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

Influenza A virus propagation in MDCK: Intracellular virus replication, virus release and cell-cycle preferential infection analysis

Cell culture-based processes for vaccine manufacturing offer advantages over egg-based processes in terms of product uniformity and sterility, production time and scaling up capacity1,2. Regarding influenza vaccines, MDCK cells are one of the host cell lines currently used to manufacture licensed products; however, virus titers remain lower compared to those obtained in eggs and further increase of specific and volumetric yields is required. To identify bottlenecks in influenza A virus (IAV) production, we thoroughly studied IAV replication in MDCK cells. For this, we analyzed different features of the infection process such as viral RNA replication, intracellular localization of viral components, virus release and morphology of the particles, and the preferential infection in different cell-cycle phases. Using synchronous infections, we found that production of infectious particles dropped much earlier than the production of total particles. Furthermore, we found that the maximum virus release rate was reached when all viral RNA species attained their maximum intracellular concentration. Using qPCR we determined that the vRNA maximum concentration per cell was 10‑fold higher than the specific viral titers obtained, indicating that vRNA concentration does not limit IAV particle assembly. When we evaluated the morphology of particles released using electron microscopy, we observed that a higher fraction of the viral particles produced at late times possess an abnormal morphology, concurring with the increased production of non-infectious viruses. Using imaging flow cytometry, we determined that the export of influenza viral genome segments (ribonucleoprotein complexes, vRNPs) from the nucleus to the cytoplasm strongly correlated with the onset of virus release. However, our results also suggest that the induction of apoptosis caused that virus assembly became deficient producing more non-infectious particles at late infection times. Lastly, using low MOI infections and imaging flow cytometry, we found that -in contrast to previous publications- IAV did not preferentially infect a specific cell cycle phase and no cell cycle arrest induction was observed during the time frame of the experiment (9 hpi). In summary, the data presented here offers a comprehensive overview of the dynamics of IAV infection in MDCK and might contribute to the development of molecular or cell culture-based strategies to improve IAV production in MDCK cells. 1 Gallo-Ramírez et al, 2015. Exp. Rev. Vaccines 14 (9). 2 Pardue et al. 2011. Exp. Rev. Vaccines 10 (8)

Antiviral Activity of Influenza A Virus Defective Interfering Particles against SARS-CoV-2 Replication In Vitro through Stimulation of Innate Immunity

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) emerged in late 2019 and resulted in a devastating pandemic. Although the first approved vaccines were already administered by the end of 2020, worldwide vaccine availability is still limited. Moreover, immune escape variants of the virus are emerging against which the current vaccines may confer only limited protection. Further, existing antivirals and treatment options against COVID-19 show only limited efficacy. Influenza A virus (IAV) defective interfering particles (DIPs) were previously proposed not only for antiviral treatment of the influenza disease but also for pan-specific treatment of interferon (IFN)-sensitive respiratory virus infections. To investigate the applicability of IAV DIPs as an antiviral for the treatment of COVID-19, we conducted in vitro co-infection experiments with cell culture-derived DIPs and the IFN-sensitive SARS-CoV-2 in human lung cells. We show that treatment with IAV DIPs leads to complete abrogation of SARS-CoV-2 replication. Moreover, this inhibitory effect was dependent on janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling. Further, our results suggest boosting of IFN-induced antiviral activity by IAV DIPs as a major contributor in suppressing SARS-CoV-2 replication. Thus, we propose IAV DIPs as an effective antiviral agent for treatment of COVID-19, and potentially also for suppressing the replication of new variants of SARS-CoV-2

Influenza A virus OP7 defective interfering particles: Cell culture-based production and antiviral efficacy in vivo

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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

The global oscillation network group site survey. II. Results

The Global Oscillation Network Group (GONG) Project will place a network of instruments around the world to observe solar oscillations as continuously as possible for three years. The Project has now chosen the six network sites based on analysis of survey data from fifteen sites around the world. The chosen sites are: Big Bear Solar Observatory, California; Mauna Loa Solar Observatory, Hawaii; Learmonth Solar Observatory, Australia; Udaipur Solar Observatory, India; Observatorio del Teide, Tenerife; and Cerro Tololo Interamerican Observatory, Chile. Total solar intensity at each site yields information on local cloud cover, extinction coefficient, and transparency fluctuations. In addition, the performance of 192 reasonable components analysis. An accompanying paper describes the analysis methods in detail; here we present the results of both the network and individual site analyses. The selected network has a duty cycle of 93.3%, in good agreement with numerical simulations. The power spectrum of the network observing window shows a first diurnal sidelobe height of 3 × 10⁻⁴ with respect to the central component, an improvement of a factor of 1300 over a single site. The background level of the network spectrum is lower by a factor of 50 compared to a single-site spectrum

Review on quality assurance along the CFRP value chain - Non-destructive testing of fabrics, preforms and CFRP by HF radio wave techniques

Eddy current testing is well established for non-destructive testing of electrical conductive materials [1]. The development of radio frequency (RF) eddy current technology with frequency ranges up to 100 MHz made it possible to extend the classical fields of application even towards less conductive materials like CFRP [2][3](Table 2). It turns out that RF eddy current technology on CFRP generates a growing number of valuable information for comprehensive material diagnostic. Both permittivity and conductivity of CFRP influence the complex impedance measured with RF eddy current devices. The electrical conductivity contains information about fiber texture like orientations, gaps or undulations in a multilayered material. The permittivity characterization influenced by dielectric properties allows the determination of local curing defects on CFRP e.g. hot spots, thermal impacts or polymer degradation. An explanation for that effect is seen in the measurement frequency range and the capacitive structure of the carbon rovings. Using radio wave frequencies for testing, the effect of displacement currents cannot be neglected anymore. The capacitive structures formed by the carbon rovings is supposed to further strengthen the dielectric influences on eddy current measurement signal [3]. This report gives an overview of several realized applications and should be understood as a general introduction of CFRP testing by HF Radio Wave techniques

Increased neutralization and IgG epitope identification after MVA-MERS-S booster vaccination against Middle East respiratory syndrome

Vaccine development is essential for pandemic preparedness. We previously conducted a Phase 1 clinical trial of the vector vaccine candidate MVA-MERS-S against the Middle East respiratory syndrome coronavirus (MERS-CoV), expressing its full spike glycoprotein (MERS-CoV-S), as a homologous two-dose regimen (Days 0 and 28). Here, we evaluate a third vaccination with MVA-MERS-S in a subgroup of trial participants one year after primary immunization. A booster vaccination with MVA-MERS-S is safe and well-tolerated. Both binding and neutralizing anti-MERS-CoV antibody titers increase substantially in all participants and exceed maximum titers observed after primary immunization more than 10-fold. We identify four immunogenic IgG epitopes, located in the receptor-binding domain (RBD, n=1) and the S2 subunit (n=3) of MERS-CoV-S. The level of baseline anti-human coronavirus antibody titers does not impact the generation of anti-MERS-CoV antibody responses. Our data support the rationale of a booster vaccination with MVA-MERS-S and encourage further investigation in larger trials