Use of the MultiNest algorithm for gravitational wave data analysis

We describe an application of the MultiNest algorithm to gravitational wave data analysis. MultiNest is a multimodal nested sampling algorithm designed to efficiently evaluate the Bayesian evidence and return posterior probability densities for likelihood surfaces containing multiple secondary modes. The algorithm employs a set of live points which are updated by partitioning the set into multiple overlapping ellipsoids and sampling uniformly from within them. This set of live points climbs up the likelihood surface through nested iso-likelihood contours and the evidence and posterior distributions can be recovered from the point set evolution. The algorithm is model-independent in the sense that the specific problem being tackled enters only through the likelihood computation, and does not change how the live point set is updated. In this paper, we consider the use of the algorithm for gravitational wave data analysis by searching a simulated LISA data set containing two non-spinning supermassive black hole binary signals. The algorithm is able to rapidly identify all the modes of the solution and recover the true parameters of the sources to high precision.Comment: 18 pages, 4 figures, submitted to Class. Quantum Grav; v2 includes various changes in light of referee's comment

Phosphorylation of MCPH1 isoforms during mitosis followed by isoform‐specific degradation by APC/C‐CDH1

Microcephalin‐1 (MCPH1) exists as 2 isoforms that regulate cyclin‐dependent kinase‐1 activation and chromosome condensation during mitosis, with MCPH1 mutations causing primary microcephaly. MCPH1 is also a tumor suppressor protein, with roles in DNA damage repair/checkpoints. Despite these important roles, there is little information on the cellular regulation of MCPH1. We show that both MCPH1 isoforms are phosphorylated in a cyclin‐dependent kinase‐1–dependent manner in mitosis and identify several novel phosphorylation sites. Upon mitotic exit, MCPH1 isoforms were degraded by the anaphase‐promoting complex/cyclosome–CDH1 E3 ligase complex. Anaphase‐promoting complex/cyclosome–CDH1 target proteins generally have D‐Box or KEN‐Box degron sequences. We found that MCPH1 isoforms are degraded independently, with the long isoform degradation being D‐Box dependent, whereas the short isoform was KEN‐Box dependent. Our research identifies several novel mechanisms regulating MCPH1 and also highlights important issues with several commercial MCPH1 antibodies, with potential relevance to previously published data.—Meyer, S. K., Dunn, M., Vidler, D. S., Porter, A., Blain, P. G., Jowsey, P. A. Phosphorylation of MCPH1 isoforms during mitosis followed by isoform‐specific degradation by APC/C‐CDH1. FASEB J. 33, 2796–2808 (2019). www.fasebj.or

High-temperature ceramic matrix composites using microwave enhanced chemical vapor infiltration

To deliver the next generation of aerospace propulsion systems, major modifications to the materials used and their manufacture are required. High-temperature ceramic fibre reinforced ceramic matrix composites (HT-CMCs), specifically SiCf/SiC, have been identified as potential candidates to operate in the hostile aero-thermo-chemical environments experienced in service without compromising structural integrity, whilst keeping mass at a premium. Presently a lack of notably higher temperature properties and durability compared to Ni-super alloys, combined with high manufacturing costs, is preventing widespread utilisation of these composites. Current advanced manufacturing techniques are able to produce these HT-CMCs, which are starting to come into service but all of these techniques introduce compromising features, such as a residual silicon phase, thermal stresses or micro cracking in the matrix microstructure. One of these advanced methods, chemical vapour infiltration (CVI), is an effective manufacturing route capable of creating near fully dense components with an extremely refined microstructure with little or no preform degradation and minimal residual stresses. CVI’s challenges, however, are three fold; i) processing uses isothermal heating rates so batch production times are typically 2 – 3 months; ii) premature pore closure results in a need for repeated machining stages to re-open the closed channels, which reduces process efficiency to between 5-10%; iii) as a consequence of the previous two points, associated costs are very high and the product expensive. Microwave energy (MCVI) has been proposed as a potential solution to heat the SiC fibre preform for CVI; it produces a favourable inverse temperature profile, meaning the temperature is hottest at the centre of the component in contrast to conventional CVI. This inverse profile initiates densification at the centre of the sample, thus avoiding surface porosity closure. It is expected that the use of a microwave-enhanced CVI processing routes could yield near fully dense products in as little as 72 – 96 hours. This poster presents an update on the forming and characterising of the SiC matrix inside the SiC fabric preform (the latter made of Tyranno ZMI, UBE industries) using the MCVI technique. Kinetics, composition, densification profile, morphology and mechanism of growth of the SiC matrix have all been observed and analysed using a suite of characterisation techniques to see the effect of changing the processing variables. Transmission electron microscopy (TEM) and high resolution scanning electron microscopy (SEM) have been used to observe the degree of crystallinity of the resulting SiC and more specifically the grain growth mechanism and thus the resulting morphology. Wave dispersive spectroscopy (WDS) and Raman has been used to determine the (consistently near stoichiometric) Si to C ratio with an accuracy of ±2% due to a small contribution from traces of oxygen present, the results corroborating the data obtained using the TEM. Raman identified the deposit as ß-SiC and, after further analysis, a number of common polytopes were found including 3C, 6H/15R and 4H. Presented results suggest MCVI is a viable method of producing SiC composites that are potentially suitable for the next generation of aerospace material, though a better understanding of the extent to which full densification can be achieved is still required

Synthesis of 4,5-diazaspiro[2.3]hexanes and 1,2-diazaspiro[3.3]heptanes as hexahydropyridazine analogues

4,5-Diazaspiro[2.3]hexanes are made by dihalocarbene addition across the exocyclic double bond of readily accessible 3-alkylidene-1,2-diazetidines. Using difluorocarbene, generated from TMSCF3/NaI, these spirocycles were produced in yields up to 97% by stereospecific addition across the alkene. Lower yields (up to 64%) were observed using more reactive dichlorocarbene, due to competitive insertion of the carbene into the N–N bond. Larger 1,2-diazaspiro[3.3]heptanes are produced by [2+2] cycloaddition of 3-alkylidene-1,2-diazetidines with tetracyanoethylene (TCNE) in up to 99% yield. These additions work with di-, tri- and tetrasubstituted alkenes, offering a practical route to rigidified analogues of the medicinally important hexahydropyridazines

Barrier-to-autointegration factor 1 protects against a basal cGAS-STING response

Although the pathogen recognition receptor pathways that activate cell-intrinsic antiviral responses are well delineated, less is known about how the host regulates this response to prevent sustained signaling and possible immune-mediated damage. Using a genome-wide CRISPR-Cas9 screening approach to identify host factors that modulate interferon-stimulated gene (ISG) expression, we identified the DNA binding protein Barrier-to-autointegration factor 1 (Banf1), a previously described inhibitor of retrovirus integration, as a modulator of basal cell-intrinsic immunity. Ablation of Banf1 by gene editing resulted in chromatin activation near host defense genes with associated increased expression of ISGs, includin

Space Environments and Spacecraft Effects Organization Concept

The National Aeronautics and Space Administration (NASA) is embarking on a course to expand human presence beyond Low Earth Orbit (LEO) while also expanding its mission to explore the solar system. Destinations such as Near Earth Asteroids (NEA), Mars and its moons, and the outer planets are but a few of the mission targets. Each new destination presents an opportunity to increase our knowledge of the solar system and the unique environments for each mission target. NASA has multiple technical and science discipline areas specializing in specific space environments disciplines that will help serve to enable these missions. To complement these existing discipline areas, a concept is presented focusing on the development of a space environments and spacecraft effects (SENSE) organization. This SENSE organization includes disciplines such as space climate, space weather, natural and induced space environments, effects on spacecraft materials and systems and the transition of research information into application. This space environment and spacecraft effects organization will be composed of Technical Working Groups (TWG). These technical working groups will survey customers and users, generate products, and provide knowledge supporting four functional areas: design environments, engineering effects, operational support, and programmatic support. The four functional areas align with phases in the program mission lifecycle and are briefly described below. Design environments are used primarily in the mission concept and design phases of a program. Engineering effects focuses on the material, component, sub-system and system-level selection and the testing to verify design and operational performance. Operational support provides products based on real time or near real time space weather to mission operators to aid in real time and near-term decision-making. The programmatic support function maintains an interface with the numerous programs within NASA, other federal government agencies, and the commercial sector to ensure that communications are well established and the needs of the programs are being met. The programmatic support function also includes working in coordination with the program in anomaly resolution and generation of lessons learned documentation. The goal of this space environment and spacecraft effects organization is to develop decision-making tools and engineering products to support all mission phases from mission concept through operations by focusing on transitioning research to application. Products generated by this space environments and effects application are suitable for use in anomaly investigations. This paper will describe the scope of the TWGs and their relationship to the functional areas, and discuss an organizational structure for this space environments and spacecraft effects organization

Business Models in a New Digital Culture: The Open Long Tail Model

New business models are emerging in global markets. Quirky is producing new products designed and developed by the community and finally produced by the 3D printing technology. Google gives his glasses to different developers who build up their own applications. Kickstarter finds the funders by the use of the crowd, paying them back with the future products. Employees, funders, customers and partners do not play a stable role with the organization but revolve around it using different form of collaborations related to the organization’s needs. In this scenario business like Amazon find out their own achievement feeding up different customers’ needs