Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes

Endometrial carcinoma is the most common gynecological malignancy in the United States. Although most women present with early disease confined to the uterus, the majority of persistent or recurrent tumors are refractory to current chemotherapies. We have identified a total of 11 different FGFR2 mutations in 3/10 (30%) of endometrial cell lines and 19/187 (10%) of primary uterine tumors. Mutations were seen primarily in tumors of the endometrioid histologic subtype (18/115 cases investigated, 16%). The majority of the somatic mutations identified were identical to germline activating mutations in FGFR2 and FGFR3 that cause Apert Syndrome, Beare-Stevenson Syndrome, hypochondroplasia, achondroplasia and SADDAN syndrome. The two most common somatic mutations identified were S252W (in eight tumors) and N550K (in five samples). Four novel mutations were identified, three of which are also likely to result in receptor gain-of-function. Extensive functional analyses have already been performed on many of these mutations, demonstrating they result in receptor activation through a variety of mechanisms. The discovery of activating FGFR2 mutations in endometrial carcinoma raises the possibility of employing anti-FGFR molecularly targeted therapies in patients with advanced or recurrent endometrial carcinoma.

Massively parallel sequencing and analysis of expressed sequence tags in a successful invasive plant

Background Invasive species pose a significant threat to global economies, agriculture and biodiversity. Despite progress towards understanding the ecological factors associated with plant invasions, limited genomic resources have made it difficult to elucidate the evolutionary and genetic factors responsible for invasiveness. This study presents the first expressed sequence tag (EST) collection for Senecio madagascariensis, a globally invasive plant species. Methods We used pyrosequencing of one normalized and two subtractive libraries, derived from one native and one invasive population, to generate an EST collection. ESTs were assembled into contigs, annotated by BLAST comparison with the NCBI non-redundant protein database and assigned gene ontology (GO) terms from the Plant GO Slim ontologies. Key Results Assembly of the 221 746 sequence reads resulted in 12 442 contigs. Over 50 % (6183) of 12 442 contigs showed significant homology to proteins in the NCBI database, representing approx. 4800 independent transcripts. The molecular transducer GO term was significantly over-represented in the native (South African) subtractive library compared with the invasive (Australian) library. Based on NCBI BLAST hits and literature searches, 40 % of the molecular transducer genes identified in the South African subtractive library are likely to be involved in response to biotic stimuli, such as fungal, bacterial and viral pathogens. Conclusions This EST collection is the first representation of the S. madagascariensis transcriptome and provides an important resource for the discovery of candidate genes associated with plant invasiveness. The over-representation of molecular transducer genes associated with defence responses in the native subtractive library provides preliminary support for aspects of the enemy release and evolution of increased competitive ability hypotheses in this successful invasive. This study highlights the contribution of next-generation sequencing to better understanding the molecular mechanisms underlying ecological hypotheses that are important in successful plant invasions.

On the computation and interpretation of auto- and cross-trispectra

This paper discusses the principal domains of auto- and cross-trispectra. It is shown that the cumulant and moment based trispectra are identical except on certain planes in trifrequency space. If these planes are avoided, their principal domains can be derived by considering the regions of symmetry of the fourth order spectral moment. The fourth order averaged periodogram will then serve as an estimate for both cumulant and moment trispectra. Statistics of estimates of normalised trispectra or tricoherence are also discussed.

Computing with motile bio-agents

We describe a model of computation of the parallel type, which we call 'computing with bio-agents', based on the concept that motions of biological objects such as bacteria or protein molecular motors in confined spaces can be regarded as computations. We begin with the observation that the geometric nature of the physical structures in which model biological objects move modulates the motions of the latter. Consequently, by changing the geometry, one can control the characteristic trajectories of the objects; on the basis of this, we argue that such systems are computing devices. We investigate the computing power of mobile bio-agent systems and show that they are computationally universal in the sense that they are capable of computing any Boolean function in parallel. We argue also that using appropriate conditions, bio-agent systems can solve NP-complete problems in probabilistic polynomial time.

Parallel implementation of stochastic simulation for large scale cellular processes

Experimental and theoretical studies have shown the importance of stochastic processes in genetic regulatory networks and cellular processes. Cellular networks and genetic circuits often involve small numbers of key proteins such as transcriptional factors and signaling proteins. In recent years stochastic models have been used successfully for studying noise in biological pathways, and stochastic modelling of biological systems has become a very important research field in computational biology. One of the challenge problems in this field is the reduction of the huge computing time in stochastic simulations. Based on the system of the mitogen-activated protein kinase cascade that is activated by epidermal growth factor, this work give a parallel implementation by using OpenMP and parallelism across the simulation. Special attention is paid to the independence of the generated random numbers in parallel computing, that is a key criterion for the success of stochastic simulations. Numerical results indicate that parallel computers can be used as an efficient tool for simulating the dynamics of large-scale genetic regulatory networks and cellular processes

Robust multidisciplinary UAS design optimisation

There are many applications in aeronautical/aerospace engineering where some values of the design parameters states cannot be provided or determined accurately. These values can be related to the geometry(wingspan, length, angles) and or to operational flight conditions that vary due to the presence of uncertainty parameters (Mach, angle of attack, air density and temperature, etc.). These uncertainty design parameters cannot be ignored in engineering design and must be taken into the optimisation task to produce more realistic and reliable solutions. In this paper, a robust/uncertainty design method with statistical constraints is introduced to produce a set of reliable solutions which have high performance and low sensitivity. Robust design concept coupled with Multi Objective Evolutionary Algorithms (MOEAs) is defined by applying two statistical sampling formulas; mean and variance/standard deviation associated with the optimisation fitness/objective functions. The methodology is based on a canonical evolution strategy and incorporates the concepts of hierarchical topology, parallel computing and asynchronous evaluation. It is implemented for two practical Unmanned Aerial System (UAS) design problems; the flrst case considers robust multi-objective (single disciplinary: aerodynamics) design optimisation and the second considers a robust multidisciplinary (aero structures) design optimisation. Numerical results show that the solutions obtained by the robust design method with statistical constraints have a more reliable performance and sensitivity in both aerodynamics and structures when compared to the baseline design.

Practical improvements to simultaneous computation of multi-view geometry and radial lens distortion

This paper discusses practical issues related to the use of the division model for lens distortion in multi-view geometry computation. A data normalisation strategy is presented, which has been absent from previous discussions on the topic. The convergence properties of the Rectangular Quadric Eigenvalue Problem solution for computing division model distortion are examined. It is shown that the existing method can require more than 1000 iterations when dealing with severe distortion. A method is presented for accelerating convergence to less than 10 iterations for any amount of distortion. The new method is shown to produce equivalent or better results than the existing method with up to two orders of magnitude reduction in iterations. Through detailed simulation it is found that the number of data points used to compute geometry and lens distortion has a strong influence on convergence speed and solution accuracy. It is recommended that more than the minimal number of data points be used when computing geometry using a robust estimator such as RANSAC. Adding two to four extra samples improves the convergence rate and accuracy sufficiently to compensate for the increased number of samples required by the RANSAC process.

An approximate Bayesian computation approach for estimating parameters of complex environmental processes in a cellular automata

Modelling an environmental process involves creating a model structure and parameterising the model with appropriate values to accurately represent the process. Determining accurate parameter values for environmental systems can be challenging. Existing methods for parameter estimation typically make assumptions regarding the form of the Likelihood, and will often ignore any uncertainty around estimated values. This can be problematic, however, particularly in complex problems where Likelihoods may be intractable. In this paper we demonstrate an Approximate Bayesian Computational method for the estimation of parameters of a stochastic CA. We use as an example a CA constructed to simulate a range expansion such as might occur after a biological invasion, making parameter estimates using only count data such as could be gathered from field observations. We demonstrate ABC is a highly useful method for parameter estimation, with accurate estimates of parameters that are important for the management of invasive species such as the intrinsic rate of increase and the point in a landscape where a species has invaded. We also show that the method is capable of estimating the probability of long distance dispersal, a characteristic of biological invasions that is very influential in determining spread rates but has until now proved difficult to estimate accurately.

Microstrip to parallel strip balun as spiral antenna feed

This paper presents the design and implementation of a microstrip to parallel strip balun which are frequently used as balanced antennas feed. This wideband balun transition is composed of a parallel strip which is connected to the spiral antenna and a microstrip line where the width of the ground plane is gradually reduced to eventually resemble the parallel strip. The taper accomplishes the mode and impedance transformation. This balun has significantly improved bandwidth characteristics. The entire circuit was fabricated on RT Duriod 5880 substrate. The circuit designs were simulated and optimised using CST Microwave Studio and the simulated results are compared with the measured results. The back-to-back microstrip to parallel strip has a return loss of better than 10 dB over a wide bandwidth from 1.75 to 15 GHz. The performance of the proposed balun was validated with the spiral antenna. The measured results were compared with the simulated results and it shows that the antenna operates well in wideband frequency range from 2.5 to 15 GHz.

Scheduling Trains with Priorities : a no-wait blocking parallel-machine job-shop scheduling model

The paper investigates train scheduling problems when prioritised trains and non-prioritised trains are simultaneously traversed in a single-line rail network. In this case, no-wait conditions arise because the prioritised trains such as express passenger trains should traverse continuously without any interruption. In comparison, non-prioritised trains such as freight trains are allowed to enter the next section immediately if possible or to remain in a section until the next section on the routing becomes available, which is thought of as a relaxation of no-wait conditions. With thorough analysis of the structural properties of the No-Wait Blocking Parallel-Machine Job-Shop-Scheduling (NWBPMJSS) problem that is originated in this research, an innovative generic constructive algorithm (called NWBPMJSS_Liu-Kozan) is proposed to construct the feasible train timetable in terms of a given order of trains. In particular, the proposed NWBPMJSS_Liu-Kozan constructive algorithm comprises several recursively-used sub-algorithms (i.e. Best-Starting-Time-Determination Procedure, Blocking-Time-Determination Procedure, Conflict-Checking Procedure, Conflict-Eliminating Procedure, Tune-up Procedure and Fine-tune Procedure) to guarantee feasibility by satisfying the blocking, no-wait, deadlock-free and conflict-free constraints. A two-stage hybrid heuristic algorithm (NWBPMJSS_Liu-Kozan-BIH) is developed by combining the NWBPMJSS_Liu-Kozan constructive algorithm and the Best-Insertion-Heuristic (BIH) algorithm to find the preferable train schedule in an efficient and economical way. Extensive computational experiments show that the proposed methodology is promising because it can be applied as a standard and fundamental toolbox for identifying, analysing, modelling and solving real-world scheduling problems.

A hybrid shifting bottleneck procedure algorithm for the parallel-machine job-shop scheduling problem

In practice, parallel-machine job-shop scheduling (PMJSS) is very useful in the development of standard modelling approaches and generic solution techniques for many real-world scheduling problems. In this paper, based on the analysis of structural properties in an extended disjunctive graph model, a hybrid shifting bottleneck procedure (HSBP) algorithm combined with Tabu Search metaheuristic algorithm is developed to deal with the PMJSS problem. The original-version SBP algorithm for the job-shop scheduling (JSS) has been significantly improved to solve the PMJSS problem with four novelties: i) a topological-sequence algorithm is proposed to decompose the PMJSS problem into a set of single-machine scheduling (SMS) and/or parallel-machine scheduling (PMS) subproblems; ii) a modified Carlier algorithm based on the proposed lemmas and the proofs is developed to solve the SMS subproblem; iii) the Jackson rule is extended to solve the PMS subproblem; iv) a Tabu Search metaheuristic algorithm is embedded under the framework of SBP to optimise the JSS and PMJSS cases. The computational experiments show that the proposed HSBP is very efficient in solving the JSS and PMJSS problems.

Using approximate Bayesian computation to estimate transmission rates of nosocomial pathogens

In this paper, we apply a simulation based approach for estimating transmission rates of nosocomial pathogens. In particular, the objective is to infer the transmission rate between colonised health-care practitioners and uncolonised patients (and vice versa) solely from routinely collected incidence data. The method, using approximate Bayesian computation, is substantially less computer intensive and easier to implement than likelihood-based approaches we refer to here. We find through replacing the likelihood with a comparison of an efficient summary statistic between observed and simulated data that little is lost in the precision of estimated transmission rates. Furthermore, we investigate the impact of incorporating uncertainty in previously fixed parameters on the precision of the estimated transmission rates.