Coalgebraic Automata Theory: Basic Results

We generalize some of the central results in automata theory to the abstraction level of coalgebras and thus lay out the foundations of a universal theory of automata operating on infinite objects. Let F be any set functor that preserves weak pullbacks. We show that the class of recognizable languages of F-coalgebras is closed under taking unions, intersections, and projections. We also prove that if a nondeterministic F-automaton accepts some coalgebra it accepts a finite one of the size of the automaton. Our main technical result concerns an explicit construction which transforms a given alternating F-automaton into an equivalent nondeterministic one, whose size is exponentially bound by the size of the original automaton.Comment: 43 page

Integrated Laboratory Demonstrations of Multi-Object Adaptive Optics on a Simulated 10-Meter Telescope at Visible Wavelengths

One important frontier for astronomical adaptive optics (AO) involves methods such as Multi-Object AO and Multi-Conjugate AO that have the potential to give a significantly larger field of view than conventional AO techniques. A second key emphasis over the next decade will be to push astronomical AO to visible wavelengths. We have conducted the first laboratory simulations of wide-field, laser guide star adaptive optics at visible wavelengths on a 10-meter-class telescope. These experiments, utilizing the UCO/Lick Observatory's Multi-Object / Laser Tomography Adaptive Optics (MOAO/LTAO) testbed, demonstrate new techniques in wavefront sensing and control that are crucial to future on-sky MOAO systems. We (1) test and confirm the feasibility of highly accurate atmospheric tomography with laser guide stars, (2) demonstrate key innovations allowing open-loop operation of Shack-Hartmann wavefront sensors (with errors of ~30 nm) as will be needed for MOAO, and (3) build a complete error budget model describing system performance. The AO system maintains a performance of 32.4% Strehl on-axis, with 24.5% and 22.6% at 10" and 15", respectively, at a science wavelength of 710 nm (R-band) over the equivalent of 0.8 seconds of simulation. The MOAO-corrected field of view is ~25 times larger in area than that limited by anisoplanatism at R-band. Our error budget is composed of terms verified through independent, empirical experiments. Error terms arising from calibration inaccuracies and optical drift are comparable in magnitude to traditional terms like fitting error and tomographic error. This makes a strong case for implementing additional calibration facilities in future AO systems, including accelerometers on powered optics, 3D turbulators, telescope and LGS simulators, and external calibration ports for deformable mirrors.Comment: 29 pages, 11 figures, submitted to PAS

Cell culture–based production of defective interfering influenza A virus particles in perfusion mode using an alternating tangential flow filtration system

Respiratory diseases including influenza A virus (IAV) infections represent a major threat to human health. While the development of a vaccine requires a lot of time, a fast countermeasure could be the use of defective interfering particles (DIPs) for antiviral therapy. IAV DIPs are usually characterized by a large internal deletion in one viral RNA segment. Consequentially, DIPs can only propagate in presence of infectious standard viruses (STVs), compensating the missing gene function. Here, they interfere with and suppress the STV replication and might act “universally” against many IAV subtypes. We recently reported a production system for purely clonal DIPs utilizing genetically modified cells. In the present study, we established an automated perfusion process for production of a DIP, called DI244, using an alternating tangential flow filtration (ATF) system for cell retention. Viable cell concentrations and DIP titers more than 10 times higher than for a previously reported batch cultivation were observed. Furthermore, we investigated a novel tubular cell retention device for its potential for continuous virus harvesting into the permeate. Very comparable performances to typically used hollow fiber membranes were found during the cell growth phase. During the virus replication phase, the tubular membrane, in contrast to the hollow fiber membrane, allowed 100% of the produced virus particles to pass through. To our knowledge, this is the first time a continuous virus harvest was shown for a membrane-based perfusion process. Overall, the process established offers interesting possibilities for advanced process integration strategies for next-generation virus particle and virus vector manufacturing. Key points • An automated perfusion process for production of IAV DIPs was established. • DIP titers of 7.40E + 9 plaque forming units per mL were reached. • A novel tubular cell retention device enabled continuous virus harvesting. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00253-021-11561-y

Single-Cell Analysis Uncovers a Vast Diversity in Intracellular Viral Defective Interfering RNA Content Affecting the Large Cell-to-Cell Heterogeneity in Influenza A Virus Replication

Virus replication displays a large cell-to-cell heterogeneity; yet, not all sources of this variability are known. Here, we study the effect of defective interfering (DI) particle (DIP) co-infection on cell-to-cell variability in influenza A virus (IAV) replication. DIPs contain a large internal deletion in one of their eight viral RNAs (vRNA) and are, thus, defective in virus replication. Moreover, they interfere with virus replication. Using single-cell isolation and reverse transcription polymerase chain reaction, we uncovered a large between-cell heterogeneity in the DI vRNA content of infected cells, which was confirmed for DI mRNAs by single-cell RNA sequencing. A high load of intracellular DI vRNAs and DI mRNAs was found in low-productive cells, indicating their contribution to the large cell-to-cell variability in virus release. Furthermore, we show that the magnitude of host cell mRNA expression (some factors may inhibit virus replication), but not the ribosome content, may further affect the strength of single-cell virus replication. Finally, we show that the load of viral mRNAs (facilitating viral protein production) and the DI mRNA content are, independently from one another, connected with single-cell virus production. Together, these insights advance single-cell virology research toward the elucidation of the complex multi-parametric origin of the large cell-to-cell heterogeneity in virus infections

Determination of the bendability of ductile materials

Understanding fracture in the bending of metal sheet is important but difficult especially for ductile materials were fracture is hard to quantify. New bend tests allow fracture analysis at higher bending strains, however, most of them are impractical for industrial application. This work investigates the link between material failure in bending of brittle and highly ductile materials and local tensile ductility which can be measured in a simple tensile test. For this, a 3-point bend test is developed based on the widely accepted VDA238-100, enabling the fracture of highly ductile aluminium alloys. The failure strain of brittle and ductile aluminium sheets in bending is determined. Uni-axial tensile tests are performed in combination with a digital image correlation (DIC) strain measurement system. Using the surface strain data, obtained from the DIC system during tensile testing and bend testing, a correlation between the local ductility in tensile testing and the fracture strain in bending was identified

Finitely generated free Heyting algebras via Birkhoff duality and coalgebra

Algebras axiomatized entirely by rank 1 axioms are algebras for a functor and thus the free algebras can be obtained by a direct limit process. Dually, the final coalgebras can be obtained by an inverse limit process. In order to explore the limits of this method we look at Heyting algebras which have mixed rank 0-1 axiomatizations. We will see that Heyting algebras are special in that they are almost rank 1 axiomatized and can be handled by a slight variant of the rank 1 coalgebraic methods

Economic precariousness: A new channel in the housing market cycle

Abstract: Demographic and institutional elements, as important drivers of the housing market, should not be neglected since it is not only financial and monetary elements that matter in the case of the housing market. In this context, one relationship, which still remains unclear, is the relationship between the housing and the labour markets. Some research has been undertaken to support the hypothesis that high rates of homeownership lead to high unemployment via increases in the reservation wage. However, further research is needed to address the possible implications of the institutional settings of the labour market in the dynamics of the housing market. The aim of this paper is to bring some light on the link between both markets. In particular, this contribution explains how the housing cycle could be ‘amplified’ via a new channel, i.e. economic precariousness, which is closely related to job insecurity. Subsequently, we provide evidence in the case of five developed economies, Ireland, the Netherlands, Spain, the United Kingdom and the United States, over the period 1985-2013.Not appicabl

Moonlighting Proteins Hal3 and Vhs3 Form a Heteromeric PPCDC with Ykl088w in Yeast CoA Biosynthesis

Premi a l'excel·lència investigadora. 2010Unlike most other organisms, the essential five-step Coenzyme A biosynthetic pathway has not been fully resolved in yeast. Specifically, the gene(s) encoding the phosphopantothenoylcysteine decarboxylase (PPCDC) activity still remains unidentified. Sequence homology analyses suggest three candidates, namely Ykl088w, Hal3 and Vhs3, as putative PPCDC enzymes in Saccharomyces cerevisiae. Interestingly, Hal3 and Vhs3 have been characterized as negative regulatory subunits of the Ppz1 protein phosphatase. Here we show that YKL088w does not encode a third Ppz1 regulatory subunit, and that the essential roles of Ykl088w and the Hal3/Vhs3 pair are complementary, cannot be interchanged and can be attributed to PPCDC-related functions. We demonstrate that while known eukaryotic PPCDCs are homotrimers, the active yeast enzyme is a heterotrimer which consists of Ykl088w and Hal3/Vhs3 monomers that separately provides two essential catalytic residues. Our results unveil Hal3/Vhs3 as moonlighting proteins, involved in both CoA biosynthesis and protein phosphatase regulation