An overview of regulatory issues that affect the development of new waste treatment technologies

The development of new and innovative waste treatment technologies can significantly benefit the U.S. Department of Energy's (DOE) environmental restoration and waste management program. New technologies are expected to facilitate faster, better, cheaper, and safer remediation of existing waste problems. To encourage and direct the development of new waste treatment and management technologies, DOE established a research, development, demonstration, testing, and evaluation (RDDT E) program. The RDDT E program is managed by DOE's Office of Technology Development. The development, acceptance, and application of new technologies involves more than simply technical problems. If the best new technologies are to be applied in the fastest and most cost-effective manner possible, DOE must consider regulatory factors early and often in the technology development process. This report presents a number of regulatory issues that are relevant to any program intended to encourage the development of new waste treatment and management technologies. The report was prepared by Pacific Northwest Laboratory. 38 refs., 6 figs., 2 tabs

Ultrafast glutamate sensors resolve high-frequency release at Schaffer collateral synapses

Glutamatergic synapses display a rich repertoire of plasticity mechanisms on many different time scales, involving dynamic changes in the efficacy of transmitter release as well as changes in the number and function of postsynaptic glutamate receptors. The genetically encoded glutamate sensor iGluSnFR enables visualization of glutamate release from presynaptic terminals at frequencies up to ∼10 Hz. However, to resolve glutamate dynamics during high-frequency bursts, faster indicators are required. Here, we report the development of fast (iGluf) and ultrafast (iGluu) variants with comparable brightness but increased Kd for glutamate (137 μM and 600 μM, respectively). Compared with iGluSnFR, iGluu has a sixfold faster dissociation rate in vitro and fivefold faster kinetics in synapses. Fitting a three-state model to kinetic data, we identify the large conformational change after glutamate binding as the rate-limiting step. In rat hippocampal slice culture stimulated at 100 Hz, we find that iGluu is sufficiently fast to resolve individual glutamate release events, revealing that glutamate is rapidly cleared from the synaptic cleft. Depression of iGluu responses during 100-Hz trains correlates with depression of postsynaptic EPSPs, indicating that depression during high-frequency stimulation is purely presynaptic in origin. At individual boutons, the recovery from depression could be predicted from the amount of glutamate released on the second pulse (paired pulse facilitation/depression), demonstrating differential frequency-dependent filtering of spike trains at Schaffer collateral boutons

Nudging service providers and assessing service trade-offs to reduce the social inefficiencies of payments for ecosystem services schemes

Socially inefficient payment for ecosystem services (PES) schemes result when adverse shifts in the provisioning of other ecosystem services (ES) or overpayment to service providers occur. To address these inefficiencies, a holistic evaluation of trade-offs between services should be conducted in parallel with determining land owners' service provisioning preferences. Recent evidence also suggests that nudging stakeholders' preferences could be a useful policy design tool to address global change challenges. Forest owners' landscape management preferences were nudged to determine the impact on the social efficiency of PES schemes for biodiversity conservation and climate change mitigation in Finland. ES indicators for biodiversity conservation, carbon storage, and the albedo effect were included with traditional provisioning services (i.e. timber) and bioenergy to assess the consequent intra-service trade-offs. Synergies in provisioning of regulating services were identified, but were found to be more efficient when the management objective is for biodiversity conservation rather than climate change regulation. Nudging led to marginal gains in service provisioning above the baseline management and above neutral owner preferences, and increased aggregate service provisioning. This demonstrates the importance of considering intra-service trade-offs and that nudging could be an important tool for designing efficient PES schemes. (C) 2015 Elsevier Ltd. All rights reserved.Peer reviewe

Intracellular machinery for the transport of AMPA receptors

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73173/1/sj.bjp.0707525.pd

The Biochemistry, Ultrastructure, and Subunit Assembly Mechanism of AMPA Receptors

The AMPA-type ionotropic glutamate receptors (AMPA-Rs) are tetrameric ligand-gated ion channels that play crucial roles in synaptic transmission and plasticity. Our knowledge about the ultrastructure and subunit assembly mechanisms of intact AMPA-Rs was very limited. However, the new studies using single particle EM and X-ray crystallography are revealing important insights. For example, the tetrameric crystal structure of the GluA2cryst construct provided the atomic view of the intact receptor. In addition, the single particle EM structures of the subunit assembly intermediates revealed the conformational requirement for the dimer-to-tetramer transition during the maturation of AMPA-Rs. These new data in the field provide new models and interpretations. In the brain, the native AMPA-R complexes contain auxiliary subunits that influence subunit assembly, gating, and trafficking of the AMPA-Rs. Understanding the mechanisms of the auxiliary subunits will become increasingly important to precisely describe the function of AMPA-Rs in the brain. The AMPA-R proteomics studies continuously reveal a previously unexpected degree of molecular heterogeneity of the complex. Because the AMPA-Rs are important drug targets for treating various neurological and psychiatric diseases, it is likely that these new native complexes will require detailed mechanistic analysis in the future. The current ultrastructural data on the receptors and the receptor-expressing stable cell lines that were developed during the course of these studies are useful resources for high throughput drug screening and further drug designing. Moreover, we are getting closer to understanding the precise mechanisms of AMPA-R-mediated synaptic plasticity