Computer Modeling Software Research Articles

EGG WHITE ALBUMIN FORM COMPLEX WITH ASPIRIN AND CAFFEINE AND ITS ROLE AS FREE RADICAL SCAVENGER

Objective: Egg white protein (ovalbumin) is well known to be freshly consumed in Indonesia as traditional medicine, or it is usually known as “Jamu.” Ovalbumin, as well as egg white albumin, is able to form complex compounds with other substances through the formation of weak chemical and physical bonds. The objective of this study is to understand the behavior of ovalbumin as radical scavenger when it binds to antioxidants such as aspirin and caffeine (as a complex). Methods: In this study, docking sites and ovalbumin as scavenger were studied using computer-modeling software. An ovalbumin was used only for computer modeling, whereas in the wet laboratory, the freeze-drying albumin was used for electron spin resonance (ESR) and Fourier transform-infrared (FTIR) spectroscopy to determine its ability as a scavenger and functional groups, respectively. Albumin solution was applied to measure the viscosity. Results: The variability of tridimensional structures of aspirin was investigated after binding with ovalbumin. However, these structures cannot be seen clearly on caffeine. The root-mean-square deviation analysis showed that aspirin, as well as caffeine, altered the dynamic conformation of ovalbumin. The complex of aspirin-ovalbumin-caffeine which was treated at a temperature of −70°C showed intermolecular force. ESR results showed that the complex compounds could effectively reduce more free radicals when compared to aspirin or caffeine. The existence of aromatic compounds (as confirmed by FTIR) was useful for the scavenger molecules and chemical interaction occurs. The viscosity of the complex was similar with normal gastric mucus, which associated with radical scavenger. Conclusion: The characters of albumin when it binds to aspirin and caffeine indicated that scavenging activity of the complex and the viscosity showed an important result to be physiological scavengers of free radicals.

Abstract 4285: Genomics-driven clustering of disease-related biomarkers identifies therapeutic options in myelodysplastic syndromes (MDS)

Abstract Hypomethylating agents (HMA) and lenalidomide (LEN) are approved and used in the treatment of patients (pts) with MDS, though these drugs fail in most pts. No method exists to predict drug response beyond associating single actionable mutations with a single drug's response. We hypothesized that MDS pts can be clustered by similarities in genomic/molecular profiles, & that each cluster may be assigned combos of FDA-approved drugs to target their unique biomarker profile. Bone marrow cells from 88 MDS pts & the MDS-L cell line were analyzed by cytogenetics & for mutations in 14 myeloid genes using NGS. 31 pts had sufficient data for analysis. 20 profiles had similar aberrations & were grouped. Genomic data from pts and MDS-L were entered into a computational biology modeling (CBM) software, which generates a disease-specific protein network map using PubMed to create digital models and identify characteristic biomarkers unique to each pt. An algorithm was created to cluster the models based on overlapping disease-specific biomarkers. Digital drug simulations (DDS) were conducted both on MDS-L & pt simulation models by quantitatively measuring drug effect on a cell growth score (CGS), a composite of cell proliferation, viability & apoptosis. DDS identified drugs by assessing their impact on disease-specific biomarkers and calculated CGSs. Predictions were validated using MTT. 14/31 MDS pt profiles, including the MDS-L cell line, clustered into 4 groups based on biomarker characteristics.MDS-L cells harbor NRAS (G12A) mutation,-7,-12,+1,+8,+19,+20 and +21. Genes associated with increased copy number (CN) include AURKA, IGFR, PAR5, MTOR, IL6, JAK3, MDM4, MYC, MCL1, COX2, PDE4A, and RCE1; genes associated with decreased CN include DUSP1, RASA1, NR3C1, IRF1, ETV6, and SHH. CBM identified active biomarkers in MDS-L cells (90RSK, MAPK7, AKT and BTK), validated by western blot. DDS predicted nelfinavir+celecoxib to be effective in MDS-L. MDS-L cells were treated with nelfinavir, celecoxib, and nelfinavir+celecoxib with increasing doses. Nelfinavir & celecoxib reduced MDS-L viability in a dose-dependent manner, while nelfinavir+celecoxib showed additive reduction of MDS-L viability. DDS was performed on each pt to predict response to HMA and LEN. Two of the clusters (n=2/cluster) were predicted to be non-responders to any SOC therapy. A third cluster (n=3) was predicted to respond to HMA, but not LEN, and the fourth cluster (n=6) showed varying or no response to either HMA/LEN. These results use a novel concept of using genomics & CBM to cluster profiles with overlapping disease-relevant biomarkers & similar drug response predictions. CBM can identify pt populations who may benefit from certain therapeutic regimens, improving response rates, & give insights into the mechanisms by which each drug impacts the MDS-specific biomarkers Citation Format: Leylah M. Drusbosky, Kimberly E. Hawkins, Amy Meacham, Elizabeth Wise, Neeraj Kumar Singh, Chandan Kumar, Sumanth M. Vasista, Rakhi P. Suseela, Taher Abbasi, Shireen Vali, Kaoru Tohyama, Maher Albitar, Peter P. Sayeski, Christopher R. Cogle. Genomics-driven clustering of disease-related biomarkers identifies therapeutic options in myelodysplastic syndromes (MDS) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4285.

Spherical versus elliptical prosthetic humeral heads: a comparison of anatomic fit

The aim of this study was to quantify the influence of prosthetic humeral head shape, as well as the number of available prosthetic head sizes, on replicating the normal humeral head anatomy during shoulder reconstructive surgery. Computer modeling software was used to create virtual sets of both spherical and elliptical prosthetic heads, which were virtually implanted into 3-dimensional computed tomography scan-based models of 79 proximal humeri. Anatomic replication was considered successful if the measured parameters (diameters of the base of the head in the frontal and sagittal planes, radii of curvature in the frontal and sagittal planes, and humeral head height) were all reproduced within 3 mm. The Fisher exact test was used to compare the percentage of successful replications for both head types and to compare differences resulting from the use of sets with fewer or more available head sizes. Statistical significance was set at P ≤ .05. Regardless of the number of available head sizes per set, it was possible to replicate the normal anatomy within 3 mm in a higher percentage of specimens using elliptical (96%-100%) as opposed to spherical (41%-78%) prosthetic heads (P ≤ .0013). Compared with use of spherical prosthetic heads, use of elliptical heads resulted in improved replication of the normal humeral head shape. In light of the emerging evidence that use of anatomically shaped prosthetic humeral heads might lead to better shoulder function and possibly improved implant survivorship, the findings of this study may have important clinical and economic implications.

Arkheia: Data Management and Communication for Open Computational Neuroscience.

Two trends have been unfolding in computational neuroscience during the last decade. First, a shift of focus to increasingly complex and heterogeneous neural network models, with a concomitant increase in the level of collaboration within the field (whether direct or in the form of building on top of existing tools and results). Second, a general trend in science toward more open communication, both internally, with other potential scientific collaborators, and externally, with the wider public. This multi-faceted development toward more integrative approaches and more intense communication within and outside of the field poses major new challenges for modelers, as currently there is a severe lack of tools to help with automatic communication and sharing of all aspects of a simulation workflow to the rest of the community. To address this important gap in the current computational modeling software infrastructure, here we introduce Arkheia. Arkheia is a web-based open science platform for computational models in systems neuroscience. It provides an automatic, interactive, graphical presentation of simulation results, experimental protocols, and interactive exploration of parameter searches, in a web browser-based application. Arkheia is focused on automatic presentation of these resources with minimal manual input from users. Arkheia is written in a modular fashion with a focus on future development of the platform. The platform is designed in an open manner, with a clearly defined and separated API for database access, so that any project can write its own backend translating its data into the Arkheia database format. Arkheia is not a centralized platform, but allows any user (or group of users) to set up their own repository, either for public access by the general population, or locally for internal use. Overall, Arkheia provides users with an automatic means to communicate information about not only their models but also individual simulation results and the entire experimental context in an approachable graphical manner, thus facilitating the user's ability to collaborate in the field and outreach to a wider audience.

Study of Water Quality Changes due to Offshore Dike Development Plan at Semarang Bay

Now, coast of Semarang Gulf is experiencing rapid growth because Semarang as a center economic growth in Central Java. On the other hand, coast of Gulf Semarang also experience a variety of very complex problems, such as tidal flood, land subsidence, as well as coastal damage due to erosion and sedimentation process. To overcome these problems BPPT and other institutions proposed construction of offshore dike. Construction of the offshore dike is a technology intervention to the marine environment that will certainly affect the hydrodynamic balance in coastal water including water quality in the Gulf of Semarang. Therefore, to determine changes in water quality that will happen is necessary to study the water quality modeling. The study was conducted by using a computational modeling software MIKE-21 Eco Lab Module from DHI. Based on this study result knowed that development offshore dike will change water quality in the west and east dam that formed. In west dam the average value of the DO decline 81.56% - 93.32 % and the average value of BOD rise from 22.01 to 31.19% and in the east dam, there is an increase average value DO of 83.19% - 75.80%, while the average value of BOD decrease by 95,04% - 96.01%. To prevent the downward trend in water quality due to the construction of the offshore dike, its necessary precautions at the upstream area before entering the Gulf of Semarang.

Assessing the Structural Basis of μ-Conotoxin KIIIA Inhibition of the Voltage-Gated Sodium Channel Nav1.7

The voltage-gated sodium channel subtype Nav1.7 has been shown to play a critical role in pain signaling, making it an important drug target. A number of peptide toxins from cone snails (conotoxins) inhibit sodium conduction through Nav1.7 with high affinity, and make potential scaffolds for selective channel inhibitors. However, the atomistic details of protein-protein interactions between conotoxins and Nav channels necessary for rational design of such inhibitors remain unclear. Our study aims to further define the molecular determinants of μ-conotoxin KIIIA action against the human Nav1.7 channel (hNav1.7). We have previously used Rosetta computational modeling software to generate preliminary molecular models of the hNav1.7 pore-forming domain based on the NavAb crystal structure (PDB ID: 3RVY). To capitalize on recent advances, we have updated our hNav1.7 homology model using the recent cryo-EM structure of the electric eel Nav1.4 channel (PDB ID: 5XSY) as a template. To test predicted pairwise contacts between toxin and channel, point mutations of hNav1.7 and conotoxin KIIIA in the putative binding site have been generated. We have identified several residues that alter the kinetics of toxin binding, notably acidic residues on the DII pore-helix. Our experimental and modeling results may be useful for rational design of novel peptides to inhibit hNav1.7 with high affinity and selectivity.

Parametric modelling design applied to weft knitted surfaces and its effects in their physical properties

This work proposes the creation of models of surfaces using a parametric computer modelling software to obtain three-dimensional structures in weft knitted fabrics produced on single needle system machines. Digital prototyping, another feature of digital modelling software, was also explored in three-dimensional drawings generated using the Rhinoceros software. With this approach, different 3D structures were developed and produced. Physical characterization tests were then performed on the resulting 3D weft knitted structures to assess their ability to promote comfort. From the obtained results, it is apparent that the developed structures have potential for application in different market segments, such as clothing and interior textiles.

Structural Determinants for the Selectivity of the Positive KCa3.1 Gating Modulator 5-Methylnaphtho[2,1-d]oxazol-2-amine (SKA-121)

Intermediate-conductance (KCa3.1) and small-conductance (KCa2) calcium-activated K+ channels are gated by calcium binding to calmodulin (CaM) molecules associated with the calmodulin-binding domain (CaM-BD) of these channels. The existing KCa activators, such as naphtho[1,2-d]thiazol-2-ylamine (SKA-31), 6,7-dichloro-1H-indole-2,3-dione 3-oxime (NS309), and 1-ethylbenzimidazolin-2-one (EBIO), activate both channel types with similar potencies. In a previous chemistry effort, we optimized the benzothiazole pharmacophore of SKA-31 toward KCa3.1 selectivity and identified 5-methylnaphtho[2,1-d]oxazol-2-amine (SKA-121), which exhibits 40-fold selectivity for KCa3.1 over KCa2.3. To understand why introduction of a single CH3 group in five-position of the benzothiazole/oxazole system could achieve such a gain in selectivity for KCa3.1 over KCa2.3, we first localized the binding site of the benzothiazoles/oxazoles to the CaM-BD/CaM interface and then used computational modeling software to generate models of the KCa3.1 and KCa2.3 CaM-BD/CaM complexes with SKA-121. Based on a combination of mutagenesis and structural modeling, we suggest that all benzothiazole/oxazole-type KCa activators bind relatively "deep" in the CaM-BD/CaM interface and hydrogen bond with E54 on CaM. In KCa3.1, SKA-121 forms an additional hydrogen bond network with R362. In contrast, NS309 sits more "forward" and directly hydrogen bonds with R362 in KCa3.1. Mutating R362 to serine, the corresponding residue in KCa2.3 reduces the potency of SKA-121 by 7-fold, suggesting that R362 is responsible for the generally greater potency of KCa activators on KCa3.1. The increase in SKA-121's KCa3.1 selectivity compared with its parent, SKA-31, seems to be due to better overall shape complementarity and hydrophobic interactions with S372 and M368 on KCa3.1 and M72 on CaM at the KCa3.1-CaM-BD/CaM interface.

Vizart Software for Balance Calculations of Material Flows in Closed Nuclear Fuel Cycle Technologies

The VIZART software for computer modeling of production operations in the reprocessing of spent nuclear fuel, fabrication of nuclear fuel, and management of radioactive wastes was developed as part of the work on the complex technology of closed NFC. It makes it possible to develop models of process schemes or individual operations and perform supporting balance calculations of material flows of the prescribed schemes. A functional for calculating the material balance of products in a scheme taking account of the equipment productivity and constructing sequence diagrams of equipment operation was developed. The presented software, unlike most general-chemical simulators, makes it possible to calculate the characteristics of products which are specific for radiochemical processes: the isotopic composition and its variation during reprocessing, radioactivity, and heat release. These characteristics are important for validating the design and structural solutions from the standpoint of nuclear and fire-explosion safety.

Numerical and Experimental Study of Resistance, Sinkage and Trim of a Container Ship

This paper presents the effectiveness of the Computational Fluid Dynamics modeling software SHIPFLOW, in determining different hydrodynamic values such as resistance, sinkage and trim for a container ship. This ship was simulated in deep water at different Froude number including service speed. The viscous, wave and total resistance were calculated for speeds ranging from 8.0 to 10.0 knots. The model scale was simulated to obtain the resistance, sinkage and trim values for these corresponding speeds. Finally, CFD values compared with the experimental values carried out in Towing Tank facilities. Experimental investigation appears to provide agreement with computed values and showing that CFD methods may adequately deal with the problem of wave interference produced by the container ship hull.

Residual stress field and distortions resulting from welding processes: numerical modelling using Sysweld

This paper concerns the study of residual stresses and distortions in fusion butt joint welding, using the computational modelling software ESI Sysweld. Thermal gradients across the part will introduce geometrical variations that cause residual stress and distortions; their study and prediction are critical to ensure a sound welding.To foresee the welding behaviour is a complex task because there are many physical-chemical phenomena involved in the welding processes. Using Sysweld - a finite element method based software - it is possible to integrate all the physical-chemical phenomena and elaborate computational models for most welding cases.A real case consisting of three sets of aluminium plates welded by laser will be studied in this paper. A finite element model is realized for each case and the results are analysed using Sysweld capabilities.

CFD Analysis of Wind Effects on High-Rise Buildings Complex "Panorama City in Bratislava"

Analysis of wind flow upon high-rise buildings is very common topic. Nowadays, there are no general or analytical ways how to analyze wind effects on irregular shaped high-rise buildings complexes. Scaled experiments tested in wind tunnels are best for precise solutions, however they are time consuming and expensive too. Therefore we use computational modeling software based on finite volume method to analyze these effects and then, thanks to these analysis we can design structures and optimize them. Paper deals with simplified 3D analysis of wind effects on high-rise buildings complex "Panorama City" located in Bratislava-Slovakia. Through this analysis we obtain results for wind speed near objects and external pressure coefficient as well. Both of them will be helpful to gain insight for future constructions or verification of already constructed ones.

Investigation of centrifugal compressor vaneless diffuser stability via a local flow angle approach

A local flow angle approach to centrifugal compressors vaneless diffuser stability is proposed. For this investigation, 12 compressors of varying geometries were simulated. This approach employs computational fluid dynamic modeling software to model each geometry. The results revealed that the width ratio of the diffuser matters. For the four geometries with b4/ R4 < 0.05, the numerical tests showed that the local flow profiles were not able to breach the Senoo line. For the two geometries with 0.05 < b4/ R4 < 0.06 the local flow angle breached the Senoo line 50% of the time. For the six cases with b4/ R4 > 0.06, the local flow angle crossed the Senoo line for all geometries except one. There were four cases with b4/ R4 > 0.075. For three of the four cases, the local flow angle approach found flow reversal at the diffuser inlet. These results show that the stability of the diffuser is dependent upon the width ratio. Also, the results demonstrated that the ability of the local flow approach is limited by the width of the diffuser. A range of applicability for the local flow approach determining the stability was found. Lastly, for geometries with comparable width ratios the radius ratio and the impeller blade number influence the stability. This leads to the conclusion that as the width ratio shrinks the flow will breakdown in the circumferential direction as opposed to the spanwise direction.

Using computational molecular modeling software to demonstrate how DNA mutations cause phenotypes

Using computational molecular modeling software to demonstrate how DNA mutations cause phenotypes

The Effect of Angulated Radius Fractures in Forearm Rotation: A Computer Based Model

Background: Forearm fractures amongst children are quite a common presentation. The accuracy of correct alignment in forearm bones is important as it determines the degree of forearm rotation (pronation-supination). However in children due to the potential for continuous growth, a degree of angulation is acceptable. The aim of this study was to determine the effect of angulation of forearm fracture on forearm rotation using computer stimulation. Methods: Using a 3D computer modelling software (Wildfire Pro Engineer 4.0, Creo by PTC, Needham, MA), an accurate to scale model of the radius and ulna was replicated from a 7 year old forearm. A realistic representation of pronation/supination of the forearm was applied and a fracture at the junction of proximal one third and distal two third was created. A rotational simulation was created and ended when maximum pronation and supination was reached. Maximum pronation and supination was reached when either no more rotation could occur due to a misalignment of the radius and ulna or there was a collision of the bones. The simulation was repeated in increments of angulation of 2° up to 26°. The angulations that resulted in a combined range of motion (50° pronation and 80° supination) less than 130° were recorded as unacceptable and the others were as acceptable. Findings: The study showed that radius angulation fracture of >16° in the proximal third of the radius would result in an unacceptable reduction of pronation-supination to less than 130°. Conclusion: Patients with more >16° of radius angulation in a distal third shaft fracture of the radius may result in clinical reduction in forearm rotation.

Using Fall-of-Potential Measurements to Improve Deep Soil Resistivity Estimates

When measuring the ground impedance of an electrically isolated grounding system, it sometimes happens that the test electrodes are placed at considerably greater distances from the installation under test than the maximum electrode spacing used during the soil resistivity measurements carried out during the predesign phase of the grounding system. As a result, ground impedance measurements carried out with the fall-of-potential method may contain valuable supplemental information about deep soil strata that can improve grounding system performance predictions made during the design phase with computer modeling software and explain discrepancies encountered between predicted and measured ground impedance values. These data can be also used during subsequent grounding design work associated with facility expansion. It is shown in this paper how, in the absence of interfering metallic infrastructure, such ground impedance measurements can be converted into apparent soil resistivity values corresponding to deeper soil layers, with an example showing how dramatic improvements in grounding system performance predictions can be obtained.

Hydraulic characteristics and performance modeling of a modified anaerobic baffled reactor (MABR)

The modified anaerobic baffled reactor (MABR) is a type of anaerobic baffled reactor (ABR) with improved design concepts and principles. Residence time distribution (RTD) analysis at hydraulic residence times (HRTs) of 12, 16, 20 and 24h was performed to investigate the mixing patterns and dead space. The BioWin computer modeling software was developed to simulate the performance of the reactor. The model was calibrated using values from experimental runs at HRTs of 12, 16, 20 and 24h and validated with experimental runs at HRTs of 8 and 10h. The results of a hydraulic characteristics study showed that the mixing patterns for all test conditions fell between plug flow and completely mixed and the longer the HRT was, the closer the mixing pattern was to plug flow. However, a negative correlation between the dead space and the mixing pattern was observed, the longer the HRT was, the greater the dead space was. The simulated values of effluent chemical oxygen demand (COD) concentration, effluent total suspended solids (TSS) concentration, biogas flow and effluent pH value were predicted with the measured values by absolute relative errors (AREs) of less than 11.7%, 12.4%, 12.9% and 4.3%, respectively, for all test conditions. The model successfully characterized the biomass characteristics in the reactor illustrate that BioWin can well reflect the actual operating performance of the MABR.

Using computer modelled life expectancy to evaluate the impact of Australian Primary Care Incentive programs for patients with type 2 diabetes

AimsTo evaluate the impact of enhanced primary care and practice incentive programs on the care of patients with type 2 diabetes in the Australian primary care setting using routinely collected data and computer modelling software. MethodsPrimary care patient data were electronically extracted from practices and inputted into the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes model. A retrospective cohort study design was employed with predicted life expectancies compared between patients who had a recorded diabetes cycle of care (DCoC) and those who did not. Changes in glycated haemoglobin (HbA1c) were also analysed using a mixed-effects regression model. Potential life expectancy gains were estimated by inputting theoretical risk factors data consistent with current guidelines. ResultsTwelve primary care practices were recruited and suitable data were available for 559 people with type 2 diabetes. Two hundred and twenty five patients (40%) were identified as having completed at least one DCoC and as a group had a predicted additional life expectancy of 0.65 years (95% CI, −0.22 to 1.5). However, once this was adjusted for comorbidities the difference reduced to 0.03 years. There was no significant difference in HbA1c levels attributable to the intervention. An estimated 0.5 year of additional life expectancy was predicted should all patients have complied with current risk factor guideline recommendations. ConclusionsComputer modelling using routinely collected primary care data can be used to evaluate the effectiveness of primary care programs. However, there are some data availability and linkage limitations in the Australian setting.

The further away they are: creative approaches to recording bird flight paths

Seeking to model the flight paths of birds as solid objects, this artistic research and development project makes use of digital data collection, computer modelling software and 3-D printing. The project tests notions of objectivity in observation. Eschewing imaginative interpretations of flight, I aspire to allow birds to transcribe their own movements with minimal human intervention. The enquiry began with a drawing process whereby flights were traced by hand on window panes, as they occurred. Subsequent work with the Structure & Motion Lab of the Royal Veterinary College has drawn on high-resolution data from free-flying birds carrying lightweight data loggers. The resulting digital models and 3-D printed models describe short bursts of flight with considerable accuracy. At the same time, the process highlights the impossibility of absolute knowledge and leads to consideration of the need to acknowledge subjectivity – and embrace reciprocity – in observing and recording the natural world.

Genomic Databases and Softwares: In Pursuit of Biological Relevance through Bioinformatics

With the completion of human genome project, a plethora of information had been available for exploring various unanswered questions related to cell and molecular biology. Bioinformatics has been instrumental in unravelling the genetic, phenotypic, structural and functional aspects of the whole genome by using this information. Genomics and proteomics have become one of the most relevant fields after the advancements in computational analysis, interpretation, and modelling software. It can not only quite categorically describe the position of nucleotides and amino acids throughout genomes and proteomes respectively, but it also helps in performing the phylogenetic analysis, search for associated transcription factors, multiple sequence alignments, and many other relevant explorations/hunts. The advances in the knowledge of genetics acquired from molecular biology and bioinformatics are applied and point towards potential therapeutic strategies such as genome editing. This review has an aim of discussing some of the bioinformatics databases and software, which has been utilized for exploring the position of a DNA sequence, any associated single nucleotide polymorphism (SNP) related to a disease, on or nearby situated transcription factor binding sites followed by multiple sequence alignment of this sequence with other organisms. This study provides the insights in to the functional elements of any DNA, RNA or Protein sequence prior to exploring the structural polymorphism, which may regulate the gene expression. Also, this review briefly discusses the tools used for programmable nuclease–based genome editing technology.