Initial crash test screening studies utilizing the NHTSA/BCL computer simulation program for collinear car/car and car/barrier collisions. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Development and use of a computer simulation model for the evaluation of design and control alternatives for intersections of minor roads with multi-lane rural highways: field studies and model validation. Interim report.

Federal Highway Administration, Washington, D.C.

Operational hybrid computer simulation for vehicle handling studies. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

The Effect of Active Student Responding in Computer-Assisted Instruction on Social-Studies Learning by Students with Learning Disabilities: A Brief Report

An alternating treatment design was used to compare the effects of three student response conditions (Clicking, Repeating, and Listening) during computer-assisted instruction on social-studies facts learning and maintenance. Results showed that all students learned and maintained more social-studies facts taught in the Repeating condition followed by the Clicking condition.

The effect of active student responding in computer -assisted instruction on social -studies learning by students with learning disabilities

The purpose of this study was to compare the effects of three student response conditions during computer-assisted instruction on the acquisition and maintenance of social-studies facts. Two of the conditions required active student responding (ASR), whereas the other required an on-task (OT) response. Participants were five fifth-grade students, with learning disabilities enrolled in a private school. An alternating treatments design with a best treatments phase was used to compare the effects of the response procedures on three major dependent measures: same-day tests, next-day tests, and maintenance tests. ^ Each week for six weeks, participants were provided daily one-to-one instruction on sets of 21 unknown social-studies facts using a hypermedia computer program, with a new set of facts being practiced each week. Each set of 21 facts was divided randomly into three conditions: Clicking-ASR, Repeating-ASR, and Listening-OT. Hypermedia lesson began weekly with the concept introduction lesson, followed by practice and testing. Practice and testing occurred four days per week, per set. During Clicking-ASR, student practice involved the selection of a social-studies response by clicking on an item with the mouse on the hypermedia card. Repeating-ASR instruction required students to orally repeat the social-studies facts when prompted by the computer. During Listening-OT, students listened to the social-studies facts being read by the computer. During weeks seven and eight, instruction occurred with seven unknown facts using only the best treatment. ^ Test results show that all for all 5 students, the Repeating-ASR practice procedure resulted in more social-studies facts stated correctly on same-day tests, next-day tests, and one-and two-week maintenance tests. Clicking-ASR was the next most effective procedure. During the seventh and eighth week of instruction when only the best practice condition was implemented, Repeating-ASR produced higher scores than all conditions (including Repeating-ASR) during the first six weeks of the study. ^ The results lend further support to the growing body of literature that demonstrates the positive relation between ASR and student achievement. Much of the ASR literature has focused on the effects of increased ASR during teacher-led or peer-mediated instruction. This study adds a dimension to that research in that it demonstrated the importance of ASR during computer-assisted instruction and further suggests that the type of ASR used during computer-assisted instruction may influence learning. Future research is needed to investigate the effectiveness of other types of ASR during computer-assisted instruction and to identify other fundamental characteristics of an effective computer-assisted instruction. ^

Creating Educational Immersive Environments Using a Computer Game Engine: Case Studies and Design Theory

This paper aims to crystallize recent research performed at the University of Worcester to investigate the feasibility of using the commercial game engine ‘Unreal Tournament 2004’ (UT2004) to produce ‘Educational Immersive Environments’ (EIEs) suitable for education and training. Our research has been supported by the UK Higher Education Academy. We discuss both practical and theoretical aspects of EIEs. The practical aspects include the production of EIEs to support high school physics education, the education of architects, and the learning of literacy by primary school children. This research is based on the development of our novel instructional medium, ‘UnrealPowerPoint’. Our fundamental guiding principles are that, first, pedagogy must inform technology, and second, that both teachers and pupils should be empowered to produce educational materials. Our work is informed by current educational theories such as constructivism, experiential learning and socio-cultural approaches as well as elements of instructional design and game principles.

Studies of Protein-Protein and Protein-Water Interactions by Small Angle X-Ray Scattering, Terahertz Spectroscopy, ASMOS, And Computer Simulation

The protein folding problem has been one of the most challenging subjects in biological physics due to its complexity. Energy landscape theory based on statistical mechanics provides a thermodynamic interpretation of the protein folding process. We have been working to answer fundamental questions about protein-protein and protein-water interactions, which are very important for describing the energy landscape surface of proteins correctly. At first, we present a new method for computing protein-protein interaction potentials of solvated proteins directly from SAXS data. An ensemble of proteins was modeled by Metropolis Monte Carlo and Molecular Dynamics simulations, and the global X-ray scattering of the whole model ensemble was computed at each snapshot of the simulation. The interaction potential model was optimized and iterated by a Levenberg-Marquardt algorithm. Secondly, we report that terahertz spectroscopy directly probes hydration dynamics around proteins and determines the size of the dynamical hydration shell. We also present the sequence and pH-dependence of the hydration shell and the effect of the hydrophobicity. On the other hand, kinetic terahertz absorption (KITA) spectroscopy is introduced to study the refolding kinetics of ubiquitin and its mutants. KITA results are compared to small angle X-ray scattering, tryptophan fluorescence, and circular dichroism results. We propose that KITA monitors the rearrangement of hydrogen bonding during secondary structure formation. Finally, we present development of the automated single molecule operating system (ASMOS) for a high throughput single molecule detector, which levitates a single protein molecule in a 10 µm diameter droplet by the laser guidance. I also have performed supporting calculations and simulations with my own program codes.

Chemometric Studies on Natural Products as Potential Inhibitors of the NADH Oxidase from Trypanosoma cruzi Using the VolSurf Approach

Natural products have widespread biological activities, including inhibition of mitochondrial enzyme systems. Some of these activities, for example cytotoxicity, may be the result of alteration of cellular bioenergetics. Based on previous computer-aided drug design (CADD) studies and considering reported data on structure-activity relationships (SAR), an assumption regarding the mechanism of action of natural products against parasitic infections involves the NADH-oxidase inhibition. In this study, chemometric tools, such as: Principal Component Analysis (PCA), Consensus PCA (CPCA), and partial least squares regression (PLS), were applied to a set of forty natural compounds, acting as NADH-oxidase inhibitors. The calculations were performed using the VolSurf+ program. The formalisms employed generated good exploratory and predictive results. The independent variables or descriptors having a hydrophobic profile were strongly correlated to the biological data.

DFT and electrochemical studies on nortriptyline oxidation sites

A study on the possible sites of oxidation and epoxidation of nortriptyline was performed using electrochemical and quantum chemical methods; these sites are involved in the biological responses (for example, hepatotoxicity) of nortriptyline and other similar antidepressants. Quantum chemical studies and electrochemical experiments demonstrated that the oxidation and epoxidation sites are located on the apolar region of nortriptyline, which will useful for understanding the molecule`s activity. Also, for the determination of the compound in biological fluids or in pharmaceutical formulations, we propose a useful analytical methodology using a graphite-polyurethane composite electrode, which exhibited the best performance when compared with boron-doped diamond or glassy carbon surfaces.

A modified epidemiological model for computer viruses

Since the computer viruses pose a serious problem to individual and corporative computer systems, a lot of effort has been dedicated to study how to avoid their deleterious actions, trying to create anti-virus programs acting as vaccines in personal computers or in strategic network nodes. Another way to combat viruses propagation is to establish preventive policies based on the whole operation of a system that can be modeled with population models, similar to those that are used in epidemiological studies. Here, a modified version of the SIR (Susceptible-Infected-Removed) model is presented and how its parameters are related to network characteristics is explained. Then, disease-free and endemic equilibrium points are calculated, stability and bifurcation conditions are derived and some numerical simulations are shown. The relations among the model parameters in the several bifurcation conditions allow a network design minimizing viruses risks. (C) 2009 Elsevier Inc. All rights reserved.

Molecular modeling and QSAR studies of a set of indole and benzimidazole derivatives as H(4) receptor antagonists

Histamine is an important biogenic amine, which acts with a group of four G-protein coupled receptors (GPCRs), namely H(1) to H(4) (H(1)R - H(4)R) receptors. The actions of histamine at H(4)R are related to immunological and inflammatory processes, particularly in pathophysiology of asthma, and H(4)R ligands having antagonistic properties could be helpful as antiinflammatory agents. In this work, molecular modeling and QSAR studies of a set of 30 compounds, indole and benzimidazole derivatives, as H(4)R antagonists were performed. The QSAR models were built and optimized using a genetic algorithm function and partial least squares regression (WOLF 5.5 program). The best QSAR model constructed with training set (N = 25) presented the following statistical measures: r (2) = 0.76, q (2) = 0.62, LOF = 0.15, and LSE = 0.07, and was validated using the LNO and y-randomization techniques. Four of five compounds of test set were well predicted by the selected QSAR model, which presented an external prediction power of 80%. These findings can be quite useful to aid the designing of new anti-H(4) compounds with improved biological response.

Computer-aided drug design and ADMET predictions for identification and evaluation of novel potential farnesyltransferase inhibitors in cancer therapy

We have used various computational methodologies including molecular dynamics, density functional theory, virtual screening, ADMET predictions and molecular interaction field studies to design and analyze four novel potential inhibitors of farnesyltransferase (FTase). Evaluation of two proposals regarding their drug potential as well as lead compounds have indicated them as novel promising FTase inhibitors, with theoretically interesting pharmacotherapeutic profiles, when Compared to the very active and most cited FTase inhibitors that have activity data reported, which are launched drugs or compounds in clinical tests. One of our two proposals appears to be a more promising drug candidate and FTase inhibitor, but both derivative molecules indicate potentially very good pharmacotherapeutic profiles in comparison with Tipifarnib and Lonafarnib, two reference pharmaceuticals. Two other proposals have been selected with virtual screening approaches and investigated by LIS, which suggest novel and alternatives scaffolds to design future potential FTase inhibitors. Such compounds can be explored as promising molecules to initiate a research protocol in order to discover novel anticancer drug candidates targeting farnesyltransferase, in the fight against cancer. (C) 2009 Elsevier Inc. All rights reserved.

Quantum-chemical, NMR and X-ray diffraction studies on (+/-)-1-[3,4-(methylenedioxy)phenyl]-2-methylaminopropane

Time-averaged conformations of (+/-)-1-[3,4-(methylenedioxy)phenyl]-2-methylaminopropane hydrochloride (MDMA, ""ecstasy"") in D(2)O, and of its free base and trifluoroacetate in CDCl(3), were deduced from their (1)H NMR spectra and used to calculate their conformer distribution. Their rotational potential energy surface (PES) was calculated at the RHF/6-31G(d,p), 133LYP/6-31G(d,p), B3LYP/cc-pVDZ and AM1 levels. Solvent effects were evaluated using the polarizable continuum model. The NMR and theoretical studies showed that, in the free base, the N-methyl group and the ring are preferentially trans. This preference is stronger in the salts and corresponds to the X-ray structure of the hydrochloride. However, the energy barriers separating these forms are very low. The X-ray diffraction crystal structures of the anhydrous salt and its monohydrate differed mainly in the trans or cis relationship of the N-methyl group to the a-methyl, although these two forms interconvert freely in solution. (C) 2007 Elsevier Inc. All rights reserved.