Minimizing the Cost of Innovative Nuclear Technology Through Flexibility: The Case of a Demonstration Accelerator-Driven Subcritical Reactor Park

Presented is a methodology to analyze the expected Levelised Cost Of Electricity (LCOE) in the face of technology uncertainty for Accelerator-Driven Subcritical Reactors (ADSRs). It shows that flexibility in the design and deployment strategy of an ADSR park demonstrator significantly reduces its expected LCOE. The methodology recognizes in the conceptual design a range of possible technological outcomes for the ADSR accelerator system. It identifies flexibility “on” and “in” the design to modify the future development path in light of such uncertain scenarios. Uncertainty and flexibility are incorporated in the ADSR valuation. The resulting economic assessment is more realistic than typical discounted cash flow analysis that does not consider a range of development outcomes, or the flexibility to change development path

Opening the black box of mixed-metal TMP metallating reagents : direct cadmation or lithium-cadmium transmetallation?

Designed to remove some of the mystery surrounding mixed-metal TMP (2,2,6,6-tetramethylpiperidide) metallating reagents, this study examines in detail "LiCd(TMP)(3)'' in its own right. Previously established as an excellent "cadmating'' (Cd-H exchange) reagent towards a wide variety of aromatic substrates, "LiCd(TMP)(3)'' has been investigated by H-1, C-13 and Cd-113 NMR studies as well as by DOSY NMR spectroscopy. This evidence puts a question mark against its ate formulation implying it exists in THF solution as two independent homometallic amides. Exploring the reactivity of "LiCd(TMP)(3)'' with anisole as a test substrate, both experimentally by NMR studies and theoretically by DFT studies suggests a two-step lithiation/transmetallation process in which the initially formed ortho-lithiated species undergoes a reaction with Cd(TMP)(2) to form new Cd-C and Li-N bonds. For completeness, the homometallic cadmium component Cd(TMP)(2) has been comprehensively characterised for the first time including a crystal structure determination revealing a near-linear N-Cd-N arrangement

X-ray crystal structures show DNA stacking advantage of terminal nitrile substitution in Ru-dppz complexes

The new complexes [Ru(TAP)2(11-CN-dppz)]2+, [Ru(TAP)2(11-Br-dppz)]2+and [Ru(TAP)2(11,12-diCN-dppz)]2+ are reported. The addition of nitrile substituents to the dppz ligand of the DNA photooxidising complex [Ru(TAP)2(dppz)]2+ promote π-stacking interactions and ordered binding to DNA, as shown by X-ray crystallography. The structure of -[Ru(TAP)2(11-CN-dppz)]2+ with the DNA duplex d(TCGGCGCCGA)2 shows, for the first time with this class of complex, a closed intercalation cavity with an AT base pair at the terminus. The structure obtained is compared to that formed with the 11-Br and 11,12-dinitrile derivatives, highlighting the stabilization of syn guanine by this enantiomer when the terminal basepair is GC. In contrast the AT basepair has the normal Watson-Crick orientation, highlighting the difference in charge distribution between the two purine bases and the complementarity of the dppz-purine interaction. The asymmetry of the cavity highlights the importance of the purine-dppz-purine stacking interaction

Towards the design of resilient waste-to-energy systems using Bayesian networks

The concept of resilience has emerged from various domains to address how systems, people and organizations can handle uncertainty. This paper presents a method to improve the resilience of an engineering system by maximizing the system economic lifecycle value, as measured by Net Present Value, under uncertainty. The method is applied to a Waste-to-Energy system based in Singapore and the impact of combining robust and flexible design strategies to improve resilience are discussed. Robust strategies involve optimizing the initial capacity of the system while Bayesian Networks are implemented to choose the flexible expansion strategy that should be deployed given the current observations of demand uncertainties. The Bayesian Network shows promise and should be considered further where decisions are more complex. Resilience is further assessed by varying the volatility of the stochastic demand in the simulation. Increasing volatility generally made the system perform worse since not all demand could be converted to revenue due to capacity constraints. Flexibility shows increased value compared to a fixed design. However, when the system is allowed to upgrade too often, the costs of implementation negates the revenue increase. The better design is to have a high initial capacity, such that there is less restriction on the demand with two or three expansions.</jats:p

Stabilization of long-looped i-motif DNA by polypyridyl ruthenium complexes

A spectroscopic study of the interactions of Λ- and Δ-[Ru(phen)2(dppz)]2+ with i-motif DNA containing thymine loops of various lengths. In the presence of i-motifs, the luminescence of the Λ enantiomer was enhanced much more than the Δ. Despite this, the effect of each enantiomer on i-motif thermal stability was comparable. The sequences most affected by [Ru(phen)2(dppz)]2+ were those with long thymine loops; this suggests that long-looped i-motifs are attractive targets for potential transition metal complex drugs and should be explored further in drug design

Novel interactions of transglutaminase-2 with heparan sulphate proteoglycans: reflection on physiological implications

This mini-review brings together information from publications and recent conference proceedings that have shed light on the biological interaction between transglutaminase-2 and heparan sulphate proteoglycans. We subsequently draw hypothesis of possible implications in the wound healing process. There is a substantial overlap in the action of transglutaminase-2 and the heparan sulphate proteoglycan syndecan-4 in normal and abnormal wound repair. Our latest findings have identified syndecan-4 as a possible binding and signalling partner of fibronectinbound TG2 and support the idea that transglutaminase-2 and syndecan-4 acts in synergy

Genetic dissection of an amygdala microcircuit that gates conditioned fear

The role of different amygdala nuclei (neuroanatomical subdivisions) in processing Pavlovian conditioned fear has been studied extensively, but the function of the heterogeneous neuronal subtypes within these nuclei remains poorly understood. Here we use molecular genetic approaches to map the functional connectivity of a subpopulation of GABA-containing neurons, located in the lateral subdivision of the central amygdala (CEl), which express protein kinase C-δ (PKC-δ). Channelrhodopsin-2-assisted circuit mapping in amygdala slices and cell-specific viral tracing indicate that PKC-δ^+ neurons inhibit output neurons in the medial central amygdala (CEm), and also make reciprocal inhibitory synapses with PKC-δ^− neurons in CEl. Electrical silencing of PKC-δ^+ neurons in vivo suggests that they correspond to physiologically identified units that are inhibited by the conditioned stimulus, called Cel_(off) units. This correspondence, together with behavioural data, defines an inhibitory microcircuit in CEl that gates CEm output to control the level of conditioned freezing

Stronger Neural Modulation by Visual Motion Intensity in Autism Spectrum Disorders

Theories of autism spectrum disorders (ASD) have focused on altered perceptual integration of sensory features as a possible core deficit. Yet, there is little understanding of the neuronal processing of elementary sensory features in ASD. For typically developed individuals, we previously established a direct link between frequency-specific neural activity and the intensity of a specific sensory feature: Gamma-band activity in the visual cortex increased approximately linearly with the strength of visual motion. Using magnetoencephalography (MEG), we investigated whether in individuals with ASD neural activity reflect the coherence, and thus intensity, of visual motion in a similar fashion. Thirteen adult participants with ASD and 14 control participants performed a motion direction discrimination task with increasing levels of motion coherence. A polynomial regression analysis revealed that gamma-band power increased significantly stronger with motion coherence in ASD compared to controls, suggesting excessive visual activation with increasing stimulus intensity originating from motion-responsive visual areas V3, V6 and hMT/V5. Enhanced neural responses with increasing stimulus intensity suggest an enhanced response gain in ASD. Response gain is controlled by excitatory-inhibitory interactions, which also drive high-frequency oscillations in the gamma-band. Thus, our data suggest that a disturbed excitatoryinhibitory balance underlies enhanced neural responses to coherent motion in ASD

Noninvasive optical inhibition with a red-shifted microbial rhodopsin

Optogenetic inhibition of the electrical activity of neurons enables the causal assessment of their contributions to brain functions. Red light penetrates deeper into tissue than other visible wavelengths. We present a red-shifted cruxhalorhodopsin, Jaws, derived from Haloarcula (Halobacterium) salinarum (strain Shark) and engineered to result in red light–induced photocurrents three times those of earlier silencers. Jaws exhibits robust inhibition of sensory-evoked neural activity in the cortex and results in strong light responses when used in retinas of retinitis pigmentosa model mice. We also demonstrate that Jaws can noninvasively mediate transcranial optical inhibition of neurons deep in the brains of awake mice. The noninvasive optogenetic inhibition opened up by Jaws enables a variety of important neuroscience experiments and offers a powerful general-use chloride pump for basic and applied neuroscience.McGovern Institute for Brain Research at MIT (Razin Fellowship)United States. Defense Advanced Research Projects Agency. Living Foundries Program (HR0011-12-C-0068)Harvard-MIT Joint Research Grants Program in Basic NeuroscienceHuman Frontier Science Program (Strasbourg, France)Institution of Engineering and Technology (A. F. Harvey Prize)McGovern Institute for Brain Research at MIT. Neurotechnology (MINT) ProgramNew York Stem Cell Foundation (Robertson Investigator Award)National Institutes of Health (U.S.) (New Innovator Award 1DP2OD002002)National Institute of General Medical Sciences (U.S.) (EUREKA Award 1R01NS075421)National Institutes of Health (U.S.) (Grant 1R01DA029639)National Institutes of Health (U.S.) (Grant 1RC1MH088182)National Institutes of Health (U.S.) (Grant 1R01NS067199)National Science Foundation (U.S.) (Career Award CBET 1053233)National Science Foundation (U.S.) (Grant EFRI0835878)National Science Foundation (U.S.) (Grant DMS0848804)Society for Neuroscience (Research Award for Innovation in Neuroscience)Wallace H. Coulter FoundationNational Institutes of Health (U.S.) (RO1 MH091220-01)Whitehall FoundationEsther A. & Joseph Klingenstein Fund, Inc.JPB FoundationPIIF FundingNational Institute of Mental Health (U.S.) (R01-MH102441-01)National Institutes of Health (U.S.) (DP2-OD-017366-01)Massachusetts Institute of Technology. Simons Center for the Social Brai

Heparan sulfate proteoglycans: structure, protein interactions and cell signaling

Heparan sulfate proteoglycans are ubiquitously found at the cell surface and extracellular matrix in all the animal species. This review will focus on the structural characteristics of the heparan sulfate proteoglycans related to protein interactions leading to cell signaling. The heparan sulfate chains due to their vast structural diversity are able to bind and interact with a wide variety of proteins, such as growth factors, chemokines, morphogens, extracellular matrix components, enzymes, among others. There is a specificity directing the interactions of heparan sulfates and target proteins, regarding both the fine structure of the polysaccharide chain as well precise protein motifs. Heparan sulfates play a role in cellular signaling either as receptor or co-receptor for different ligands, and the activation of downstream pathways is related to phosphorylation of different cytosolic proteins either directly or involving cytoskeleton interactions leading to gene regulation. The role of the heparan sulfate proteoglycans in cellular signaling and endocytic uptake pathways is also discussed.Proteoglicanos de heparam sulfato são encontrados tanto superfície celular quanto na matriz extracelular em todas as espécies animais. Esta revisão tem enfoque nas características estruturais dos proteoglicanos de heparam sulfato e nas interações destes proteoglicanos com proteínas que levam à sinalização celular. As cadeias de heparam sulfato, devido a sua variedade estrutural, são capazes de se ligar e interagir com ampla gama de proteínas, como fatores de crescimento, quimiocinas, morfógenos, componentes da matriz extracelular, enzimas, entreoutros. Existe uma especificidade estrutural que direciona as interações dos heparam sulfatos e proteínas alvo. Esta especificidade está relacionada com a estrutura da cadeia do polissacarídeo e os motivos conservados da cadeia polipeptídica das proteínas envolvidas nesta interação. Os heparam sulfatos possuem papel na sinalização celular como receptores ou coreceptores para diferentes ligantes. Esta ligação dispara vias de sinalização celular levam à fosforilação de diversas proteínas citosólicas ou com ou sem interações diretas com o citoesqueleto, culminando na regulação gênica. O papel dos proteoglicanos de heparam sulfato na sinalização celular e vias de captação endocítica também são discutidas nesta revisão.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo (UNIFESP) Departamento de BioquímicaUniversidade Federal de São Paulo (UNIFESP) Departamento de OftalmologiaUNIFESP, Depto. de BioquímicaUNIFESP, Depto. de OftalmologiaSciEL