DCMS: A data analytics and management system for molecular simulation

Molecular Simulation (MS) is a powerful tool for studying physical/chemical features of large systems and has seen applications in many scientific and engineering domains. During the simulation process, the experiments generate a very large number of atoms and intend to observe their spatial and temporal relationships for scientific analysis. The sheer data volumes and their intensive interactions impose significant challenges for data accessing, managing, and analysis. To date, existing MS software systems fall short on storage and handling of MS data, mainly because of the missing of a platform to support applications that involve intensive data access and analytical process. In this paper, we present the database-centric molecular simulation (DCMS) system our team developed in the past few years. The main idea behind DCMS is to store MS data in a relational database management system (DBMS) to take advantage of the declarative query interface (i.e., SQL), data access methods, query processing, and optimization mechanisms of modern DBMSs. A unique challenge is to handle the analytical queries that are often compute-intensive. For that, we developed novel indexing and query processing strategies (including algorithms running on modern co-processors) as integrated components of the DBMS. As a result, researchers can upload and analyze their data using efficient functions implemented inside the DBMS. Index structures are generated to store analysis results that may be interesting to other users, so that the results are readily available without duplicating the analysis. We have developed a prototype of DCMS based on the PostgreSQL system and experiments using real MS data and workload show that DCMS significantly outperforms existing MS software systems. We also used it as a platform to test other data management issues such as security and compression

The role of Sdh4p Tyr-89 in ubiquinone reduction by the Saccharomyces cerevisiae succinate dehydrogenase

AbstractSuccinate dehydrogenase (complex II or succinate:ubiquinone oxidoreductase) is a tetrameric, membrane-bound enzyme that catalyzes the oxidation of succinate and the reduction of ubiquinone in the mitochondrial respiratory chain. Two electrons from succinate are transferred one at a time through a flavin cofactor and a chain of iron–sulfur clusters to reduce ubiquinone to an ubisemiquinone intermediate and to ubiquinol. Residues that form the proximal quinone-binding site (QP) must recognize ubiquinone, stabilize the ubisemiquinone intermediate, and protonate the ubiquinone to ubiquinol, while minimizing the production of reactive oxygen species. We have investigated the role of the yeast Sdh4p Tyr-89, which forms a hydrogen bond with ubiquinone in the QP site. This tyrosine residue is conserved in all succinate:ubiquinone oxidoreductases studied to date. In the human SDH, mutation of this tyrosine to cysteine results in paraganglioma, tumors of the parasympathetic ganglia in the head and neck. We demonstrate that Tyr-89 is essential for ubiquinone reductase activity and that mutation of Tyr-89 to other residues does not increase the production of reactive oxygen species. Our results support a role for Tyr-89 in the protonation of ubiquinone and argue that the generation of reactive oxygen species is not causative of tumor formation

Using lambda networks to enhance performance of interactive large simulations

The ability to use a visualisation tool to steer large simulations provides innovative and novel usage scenarios, e.g. the ability to use new algorithms for the computation of free energy profiles along a nanopore [1]. However, we find that the performance of interactive simulations is sensitive to the quality of service of the network with variable latency and packet loss in particular having a detrimental effect The use of dedicated networks (provisioned in this case as a circuit-switched point-to-point optical lightpath or lambda) can lead to significant (50% or more) performance enhancement, When funning on say 128 or 256 processors of a high-end supercomputer this saving has a significant value. We perform experiments to understand the impact of network characteristics on the performance of a large parallel classical molecular dynamics simulation when coupled interactively to a remote visualisation tool. This paper discusses the experiments performed and presents the results from the systematic studies. © 2006 IEEE.Published versio

High-mobility two-dimensional hole gases in III-V semiconductor heterostructures: growth and transport properties

In this work, we investigated very high quality carbon-doped two-dimensional hole gases (2DHGs). The first part deal with high-mobility GaAs/AlGaAs quantum wells (QWs). Optimizing the heterostructure design, the hole mobility was extremely increased. Quantum Hall effect, photoconductivity effect, Rashba spin splitting, fractional quantum Hall effect (revealing interesting anisotropy in the thermally activated transport) and the band structure were investigated. In the second part, we studied InAs/InGaAs/InAlAs QWs with high spin-orbit coupling. A great success was the preparation of a carbon p-type doping in QWs with high indium content. A conductivity type inversion from p- to n-type with changing composition was observed. The heterostructures exhibit weak-antilocalization, hole-hole interaction effect and strong transport anisotropy. The spin splitting can be engineered providing small changes in the structure design. Both topics are of major interest for spintronics research

Metabolic Pathway Analysis: from small to genome-scale networks

The need for mathematical modelling of biological processes has grown alongside with the achievements in the experimental field leading to the appearance and development of new fields like systems biology. Systems biology aims at generating new knowledge through modelling and integration of experimental data in order to develop a holistic understanding of organisms. In the first part of my PhD thesis, I compare two different levels of abstraction used for computing metabolic pathways, constraint-based and graph theoretical methods. I show that the current representations of metabolism as a simple graph correspond to wrong mathematical descriptions of metabolic pathways. On the other hand, the use of stoichiometric information and convex analysis as modelling framework like in elementary flux mode analysis, allows to correctly predict metabolic pathways. In the second part of the thesis, I present two of the first methods, based on elementary flux mode analysis, that can compute metabolic pathways in such large metabolic networks: the K-shortest EFMs method and the EFMEvolver method. These methods contribute to an enrichment of the mathematical tools available to model cell biology and more precisely, metabolism. The application of these new methods to biotechnological problems is also explored in this part. In the last part of my thesis, I give an overview of recent achievements in metabolic network reconstruction and constraint-based modelling as well as open issues. Moreover, I discuss possible strategies for integrating experimental data with elementary flux mode analysis. Further improvements in elementary flux mode computation on that direction are put forward

A simulation method for the wetting dynamics of liquid droplets on deformable membranes

Biological cells utilize membranes and liquid-like droplets, known as biomolecular condensates, to structure their interior. The interaction of droplets and membranes, despite being involved in several key biological processes, is so far little understood. Here, we present a first numerical method to simulate the continuum dynamics of droplets interacting with deformable membranes via wetting. The method combines the advantages of the phase-field method for multi-phase flow simulation and the arbitrary Lagrangian-Eulerian (ALE) method for an explicit description of the elastic surface. The model is thermodynamically consistent, coupling bulk hydrodynamics with capillary forces, as well as bending, tension, and stretching of a thin membrane. The method is validated by comparing simulations for single droplets to theoretical results of shape equations, and its capabilities are illustrated in 2D and 3D axisymmetric scenarios

Tools for Biomolecular Modeling and Simulation

Electrostatic interactions play a pivotal role in understanding biomolecular systems, influencing their structural stability and functional dynamics. The Poisson-Boltzmann (PB) equation, a prevalent implicit solvent model that treats the solvent as a continuum while describes the mobile ions using the Boltzmann distribution, has become a standard tool for detailed investigations into biomolecular electrostatics. There are two primary methodologies: grid-based finite difference or finite element methods and body-fitted boundary element methods. This dissertation focuses on developing fast and accurate PB solvers, leveraging both methodologies, to meet diverse scientific needs and overcome various obstacles in the field

Bioengineering Analysis of Traumatic Brain Injury

Traumatic brain injury (TBI) is a serious health concern affecting over a million people in the UK. Brain shift and herniation, which are closely related to severe disability or death, are important signs of abnormally elevated intracranial pressure (ICP) or space-occupying intracranial mass after trauma. This research aims to use medical image computing and biomechanical modelling techniques to characterise the specific deformation field of brain tissues under various TBI scenarios and strengthen the biomechanical understanding across the full spectrum of TBI. Medical image computing provides the research with a solid clinical grounding. To better interpret the neuro-images, three computational tools have been developed, including a CT preprocessing pipeline, an automatic mid-sagittal plane detector and an automatic brain extractor. Using these tools, a novel concept of midplane shift (MPS) is developed to quantitatively evaluate the brain herniation condition across the mid-sagittal plane. In the meantime, a lesion heatmap is generated to quantify the asymmetric haematoma volumes across the mid-sagittal plane. The MPS heatmaps generated for 33 TBI patients with heterogeneous brain pathologies demonstrate highly similar shift patterns. Together with the lesion heatmap, a brain deformation mechanism has been presented: the brain will not deform randomly in response to trauma, instead, it will only deform in a regulated mechanism so that the deformation is directed and restricted to the soft ventricular region, thanks to the anatomic structures of the head such as the falx. The MPS heatmap, the lesion heatmap, together with the novel CT parameters derived from them, provide a rich abundance of information on intracranial brain herniation, for a more complete overview of TBI from medical images. Biomechanical modelling, being one of the most important tools in trauma biomechanics, has been used to quantitatively simulate the brain shift and herniation condition caused by various intracranial lesions and increasing ICP. Preliminary finite element models reconstructed from the Virtual Human Project have demonstrated some limitations. To resolve the observed deficiencies, an advanced high-fidelity patient-specific FE brain model is constructed and explicitly assessed to optimise its injury simulation performance with the help of the developed medical image computing tools. During simulation, the patient-specific traumatic injuries have been reconstructed by imposing both the primary lesion and the secondary injury. The primary lesion simulation is achieved mechanically by ``indenting" a rigid lesion surface simulating the shape of the haematoma to the brain model. While the secondary swelling is modelled with a thermal-expansion-based method to simulate the bulging brain. Using this approach, the observed brain herniation can be decomposed into a deformation due to pure mass effect of space-occupying primary lesion and a shift as a result of secondary swelling. The head injuries of six different TBI patients have been reconstructed and simulated using the prescribed method. The realistic case study suggested that the subdural haematoma patients, as compared to the epidural haematoma patients, were exposed to more significant secondary swelling, which agrees well with the historical clinical findings. In addition to the realistic TBI case studies, an idealised traumatic lesion simulation is performed to investigate the role of lesion morphology and the lesion locations of onsets, in brain herniations during TBI. It is suggested by the idealised TBI cases that the brain is more sensitive to lesion that is more concentrated spatially, if lesion volumes and lesion locations were exactly the same. Moreover, in terms of lesion locations, lesions that strikes on the temporal region and the anterior region are more likely to lead to greater brain deformation, if other lesion morphologies were equal and no secondary swelling considered. Ultimately, the developed tools are expected to help clinicians better understand and predict the brain behaviour after the onset of TBI and during subsequent injury evolution.WD Armstrong Trus

Software Defined Networks based Smart Grid Communication: A Comprehensive Survey

The current power grid is no longer a feasible solution due to ever-increasing user demand of electricity, old infrastructure, and reliability issues and thus require transformation to a better grid a.k.a., smart grid (SG). The key features that distinguish SG from the conventional electrical power grid are its capability to perform two-way communication, demand side management, and real time pricing. Despite all these advantages that SG will bring, there are certain issues which are specific to SG communication system. For instance, network management of current SG systems is complex, time consuming, and done manually. Moreover, SG communication (SGC) system is built on different vendor specific devices and protocols. Therefore, the current SG systems are not protocol independent, thus leading to interoperability issue. Software defined network (SDN) has been proposed to monitor and manage the communication networks globally. This article serves as a comprehensive survey on SDN-based SGC. In this article, we first discuss taxonomy of advantages of SDNbased SGC.We then discuss SDN-based SGC architectures, along with case studies. Our article provides an in-depth discussion on routing schemes for SDN-based SGC. We also provide detailed survey of security and privacy schemes applied to SDN-based SGC. We furthermore present challenges, open issues, and future research directions related to SDN-based SGC.Comment: Accepte