a structure consisting of DNA and histone proteins, is mediated through histone post-translational modifications (PTMs) and effector proteins. HP1a and PRC2 are recruited to repressive PTMs (H3K9me3, H3K27me3) and enable heterochromatin formation, which leads to gene silencing. During the DNA damage response, tight spatial and temporal control of the chromatin compaction state is required and novel PTMs are installed to guide proteins through dynamic signalling pathways. In the RNF168-mediated signalling cascade, appropriate DNA repair mechanisms are selected through ubiquitination (H2AK15ub) of chromatin. Improper regulation of these processes leads to cancer and neurodegenerative diseases. Here, we present a method to study chromatin-protein interactions employing total internal reflection fluorescence microscopy (TIRFM) and in vitro chromatin assembly of chemically defined, modified histones. Colocalization experiments of fluorescently labelled chromatin fibres and proteins allowed us to observe dynamic chromatin-protein interactions on the single-molecule level. We tested different binding models of HP1a, and we measured a highly dynamic behaviour of HP1a towards chromatin in dependence of the available binding sites or HP1a concentration. HP1a dimerization allows multivalent binding, increased chromatin association and decreased dissociation and thus leads to a more stable mode of chromatin binding. Further, we studied PRC2 recruitment to chromatin and DNA in dependence of the accessory factor PHF1. We measured increased residence times of PRC2 when PHF1 was included. Structure prediction and mutagenesis studies identified a novel winged-helix (WH) motif of PHF1, which was responsible for the enhanced binding effect in PRC2-PHF1 measurements. Moreover, binding of PRC2 towards chromatin was prolonged in the presence of H3K27me3, H3K27M or H3K36me3 histone PTMs. Next, we characterized the chromatin writer RNF168. We show altered ubiquitination activities dependent on accessibility of the nucleosome acidic patch, which was tested by addition of a competitor (RAPTA-C) or by introducing H4K16 acetylation, which leads to an open chromatin conformation. RNF168 is a multivalent reader of ubiquitin marks and we show binding specificity of ubiquitin binding module 1 (UDM1) towards native and synthetic K63-linked ubiquitin chains, while no interaction with K48-linked ubiquitin chains was detected. In contrast, we could not determine a clear contribution of the second binding module (UDM2), which recognizes H2A.XK15ub. In summary, we gained insight into different binding modes of HP1a, PRC2 and RNF168. Understanding basal protein binding mechanisms and chromatin regulation is essential to find new drug targets.

Mit meiner Diplomarbeit m��chte ich f��r meine Heimatgemeinde M��hlbach ein Konzept entwickeln, welches auf Nachhaltigkeit setzt und einen Mehrwert f��r den Ort schafft. Ziel der Arbeit ist es den Ort zu analysieren, sein Potential zu erfassen und anschlie��end mit Hilfe des neuen Konzeptes die Nutzung der Ortschaft positiv zu verst��rken und dadurch einen Mehrwert f��r das gesamte Dorf zu schaffen. Dies soll durch die Nutzung und Neugestaltung leerstehender Geb��ude und/oder durch den Neubau eines Geb��udes erreicht werden. In Zusammenarbeit mit dem Institut f��r Raumgestaltung und nachhaltiges Entwerfen soll ein Konzept f��r den Ort entwickelt werden, welche sich mit den Menschen, der Geschichte, den Traditionen und den Vorz��gen des Ortes sowie des Landes auseinander setzt. Wie sowohl meine bisherigen Analysen als auch die Grundlagenanalyse, welche im Mai 2012 von CIMA f��r die Gemeinde durchgef��hrt wurde, zeigen, ist Tourismus das tragende Element der Su-dtiroler und auch der M��hlbacher Wirtschaft. Mit Hilfe des Tourismus sollen jedoch auch die anderen Wirtschaftszweige gest��rkt und besser in das Dorfgeschehen einbezogen werden. Mit Schwerpunkt auf Nachhaltigkeit sollen lokale und regionale Unternehmen einbezogen und lokale Produkte sowie Rohstoffe verwendet werden. Sei es in der Produktion und Ausf��hrung der Geb��ude als auch in der Bewirtschaftung und langfristigen Nutzung. Idee f��r die Nutzung der bestehenden Bausubstanz und des Neubaus ist der Entwurf eines Gourmetrestaurants, mehreren Ferienappartements sowie eines Gesch��ftes, welches auf Einwegverpackungen verzichtet und regionale Produkte anbietet. Die einzelnen Entw��rfe sollen f��r sich selbst stehen und auf die ortsbezogenen Identit��ten eingehen, jedoch sich als Ganzes verkaufen und als eine Marke sowohl gestalterisch als auch wirtschaftlich zusammen funktionieren., With my thesis I would like to develop a concept, which sets on sustainability and creates an increase in value for my hometown Muehlbach. The objective of the thesis is to analyse the place, capture its potential and with the help of the new concept subsequently strengthen the use of the locality and create an increase in value for the entire village. This should be achieved by the use and reorganization of empty buildings and/or by a new building. In co-operation with the Department of Spatial and Sustainable Design a concept for the place is to be developed, which argues with the humans, the history, the traditions and the advantages of the place as well as the country apart. As my past analyses and the basic analysis, which were accomplished in May 2012 by CIMA for the community, show is tourism the basic element of the South Tyrolean and also the Muehlbacher economy. With the help of the tourism other industries should be strengthened and included better into the village happening. With emphasis on sustainability local and regional companies are to be involved and local products as well as local raw materials are to be used. Be it in production and execution of the buildings as well as in the management and long-term usage. Idea for the use of the existing built volumes and the new building is the draft of a gourmet restaurant, several holiday apartments as well as a store, which renounces on one-way packaging and offers regional products. The individual drafts are to stand for itself and deal with the local identities, sell themselves though as a whole business and function as a brand artistic and economically together.

The macroeconomic implications of firms’ lumpy investment behavior are subject to ongoing research. Lumpy investment results from fixed capital adjustment costs which give firms an incentive to reduce the frequency of capital adjustments. However, previous studies have underestimated the lumpiness. Their assumption of constant capital utilization reduces firms’ incentives to undertake large investments as it prevents reserve capacity building. This paper shows that if capacity utilization is allowed to vary, firms optimally undertake larger investments and leave parts of the new capital stock idle for some periods, thereby reducing the frequency of investment activities. Using a dynamic stochastic general equilibrium model with fixed capital adjustment costs, heterogeneous firms, variable utilization, and aggregate technology shocks, I numerically compute firms’ optimal decisions on investment, utilization and labor demand. Compared to the constant utilization model, the findings reveal magnified investment lumpiness: Firms adjust capital less frequently, but invest more when they adjust. However, this appears to be of minor macroeconomic relevance: Moments and impulse responses of macroeconomic quantities change in a similar way when variable utilization is introduced in a lumpy or in a frictionless model. New empirical evidence based on firm-level panel data confirms some of the theoretical findings.

This paper proposes a new method for welfare analysis of unfunded social security systems. Based on an overlapping generations model with endogenous labor supply, we derive a formula for the evaluation of existing pay-as-you-go social security systems that depends on impulse response functions and projected growth rates only. We propose an implementation strategy based on reduced form estimates of a VAR model that is valid under weak assumptions about the deep structure of the model. Our method is related to the sufficient statistic approach (Chetty, 2009). For the current system in the United States, we find that a transitory increase in the payroll tax rate along with higher pension benefits leads to a welfare increase mainly due to welfare gains of today’s retirees. A scenario analysis demonstrates the robustness of this result.

Sudden stops in capital inflows were a main characteristic of the emerging market crisis during the 1990’s. Concerns about them have recurred in the light of recently increased global stability risk and the quantitative easing that led to substantial capital inflows in emerging economies. We add to the empirical literature that relies on a univariate approach by using a multivariate framework to assess the effect of sudden stops on economic growth and by the identification of sudden stop shocks using a Markov switching VAR and sign restrictions. The Markov switching VAR approach dates sudden stop periods comparable to the existing literature. It reveals a significant negative influence of the regime switch on economic growth that is robust across different estimation methods. Moreover, the Markov switching VAR also indicates that the reaction of macroeconomic variables to the identified shock based on sign restrictions is regime dependent.