A study of the viability of obtaining a generic animation of the foot while walking for the virtual testing of footwear using dorsal pressures

Establishing the appropriate pressure exerted by the shoe upper over the foot surface is fundamental for the design of specific footwear, although measuring the dorsal pressures can also provide important additional information. In previous works, a virtual simulator to perform studies of comfort and functionality in CAD footwear design was presented. This paper describes the procedure carried out to obtain the foot animations used in this simulator. The virtual feet used in the simulator are feet without a standard form scanned in a static way. Their movements are rebuilt from the register of movements of several foot anatomical points during a complete step. The dorsal pressures exerted by some shoe uppers on these anatomical points were measured for several subjects and used to establish the viability of the use of these animations in a virtual simulator for footwear.     

Total Hourglass Control - A Robust Finite Element Formulation for the Calculation of Organ Deformations

For use in a virtual reality based laparoscopic surgery simulator methods have been developed to model the mechanical behavior of soft tissue. Explicit Finite Element analysis turned out to be a robust basis when the approximation of hyperelastic materials is used. To reduce calculation times reduced volume integration schemes were applied, where classical hourglass control leads to drastic errors which make a simulation expanding over a long period of time impossible. Therefore, the total hourglass control scheme was developed and is presented here for several material laws. This new formulation takes the existence of the elastic potential of a hyperelastic material into account and leads to robust simulations without loss of accuracy. This is demonstrated with the off-line simulation of a model of an uterus and its adnexe.     

Effect of joint laxity on polyethylene wear in total knee replacement

Experimental simulator studies are frequently performed to evaluate wear behavior in total knee replacement. It is vital that the simulation conditions match the physiological situation as closely as possible. To date, few experimental wear studies have examined the effects of joint laxity on wear and joint kinematics and the absence of the anterior cruciate ligament has not been sufficiently taken into account in simulator wear studies.The aim of this study was to investigate different ligament and soft tissue models with respect to wear and kinematics.A virtual soft tissue control system was used to simulate different motion restraints in a force-controlled knee wear simulator.The application of more realistic and sophisticated ligament models that considered the absence of anterior cruciate ligament lead to a significant increase in polyethylene wear (p=0.02) and joint kinematics (p<0.01). We recommend the use of more complex ligament models to appropriately simulate the function of the human knee joint and to evaluate the wear behavior of total knee replacements. A feasible simulation model is presented.     

Testing methods in species distribution modelling using virtual species: what have we learnt and what are we missing?

Species distribution models (SDMs) have become one of the major predictive tools in ecology. However, multiple methodological choices are required during the modelling process, some of which may have a large impact on forecasting results. In this context, virtual species, i.e. the use of simulations involving a fictitious species for which we have perfect knowledge of its occurrence–environment relationships and other relevant characteristics, have become increasingly popular to test SDMs. This approach provides for a simple virtual ecologist framework under which to test model properties, as well as the effects of the different methodological choices, and allows teasing out the effects of targeted factors with great certainty. This simplification is therefore very useful in setting up modelling standards and best practice principles. As a result, numerous virtual species studies have been published over the last decade. The topics covered include differences in performance between statistical models, effects of sample size, choice of threshold values, methods to generate pseudo‐absences for presence‐only data, among many others. These simulations have therefore already made a great contribution to setting best modelling practices in SDMs. Recent software developments have greatly facilitated the simulation of virtual species, with at least three different packages published to that effect. However, the simulation procedure has not been homogeneous, which introduces some subtleties in the interpretation of results, as well as differences across simulation packages. Here we 1) review the main contributions of the virtual species approach in the SDM literature; 2) compare the major virtual species simulation approaches and software packages; and 3) propose a set of recommendations for best simulation practices in future virtual species studies in the context of SDMs.     

WinBEST-KIT: Windows-based biochemical reaction simulator for metabolic pathways

We have implemented an efficient, user-friendly biochemical reaction simulator called Web-based BEST-KIT (Biochemical Engineering System analyzing Tool-KIT) for analyzing large-scale nonlinear networks such as metabolic pathways. Users can easily design and analyze an arbitrary reaction scheme through the Internet and an efficient graphical user interface without considering the mathematical equations. The reaction scheme can include several reaction types, which are represented by both the mass action law (mass balance) and approximated velocity functions of enzyme kinetics at steady state, such as Michaelis-Menten, Hill cooperative, Competitive inhibition. However, since all modules in Web-based BEST-KIT have been developed in Java applet style, users cannot optionally make use of original mathematical equations in addition to the prepared equations. In the present study, we have developed a new version of BEST-KIT (for Microsoft Windows called WinBEST-KIT) to allow users to define original mathematical equations and to customize these equations very easily as user-defined reaction symbols. The following powerful system-analytical methods are prepared for system analysis: time-course calculation, parameter scanning, estimation of the values of unknown kinetic parameters based on experimentally observed time-course data of reactants, dynamic response of reactants against virtual external perturbations, and real-time simulation (Virtual Dry Lab).     

CADCS simulation of the closed-loop cardiovascular system

A pulsatile simulator of the closed-loop cardiovascular system, designed to solve simulation, identification and control problems in a research and education context, is presented. Its implimentation makes use of a command-driven interactive program for simulation of non-linear ordinary differential equations. The flexibility of the simulator is demonstrated by the results presented which refer to a basal steady-state circulatory condition as well as a transient induced by an abrupt change in peripheral resistance.     

Testing the effectiveness of two natural selection simulations in the context of a large-enrollment undergraduate laboratory class

Background

Simulations can be an active and engaging way for students to learn about natural selection, and many have been developed, including both physical and virtual simulations. In this study we assessed the student experience of, and learning from, two natural selection simulations, one physical and one virtual, in a large enrollment introductory biology lab course. We assigned students to treatments (the physical or virtual simulation activity) by section and assessed their understanding of natural selection using a multiple-choice pre-/post-test and short-answer responses on a post-lab assignment. We assessed student experience of the activities through structured observations and an affective survey.

Results

Students in both treatments showed increased understanding of natural selection after completing the simulation activity, but there were no differences between treatments in learning gains on the pre-/post-test, or in the prevalence of concepts and misconceptions in written answers. On a survey of self-reported enjoyment they rated the physical activity significantly higher than the virtual activity. In classroom observations of student behavior, we found significant differences in the distribution of behaviors between treatments, including a higher frequency of off-task behavior during the physical activity.

Conclusions

Our results suggest that both simulations are valuable active learning tools to aid students’ understanding of natural selection, so decisions about which simulation to use in a given class, and how to best implement it, can be motivated by contextual factors.

     

A computer-based simulation of childbirth using the partial Dirichlet–Neumann contact method with total Lagrangian explicit dynamics on the GPU

During physiological or ‘natural’ childbirth, the fetal head follows a distinct motion pattern—often referred to as the cardinal movements or ‘mechanisms’ of childbirth—due to the biomechanical interaction between the fetus and maternal pelvic anatomy. The research presented in this paper introduces a virtual reality-based simulation of physiological childbirth. The underpinning science is based on two numerical algorithms including the total Lagrangian explicit dynamics method to calculate soft tissue deformation and the partial Dirichlet–Neumann contact method to calculate the mechanical contact interaction between the fetal head and maternal pelvic anatomy. The paper describes the underlying mathematics and algorithms of the solution and their combination into a computer-based implementation. The experimental section covers first a number of validation experiments on simple contact mechanical problems which is followed by the main experiment of running a virtual reality childbirth. Realistic mesh models of the fetus, bony pelvis and pelvic floor muscles were subjected to the intra-uterine expulsion forces which aim to propel the virtual fetus through the virtual birth canal. Following a series of simulations, taking variations in the shape and size of the geometric models into account, we consistently observed the cardinal movements in the simulator just as they happen in physiological childbirth. The results confirm the potential of the simulator as a predictive tool for problematic childbirths subject to patient-specific adaptations.

     

Mobile learning applications to improve invertebrate zoology online teaching

The use of new technologies including personal mobile devices has become an indispensable tool in our daily lives, and thus its presence in education is becoming ever more ubiquitous. In the current scenario imposed by the COVID‐19 pandemic, in which in‐person presence in classrooms has been enormously reduced at all educational levels, the use of mobile learning and cutting‐edge methods can greatly improve the way students learn and enhance their online‐learning experience. Mobile applications, combined with extended reality technologies such as virtual reality (VR) and augmented reality (AR), are powerful tools that connect real and virtual environments and allow higher interaction for the user. We have leveraged the advantages of mobile learning and extended reality technologies to develop a series of mobile applications and associated educational activities for university‐level courses involving invertebrate zoology field work. In particular, we have developed (a) a VR SCUBA diving video to explore the diversity of a marine protected area; (b) an AR mobile app to visualize 3D models of marine invertebrates; and (c) a mobile‐based catalogue to explore the terrestrial biodiversity of one of the most diverse regions of Spain. Here we provide detailed information describing the design and creation of these tools, as well as their application in class, to facilitate and encourage their use in higher education. Despite the relatively recent application of these technologies in education, they have an enormous potential: they improve student motivation and learning, can be adapted to different learning styles, reduce social inequalities, and facilitate inclusiveness and diversity practices in the classroom.     

Analysis of mechanistic pathway models in drug discovery: p38 pathway

Mechanistic models of signal transduction have emerged as valuable tools for untangling complex signaling networks and gaining detailed insight into pathway dynamics. The natural extension of these tools is for the design of therapeutic strategies. We have generated a novel computational model of lipopolysaccharide-induced p38 signaling in the context of TNF-alpha production in inflammatory disease. Using experimental measurement of protein levels and phospho-protein time courses, populations of model parameters were estimated. With a collection of parameter sets, reflecting virtual diversity, we step through analysis of the p38 signaling pathway model to answer specific drug discovery questions regarding target prioritization, inhibitor simulation, model robustness and co-drugging. We demonstrate that target selection cannot be assessed independently from inhibitor mechanism of action and is also linked with robustness to cellular variability. Finally, we assert that in the face of parameter uncertainty one can still uncover consistent findings that can guide drug discovery efforts.     

How to choose relevant multiple receptor conformations for virtual screening: a test case of Cdk2 and normal mode analysis

Better treatment of protein flexibility is essential in structure-based drug design projects such as virtual screening and protein-ligand docking. Diversity in ligand-binding mechanisms and receptor conformational changes makes it difficult to treat dynamic features of the receptor during the docking simulation. Thus, the use of pregenerated multiple receptor conformations is applied today in virtual screening studies. However, generation of a small relevant set of receptor conformations remains challenging. To address this problem, we propose a new protocol for the generation of multiple receptor conformations via normal mode analysis and for the selection of several receptor conformations suitable for docking/virtual screening. We validated this protocol on cyclin-dependent kinase 2, which possesses a binding site located at the interface between two subdomains and is known to undergo significant conformational changes in the active site region upon ligand binding. We believe that the suggested rules for the choice of suitable receptor conformations can be applied to other targets when dealing with in silico screening on flexible receptors.     

Guaranteeing the quality of multidimensional analysis in data warehouses of simulation results: Application to pesticide transfer data produced by the MACRO model

Currently, the vital impact of environmental pollution on economic, social and health dimensions has been recognized. The need for theoretical and implementation frameworks for the acquisition, modeling and analysis of environmental data as well as tools to conceive and validate scenarios is becoming increasingly important. For these reasons, different environmental simulation models have been developed. Researchers and stakeholders need efficient tools to store, display, compare and analyze data that are produced by simulation models. One common way to manage simulation results is to use text files; however, text files make it difficult to explore the data. Spreadsheet tools (e.g., OpenOffice, MS Excel) can help to display and analyze model results, but they are not suitable for very large volumes of information. Recently, some studies have shown the feasibility of using Data Warehouse (DW) and On-Line Analytical Processing (OLAP) technologies to store model results and to facilitate model visualization, analysis and comparisons. These technologies allow model users to easily produce graphical reports and charts. In this paper, we address the analysis of pesticide transfer simulation results by warehousing and OLAPing data, for which the data results from the MACRO simulation model. This model simulates hydrological transfers of pesticides at the plot scale. We demonstrate how the simulation results can be managed using DW technologies. We also demonstrate how the use of integrity constraints can improve OLAP analysis. These constraints are used to maintain the quality of the warehoused data as well as to maintain the aggregations and queries, which will lead to better analysis, conclusions and decisions.     

Computer simulations: tools for population and evolutionary genetics

Computer simulations are excellent tools for understanding the evolutionary and genetic consequences of complex processes whose interactions cannot be analytically predicted. Simulations have traditionally been used in population genetics by a fairly small community with programming expertise, but the recent availability of dozens of sophisticated, customizable software packages for simulation now makes simulation an accessible option for researchers in many fields. The in silico genetic data produced by simulations, along with greater availability of population-genomics data, are transforming genetic epidemiology, anthropology, evolutionary and population genetics and conservation. In this Review of the state-of-the-art of simulation software, we identify applications of simulations, evaluate simulator capabilities, provide a guide for their use and summarize future directions.     

Enhancements to the Rosetta Energy Function Enable Improved Identification of Small Molecules that Inhibit Protein-Protein Interactions

Protein-protein interactions are among today’s most exciting and promising targets for therapeutic intervention. To date, identifying small-molecules that selectively disrupt these interactions has proven particularly challenging for virtual screening tools, since these have typically been optimized to perform well on more “traditional” drug discovery targets. Here, we test the performance of the Rosetta energy function for identifying compounds that inhibit protein interactions, when these active compounds have been hidden amongst pools of “decoys.” Through this virtual screening benchmark, we gauge the effect of two recent enhancements to the functional form of the Rosetta energy function: the new “Talaris” update and the “pwSHO” solvation model. Finally, we conclude by developing and validating a new weight set that maximizes Rosetta’s ability to pick out the active compounds in this test set. Looking collectively over the course of these enhancements, we find a marked improvement in Rosetta’s ability to identify small-molecule inhibitors of protein-protein interactions.     

Modeling and simulating biogeochemical cycles: the BCS freeware

The use of simulation is a scientifically-recognized way of studying biogeochemical cycles, mainly when consecutive disturbances are made. As a pedagogical tool, simulation helps students gain insight into the response dynamics of the respective biogeochemical cycle. The development of simulation tools for educational purposes has not progressed much for the last couple of decades, despite advances in computer science. Trying to fill in that gap, this paper presents the biogeochemical cycles simulator (BCS) freeware, a more user-friendly replacement for older simulators. The BCS is a light-weight, user-friendly, Windows®-based simulator. Using the sulfur biogeochemical cycle as an example, the simulation results from two sequential disturbances were compared with those of the former tools: the sum of relative errors between the three tools was never greater than 2.7%. Moreover, a real-world event (Mount Pinatubo’s Eruption 1991) was also simulated, giving similar results to those actually measured. The major improvements made include: a friendly graphical user interface, unlimited number of reservoirs, direct input of mass fluxes, multi-disturbance assessment, and fully customizable plots. The BCS freeware has been used in case studies, in a biogeochemical cycles course of a B.S. in Chemistry at the University of São Paulo, Brazil. Simulations helped students to develop decision-making and group-working skills, as well as enhanced data interpretation. Moreover, the students were able to recognize how even small disturbances can cause short- and long-term impacts on biogeochemical cycles. A set of possible strategies for using BCS as an educational tool is also provided in this work.

     

Hypothesis generation in signaling networks.

Biological signaling networks comprise the chemical processes by which cells detect and respond to changes in their environment. Such networks have been implicated in the regulation of important cellular activities, including cellular reproduction, mobility, and death. Though technological and scientific advances have facilitated the rapid accumulation of information about signaling networks, utilizing these massive information resources has become infeasible except through computational methods and computer-based tools. To date, visualization and simulation tools have received significant emphasis. In this paper, we present a graph-theoretic formalization of biological signaling network models that are in wide but informal use, and formulate two problems on the graph: the Constrained Downstream and Minimum Knockout Problems. Solutions to these problems yield qualitative tools for generating hypotheses about the networks, which can then be experimentally tested in a laboratory setting. Using established graph algorithms, we provide a solution to the Constrained Downstream Problem. We also show that the Minimum Knockout Problem is NP-Hard, propose a heuristic, and assess its performance. In tests on the Epidermal Growth Factor Receptor (EGFR) network, we find that our heuristic reports the correct solution to the problem in seconds. Source code for the implementations of both solutions is available from the authors upon request.     

Neutral, acidic, and basic derivatives of anthranilamide that confer different formal charge to reducing oligosaccharides

To facilitate the use of oligosaccharides as analytical tools in biological studies, we have designed, synthesized, and conjugated to maltosaccharides a novel series of homologous small fluorescent moieties that differ in formal charge. These moieties are amide derivatives of anthranilic acid: uncharged N-(2-aminobenzoyl)glycinamide (ABGlyAmide; 2), acidic N,N-dimethyl-N(')-(2-aminobenzoyl)ethylenediamine (ABGlyDIMED; 3), and basic N-(2-aminobenzoyl)glycine (ABGly; 1). Routes for synthesis and optimal reaction conditions for glycoconjugation by conventional reductive amination are presented, as is the compatibility of these adducts with common analytical and preparative chromatographic methods, including RP-HPLC and HPAEC-PAD. These novel anthranilic acid derivatives confer both fluorescence and defined charge to oligosaccharides, and so enhance the repertoire of chromatographic and analytical methods for which anthranilic acid can be used. Furthermore, because glucosaccharides have rigid solution structure, these small fluorescent adducts with different formal charge are ideal tools for molecular sizing studies of membrane pores.     

Implementing relevance feedback in ligand-based virtual screening using Bayesian inference network

Recently, the use of the Bayesian network as an alternative to existing tools for similarity-based virtual screening has received noticeable attention from researchers in the chemoinformatics field. The main aim of the Bayesian network model is to improve the retrieval effectiveness of similarity-based virtual screening. To this end, different models of the Bayesian network have been developed. In our previous works, the retrieval performance of the Bayesian network was observed to improve significantly when multiple reference structures or fragment weightings were used. In this article, the authors enhance the Bayesian inference network (BIN) using the relevance feedback information. In this approach, a few high-ranking structures of unknown activity were filtered from the outputs of BIN, based on a single active reference structure, to form a set of active reference structures. This set of active reference structures was used in two distinct techniques for carrying out such BIN searching: reweighting the fragments in the reference structures and group fusion techniques. Simulated virtual screening experiments with three MDL Drug Data Report data sets showed that the proposed techniques provide simple ways of enhancing the cost-effectiveness of ligand-based virtual screening searches, especially for higher diversity data sets.     

Telepathology and continuous education: important tools for pathologists of developing countries

Education shows that active participation allows the best development of skills to acquire, and the results are better when the information is well documented. Now, with digital images and the Internet, in the case of the Static Telepathology (ST), it is easy to share macroscopic and microscopic photographs. The progress of the technologies enabled a form of Dynamic Telepathology (DT) named "virtual slides", with navigation tools, and can be moved around changing powers as desired, making any personal computer into a digital microscope. The use of these tools in continuous education leads to optimal development of knowledge. We reported the experience of a Latin-American Pathologist from La Rioja, a small Province of Argentina, and we also mentioned the electronic publications in Virtual Hispano-American Congresses of Pathology (VHACP) since 1997(18 reports in the case of ST) and in two Virtual Slide Congress (VSC). In the 1st (2005) and 2nd (2007) Internet VSCs two of our cases were digitized in Spain (case 1 and 3 respectively). In these Virtual Slides, the microscopic images can be moved remotely from any computer connected to the Internet, we should recognize that it will become a valuable continuing Medical Education tool in microscopy, probably related to the phrase "a picture is worth more than a thousand words", then we might add; "what about thousands of images?" Similarly, the autoevaluation test is very important. ST and DT, in support of Virtual Congresses allows learning, teaching and sharing of diseases in scientific presentations and the exchange of views in the forums, these are the optimum material for distance education. In addition we received CDs or DVDs and certificates as authors, recognized by European Institutions. The active participation and the autoevaluation test are the best tools for continuous medical education in telepathology, not only for pathologists in developing countries but for the entire world.     

Undergraduate structural biology education: A shift from users to developers of computation and simulation tools

The use of theory and simulation in undergraduate education in biochemistry, molecular biology, and structural biology is now common, but the skills students need and the curriculum instructors have to train their students are evolving. The global pandemic and the immediate switch to remote instruction forced instructors to reconsider how they can use computation to teach concepts previously approached with other instructional methods. In this review, we survey some of the curricula, materials, and resources for instructors who want to include theory, simulation, and computation in the undergraduate curriculum. There has been a notable progression from teaching students to use discipline-specific computational tools to developing interactive computational tools that promote active learning to having students write code themselves, such that they view computation as another tool for solving problems. We are moving toward a future where computational skills, including programming, data analysis, visualization, and simulation, will no longer be considered an optional bonus for students but a required skill for the 21st century STEM (Science, Technology, Engineering, and Mathematics) workforce; therefore, all physical and life science students should learn to program in the undergraduate curriculum.