Continued False-Positive Detection of SARS-CoV-2 by Electron Microscopy

Peer Reviewe

BUSINESS PROCESS MODEL ANTI-PATTERNS: A BIBLIOGRAPHY AND TAXONOMY OF PUBLISHED WORK

Patterns have been proven to be useful for documenting reusable solutions to common problems. A recently published bibliography of business process model patterns shed light into the various types of patterns by providing a systematic categorization of these patterns. In this way, such classification improves the understanding of business process model patterns. Anti-patterns document a counterproductive solution to a commonly occurring problem. While a classification for the large body of literature on business process model patterns is available, a structured bibliography of anti-patterns is missing. Related work on anti-patterns discusses patterns for common modeling errors, problems in business process models as well as in the business processes. Modeling experts should be aware of all these types of anti-patterns. To fill this gap, this paper presents a bibliography of business process model anti-patterns and a taxonomy of anti-patterns that has been developed using an established approach for taxonomy development. Both are based on an literature review and are valuable for people during the design and analysis phases of business processes since knowledge about anti-patterns in business process models helps for increasing their quality. Our overview should also be useful for developers of modeling tools who wish to make the modeler aware of potential modeling problems

Visualization of SARS-CoV-2 particles in naso/oropharyngeal swabs by thin section electron microscopy

Background SARS-CoV-2 replicates efficiently in the upper airways of humans and produces high loads of virus RNA and, at least in the initial phase after infection, many infectious virus particles. Studying virus ultrastructure, such as particle integrity or presence of spike proteins, and effects on their host cells in patient samples is important to understand the pathogenicity of SARS-CoV-2. Methods Suspensions from swab samples with a high load of virus RNA (Ct < 20) were sedimented by desktop ultracentrifugation and prepared for thin section electron microscopy using a novel method which is described in detail. Embedding was performed in Epon or in LR White resin using standard or rapid protocols. Thin sections were examined using transmission electron microscopy. Results Virus particles could be regularly detected in the extracellular space, embedded in a background of heterogenous material (e.g. vesicles and needle-like crystals), and within ciliated cells. Morphology (i.e. shape, size, spike density) of virus particles in the swab samples was very similar to particle morphology in cell culture. However, in some of the samples the virus particles hardly revealed spikes. Infected ciliated cells occasionally showed replication organelles, such as double-membrane vesicles. The most common cells in all samples were keratinocytes from the mucosa and bacteria. Conclusions The new method allows the ultrastructural visualization and analysis of coronavirus particles and of infected host cells from easy to collect naso/oropharyngeal patient swab samples.Peer Reviewe

A comparative survey of business process similarity measures

Abstract. Similarity measures for business process models have been suggested for different purposes such as measuring compliance between reference and actual models, searching for related models in a repository, or locating services that adhere to a specification given by a process model. The aim of our article is to provide a comprehensive survey on techniques to define and calculate such similarity measures. As the measures differ in many aspects, it is an interesting question how different measures rank &quot;similarity&quot; within the same set of models. We investigated, how different kinds of changes in a model influence the values of different similarity measures that have been published in academic literature. Furthermore, we identified eight properties that a similarity measure should have from a theoretical point of view and analysed how these properties are fulfilled by the different measures. Our results show that there are remarkable differences among existing measures. We give some recommendations which type of measure is useful for which kind of application

Morphometry of SARS-CoV and SARS-CoV-2 particles in ultrathin plastic sections of infected Vero cell cultures

SARS-CoV-2 is the causative of the COVID-19 disease, which has spread pandemically around the globe within a few months. It is therefore necessary to collect fundamental information about the disease, its epidemiology and treatment, as well as about the virus itself. While the virus has been identified rapidly, detailed ultrastructural analysis of virus cell biology and architecture is still in its infancy. We therefore studied the virus morphology and morphometry of SARS-CoV-2 in comparison to SARS-CoV as it appears in Vero cell cultures by using conventional thin section electron microscopy and electron tomography. Both virus isolates, SARS-CoV Frankfurt 1 and SARS-CoV-2 Italy-INMI1, were virtually identical at the ultrastructural level and revealed a very similar particle size distribution with a median of about 100 nm without spikes. Maximal spike length of both viruses was 23 nm. The number of spikes per virus particle was about 30% higher in the SARS-CoV than in the SARS-CoV-2 isolate. This result complements a previous qualitative finding, which was related to a lower productivity of SARS-CoV-2 in cell culture in comparison to SARS-CoV.Peer Reviewe

Some remarks on the notions of general covariance and background independence

In the first part of this paper I review some of the difficulties that seem to obstruct generally valid definitions of "general covariance" and/or "background independence" The second and more historical part deals with a rather strange argument that Einstein put forward in his 1913 "Entwurf paper" with M. Grossmann to discredit scalar theories of gravity in order to promote general covariance.Comment: 26 pages, 3 figures. Contribution to ``An assessment of current paradigms in the physics of fundamental interactions'', edited by I.O. Stamatescu (Springer Verlag, to appear

Rapid and Robust Continuous Purification of High-Titer Hepatitis B Virus for In Vitro and In Vivo Applications

Available treatments for hepatitis B can control the virus but are rarely curative. This led to a global initiative to design new curative therapies for the 257 million patients affected. Discovery and development of these new therapies is contingent upon functional in vitro and in vivo hepatitis B virus (HBV) infection models. However, low titer and impurity of conventional HBV stocks reduce significance of in vitro infections and moreover limit challenge doses in current in vivo models. Therefore, there is a critical need for a robust, simple and reproducible protocol to generate high-purity and high-titer infectious HBV stocks. Here, we outline a three-step protocol for continuous production of high-quality HBV stocks from supernatants of HBV-replicating cell lines. This purification process takes less than 6 h, yields to high-titer stocks (up to 1 × 1011 enveloped, DNA-containing HBV particles/mL each week), and is with minimal equipment easily adaptable to most laboratory settings.Peer Reviewe