The flavin-containing monooxygenase 2 gene (FMO2) of humans, but not of other primates, encodes a truncated, nonfunctional protein

Flavin-containing monooxygenases (FMOs) are NADPH-dependent flavoenzymes that catalyze the oxidation of heteroatom centers in numerous drugs and xenobiotics. FMO2, or "pulmonary" FMO, one of five forms of the enzyme identified in mammals, is expressed predominantly in lung and differs from other FMOs in that it can catalyze the N-oxidation of certain primary alkylamines. We describe here the isolation and characterization of cDNAs for human FMO2. Analysis of the sequence of the cDNAs and of a section of the corresponding gene revealed that the major FMO2 allele of humans encodes a polypeptide that, compared with the orthologous protein of other mammals, lacks 64 amino acid residues from its C terminus. Heterologous expression of the cDNA revealed that the truncated polypeptide was catalytically inactive. The nonsense mutation that gave rise to the truncated polypeptide, a C --> T transition in codon 472, is not present in the FMO2 gene of closely related primates, including gorilla and chimpanzee, and must therefore have arisen in the human lineage after the divergence of the Homo and Pan clades. Possible mechanisms for the fixation of the mutation in the human population and the potential significance of the loss of functional FMO2 in humans are discussed.     

Multiscale computation for bioartificial soft tissues with complex geometries

The mechanical function of soft collagenous tissues is inherently multiscale, with the tissue dimension being in the centimeter length scale and the underlying collagen network being in the micrometer length scale. This paper uses a volume averaging multiscale model to predict the collagen gel mechanics. The model is simulated using a multiscale component toolkit that is capable of dealing with any 3D geometries. Each scale in the multiscale model is treated as an independent component that exchanges the deformation and average stress information through a scale-linking operator. An arterial bifurcation was simulated using the multiscale model, and the results demonstrated that the mechanical response of the soft tissues is strongly sensitive to the network orientation and fiber-to-fiber interactions.     

Mesh generation for confined fusion plasma simulation

XGC1 and M3D-C ¹ are two fusion plasma simulation codes being developed at Princeton Plasma Physics Laboratory. XGC1 uses the particle-in-cell method to simulate gyrokinetic neoclassical physics and turbulence (Chang et al. Phys Plasmas 16(5):056108, 2009; Ku et al. Nucl Fusion 49:115021, 2009; Admas et al. J Phys 180(1):012036, 2009). M3D-\(C^1\) solves the two-fluid resistive magnetohydrodynamic equations with the \(C^1\) finite elements (Jardin J comput phys 200(1):133–152, 2004; Jardin et al. J comput Phys 226(2):2146–2174, 2007; Ferraro and Jardin J comput Phys 228(20):7742–7770, 2009; Jardin J comput Phys 231(3):832–838, 2012; Jardin et al. Comput Sci Discov 5(1):014002, 2012; Ferraro et al. Sci Discov Adv Comput, 2012; Ferraro et al. International sherwood fusion theory conference, 2014). This paper presents the software tools and libraries that were combined to form the geometry and automatic meshing procedures for these codes. Specific consideration has been given to satisfy the mesh configuration and element shape quality constraints of XGC1 and M3D-\(C^1\).     

Collaborative software infrastructure for adaptive multiple model simulation

This paper presents a software infrastructure being developed to support the implementation of adaptive multiple model simulations. The paper first describes an abstraction of single and multiple model simulations into the individual operational components with a focus on the relationships and transformations that relate them. Building on that abstraction, consideration is then given to how adaptively controlled multiple model simulations can be constructed using existing simulation components interacting through functional interfaces. This includes addressing how experts would provide the infrastructure with the needed components and define the relations and transformations needed to interact with other components, and for users to define the simulations they wish to be executed. Next, a discussion of the software environment used to implement the multiple model simulation infrastructure is given. Finally, there is discussion of the implementation, using this infrastructure, of two multiscale and one multiple fidelity model simulation applications.     

Computationally intensive econometrics using a distributed matrix-programming language

This paper reviews the need for powerful computing facilities in econometrics, focusing on concrete problems which arise in financial economics and in macroeconomics. We argue that the profession is being held back by the lack of easy-to-use generic software which is able to exploit the availability of cheap clusters of distributed computers. Our response is to extend, in a number of directions, the well-known matrix-programming interpreted language Ox developed by the first author. We note three possible levels of extensions: (i) Ox with parallelization explicit in the Ox code; (ii) Ox with a parallelized run-time library; and (iii) Ox with a parallelized interpreter. This paper studies and implements the first case, emphasizing the need for deterministic computing in science. We give examples in the context of financial economics and time-series modelling.     

Automated adaptive 3D forming simulation processes

In this study, an automated adaptive mesh control scheme, based on local mesh modifications, is developed for the finite element simulations of 3D metal-forming processes. Error indicators are used to control the mesh discretization errors, and an h-adaptive procedure is conducted. The mesh size field used in the h-adaptive procedure is processed to control the discretization and geometric approximation errors of the evolving workpiece mesh. Industrial problems are investigated to demonstrate the capabilities of the developed scheme.     

Services via mobility portals

This paper examines the importance of mobility portal services and the technologies that will be essential in delivering content over next generation network technologies. A broad range of related issues is discussed, from the devices the service user can employ and the underlying technology and infrastructure required, through to the challenges faced by the providers of such services