MicroRNAs as Clinical Biomarkers and Therapeutic Tools in Perioperative Medicine

Over the past decade, evolutionarily conserved, noncoding small RNAs-so-called microRNAs (miRNAs)-have emerged as important regulators of virtually all cellular processes. miRNAs influence gene expression by binding to the 3'-untranslated region of protein-coding RNA, leading to its degradation and translational repression. In medicine, miRNAs have been revealed as novel, highly promising biomarkers and as attractive tools and targets for novel therapeutic approaches. miRNAs are currently entering the field of perioperative medicine, and they may open up new perspectives in anesthesia, critical care, and pain medicine. In this review, we provide an overview of the biology of miRNAs and their potential role in human disease. We highlight current paradigms of miRNA-mediated effects in perioperative medicine and provide a survey of miRNA biomarkers in the field known so far. Finally, we provide a perspective on miRNA-based therapeutic opportunities and perspectives. (Anesth Analg 2018;126: 670-81

Solving the nuclear dismantling project scheduling problem by combining mixed-integer and constraint programming techniques and metaheuristics

Scheduling of megaprojects is very challenging because of typical characteristics, such as expected long project durations, many activities with multiple modes, scarce resources, and investment decisions. Furthermore, each megaproject has additional specific characteristics to be considered. Since the number of nuclear dismantling projects is expected to increase considerably worldwide in the coming decades, we use this type of megaproject as an application case in this paper. Therefore, we consider the specific characteristics of constrained renewable and non-renewable resources, multiple modes, precedence relations with and without no-wait condition, and a cost minimisation objective. To reliably plan at minimum costs considering all relevant characteristics, scheduling methods can be applied. But the extensive literature review conducted did not reveal a scheduling method considering the special characteristics of nuclear dismantling projects. Consequently, we introduce a novel scheduling problem referred to as the nuclear dismantling project scheduling problem. Furthermore, we developed and implemented an effective metaheuristic to obtain feasible schedules for projects with about 300 activities. We tested our approach with real-life data of three different nuclear dismantling projects in Germany. On average, it took less than a second to find an initial feasible solution for our samples. This solution could be further improved using metaheuristic procedures and exact optimisation techniques such as mixed-integer programming and constraint programming. The computational study shows that utilising exact optimisation techniques is beneficial compared to standard metaheuristics. The main result is the development of an initial solution finding procedure and an adaptive large neighbourhood search with iterative destroy and recreate operations that is competitive with state-of-the-art methods of related problems. The described problem and findings can be transferred to other megaprojects

Knockdown of INPP5K compromises the differentiation of N2A cells

Inositol polyphosphate 5-phosphatase K (INPP5K), also known as SKIP (skeletal muscle and kidney-enriched inositol phosphatase), is a cytoplasmic enzyme with 5-phosphatase activity toward phosphoinositides (PIs). Mutations in INPP5K are associated with autosomal recessive congenital muscular dystrophy with cataracts and intellectual disability (MDCCAID). Notably, muscular dystrophy is characterized by the hypoglycosylation of dystroglycan. Thus, far, the underlying mechanisms are only partially understood. In this study, we show that INPP5K expression increases during brain development. Knockdown of INPP5K in the neuroblastoma-derived cell line N2A impaired their neuronal-like differentiation and interfered with protein glycosylation

NKCC1, an Elusive Molecular Target in Brain Development: Making Sense of the Existing Data

Ionotropic GABA transmission is mediated by anion (mainly Cl−)-permeable GABAA receptors (GABAARs). In immature neurons, GABA exerts depolarizing and sometimes functionally excitatory actions, based on active uptake of Cl− by the Na-K-2Cl cotransporter NKCC1. While functional evidence firmly shows NKCC1-mediated ion transport in immature and diseased neurons, molecular detection of NKCC1 in the brain has turned out to be extremely difficult. In this review, we describe the highly inconsistent data that are available on the cell type-specific expression patterns of the NKCC1 mRNA and protein in the CNS. We discuss the major technical caveats, including a lack of knock-out-controlled immunohistochemistry in the forebrain, possible effects of alternative splicing on the binding of antibodies and RNA probes, and the wide expression of NKCC1 in different cell types, which make whole-tissue analyses of NKCC1 useless for studying its neuronal expression. We also review novel single-cell RNAseq data showing that most of the NKCC1 in the adult CNS may, in fact, be expressed in non-neuronal cells, especially in glia. As future directions, we suggest single-cell NKCC1 mRNA and protein analyses and the use of genetically tagged endogenous proteins or systematically designed novel antibodies, together with proper knock-out controls, for the visualization of endogenous NKCC1 in distinct brain cell types and their subcellular compartments

Towards a Flexible Approach to Transfer Machine Operation Know-How from Experts to Beginners with AI

Training new users at a production machine is a time intensive and expensive task. To reduce the effort in this task we examine the possibilities of enhancing a production machine with a system that is able to learn from its users and teach inexperienced users this knowledge: Self-Learning and Self-Explanatory Machine SLEM. The learning process of SLEM relies on watching an experienced user working on a machine using camera-based human activity recognition which predicts the acitivities based on the estimated human skeleton in the video stream. SLEM must be able to work with little data to reduce the learning time as much as possible. Thus, this paper shows that training an activity recognition model solely on one experienced individual’s actions can lead to comparatively high activity recognition accuracy despite the low data variety. The results show that training on a single-person dataset can reach relatively high accuracy levels and is a suitable way of training the model in the industrial setting. For the teaching process, in which the system has to compare the actual activities with the target acitivities to give feedback, the activity recognition has to run in real-time. Different amounts of input data for the activity recognition model are examined and lead to a configuration with little accuracy loss and sufficient latency performance

Automated Stamp Forming of Continuous Fiber Reinforced Thermoplastics for Complex Shell Geometries

This research describes the development of a fully automated forming process of continuous FRP to assemble a down scaled battery tray for a plug-in-hybrid automobile. The paper presents the results of forming experiments and a restraint approach to avoid wrinkling, an FEM forming simulation to detect the wrinkling behavior, shear effects and temperature trajectories for the consolidation at the end of the forming step, and a multi material gripper-system used for handling and preforming. The gripper system is capable of handling continuous FRP in different states and features a pneumatic stamp to pre-drape the heated organic sheet.BMBF/Open Hybrid LabFactor

Wo steht die Jugendforschung heute?

Der Text leistet eine Ortsbestimmung der deutschen Jugendforschung, die im Rahmen des 18. DJI-Symposiums 2003 in Berlin mit dem Programmthema 'Jugendforschung zwischen Tradition und Innovation. Bilanz und Ausblick nach vier Jahrzehnten' diskutiert wird. Dazu werden in einem ersten Abschnitt die Grundzüge der Podiumsdiskussion 'Wo steht die Jugendforschung heute' dargelegt. Sie umfassen die folgenden Thesen der Debatte: (1) Gemeinsame inhaltliche Bezugspunkte sind in der Jugendforschung kaum auszumachen, zu breit und heterogen sind die Fragestellungen, methodologischen Zugänge, die Analyseebenen und Datensätze sowie das bunte Spektrum der Ergebnisse. (2) Es ist eine gegenseitige Abschottung von Jugendforschung und Schul- bzw. Schülerinnen- und Schülerforschung zu beobachten, als ob es sich um zwei Welten handeln würde, während doch zugleich immer wieder die Akteursperspektive als zentraler Ausgangspunkt der Forschung postuliert wird. (3) Die Jugendforschung unterliegt einer fortschreitenden Versozialwissenschaftlichung. Daran knüpft im zweiten Teil eine kritische Nachlese der Podiumsdiskussion 'Jugendforschung ohne Biss, oder: die Zukunft ist europäisch (oder gar nicht)'. Beide Abschnitte bringen persönliche Meinungen und Wertungen zum Ausdruck und nicht etwa institutionelle 'Verlautbarungen des DJI'. So spiegeln sie auch den Zustand der deutschen Jugendforschung, die - trotz oder gerade wegen ihrer Medienwirksamkeit und Fülle - keinen klar definierbaren wissenschaftlichen Korpus mehr darstellt und ihren Gegenstand, die Jugend, derzeit nicht mehr eindeutig zu bestimmen vermag. (ICG2

Throughput Analysis for Layout Optimisation of Modular Conveyor Systems

In this paper, objective functions for the optimisation of modular conveyor systems will be introduced. Modular conveyor systems consist of conventional as well as modular conveyor hardware, which are arranged in form of matrix-like layouts. The aim of an ongoing research project is to provide small and medium-sized enterprises with a user-friendly decision support for the selection and planning of modular conveyor systems. For this purpose, the conveyor systems should be evaluated according to the objectives throughput and space requirement. Therefore, mathematical equations have been developed, which enable a fast and precise evaluation of layouts. The paper focuses mainly on the efficient calculation of the throughput. The result quality of the evaluation equations regarding the throughput was proven by a simulation of example systems