Impact of host DNA and sequencing depth on the taxonomic resolution of whole metagenome sequencing for microbiome analysis

The amount of host DNA poses a major challenge to metagenome analysis. However, there is no guidance on the levels of host DNA, nor on the depth of sequencing needed to acquire meaningful information from whole metagenome sequencing (WMS). Here, we evaluated the impact of a wide range of amounts of host DNA and sequencing depths on microbiome taxonomic profiling using WMS. Synthetic samples with increasing levels of host DNA were created by spiking DNA of a mock bacterial community, with DNA from a mouse-derived cell line. Taxonomic analysis revealed that increasing proportions of host DNA led to decreased sensitivity in detecting very low and low abundant species. Reduction of sequencing depth had major impact on the sensitivity of WMS for profiling samples with 90% host DNA, increasing the number of undetected species. Finally, analysis of simulated datasets with fixed depth of 10 million reads confirmed that microbiome profiling becomes more inaccurate as the level of host DNA increases in a sample. In conclusion, samples with high amounts of host DNA coupled with reduced sequencing depths, decrease WMS coverage for characterization of the microbiome. This study highlights the importance of carefully considering these aspects in the design of WMS experiments to maximize microbiome analyses.This work was supported by European Regional Development Funds (ERDF) funds through the COMPETE 2020 – Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by FCT – Fundação para a Ciência e a Tecnologia (POCI-01-0145-FEDER-032532). JP-M and IP-R have fellowships from FCT (PD/BD/114014/2015 and SFRH/BD/110803/2015, respectively) through Programa Operacional Capital Humano (POCH) and the European Social Fund. JP-M’s have fellowship from the framework of FCT’s Ph.D. Program Biotech Health (Ref. PD/0016/2012)

The FLASHForward Facility at DESY

The FLASHForward project at DESY is a pioneering plasma-wakefield acceleration experiment that aims to produce, in a few centimetres of ionised hydrogen, beams with energy of order GeV that are of quality sufficient to be used in a free-electron laser. The plasma wave will be driven by high-current density electron beams from the FLASH linear accelerator and will explore both external and internal witness-beam injection techniques. The plasma is created by ionising a gas in a gas cell with a multi-TW laser system, which can also be used to provide optical diagnostics of the plasma and electron beams due to the <30 fs synchronisation between the laser and the driving electron beam. The operation parameters of the experiment are discussed, as well as the scientific program.Comment: 19 pages, 9 figure

Optical plasma torch electron bunch generation in plasma wakefield accelerators

A novel, flexible method of witness electron bunch generation in plasma wakefield accelerators is described. A quasistationary plasma region is ignited by a focused laser pulse prior to the arrival of the plasma wave. This localized, shapeable optical plasma torch causes a strong distortion of the plasma blowout during passage of the electron driver bunch, leading to collective alteration of plasma electron trajectories and to controlled injection. This optically steered injection is more flexible and faster when compared to hydro-dynamically controlled gas density transition injection methods

Hot spots and dark current in advanced plasma wakefield accelerators

Dark current can spoil witness bunch beam quality and acceleration efficiency in particle beam-driven plasma wakefield accelerators. In advanced schemes, hot spots generated by the drive beam or the wakefield can release electrons from higher ionization threshold levels in the plasma media. These electrons may be trapped inside the plasma wake and will then accumulate dark current, which is generally detrimental for a clear and unspoiled plasma acceleration process. Strategies for generating clean and robust, dark current free plasma wake cavities are devised and analyzed, and crucial aspects for experimental realization of such optimized scenarios are discussed

Energy-Spread Preservation and High Efficiency in a Plasma-Wakefield Accelerator

Energy-efficient plasma-wakefield acceleration of particle bunches with low energy spread is a promising path to realizing compact free-electron lasers and particle colliders. High efficiency and low energy spread can be achieved simultaneously by strong beam loading of plasma wakefields when accelerating bunches with carefully tailored current profiles [M. Tzoufras et al., Phys. Rev. Lett. 101, 145002 (2008)PRLTAO0031-900710.1103/PhysRevLett.101.145002]. We experimentally demonstrate such optimal beam loading in a nonlinear electron-driven plasma accelerator. Bunches with an initial energy of 1 GeV were accelerated by 45 MeV with an energy-transfer efficiency of (42±4)% at a gradient of 1.3  GV/m while preserving per-mille energy spreads with full charge coupling, demonstrating wakefield flattening at the few-percent level

All-optical density downramp injection in electron-driven plasma wakefield accelerators

Injection of well-defined, high-quality electron populations into plasma waves is a key challenge of plasma wakefield accelerators. Here, we report on the first experimental demonstration of plasma density downramp injection in an electron-driven plasma wakefield accelerator, which can be controlled and tuned in all-optical fashion by mJ-level laser pulses. The laser pulse is directed across the path of the plasma wave before its arrival, where it generates a local plasma density spike in addition to the background plasma by tunnelling ionization of a high ionization threshold gas component. This density spike distorts the plasma wave during the density downramp, causing plasma electrons to be injected into the plasma wave. By tuning the laser pulse energy and shape, highly flexible plasma density spike profiles can be designed, enabling dark current free, versatile production of high-quality electron beams. This in turn permits creation of unique injected beam configurations such as counter-oscillating twin beamlets

Tunable and precise two-bunch generation at FLASHForward

Beam-driven plasma-wakefield acceleration based on external injection has the potential to significantly reduce the size of future accelerators. Stability and quality of the acceleration process substantially depends on the incoming bunch parameters. Precise control of the current profile is essential for optimising energy-transfer efficiency and preserving energy spread. At the FLASHForward facility, driver--witness bunch pairs of adjustable bunch length and separation are generated by a set of collimators in a dispersive section, which enables fs-level control of the longitudinal bunch profile. The design of the collimator apparatus and its commissioning is presented.Comment: 7 pages, 5 figures, to be published in the proceedings of the 4th European Advanced Accelerator Concepts Workshop, 15-21 September 2019, La Biodola Bay, Isola d'Elba, Ital

Willingness to Accept Equals Willingness to Pay for Labor Market Estimates of the Value of Statistical Life

Our research clarifies the conceptual linkages among willingness to pay for additional safety, willingness to accept less safety, and the value of statistical life (VSL). We present econometric estimates that in the important case of workers' decisions concerning exposure to fatal injury risk there is no statistically significant divergence between willingness to accept and willingness to pay. Our focal result contrasts with the literature documenting a considerable asymmetry in tradeoff rates for increases and decreases in risk. An important implication for policy is that it is reasonable to use labor market estimates of VSL as a measure of the willingness to pay for additional safety