Ebola hemorrhagic fever, also known as Ebola virus disease or EVD, is one of the most dangerous viral diseases in humans and animals. In this open-label, dose-escalation clinical trial, we assessed the safety, side effects, and immunogenicity of a novel, heterologous prime-boost vaccine against Ebola, which was administered in 2 doses to 84 healthy adults of both sexes between 18 and 55 years. The vaccine consists of live-attenuated recombinant vesicular stomatitis virus (VSV) and adenovirus serotype-5 (Ad5) expressing Ebola envelope glycoprotein. The most common adverse event was pain at the injection site, although no serious adverse events were reported. The vaccine did not significantly impact blood, urine, and immune indices. Seroconversion rate was 100 %. Antigen-specific IgG geometric mean titer at day 42 was 3,277 (95 % confidence interval 2,401–4,473) in volunteers immunized at full dose. Neutralizing antibodies were detected in 93.1 % of volunteers immunized at full dose, with geometric mean titer 20. Antigen-specific response in peripheral blood mononuclear cells was also detected in 100 % of participants, as well as in CD4+ and CD8+ T cells in 82.8 % and 58.6 % of participants vaccinated at full dose, respectively. The data indicate that the vaccine is safe and induces strong humoral and cellular immune response in up to 100 % of healthy adult volunteers, and provide a rationale for testing efficacy in Phase III trials. Indeed, the strong immune response to the vaccine may elicit long-term protection. This trial was registered with grls.rosminzdrav.ru (No. 495*), and with zakupki.gov.ru (No. 0373100043215000055).

We consider the mathematical background of the wavefront sensor type that is widely used in Adaptive Optics systems for astronomy, microscopy, and ophthalmology. The theoretical analysis of the pyramid sensor forward operators presented in this paper is aimed at a subsequent development of fast and stable algorithms for wavefront reconstruction from data of this sensor type. In our analysis we allow the sensor to be utilized in both the modulated and non-modulated fashion. We derive detailed mathematical models for the pyramid sensor and the physically simpler roof wavefront sensor as well as their various approximations. Additionally, we calculate adjoint operators which build preliminaries for the application of several iterative mathematical approaches for solving inverse problems such as gradient based algorithms, Landweber iteration or Kaczmarz methods.

We present a fast method for the wavefront reconstruction from pyramid wavefront sensor (P-WFS) measurements. The method is based on an analytical relation between pyramid and Shack-Hartmann sensor (SH-WFS) data. The algorithm consists of two steps--a transformation of the P-WFS data to SH data, followed by the application of cumulative reconstructor with domain decomposition, a wavefront reconstructor from SH-WFS measurements. The closed loop simulations confirm that our method provides the same quality as the standard matrix vector multiplication method. A complexity analysis as well as speed tests confirm that the method is very fast. Thus, the method can be used on extremely large telescopes, e.g., for eXtreme adaptive optics systems.

The European Extremely Large Telescope (ELT) is a 39 m large, ground-based optical and near-to mid-infrared telescope under construction in the Chilean Atacama desert. Operation is planned to start around the middle of the next decade. All first light instruments will come with wavefront sensing devices that allow control of the ELT's intrinsic M4 and M5 wavefront correction units, thus building an adaptive optics (AO) system. To take advantage of the ELT's optical performance, full diffraction-limited operation is required and only a high performance AO system can deliver this. Further technically challenging requirements for the AO come from the exoplanet research field, where the task to resolve the very small angular separations between host star and planet, has also to take into account the high-contrast ratio between the two objects. We present in detail the results of our simulations and their impact on high-contrast imaging in order to find the optimal wavefront sensing device for the METIS instrument. METIS is the mid-infrared imager and spectrograph for the ELT with specialised high-contrast, coronagraphic imaging capabilities, whose performance strongly depends on the AO residual wavefront errors. We examined the sky and target sample coverage of a generic wavefront sensor in two spectral regimes, visible and near-infrared, to pre-select the spectral range for the more detailed wavefront sensor type analysis. We find that the near-infrared regime is the most suitable for METIS. We then analysed the performance of Shack-Hartmann and pyramid wavefront sensors under realistic conditions at the ELT, did a balancing with our scientific requirements, and concluded that a pyramid wavefront sensor is the best choice for METIS. For this choice we additionally examined the impact of noncommon path aberrations, of vibrations, and the long-term stability of the SCAO system including high-contrast imaging performance.Keywords Single conjugate adaptive optics · SCAO · ELT · Pyramid wavefront sensor · Shack-Hartmann wavefront sensor · Fragmented pupil · Low wind effect · Non-common path aberrations · High-contrast imaging

The generation of Extremely Large Telescopes (ELTs) with mirror diameters up to 40 m has thick secondary mirror support structures (also known as spider legs), which cause difficulties in the wavefront reconstruction process. These spider legs create areas where the information of the phase is disconnected on the wavefront sensor detector, leading to pupil fragmentation and a loss of data on selected subapertures. The effects on wavefront reconstruction are differential pistons between segmented areas, leading to poor wavefront reconstruction. The resulting errors make the majority of existing control algorithms unfeasible for telescope systems having spider legs incorporated. A solution, named the split approach, is presented, which suggests to separate reconstruction of segment piston modes from the rest of the wavefront. Further, two methods are introduced for the direct reconstruction of the segment pistons. Due to the separate handling of the piston offsets on the segments, the split approach makes any of the existing phase reconstruction algorithms developed for nonsegmented pupils suitable for wavefront control in the presence of telescope spiders. We present end-to-end simulation results showing accurate, stable, and extremely fast wavefront reconstruction for the first light instrument mid-infrared ELT imager and spectograph of the ELT that is currently under construction.

In this paper, we address the inverse problem of fast, stable, and high-quality wavefront reconstruction from pyramid wavefront sensor data for Adaptive Optics systems on Extremely Large Telescopes. For solving the indicated problem we apply well-known iterative mathematical algorithms, namely conjugate gradient, steepest descent, Landweber, Landweber-Kaczmarz and steepest descent-Kaczmarz iteration based on theoretical studies of the pyramid wavefront sensor. We compare the performance (in terms of correction quality and speed) of these algorithms in end-to-end numerical simulations of a closed adaptive loop. The comparison is performed in the context of a high-order SCAO system for METIS, one of the first-light instruments currently under design for the Extremely Large Telescope. We show that, though being iterative, the analyzed algorithms, when applied in the studied context, can be implemented in a very efficient manner, which reduces the related computational effort significantly. We demonstrate that the suggested analytically developed approaches involving iterative algorithms provide comparable quality to standard matrix-vector-multiplication methods while being computationally cheaper.

In this paper, we present two novel algorithms for wavefront reconstruction from pyramid-type wavefront sensor data. An overview of the current state-of-the-art in the application of pyramid-type wavefront sensors shows that the novel algorithms can be applied in various scientific fields such as astronomy, ophthalmology, and microscopy. Assuming a computationally very challenging setting corresponding to the extreme adaptive optics (XAO) on the European Extremely Large Telescope, we present the results of the performed end-to-end simulations and compare the achieved AO correction quality (in terms of the long-exposure Strehl ratio) to other methods, such as matrix-vector multiplication and preprocessed cumulative reconstructor with domain decomposition. Also, we provide a comparison in terms of applicability and computational complexity and closed-loop performance of our novel algorithms to other methods existing for this type of sensor.

Pyramid wavefront sensors are planned to be a part of many instruments that are currently under development for the extremely large telescopes (ELT). The unprecedented scales of the upcoming ELT-era instruments are inevitably connected with serious challenges for wavefront reconstruction and control algorithms. Apart from the huge number of correcting elements to be controlled in real-time, real-life features such as the segmentation of the telescope pupil, the low wind effect, the nonlinearity of the pyramid sensor, and the noncommon path aberrations will have a significantly larger impact on the imaging quality in the ELT framework than they ever had before. We summarize various kinds of wavefront reconstruction algorithms for the pyramid wavefront sensor. Based on several forward models, different algorithms were developed in the last decades for linear and nonlinear wavefront correction. The core ideas of the algorithms are presented, and a detailed comparison of the presented methods with respect to underlying pyramid sensor models, computational complexities, and reconstruction qualities is given. In addition, we review the existing and possible solutions for the above-named real-life phenomena. At the same time, directions for further investigations are sketched.