Evaluating the demand side: New challenges for evaluation

Evaluation of research and innovation policy faces radical challenges arising from a new policy emphasis upon demand-side measures and linked to this an understanding of innovation policy as a means to achieve societal goals. This article considers the implications for the practice of evaluation at both micro and meso-levels. It uses the exemplar of an evaluation design for the European Union's Lead Market Initiative to expose the extent to which classical approaches to evaluation are valid and where new issues arise. Some problems highlighted include the difficulty of establishing a relevant baseline, the inability of public statistics constructed in supply-side mode to capture actions, the need to engage with actors who do not necessarily see themselves as part of the initiative being evaluated, long timescales and potential wide geographical scope, measures that span from micro to macro, and blurred boundaries between implementation and impact. It is concluded that there is a key role for evaluators to become involved in co-learning and co-evolution of these policy instruments in a manner analogous to the relationship between evaluation and policy development that characterized the emergence of collaborative R&D support programmes

Reactor Safety Research Programs Quarterly Report October - December 1980

This document summarizes the work performed by Pacific Northwest laboratory (PNL) from October 1 through December 31, 1981, for the Division of Accident Evaluation, U.S. Nuclear Regulatory Commission (NRC). Evaluations of nondestructive examination (NDE) techniques and instrumentation are reported; areas of investigation include demonstrating the feasibility of determining the strength of structural graphite, evaluating the feasibility of detecting and analyzing flaw growth in reactor pressure boundary systems, examining NDE reliability and probabilistic fracture mechanics, and assessing the integrity of pressurized water reactor (PWR) steam generator tubes where serviceinduced degradation has been indicated. Experimental data and analytical models are being provided to aid in decision-making regarding pipe-to-pipe impacts following postulated breaks in high-energy fluid system piping. Core thermal models are being developed to provide better digital codes to compute the behavior of full-scale reactor systems under postulated accident conditions. Fuel assemblies and analytical support are being provided for experimental programs at other facilities. These programs include loss-of-coolant accident (LOCA) simulation tests at the NRU reactor, Chalk River, Canada; fuel rod deformation, severe fuel damage, and post accident coolability tests for the ESSOR reactor Super Sara Test Program, lspra, Italy; the instrumented fuel assembly irradiation program at Halden, Norway; and experimental programs at the Power Burst Facility, Idaho National Engineering Laboratory (INEL), Idaho Falls, Idaho. These programs will provide data for computer modeling of reactor system and fuel performance during various abnormal operating conditions

Reactor Safety Research Programs

This document summarizes the work performed by Pacific Northwest Laboratory (PNL) from January 1 through March 31, 1981, for the Division of Reactor Safety Research within the U.S. Nuclear Regulatory Commission (NRC). Evaluations of nondestructive examination (NDE) techniques and instrumentation are reported; areas of investigation include demonstrating the feasibility of determining the strength of structural graphite, evaluating the feasibility of detecting and analyzing flaw growth in reactor pressure boundary systems, examining NDE reliability and probabilistic fracture mechanics, and assessing the integrity of pressurized water reactor (PWR) steam generator tubes where service-induced degradation has been indicated. Experimental data and analytical models are being provided to aid in decision-making regarding pipeto- pipe impacts following postulated breaks in high-energy fluid system piping. Core thermal models are being developed to provide better digital codes to compute the behavior of full-scale reactor systems under postulated accident conditions. Fuel assemblies and analytical support are being provided for experimental programs at other facilities. These programs include loss-ofcoolant accident (LOCA) simulation tests at the NRU reactor, Chalk River, Canada; fuel rod deformation, severe fuel damage, and postaccident coolability tests for the ESSOR reactor Super Sara Test Program, Ispra, Italy; the instrumented fuel assembly irradiation program at Halden, Norway; and experimental programs at the Power Burst Facility, Idaho National Engineering Laboratory (INEL). These programs will provide data for computer modeling of reactor system and fuel performance during various abnormal operating conditions

Reactor Safety Research Programs Quarterly Report April- June 1981

This document summarizes the work performed by Pacific Northwest laboratory (PNL} from April1 through June 30, 1981, for the Division of Reactor Safety Research within the U.S. Nuclear Regulatory Commission (NRC). Evaluations of nondestructive examination (NDE) techniques and instrumentation are reported; areas of investigation include demonstrating the feasibility of determining the strength of structural graphite, evaluating the feasibility of detecting and analyzing flaw growth in reactor pressure boundary systems, examining NDE reliability and probabilistic fracture mechanics, and assessing the integrity of pressurized water reactor (PWR) steam generator tubes where service-induced degradation has been indicated. Experimental data and analytical models are being provided to aid in decision-making regarding pipe-to-pipe impacts following postulated breaks in high-energy fluid system piping. Core thermal models are being developed to provide better digital codes to compute the behavior of full-scale reactor systems under postulated accident conditions. Fuel assemblies and analytical support are being provided for experimental programs at other facilities. These programs include loss-of-coolant accident (LOCA) simulation tests at the NRU reactor, Chalk River, Canada; fuel rod deformation, severe fuel damage, and postaccident coolability tests for the ESSOR reactor Super Sara Test Program, lspra, Italy; the instrumented fuel assembly irradiation program at Halden, Norway; and experimental programs at the Power Burst Facility, Idaho National Engineering Laboratory {INEL). These programs will provide data for computer modeling of reactor system and fuel performance during various abnormal operating conditions

Bottom-Up Cubosome Synthesis Without Organic Solvents

This dataset contains processed SAXS data for mixtures of phytantriol with different diluents, and also following bottom-up synthesis of cubosomes. This data was collected to demonstrate the phase formations of phytantriol under different conditions.SAXS data was collected on an Anton-Parr SAXSpoint 2.0.SAXS data was collected on an Anton-Parr SAXSpoint 2.0, using an SDD of 556.9mm. The instrument is known to have a single dead pixel which sometimes results in an anomolous single-point peak

Microglia in aging and Alzheimer’s disease: A comparative species review

Microglia are the primary immune cells of the central nervous system that help nourish and support neurons, clear debris, and respond to foreign stimuli. Greatly impacted by their environment, microglia go through rapid changes in cell shape, gene expression, and functional behavior during states of infection, trauma, and neurodegeneration. Aging also has a profound effect on microglia, leading to chronic inflammation and an increase in the brain’s susceptibility to neurodegenerative processes that occur in Alzheimer’s disease. Despite the scientific community’s growing knowledge in the field of neuroinflammation, the overall success rate of drug treatment for age-related and neurodegenerative diseases remains incredibly low. Potential reasons for the lack of translation from animal models to the clinic include the use of a single species model, an assumption of similarity in humans, and ignoring contradictory data or information from other species. To aid in the selection of validated and predictive animal models and to bridge the translational gap, this review evaluates similarities and differences among species in microglial activation and density, morphology and phenotype, cytokine expression, phagocytosis, and production of oxidative species in aging and Alzheimer’s disease

Mechanisms Regulating the Association of Protein Phosphatase 1 with Spinophilin and Neurabin

Protein phosphorylation is a key mediator of signal transduction, allowing for dynamic regulation of substrate activity. Whereas protein kinases obtain substrate specificity by targeting specific amino acid sequences, serine/threonine phosphatase catalytic subunits are much more promiscuous in their ability to dephosphorylate substrates. To obtain substrate specificity, serine/threonine phosphatases utilize targeting proteins to regulate phosphatase subcellular localization and catalytic activity. Spinophilin and its homologue neurabin are two of the most abundant dendritic spine-localized protein phosphatase 1 (PP1) targeting proteins. The association between spinophilin and PP1 is increased in the striatum of animal models of Parkinson's disease (PD). However, mechanisms that regulate the association of spinophilin and neurabin with PP1 are unclear. Here, we report that the association between spinophilin and PP1α or PP1γ1 was increased by CDK5 expression and activation in a heterologous cell system. This increased association is at least partially due to phosphorylation of PP1. Conversely, CDK5 expression and activation decreased the association of PP1 with neurabin. As with dopamine depletion, methamphetamine (METH) abuse causes persistent alterations in dopamine signaling which influence striatal medium spiny neuron function and biochemistry. Moreover, both METH toxicity and dopamine depletion are associated with deficits in motor control and motor learning. Pathologically, we observed a decreased association of spinophilin with PP1 in rat striatum evaluated one month following a binge METH paradigm. Behaviorally, we found that loss of spinophilin recapitulates rotarod pathology previously observed in dopamine-depleted and METH-treated animals. Together, these data have implications in multiple disease states associated with altered dopamine signaling such as PD and psychostimulant drug abuse and delineate a novel mechanism by which PP1 interactions with spinophilin and neurabin may be differentially regulated

Behavioral and neurochemical studies of inherited manganese-induced dystonia-parkinsonism in Slc39a14-knockout mice

Inherited autosomal recessive mutations of the manganese (Mn) transporter gene SLC39A14 in humans, results in elevated blood and brain Mn concentrations and childhood-onset dystonia-parkinsonism. The pathophysiology of this disease is unknown, but the nigrostriatal dopaminergic system of the basal ganglia has been implicated. Here, we describe pathophysiological studies in Slc39a14-knockout (KO) mice as a preclinical model of dystonia-parkinsonism in SLC39A14 mutation carriers. Blood and brain metal concentrations in Slc39a14-KO mice exhibited a pattern similar to the human disease with highly elevated Mn concentrations. We observed an early-onset backward-walking behavior at postnatal day (PN) 21 which was also noted in PN60 Slc39a14-KO mice as well as dystonia-like movements. Locomotor activity and motor coordination were also impaired in Slc39a14-KO relative to wildtype (WT) mice. From a neurochemical perspective, striatal dopamine (DA) and metabolite concentrations and their ratio in Slc39a14-KO mice did not differ from WT. Striatal tyrosine hydroxylase (TH) immunohistochemistry did not change in Slc39a14-KO mice relative to WT. Unbiased stereological cell quantification of TH-positive and Nissl-stained estimated neuron number, neuron density, and soma volume in the substantia nigra pars compacta (SNc) was the same in Slc39a14-KO mice as in WT. However, we measured a marked inhibition (85–90%) of potassium-stimulated DA release in the striatum of Slc39a14-KO mice relative to WT. Our findings indicate that the dystonia-parkinsonism observed in this genetic animal model of the human disease is associated with a dysfunctional but structurally intact nigrostriatal dopaminergic system. The presynaptic deficit in DA release is unlikely to explain the totality of the behavioral phenotype and points to the involvement of other neuronal systems and brain regions in the pathophysiology of the disease