Nonlinear Dynamic Phenomena in Macroscopic Tunneling

Numerical simulations of the NLSE (or GPE) are presented demonstrating emission of short pulses of the matter (light) density formed in the course of tunneling in wave-guided light and/or trapped BEC. The phenomenon is observed under various conditions, for nonlinearities of different signs, zero nonlinearity included. We study, both numerically and analytically, pulsations of matter (light) remaining within the trap and use the results in order to induce emission of sequential pulses by properly narrowing the trap. This allows us to propose a mechanism for a realization of Atom Pulse Laser.Comment: 14 pages, 6 figure

Affinity of Tau antibodies for solubilized pathological Tau species but not their immunogen or insoluble Tau aggregates predicts in vivo and ex vivo efficacy

BACKGROUND: A few tau immunotherapies are now in clinical trials with several more likely to be initiated in the near future. A priori, it can be anticipated that an antibody which broadly recognizes various pathological tau aggregates with high affinity would have the ideal therapeutic properties. Tau antibodies 4E6 and 6B2, raised against the same epitope region but of varying specificity and affinity, were tested for acutely improving cognition and reducing tau pathology in transgenic tauopathy mice and neuronal cultures. RESULTS: Surprisingly, we here show that one antibody, 4E6, which has low affinity for most forms of tau acutely improved cognition and reduced soluble phospho-tau, whereas another antibody, 6B2, which has high affinity for various tau species was ineffective. Concurrently, we confirmed and clarified these efficacy differences in an ex vivo model of tauopathy. Alzheimer’s paired helical filaments (PHF) were toxic to the neurons and increased tau levels in remaining neurons. Both toxicity and tau seeding were prevented by 4E6 but not by 6B2. Furthermore, 4E6 reduced PHF spreading between neurons. Interestingly, 4E6’s efficacy relates to its high affinity binding to solubilized PHF, whereas the ineffective 6B2 binds mainly to aggregated PHF. Blocking 4E6's uptake into neurons prevented its protective effects if the antibody was administered after PHF had been internalized. When 4E6 and PHF were administered at the same time, the antibody was protective extracellularly. CONCLUSIONS: Overall, these findings indicate that high antibody affinity for solubilized PHF predicts efficacy, and that acute antibody-mediated improvement in cognition relates to clearance of soluble phospho-tau. Importantly, both intra- and extracellular clearance pathways are in play. Together, these results have major implications for understanding the pathogenesis of tauopathies and for development of immunotherapies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13024-016-0126-z) contains supplementary material, which is available to authorized users

Underground railroads: citizen entitlements and unauthorized mobility in the antebellum period and today

In recent years, some scholars and prominent political figures have advocated the deepening of North American integration on roughly the European Union model, including the creation of new political institutions and the free movement of workers across borders. The construction of such a North American Union, if it included even a very thin trans-state citizenship regime, could represent the most significant expansion of individual entitlements in the region since citizenship was extended to former slaves in the United States. With such a possibility as its starting point, this article explores some striking parallels between the mass, legally prohibited movement across boundaries by fugitive slaves in the pre-Civil War period, and that by current unauthorized migrants to the United States. Both were, or are, met on their journeys by historically parallel groups of would-be helpers and hinderers. Their unauthorized movements in both periods serve as important signals of incomplete entitlements or institutional protections. Most crucially, moral arguments for extending fuller entitlements to both groups are shown here to be less distinct than may be prima facie evident, reinforcing the case for expanding and deepening the regional membership regime

Tourism Innovation: Integrating Ginseng into Spa Development: A Case Study of Sunmore Ginseng Health Spa in Kamloops, BC, Canada

Although innovation research has built a solid ground in the realms of nature science and technology, for examples, innovation study in the field of engineering looks at the development of new processes; innovation study in the field of medicine focuses on the development of new devices, drugs and practices, it has not obtained its proper respect as a critical topic in social science, particularly in tourism research. Innovation study in tourism is surprisingly limited and still in a phase of infancy. The purpose of this study is to further explore the notion of innovation in the context of tourism based on earlier scholars’ research. To provide more practical and industrial insights into the understanding of how innovation works in tourism, our researchers conduct a case study of Sunmore Ginseng Health Spa to examine its application of the established innovation concepts and paradigms, as well as the fitness for Abernathy and Clark’s innovation model. Sunmore Ginseng Spa, a health spa in Canada, is located in Kamloops, BC. It is operated as a day spa. The spa is characterized by four functioned suites with the themes from Chinese ancient philosophy: Gold, Wood, Water and Fire. The services offered at Sunmore spa include Swedish massage, aromatherapy massage, reflexology, body wrap, salt glow, facials, and ginseng steaming and sauna. The study found Sunmore Ginseng Health Spa fits well the right upper quadrant of the model which is named ‘architectural innovation’. In line with the ‘experience economy’, Sunmore Ginseng Health Spa may also be considered a good example of ‘experience innovation’. In addition, the research also identified several emergent themes from tourism innovations such as service differentiation, ‘high-tech. and high- touch’, and experience innovation in the experience economy. Future research should further look into the main drivers of tourism innovation, the relationship between innovation and entrepreneurship, the development of innovation models for specific service sub-sectors, as well as the roles of innovation in the experience economy

Energy-aware simulation with DVFS

International audienceIn recent years, research has been conducted in the area of large systems models, especially distributed systems, to analyze and understand their behavior. Simulators are now commonly used in this area and are becoming more complex. Most of them provide frameworks for simulating application scheduling in various Grid infrastructures, others are specifically developed for modeling networks, but only a few of them simulate energy-efficient algorithms. This article describes which tools need to be implemented in a simulator in order to support energy-aware experimentation. The emphasis is on DVFS simulation, from its implementation in the simulator CloudSim to the whole methodology adopted to validate its functioning. In addition, a scientific application is used as a use case in both experiments and simulations, where the close relationship between DVFS efficiency and hardware architecture is highlighted. A second use case using Cloud applications represented by DAGs, which is also a new functionality of CloudSim, demonstrates that the DVFS efficiency also depends on the intrinsic middleware behavior

Hyperexcitability of the local cortical circuit in mouse models of tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is a neurogenetic disorder associated with epilepsy, intellectual disabilities, and autistic behaviors. These neurological symptoms result from synaptic dysregulations, which shift a balance between excitation and inhibition. To decipher the synaptic substrate of hyperexcitability, we examined pan-neuronal Tsc1 knockout mouse and found a reduction in surface expression of a GABA receptor (GABAR) subunit but not AMPA receptor (AMPAR) subunit. Using electrophysiological recordings, we found a significant reduction in the frequency of GABAR-mediated miniature inhibitory postsynaptic currents (GABAR-mIPSCs) but not AMPAR-mediated miniature excitatory postsynaptic currents (AMPAR-mEPSCs) in layer 2/3 pyramidal neurons. To determine a subpopulation of interneurons that are especially vulnerable to the absence of TSC1 function, we also analyzed two strains of conditional knockout mice targeting two of the prominent interneuron subtypes that express parvalbumin (PV) or somatostatin (SST). Unlike pan-neuronal knockout mice, both interneuron-specific Tsc-1 knockout mice did not develop spontaneous seizures and grew into adults. Further, the properties of AMPAR-mEPSCs and GABAR-mIPSCs were normal in both Pv-Cre and Sst-Cre x Tsc1fl/fl knockout mice. These results indicate that removal of TSC1 from all neurons in a local cortical circuit results in hyperexcitability while connections between pyramidal neurons and interneurons expressing PV and SST are preserved in the layer 2/3 visual cortex. Our study suggests that another inhibitory cell type or a combination of multiple subtypes may be accountable for hyperexcitability in TSC. Keywords: Tuberous sclerosis complex; E/I balance; AMPA receptor; GABA receptor; Autism; Epilepsy; mTOR pathwa

The positive effect on ketamine as a priming adjuvant in antidepressant treatment.

Ketamine is an anesthetic with antidepressant properties. The rapid and lasting effect of ketamine observed in preclinical and clinical research makes it a promising therapeutic to improve current major depression (MD) treatment. Our work intended to evaluate whether the combined use of classic antidepressants (imipramine or fluoxetine) and ketamine would improve the antidepressant response. Using an animal model of depressive-like behavior, we show that the addition of ketamine to antidepressants anticipates the behavioral response and accelerates the neuroplastic events when compared with the use of antidepressants alone. In conclusion, our results suggest the need for a reappraisal of the current pharmacological treatment of MD.This work is supported by the Fundação para a Ciência e Tecnologia (FCT) grant SFRH/SINTD/60126/200

Isotopic biases for actinide-only burnup credit

The primary purpose of this paper is to present the new methodology for establishing bias and uncertainty associated with isotopic prediction in spent fuel assemblies for burnup credit analysis. The analysis applies to the design of criticality control systems for spent fuel casks. A total of 54 spent fuel samples were modeled and analyzed using the Shielding Analyses Sequence (SAS2H). Multiple regression analysis and a trending test were performed to develop isotopic correction factors for 10 actinide burnup credit isotopes. 5 refs., 1 tab

Kinase and phosphatase engagement is dissociated between memory formation and extinction

Associative long-term memories (LTMs) support long-lasting behavioural changes resulting from sensory experiences. Retrieval of a stable LTM by means of a large number of conditioned stimulus (CS) alone presentations produces inhibition of the original memory through extinction. Currently, there are two opposing hypotheses to account for the neural mechanisms supporting extinction. The unlearning hypothesis posits that extinction affects the original memory trace by reverting the synaptic changes supporting LTM. On the contrary, the new learning hypothesis proposes that extinction is simply the formation of a new associative memory that inhibits the expression of the original one. We propose that detailed analysis of extinction-associated molecular mechanisms could help distinguish between these hypotheses. Here we will review experimental evidence regarding the role of protein kinases and phosphatases on LTM formation and extinction. Even though kinases and phosphatases regulate both memory processes, their participation appears to be dissociated. LTM formation recruits kinases, but is constrained by phosphatases. Memory extinction presents a more diverse molecular landscape, requiring phosphatases and some kinases, but also being constrained by kinase activity. Based on the available evidence, we propose a new theoretical model for memory extinction: a neuronal segregation of kinases and phosphatases supports a combination of time-dependent reversible inhibition of the original memory (CS-US), with establishment of a new associative memory trace (CS-noUS)

AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity.

AKT is a kinase regulating numerous cellular processes in the brain, and mutations in AKT are known to affect brain function. AKT is indirectly implicated in synaptic plasticity, but its direct role has not been studied. Moreover, three highly related AKT isoforms are expressed in the brain, but their individual roles are poorly understood. We find in Mus musculus, each AKT isoform has a unique expression pattern in the hippocampus, with AKT1 and AKT3 primarily in neurons but displaying local differences, while AKT2 is in astrocytes. We also find isoform-specific roles for AKT in multiple paradigms of hippocampal synaptic plasticity in area CA1. AKT1, but not AKT2 or AKT3, is required for L-LTP through regulating activity-induced protein synthesis. Interestingly, AKT activity inhibits mGluR-LTD, with overlapping functions for AKT1 and AKT3. In summary, our studies identify distinct expression patterns and roles in synaptic plasticity for AKT isoforms in the hippocampus