Functional Mode Analysis Research Articles

Perawatan Preventive Maintenance Mobil Satlantas Model Sedan Mazda dengan Metode Reliability Centered Maintenance pada Polres Kota X

The aim of this research is to find out the preventive maintenance of Mazda Sedan Model Traffic Cars using the reliability centered maintenance method at the City functional block diagram, determining system function and functional failure, failure mode and effect analysis, logic tree analysis, and task selection. The results of this research are that the maintenance system for traffic vehicle units carries out routine check-ups every 5,000 kilometers or every 3 months and for brake and tire components every 10,000 kilometers or 6 months, the damage that appears with the current maintenance system is the break caliper (right front), hose (water pump), and ball joint, factors that arise with current maintenance problems are safety problems, proposed improvements that need to be made to resolve the problem are preventive maintenance for the break caliper (right front), hose (water pump), and ball joint every 11000 hours or 458 days.

Integration of systems design and risk management through model‐based systems development

AbstractModel‐based systems engineering is a powerful methodology to develop safety‐critical systems. The use of the system model as a single source of truth for risk and dependability analysis results in a consistent and complete assessment. Besides, representation and logging of the assessment within the model result in a complete and up‐to‐date single source of information that can be used during the device certification as well. This paper aims to provide a comprehensive risk management SysML profile that includes interconnected safety analysis [functional hazard assessment (FHA), fault tree, and failure mode and effect analysis (FTA, FMEA)], control measure, and evaluation model elements in compliance with the medical standards. Model‐based risk assessment of a point‐of‐care diagnostic device for sepsis has been shown as a case study to show the implementation of the profile. This device is a standalone unit and the test results obtained directly affect the patient. Therefore, both the top‐down (FHA and FTA) and bottom‐up (FMEA) safety assessment methods have been used. Another objective of the study is to define a systematic and holistic method to perform fault tree analysis, not only from the system architecture models but also from the functional, activity, and sequence diagrams of the system model.

Druggable Hot Spots in the Schistosomiasis Cathepsin B1 Target Identified by Functional and Binding Mode Analysis of Potent Vinyl Sulfone Inhibitors.

Schistosomiasis, a parasitic disease caused by blood flukes of the genus Schistosoma, is a global health problem with over 200 million people infected. Treatment relies on just one drug, and new chemotherapies are needed. Schistosoma mansoni cathepsin B1 (SmCB1) is a critical peptidase for the digestion of host blood proteins and a validated drug target. We screened a library of peptidomimetic vinyl sulfones against SmCB1 and identified the most potent SmCB1 inhibitors reported to date that are active in the subnanomolar range with second order rate constants (k2nd) of ∼2 × 105 M–1 s–1. High resolution crystal structures of the two best inhibitors in complex with SmCB1 were determined. Quantum chemical calculations of their respective binding modes identified critical hot spot interactions in the S1′ and S2 subsites. The most potent inhibitor targets the S1′ subsite with an N-hydroxysulfonic amide moiety and displays favorable functional properties, including bioactivity against the pathogen, selectivity for SmCB1 over human cathepsin B, and reasonable metabolic stability. Our results provide structural insights for the rational design of next-generation SmCB1 inhibitors as potential drugs to treat schistosomiasis.

Preliminary reliability and safety assessment methodology for trans-atmospheric transportation systems

PurposeThis paper aims to propose a methodology for a safety and reliability assessment for the conceptual and preliminary design of very complex and disrupting innovative systems like trans-atmospheric vehicles. The proposed methodology differs from existing ones because it does not rely on statistical data at aircraft-level but exploits the statistical population at components-level only. For the sake of clarity, the paper provides some preliminary results of the application of the methodology at system level. The example deals with the safety and reliability assessment of a very complex propulsion system aimed at guaranteeing vertical take-off and landing capabilities of a suborbital vehicle.Design/methodology/approachThe proposed methodology is strongly based on a systems engineering approach. It exploits safety and reliability assessment analyses which have already been developed in both aeronautical and space engineering domains, but it combines them in an innovative way to overcome the lack of statistics at aircraft level. The methodology consists of two different steps: a qualitative top-down process, allowing a functional and physical decomposition of the transportation system and a following quantitative bottom-up approach, which provides the estimation of system-level reliability and safety characteristics starting from the statistical estimation of the components’ characteristics.FindingsThe paper presents a new methodology for the preliminary reliability and safety assessment of innovative transportation systems, such as hypersonic transportation systems. The envisaged methodology will overcome the poorness of statistical data that is usually affecting the conceptual design of breakthrough systems.Research limitations/implicationsThe paper shows the application of the articulated methodology to a limited case study. A complete example of application of the methodology to estimate safety and reliability characteristics at vehicle level will be provided in feature works.Practical implicationsThe methodology has been proposed to be exploited in international research activities in the field of hypersonic transportation systems. Furthermore, a massive application of this approach would allow to create a database for the generation and the update of semi-empirical models focused on high-level estimations of reliability, availability, maintainability and safety (RAMS) characteristics. Moreover, the proposed safety assessment has been conceived to be fully integrated within a typical conceptual design process.Originality/valueThe existing literature about safety and reliability assessment at the early design stages proposes pure statistical approaches which are usually not applicable to highly innovative products, where the statistical population is not existing, for example, in the case of trans-atmospheric vehicles. This paper describes how to overcome this problem, through the exploitation of statistical data at components-level only through the combination of these data to estimate RAMS characteristics at aircraft-level thanks to functional analysis, concept of operations and typical safety assessment tools, like functional hazard analysis, failure mode and effect analysis, reliability block diagram and fault tree analysis.

Reliability based maintenance methodology for sustainable transport asset management

Functional failures and structural deterioration defects are among the leading causes of growing failure probabilities of the road systems and networks. Thus, asset maintenance intervention is an essential task for the unified management of road assets and systems. The objective of this research is to consider reliability based probabilistic approach established on functional failure mode, effects and criticality analysis parametric reliability analysis, risk-based assessment and strategic asset deterioration decisions. The combined progressive assessment frameworks and algorithms based procedures utilize service inspection, safety inspection and survey inputs. The illustrated reliability maintenance based methodologies offer sustainable asset management for highway transport infrastructure and systems with emphasis on resolutions to their functional failures, defect related risk and appropriate deterioration treatment.

Dipole Order in Halide Perovskites: Polarization and Rashba Band Splittings

ABX3 (A = organic cation; B = Sn, Pb; and X = halogen) organohalide perovskites have recently attracted much attention for their photovoltaic applications. Such hybrid compounds are derived from the replacement of the inorganic monovalent metal element by an organic cation, for example, methylammonium ion (MA = CH3NH3+) and formamidinium ion (FA= +HC(NH2)2). In particular, since the organic cations are polar, it is interesting to investigate their possible long-range ordering and the corresponding Rashba spin-split bands. In this work, by using density functional theory calculations, we estimate the ferroelectric polarization corresponding to a complete ordering of dipole moments for the optimized structures of 12 perovskite halides, with A = MA, FA; B = Pb, Sn; X = Cl, Br, I. The adiabatic path and functional mode analysis have been discussed for all cases. The calculated values of the polarization may be as high as a conventional inorganic ferroelectric compound, such as BaTiO3. The concomitant inversio...

Functional Mode Singlet Fission Theory

Singlet fission is a multiple exciton generation process that splits a singlet exciton (S0S1) into a correlated triplet pair (T1T1), affording a route to overcome the long-standing Shockley–Queisser thermodynamic limit for solar energy conversion. A new theory, based on multiconfiguration-constrained density functional theory and functional mode analysis, has been developed to model intermolecular singlet fission in organic photovoltaics. Specifically, constrained density functional theory is first employed to construct molecular orbitals for the six spin configurations comprising T1T1, the diabatic product state. In a subsequent step, linear response time-dependent density functional theory is utilized to formulate the S0S1 diabatic reactant state. Functional mode analysis is then applied to a thermalized ensemble of diabatic energy gaps to ascertain the reaction coordinate for the S0S1 → T1T1 transition. If singlet fission is assumed to follow a direct route, its rate may be evaluated using a modified Jortner formula within strong vibronic coupling regime. In contrast, second-order perturbation theory must be adopted to treat alternate pathways that are mediated by a charge-transfer (CT) intermediate. As shown through numerical simulations of single crystal tetracene, our theory reveals the direct mechanism to be the primary transition path, with an experimentally consistent singlet fission rate of 0.02 ps–1. CT pathways are effectively blocked due to a substantially diminished vibrational resonance among participating states. Our results have broad applicability, as only trivial alterations are needed to enable our new theory to model vibrationally modulated singlet fission using time-delayed pulse sequences.

Tsx as a Nucleoside Channel

Tsx proteins form a family of widespread bacterial outer membrane channels that show a strong substrate specificity for nucleosides. X-ray crystallographic structures for E. coli Tsx were previously determined with the channel substrates uracil and thymidine. The substrates bind at two binding sites inside the channel. We use these structures as the starting points to study the nature of interactions of the channel with the nucleosides using molecular dynamics simulations to understand what confers the specificity for nucleoside substrates. We calculate the relative free energy of binding for these sites and the free energy barriers within the Tsx channel from umbrella sampling simulations. Additionally, we parametrize the nucleoside analogue drug Floxuridine and compare its translocation to natural substrates of the Tsx channel to explore the potential usefulness of Tsx proteins as anti-microbial drug delivery pathways. Using applied electric field simulations, we calculate the ionic conductivity of the channel and explore the gating behavior that modulates the ionic current using the functional mode analysis method.

Thermal Isomerization Mechanism in Dronpa and Its Mutants.

The photoswitching speed of the reversibly switchable fluorescent proteins (RSFPs) from the family of green fluorescent proteins (GFPs) changes upon mutation which is of direct importance for various high-resolution techniques. Dronpa is one of the most used RSFPs. Its point mutants rsFastLime (Dronpa V157G) and rsKame (Dronpa V157L) exhibit a striking difference in their photoswitching speed. Here the QM/MM on-the-fly string method is used in order to explore the details of the thermal isomerization mechanism. The four principal ways in which isomerization may occur have been scrutinized for each of the three proteins. It has been shown that thermal isomerization occurs via a one-bond-flip mechanism in all three proteins, although, in rsKame, where the chromophore is constrained more, the activation free energy difference between hula-twist and one-bond-flip is significantly smaller. Functional mode analysis has been applied to examine the motions of the amino acids during the isomerization. It clearly identifies the importance of Val/Leu 157 as well as the amino acids in the α-helix during the isomerization.

Theoretical study of normal Raman spectra and SERS of benzyl chloride and benzyl radical on silver electrodes

Electrochemical surface‐enhanced Raman spectroscopy has been used to characterize adsorbed species widely but rarely to reaction intermediates on electrodes. In previous studies, the observed surface‐enhanced Raman spectroscopy signals were proposed from benzyl species due to the electrochemical reduction of benzyl chloride on silver electrode surfaces. In this work, we reinvestigated the vibrational assignments of benzyl chloride and benzyl radical as the reaction intermediate. On the basis of density functional theory calculations and normal mode analysis, our systematic results provide more reasonable new assignments for both surface species. Further, we investigated adsorption configurations, binding energies, and vibrational frequency shifts of benzyl radical interacting with silver. Our calculated results show that the wagging vibration displays significant vibrational frequency shift, strong coupling with some intramolecular modes in the phenyl ring, and significant changes in intensity of Raman signals. The study also provides absolute Raman intensity in benzyl halides and discusses the enhancement effect mainly due to the binding interaction with respect to free benzyl radical. Copyright © 2016 John Wiley & Sons, Ltd.

Characterization of the AXH domain of Ataxin-1 using enhanced sampling and functional mode analysis.

Ataxin-1 is the protein responsible for the Spinocerebellar ataxia type 1, an incurable neurodegenerative disease caused by polyglutamine expansion. The AXH domain plays a pivotal role in physiological functions of Ataxin-1. In Spinocerebellar ataxia 1, the AXH domain is involved in the misfolding and aggregation pathway. Here molecular modeling is applied to investigate the protein-protein interactions contributing to the AXH dimer stability. Particular attention is focused on: (i) the characterization of AXH monomer-monomer interface; (ii) the molecular description of the AXH monomer-monomer interaction dynamics. Technically, an approach based on functional mode analysis, here applied to replica exchange molecular dynamics trajectories, was employed. The findings of this study are consistent with previous experimental results and elucidate the pivotal role of the I580 residue in mediating the AXH monomer-monomer interaction dynamics.

Functional Mode Hot Electron Transfer Theory

Charge carriers that have been driven out of thermal equilibrium by their excessive vibrational energies are termed hot carriers. A theory has been developed to model the injection of these vibrationally excited electrons by explicitly accounting for the time-dependent thermal relaxation of the electron-transfer driving vibrational mode, as ascertained using functional mode analysis. Specifically, the thermal relaxation rate of the driving mode is first determined through the so-called frozen-phonon approach after which the energy-dependent line shape function is revisited to include memory effects for the vibrational quanta within the framework of Fermi’s golden rule. As shown by the numerical simulations of a 6-methyl-azulene-2-carboxylic acid dye molecule bound to an anatase TiO2[101] surface, our new theory not only yields persistently faster electron injection rates with higher incident photon energy but also exhibits a sharp increase when the vibrational quanta of the photoexcited dye molecule chang...

Molecular Dynamic Indicators of the Photoswitching Properties of Green Fluorescent Proteins.

Reversibly photoswitchable fluorescent proteins (RSFPs) are highly useful probes for a range of applications including diffraction-unlimited fluorescence microscopy. It was previously shown that reversible photoswitching not only involves cis-trans isomerization and protonation-deprotonation of the chromophore but also results in a marked difference in β-barrel flexibility. In this work, we performed flexibility profiling and functional mode analysis (FMA) using molecular dynamics calculations to study how the flexibility of the RSFP β-barrel influences the photoswitching properties of several fluorescent proteins. We also used Partial Least-Squared (PLS) FMA to detect promising mutation sites for the modulation of photoswitching properties of RSFPs. Our results show that the flexibility of RSFP does depend on its state with a systematically higher flexibility in the dark state compared to the bright state. In particular our method highlights the importance of Val157 in Dronpa, which upon mutation yields a striking difference in the collective motions of the two mutants. Overall, we show that PLS-FMA yields information, complementary to static structures, that can guide the rational design of fluorescent proteins.

Ferroelectric Polarization of CH3NH3PbI3: A Detailed Study Based on Density Functional Theory and Symmetry Mode Analysis.

Ferroelectricity in halide perovskites currently represents a crucial issue, as it may have an important role for the enhancement of solar cells efficiency. Simulations of ferroelectric properties based on density functional theory are conceptually more demanding compared with "conventional" inorganic ferroelectrics due to the presence of both organic and inorganic components in the same compound. Here we present a detailed study focused on the prototypical CH3NH3PbI3 perovskite. By using density functional theory combined with symmetry mode analysis, we disentangle the contributions of the methylammonium cations and the role of the inorganic framework, therefore suggesting possible routes to enhance the polarization in this compound. Our estimate of the polarization for the tetragonal phase at low temperature is ∼4.42 μC/cm(2), which is substantially lower than that of traditional perovskite oxides.

His 95 Acts as a pH Gate in Aquaporin-4

Aquaporins are trans-membrane channels that are responsible for the permeation of water across the cell boundary. Responding to environmental stresses such as osmolarity, voltage and pH is an important aspect of regulation of channel permeability. We demonstrate that aquaporin-4, a membrane water channel modulates water transport via pH sensing. Aquaporin-4 is expressed mostly on the cytoplasmic membrane of cells of the nervous system. It has been implicated in the formation of edema during stress caused to the brain and thus has medical relevance. In this work we combine a Molecular Dynamics based computational approach with empirical methods to identify the molecular mechanism involved in the regulation of the channel via pH. Using a Partial Least Squares (PLS) based machine learning algorithm, we perform Functional Mode Analysis (FMA) to elucidate collective motions in the protein that are responsible for opening and closing the channel pore. We find that the protonation of conserved histidine residue H95 opens the channel and locally increases the pore radius. We employ Essential Dynamics (ED) simulations to ascertain that the collective mode identified by the computational method can indeed switch the protein function on and off. This mechanism is then tested experimentally by expressing the protein on Xenopus oocytes. By controlling the pH on either side of the cell boundary the location of the pH sensor is identified with respect to the cell membrane. Finally using mutational analysis it is established that H95 is the residue responsible for the pH sensing.

Investigating the Structure and Dynamics of the PIK3CA Wild-Type and H1047R Oncogenic Mutant

The PIK3CA gene is one of the most frequently mutated oncogenes in human cancers. It encodes p110α, the catalytic subunit of phosphatidylinositol 3-kinase alpha (PI3Kα), which activates signaling cascades leading to cell proliferation, survival, and cell growth. The most frequent mutation in PIK3CA is H1047R, which results in enzymatic overactivation. Understanding how the H1047R mutation causes the enhanced activity of the protein in atomic detail is central to developing mutant-specific therapeutics for cancer. To this end, Surface Plasmon Resonance (SPR) experiments and Molecular Dynamics (MD) simulations were carried out for both wild-type (WT) and H1047R mutant proteins. An expanded positive charge distribution on the membrane binding regions of the mutant with respect to the WT protein is observed through MD simulations, which justifies the increased ability of the mutated protein variant to bind to membranes rich in anionic lipids in our SPR experiments. Our results further support an auto-inhibitory role of the C-terminal tail in the WT protein, which is abolished in the mutant protein due to loss of crucial intermolecular interactions. Moreover, Functional Mode Analysis reveals that the H1047R mutation alters the twisting motion of the N-lobe of the kinase domain with respect to the C-lobe and shifts the position of the conserved P-loop residues in the vicinity of the active site. These findings demonstrate the dynamical and structural differences of the two proteins in atomic detail and propose a mechanism of overactivation for the mutant protein. The results may be further utilized for the design of mutant-specific PI3Kα inhibitors that exploit the altered mutant conformation.

Study of safety features and accident scenarios in a fusion DEMO reactor

After the Fukushima Dai-ichi nuclear accident, a need for assuring safety of fusion energy has grown in the Japanese (JA) fusion research community. DEMO safety research has been launched as a part of Broader Approach DEMO Design Activities (BA-DDA). This paper reports progress in the fusion DEMO safety research conducted under BA-DDA. Safety requirements and evaluation guidelines have been, first of all, established based on those established in the Japanese ITER site invitation activities. The radioactive source terms and energies that can mobilize such source terms have been assessed for a reference DEMO concept. This concept employs in-vessel components that are cooled by pressurized water and built of a low activation ferritic steel (F82H), contains solid pebble beds made of lithium-titanate (Li2TiO3) and beryllium–titanium (Be12Ti) for tritium breeding and neutron multiplication, respectively. It is shown that unlike the energies expected in ITER, the enthalpy in the first wall/blanket cooling loops is large compared to the other energies expected in the reference DEMO concept. Reference accident event sequences in the reference DEMO in this study have been analyzed based on the Master Logic Diagram and Functional Failure Mode and Effect Analysis techniques. Accident events of particular concern in the DEMO have been selected based on the event sequence analysis and the hazard assessment.

Multi-Hierarchical Functional Directed Graph Modeling Method for Aircraft System Fault Diagnosis

In order to diagnosing new fault for hybrid system which is lack of experiential knowledge and historic knowledge, semi-quantitative fault diagnosis method based on graph theory and fuzzy theory combined with functional fault analysis (FFA) theories and Failure Mode and Effects Analysis (FMEA) is studied. And a multi-hierarchical functional directed graph modeling method is proposed for aircraft system fault diagnosis. Nacelle Anti-Ice subsystem of an aero engine is taken as a specific application to present the detailed MHFDG modeling method. The proposed modeling method is suitable for fault diagnosis of newly developed hybrid system.

Solute Permeation in Aquaporin Channels

Solute permeation in the aquaporin family is governed via a diverse selection of mechanisms. Extrinsic regulators, such as changes in environmental pH conditions or covalent modifications, such as phosphorylation, are known to provide means for the channel to modify its permeability. These mechanisms are responsible for enabling biological organisms, at a cellular level, to fine tune their responses to osmotic changes that take place in their environment. Also, it has been experimentally observed that the members of Aquaporin protein family demonstrate strong specificity for their solutes and yet are responsible for a permeation of a variety of substrates such as water, glycerol and ammonia. The molecular details underlying the permeation specificity of these substrates are not wholly understood.Computational molecular dynamics can be used to study the intricacies involved in these regulatory functions at atomistic level. Simulations can provide valuable insights into how aquaporins control their specificity and permeability, as well as means to facilitate the flexibility of their permeates. We apply Functional Mode Analysis (FMA) and Principal Component Analysis (PCA) to identify the structural states as well as highly correlated dynamic modes that contribute to the regulation of the permeation in Aquaporins. These methods can also be used to provide input to experimental studies to validate the results of such computational investigations. Here we study a diverse array of aquaporin family proteins to create theoretical models in order to complement empirical observations of solute specificity and the gating of the aquaporin channels.

How the Dynamics of the Metal-Binding Loop Region Controls the Acid Transition in Cupredoxins

Many reduced cupredoxins undergo a pH-dependent structural rearrangement, triggered by protonation of the His ligand belonging to the C-terminal hydrophobic loop, usually termed the acid transition. At variance with several members of the cupredoxin family, the acid transition is not observed for azurin (AZ). We have addressed this issue by performing molecular dynamics simulations of AZ and four mutants, in which the C-terminal loop has been replaced with those of other cupredoxins or with polyalanine loops. All of the loop mutants undergo the acid transition in the pH range of 4.4-5.5. The main differences between AZ and its loop mutants are the average value of the active site solvent accessible surface area and the extent of its fluctuations with time, together with an altered structure of the water layer around the copper center. Using functional mode analysis, we found that these variations arise from changes in nonbonding interactions in the second coordination sphere of the copper center, resulting from the loop mutation. Our results strengthen the view that the dynamics at the site relevant for function and its surroundings are crucial for protein activity and for metal-containing electron transferases.