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ZusammenfassungDie Digitalisierung bietet Unternehmen umfassende Möglichkeiten, sich weiterzuentwickeln und ihre Wettbewerbsfähigkeit zu steigern. Unter anderem erlaubt sie die Verknüpfung physischer Produkte mit datenbasierten Zusatzleistungen als hybride Wertschöpfung. Für deren erfolgreiche Umsetzung sind entsprechende Geschäftsmodelle und eine passende Arbeitsgestaltung erforderlich. Vor diesem Hintergrund werden grundlegende Begriffe erläutert, das Forschungsprojekt AnGeWaNt beschrieben und die Struktur des vorliegenden Buchs dargestellt: Von der Entwicklung hybrider Geschäftsmodelle über Änderungsbedarfe an Organisationsstrukturen, Zusammenarbeitsformen und Kompetenzprofilen bis hin zur digitalen Unterstützung hoheitlicher Prozesse.

SRPRA and SRP19 are novel genes affected in congenital neutropenia and essential for granule protein processing.Comparative proteomics in neutrophil granulocytesThe mechanisms of coordinated changes in proteome composition and their relevance for the differentiation of neutrophil granulocytes are not well studied. Here, we discover two novel human genetic defects in SRPRA and SRP19, constituents of the mammalian co-translational targeting machinery and characterize their role in neutrophil granulocyte differentiation. We systematically study the proteome of neutrophil granulocytes from patients with variants in the signal recognition particle (SRP) genes, HAX1, and ELANE and identify global as well as specific proteome aberrations. Using in vitro differentiation of human induced pluripotent stem cells and in vivo zebrafish models, we study the effects of SRP-deficiency on neutrophil granulocyte development. In a heterologous cell-based inducible protein expression system, we validate the effects conferred by SRP dysfunction for selected proteins that we identified in our proteome screen. Thus, SRP-dependent protein processing, intracellular trafficking and homeostasis are critically important for the differentiation of neutrophil granulocytes.

Die Digitalisierung und damit die Vernetzung von Maschinen und Daten in Echtzeit ermöglichen Unternehmen, mit sogenannten Smarten Services zusätzliche Wertschöpfung zu erzielen. Im Zuge der Hybridisierung ergeben sich vielfach Veränderungen in den Unternehmen. Die Veränderung von Arbeitsaufgaben bedingt, dass neue Kompetenzbedarfe entstehen. Der Beitrag beleuchtet die wesentlichen Veränderungen und Kompetenzbedarfe im Vertriebsbereich von Anwenderunternehmen aus einem praxisnahen Forschungsprojekt.

Aminoacyl-tRNA synthetases (ARSs) catalyze the first step of protein biosynthesis (canonical function) and have additional (non-canonical) functions outside of translation. Bi-allelic pathogenic variants in genes encoding ARSs are associated with various recessive mitochondrial and multisystem disorders. We describe here a multisystem clinical phenotype based on bi-allelic mutations in the two genes (FARSA, FARSB) encoding distinct subunits for tetrameric cytosolic phenylalanyl-tRNA synthetase (FARS1). Interstitial lung disease with cholesterol pneumonitis on histology emerged as an early characteristic feature and significantly determined disease burden. Additional clinical characteristics of the patients included neurological findings, liver dysfunction, and connective tissue, muscular and vascular abnormalities. Structural modeling of newly identified missense mutations in the alpha subunit of FARS1, FARSA, showed exclusive mapping to the enzyme's conserved catalytic domain. Patient-derived mutant cells displayed compromised aminoacylation activity in two cases, while remaining unaffected in another. Collectively, these findings expand current knowledge about the human ARS disease spectrum and support a loss of canonical and non-canonical function in FARS1-associated recessive disease.

Digitalization is a process that started already years ago and shows increasing dynamics. Since latest the year 2011 – when the vision of Industry 4.0 was presented – digitalization dynamics increase also in production industry. Simultaneously, manifold and partially far reaching expectations on the digitalization’s impact on productivity and its management as well as on employees and work design came up. To gain information on the current state of digitalization as well as the related experiences and expectations three studies have been conducted by ifaa in the years 2015, 2017 and 2019 in the German metal and electrical industry. Now integrated analyses of these studies and especially of some replicated questions have been conducted to recognize development tendencies and gain further knowledge on the digitalization’s development. In this way, several development tendencies were found, and assumptions were derived for explaining them. These include expectations on productivity gain, importance of digitalization for selected fields of application, the use of lean methods and holistic approaches as well as the impact on employees, their number, and their flexibility.

We describe a cohort of 25 Iranian patients with infantile inflammatory bowel disease (IBD), 14 (56%) of whom had monogenic defects. After proper screening, patients were referred for whole exome sequencing (WES). Four patients had missense mutations in the

Kurzfassung Digitale Technologien und selbstlernende Software (inkl. Künstliche Intelligenz, KI) verändern die Art und Weise, wie wir in Zukunft arbeiten werden. Dies stellt viele Betriebe vor die Herausforderung, neuartige Lösungen und Maßnahmen für eine produktive, sichere und gesundheitsgerechte Arbeitsgestaltung mit KI zu generieren und umzusetzen. In diesem Beitrag werden erste Beispiele sowie zwei konkrete Instrumente zur Nutzung von KI für eine produktive und präventive Arbeitsgestaltung vorgestellt.

Since latest the presentation of the concept of Industry 4.0 digitalization is increasingly implemented in industry and especially in production industry. Along with this development the availability and handling of data in production enterprises have been improved and are still objective of further improvements. Additionally, data are the basis for implementing artificial intelligence and using its potentials for many purposes. One of these can be supporting employees completing their tasks. Both, digitalization, and artificial intelligence lead to changes in work design, work processes and organizational structures. Thus, they also have an impact on occupational safety and health and require identifying and assessing the consequences for the physical and mental health of employees. The risk assessment is an essential part of occupational safety and health. It has to be performed for instance in case that new machines or devices will be procured. Further questions in this context concern possibly arising fears of employees, having little experience with new technologies, or the fit of existing and required skills for new technologies. Structured by informational and energetic types of work as well as the design areas technology, organization, and personnel the opportunities of digitalization and artificial intelligence are described within this contribution. Equally, the impact on occupational safety and health is discussed. Finally, the implementation of digitalization and artificial intelligence is outlined and an outlook on future standardization activities is given.

The Human Phenotype Ontology (HPO, https://hpo.jax.org) was launched in 2008 to provide a comprehensive logical standard to describe and computationally analyze phenotypic abnormalities found in human disease. The HPO is now a worldwide standard for phenotype exchange. The HPO has grown steadily since its inception due to considerable contributions from clinical experts and researchers from a diverse range of disciplines. Here, we present recent major extensions of the HPO for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas. For example, the seizure subontology now reflects the International League Against Epilepsy (ILAE) guidelines and these enhancements have already shown clinical validity. We present new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease. These efforts will benefit software such as Exomiser by improving the accuracy and scope of cross-species phenotype matching. The computational modeling strategy used by the HPO to define disease entities and phenotypic features and distinguish between them is explained in detail.We also report on recent efforts to translate the HPO into indigenous languages. Finally, we summarize recent advances in the use of HPO in electronic health record systems.

Arbeit in der digitalisierten Welt : Praxisbeispiele und Gestaltungslösungen aus dem BMBF-Förderschwerpunkt / Wilhelm Bauer, Susanne Mütze-Niewöhner, Sascha Stowasser, Claus Zanker, Nadine Müller (Hrsg.); Berlin : Springer Vieweg 1-15 (2021). doi:10.1007/978-3-662-62215-5_1, Published by Springer Vieweg, Berlin

ZusammenfassungDigitalisierung, Industrie 4.0 und künstliche Intelligenz (KI) bieten Unternehmen neue Chancen, um Produkte, Dienstleistungen und Leistungserstellungsprozesse zu gestalten und ihre Produktivität und damit Wettbewerbsfähigkeit zu verbessern. Gleichzeitig führen die damit verbundenen Veränderungen in der Arbeitswelt aber auch zu veränderten Rahmenbedingungen, Strukturen und Anforderungen. Um diesen Veränderungen gerecht zu werden, müssen bisherige Ansätze des Produktivitätsmanagements an die neuen Bedingungen angepasst werden. Nur so kann ein produktivitätssteigernder und damit erfolgreicher Einsatz neuer Technologien und digitaler Wandel hin zur vernetzten Produktion in einer Industrie 4.0 sichergestellt werden. Dieser Beitrag beschreibt die neuen Anforderungen an das Produktivitätsmanagement und gibt eine Handlungsempfehlung, wie dies in digitalisierten und vernetzten Arbeitswelten der Zukunft erfolgreich gestaltet und praktisch umgesetzt werden kann.

ZusammenfassungDie Digitalisierung und ihre Potenziale für die Arbeitsgestaltung werden in diesem einleitenden Überblicksbeitrag kurz umrissen. Vor diesem Hintergrund werden der Förderschwerpunkt „Arbeit in der digitalisierten Welt“ und seine Begleitung durch das Projekt TransWork beschrieben. Die damit verbundene Strukturierung der insgesamt 29 begleiteten Projekte in Schwerpunktgruppen wird erläutert und die Schwerpunktgruppe „Produktivitätsmanagement“ näher dargestellt. Schließlich werden das vorliegende Werk und der handlungsleitende Aufbau der Beiträge aus der Schwerpunktgruppe beschrieben: vom praktischen Anwendungsbeispiel über ein schrittweises Vorgehen bis hin zu zentralen Ergebnissen und Lessons Learned.

Digitalization changes the handling of data and information by offering new and extended opportunities for collecting, transferring, evaluating and exploiting information. This allows increases in effectiveness and efficiency and also opens new opportunities for productivity management. To analyze how these opportunities are used in the German industry and which potential for further development is estimated, the Institute of Applied Industrial Engineering and Ergonomics conducted an online survey querying specialists and managers in the year 2019. Partial results for the German metal and electrical industry are described and discussed in this contribution. They prove the increasing use of digitalization and the related expectations within this significant industrial branch.

Human-Robot Collaboration (HRC) is associated with the digital transformation of industrial processes. This paper provides an overview of potential fields of HRC implementation followed by a six-step procedure for analyzing potential workplaces for HRC suitability. Finally, an industry-based case study is presented, in which this procedure was applied and a productivity increase as well as a reduction of physical strain on the workers was achieved. It is shown that a structured integration of HRC into existing workplaces is worthwhile to gain the best results both for workers as well as the operating corporation.

Against the background of demographic change, stress-optimized deployment scheduling can help to achieve the ability of employees to work in assembly areas over an extended working lifetime. However, realizing an optimal assignment of personnel from an ergonomic point of view often requires qualifying employees to process new tasks. When employees are for the first time confronted with unfamiliar sensorimotor tasks they have to learn task-specific skills. This includes being provided with an introduction to the new task as well as subsequent practice until achieving a reference performance. For introduction purposes a variety of work instructions can be used; each of them is assumed to have a different effect on learning. To assess this influence quantitatively, a laboratory study was conducted. The study focused on the repeated assembly of a carburetor which was executed by participants which received either a previous interactive filmbased instruction as well as a graphical task description or received only the graphical task description. The results show the instruction’s influence on execution times as well as on assembly errors to be significant.

Digitalization, artificial intelligence (AI) and in particular increased availability of data enables companies to develop new or changed business models and generate additional revenues. In order to use these potentials successfully, the implementation of hybrid business models and new technologies often also requires a change in the existing management and corporate culture. Nevertheless, many companies neglect to accompany technological changes by developing the skills of managers and employees. Therefore, the Institute of Applied Industrial Engineering and Ergonomics conducted a Germany-wide online survey of specialists and executives (n = 178) to analyze the status quo and the requirements for personal development and leadership of companies from the German metal and electrical industry [1, 2].

Die Digitalisierung wird im industriellen Umfeld immer mehr genutzt, um Prozesse weiterzuentwickeln und die Produktivitat zu steigern. In der Folge ist eine steigende Zahl an Praxisbeispielen verfugbar. Um die hohe Zahl an Beispielen zu strukturieren und einer Analyse zuganglich zu machen, wurde ein Ordnungs- und Gestaltungsrahmen entwickelt, in dem die Beispiele jeweils nach dem angestrebten Produktivitatsziel, der Stufe im Datenhandhabungsprozess und der Arbeitsform gegliedert werden. Durch Einordnung von 122 Praxisbeispielen zeigen sich Schwerpunkte im Bereich quantitativer Veranderungen von Input und Output sowie bei informatorisch gepragten Arbeitsformen. Diese Schwerpunkte werden entlang des Datenhandhabungsprozess analysiert und die dabei abgedeckten Einsatz- bzw. Anwendungsspektren aufgezeigt. Zudem werden schwach besetzte Bereiche des Ordnungs- und Gestaltungsrahmens aufgezeigt und diskutiert. Praktische Relevanz: Vor dem Hintergrund der vielfaltigen Moglichkeiten zur Nutzung der Digitalisierung im industriellen Umfeld ist es gerade fur kleine und mittlere Unternehmen erforderlich, Orientierung zu erhalten. Im Beitrag wird ein Ordnungs- und Gestaltungsrahmen vorgestellt, der diesen Bedarf adressiert. Darin lassen sich bestehende Praxisbeispiele nach ihrer Produktivitatswirkung einordnen bzw. gezielt auswahlen. Zudem wird durch die Einordnung einer Vielzahl an Beispielen in den Ordnungs- und Gestaltungsrahmen deutlich, in welchen Bereichen die Digitalisierung derzeit stark bzw. schwach genutzt wird.

Kurzfassung Die Digitalisierung bietet Möglichkeiten, die Gestaltung von Informationsflüssen zu verbessern. Für produzierende Unternehmen ergeben sich daraus Chancen zur betriebsspezifischen Optimierung ihrer Prozesse und zur Verbesserung ihrer Produktivität. Im Beitrag werden Auszüge der Ergebnisse einer Befragungsstudie unter Fach- und Führungskräften aus der deutschen Metall- und Elektroindustrie zu deren Produktivitätsmanagement dargestellt, in der besonders auf die Chancen der Digitalisierung Bezug genommen wird.

Summary Despite their fundamental role in various biological processes, the analysis of small RNA sequencing data remains a challenging task. Major obstacles arise when short RNA sequences map to multiple locations in the genome, align to regions that are not annotated or underwent post-transcriptional changes which hamper accurate mapping. In order to tackle these issues, we present a novel profiling strategy that circumvents the need for read mapping to a reference genome by utilizing the actual read sequences to determine expression intensities. After differential expression analysis of individual sequence counts, significant sequences are annotated against user defined feature databases and clustered by sequence similarity. This strategy enables a more comprehensive and concise representation of small RNA populations without any data loss or data distortion. Availability and implementation Code and documentation of our R package at http://ibis.helmholtz-muenchen.de/deus/. Supplementary information Supplementary data are available at Bioinformatics online.

Industrie 4.0 und die damit verbundenen Potenziale fur die Produktion wurden vor rund funf Jahren der Offentlichkeit vorgestellt. Seitdem ist das Thema in den Medien zunehmend prasent und u. a. Gegenstand zahlreicher abgeschlossener sowie andauernder und geplanter Forschungsvorhaben. Uber die Bekanntheit des Begriffs, seines Inhalts und seine Bedeutung in der Breite der von kleinen und mittleren Unternehmen gepragten deutschen Industrie ist dagegen wenig bekannt. Vor diesem Hintergrund wurde eine Online-Befragung in der Metall- und Elektroindustrie durchgefuhrt, an der nahezu 500 Unternehmen beteiligt waren. Es zeigte sich, dass der Begriff zwar in rund 90 % der Unternehmen bekannt ist, jedoch lediglich bei etwa 30 % ein klares Verstandnis uber dessen Inhalt besteht. Dabei werden mehrheitlich Begriffe wie Vernetzung, Produktion und Digitalisierung genannt. Daruber hinaus wurden u. a. die derzeitigen Aktivitaten der Unternehmen (Umsetzungsgrad) sowie die mit Industrie 4.0 verbundenen Erwartungen erfragt. Im Beitrag werden die Befragungsergebnisse ausfuhrlich beschrieben und veranschaulicht. Zudem erlauben einzelne Bezuge zu einer vorangegangenen Befragung eine Einordnung der zeitlichen Entwicklung verschiedener Aspekte im Sinne einer Langsschnittbetrachtung. Praktische Relevanz Die Kenntnis des vorherrschenden Verstandnisses von Industrie 4.0 und der damit verbundenen Erwartungen sowie der bestehenden Aktivitaten und Einsatzschwerpunkte in den Unternehmen ist erforderlich, um Forschungsbedarfe aufzuzeigen und um Unternehmen zielgerichtete Unterstutzung anbieten zu konnen.

Summary Analysis of Next Generation Sequencing (NGS) data requires the processing of large datasets by chaining various tools with complex input and output formats. In order to automate data analysis, we propose to standardize NGS tasks into modular workflows. This simplifies reliable handling and processing of NGS data, and corresponding solutions become substantially more reproducible and easier to maintain. Here, we present a documented, linux-based, toolbox of 42 processing modules that are combined to construct workflows facilitating a variety of tasks such as DNAseq and RNAseq analysis. We also describe important technical extensions. The high throughput executor (HTE) helps to increase the reliability and to reduce manual interventions when processing complex datasets. We also provide a dedicated binary manager that assists users in obtaining the modules’ executables and keeping them up to date. As basis for this actively developed toolbox we use the workflow management software KNIME. Availability and Implementation See http://ibisngs.github.io/knime4ngs for nodes and user manual (GPLv3 license) Supplementary information Supplementary data are available at Bioinformatics online.

There is an increasing need to use genome and transcriptome sequencing to genetically diagnose patients suffering from suspected monogenic rare diseases. The proper detection of compound heterozygous variant combinations as disease-causing candidates is a challenge in diagnostic workflows as haplotype information is lost by currently used next-generation sequencing technologies. Consequently, computational tools are required to phase, or resolve the haplotype of, the high number of heterozygous variants in the exome or genome of each patient. Here we present SmartPhase, a phasing tool designed to efficiently reduce the set of potential compound heterozygous variant pairs in genetic diagnoses pipelines. The phasing algorithm of SmartPhase creates haplotypes using both parental genotype information and reads generated by DNA or RNA sequencing and is thus well suited to resolve the phase of rare variants. To inform the user about the reliability of a phasing prediction, it computes a confidence score which is essential to select error-free predictions. It incorporates existing haplotype information and applies logical rules to determine variants that can be excluded as causing a recessive, monogenic disease. SmartPhase can phase either all possible variant pairs in predefined genetic loci or preselected variant pairs of interest, thus keeping the focus on clinically relevant results. We compared SmartPhase to WhatsHap, one of the leading comparable phasing tools, using simulated data and a real clinical cohort of 921 patients. On both data sets, SmartPhase generated error-free predictions using our derived confidence score threshold. It outperformed WhatsHap with regard to the percentage of resolved pairs when parental genotype information is available. On the cohort data, SmartPhase enabled on average the exclusion of approximately 22% of the input variant pairs in each singleton patient and 44% in each trio patient. SmartPhase is implemented as an open-source Java tool and freely available at http://ibis.helmholtz-muenchen.de/smartphase/.

The increasing use of digital information and communication technologies in all areas of life – also referred to as digitalization – opens up new opportunities for handling and using information. Thus, also for productivity management in producing companies a wide range of opportunities is expected. For getting further and more detailed information on these expectations, 74 experts of the German metal and electrical industry have been queried in an online survey in 2017. Due to digitalization, the experts estimate an average increase of productivity until 2025 of 32%. This increase of productivity is enabled by a facilitated collection, distribution, analysis and usage of data. Furthermore, the impacts on human factors and the requirements for realizing the expected benefits were queried and are described in this contribution.

Das folgende Kapitel gibt einen Uberblick uber die technischen Neuerungen („Treiber“), welche sich durch die fortschreitende Entwicklung der Informations- und Kommunikationstechnologie (IKT) ergeben. Basierend auf den Ergebnissen einer Literaturrecherche sowie Meinungen von Digitalisierungsexperten verschiedener Betriebe werden die Potenziale und Konsequenzen fur die Fuhrung und die Unternehmensorganisation erlautert. Hierzu werden erste Handlungsfelder fur eine gesunde und produktive Fuhrung und Organisation in der Arbeitswelt 4.0 festgelegt.

For companies in high-wage countries high productivity is essential in order to survive in international competition. Digitalization opens up new possibilities to manage and increase productivity. Therefore, it is necessary to develop strategies for the productivity management of work systems, which are increasingly embossed by digitalization, and to consider the specific framework conditions and requirements of the companies. The paper presents a framework for a systematical design of productivity strategies and explains conceptual potentials for the design of strategies. The application of this framework is described by practice-oriented examples. Furthermore, its alignment with practical approaches is shown including an outlook on further requirements for successful implementation of strategies.

High productivity is essential for companies in order to survive in international competition, especially for those located in high-wage countries. Recent developments of digitalization open up new opportunities to manage and increase productivity. The development of company-specific strategies for the management of productivity, which are increasingly embossed by digitalization, is therefore an elementary task. This paper presents a framework for systematic design of productivity strategies for industrial production and explains conceptual potentials for the design of strategies. A detailed description of terms provides the necessary understanding. The framework encompasses three axes, the goal of productivity, the application of digital information management in industrial production and the different direct production areas as well as indirect supporting areas. The application of this framework is described for different corporate levels considering task- and goal-setting for various time horizons as well as an integrative view on technological, organizational and personnel aspects.

The proceeding digitalization in industrial context is named as transformation to Industrie 4.0. This term has been presented to the public already 5 years ago and was chosen to point out the meaning of the corresponding changes for industrial production. Since then the term has become very present in media and is often discussed controversially. To identify its perception in small and medium enterprises—the main part of the German industry—a survey has been conducted. Queried were nearly 500 participants in management positions from the Metal and Electrical Industry. The survey’s results prove that the term is very well known while its meaning is often unclear. Furthermore, it was found that Industrie 4.0 is introduced preferentially in production, planning/control, logistics, supply chain management and storage. These fields of usage and the tasks characteristically performed within, indicate fields of action for work design. Structured by informational and energetic work forms as well as technical, organizational and personal aspects, many options for work design are described in detail.

Neutrophil granulocyte play pivotal roles in inflammatory responses, immune defence, tissue remodeling, and cancer control. Studying rare patients with defects in differentiation and/or function of neutrophil granulocytes highlights genes and pathways orchestrating these important cellular functions. A previously not appreciated role of the signal recognition particle (SRP) has emerged when monoallelic mutations in SRP54 were associated with congenital neutropenia and pancreatic insufficiency. The eukaryotic SRP is composed of six distinct polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72) bound to an RNA molecule (the 7SL RNA). SRP and its receptor (SRPRA and SRPRB) cooperatively transport nascent proteins emerging from ribosome to the endoplasmic reticulum (ER) lumen via a protein-conducting channel. We hypothesized that other constituents of the SRP may be involved in the pathophysiology of congenital neutropenia and that disturbances of the SRP may result in defective proteostasis in neutrophil granulocytes. By virtue of our international Care-for-Rare Alliance we identified three kindred with molecularly unsolved congenital neutropenia. Exome-sequencing revealed a de novo monoallelic mutation in SRPRA in one individual in one family and a homozygous splice-site mutation in SRP19 in five individuals from two families. Clinically, all patients with mutations in SRPRA and SRP19 suffered from various degrees of neutropenia and susceptibility to bacterial infections. Pancreatic insufficiency was only seen in patients with mutation in SRPRA, whereas SRP19 deficiency was not associated with any non-hematopoietic symptoms. To functionally validate these novel genetic variants, we set up an in-vitro neutrophil differentiation system allowing us to model the genetic defects in human SRP complex subunits. We introduced patient-specific mutations (SRPRA Q464E and SRP19 c.189+5G>A) into wildtype iPS cells using CRISPR-Cas9 editing. The engineered cells were differentiated into bona fide neutrophil granulocytes. In vitro generated wildtype neutrophil granulocytes had a high degree of resemblance to primary peripheral blood neutrophil granulocytes, as evidenced by phenotypic (light microscopy, cell surface markers, gene expression) and functional (phagocytosis, bacterial killing, rolling and adhesion, chemotaxis) characteristics. In striking contrast to wildtype iPS cells, both SRPRA and SRP19 mutated iPS cells had a significantly reduced capacity to differentiate into neutrophil granulocytes, as shown by colony-forming unit assays and phenotypic analysis. Furthermore, in vitro generated neutrophil granulocytes had higher susceptibility to apoptosis and evidence of increased unfolded protein responses. We went on to characterize the proteome of primary neutrophil granulocytes from patients with SRP-defects by data-independent proteomics technology. Interestingly, neutrophil granulocytes with defects in SRP constituents shared a significantly reduced abundance of the proteins Pentraxin-3 (PTX3) and Glucuronidase Beta (GUSB). These findings were confirmed in both non-hematopoietic HELA cells and promyelocytic HL60 leukemia cells engineered to express the respective SRP mutants. Upon genetic reconstitution, the aberrant protein expression was re-established. In summary, our studies define novel genetic defects causing congenital neutropenia and highlight the relevance of coordinated protein trafficking pathways and homeostasis for physiological differentiation and function of human neutrophil granulocytes. Disclosures No relevant conflicts of interest to declare.

Flexible Produktionssysteme, wie sie im Beitrag von Garrel et al. ausfuhrlich beschrieben sind, ermoglichen es Unternehmen, unterschiedlichste Produkte zu fertigen und so veranderliche Markt- bzw. Kundenanforderungen zu erfullen. In diesem Zusammenhang sind oftmals Lose mit geringen Grosen kurzfristig herzustellen und auszuliefern. Dies erfordert, dass die an der Produktion beteiligten Arbeitspersonen uber die notwendigen Fertigkeiten zur Ausfuhrung der einzelnen Aufgaben bereits verfugen oder sie sich kurzfristig aneignen konnen. Folglich ist bei der Zuordnung von Arbeitsaufgaben zu Arbeitspersonen zu beachten, dass entweder alle Arbeitspersonen uber die zur Ausfuhrung der ihnen anvertrauten Aufgaben erforderlichen Fertigkeiten verfugen oder dass ggf. erforderliche Fertigkeiten unter den jeweiligen Rahmenbedingungen im Produktionsumfeld schnell und leicht erworben werden konnen. Dabei bedeutet Erwerben, dass die jeweilige Fertigkeit erlernt und geubt wird, so dass eine entsprechende Qualifikation entsteht (Schlick et al. 2010a). Der fur das Erwerben der Fertigkeit bzw. der entsprechenden Qualifikation notwendige Zeitraum wird als Lernzeit bezeichnet. Wahrend dieses Zeitraums konnen Referenzleistungen, die ublicherweise in Form von Vorgabezeiten festgelegt sind, nicht erreicht werden (Rohmert et al. 1974). In Folge dessen kann das Produktionssystem, in dem diese Aufgaben ausgefuhrt werden, die bei Referenzleistung vorgesehene Ausbringungsmenge nicht erreichen.