Unravelling the Complexity of Supply Chain Volatility Management

Managing supply chain volatility (SCV) is often identified as one of the major challenges of modern supply chain management. While research has predominantly focused on describing the multidimensional areas of SCV and its negative impacts, clear guidelines on how to manage SCV for efficiency, and prioritize the areas on which to focus, are sparse. This study seeks to fill this gap in the research by: (1) assessing the relative impact of SCV sources, and (2) proposing means to deal with them. Based on an Analytical Hierarchy Process conducted with 17 SCM practitioners, the paper assesses the relative impact of sources of SCV, and further contextualizes them according to factors such as product lead time and production strategy, providing more fine-grained insights for SC managers seeking to manage SCV. Subsequently, the paper applies the Nominal Group Technique with the same group of practitioners in order to identify and condense strategies for dealing with the most impactful sources of SCV (intra-organizational misalignment, inaccurate forecasting, long lead times, erratic behavior of decision makers in the supply chain, erratic behavior of customers, and high level of competition), leading to a set of 44 SCV-management strategies

Overcoming Barriers in Supply Chain Analytics—Investigating Measures in LSCM Organizations

While supply chain analytics shows promise regarding value, benefits, and increase in performance for logistics and supply chain management (LSCM) organizations, those organizations are often either reluctant to invest or unable to achieve the returns they aspire to. This article systematically explores the barriers LSCM organizations experience in employing supply chain analytics that contribute to such reluctance and unachieved returns and measures to overcome these barriers. This article therefore aims to systemize the barriers and measures and allocate measures to barriers in order to provide organizations with directions on how to cope with their individual barriers. By using Grounded Theory through 12 in-depth interviews and Q-Methodology to synthesize the intended results, this article derives core categories for the barriers and measures, and their impacts and relationships are mapped based on empirical evidence from various actors along the supply chain. Resultingly, the article presents the core categories of barriers and measures, including their effect on different phases of the analytics solutions life cycle, the explanation of these effects, and accompanying examples. Finally, to address the intended aim of providing directions to organizations, the article provides recommendations for overcoming the identified barriers in organizations

Digital Supply Chain Twins in Practice: Outlining the Technological and Organizational Requirements for Successful Implementation

Digital supply chain twins (DSCT) are often considered as one of the most promising technologies to efficiently and proactively manage increasingly complex international logistics networks in the future. Despite the recognition of the potential, the concrete development of digital twins of logistics networks is still in earlier stages in practice. Most twins focus on mapping digital twins of logistics assets or sites rather than elevating the technology to a network level. Building on the Nominal Group Technique among 18 logistics managers this study seeks to investigate the requirements of successful DSCT implementation at a network level. The study shows that while there are various technological requirements that need to be created for the development, it is also DSCT-specific intra- and inter-organizational requirements that influence the successful implementation and use of DSCTs

Digital Supply Chain Twins—Conceptual Clarification, Use Cases and Benefits

Background: Digital supply chain twins (DSCT) are gaining increased attention in academia and practice as they emerge as one of the most important trends in logistics and supply chain management (LSCM). Still, there seems to be no common understanding of the term in scientific literature. Moreover, the broad field of LSCM allows for a multitude of feasible application areas and use cases, yet there exists no conclusive list of them as to date. Methods: This study builds upon a systematic literature review of 66 DSCT articles to identify application areas of DSCT in LSCM as well as specific use cases and their respective intended benefits. Results: To start with, the study derives a unified definition of DSCTs, including possible scopes of applications. Afterwards, five application areas of DSCT in LSCM are synthesized as well as 14 individual use cases and their respective intended benefits. Conclusions: The study leads towards a conceptual clarification of DSCT that is of importance for research and practice alike. For managers it additionally provides up-to-date use cases to guide DSCT applications in practice

Solution conformations of a linked construct of the Zika virus NS2B-NS3 protease

The Zika virus presents a serious risk for global health. Crystal structures of different constructs of the Zika virus NS2B-NS3 protease (NS2B-NS3pro) have been determined with the aim to provide a basis for rational drug discovery. In these structures, the C-terminal β-hairpin of NS2B, NS2Bc, was observed to be either disordered (open conformation) or bound to NS3pro complementing the substrate binding site (closed conformation). Enzymatically active constructs of flaviviral NS2B-NS3 proteases commonly used for inhibitor testing contain a covalent peptide linker between NS2B and NS3pro. Using a linked construct of Zika virus NS2B-NS3pro, we studied the location of NS2Bc relative to NS3pro in solution by pseudocontact shifts generated by a paramagnetic lanthanide tag attached to NS3pro. Both closed and open conformations were observed with different inhibitors. As the NS2B co-factor is involved in substrate binding of flaviviral NS2B-NS3 proteases, the destabilization of the closed conformation in the linked construct makes it an attractive tool to search for inhibitors that interfere with the formation of the enzymatically active, closed conformation.C.N. thanks the Alexander vonHumbolt Foundation for a Feodor-Lynen fellowship. Financialsupport by the Australian Research Council is gratefully acknowl-edged. C.K. acknowledges support by the Deutsche For-schungsgemeinschaft, grant KL 1356/3

The capacity of Aspergillus niger to sense and respond to cell wall stress requires at least three transcription factors: RlmA, MsnA and CrzA

Background: Cell wall integrity, vesicle transport and protein secretion are key factors contributing to the vitality and productivity of filamentous fungal cell factories such as Aspergillus niger. In order to pioneer rational strain improvement programs, fundamental knowledge on the genetic basis of these processes is required. The aim of the present study was thus to unravel survival strategies of A. niger when challenged with compounds interfering directly or indirectly with its cell wall integrity: calcofluor white, caspofungin, aureobasidin A, FK506 and fenpropimorph. Results: Transcriptomics signatures of A. niger and phenotypic analyses of selected null mutant strains were used to predict regulator proteins mediating the survival responses against these stressors. This integrated approach allowed us to reconstruct a model for the cell wall salvage gene network of A. niger that ensures survival of the fungus upon cell surface stress. The model predicts that (i) caspofungin and aureobasidin A induce the cell wall integrity pathway as a main compensatory response via induction of RhoB and RhoD, respectively, eventually activating the mitogen-activated protein kinase kinase MkkA and the transcription factor RlmA. (ii) RlmA is the main transcription factor required for the protection against calcofluor white but it cooperates with MsnA and CrzA to ensure survival of A. niger when challenged with caspofungin and aureobasidin A. (iii) Membrane stress provoked by aureobasidin A via disturbance of sphingolipid synthesis induces cell wall stress, whereas fenpropimorph-induced disturbance of ergosterol synthesis does not. Conclusion: The present work uncovered a sophisticated defence system of A. niger which employs at least three transcription factors - RlmA, MsnA and CrzA – to protect itself against cell wall stress. The transcriptomic data furthermore predicts a fourth transfactor, SrbA, which seems to be specifically important to survive fenpropimorph-induced cell membrane stress. Future studies will disclose how these regulators are interlocked in different signaling pathways to secure survival of A. niger under different cell wall stress conditions

Updating genome annotation for the microbial cell factory Aspergillus niger using gene co-expression networks

A significant challenge in our understanding of biological systems is the high number of genes with unknown function in many genomes. The fungal genus Aspergillus contains important pathogens of humans, model organisms, and microbial cell factories. Aspergillus niger is used to produce organic acids, proteins, and is a promising source of new bioactive secondary metabolites. Out of the 14,165 open reading frames predicted in the A. niger genome only 2% have been experimentally verified and over 6,000 are hypothetical. Here, we show that gene co-expression network analysis can be used to overcome this limitation. A meta-analysis of 155 transcriptomics experiments generated co-expression networks for 9,579 genes (∼65%) of the A. niger genome. By populating this dataset with over 1,200 gene functional experiments from the genus Aspergillus and performing gene ontology enrichment, we could infer biological processes for 9,263 of A. niger genes, including 2,970 hypothetical genes. Experimental validation of selected co-expression sub-networks uncovered four transcription factors involved in secondary metabolite synthesis, which were used to activate production of multiple natural products. This study constitutes a significant step towards systems-level understanding of A. niger, and the datasets can be used to fuel discoveries of model systems, fungal pathogens, and biotechnology.DFG, 325093850, Open Access Publizieren 2017 - 2018 / Technische Universität BerlinEC/FP7/607332/EU/Quantitative Biology for Fungal Secondary Metabolite Producers/QuantFun

The low affinity glucose transporter HxtB is also involved in glucose signalling and metabolism in Aspergillus nidulans

One of the drawbacks during second-generation biofuel production from plant lignocellulosic biomass is the accumulation of glucose, the preferred carbon source of microorganisms, which causes the repression of hydrolytic enzyme secretion by industrially relevant filamentous fungi. Glucose sensing, subsequent transport and cellular signalling pathways have been barely elucidated in these organisms. This study therefore characterized the transcriptional response of the filamentous fungus Aspergillus nidulans to the presence of high and low glucose concentrations under continuous chemostat cultivation with the aim to identify novel factors involved in glucose sensing and signalling. Several transcription factor- and transporter-encoding genes were identified as being differentially regulated, including the previously characterized glucose and xylose transporter HxtB. HxtB was confirmed to be a low affinity glucose transporter, localizing to the plasma membrane under low- and high-glucose conditions. Furthermore, HxtB was shown to be involved in conidiation-related processes and may play a role in downstream glucose signalling. A gene predicted to encode the protein kinase PskA was also identified as being important for glucose metabolism. This study identified several proteins with predicted roles in glucose metabolic processes and provides a foundation for further investigation into the response of biotechnologically important filamentous fungi to glucose