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At least 55 records · Page 3

Metal-organic frameworks for the storage and delivery of biologically active hydrogen sulfide

Hydrogen sulfide is an extremely toxic gas that is also of great interest for biological applications when delivered in the correct amount and at the desired rate. Here we show that the highly porous metal-organic frameworks with the CPO-27 structure can bind the hydrogen sulfide relatively strongly, allowing the storage of the gas for at least several months. Delivered gas is biologically active in preliminary vasodilation studies of porcine arteries, and the structure of the hydrogen sulfide molecules inside the framework has been elucidated using a combination of powder X-ray diffraction and pair distribution function analysis.

08 HYDROGEN↗

Alginate–peptide amphiphile core–shell microparticles as a targeted drug delivery system

We describe in this work the synthesis of microparticles with a doxorubicin drug conjugated alginate core and a shell of peptide amphiphile nanofibres functionalized for targeting the folate receptor. The spherical geometry of the particle core allows high drug loading per surface area, whereas the nanoscale fibrous shell formed by self-assembly of peptide amphiphiles offers a high surface to volume ratio that is ideal for targeting. Furthermore, the synthesised microparticles have a 60-fold higher cytotoxicity against MDA-MB-231 breast cancer cells compared to non-targeting particles.

77 NANOSCIENCE AND NANOTECHNOLOGY↗

Water-Assisted Proton Delivery and Removal in bio-inspired Hydrogen Production Catalysts

Electrocatalysts for H2 production are envisioned to play an important role in renewable energy utilization systems. Nickel-based catalysts featuring pendant amines functioning as proton relays in the second coordination sphere of a metal center have led to catalysts achieving turnover frequencies as high as 107 s-1 for H2 production. The fastest rates are observed when water is present in solution, with rates up to 102 times faster than dry conditions. The focus of this paper is to provide mechanistic insight into the unexpected enhancement due to water. Addition of H2 to [Ni(PR2NR´2)2]2+ was previously shown to give three isomers of a Ni(0) product with two protonated amines, where the N-H can be endo or exo to the Ni. By investigating the deprotonation of two N-protonated Ni(0) intermediates resulting from H2 addition to to [Ni(PR2NR´2)2]2+, we observe an enhancement in the rate of deprotonation for protons positioned on the pendant amine next to the metal (endo) vs. protons that are positioned away from the metal (exo). Computational studies suggest that steric accessibility and desolvation energy of the deprotonating base are responsible for limiting endo deprotonation. The significant reduction in this barrier observed in the presence of water has important implications for disfavoring less productive catalytic pathways and increasing catalytic rates. This research was supported as part of the Center for Molecular Electrocatalysis, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences. Pacific Northwest National Laboratory is operated by Battelle for the U.S. Department of Energy.

Ho, Ming-Hsun↗

Ceramic micro-injection molded nozzles for serial femtosecond crystallography sample delivery

Serial femtosecond crystallography (SFX) using X-ray Free-Electron Lasers (XFELs) allows for room temperature protein structure determination without evidence of conventional radiation damage. In this method, a liquid suspension of protein microcrystals can be delivered to the X-ray beam in vacuum as a micro-jet, which replenishes the crystals at a rate that exceeds the current XFEL pulse repetition rate. Gas dynamic virtual nozzles produce the required micrometer-sized streams by the focusing action of a coaxial sheath gas and have been shown to be effective for SFX experiments. Here, we describe the design and characterization of such nozzles assembled from ceramic micro-injection molded outer gas-focusing capillaries. Trends of the emitted jet diameter and jet length as a function of supplied liquid and gas flow rates are measured by a fast imaging system. The observed trends are explained by derived relationships considering choked gas flow and liquid flow conservation. Finally, the performance of these nozzles in a SFX experiment is presented, including an analysis of the observed background.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Negative Cooperativity in the Nitrogenase Fe Protein Electron Delivery Cycle

Nitrogenase catalyzes the ATP-dependent reduction of dinitrogen (N2) to two ammonia (NH3) molecules. Catalysis involves the participation of two protein components designated the MoFe and Fe proteins. Electron transfer (ET) from the Fe protein to the catalytic MoFe protein involves a series of synchronized events requiring the transient association of one Fe protein with each aß half of the MoFe protein. This process is referred to as the Fe protein cycle and includes: binding of two ATP to an Fe protein, association of an Fe protein with the MoFe protein, ET from the Fe protein to the MoFe protein, hydrolysis of two ATP to two ADP and two Pi for each ET, Pi release, and dissociation of oxidized Fe protein-(ADP)2 from the MoFe protein. Because the MoFe protein tetramer has two separate aß active units, it has the capacity to participate in two independent Fe protein cycles. The present work examines whether the two catalytic halves of an individual MoFe protein function independently or, instead, communicate with each other during catalysis. Kinetic analyses of ET, ATP hydrolysis, and Pi release during the pre-steady state phase indicate that the two halves of the complex in fact cooperate. A global fit of the data is consistent with a two-branch negative-cooperativity kinetic model. A possible mechanism for communication between the two halves of nitrogenase is suggested by normal-mode calculations suggesting correlated and anti-correlated motions between the two nitrogenase halves.

Danyal, Karamatullah↗

MO-G-BRE-04: Automatic Verification of Daily Treatment Deliveries and Generation of Daily Treatment Reports for a MR Image-Guided Treatment Machine

Purpose: Two aims of this work were to develop a method to automatically verify treatment delivery accuracy immediately after patient treatment and to develop a comprehensive daily treatment report to provide all required information for daily MR-IGRT review. Methods: After systematically analyzing the requirements for treatment delivery verification and understanding the available information from a novel MR-IGRT treatment machine, we designed a method to use 1) treatment plan files, 2) delivery log files, and 3) dosimetric calibration information to verify the accuracy and completeness of daily treatment deliveries. The method verifies the correctness of delivered treatment plans and beams, beam segments, and for each segment, the beam-on time and MLC leaf positions. Composite primary fluence maps are calculated from the MLC leaf positions and the beam-on time. Error statistics are calculated on the fluence difference maps between the plan and the delivery. We also designed the daily treatment delivery report by including all required information for MR-IGRT and physics weekly review - the plan and treatment fraction information, dose verification information, daily patient setup screen captures, and the treatment delivery verification results. Results: The parameters in the log files (e.g. MLC positions) were independently verified and deemed accurate and trustable. A computer program was developed to implement the automatic delivery verification and daily report generation. The program was tested and clinically commissioned with sufficient IMRT and 3D treatment delivery data. The final version has been integrated into a commercial MR-IGRT treatment delivery system. Conclusion: A method was developed to automatically verify MR-IGRT treatment deliveries and generate daily treatment reports. Already in clinical use since December 2013, the system is able to facilitate delivery error detection, and expedite physician daily IGRT review and physicist weekly chart review.

60 APPLIED LIFE SCIENCES↗

Quality assurance for online adapted treatment plans: Benchmarking and delivery monitoring simulation

Purpose: An important challenge facing online adaptive radiation therapy is the development of feasible and efficient quality assurance (QA). This project aimed to validate the deliverability of online adapted plans and develop a proof-of-concept online delivery monitoring system for online adaptive radiation therapy QA. Methods: The first part of this project benchmarked automatically online adapted prostate treatment plans using traditional portal dosimetry IMRT QA. The portal dosimetry QA results of online adapted plans were compared to original (unadapted) plans as well as randomly selected prostate IMRT plans from our clinic. In the second part, an online delivery monitoring system was designed and validated via a simulated treatment with intentional multileaf collimator (MLC) errors. This system was based on inputs from the dynamic machine information (DMI), which continuously reports actual MLC positions and machine monitor units (MUs) at intervals of 50 ms or less during delivery. Based on the DMI, the system performed two levels of monitoring/verification during the delivery: (1) dynamic monitoring of cumulative fluence errors resulting from leaf position deviations and visualization using fluence error maps (FEMs); and (2) verification of MLC positions against the treatment plan for potential errors in MLC motion and data transfer at each control point. Validation of the online delivery monitoring system was performed by introducing intentional systematic MLC errors (ranging from 0.5 to 2 mm) to the DMI files for both leaf banks. These DMI files were analyzed by the proposed system to evaluate the system’s performance in quantifying errors and revealing the source of errors, as well as to understand patterns in the FEMs. In addition, FEMs from 210 actual prostate IMRT beams were analyzed using the proposed system to further validate its ability to catch and identify errors, as well as establish error magnitude baselines for prostate IMRT delivery. Results: Online adapted plans were found to have similar delivery accuracy in comparison to clinical IMRT plans when validated with portal dosimetry IMRT QA. FEMs for the simulated deliveries with intentional MLC errors exhibited distinct patterns for different MLC error magnitudes and directions, indicating that the proposed delivery monitoring system is highly specific in detecting the source of errors. Implementing the proposed QA system for online adapted plans revealed excellent delivery accuracy: over 99% of leaf position differences were within 0.5 mm, and >99% of pixels in the FEMs had fluence errors within 0.5 MU. Patterns present in the FEMs and MLC control point analysis for actual patient cases agreed with the error pattern analysis results, further validating the system’s ability to reveal and differentiate MLC deviations. Calculation of the fluence map based on the DMI was performed within 2 ms after receiving each DMI input. Conclusions: The proposed online delivery monitoring system requires minimal additional resources and time commitment to the current clinical workflow while still maintaining high sensitivity to leaf position errors and specificity to error types. The presented online delivery monitoring system therefore represents a promising QA system candidate for online adaptive radiation therapy.

07 ISOTOPE AND RADIATION SOURCES↗

Optimization of battery swapping infrastructure for e-commerce drone delivery

Drone delivery is widely-researched to alter the current e-commerce delivery convention for providing short delivery lead times. Yet, flight range of drones, constrained by the available battery technology, sets a milestone toward realizing the sole-drone delivery. To tackle with the flight range limitation, locating automated battery swapping machines (ABSM) have been proposed and a few studies modeled the problem. Using the ABSMs, drones can be loaded with fully-charged batteries along the route to a demand location. Here, we introduce a mixed-integer nonlinear program to model the problem. The objective of the program is to optimally select ABSM locations, determine the delivery-mode choices (drone-only, truck-only, and mixed delivery) of demand locations, find drone delivery routes, and approximate the baseline requirements for the number of drones and batteries needed. The program minimizes the overall delivery system costs including: ABSM, delivery, drone ownership, battery inventory, and service congestion. A cutting-plane method is developed to find exact solutions in finite iterations. Computational experiments showed that the method quickly yields the optimal solution to instances with less than 60 ABSM candidates and 20 demand locations. A case study shows that the optimal drone delivery infrastructure can save almost 20% cost compared to the conventional truck-only delivery. Sensitivity analyses were conducted to reveal the impact of key parameters in the decision-making and found that a decrease in the ABSM and drone costs highly affect the system cost.

25 ENERGY STORAGE↗