Variant flexibility in assembly line balancing under the premise of feasibility robustness

The final assembly of vehicles is frequently designed as a mixed model line which produces effectively at a fixed ratio of variants. Market forecasts indicate a volatile future demand for different types of vehicles such as electrified vehicles. The resulting uncertainty of demand affects the task of line balancing assembly lines. This paper presents a new planning method to provide decision support for line balancing with inherent variant flexibility while maintaining feasibility robustness. Therefore a combined approach of scenario analyses and line balancing optimization is developed. This approach is applied to a use case in automotive industry

Towards planning and control in cognitive factories - A generic model including learning effects and knowledge transfer across system entities

Cognitive abilities allow robots to learn and reason from their environment. The gained knowledge can then be incorporated into the robot’s actions which in turn affect the environment. Therefore, a cognitive robot is no longer a static system that performs actions based on a pre-defined set of rules but a complex entity that dynamically adjusts over time. With this, challenges arise for production systems that need to observe and ideally anticipate the cognitive robot’s behavior. Often, digital twins are employed to test and optimize production control systems. This paper presents a generic approach to characterize, model and simulate learning processes and formalized knowledge in hybrid production systems assuming different station types with learning effects. Thereby, quantitative and qualitative learning processes are mapped including knowledge sharing and transfer across entities. A modular and parameterizable design enables the adjustment to different use cases. Eventually, the model is instantiated as a digital twin of a real production system for product disassembly employing cognitive-autonomous robots among human operators and rigidly automated machines. The model shows great potential to be integrated into test beds for planning and control systems of cognitive factories

Improvement in children’s fine motor skills following a computerized typing intervention

Children spend a large proportion of their school day engaged in tasks that require manual dexterity. If children experience difficulties with their manual dexterity skills it can have a consequential effect on their academic achievement. The first aim of this paper was to explore whether an online interactive typing intervention could improve children’s scores on a standardised measure of manual dexterity. The second aim was to implement a serial reaction time tapping task as an index of children's finger movement learning, and to see whether performance on this task would improve after the intervention. Seventy-eight typically developing children aged between 8 and 10 were tested at their school on the pre-intervention Movement Assessment Battery for Children (2 nd edition; MABC-2) and tapping tasks. Twenty-eight of these children volunteered to be randomly allocated to the intervention or control group. Children in the intervention group had a choice of two online games to play at home over a period of four weeks, while the children in the control group were not given these games to play. The intervention and control groups were then re-tested on the MABC-2 manual dexterity and the tapping task. Children in the intervention group significantly improved their manual dexterity scores in the MABC-2 compared to the control group. On average, all children learnt the tapping sequence, however, there were no group differences and no effect of the intervention on the tapping task. These results have important implications for implementing a freely available, easy to administer, fun and interactive intervention to help children improve their manual dexterity skills

A novel CHCHD10 mutation implicates a Mia40-dependent mitochondrial import deficit in ALS

CHCHD10 mutations are linked to amyotrophic lateral sclerosis, but their mode of action is unclear. In a 29-year-old patient with rapid disease progression, we discovered a novel mutation (Q108P) in a conserved residue within the coiled-coil-helix-coiled-coil-helix (CHCH) domain. The aggressive clinical phenotype prompted us to probe its pathogenicity. Unlike the wild-type protein, mitochondrial import of CHCHD10 Q108P was blocked nearly completely resulting in diffuse cytoplasmic localization and reduced stability. Other CHCHD10 variants reported in patients showed impaired mitochondrial import (C122R) or clustering within mitochondria (especially G66V and E127K) often associated with reduced expression. Truncation experiments suggest mitochondrial import of CHCHD10 is mediated by the CHCH domain rather than the proposed N-terminal mitochondrial targeting signal. Knockdown of Mia40, which introduces disulfide bonds into CHCH domain proteins, blocked mitochondrial import of CHCHD10. Overexpression of Mia40 rescued mitochondrial import of CHCHD10 Q108P by enhancing disulfide-bond formation. Since reduction in CHCHD10 inhibits respiration, mutations in its CHCH domain may cause aggressive disease by impairing mitochondrial import. Our data suggest Mia40 upregulation as a potential therapeutic salvage pathway

Control of Flowering and Cell Fate by LIF2, an RNA Binding Partner of the Polycomb Complex Component LHP1

Polycomb Repressive Complexes (PRC) modulate the epigenetic status of key cell fate and developmental regulators in eukaryotes. The chromo domain protein LIKE HETEROCHROMATIN PROTEIN1 (LHP1) is a subunit of a plant PRC1-like complex in Arabidopsis thaliana and recognizes histone H3 lysine 27 trimethylation, a silencing epigenetic mark deposited by the PRC2 complex. We have identified and studied an LHP1-Interacting Factor2 (LIF2). LIF2 protein has RNA recognition motifs and belongs to the large hnRNP protein family, which is involved in RNA processing. LIF2 interacts in vivo, in the cell nucleus, with the LHP1 chromo shadow domain. Expression of LIF2 was detected predominantly in vascular and meristematic tissues. Loss-of-function of LIF2 modifies flowering time, floral developmental homeostasis and gynoecium growth determination. lif2 ovaries have indeterminate growth and produce ectopic inflorescences with severely affected flowers showing proliferation of ectopic stigmatic papillae and ovules in short-day conditions. To look at how LIF2 acts relative to LHP1, we conducted transcriptome analyses in lif2 and lhp1 and identified a common set of deregulated genes, which showed significant enrichment in stress-response genes. By comparing expression of LHP1 targets in lif2, lhp1 and lif2 lhp1 mutants we showed that LIF2 can either antagonize or act with LHP1. Interestingly, repression of the FLC floral transcriptional regulator in lif2 mutant is accompanied by an increase in H3K27 trimethylation at the locus, without any change in LHP1 binding, suggesting that LHP1 is targeted independently from LIF2 and that LHP1 binding does not strictly correlate with gene expression. LIF2, involved in cell identity and cell fate decision, may modulate the activity of LHP1 at specific loci, during specific developmental windows or in response to environmental cues that control cell fate determination. These results highlight a novel link between plant RNA processing and Polycomb regulation

Dating Violence Among Sexual & Gender Diverse Youth: A Systematic Scoping Review

The purpose of this project is to develop a synthesis of the current research evidence on adolescent dating violence prevalence, risk and protective factors, physical, mental and social impacts, and evidence-based prevention programming for sexual and gender diverse youth

SARS‐CoV‐2 outbreak investigation in a German meat processing plant

Abstract We describe a multifactorial investigation of a SARS‐CoV‐2 outbreak in a large meat processing complex in Germany. Infection event timing, spatial, climate and ventilation conditions in the processing plant, sharing of living quarters and transport, and viral genome sequences were analyzed. Our results suggest that a single index case transmitted SARS‐CoV‐2 to co‐workers over distances of more than 8 m, within a confined work area in which air is constantly recirculated and cooled. Viral genome sequencing shows that all cases share a set of mutations representing a novel sub‐branch in the SARS‐CoV‐2 C20 clade. We identified the same set of mutations in samples collected in the time period between this initial infection cluster and a subsequent outbreak within the same factory, with the largest number of confirmed SARS‐CoV‐2 cases in a German meat processing facility reported so far. Our results indicate climate conditions, fresh air exchange rates, and airflow as factors that can promote efficient spread of SARS‐CoV‐2 via long distances and provide insights into possible requirements for pandemic mitigation strategies in industrial workplace settings

Dicer in Macrophages Prevents Atherosclerosis by Promoting Mitochondrial Oxidative Metabolism

Background: Alternative macrophage activation, which relies on mitochondrial oxidative metabolism, plays a central role in the resolution of inflammation and prevents atherosclerosis. Moreover, macrophages handle large amounts of cholesterol and triglycerides derived from the engulfed modified lipoproteins during atherosclerosis. Although several microRNAs regulate macrophage polarization, the role of the microRNA-generating enzyme Dicer in macrophage activation during atherosclerosis is unknown. Methods: To evaluate the role of Dicer in atherosclerosis, Apoe(-/-) mice with or without macrophage-specific Dicer deletion were fed a high-fat diet for 12 weeks. Anti-argonaute 2 RNA immunoprecipitation chip and RNA deep sequencing combined with microRNA functional screening were performed in the Dicer wild-type and knockout bone marrow-derived macrophages to identify the individual microRNAs and the mRNA targets mediating the phenotypic effects of Dicer. The role of the identified individual microRNA and its target in atherosclerosis was determined by tail vein injection of the target site blockers in atherosclerotic Apoe(-/-) mice. Results: We show that Dicer deletion in macrophages accelerated atherosclerosis in mice, along with enhanced inflammatory response and increased lipid accumulation in lesional macrophages. In vitro, alternative activation was limited whereas lipid-filled foam cell formation was exacerbated in Dicer-deficient macrophages as a result of impaired mitochondrial fatty acid oxidative metabolism. Rescue of microRNA (miR)-10a, let-7b, and miR-195a expression restored the oxidative metabolism in alternatively activated Dicer-deficient macrophages. Suppression of ligand-dependent nuclear receptor corepressor by miR-10a promoted fatty acid oxidation, which mediated the lipolytic and anti-inflammatory effect of Dicer. miR-10a expression was negatively correlated to the progression of atherosclerosis in humans. Blocking the interaction between ligand-dependent nuclear receptor corepressor and miR-10a by target site blockers aggravated atherosclerosis development in mice. Conclusions: Dicer plays an atheroprotective role by coordinately regulating the inflammatory response and lipid metabolism in macrophages through enhancing fatty acid-fueled mitochondrial respiration, suggesting that promoting Dicer/miR-10a-dependent metabolic reprogramming in macrophages has potential therapeutic implications to prevent atherosclerosis