Dynamic computer simulations of electrophoresis: a versatile research and teaching tool

Software is available, which simulates all basic electrophoretic systems, including moving boundary electrophoresis, zone electrophoresis, ITP, IEF and EKC, and their combinations under almost exactly the same conditions used in the laboratory. These dynamic models are based upon equations derived from the transport concepts such as electromigration, diffusion, electroosmosis and imposed hydrodynamic buffer flow that are applied to user-specified initial distributions of analytes and electrolytes. They are able to predict the evolution of electrolyte systems together with associated properties such as pH and conductivity profiles and are as such the most versatile tool to explore the fundamentals of electrokinetic separations and analyses. In addition to revealing the detailed mechanisms of fundamental phenomena that occur in electrophoretic separations, dynamic simulations are useful for educational purposes. This review includes a list of current high-resolution simulators, information on how a simulation is performed, simulation examples for zone electrophoresis, ITP, IEF and EKC and a comprehensive discussion of the applications and achievements.

Radiation dose reduction in computer assisted navigation for functional endoscopic sinus surgery--cadaver head experiments and clinical implementation

Computed tomography based navigation for endoscopic sinus surgery is inflationary used despite of major public concern about iatrogenic radiation induced cancer risk. Studies on dose reduction for CAS-CT are almost nonexistent. We validate the use of radiation dose reduced CAS-CT for clinically applied surface registration.

Comparison of three optical tracking systems in a complex navigation scenario

Three-dimensional rotational X-ray imaging with the SIREMOBIL Iso-C3D (Siemens AG, Medical Solutions, Erlangen, Germany) has become a well-established intra-operative imaging modality. In combination with a tracking system, the Iso-C3D provides inherently registered image volumes ready for direct navigation. This is achieved by means of a pre-calibration procedure. The aim of this study was to investigate the influence of the tracking system used on the overall navigation accuracy of direct Iso-C3D navigation. Three models of tracking system were used in the study: Two Optotrak 3020s, a Polaris P4 and a Polaris Spectra system, with both Polaris systems being in the passive operation mode. The evaluation was carried out at two different sites using two Iso-C3D devices. To measure the navigation accuracy, a number of phantom experiments were conducted using an acrylic phantom equipped with titanium spheres. After scanning, a special pointer was used to pinpoint these markers. The difference between the digitized and navigated positions served as the accuracy measure. Up to 20 phantom scans were performed for each tracking system. The average accuracy measured was 0.86 mm and 0.96 mm for the two Optotrak 3020 systems, 1.15 mm for the Polaris P4, and 1.04 mm for the Polaris Spectra system. For the Polaris systems a higher maximal error was found, but all three systems yielded similar minimal errors. On average, all tracking systems used in this study could deliver similar navigation accuracy. The passive Polaris system showed ? as expected ? higher maximal errors; however, depending on the application constraints, this might be negligible.

Wow! Linear systems and signal processing is fun!

We describe a recent offering of a linear systems and signal processing course for third-year electrical and computer engineering students. This course is a pre-requisite for our first digital signal processing course. Students have traditionally viewed linear systems courses as mathematical and extremely difficult. Without compromising the rigor of the required concepts, we strived to make the course fun, with application-based hands-on laboratory projects. These projects can be modified easily to meet specific instructors' preferences. © 2011 IEEE.(17 refs)

Regulatory mechanism of the light-activable allosteric switch LOV-TAP for the control of DNA binding: a computer simulation study

The spatio-temporal control of gene expression is fundamental to elucidate cell proliferation and deregulation phenomena in living systems. Novel approaches based on light-sensitive multiprotein complexes have recently been devised, showing promising perspectives for the noninvasive and reversible modulation of the DNA-transcriptional activity in vivo. This has lately been demonstrated in a striking way through the generation of the artificial protein construct light-oxygen-voltage (LOV)-tryptophan-activated protein (TAP), in which the LOV-2-Jα photoswitch of phototropin1 from Avena sativa (AsLOV2-Jα) has been ligated to the tryptophan-repressor (TrpR) protein from Escherichia coli. Although tremendous progress has been achieved on the generation of such protein constructs, a detailed understanding of their functioning as opto-genetical tools is still in its infancy. Here, we elucidate the early stages of the light-induced regulatory mechanism of LOV-TAP at the molecular level, using the noninvasive molecular dynamics simulation technique. More specifically, we find that Cys450-FMN-adduct formation in the AsLOV2-Jα-binding pocket after photoexcitation induces the cleavage of the peripheral Jα-helix from the LOV core, causing a change of its polarity and electrostatic attraction of the photoswitch onto the DNA surface. This goes along with the flexibilization through unfolding of a hairpin-like helix-loop-helix region interlinking the AsLOV2-Jα- and TrpR-domains, ultimately enabling the condensation of LOV-TAP onto the DNA surface. By contrast, in the dark state the AsLOV2-Jα photoswitch remains inactive and exerts a repulsive electrostatic force on the DNA surface. This leads to a distortion of the hairpin region, which finally relieves its tension by causing the disruption of LOV-TAP from the DNA.

A novel computer simulation method for simulating the multiscale transduction dynamics of signal proteins

Signal proteins are able to adapt their response to a change in the environment, governing in this way a broad variety of important cellular processes in living systems. While conventional molecular-dynamics (MD) techniques can be used to explore the early signaling pathway of these protein systems at atomistic resolution, the high computational costs limit their usefulness for the elucidation of the multiscale transduction dynamics of most signaling processes, occurring on experimental timescales. To cope with the problem, we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1), recently employed to control the motility of cancer cells through light stimulus. More specifically, we show that their signaling pathways begin with a residual re-arrangement and subsequent H-bond formation of amino acids near to the flavin-mononucleotide chromophore, causing a coupling between β-strands and subsequent detachment of a peripheral α-helix from the AsLOV2-domain. In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding. These applications demonstrate that our approach reliably reproduces the signaling pathways of complex signal proteins, ranging from nanoseconds up to seconds at affordable computational costs.

The foundations of computer assisted surgery

Using navigation systems in general orthopaedic surgery and, in particular, knee replacement is becoming more and more accepted. This paper describes the basic technological concepts of modern computer assisted surgical systems. It explains the variation in currently available systems and outlines research activities that will potentially influence future products. In general, each navigation system is defined by three components: (1) the therapeutic object is the anatomical structure that is operated on using the navigation system, (2) the virtual object represents an image of the therapeutic object, with radiological images or computer generated models potentially being used, and (3) last but not least, the navigator acquires the spatial position and orientation of instruments and anatomy thus providing the necessary data to replay surgical action in real-time on the navigation system's screen.