life science

Vehicular causation factors and conceptual design modifications to reduce aortic strain in numerically reconstructed real world nearside lateral automotive crashes

This study aims to find an effective means of substantially improving the outcome of motor vehicle crash induced aortic injuries. A DOCE study was performed on 16 different combinations of five design factors generated using a Latin Square method in modeFRONTIER 4.0. The experiment utilized FE vehicle models and the Wayne State Human Body Model.

Smoothened (SMO) receptor mutations dictate resistance to vismodegib in basal cell carcinoma

This report is on the molecular mechanisms of resistance to vismodegib in two cases of basal cell carcinoma, with clinical, molecular and in silico evidence of primary and acquired SMO mutation-mediated resistance. The entire MM-PBSA computational procedure was optimized by modeFRONTIER.

Automated Deployment of System Models via Functional Mockup Interface with Excel and modeFRONTIER

This presentation provides a brief overview of FMI with a focus on end-user value and demonstrates a method for automated deployment of system models in Modelica as simulators in Microsoft Excel using Functional Mockup Interface (FMI) and FMI Add-in for Excel. Using existing interfaces, integration with modeFRONTIER is demonstrated and exercised with several different example system models in different physical domains.

Application of Optimization Methodology and Specimen Specific Finite Element Models for Investigating Material Properties of Rat Skull

This study represents a preliminary effort in the development and validation of FE models for the rat skull used to predict the reaction of traumatic brain injuries (TBI) in humans. modeFRONTIER automatically updated input parameters and submitted new keyword files to LS-DYNA, which ran in MPP mode, to reduce the time needed in completely the task. This same method can be used to other reverse engineering procedures to obtain accurate material parameters for FE models development.

modeFRONTIER Application in Biotechnology - Unbiased Guidelines for Driving Rational Enzyme Evolution

Researchers must improve the efficiency of the biocatalyst to make them available for industrial use. A scoring function integrating an empirical approach was used to maximize the predictive capability and control the engineered enzyme performance. modeFRONTIER’s selection of genetic algorithms empowered researchers to mimic natural evolution, thus providing valuable insight when grading the engineered enzyme quality.

Development and optimization of hydroxyapatite-ß-TCP functionally gradated biomaterial

In this work a method of optimization of mechanical behaviour of an FGM biomaterial coating or scaffold composed of HAP and beta-tricalcium phosphate (ß-TCP) is considered. For coating on titanium-based substrates which have anatase (TiO2) top layer, thermodynamic equilibrium was analysed and the “safe” compositional path was found to ensure preservation of original ceramic phases during processing. 

An integrated Platform for Automatic Design and Screening of Virtual Mutants Based on 3D-QSAR analysis

An innovative application of 3D-QSAR methodology to the rational design of enzymes is here reported. The introduction of amidase activity inside the scaffold of lipase B from Candida antarctica (CaLB) was studied and 3D-QSAR models were constructed to correlate the structures of a set of CaLB mutants with their experimentally measured activities.

Finite element reconstruction of real world aortic injury in near-side lateral automotive crashes with conceptual countermeasures

Traumatic rupture of the aorta (TRA) remains the second most common cause of death associated with motor vehicle crashes after brain injury. On an average, nearly 8,000 people die annually in the United States due to blunt injury to the aorta. It is observed that more than 80% of occupants who suffer an aortic injury die at the scene due to exsanguination into the chest. With the advent of more accurate and established human body finite element (FE) models, FE crash reconstruction methods may become a valuable tool when assessing crash scenarios and occupant injury mechanisms. The current study is divided into five main aims, near side left lateral real world finite element reconstructions, sensitivity study, thresholds for TRA, aorta mechanics in racing crashes and conceptual countermeasures. In the first study eight nearside left lateral impacts, in which a TRA occurred, were reconstructed using a combination of real world crash data reported in the Crash Injury Research and Engineering.

Another Brick in the Wall. Validation of the σ1 Receptor 3D Model by Computer-Assisted Design, Synthesis and Activity of New o1 Ligands

Originally considered an enigmatic polypeptide, the σ1 receptor has recently been identified as a unique ligand regulated protein. Many studies have shown the potential of σ1 receptor ligands for the treatment of various diseases of the central nervous system (CNS); nevertheless, almost no information about the 3D structure of the receptor and/or the possible modes of interaction of the σ1 protein with its ligands have been unveiled so far.

Identification of RC-33 as a potent and selective o1 receptor agonist potentiating NGFinduced neurite outgrowth in PC12 cells. Part 2 g-scale synthesis, physicochemical characterization and in vitro metabolic stability

Strong pharmacological evidences indicate that σ1 receptors are implicated in the pathophysiology  of all major CNS disorders. In the last years our research group has conducted extensive studies aimed at discovering novel σ1 ​ligands and we recently selected (R/S)-RC-33 as a novel potent and selective σ1  receptor agonist.