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Additional file 1. Supplementary information and data: Additional information on cell lines, bioinformatic data processing, CRISPR/Cas9-mediated knock-out of DIAPH2, flow cytometry for CD44 and CD24 expression, miRNA library preparation and next generation sequencing, Luciferase-reporter assay. Supplementary data summarized in tables: cell lines, antibodies, primers sequences, top up- and down-regulated miRNAs in microarray analysis: RDEB-cSCC versus RDEB-KCs, and HC-cSCC versus HC-KC, miR-10b target selection and validation. Supplementary experimental data in figures: miR-10b target selection and validation; controls for miRNA probe specificity in in situ hybridization on FFPE tissue sections; miRNA probe specificity for in situ hybridization on cultured cells and single cell resolution image-based data analysis workflow; miRNA probe specificity for in situ hybridization on cultured cells; generation of experimental cell lines; characterization of experimental cell lines; validation of miR-10b targets HOXD10 and DIAPH2; survival analysis and target evaluation.

Human skin contains a population of memory T cells that supports tissue homeostasis and provides protective immunity. The study of human memory T cells is often restricted to in vitro studies and to human PBMC serving as primary cell source. Because the tissue environment impacts the phenotype and function of memory T cells, it is crucial to study these cells within their tissue. Here we utilized immunodeficient NOD-scid IL2rnull (NSG) mice that carried in vivo-generated engineered human skin (ES). ES was generated from human keratinocytes and fibroblasts and was initially devoid of skin-resident immune cells. Upon adoptive transfer of human PBMC, this reductionist system allowed us to study human T cell recruitment from a circulating pool of T cells into non-inflamed human skin in vivo. Circulating human memory T cells preferentially infiltrated ES and showed diverse functional profiles of T cells found in fresh human skin. The chemokine and cytokine microenvironment of ES closely resembled that of non-inflamed human skin. Upon entering the ES T cells assumed a resident memory T cell-like phenotype in the absence of infection, and a proportion of these cutaneous T cells can be locally activated upon injection of monocyte derived dendritic cells (moDCs) that presented Candida albicans. Interestingly, we found that CD69+ memory T cells produced higher levels of effector cytokines in response to Candida albicans, compared to CD69- T cells. Overall, this model has broad utility in many areas of human skin immunology research, including the study of immune-mediated skin diseases. (VLID)5327496

Mutations within the COL7A1 gene underlie the inherited recessive subtype of the blistering skin disease dystrophic epidermolysis bullosa (RDEB). Although gene replacement approaches for genodermatoses are clinically advanced, their implementation for RDEB is challenging and requires endogenous regulation of transgene expression. Thus, we are using spliceosome-mediated RNA trans-splicing (SMaRT) to repair mutations in COL7A1 at the mRNA level. Here, we demonstrate the capability of a COL7A1-specific RNA trans-splicing molecule (RTM), initially selected using a fluorescence-based screening procedure, to accurately replace COL7A1 exons 1 to 64 in an endogenous setting. Retroviral RTM transduction into patient-derived, immortalized keratinocytes resulted in an increase in wild-type transcript and protein levels, respectively. Furthermore, we revealed accurate deposition of recovered type VII collagen protein within the basement membrane zone of expanded skin equivalents using immunofluorescence staining. In summary, we showed for the first time the potential of endogenous 5′ trans-splicing to correct pathogenic mutations within the COL7A1 gene. Therefore, we consider 5′ RNA trans-splicing a suitable tool to beneficially modulate the RDEB-phenotype, thus targeting an urgent need of this patient population.

Chinoline alkaloids found in Cinchona bark still play an important role in medicine, for example as antimalarial and antiarrhythmic drugs. For the first time Supercritical Fluid Chromatography has been utilized for their separation. Six respective derivatives (dihydroquinidine, dihydroquinine, quinidine, quinine, cinchonine and cinchonidine) could be resolved in less than 7 min, and three of them quantified in crude plant extracts. The optimum stationary phase showed to be an Acquity UPC2 Torus DEA 1.7 μm column, the mobile phase comprised of CO2, acetonitrile, methanol and diethylamine. Method validation confirmed that the procedure is selective, accurate (recovery rates from 97.2% to 103.7%), precise (intra-day ≤2.2%, inter-day ≤3.0%) and linear (R2 ≥ 0.999); at 275 nm the observed detection limits were always below 2.5 μg/ml. In all of the samples analyzed cinchonine dominated (1.87%–2.30%), followed by quinine and cinchonidine. Their total content ranged from 4.75% to 5.20%. These values are in good agreement with published data, so that due to unmatched speed and environmental friendly character SFC is definitely an excellent alternative for the analysis of these important natural products.

Chronic wounding as a result of recurrent skin blistering in the painful genetic skin disease epidermolysis bullosa, may lead to life-threatening infections, increased risk of tumor formation, and other serious medical complications. Therefore, epidermolysis bullosa patients have an urgent need for optimal wound care and tissue regeneration. Therapeutic strategies using gene-, protein-, and cell-therapies are being developed to improve clinical symptoms, and some of them have already been investigated in early clinical trials. The most favorable options of functional therapies include gene replacement, gene editing, RNA targeting, and harnessing natural gene therapy. This review describes the current progress of the different approaches targeting autologous skin cells, and will discuss the benefits and challenges of their application.

Functional impairment or complete loss of type VII collagen, caused by mutations within COL7A1, lead to the severe recessive form of the skin blistering disease dystrophic epidermolysis bullosa (RDEB). Here, we successfully demonstrate RNA trans-splicing as an auspicious repair option for mutations located in a wide range of exons by fully converting an RDEB phenotype in an ex vivo pre-clinical mouse model based on xenotransplantation. Via a self-inactivating (SIN) lentiviral vector a 3′ RNA trans-splicing molecule, capable of replacing COL7A1 exons 65–118, was delivered into type VII collagen deficient patient keratinocytes, carrying a homozygous mutation in exon 80 (c.6527insC). Following vector integration, protein analysis of an isolated corrected single cell clone showed secretion of the corrected type VII collagen at similar levels compared to normal keratinocytes. To confirm full phenotypic and long-term correction in vivo, patches of skin equivalents expanded from the corrected cell clone were grafted onto immunodeficient mice. Immunolabelling of 12 weeks old skin specimens showed strong expression of human type VII collagen restricted to the basement membrane zone. We demonstrate that the RNA trans-splicing technology combined with a SIN lentiviral vector is suitable for an ex vivo molecular therapy approach and thus adaptable for clinical application.

Marine species have evolved a variety of physical or chemical strategies to diminish damage from elevated environmental ultraviolet radiation. Mycosporine-like amino acids, a group of widely distributed small water soluble compounds, are biologically relevant because of their photo-protective potential. In addition, presumed antioxidant and skin protective strategies raise the interest for possible medicinal and cosmetic applications. In this study the first CE method for the quantification of mycosporine-like amino acids in marine species is presented. A borate buffer system consisting of 30 mM sodium tetraborate in water at a pH-value of 10.3 enabled the baseline separation of five MAAs, namely palythine, mycosporine-serinol, asterina-330, shinorine and porphyra-334, in 27 min. Separation voltage, temperature and detection wavelength were 25 kV, 25 °C and 320 nm, respectively. The optimized method was fully validated and applied for the quantitative determination of MAAs in the marine macroalgae Palmaria palmata, Porphyra umbilicalis, and Porphyra sp., as well as the lichen Lichina pygmaea.

Dystrophic epidermolysis bullosa (DEB) is a blistering skin disease caused by mutations in the gene COL7A1 encoding collagen VII. DEB can be inherited as recessive DEB (RDEB) or dominant DEB (DDEB) and is associated with a high wound burden. Perpetual cycles of wounding and healing drive fibrosis in DDEB and RDEB, as well as the formation of a tumor-permissive microenvironment. Prolonging wound-free episodes by improving the quality of wound healing would therefore confer substantial benefit for individuals with DEB. The collagenous domain of collagen VII is encoded by 82 in-frame exons, which makes splice-modulation therapies attractive for DEB. Indeed, antisense oligonucleotide–based exon skipping has shown promise for RDEB. However, the suitability of antisense oligonucleotides for treatment of DDEB remains unexplored. Here, we developed QR-313, a clinically applicable, potent antisense oligonucleotide specifically targeting exon 73. We show the feasibility of topical delivery of QR-313 in a carbomer-composed gel for treatment of wounds to restore collagen VII abundance in human RDEB skin. Our data reveal that QR-313 also shows direct benefit for DDEB caused by exon 73 mutations. Thus, the same topically applied therapeutic could be used to improve the wound healing quality in RDEB and DDEB.

The eyes are a particularly interesting modality for cognitive industrial assistance systems, as gaze analysis can reveal cognition- and task-related aspects, while gaze interaction depicts a lightweight and fast method for hands-free machine control. In this paper, we present mobEYEle, a body-worn eye tracking platform that performs the entire computation directly on the user, as opposed to primarily streaming the data to a centralized unit for online processing and hence restricting its pervasiveness. The applicability of the platform is demonstrated throughout extensive performance and battery runtime tests. Moreover, a self-contained calibration method is outlined that enables the usage of mobEYEle without any supervisor nor digital screen.

This paper motivates the employment of a cognitive headgear in the context of two concrete human-in-the-loop industrial use cases. However, the distinct design and implementation of such a headgear is strongly task-dependent and no one-fits-all solution exists. To overcome that, a computer-aided design process is proposed that allows the design of a device truly tailored to the individual needs. Further, the features and components required to support workers in the identified scenarios are depicted, including image-based worker localization, gaze-based skill-level detection, workflow recognition using head-worn sensors and multimodal assistance. Finally, early functional prototypes are illustrated.

As one of the most frequently occurring monomers in the biosphere, glucosamine is a valuable metabolite for several applications. Although microbial glucosamine production is still in its infancy, it offers the possibility to circumvent problems associated with traditional production by hydrolysis. Of particular interest is a study with Aspergillus niger, which reports for the first time high glucosamine excretion in the early phase of citric acid production. These results have relevance for both the commercial glucosamine production and deeper insight into the regulation of organic acid excretion in fungi. To investigate glucosamine excretion, we performed bioreactor batch cultivations with Penicillium ochrochloron CBS123.824 and A. niger CBS120.49 using cultivation conditions which are known to trigger the production of citric acid. Glucosamine detection in culture filtrates was achieved by two photometric methods, High performance liquid chromatography with evaporative light scattering detection (HPLC-ELSD) and HPLC with mass spectrometry detection (HPLC-MS). Surprisingly, we detected no glucosamine at all. Based on a critical review of published data for A. niger, we conclude that the reported high levels of excreted glucosamine might be an experimental artifact. However, growth experiments with glucosamine as a combined or single source for carbon or nitrogen showed that both organisms are in principle able to transport glucosamine across their plasma membrane, which is a prerequisite for the excretion of glucosamine.

International audience

In natural language processing (NLP), cross-domain text classification problems like cross-topic, cross-genre or cross-language authorship attribution are characterized by having different contexts for training and testing data. That is, learning algorithms which are trained on the specific properties of the training data have to make predictions on test data which comprises substantially different properties. To this end, the corpora that are used for analyses in cross-domain problems are limited in size and variation, decreasing the expressive power and generalizability of the proposed solutions. In this paper, we present a methodological framework and toolset for dynamically creating cross-domain datasets by utilizing millions of Reddit comments. We show that different types of cross-domain datasets such as cross-topic or cross-lingual corpora can be constructed, and demonstrate a wide variety of use cases, including previously unfeasible analyses like cross-lingual authorship attribution on original, non-translated texts. Using state-of-the-art authorship attribution methods, we show the potential of a cross-topic corpus generated by our framework when compared to the corpora that were used in related approaches, and enable the advance of research previously limited by corpora availability.

Introduction Multidisciplinary, complex rehabilitation interventions are an important part of the treatment of chronic diseases. However, little is known about the effectiveness of routine rehabilitation interventions within the German healthcare system. Due to the nature of the social insurance system in Germany, randomised controlled trials examining the effects of rehabilitation interventions are challenging to implement and scarcely accessible. Consequently, alternative pre-post designs can be employed to assess pre-post effects of medical rehabilitation programmes. We present a protocol of systematic review and meta-analysis methods to assess the pre-post effects of rehabilitation interventions in Germany. Methods and analysis The respective study will be conducted within the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A systematic literature review will be conducted to identify studies reporting the pre-post effects (start of intervention vs end of intervention or later) in German healthcare. Studies investigating the following disease groups will be included: orthopaedics, rheumatology, oncology, pulmonology, cardiology, endocrinology, gastroenterology and psychosomatics. The primary outcomes of interest are physical/mental quality of life, physical functioning and social participation for all disease groups as well as pain (orthopaedic and rheumatologic patients only), blood pressure (cardiac patients only), asthma control (patients with asthma only), dyspnoea (patients with chronic obstructive pulmonary disease only) and depression/anxiety (psychosomatic patients only). We will invite the principal investigators of the identified studies to provide additional individual patient data. We aim to perform the meta-analyses using individual patient data as well as aggregate data. We will examine the effects of both study-level and patient-level moderators by using a meta-regression method. Ethics and dissemination Only studies that have received institutional approval from an ethics committee and present anonymised individual patient data will be included in the meta-analysis. The results will be presented in a peer-reviewed publication and at research conferences. A declaration of no objection by the ethics committee of the University of Würzburg is available (number 20180411 01). Trial registration number CRD42018080316.

eingereicht von Lisa Muraurer BSc Universität Linz, Masterarbeit, 2019

Smart factories, in which processes are partially or completely automated and digitalized, are the future. Automobile production is also currently undergoing said change towards ‘Industry 4.0’. While the degree of automation is very high in car body construction due to the use of robots, the degree of automation in logistics varies depending on the process. By contrast, in transportation processes, such as the use of tugger trains, autonomous transport systems or forklifts, automation is at a very advanced stage of development. In picking processes the employee continues to be at the center of attention due to his flexibility in movement sequences and grasping. Assistance systems such as smart glasses, smart watches or scanner gloves can nevertheless support employees and provide process improvements. The present research project focuses on the use of Augmented Reality (AR) technologies, in particular the usage of smart glasses in manual man-to-goods order picking processes. The required information for order picking is displayed in smart glasses in the picker’s field of view. In scientific research, their usage has been tested primarily under laboratory conditions. I subsequently identified a research gap investigating a full shift usage of smart glasses under real industrial production conditions. For this reason, the present PhD thesis includes a full shift field study, which examines the impact of the smart glasses usage in order picking processes on the employee and the process. As a first step, a process for shop floor employee involvement in innovation projects based on Rogers’ ‘Diffusion of Innovations’ will be developed. Afterwards, the suitability of workstations for AR-usage will be evaluated using the Rasmussen skills-rules-knowledge-framework. In addition, an objective procedure for classifying individual activities into Rasmussen’s framework will be developed. After selecting the test workstation, which contains most of the process steps supportable by AR-technologies, I will compare scanning mechanisms for the interaction with the warehouse management system. The core of the research project is a full shift field study with 23 employees in automotive assembly supply, which examines the impact of a smart glasses usage on the number of errors, the error types, the task completion time, the attention, the subjective strain, the visual fatigue of the employees and the likelihood of symptomatic occurrence of simulator sickness. In contrast to most existing studies, the field study is conducted in real production in accordance to the rhythm of the assembly line. The test system is connected to the warehouse management system. Employees interact with the warehouse management system with the aid of a scanner. The age range of the participants represents the regular workforce. Besides that, I will select a smart glasses hardware, which enables the inclusion of corrective glasses wearers. All the above points contribute to a test under real industrial conditions. As a basis for comparison serves the previous process, which displays the picking orders on a monitor attached to the target shelf. In this system a scan glove is used as interaction mechanism. The evaluation of the study results determine a time saving of 22% and an error reduction of at least 33%, depending on the error type. Due to these promising results, I explain further steps for series introduction. In addition, I discuss further potentials of the usage of data glasses in order picking processes. Smarte Fabriken, in welchen Prozesse teilweise oder gänzlich automatisiert und digitalisiert sind, sind die Zukunft. Auch die Automobilproduktion befindet sich derzeit in diesem Wandel hin zur „Industrie 4.0“. Während beispielsweise im Karosseriebau der Automatisierungsgrad durch den Einsatz von Robotern sehr hoch ist, ist er in der Logistik prozessspezifisch unterschiedlich ausgeprägt. Bei Transportprozessen, wie dem Einsatz von Routenzügen, fahrerlosen Transportsystemen oder Gabelstaplern, ist der Entwicklungsstand der Automatisierung sehr weit fortgeschritten. In Kommissionierprozessen hingegen steht der Mitarbeiter durch seine Flexibilität in Bewegungsabläufen und im Greifen weiterhin im Mittelpunkt. Der Einsatz von Assistenzsystemen wie Datenbrillen, Smart Watches oder Scanner-Handschuhen kann dennoch Mitarbeiter unterstützen und Prozessverbesserungen hervorrufen. In dem vorliegenden Forschungsprojekt steht der Einsatz von Augmented Reality (AR)-Technologien, insbesondere der Einsatz von Smart Glasses, in der manuellen Mann-zur-Ware Kommissionierung im Fokus der Betrachtung. Dabei werden dem Mitarbeiter die zum Kommissionieren benötigten Informationen in einer Datenbrille im Sichtfeld angezeigt. In der Wissenschaft wurde ein Einsatz vor allem in Laborstudien getestet. Eine Studie über eine volle Schicht im industriellen Kontext wird als Forschungslücke angegeben. Aus diesem Grund beinhaltet die vorliegende Doktorarbeit eine Feldstudie im Vollschichtbetrieb, welche die Auswirkungen der Nutzung von Smart Glasses in der Kommissionierung auf den Mitarbeiter und den Prozess untersucht. Als ersten Schritt wird ein Prozess zur Mitarbeitereinbeziehung in Innovationsprojekten am Shop Floor basierend auf Rogers „Diffusion of Innovations“ erarbeitet. Im Anschluss wird ein für den AR-Einsatz geeigneter Arbeitsplatz mithilfe des Rasmussen-Modells menschlichen Verhaltens ausgewählt. Dazu wird ein objektives Verfahren zur Klassifizierung einzelner Aktivitäten in das Rasmussen-Modell entwickelt. Nach der Auswahl des Arbeitsplatzes, welcher die meisten durch AR-Technologien unterstützbare Prozessschritte enthält, werden Scan-Mechanismen zur Interaktion mit dem Warehouse Management System verglichen. Kern des Forschungsprojekts ist ein Vollschicht-Feldversuch mit 23 Mitarbeitern in der automobilen Montageversorgung, welcher die Auswirkungen des Einsatzes von Datenbrillen auf die Fehleranzahl, die Fehlerart, die Durchführungszeit, auf die Aufmerksamkeit, die subjektive Beanspruchung, die visuelle Ermüdung der Mitarbeiter und eine mögliche auftretende Simulatorkrankheit untersucht. Im Gegensatz zu den meisten bereits existierenden Studien erfolgt der Versuch im Realbetrieb unter Einhaltung des Produktionstakts. Dabei wird das Testsystem an das Warehouse Management System angebunden. Die Interaktion wird durch den Mitarbeiter selbst und nicht über einen Wizard-of-Oz-Ansatz durchgeführt. Die Altersspanne der Teilnehmer deckt im Versuch die gesamte Breite der Belegschaft ab. Darüber hinaus wird eine Datenbrillen-Hardware genutzt, welche die Einbeziehung von Brillenträgern ermöglicht. All die oben genannten Punkte führen zu einem Versuch unter Realbedingungen. Als Vergleichsbasis dient der jetzige Prozess, welcher die Kommissionieraufträge auf einem am Zielregal mitgeführten Monitor darstellt. Als Interaktionsmechanismus im bisherigen System dient ein Scan-Handschuh. Nach der Auswertung der Ergebnisse der Probandenstudie, welche u.a. eine Zeiteinsparung von 22% und eine Fehlerreduzierung von mindestens 33%, abhängig von der Fehlerart, nachweist, werden weitere Schritte zur Serieneinführung aufgezeigt. Darüber hinaus werden weitere Potenziale des Einsatzes von Datenbrillen in der Kommissionierung diskutiert.

Human skin contains a population of memory T cells that support tissue homeostasis and provide protective immunity. The study of human memory T cells is often restricted to in vitro studies and to human PBMC serving as primary cell source. Because the tisse environment impacts the phenotype and function of memory T cells, it is crucial to study these cells within their tissue. Here we utilized immunodeficient NOD-scid IL2rγnull (NSG) mice that carried in vivo-generated engineered human skin (ES). ES were generated from human keratinocytes and fibroblasts and is initially devoid of skin-resident immune cells. Upon adoptive transfer of human PBMC this reductionist system allowed to study human T cell recruitment from a circulating pool of T cells into non-inflamed human skin in vivo. Circulating human memory T cells preferentially infiltrated ES and showed diverse functional profiles of T cells found in fresh human skin. The chemokine and cytokine microenvironment of ES closely resembled that of non-inflamed human skin. Upon entering the ES T cells assumed a resident memory T cell-like phenotype in the absence of infection, and a proportion of these cutaneous T cells can be locally activated upon injection of monocyte derived dendritic cells (moDCs) that presented Candida albicans. Interestingly, we found that CD69+ memory T cells produced higher levels of effector cytokines in response to Candida albicans, compared to CD69- T cells. Overall, this model has broad utility in many areas of human skin immunology research, including the study of immune-mediated skin diseases.

RNA trans-splicing has become a versatile tool in the gene therapy of monogenetic diseases. This technique is especially valuable for the correction of mutations in large genes such as COL7A1, which underlie the dystrophic subtype of the skin blistering disease epidermolysis bullosa. Over 800 mutations spanning the entire length of the COL7A1 gene have been associated with defects in type VII collagen, leading to excessive fragility of epithelial tissues, the hallmark of dystrophic epidermolysis bullosa (DEB). In the present study, we designed an RNA trans-splicing molecule (RTM) that is capable of repairing any given mutation within a 4200 nucleotide region spanning the 3′ half of COL7A1. The selected RTM, RTM28, was able to induce accurate trans-splicing into endogenous COL7A1 pre-mRNA transcripts in a type VII collagen-deficient DEB patient-derived cell line. Correct trans-splicing was detected at the RNA level by semiquantitative RT-PCR and correction of full-length type VII collagen was confirmed at the protein level by immunofluorescence and western blot analyses. Our results demonstrate that RTM28, which covers >60% of all mutations reported in DEB and is thus the longest RTM described so far for the repair of COL7A1, represents a promising candidate for therapeutic applications.

A knot polymer, poly[bis(2-acryloyl)oxyethyl disulphide-co-2-(dimethylamino) ethyl methacrylate] (DSP), was synthesized, optimized and evaluated as a non-viral vector for gene transfection for skin cells, keratinocytes. With recessive dystrophic epidermolysis bullosa keratinocytes (RDEBK-TA4), the DSP exhibited high transfection efficacy with both Gaussia luciferase marker DNA and the full length COL7A1 transcript encoding the therapeutic type VII collagen protein (C7). The effective restoration of C7 in C7 null-RDEB skin cells indicates that DSP is promising for non-viral gene therapy of recessive dystrophic epidermolysis bullosa (RDEB).

We propose the idea of a powerful mobile eye tracking platform that enables whole new ways of explicit and implicit human-machine interactions in complex industrial settings. The system is based on two hardware components (NVIDIA Jetson TX2, Pupil labs eye tracker) and a message-oriented framework for real-time processing [1]. The design is described and potential use cases are sketched.

Although, gaze-based interaction has been investigated since the 1980s and provides promising concepts to realize cognitive systems and support universal interaction within distributed environments, the main challenges, such as the Midas touch problem [16] or calibration are still frequent topics of research. In this work, Natural Pursuit Calibration is presented, which is a comfortable, unobtrusive technique enabling ongoing attention detection and eye tracker calibration within an off-screen context. The user is able to perform calibration, without a digital user interface, artificial annotation of the environment nor further assistance, by simply following any arbitrary moving target. Due to the characteristics of the calibration process, it can be executed simultaneously to any primary task, without active user participation. A two-stage evaluation process is conducted to (i) optimize parameter settings in a first setup and (ii) compare the accuracy as well as the user acceptance of the proposed procedure to prevailing calibration techniques.

We have studied photodetachment of the amidogen anion

Analyzing innovation implementation processes in theory and in the industry different approaches are observable. Whilst in Rogers’ ‘Diffusion of Innovations’ the future user is the initiator of the implementation process, the situation is different for shop floor innovations. Mostly, it is a planner or an innovation scouting department, who decide to implement a new technology. The workers as future users will be involved later for the purpose of a proof-of-concept. This late time of user involvement often leads to a low acceptance rate. In order to enhance user acceptance in a shop floor context this paper proposes a user-centered approach of innovation implementation based on Roger’s model. As a first step of the industrial application, I conduct guided interviews to involve workers into the process of my innovation use-case on smart glasses in order picking processes.

A novel polymer monolith based on the dicationic crosslinker 3,3′-(hexane-1,6-diyl)bis(1-vinylimidazolium) bromide, the monomer 1-vinylimidazole and a ternary porogen mixture (1-propanol, decan-1-ol and water) was developed and optimized for capillary electrochromatography. This aim was accomplished by adjusting the composition of individual constituents in the polymerization mixture and monitored based on several relevant parameters (e.g. pore structure by scanning electron microscopy, generation of electroosmotic flow, or permeability of material). The ultimately selected composition yielded a monolithic phase which excellently resolved six methylxanthines (including caffeine, theobromine and theophylline) in 15 min. Key requirements concerning the utilized buffer were an acidic pH of 3 and the addition of 50% acetonitrile; additionally, a negative voltage (−25 kV) had to be applied during analyses. The proposed separation mechanism was mixed mode, i.e. the combination of electrostatic repulsion and hydrophobic interaction. Monolith fabrication as well as separation efficiency were found to be highly repeatable, the material was mechanically stable and useable for at least 150 injections. Thus the presented stationary phase is definitely a very promising option for CEC.

Augmented Reality (AR)-technologies are an important part in the change towards digital manufacturing. Fields of application are assembly, order picking and maintenance. For a full-shift study evaluating smart glasses in order picking processes, we selected the most suitable workplace in logistics area using Rasmussen’s Skills-Rules-Knowledge framework. Since the classification into Rasmussen’s three levels of human behavior has been quite subjective so far, we propose a more objective approach based on a pairwise comparison and a cost-utility analysis. Developing this method, we define numeric boundaries between the three levels of Rasmussen’s framework. After the evaluation by ten experts, we selected the best workstation for our future full-shift study at BMW Plant Munich.

Recently, there has been increased interest in eye tracking and eye-based human-computer interaction research, as gaze reveals attention and intention information, making it highly interesting as an input modality for cognitive assistant systems. In this paper, we present how to apply gaze-awareness in an industrial environment to create such a cognitive assistant system. A prototypical system was built upon a mobile eye tracker, that analyses the user's field of view, to recognize possible objects of interest, while simultaneously checking for gaze fixations. A twenty-one participants user study was carried out, which builds upon established hypothesis of a correlation between eye fixations and the relevance of objects and additionally shows that this relationship changes over multiple tasks and runs, revealing learning improvements and task difficulty. Both features are vital for a reduction of amount of the support an assistance system provides towards its users, resulting in an overall better user experience.

Order picking is a difficult and cognitively demanding task. Traditionally textual instructions are helping new workers to learn different picking routines. However, the textual instructions are sometimes not written in the workers ' native languages. In the area of Industry 4.0, where digital functions are finding their way into manufacturing processes, language-independent instructions are possible. Through a user study with 15 participants, we compare textual feedback in the workers' native language, textual feedback that is written in an unknown foreign language, and visual Augmented Reality (AR) feedback. We found that AR feedback is significantly faster and leads to a lower perceived cognitive load.

In recent years, RNA trans-splicing has emerged as a suitable RNA editing tool for the specific replacement of mutated gene regions at the pre-mRNA level. Although the technology has been successfully applied for the restoration of protein function in various genetic diseases, a higher trans-splicing efficiency is still desired to facilitate its clinical application. Here, we describe a modified, easily applicable, fluorescence-based screening system for the generation and analysis of antisense molecules specifically capable of improving the RNA reprogramming efficiency of a selected KRT14-specific RNA trans-splicing molecule. Using this screening procedure, we identified several antisense RNAs and short rationally designed oligonucleotides, which are able to increase the trans-splicing efficiency. Thus, we assume that besides the RNA trans-splicing molecule, short antisense molecules can act as splicing modulators, thereby increasing the trans-splicing efficiency to a level that may be sufficient to overcome the effects of certain genetic predispositions, particularly those associated with dominantly inherited diseases.

eingereicht von Johannes Murauer Universität Linz, Diplomarbeit, 2018

This paper summarizes our contribution to the CrowdAI music genre classification challenge "Learning to Recognise Musical Genre from Audio on the Web'' as part of the WebConference 2018. We utilize different approaches from the field of music analysis to predict the music genre of given mp3 music files, including a convolutional neural network for spectrogram classification, deep neural networks and ensemble methods using various numerical audio features. Our best results were obtained by an extreme gradient boosting classifier.