Towards Quantitative Factory Life Cycle Evaluation

Manufacturing companies face the challenge of understanding and improving complex factory systems in order to stay competitive in a turbulent environment. Interrelated and overlapping life cycles of products and physical factory elements (e.g. machine tools, technical building services, building shell) are challenges to be handled in factory planning and operation. This work discusses both qualitative and quantitative factory life cycle models, analyzing addressed sustainability goals. Due to the lack of quantitative life cycle description models on higher system levels, a concept for aggregating life cycle models from shop floor up to site level is developed. The concept is consequently applied in a case study where cost curves are calculated over the factory's life span and are aggregated to support factory planning and operation. © 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license

Fucose Binding Cancels out Mechanical Differences between Distinct Human Noroviruses

The majority of nonbacterial gastroenteritis in humans and livestock is caused by noroviruses.Like most RNA viruses, frequent mutations result in various norovirus variants. The strain-dependentbinding profiles of noroviruses to fucose are supposed to facilitate norovirus infection. It remains unclear, however, what the molecular mechanism behind strain-dependent functioning is. In this study,by applying atomic force microscopy (AFM) nanoindentation technology, we studied norovirus-likeparticles (noroVLPs) of three distinct human norovirus variants. We found differences in viral mechanical properties even between the norovirus variants from the same genogroup. The noroVLPswere then subjected to fucose treatment. Surprisingly, after fucose treatment, the previously foundconsiderable differences in viral mechanical properties among these variants were diminished. Weattribute a dynamic switch of the norovirus P domain upon fucose binding to the reduced differencesin viral mechanical properties across the tested norovirus variants. These findings shed light on themechanisms used by norovirus capsids to adapt to environmental changes and, possibly, increasecell infection. Hereby, a new step towards connecting viral mechanical properties to viral prevalenceis taken.<br/

A community-powered search of machine learning strategy space to find NMR property prediction models

The rise of machine learning (ML) has created an explosion in the potential strategies for using data to make scientific predictions. For physical scientists wishing to apply ML strategies to a particular domain, it can be difficult to assess in advance what strategy to adopt within a vast space of possibilities. Here we outline the results of an online community-powered effort to swarm search the space of ML strategies and develop algorithms for predicting atomic-pairwise nuclear magnetic resonance (NMR) properties in molecules. Using an open-source dataset, we worked with Kaggle to design and host a 3-month competition which received 47,800 ML model predictions from 2,700 teams in 84 countries. Within 3 weeks, the Kaggle community produced models with comparable accuracy to our best previously published "in-house" efforts. A meta-ensemble model constructed as a linear combination of the top predictions has a prediction accuracy which exceeds that of any individual model, 7-19x better than our previous state-of-the-art. The results highlight the potential of transformer architectures for predicting quantum mechanical (QM) molecular properties

Molecular landscape and prognostic impact of FLT3 -ITD insertion site in acute myeloid leukemia : RATIFY study results

In acute myeloid leukemia (AML) internal tandem duplications of the FLT3 gene (FLT3- ITD) are associated with poor prognosis. Retrospectively, we investigated the prognostic and predictive impact of FLT3 -ITD insertion site (IS) in 452 patients randomized within the RATIFY trial, which evaluated midostaurin additionally to intensive chemotherapy. Next-generation sequencing identified 908 ITDs, with 643 IS in the juxtamembrane domain (JMD) and 265 IS in the tyrosine kinase domain-1 (TKD1). According to IS, patients were categorized as JMDsole (n = 251, 55%), JMD and TKD1 (JMD/TKD1; n = 117, 26%), and TKD1sole (n = 84, 19%). While clinical variables did not differ among the 3 groups, NPM1 mutation was correlated with JMDsole (P = 0.028). Overall survival (OS) differed significantly, with estimated 4-year OS probabilities of 0.44, 0.50, and 0.30 for JMDsole, JMD/TKD1, and TKD1sole, respectively (P = 0.032). Multivariate (cause-specific) Cox models for OS and cumulative incidence of relapse using allogeneic hematopoietic cell transplantation (HCT) in first complete remission as a time-dependent variable identified TKD1sole as unfavorable and HCT as favorable factors. In addition, Midostaurin exerted a significant benefit only for JMDsole. Our results confirm the distinct molecular heterogeneity of FLT3 -ITD and the negative prognostic impact of TKD1 IS in AML that was not overcome by midostaurin

Norovirus–glycan interactions — how strong are they really?

Infection with human noroviruses requires attachment to histo blood group antigens (HBGAs) via the major capsid protein VP1 as a primary step. Several crystal structures of VP1 protruding domain dimers, so called P-dimers, complexed with different HBGAs have been solved to atomic resolution. Corresponding binding affinities have been determined for HBGAs and other glycans exploiting different biophysical techniques, with mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy being most widely used. However, reported binding affinities are inconsistent. At the extreme, for the same system MS detects binding whereas NMR spectroscopy does not, suggesting a fundamental source of error. In this short essay, we will explain the reason for the observed differences and compile reliable and reproducible binding affinities. We will then highlight how a combination of MS techniques and NMR experiments affords unique insights into the process of HBGA binding by norovirus capsid proteins