New design of electrostatic mirror actuators for application in high-precision interferometry

We describe a new geometry for electrostatic actuators to be used in sensitive laser interferometers, suited for prototype and table top experiments related to gravitational wave detection with mirrors of 100 g or less. The arrangement consists of two plates at the sides of the mirror (test mass), and therefore does not reduce its clear aperture as a conventional electrostatic drive (ESD) would do. Using the sample case of the AEI-10 m prototype interferometer, we investigate the actuation range and the influence of the relative misalignment of the ESD plates with respect to the test mass. We find that in the case of the AEI-10 m prototype interferometer, this new kind of ESD could provide a range of 0.28 μm when operated at a voltage of 1 kV. In addition, the geometry presented is shown to provide a reduction factor of about 100 in the magnitude of the actuator motion coupling to the test mass displacement. We show that therefore in the specific case of the AEI-10 m interferometer, it is possible to mount the ESD actuators directly on the optical table without spoiling the seismic isolation performance of the triple stage suspension of the main test masses

Control sideband generation for dual-recycled laser interferometric gravitational wave detectors

We present a discussion of the problems associated with generation of multiple control sidebands for length sensing and control of dual-recycled, cavity-enhanced Michelson interferometers and the motivation behind more complicated sideband generation methods. We focus on the Mach–Zehnder interferometer as a topological solution to the problem and present results from tests carried out at the Caltech 40 m prototype gravitational wave detector. The consequences for sensing and control for advanced interferometry are discussed, as are the implications for future interferometers such as Advanced LIGO

Demonstration of detuned dual recycling at the Garching 30m laser interferometer

Dual recycling is an advanced optical technique to enhance the signal-to-noise ratio of laser interferometric gravitational wave detectors in a limited bandwidth. To optimise the center of this band with respect to Fourier frequencies of expected gravitational wave signals detuned dual recycling has to be implemented. We demonstrated detuned dual recycling on a fully suspended 30m prototype interferometer. A control scheme that allows to tune the detector to different frequencies will be outlined. Good agreement between the experimental results and numerical simulations has been achieved.Comment: 9 page

Optimal time-domain combination of the two calibrated output quadratures of GEO 600

GEO 600 is an interferometric gravitational wave detector with a 600 m arm-length and which uses a dual-recycled optical configuration to give enhanced sensitivity over certain frequencies in the detection band. Due to the dual-recycling, GEO 600 has two main output signals, both of which potentially contain gravitational wave signals. These two outputs are calibrated to strain using a time-domain method. In order to simplify the analysis of the GEO 600 data set, it is desirable to combine these two calibrated outputs to form a single strain signal that has optimal signal-to-noise ratio across the detection band. This paper describes a time-domain method for doing this combination. The method presented is similar to one developed for optimally combining the outputs of two colocated gravitational wave detectors. In the scheme presented in this paper, some simplifications are made to allow its implementation using time-domain methods

Birefringence-induced losses in interferometers

In interferometers one conceivable loss mechanism is depolarization of the light by inherent or thermally induced birefringence in optical substrates or coatings. The magnitude of this effect is determined quantitatively and compared with the losses due to thermal lensing

C1 metabolism and CVD outcomes in older adults

CVD is the most common cause of death in people over 65 years. This review considers the latest evidence for a potential protective effect of C1 donors (folate and the metabolically related B-vitamins) in CVD. Such an effect may or may not be mediated via the role of these nutrients in maintaining plasma homocysteine concentrations within a desirable range. Despite predictions from epidemiological studies that lowering plasma homocysteine would reduce cardiovascular risk, several secondary prevention trials in at-risk patients published since 2004 have failed to demonstrate a benefit of homocysteine-lowering therapy with B-vitamins on CVD events generally. All these trials were performed in CVD patients with advanced disease; thus current evidence suggests that intervention with high-dose folic acid is of no benefit in preventing another event, at least in the case of heart disease. The evidence at this time, however, is stronger for stroke, with meta-analyses of randomised trials showing that folic acid reduces the risk of stroke, particularly in people with no history of stroke. Genetic studies provide convincing evidence to support a causal relationship between sub-optimal B-vitamin status and CVD. People homozygous for the common C677T variant in the gene encoding the folate-metabolising enzyme, methylenetetrahydrofolate reductase (MTHFR), typically have a 14–21% higher risk of CVD. Apart from folate, riboflavin is required as a co-factor for MTHFR. New evidence shows that riboflavin intervention results in marked lowering of blood pressure, specifically in patients with the MTHFR 677TT genotype. This novel gene–nutrient interaction may provide insights as to the mechanism that links C1 metabolism with CVD outcomes.</jats:p

How reliable are Chinese hamster ovary (CHO) cell genome-scale metabolic models?

Genome-scale metabolic models (GEMs) possess the power to revolutionize bioprocess and cell line engineering workflows thanks to their ability to predict and understand whole-cell metabolism in silico. Despite this potential, it is currently unclear how accurately GEMs can capture both intracellular metabolic states and extracellular phenotypes. Here, we investigate this knowledge gap to determine the reliability of current Chinese hamster ovary (CHO) cell metabolic models. We introduce a new GEM, iCHO2441, and create CHO-S and CHO-K1 specific GEMs. These are compared against iCHO1766, iCHO2048, and iCHO2291. Model predictions are assessed via comparison with experimentally measured growth rates, gene essentialities, amino acid auxotrophies, and 13C intracellular reaction rates. Our results highlight that all CHO cell models are able to capture extracellular phenotypes and intracellular fluxes, with the updated GEM outperforming the original CHO cell GEM. Cell line-specific models were able to better capture extracellular phenotypes but failed to improve intracellular reaction rate predictions in this case. Ultimately, this work provides an updated CHO cell GEM to the community and lays a foundation for the development and assessment of next-generation flux analysis techniques, highlighting areas for model improvements

Genome-scale models as a vehicle for knowledge transfer from microbial to mammalian cell systems

With the plethora of omics data becoming available for mammalian cell and, increasingly, human cell systems, Genome-scale metabolic models (GEMs) have emerged as a useful tool for their organisation and analysis. The systems biology community has developed an array of tools for the solution, interrogation and customisation of GEMs as well as algorithms that enable the design of cells with desired phenotypes based on the multi-omics information contained in these models. However, these tools have largely found application in microbial cells systems, which benefit from smaller model size and ease of experimentation. Herein, we discuss the major outstanding challenges in the use of GEMs as a vehicle for accurately analysing data for mammalian cell systems and transferring methodologies that would enable their use to design strains and processes. We provide insights on the opportunities and limitations of applying GEMs to human cell systems for advancing our understanding of health and disease. We further propose their integration with data-driven tools and their enrichment with cellular functions beyond metabolism, which would, in theory, more accurately describe how resources are allocated intracellularly