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[en] Hydrophobicity is known to play a key role in the biological distribution of materials but is often an overlooked parameter when conjugating targeting agents, drugs, and dyes to dendrimers. This review examines the impact of hydrophobic variation in stochastically conjugated dendrimers as well as materials where synthetic methods or approaches to purification provide more controlled samples. Hydrophobic interactions are considered for three general classes: (1) terminal functional group modifications, (2) bioactive small molecules chosen to interact with receptors and proteins as targeting agents and/or drugs, and (3) imaging agents to track biological activity. Impacts on membrane interaction and cellular uptake, biodistribution, interaction with transport proteins, and pharmacokinetics are discussed. The size range of the dendrimers discussed is ~ 1–10 nm.
[en] Spatial stochastic molecular simulations in biology are limited by the intense computation required to track molecules in space either in a discrete time or discrete space framework, which has led to the development of parallel methods that can take advantage of the power of modern supercomputers in recent years. We systematically test suggested components of stochastic reaction-diffusion operator splitting in the literature and discuss their effects on accuracy. We introduce an operator splitting implementation for irregular meshes that enhances accuracy with minimal performance cost. We test a range of models in small-scale MPI simulations from simple diffusion models to realistic biological models and find that multi-dimensional geometry partitioning is an important consideration for optimum performance. We demonstrate performance gains of 1-3 orders of magnitude in the parallel implementation, with peak performance strongly dependent on model specification.
[en] Most existing flocking algorithms assume one single virtual leader and rely on information on both relative positions and relative velocities among neighboring agents. In this paper, the problem of controlling a flock of mobile autonomous agents to follow multiple virtual leaders is investigated by using only position information in the sense that agents with the same virtual leader asymptotically attain the same velocity and track the corresponding virtual leader based on only position measurements. A flocking algorithm is proposed under which every agent asymptotically attains its desired velocity, collision between agents can be avoided, and the final tight formation minimizes all agents' global potentials. A simulation example is presented to verify and illustrate the theoretical results. (general)
[en] The authors present the results of a year-long survey of the indoor radon concentration levels in the FYR of Macedonia. A total number of 437 dwellings in eight statistical regions were subject to radon concentration measurements by using CR-39 track detectors. The annual mean indoor radon concentration in each measuring site was estimated from the four individual measurements with 3 months duration. The measuring period was from December 2008 to December 2009. The distribution of the results was nearly log-normal. The arithmetic and geometric mean values of the annual mean value of radon concentration were estimated to be 105±84 and 84*/1.9 Bq m-3, respectively. The annual effective dose due to indoor exposure to radon in the dwellings was estimated to be 2.1*/1.9 mSv y-1. (authors)
[en] Purpose: Investigate capability and accuracy of Kinect v2 camera for tracking respiratory motion to use as a tool during 4DCT or in combination with motion management during radiotherapy treatments. Methods: Utilizing the depth sensor on the Kinect as well as code written in C#, the respiratory motion of a patient was tracked by recording the depth (distance) values obtained at several points on the patient. Respiratory traces were also obtained using Varian’s RPM system, which traces the movement of a propriety marker placed on the patient’s abdomen, as well as an Anzai belt, which utilizes a pressure sensor to track respiratory motion. With the Kinect mounted 60 cm above the patient and pointing straight down, 11 breathing cycles were recorded with each system simultaneously. Relative displacement values during this time period were saved to file. While RPM and the Kinect give displacement values in distance units, the Anzai system has arbitrary units. As such, displacement for all three are displayed relative to the maximum value for the time interval from that system. Additional analysis was performed between RPM and Kinect for absolute displacement values. Results: Analysis of the data from all three systems indicates the relative motion obtained from the Kinect is both accurate and in sync with the data from RPM and Anzai. The absolute displacement data from RPM and Kinect show similar displacement values throughout the acquisition except for the depth obtained from the Kinect during maximum exhalation (largest distance from Kinect). Conclusion: By simply utilizing the depth data of specific points on a patient obtained from the Kinect, respiratory motion can be tracked and visualized with accuracy comparable to that of the Varian RPM and Anzai belt.
[en] Purpose: Registration is one of the key technical components in an image-guided navigation system. A large number of 2D/3D registration algorithms have been previously proposed, but have not been able to transition into clinical practice. The authors identify the primary reason for the lack of adoption with the prerequisite for a sufficiently accurate initial transformation, mean target registration error of about 10 mm or less. In this paper, the authors present two interactive initialization approaches that provide the desired accuracy for x-ray/MR and x-ray/CT registration in the operating room setting. Methods: The authors have developed two interactive registration methods based on visual alignment of a preoperative image, MR, or CT to intraoperative x-rays. In the first approach, the operator uses a gesture based interface to align a volume rendering of the preoperative image to multiple x-rays. The second approach uses a tracked tool available as part of a navigation system. Preoperatively, a virtual replica of the tool is positioned next to the anatomical structures visible in the volumetric data. Intraoperatively, the physical tool is positioned in a similar manner and subsequently used to align a volume rendering to the x-ray images using an augmented reality (AR) approach. Both methods were assessed using three publicly available reference data sets for 2D/3D registration evaluation. Results: In the authors' experiments, the authors show that for x-ray/MR registration, the gesture based method resulted in a mean target registration error (mTRE) of 9.3 ± 5.0 mm with an average interaction time of 146.3 ± 73.0 s, and the AR-based method had mTREs of 7.2 ± 3.2 mm with interaction times of 44 ± 32 s. For x-ray/CT registration, the gesture based method resulted in a mTRE of 7.4 ± 5.0 mm with an average interaction time of 132.1 ± 66.4 s, and the AR-based method had mTREs of 8.3 ± 5.0 mm with interaction times of 58 ± 52 s. Conclusions: Based on the authors' evaluation, the authors conclude that the registration approaches are sufficiently accurate for initializing 2D/3D registration in the OR setting, both when a tracking system is not in use (gesture based approach), and when a tracking system is already in use (AR based approach)
[en] Gas target systems have been used for decades on cyclotrons to produce radionuclides for medical imaging. However, the activity recovered from such targets is often lower than its theoretically predicted value. Past research has suggested that nuclide interactions with the walls of the target body may play a key role in the loss of recoverable radionuclide activity. Here, we consider gas targets and modify the standard radionuclide production equation by adding a loss term representing radionuclides depositing on the walls of the target. We derive the form of the deposition term based on a simple adsorption model which is then linearized by solving for leading order terms. The resulting production equation uses one fitting parameter to give an estimate of the recoverable activity produced in a target system, taking adsorption into account. The model is then fit to six data series, taken in-house and reported in the literature and a parity plot compares model predictions to experimental data. The model is able to better track the data than any previous models, and points towards a phenomenological understanding of adsorption in target systems. (paper)
[en] The adenovirus E4-ORF3 protein promotes viral replication by relocalizing cellular proteins into nuclear track structures, interfering with potential anti-viral activities. E4-ORF3 targets transcriptional intermediary factor 1 alpha (TIF1α), but not homologous TIF1β. Here, we introduce TIF1γ as a novel E4-ORF3-interacting partner. E4-ORF3 relocalizes endogenous TIF1γ in virus-infected cells in vivo and binds to TIF1γ in vitro. We used the homologous nature, yet differing binding capabilities, of these proteins to study how E4-ORF3 targets proteins for track localization. We mapped the ability of E4-ORF3 to interact with specific TIF1 subdomains, demonstrating that E4-ORF3 interacts with the Coiled-Coil domains of TIF1α, TIF1β, and TIF1γ, and that the C-terminal half of TIF1β interferes with this interaction. The results of E4-ORF3-directed TIF1 protein relocalization assays performed in vivo were verified using coimmunoprecipitation assays in vitro. These results suggest that E4-ORF3 targets proteins for relocalization through a loosely homologous sequence dependent on accessibility.
[en] Purpose: With increasing numbers of cancer patients being diagnosed and the complexity of radiotherapy treatments rising it’s paramount that patient plan development continues to stay fluid within the clinic. In order to maintain a high standard of care and clinical efficiency the establishment of a tracking system for patient plan development allows healthcare providers to view real time plan progression and drive clinical workflow. In addition, it provides statistical datasets which can further identify inefficiencies within the clinic. Methods: An application was developed utilizing Microsoft’s ODBC SQL database engine to track patient plan status throughout the treatment planning process while also managing key factors pertaining to the patient’s treatment. Pertinent information is accessible to staff in many locations, including tracking monitors within dosimetry, the clinic network for both computers and handheld devices, and through email notifications. Plans are initiated with a CT and continually tracked through planning stages until final approval by staff. Patient’s status is dynamically updated by the physicians, dosimetrists, and medical physicists based on the stage of the patient’s plan. Results: Our application has been running over a six month period with all patients being processed through the system. Modifications have been made to allow for new features to be implemented along with additional tracking parameters. Based on in-house feedback, the application has been supportive in streamlining patient plans through the treatment planning process and data has been accumulating to further improve procedures within the clinic. Conclusion: Over time the clinic will continue to track data with this application. As data accumulates the clinic will be able to highlight inefficiencies within the workflow and adapt accordingly. We will add in new features to help support the treatment planning process in the future.