Abstract P4-01-08: Specific detection of anti-Her2 PEGylated PrecisionMRX® nanoparticles measured using superparamagnetic relaxometry

We report on the use of Superparamagnetic Relaxometry (SPMR) as a technique for monitoring the distribution of superparamagnetic magnetite (Fe3O4) nanoparticles in vivo. SPMR uses superconducting quantum interference device (SQUID) sensors to measure the remnant magnetization of nanoparticles bound to cells following a brief magnetizing pulse. Unbound nanoparticles are not detected, making SPMR uniquely capable of discriminating between nanoparticles that are circulating freely in the bloodstream from those that have been immobilized in organs and tissues throughout the body. The rate of clearance of magnetic nanoparticles from circulation is largely dependent on their hydrodynamic diameter and surface chemistry. In this study, biodistribution of PrecisionMRX™ nanoparticles with 25 nm cores and two different surface coatings were followed using the MRX™ instrument. In independent experiments, negatively charged carboxylate nanoparticles and methoxy-PEG (mPEG) functionalized nanoparticles with a near neutral charge were suspended in 100 μL of saline. Nanoparticle suspensions were injected intravenously via tail vein into Balb/C mice at a dose of 5 mg/kg of body mass, while control mice were injected with 100 μL of saline solution. Mice were measured individually on the MRX instrument at successive time points over the course of 24 hours. At selected intervals during the 24 hour period, mice were euthanized, exsanguinated, and organs harvested for ex vivo measurements on the MRX. Organs and blood were subsequently assayed for iron content. MRX measurements of mice injected with carboxylate nanoparticles showed a strong magnetic signal localized in the region of liver that reached a maximum several minutes after injection. The negative surface charge of the carboxylate nanoparticles likely resulted in their rapid opsonization in the blood and removal from circulation by phagocytic cells in the liver. Conversely, MRX measurements of mice injected with mPEG coated nanoparticles indicated an extended circulation time, with a gradually increasing magnetic signal in the liver that had not yet reached a maximum after four hours. Together, these experiments demonstrate the utility in using SPMR to measure the clearance of nanoparticles from the bloodstream following injection, an important parameter in the design of optimal coatings for in vivo diagnostic and therapeutic use. This work was performed, in part, at the Center for Integrated Nanotechnologies, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000. Citation Format: Andrew Gomez, Kayla E. Minser, Caroline L. Weldon, Bill Anderson, Todor Karaulanov, Helen J. Hathaway, Dale L. Huber, Edward R. Flynn, Erika Vreeland. Monitoring in vivo biodistribution of superparamagnetic nanoparticles using superparamagnetic relaxometry (SPMR). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4239.

Sandia National Laboratories, New Mexico (SNL/NM) is a government-owned/contractor operated facility. Sandia Corporation (Sandia), a wholly owned subsidiary of Lockheed Martin Corporation (LMC), manages and operates the laboratory for the U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA). The DOE/NNSA, Sandia Site O ffice (SSO) administers the contract and oversees contractor operations at the site. This annual report summarizes data and the compliance status of Sandia Corporation’s environmental protection and monitoring programs through December 31, 2009. Major environmental programs include air quality, water quality, groundwater protection, terrestrial surveillance, waste management, pollution prevention (P2), environmental restoration (ER), oil and chemical spill prevention, and implementation of the National Environmental Policy Act (NEPA). Environmental monitoring and surveillance programs are required by DOE Order 450.1A, Environmental Protection Program (DOE 2008a) and DOE Manual 231.1-1A, Environment, Safety, and Health Reporting (DOE 2007).

Metallic Zn is a nearly ideal anode for grid and long duration energy storage applications owing to its low cost (ca. 2 USD kg−1), existing supply chain, environmental benignity, relative safety, and high stability in water [−0.76 V vs standard hydrogen electrode (SHE)]. The high theoretical capacity (2e− @ 820 mAh g−1 and 5855 mA h cm−3), and overall low polarizability (6 × 10−8 Ω m) further motivate Zn-based battery development as alternatives to lead acid and lithium-ion batteries, despite their considerably lower operating voltages (< 2V).Despite many recent advances, the high-capacity utilization of Zn for thousands of cycles remains a challenge, with cycle life typically obtained at the expense of energy density. We recently began investigating the ability to cycle metallic zinc electrodes in mildly acidic electrolytes at high areal and volumetric capacities, properties that are requisite to take studies from the laboratory and adapt them to a commercial battery technology to support grid and long duration energy storage needs. This endeavor, and the results from it, which will be covered in this talk, led us to further question the exact cycling mechanism of zinc.As an example, cycling in zinc sulfate-based electrolytes results in the formation of zinc hydroxy sulfate, or ZHS (with a general formula of Zn x (OH) 2x-2y (SO4) y ·nH2O). Replacing the sulfate anion in the electrolyte (w/ e.g. chloride, nitrate, acetate, formate, etc.) leads to the similar ZHS analogues (Zn x (OH) 2x-2y (X) y ·nH2O), where X= anion.However, the viewpoint obtained from recent literature is that 1.) the exact cycling mechanism of Zn in mildly acidic electrolytes is unknown; 2.) the ZHS formation at the anode is considered largely irreversible and 3.) that the ZHS is derived primarily from a hydrogen evolution reaction, which causes a corresponding local increase in pH, that in the presence of e.g. Zn2+ , Xn- leads to the precipitation/crystallization of the ZHS phase. This mechanism, if correct, clearly poses challenges as it involves the consumption of both electrolyte and active material, which would preclude any long-term cycling, especially at high Zn utilization.In this talk, we will present cycling data and our results from specific inquiries into evaluating proposed mechanisms for the electrochemical cycling mechanism of zinc in mildly acidic electrolytes. Additionally, the effect of the electrolyte anion (Xn-) on cycle life as well as the structure, morphology, and functionality of the as-formed interphase will be discussed.This material is based upon work supported by the U.S. Department of Energy, Office of Electricity (OE), Energy Storage Division. This work was performed, in part, at the Center for Integrated Nanotechnologies, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science. Sandia National Laboratories is a multi-program laboratory managed and operated by National Technology and Engineering Solutions of Sandia, LLC, a wholly owned subsidiary of Honeywell International, Inc., for the U.S. Department of Energy’s National Nuclear Security Administration under contract DE-NA-0003525. This paper describes objective technical results and analysis. Any subjective views or opinions that might be expressed in the paper do not necessarily represent the views of the U.S. Department of Energy or the United States Government.

Sandia National Laboratories is a multi-purpose engineering and science laboratory owned by the U.S. Department of Energy (DOE)/National Nuclear Security Administration and managed and operated by Sandia Corporation (Sandia), a wholly-owned subsidiary of Lockheed Martin Corporation. This Solid Waste Management Unit (SWMU) Assessment Report (SAR) for the Sandia National Laboratories, New Mexico (SNL/NM), Coyote Test Field, Building 9960 Surface Discharge, has been prepared in accordance with Section V of the Compliance Order on Consent (the Consent Order) between the New Mexico Environment Department (NMED), DOE, and Sandia (NMED April 2004). The DOE and Sandia formally notified the NMED of this newly identified or suspected SWMU or Area of Concern (AOC) by letter dated December 9, 2014. This SAR is being submitted in accordance with the NMED Hazardous Waste Bureau (HWB) letter dated February 16, 2015 letter (Kieling February 2015). This SAR presents the available information for the Building 9960 Surface Discharge, including location, designation of type and function, a general description, the operational dates, waste characteristics, and a summary of existing analytical wastewater and soil data

In the field of semiconductor quantum dot spin qubits, there is growing interest in leveraging the unique properties of hole-carrier systems and their intrinsically strong spin-orbit coupling to engineer novel spin qubits. In contrast to the weak spin-orbit interaction found in Si, strong spin-orbit coupling in Ge may allow purely electrical spin control using the electric field component of a microwave drive signal applied to a confinement gate, without the need for additional components such as microwave stripline antennas or micromagnets. A crucial aspect in the search for alternative semiconductor qubit host materials is the need to maintain the advantages of existing platforms such as Si: low disorder, long coherence times, extensibility, and semiconductor foundry compatibility. Recent advances in semiconductor heterostructure growth have made available high quality, undoped Ge/SiGe quantum wells that can serve as hosts for hole spin qubits. These quantum wells consist of a pure strained Ge layer flanked by Ge-rich SiGe layers above and below, grown by reduced pressure chemical vapor deposition. Isotopic enrichment is possible if required. The heavy hole charge carriers are characterized by a small effective mass m* ~ 0.08m 0 (about 2.4x lighter than for electrons in Si), high mobility μ ≥ 1E5 cm2/Vs, and highly anisotropic g-factors. The small effective mass should allow relatively large and easily-coupled quantum dots. The next-nearest light hole band is theoretically predicted to be on the order of ~ 100 meV below the heavy hole band. The p-orbital character of the hole wavefunction may provide an advantage in minimizing contact hyperfine interactions with nonzero-spin lattice nuclei. There is both theoretical and experimental evidence of a cubic Rashba-type spin-orbit interaction in this material, whose large strength is manifest as a spin-orbit length on the order of 1 micrometer. An additional advantage over Si is that the two-dimensional band structure of Ge quantum wells does not feature valley states, which can present difficulties for qubit operations. Here, we will describe our ongoing efforts to prepare spin qubits in this platform, including development of gated device architectures, device tuning protocols, and charge-sensing capabilities. Initial work focused on single-layer gate layouts, in which lithographically-defined single and double quantum dots were demonstrated at dilution refrigerator temperatures. Charging energies of ~ 1.7 meV were observed. These devices featured a broad and shallow potential landscape, and only a small number of holes could be confined to a quantum dot. Although adjacent quantum dots could be coupled to one another, this coupling was not easily tuned using this gate design. These limitations in the confinement and control of quantum dots motivated the subsequent adoption of multilayer gate-stack architectures, similar to what has been demonstrated in Si. Our three-layer devices feature gate electrodes designed for accumulation of holes, local depletion to form quantum dots, and selective isolation/screening of electric fields. Device structures feature Ti/Pt gates, ALD oxide dielectrics, and implanted ohmic contacts. Symmetrically constructed devices comprise two gated channels for quantum dot confinement, one to be used as the quantum dot under study and the other operated as a local charge sensor. By monitoring the conductance of the charge sensor as the quantum dot is tuned, we can remotely determine the dot’s occupation number, in principle down to the last hole. Iterative cycles of device fabrication and measurement, combined with numerical modeling, have allowed continuous improvements to the device design. Early three-layer device designs suffered from poor isolation between the upper and lower mirror-symmetric device channels. Numerical modeling showed (and measurements have confirmed) that an additional isolation gate could allow improved autonomy of the two channels while maintaining their electrostatic coupling needed for charge sensing. Ongoing, simulation-informed work to fine-tune the device geometry, as well as efforts toward a qubit demonstration, will be discussed. This work was funded, in part, by the Laboratory Directed Research and Development Program and performed, in part, at the Center for Integrated Nanotechnologies, an Office of Science User Facility operated for the US Department of Energy (DOE) Office of Science. Sandia National Laboratories is a multi-mission laboratory managed and operated by National Technology & Engineering Solutions of Sandia, LLC, a wholly owned subsidiary of Honeywell International Inc., for the US Department of Energy’s National Nuclear Security Administration under contract DE-NA-0003525. The views expressed in this article do not necessarily represent the views of the US Department of Energy or the United States Government. The work at NTU was supported by the Ministry of Science and Technology (107-2622-8-002-018-). Figure 1

Tonopah Test Range (TTR) in Nevada and Kauai Test Facility (KTF) in Hawaii are government-owned, contractor-operated facilities operated by Sandia Corporation, a subsidiary of Lockheed Martin Corporation. The U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA), through the Sandia Site Office (SSO), in Albuquerque, NM, oversees TTR and KTF's operations. Sandia Corporation conducts operations at TTR in support of DOE/NNSA's Weapons Ordnance Program and has operated the site since 1957. Westinghouse Government Services subcontracts to Sandia Corporation in administering most of the environmental programs at TTR. Sandia Corporation operates KTF as a rocket preparation launching and tracking facility. This Annual Site Environmental Report (ASER) summarizes data and the compliance status of the environmental protection and monitoring program at TTR and KTF through Calendar Year (CY) 2002. The compliance status of environmental regulations applicable at these sites include state and federal regulations governing air emissions, wastewater effluent, waste management, terrestrial surveillance, and Environmental Restoration (ER) cleanup activities. Sandia Corporation is responsible only for those environmental program activities related to its operations. The DOE/NNSA, Nevada Site Office (NSO) retains responsibility for the cleanup and management of ER TTR sites. Currently, there are no ER Sites at KTF. Environmental monitoring and surveillance programs are required by DOE Order 5400.1, General Environmental Protection Program (DOE 1990) and DOE Order 231.1, Environment, Safety, and Health Reporting (DOE 1996).

Olivine lithium iron phosphate (LiFePO4) is a technologically important electrode material for lithium-ion batteries and a model system for studying electrochemically-driven phase transformations. Despite extensive studies, many aspects of the phase transformation and Li transport in LiFePO4 are still not well understood. Here we combine operando hard X-ray spectroscopic imaging and phase-field modeling to elucidate the delithiation dynamics of single-crystal LiFePO4 microrods with long-axis along the [010] direction. Our study reveals two-dimensional Li diffusivity in microsized LiFePO4 particles containing ~3% Li-Fe antisite defects and provides direct evidence for the previously predicted surface-reaction-limited phase boundary migration mechanism for the first time. Further, a new hybrid mode of phase growth is discovered, in which phase boundary movement is controlled by surface reaction or Li diffusion in different crystallographic directions. These findings uncover the rich phase transformation behaviors in LiFePO4 and intercalation compounds in general and can help the design of better electrodes. Acknowledgments This research was supported by U.S. National Science Foundation grant DMR-1106184 and DMR-1508558 for the synthesis and characterization of the material, and the UW-Madison WEI Seed Grant for the TXM-XANES studies (to S.J.). Material characterization is also partially supported by U.S. Department of Energy (DOE), Office of Science, Office of Basic Energy Sciences under Contract No. DE-SC0002626 (to Y.M.C.). Theoretical modeling and analysis (L.H. and M.T.) are supported by U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-SC0014435. The operando TXM-XANES experiments were performed at beamline X8c, National Synchrotron Light Source I, Brookhaven National Laboratory, which are supported by the U.S. DOE, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-98CH10886. Use of the Advanced Photon Source, an Office of Science User Facility operated for the U.S. DOE, Office of Science by Argonne National Laboratory, was supported by the U.S. DOE under Contract No. DE-AC02-06CH11357. L.L also thanks Vilas Research Travel Awards for partially supporting the travel to the synchrotron facilities. The authors thank Olaf J. Borkiewicz and Kamila M. Wiaderek for helping to collect powder X-ray diffraction data of LiFePO4 reported in this work. We acknowledge supercomputing allocations provided by the Texas Advanced Computing Center (TACC) at The University of Texas, and also the National Energy Research Scientific Computing Center, a DOE Office of Science User Facility supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. The research also uses HPC resources supported in part by the Big-Data Private-Cloud Research Cyberinfrastructure MRI-award funded by NSF under grant CNS-1338099 and by Rice University. Figure 1

Sandia National Laboratories, New Mexico (SNL/NM) is a government-owned/contractor-operated laboratory. Sandia Corporation (Sandia), a wholly owned subsidiary of Lockheed Martin Corporation, manages and operates SNL/NM for the U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA). The DOE/NNSA Sandia Field Office administers the contract and oversees contractor operations at the site. Sandia conducts two types of groundwater surveillance monitoring at SNL/NM: (1) on a site-wide basis as part of the SNL/NM Long-Term Stewardship (LTS) Program's Groundwater Monitoring Program (GMP) Groundwater Surveillance Task and (2) as site-specific groundwater monitoring at LTS/Environmental Restoration (ER) Operations sites with ongoing groundwater investigations.

At sufficiently high concentrations, many surfactants can direct electrodeposited or chemically reduced metals to form nanoporous structures. The surfactants can be small molecules, block copolymers, or polymers with functional endgroups. Under some conditions, the pores exhibit uniform, tunable sizes and long-range ordering. We will present a brief overview of demonstrations of these phenomena from the literature, and then focus on our own efforts to produce and characterize various forms of nanoporous palladium, a material of interest for energy storage, hydrogen storage, gas separation and sensing, and catalysis applications. We have used liquid-cell transmission electron microscopy and small-angle neutron scattering to study the mechanisms of particle growth in the presence of surfactants. Our results suggest that Pd nanoparticles form and sinter around micelles present in the aqueous phase. Changing the size of the surfactant molecules affects the size of these micelles, and ultimately determines the pore dimensions. Careful control of surfactant self-assembly and particle growth conditions is required to obtain long-range order. However, porosity that is more disordered, but still of quite uniform size distribution, can be obtained under much more relaxed conditions, and lower surfactant concentrations. We believe that interactions between the surfactants and the metal surfaces are more influential in these cases. The flexible range of conditions under which surfactants are able to induce nanoporosity suggests that this technology could prove to be a valuable synthetic method for energy materials with high power densities, as well as chemical engineering materials with high surface reaction rates. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000. The Lujan Neutron Scattering Center at LANSCE is funded by the DOE Office of Basic Energy Sciences and Los Alamos National Laboratory under DOE Contract DE-AC52-06NA25396. The work was funded in part by Sandia’s Laboratory-Directed Research and Development program.

Behind-the-meter storage (BTMS) encompasses storage and distribution systems that bypass the electric grid. For example, energy stored in BTMS stationary batteries can be used for various purposes including electric vehicle charging or lowering the cooling load demands for large buildings. Many previous studies have focused on Li4Ti5O12/LiMn2O4 (LTO/LMO) batteries for BTMS applications1–3 rather than the more conventional electric vehicles comprised of graphite anodes paired with LiFePO4 or layered oxide materials. LTO/LMO batteries are appropriate for BTMS because they provide a favorable balance of cost, safety, and cycle life, which are the most important criteria for BTMS batteries. LTO’s minimal strain, high operating voltage, and relatively earth abundant materials promote cyclability, safety, and reasonable cost.4 LMO is very attractive to pair with LTO for BTMS applications due to abundancy of Mn, safety, and relatively high operating voltage to enable a higher voltage when paired with LTO.5 While LTO/LMO fulfills many requirements for BTMS applications, the high voltage of LTO and the low capacity of LMO limit energy density and specific energy. Improving energy density has the potential to decrease cost in addition to enabling a smaller battery footprint for space-constrained BTMS applications.With the goal of increasing the cathode capacity at high voltage to improve the BTMS battery energy density relative to LTO/LMO, we investigated LTO paired with LiNi0.90Mn0.05Co0.05O2 (NMC90-5-5). We selected NMC90-5-5 for its low Co content to minimize the impact of the cost volatility and supply chain challenges with Co in accordance with BTMS program goals. We investigated long term cycle life and rate capability of LTO/NMC90-5-5 coin cells with two different N/P ratios and two different charge termination potentials. Without the risk of Li plating at high LTO potentials, the cathode can be safely oversized in LTO systems (N/P < 1) such that the excess cathode capacity provides additional Li inventory to overcome losses during cycling and enables longer cycle life. We compared cells fabricated with N/P < 1 with N/P > 1 and we found that cells with N/P < 1 provided higher cell capacity during 1000 cycle tests. We also varied the full cell termination charge potential (2.6 V versus 2.7 V) for each N/P condition. While the 2.7 V termination potential enabled higher capacity, the 2.6 V termination enabled more stable cycling during 1000 cycle tests. Furthermore, because high Ni content layered oxide systems typically exhibit safety challenges,6,7 we also fabricated 18650 LTO/NMC90-5-5 full cells for accelerating rate calorimetry (ARC) testing. ARC testing revealed a significantly lower heating rate as well as a higher temperature where the max heating rate occurred for cells cycled to 2.6 V versus 2.7 V. These data suggest that the termination potential in NMC90-5-5 is critical for optimizing these cathodes for the long cycle life and safety required for BTMS applications.This work was authored in part by the National Renewable Energy Laboratory, operated by Alliance for Sustainable Energy, LLC, for the U.S. Department of Energy (DOE) under Contract No. DE-AC36-08GO28308. This work was performed, in part, at Sandia National Laboratories, a multi-mission laboratory managed and operated by National Technology & Engineering Solutions of Sandia, LLC (NTESS), a wholly owned subsidiary of Honeywell International Inc., for the U.S. Department of Energy’s National Nuclear Security Administration (DOE/NNSA) under contract DE-NA0003525. Funding was provided by the U.S. Department of Energy's Vehicle Technologies Office under the Behind-the-Meter Storage (BTMS) Consortium directed by Samuel Gillard and managed by Anthony Burrell. The electrodes used in this manuscript are from Argonne's Cell Analysis, Modeling and Prototyping (CAMP) Facility, which is fully supported by the DOE Vehicle Technologies Office (VTO). The views expressed in the article do not necessarily represent the views of the DOE or the U.S. Government. The U.S. Government retains and the publisher, by accepting the article for publication, acknowledges that the U.S. Government retains a nonexclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this work, or allow others to do so, for U.S. Government purposes.(1) Y. Ha et al., Journal of The Electrochemical Society 2023, 170 (5), 050520.(2) Y. Ha et al., Journal of The Electrochemical Society 2021, 168 (11), 110536.(3) Y. Ha et al., Energy Storage Materials 2021, 38, 581–589.(4) G. Xu et al., Coordination Chemistry Reviews 2017, 343, 139–184.(5) Z. Radzi et al. Journal of Electroanalytical Chemistry 2022, 116623.(6) L. Gan et al., Applied Physics Letters 2022, 121 (20).(7) J. Lamb et al., Journal of The Electrochemical Society 2021, 168 (6), 060516.

Sandia National Laboratories is a multiprogram laboratory managed and operated by Sandia Corporation (Sandia), a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy’s National Nuclear Security Administration under contract DE-AC04-94AL85000. This Annual Site Environmental Report summarizes data and the compliance status of Sandia’s sustainability, environmental protection, and monitoring programs at Sandia National Laboratories, New Mexico, during calendar year 2014. Major environmental programs include air quality, water quality, groundwater protection, terrestrial surveillance, waste management, pollution prevention, environmental restoration, oil and chemical spill prevention, and implementation of the National Environmental Policy Act. Environmental monitoring and surveillance programs are required by DOE O 231.1B, Change 1, Environment, Safety, and Health Reporting.

We study the use of nanoelectrode arrays (NEAs), consisting of billions/cm2 of ~ 75 nm diameter electrodes, for the electrochemical analysis of ionic halogen species in water. Such NEA sensors were previously demonstrated to detect part-per-billion (ppb) levels of Pb-ions in aqueous solutions without supporting electrolytes. Briefly, the individual electrodes in the NEA can be tailored with sufficient separation coupled with pore-depth control so that each experiences non-overlapping hemispherical diffusion zones within which the ionic flux of an analyte is independent of time. This geometry is well-suited for trace-level detection, as fast voltage sweeps result in a large and steady-state current density. With optimized design, the additive response from the plethora of nanoelectrodes leads to an orders-of-magnitude analytical advantage for electrochemical detection compared to conventional (mm) sized disc electrodes using sweep or pulse voltammetric techniques. NEAs are fabricated by anodizing RF-sputter deposited Al films on a substrate-of-choice, resulting in billions/cm2 tailored with controllable pore diameters. Each nanopore is partially filled via electrochemical plating with an appropriate working electrode material, such as Au, Pt or Ni. A thin W film is beneath the nanopore template for both processing assistance and to provide a backside electrical contact in parallel to every nanoelectrode. In the case that the NEA is recessed within the porous alumina, a thin conducting film can be added to the topside to function as a counter/pseudo-reference electrode. In some situations, the counter electrode can also serve as an ion collector, preconcentrating ionic species near the pore openings prior to beginning an electrochemical measurement. Using such NEA sensors, we will demonstrate trace detection levels for both Cl and I ionic species in water, and compare the limits-of-detection with conventional electrodes. In addition, we explore the possibility of using NEA sensors to detect halogens in the gas phase. By manipulating the NEA structure, the monitoring capability may be extended to gas phase detection of Cl2 or I2. Such gas-phase detection is possible by utilizing the natural humidity in air condensing on the nanopore walls above the recessed working electrodes. Indirect sensing of such gases occurs after they dissolve in the pore water to form electrochemically detectable halogen species. Notably, the electrochemical measurement is achieved with simple, condensed humidity as the sole ionically conducting phase, without the need for a supporting electrolyte. This is because the high resistivity of water† is mitigated by the short ionic path length: the net solution resistance is small because of the sub-micron distance separating the NEA electrodes from the counter/pseudo-reference electrode sputtered upon the surface of the opposite (open) end of the pore. †The conductivity of humidity levels we consider in this study range from 10-6 S/m (humidity from DI water) to 10-3-10-4 S/m (conductivity range of natural humidity across the USA as monitored by the National Atmospheric Deposition Program’s National Trend Network). This work is supported by the Laboratory Directed Research and Development program at Sandia National Laboratories. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Binary-discrimination tasks useful to arms-control-treaty verification were performed by applying mathematical observer models used by the medical-imaging community. It is a difficult task, as the monitor needs to verify a measured object is a warhead while the host wants to prevent dissemination of sensitive information on their weapons. Inspection objects were classified by their projection data, without reconstructing an image, which often contains sensitive information. Furthermore, the models process data event-by-event, with only a scalar test statistic being updated before the observed data is purged from memory, preventing the aggregation of information which would be sensitive. Template matching models were developed from a set of calibration data on these objects, with the ultimate goal being to develop an observer model that stores only non-sensitive information sufficient for confirmation. These models were also analyzed in the presence of nuisance parameters — unknowns in the objects or imaging system that affect the projection data but aren't of interest to the discrimination task. Examples of these include object location and orientation. The Hotelling observer and channelized Hotelling observer were modeled and their benefits to information security analyzed. The Hotelling observer-the ideal linear observer when the statistics of the data are Gaussian-stores only a set of weights which are the product of the inverse average covariance matrix and difference in mean data between the two objects in the discrimination task. When testing a source, an inner product of the Hotelling weights and binned testing data is taken, resulting in a scalar that is thresholded to make a decision. If nuisance parameters are present, the mean and covariance matrix are found by averaging not only over the always present Poisson noise, but the nuisance parameter distributions as well. Hence, even if detector data is gathered from multiple realizations of an object, the Hotelling weights will be a single smeared out data set the size of the measured data. The Hotelling weights also sifts out all information other than the differences between the two objects. Hence, if the monitor was to gain access to the weights and apply the inverse to their test statistic, they could only back out a scaled version of the template, not the image. The channelized Hotelling observer-a common tool used in medical image quality assessment-was also investigated. This method drastically reduces the size of the data by applying a channeiizing matrix to the binned testing data set. An optimal set of weights for the channelized data can then be found, and the inner product between these weights and the channelized vector results in the scalar test statistic. Optimal performance is retained by optimizing the matrix to maximize the SNR2 between the test-statistic distributions for the two sources in the task. The channelized Hotelling observer gives the monitor access to multiple non-sensitive test statistics. In practice, the channelizing matrix could be implemented in hardware or software behind an information barrier. The addition of penalty terms to the channelized Hotelling observer offers further potential for this method. Individual channel performance could be penalized, leading to a large number of non-sensitive channels that the monitor can use to verify the channelization routine is working as described without gaining access to sensitive information. Noise could be added to the resulting channels, causing additional reduction of the total stored information. Finally, if the host can define what information in its object geometries is sensitive in advance, they could optimize the differences between the two objects in the task while penalizing out the sensitive information, creating a non-sensitive channeiizing matrix that could be shared with the monitor. To test these models, Monte Carlo simulations were performed with the GEANT4 toolkit. Photons were tracked from plutonium inspection objects developed by Idaho National Laboratory. We simulated the Fast-Neutron Imaging system designed by Oak Ridge National Laboratory and Sandia National Laboratories, which consists of 40×40 1cm2 liquid scintillator pixels with a plastic coded aperture. Observer models were evaluated using the area under the ROC curve. This work is supported by the Office of Defense Nuclear Nonproliferation Research and Development, Nuclear Weapon and Material Security Team. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000. (SAND2015-10391A).

This SAND report provides the technical progress through April 2005 of the Sandia-led project, "Carbon Sequestration in Synechococcus Sp.: From Molecular Machines to Hierarchical Modeling," funded by the DOE Office of Science Genomics:GTL Program. Understanding, predicting, and perhaps manipulating carbon fixation in the oceans has long been a major focus of biological oceanography and has more recently been of interest to a broader audience of scientists and policy makers. It is clear that the oceanic sinks and sources of CO2 are important terms in the global environmental response to anthropogenic atmospheric inputs of CO2 and that oceanic microorganisms play a key role in this response. However, the relationship between this global phenomenon and the biochemical mechanisms of carbon fixation in these microorganisms is poorly understood. In this project, we will investigate the carbon sequestration behavior of Synechococcus Sp., an abundant marine cyanobacteria known to be important to environmental responses to carbon dioxide levels, through experimental and computational methods. This project is a combined experimental and computational effort with emphasis on developing and applying new computational tools and methods. Our experimental effort will provide the biology and data to drive the computational efforts and include significant investment in developing new experimental methods for uncovering protein partners, characterizing protein complexes, identifying new binding domains. We will also develop and apply new data measurement and statistical methods for analyzing microarray experiments. Computational tools will be essential to our efforts to discover and characterize the function of the molecular machines of Synechococcus. To this end, molecular simulation methods will be coupled with knowledge discovery from diverse biological data sets for high-throughput discovery and characterization of protein-protein complexes. In addition, we will develop a set of novel capabilities for inference of regulatory pathways in microbial genomes across multiple sources of information through the integration of computational and experimental technologies. These capabilities will be applied to Synechococcus regulatory pathways to characterize their interaction map and identify component proteins in these - 4 -pathways. We will also investigate methods for combining experimental and computational results with visualization and natural language tools to accelerate discovery of regulatory pathways. The ultimate goal of this effort is develop and apply new experimental and computational methods needed to generate a new level of understanding of how the Synechococcus genome affects carbon fixation at the global scale. Anticipated experimental and computational methods will provide ever-increasing insight about the individual elements and steps in the carbon fixation process, however relating an organism's genome to its cellular response in the presence of varying environments will require systems biology approaches. Thus a primary goal for this effort is to integrate the genomic data generated from experiments and lower level simulations with data from the existing body of literature into a whole cell model. We plan to accomplish this by developing and applying a set of tools for capturing the carbon fixation behavior of complex of Synechococcus at different levels of resolution. Finally, the explosion of data being produced by high-throughput experiments requires data analysis and models which are more computationally complex, more heterogeneous, and require coupling to ever increasing amounts of experimentally obtained data in varying formats. These challenges are unprecedented in high performance scientific computing and necessitate the development of a companion computational infrastructure to support this effort. More information about this project can be found at www.genomes-to-life.org Acknowledgment We want to gratefully acknowledge the contributions of: Grant Heffelfinger1*, Anthony Martino2, Brian Palenik6, Andrey Gorin3, Ying Xu10,3, Mark Daniel Rintoul1, Al Geist3, Matthew Ennis1, with Pratul Agrawal3, Hashim Al-Hashimi8, Andrea Belgrano12, Mike Brown1, Xin Chen9, Paul Crozier1, PguongAn Dam10, Jean-Loup Faulon2, Damian Gessler12, David Haaland1, Victor Havin4, C.F. Huang5, Tao Jiang9, Howland Jones1, David Jung3, Katherine Kang14, Michael Langston15, Shawn Martin1, Shawn Means1, Vijaya Natarajan4, Roy Nielson5, Frank Olken4, Victor Olman10, Ian Paulsen14, Steve Plimpton1, Andreas Reichsteiner5, Nagiza Samatova3, Arie Shoshani4, Michael Sinclair1, Alex Slepoy1, Shawn Stevens8, Charlie Strauss5, Zhengchang Su10, Ed Thomas1, Jerilyn Timlin1, WimVermaas13, Xiufeng Wan11, HongWei Wu10, Dong Xu11, Grover Yip8, Erik Zuiderweg8 *Author to whom correspondence should be addressed (gsheffe@sandia.gov) 1. Sandia National Laboratories, Albuquerque, NM 2. Sandia National Laboratories, Livermore, CA 3. Oak Ridge National Laboratory, Oak Ridge, TN 4. Lawrence Berkeley National Laboratory, Berkeley, CA 5. Los Alamos National Laboratory, Los Alamos, NM 6. University of California, San Diego 7. University of Illinois, Urbana/Champaign 8. University of Michigan, Ann Arbor 9. University of California, Riverside 10. University of Georgia, Athens 11. University of Missouri, Columbia 12. National Center for Genome Resources, Santa Fe, NM 13. Arizona State University 14. The Institute for Genomic Research 15. University of Tennessee 5 Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the United States Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL8500.

As the extent of the shortage becomes clear, an interagency task force is giving scientific users priority, but some say the material is not available at any price.