Promotion of Homologous Recombination and Genomic Stability by RAD51AP1 via RAD51 Recombinase Enhancement

Homologous recombination (HR) repairs chromosome damage and is indispensable for tumor suppression in humans. RAD51 mediates the DNA strand-pairing step in HR. RAD51 associated protein 1 (RAD51AP1) is a RAD51-interacting protein whose function has remained elusive. Knockdown of RAD51AP1 in human cells by RNA interference engenders sensitivity to different types of genotoxic stress, and RAD51AP1 is epistatic to the HR protein XRCC3. Moreover, RAD51AP1-depleted cells are impaired for the recombinational repair of a DNA double-strand break and exhibit chromatid breaks both spontaneously and upon DNA-damaging treatment. Purified RAD51AP1 binds both dsDNA and a D loop structure and, only when able to interact with RAD51, greatly stimulates the RAD51-mediated D loop reaction. Biochemical and cytological results show that RAD51AP1 functions at a step subsequent to the assembly of the RAD51-ssDNA nucleoprotein filament. Our findings provide evidence that RAD51AP1 helps maintain genomic integrity via RAD51 recombinase enhancement.

Effect of hydrophilicity of carbon nanotube arrays on the release rate and activity of recombinant human bone morphogenetic protein-2

Novel nanostructures such as vertically aligned carbon nanotube (CNT) arrays have received increasing interest as drug delivery carriers. In the present study, two CNT arrays with extreme surface wettabilities are fabricated and their effects on the release of recombinant human bone morphogenetic protein-2 (rhBMP-2) are investigated. It is found that the superhydrophilic arrays retained a larger amount of rhBMP-2 than the superhydrophobic ones. Further use of a poloxamer diffusion layer delayed the initial burst and resulted in a greater total amount of rhBMP-2 released from both surfaces. In addition, rhBMP-2 bound to the superhydrophilic CNT arrays remained bioactive while they denatured on the superhydrophobic surfaces. These results are related to the combined effects of rhBMP-2 molecules interacting with poloxamer and the surface, which could be essential in the development of advanced carriers with tailored surface functionalities.

A control theoretic paradigm for cell signaling networks : a simple complexity for a sensitive robustness

The fields of molecular biology and cell biology are being flooded with complex genomic and proteomic datasets of large dimensions. We now recognize that each molecule in the cell and tissue can no longer be viewed as an isolated entity. Instead, each molecule must be considered as one member of an interacting network. Consequently, there is an urgent need for mathematical models to understand the behavior of cell signaling networks in health and in disease.

Self-interaction of magnetoplasma surface waves at a plasma-metal boundary

We investigate nonlinear self-interacting magnetoplasma surface waves (SW) propagating perpendicular to an external magnetic field at a plasma-metal boundary. We obtain the nonlinear dispersion equation and nonlinear Schroedinger equation for the envelope field of the SW. The solution to this equation is studied with regard to stability relative to longitudinal and transverse perturbations.

Perceptions of document relevance

This article presents a study of how humans perceive and judge the relevance of documents. Humans are adept at making reasonably robust and quick decisions about what information is relevant to them, despite the ever increasing complexity and volume of their surrounding information environment. The literature on document relevance has identified various dimensions of relevance (e.g., topicality, novelty, etc.), however little is understood about how these dimensions may interact. We performed a crowdsourced study of how human subjects judge two relevance dimensions in relation to document snippets retrieved from an internet search engine. The order of the judgment was controlled. For those judgments exhibiting an order effect, a q–test was performed to determine whether the order effects can be explained by a quantum decision model based on incompatible decision perspectives. Some evidence of incompatibility was found which suggests incompatible decision perspectives is appropriate for explaining interacting dimensions of relevance in such instances.

Tailoring of ion species composition in complex plasmas with charge exchange collisions

A generic approach towards tailoring of ion species composition in reactive plasmas used for nanofabrication of various functional nanofilms and nanoassemblies, based on a simplified model of a parallel-plate rf discharge, is proposed. The model includes an idealized reactive plasma containing two neutral and two ionic species interacting via charge exchange collisions in the presence of a microdispersed solid component. It is shown that the number densities of the desired ionic species can be efficiently managed by adjusting the dilution of the working gas in a buffer gas, rates of electron impact ionization, losses of plasma species on the discharge walls, and surfaces of fine particles, charge exchange rates, and efficiency of three-body recombination processes in the plasma bulk. The results are relevant to the plasma-aided nanomanufacturing of ordered patterns of carbon nanotip and nanopyramid microemitters.

Functional role for senataxin, defective in ataxia oculomotor apraxia type 2, in transcriptional regulation

Ataxia oculomotor apraxia type 2 (AOA2) is an autosomal recessive neurodegenerative disorder characterized by cerebellar ataxia and oculomotor apraxia. The gene mutated in AOA2, SETX, encodes senataxin, a putative DNA/RNA helicase which shares high homology to the yeast Sen1p protein and has been shown to play a role in the response to oxidative stress. To investigate further the function of senataxin, we identified novel senataxin-interacting proteins, the majority of which are involved in transcription and RNA processing, including RNA polymerase II. Binding of RNA polymerase II to candidate genes was significantly reduced in senataxin deficient cells and this was accompanied by decreased transcription of these genes, suggesting a role for senataxin in the regulation/modulation of transcription. RNA polymerase II-dependent transcription termination was defective in cells depleted of senataxin in keeping with the observed interaction of senataxin with poly(A) binding proteins 1 and 2. Splicing efficiency of specific mRNAs and alternate splice-site selection of both endogenous genes and artificial minigenes were altered in senataxin depleted cells. These data suggest that senataxin, similar to its yeast homolog Sen1p, plays a role in coordinating transcriptional events, in addition to its role in DNA repair.

Using enterprise information architecture methods to model wicked problems in information systems design research

Design Science is the process of solving ‘wicked problems’ through designing, developing, instantiating, and evaluating novel solutions (Hevner, March, Park and Ram, 2004). Wicked problems are described as agent finitude in combination with problem complexity and normative constraint (Farrell and Hooker, 2013). In Information Systems Design Science, determining that problems are ‘wicked’ differentiates Design Science research from Solutions Engineering (Winter, 2008) and is a necessary part of proving the relevance to Information Systems Design Science research (Hevner, 2007; Iivari, 2007). Problem complexity is characterised as many problem components with nested, dependent and co-dependent relationships interacting through multiple feedback and feed-forward loops. Farrell and Hooker (2013) specifically state for wicked problems “it will often be impossible to disentangle the consequences of specific actions from those of other co-occurring interactions”. This paper discusses the application of an Enterprise Information Architecture modelling technique to disentangle the wicked problem complexity for one case. It proposes that such a modelling technique can be applied to other wicked problems and can lay the foundations for proving relevancy to DSR, provide solution pathways for artefact development, and aid to substantiate those elements required to produce Design Theory.

Yhh1p/Cft1p directly links poly(A) site recognition and RNA polymerase II transcription termination

RNA polymerase II (pol II) transcription termination requires co‐transcriptional recognition of a functional polyadenylation signal, but the molecular mechanisms that transduce this signal to pol II remain unclear. We show that Yhh1p/Cft1p, the yeast homologue of the mammalian AAUAAA interacting protein CPSF 160, is an RNA‐binding protein and provide evidence that it participates in poly(A) site recognition. Interestingly, RNA binding is mediated by a central domain composed of predicted β‐propeller‐forming repeats, which occurs in proteins of diverse cellular functions. We also found that Yhh1p/Cft1p bound specifically to the phosphorylated C‐terminal domain (CTD) of pol II in vitro and in a two‐hybrid test in vivo. Furthermore, transcriptional run‐on analysis demonstrated that yhh1 mutants were defective in transcription termination, suggesting that Yhh1p/Cft1p functions in the coupling of transcription and 3′‐end formation. We propose that direct interactions of Yhh1p/Cft1p with both the RNA transcript and the CTD are required to communicate poly(A) site recognition to elongating pol II to initiate transcription termination.

Solid-state assemblies and optical properties of conjugated oligomers combining fluorene and thiophene units

Two conjugated oligomers, representing elementary segments of fluorene-thiophene copolymers, are compared in terms of the microscopic morphology and the optical properties of thin deposits. The atomic force microscopy morphological data and the solid-state absorption and emission spectra are interpreted in terms of the assembly of the conjugated molecules. The compound with a terthiophene central unit and fluorene end-groups shows well-defined monolayer-by-monolayer assembly into micrometer-long stripe-like structures, with a crystalline herringbone-type organization within the monolayers. Polarized confocal microscopy indicates a strong orientation of the crystalline domains within the stripes. In contrast, the compound with a terfluorene central unit and thiophene end groups forms no textured aggregates and the optical spectra in the solid-state are very similar to those recorded in solution, suggesting that the molecules interact only weakly in the solid. The difference in behaviour between the two compounds most probably originates from their different capability to form densely-packed assemblies of interacting π-systems.

A comparison of factors influencing perceived risk by French and Australian cyclists and drivers

Differences in the levels of risk perceived by cyclists and car drivers may contribute to the dangers in their interactions. Levels of perceived risk have been shown to vary according to personal and environmental factors and between countries. Cycling rates in France are higher than in Australia, particularly among women. This study investigated whether cultural differences between France and Australia are reflected in perceived risks for experienced adult cyclists and drivers in the two countries. In online surveys, regular cyclists (France 336, Australia 444) and drivers (France 92, Australia 151) were asked to rate the level of risk in six situations: failure to yield; going through a red light; not signalling when turning; swerving; tail-gating; and not checking traffic. The effects of type of interacting vehicle and participant type on perceived risk were similar in France and Australia. However, the influence of responsibility for the risky behaviour differed according to participant type, type of situation and nationality. When the bicycle rider committed the road rule violation, Australian cyclists and drivers gave higher risk ratings than French cyclists and drivers. In both countries, cyclists rated themselves significantly higher than drivers on the perceived control and overconfidence subscales of the perceived skill measure. The French cyclists rated themselves higher than Australian cyclists on these scales, which could be responsible for overall lower perceived risk levels when interacting with a bike. Australian cyclists rated themselves significantly lower than drivers on the incompetence subscale but French cyclists rated themselves higher than drivers. In both countries incompetence scores were positively related to levels of perceived risk. Weekly time was associated with perceived risk in Australia but not in France. Frequency of traffic violations was not associated with perceived risk in either country. In conclusion, levels of perceived risk differed between drivers and cyclists in both countries and were influenced by type of interacting vehicle, experience and perceived skill. However, some differences between the results from the two countries merit further investigation to shed light on potential improvements in safety and cycling participation.

Collective motion of dimers

We consider a discrete agent-based model on a one-dimensional lattice and a two-dimensional square lattice, where each agent is a dimer occupying two sites. Agents move by vacating one occupied site in favor of a nearest-neighbor site and obey either a strict simple exclusion rule or a weaker constraint that permits partial overlaps between dimers. Using indicator variables and careful probability arguments, a discrete-time master equation for these processes is derived systematically within a mean-field approximation. In the continuum limit, nonlinear diffusion equations that describe the average agent occupancy of the dimer population are obtained. In addition, we show that multiple species of interacting subpopulations give rise to advection-diffusion equations. Averaged discrete simulation data compares very well with the solution to the continuum partial differential equation models. Since many cell types are elongated rather than circular, this work offers insight into population-level behavior of collective cellular motion.

Building macroscale models from microscale probabilistic models : a general probabilistic approach for nonlinear diffusion and multispecies phenomena

A discrete agent-based model on a periodic lattice of arbitrary dimension is considered. Agents move to nearest-neighbor sites by a motility mechanism accounting for general interactions, which may include volume exclusion. The partial differential equation describing the average occupancy of the agent population is derived systematically. A diffusion equation arises for all types of interactions and is nonlinear except for the simplest interactions. In addition, multiple species of interacting subpopulations give rise to an advection-diffusion equation for each subpopulation. This work extends and generalizes previous specific results, providing a construction method for determining the transport coefficients in terms of a single conditional transition probability, which depends on the occupancy of sites in an influence region. These coefficients characterize the diffusion of agents in a crowded environment in biological and physical processes.

A random key genetic algorithm for live migration of multiple virtual machines in data centers

Live migration of multiple Virtual Machines (VMs) has become an integral management activity in data centers for power saving, load balancing and system maintenance. While state-of-the-art live migration techniques focus on the improvement of migration performance of an independent single VM, only a little has been investigated to the case of live migration of multiple interacting VMs. Live migration is mostly influenced by the network bandwidth and arbitrarily migrating a VM which has data inter-dependencies with other VMs may increase the bandwidth consumption and adversely affect the performances of subsequent migrations. In this paper, we propose a Random Key Genetic Algorithm (RKGA) that efficiently schedules the migration of a given set of VMs accounting both inter-VM dependency and data center communication network. The experimental results show that the RKGA can schedule the migration of multiple VMs with significantly shorter total migration time and total downtime compared to a heuristic algorithm.

Approximate Bayesian Computation for astronomical model analysis : a case study in galaxy demographics and morphological transformation at high redshift

Approximate Bayesian Computation’ (ABC) represents a powerful methodology for the analysis of complex stochastic systems for which the likelihood of the observed data under an arbitrary set of input parameters may be entirely intractable – the latter condition rendering useless the standard machinery of tractable likelihood-based, Bayesian statistical inference [e.g. conventional Markov chain Monte Carlo (MCMC) simulation]. In this paper, we demonstrate the potential of ABC for astronomical model analysis by application to a case study in the morphological transformation of high-redshift galaxies. To this end, we develop, first, a stochastic model for the competing processes of merging and secular evolution in the early Universe, and secondly, through an ABC-based comparison against the observed demographics of massive (Mgal > 1011 M⊙) galaxies (at 1.5 < z < 3) in the Cosmic Assembly Near-IR Deep Extragalatic Legacy Survey (CANDELS)/Extended Groth Strip (EGS) data set we derive posterior probability densities for the key parameters of this model. The ‘Sequential Monte Carlo’ implementation of ABC exhibited herein, featuring both a self-generating target sequence and self-refining MCMC kernel, is amongst the most efficient of contemporary approaches to this important statistical algorithm. We highlight as well through our chosen case study the value of careful summary statistic selection, and demonstrate two modern strategies for assessment and optimization in this regard. Ultimately, our ABC analysis of the high-redshift morphological mix returns tight constraints on the evolving merger rate in the early Universe and favours major merging (with disc survival or rapid reformation) over secular evolution as the mechanism most responsible for building up the first generation of bulges in early-type discs.