Electron-hole coherent states for the Bogoliubov-de Gennes equation

We construct a new set of generalized coherent states, the electron-hole coherent states, for a (quasi-)spin particle on the infinite line. The definition is inspired by applications to the Bogoliubov-de Gennes equations where the quasi-spin refers to electron- and hole-like components of electronic excitations in a superconductor. Electron-hole coherent states generally entangle the space and the quasi-spin degrees of freedom. We show that the electron-hole coherent states allow obtaining a resolution of unity and form minimum uncertainty states for position and velocity where the velocity operator is defined using the Bogoliubov-de Gennes Hamiltonian. The usefulness and the limitations of electron-hole coherent states and the phase space representations built from them are discussed in terms of basic applications to the Bogoliubov-de Gennes equation such as Andreev reflection.Comment: 18 page

A Query Language for Software Architecture Information (Extended version)

Software maintenance is an important part of a software system's life cycle. Maintenance tasks of existing software systems suffer from architecture information that is diverging over time (architectural drift). The Digital Architecture Twin (DArT) can support software maintenance by providing up-to-date architecture information. For this, the DArT gathers such information and co-evolves with a software system, enabling continuous reverse engineering. But the crucial link for stakeholders to retrieve this information is missing. To fill this gap, we contribute the Architecture Information Query Language (AIQL), which enables stakeholders to access up-to-date and tailored architecture information. We derived four application scenarios in the context of continuous reverse engineering. We showed that the AIQL provides the required functionality to formulate queries for the application scenarios and that the language scales for use with real-world software systems. In a user study, stakeholders agreed that the language is easy to understand and assessed its value to the specific stakeholder for the application scenarios

Evidence of increasing functional differentiation in pottery use among Late Holocene maritime foragers in northern Japan

Hamanaka 2 is a multi-phase coastal site in Rebun Island with a ~ 3000-year occupation sequence extending from the final-stage Jōmon and Okhotsk to the Ainu Culture period (1050 BCE-1850 CE). To examine long-term trends in food processing at the site, we collected 66 ceramic sherds across six distinct cultural layers from the Final Jōmon to the Late Okhotsk period for lipid residue analysis. Given the site's beachfront location in an open bay, with ready access to abundant maritime resources, we predicted that the pottery would consistently have been used to process aquatic resources throughout all cultural periods. Though aquatic lipids dominated across the site sequence, the history of pottery use at the site proved more complex. Evidence of plant processing was found in all cultural phases, and from the Epi-Jōmon/Late Final Jōmon transition onwards 30% of the vessels were being used to process mixed dishes that combined both marine and terrestrial resources. By the start of the Okhotsk phase, separate sets of resources were being processed in different pots, suggesting functional differentiation in the use of pottery, and the rise of new kinds of cuisine – including the processing of millet. We tentatively explain these results as a consequence of the growing incorporation of Rebun Island into wider regional trade and interaction networks, which brought new kinds of resources and different social dynamics to Northern Hokkaido in the Late Holocene

Production of a fusogenic oncolytic rVSV-NDV virus: Cell-line screening and process development in small-scale suspension cultures

Fusogenic oncolytic viruses represent a novel class of immunotherapeutics, which offer hope for the treatment of otherwise incurable cancers. Their enhanced intratumoral spread through syncytia formation allows for a potent mechanism of tumor cell death and induction of antitumor immune responses [1]. While the ability of these viruses to induce cell-cell fusion reactions offers numerous beneficial properties, it also presents unique challenges for large-scale clinical-grade manufacturing. Infected cells rapidly fuse with surrounding cells, resulting in large multinucleated syncytia, which quickly die before high titers of the virus can be produced or released [2]. Here, we evaluated the production of a novel hyper-fusogenic hybrid of vesicular stomatitis virus and Newcastle disease virus (rVSV-NDV) in four different suspension cell lines. Cell growth, metabolism, and virus productivity were characterized for each candidate respectively. Permissiveness was evaluated based on extracellular infectious virus titer and cell-specific virus yields (CSVY). For the purpose of process intensification, virus adaptation, and multiplicity of infection (MOI) screenings were conducted in small-scale and confirmed in a 1 L bioreactor. BHK-21 and HEK293SF were identified as promising candidates for rVSV-NDV production, yielding infectious titers at infection cell concentrations of 2.0 E06 cells/mL of up to 3.0 E08 TCID50/mL and 7.5 E07 TCID50/mL, and CSVYs of 153 and 9, respectively. Oncolytic potency was not affected by production in suspension cultures compared to the reference stock produced in adherent AGE1.CR.pIX cultures. Overall, promising suspension cell substrates were identified for a highly efficient and scalable production process of this fusogenic rVSV-NDV. This paves the way for an efficient large-scale manufacturing process, which can be further intensified towards high cell density production in order to provide sufficient virus material for conducting a phase I clinical trial of oncolytic VSV-NDV in cancer patients. 1. Krabbe, T. and J. Altomonte, Fusogenic Viruses in Oncolytic Immunotherapy. Cancers (Basel), 2018. 10(7). 2. Abdullahi, S., et al., A Novel Chimeric Oncolytic Virus Vector for Improved Safety and Efficacy as a Platform for the Treatment of Hepatocellular Carcinoma. J Virol, 2018. 92(23)

Production of a fusogenic oncolytic rVSV-NDV virus in perfusion processes

Oncolytic viruses (OVs), as a therapeutic vaccine, offer an elegant approach to cancer therapy. On the one side they have the ability to cause direct tumor cell lysis, on the other side they can stimulate immune responses directed against the tumor. By expressing endogenous or heterologous fusion glycoproteins, an enhanced intratumoral spread via syncytia formation can be achieved. Rapid and efficient fusion of infected cells may result in large multinucleated syncytia, in which cells quickly die before high titers are reached [1]. Prospective treatment with OVs will require manufacturing processes that enable the production of a very high number of doses with high titers. As a first step towards this goal, suspension cell substrates were identified to develop a highly efficient and scalable production process of a novel hyper-fusogenic hybrid of vesicular stomatitis virus and Newcastle disease virus (rVSV-NDV). Please click Download on the upper right corner to see the full abstract

Integrated end-to-end MVA viral vector production: Perfusion culture shows economical advantage over batch culture

Modified Vaccinia Ankara (MVA) virus is a promising viral vector for gene therapy. Several pre-clinical and clinical trials are currently being conducted with MVA as a live vector vaccine against COVID-19, Ebola disease, influenza or various types of cancers. For most applications, a large amount of the vector will be required (\u3e108 infectious virus per dose). High cell concentrations are favorable for developing high-yield MVA vector production systems. Efficient production of MVA in an avian suspension cell line (AGE1.CR.pIX) cultivated in perfusion mode with a membrane-based cell retention system has previously been demonstrated. However, up to now a direct harvest through the membrane for a continuous integrated process was not feasible. Please click Additional Files below to see the full abstract

Strong in-plane anisotropy in the electronic structure of fixed-valence β\beta-LuAlB4_4

The origin of intrinsic quantum criticality in the heavy-fermion superconductor $\beta$-YbAlB$_4$ has been attributed to strong Yb valence fluctuations and its peculiar crystal structure. Here, we assess these contributions individually by studying the isostructural but fixed-valence compound $\beta$-LuAlB$_4$. Quantum oscillation measurements and DFT calculations reveal a Fermi surface markedly different from that of $\beta$-YbAlB$_4$, consistent with a `large' Fermi surface there. We also find an unexpected in-plane anisotropy of the electronic structure, in contrast to the isotropic Kondo hybridization in $\beta$-YbAlB$_4$.Comment: 6 pages, 4 figure