scholarly journals The genome design suite: enabling massive in-silico experiments to design genomes

2019 ◽  
Author(s):  
Oliver Chalkley ◽  
Oliver Purcell ◽  
Claire Grierson ◽  
Lucia Marucci
Keyword(s):  
In Silico ◽  
Large Scale ◽  
Computational Models ◽  
Solution Space ◽  
Mycoplasma Genitalium ◽  
Specific Model ◽  
Computer Clusters ◽  
Optimisation Algorithms ◽  
Genome Design

AbstractMotivationComputational biology is a rapidly developing field, and in-silico methods are being developed to aid the design of genomes to create cells with optimised phenotypes. Two barriers to progress are that in-silico methods are often only developed on a particular implementation of a specific model (e.g. COBRA metabolic models) and models with longer simulation time inhibit the large-scale in-silico experiments required to search the vast solution space of genome combinations.ResultsHere we present the genome design suite (PyGDS) which is a suite of Python tools to aid the development of in-silico genome design methods. PyGDS provides a framework with which to implement phenotype optimisation algorithms on computational models across computer clusters. The framework is abstract allowing it to be adapted to utilise different computer clusters, optimisation algorithms, or design goals. It implements an abstract multi-generation algorithm structure allowing algorithms to avoid maximum simulation times on clusters and enabling iterative learning in the algorithm. The initial case study will be genome reduction algorithms on a whole-cell model of Mycoplasma genitalium for a PBS/Torque cluster and a Slurm cluster.AvailabilityThe genome design suite is written in Python for Linux operating systems and is available from GitHub on a GPL open-source [email protected], [email protected], and [email protected].

scholarly journals Assessment of the Peak Response of a 5MW HAWT Under Combined Wind and Seismic Induced Loads

2017 ◽  
Vol 11 (1) ◽  
pp. 441-457 ◽  
Author(s):  
Alberto Maria Avossa ◽  
Cristoforo Demartino ◽  
Francesco Ricciardelli
Keyword(s):  
Wind Turbines ◽  
Large Scale ◽  
Seismic Vulnerability ◽  
Specific Model ◽  
Demand Model ◽  
Horizontal Axis Wind Turbine ◽  
Ground Acceleration ◽  
Peak Response ◽  
Wind Actions

Background and Objective:The rapid growth of the wind energy industry has brought the construction of large-scale wind turbines with the aim of increasing their performance and profits to areas characterized by high seismic hazard. Previous research demonstrated the seismic vulnerability of large-scale wind turbines when seismic and wind actions are considered simultaneously in the demand model. In this study, the response of the supporting structure of a land-based horizontal axis wind turbine under the combined effects induced by wind and earthquake is presented.Method:Using a decoupled approach, numerical simulations of the wind and seismic loads effects are performed separately using a specific model for the aerodynamic damping and then joined. Both simulations are done using free open-source software that are FAST simulating the aerodynamic response of the rotor and OpenSees simulating the dynamic behaviour of the tower. The fitted generalized extreme value distributions of the multi-hazard peak response in terms of base moment and shear, total drift, and top rotation are calculated for different seismic and wind load intensities by means of Monte Carlo simulations. The analyses are referred to the specific case study of a land-based wind generator.Results and Conclusion:The maximum demand is associated with the operational rated scenario and for high values of the peak ground acceleration, only the parked condition leads to larger values of the response if compared to others. The analyses showed that it is essential to consider the combined seismic and wind actions in the demand model to derive a complete multi-risk analysis of the land-based structures.

scholarly journals Designing Minimal Genomes Using Whole-Cell Models

2018 ◽  
Author(s):  
Joshua Rees ◽  
Oliver Chalkley ◽  
Sophie Landon ◽  
Oliver Purcell ◽  
Lucia Marucci ◽  
...  
Keyword(s):  
In Silico ◽  
Genome Engineering ◽  
Cell Model ◽  
Mycoplasma Genitalium ◽  
Computational Design ◽  
Functional Assay ◽  
Proof Of Concept ◽  
Computational Tools ◽  
Whole Cell ◽  
Genome Design

AbstractIn the future, entire genomes tailored to specific functions and environments could be designed using computational tools. However, computational tools for genome design are currently scarce. Here we present algorithms that enable the use of design-simulate-test cycles for genome design, using genome minimisation as a proof-of-concept. Minimal genomes are ideal for this purpose as they have a simple functional assay, the cell either replicates or not. We used the first (and currently only published) whole-cell model, for the bacterium Mycoplasma genitalium. Our computational design-simulate-test cycles discovered novel in-silico minimal genomes smaller than JCVI-Syn3.0, a bacteria with, currently, the smallest genome that can be grown in pure culture. In the process, we identified 10 low essentiality genes, 18 high essentiality genes, and produced evidence for at least two Mycoplasma genitalium in-silico minimal genomes. This work brings combined computational and laboratory genome engineering a step closer.

Optimizing Skip Stop Service in Passenger Rail Transportation

2012 ◽  
Author(s):  
Samuel L. Sogin ◽  
Brennan M. Caughron ◽  
Samantha G. Chadwick
Keyword(s):  
Genetic Algorithm ◽  
Large Scale ◽  
Solution Space ◽  
Mixed Integer ◽  
Rail Transportation ◽  
Travel Times ◽  
Passenger Rail ◽  
Optimal Balance ◽  
Passenger Travel

Two-track passenger rail lines typically operate with all trains serving every station. Without additional infrastructure, transit planners have limited options to improve travel times. Service could be improved by operating a skip-stop service where trains only serve a subset of all the station stops. A skip-stop pattern must find an optimal balance between faster passenger travel times and lower service frequencies at each station. A mixed integer formulation is proposed to analyze this tradeoff; however, the mixed integer formulation could not scale efficiently to analyze a large scale commuter line. A genetic algorithm is presented to search the solution space incorporating a larger problem scope and complexity. In a case study of a Midwest commuter line, overall passenger travel time could be decreased by 9.5%. Both analyses can give insights to transit operators on how to improve their service to their customers and increase ridership.

scholarly journals Cells in Silico – introducing a high-performance framework for large-scale tissue modeling

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Marco Berghoff ◽  
Jakob Rosenbauer ◽  
Felix Hoffmann ◽  
Alexander Schug
Keyword(s):  
In Silico ◽  
High Performance ◽  
Large Scale ◽  
Computational Models ◽  
Modular Design ◽  
Model Simulation ◽  
Three Dimensional ◽  
Cellular Potts Model ◽  
Performance Framework ◽  
Wide Range

Abstract Background Discoveries in cellular dynamics and tissue development constantly reshape our understanding of fundamental biological processes such as embryogenesis, wound-healing, and tumorigenesis. High-quality microscopy data and ever-improving understanding of single-cell effects rapidly accelerate new discoveries. Still, many computational models either describe few cells highly detailed or larger cell ensembles and tissues more coarsely. Here, we connect these two scales in a joint theoretical model. Results We developed a highly parallel version of the cellular Potts model that can be flexibly applied and provides an agent-based model driving cellular events. The model can be modular extended to a multi-model simulation on both scales. Based on the NAStJA framework, a scaling implementation running efficiently on high-performance computing systems was realized. We demonstrate independence of bias in our approach as well as excellent scaling behavior. Conclusions Our model scales approximately linear beyond 10,000 cores and thus enables the simulation of large-scale three-dimensional tissues only confined by available computational resources. The strict modular design allows arbitrary models to be configured flexibly and enables applications in a wide range of research questions. Cells in Silico (CiS) can be easily molded to different model assumptions and help push computational scientists to expand their simulations to a new area in tissue simulations. As an example we highlight a 10003 voxel-sized cancerous tissue simulation at sub-cellular resolution.

A Family With Autosomal-Dominant Progressive Sensorineural Hearing Loss

1996 ◽  
Vol 5 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Chris Halpin ◽  
Barbara Herrmann ◽  
Margaret Whearty
Keyword(s):  
Speech Production ◽  
Hearing Aids ◽  
Role Models ◽  
Speech Intelligibility ◽  
Large Scale ◽  
Speech Language Pathology ◽  
The Family ◽  
Patient Will ◽  
Language Pathology

The family described in this article provides an unusual opportunity to relate findings from genetic, histological, electrophysiological, psychophysical, and rehabilitative investigation. Although the total number evaluated is large (49), the known, living affected population is smaller (14), and these are spread from age 20 to age 59. As a result, the findings described above are those of a large-scale case study. Clearly, more data will be available through longitudinal study of the individuals documented in the course of this investigation but, given the slow nature of the progression in this disease, such studies will be undertaken after an interval of several years. The general picture presented to the audiologist who must rehabilitate these cases is that of a progressive cochlear degeneration that affects only thresholds at first, and then rapidly diminishes speech intelligibility. The expected result is that, after normal language development, the patient may accept hearing aids well, encouraged by the support of the family. Performance and satisfaction with the hearing aids is good, until the onset of the speech intelligibility loss, at which time the patient will encounter serious difficulties and may reject hearing aids as unhelpful. As the histological and electrophysiological results indicate, however, the eighth nerve remains viable, especially in the younger affected members, and success with cochlear implantation may be expected. Audiologic counseling efforts are aided by the presence of role models and support from the other affected members of the family. Speech-language pathology services were not considered important by the members of this family since their speech production developed normally and has remained very good. Self-correction of speech was supported by hearing aids and cochlear implants (Case 5’s speech production was documented in Perkell, Lane, Svirsky, & Webster, 1992). These patients received genetic counseling and, due to the high penetrance of the disease, exhibited serious concerns regarding future generations and the hope of a cure.

The Boeing 787 Dreamliner--A case study in large-scale design integration

2008 ◽  
Author(s):  
D. L. McMullin ◽  
A. R. Jacobsen ◽  
D. C. Carvan ◽  
R. J. Gardner ◽  
J. A. Goegan ◽  
...  
Keyword(s):  
Large Scale ◽  
Design Integration ◽  
Scale Design

Disruptive innovation and operationalization in local and sustainable food systems: Examining the University of Toronto-Local Food Plus partnership

2019 ◽  
Vol 6 (1) ◽  
pp. 120-139
Author(s):  
Lori Stahlbrand
Keyword(s):  
Food Systems ◽  
Large Scale ◽  
Food System ◽  
Local Food ◽  
Disruptive Innovation ◽  
Government Support ◽  
Sustainable Food ◽  
University Of Toronto ◽  
The University

This paper traces the partnership between the University of Toronto and the non-profit Local Food Plus (LFP) to bring local sustainable food to its St. George campus. At its launch, the partnership represented the largest purchase of local sustainable food at a Canadian university, as well as LFP’s first foray into supporting institutional procurement of local sustainable food. LFP was founded in 2005 with a vision to foster sustainable local food economies. To this end, LFP developed a certification system and a marketing program that matched certified farmers and processors to buyers. LFP emphasized large-scale purchases by public institutions. Using information from in-depth semi-structured key informant interviews, this paper argues that the LFP project was a disruptive innovation that posed a challenge to many dimensions of the established food system. The LFP case study reveals structural obstacles to operationalizing a local and sustainable food system. These include a lack of mid-sized infrastructure serving local farmers, the domination of a rebate system of purchasing controlled by an oligopolistic foodservice sector, and embedded government support of export agriculture. This case study is an example of praxis, as the author was the founder of LFP, as well as an academic researcher and analyst.

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