Neural cytoskeleton capabilities for learning and memory

This paper proposes a physical model involving the key structures within the neural cytoskeleton as major players in molecular-level processing of information required for learning and memory storage. In particular, actin filaments and microtubules are macromolecules having highly charged surfaces that enable them to conduct electric signals. The biophysical properties of these filaments relevant to the conduction of ionic current include a condensation of counterions on the filament surface and a nonlinear complex physical structure conducive to the generation of modulated waves. Cytoskeletal filaments are often directly connected with both ionotropic and metabotropic types of membrane-embedded receptors, thereby linking synaptic inputs to intracellular functions. Possible roles for cable-like, conductive filaments in neurons include intracellular information processing, regulating developmental plasticity, and mediating transport. The cytoskeletal proteins form a complex network capable of emergent information processing, and they stand to intervene between inputs to and outputs from neurons. In this manner, the cytoskeletal matrix is proposed to work with neuronal membrane and its intrinsic components (e.g., ion channels, scaffolding proteins, and adaptor proteins), especially at sites of synaptic contacts and spines. An information processing model based on cytoskeletal networks is proposed that may underlie certain types of learning and memory

Chaos in neural networks with a nonmonotonic transfer function

Time evolution of diluted neural networks with a nonmonotonic transfer function is analitically described by flow equations for macroscopic variables. The macroscopic dynamics shows a rich variety of behaviours: fixed-point, periodicity and chaos. We examine in detail the structure of the strange attractor and in particular we study the main features of the stable and unstable manifolds, the hyperbolicity of the attractor and the existence of homoclinic intersections. We also discuss the problem of the robustness of the chaos and we prove that in the present model chaotic behaviour is fragile (chaotic regions are densely intercalated with periodicity windows), according to a recently discussed conjecture. Finally we perform an analysis of the microscopic behaviour and in particular we examine the occurrence of damage spreading by studying the time evolution of two almost identical initial configurations. We show that for any choice of the parameters the two initial states remain microscopically distinct.Comment: 12 pages, 11 figures. Accepted for publication in Physical Review E. Originally submitted to the neuro-sys archive which was never publicly announced (was 9905001

Comment on "On the subtleties of searching for dark matter with liquid xenon detectors"

In a recent manuscript (arXiv:1208.5046) Peter Sorensen claims that XENON100's upper limits on spin-independent WIMP-nucleon cross sections for WIMP masses below 10 GeV "may be understated by one order of magnitude or more". Having performed a similar, though more detailed analysis prior to the submission of our new result (arXiv:1207.5988), we do not confirm these findings. We point out the rationale for not considering the described effect in our final analysis and list several potential problems with his study.Comment: 3 pages, no figure

Zeta Inhibitory Peptide attenuates learning and memory by inducing NO-mediated downregulation of AMPA receptors

Zeta inhibitory peptide (ZIP), a PKMζ inhibitor, is widely used to interfere with the main- tenance of acquired memories. ZIP is able to erase memory even in the absence of PKMζ, via an unknown mechanism. We found that ZIP induces redistribution of the AMPARGluA1 in HEK293 cells and primary cortical neurons, and decreases AMPAR-mediated currents in the nucleus accumbens (NAc). These effects were mimicked by free arginine or by a modified ZIP in which all but the arginine residues were replaced by alanine. Redistribution was blocked by a peptidase-resistant version of ZIP and by treatment with the nitric oxide (NO)- synthase inhibitor L-NAME. ZIP increased GluA1-S831 phosphorylation and ZIP-induced redistribution was blocked by nitrosyl-mutant GluA1-C875S or serine-mutant GluA1-S831A. Introducing the cleavable arginine-alanine peptide into the NAc attenuated expression of cocaine-conditioned reward. Together, these results suggest that ZIP may act as an arginine donor, facilitating NO-dependent downregulation of AMPARs, thereby attenuating learning and memory

Removing krypton from xenon by cryogenic distillation to the ppq level

The XENON1T experiment aims for the direct detection of dark matter in a cryostat filled with 3.3 tons of liquid xenon. In order to achieve the desired sensitivity, the background induced by radioactive decays inside the detector has to be sufficiently low. One major contributor is the $\beta$-emitter $^{85}$Kr which is an intrinsic contamination of the xenon. For the XENON1T experiment a concentration of natural krypton in xenon $\rm{^{nat}}$Kr/Xe < 200 ppq (parts per quadrillion, 1 ppq = 10$^{-15}$ mol/mol) is required. In this work, the design of a novel cryogenic distillation column using the common McCabe-Thiele approach is described. The system demonstrated a krypton reduction factor of 6.4$\cdot$10$^5$ with thermodynamic stability at process speeds above 3 kg/h. The resulting concentration of $\rm{^{nat}}$Kr/Xe < 26 ppq is the lowest ever achieved, almost one order of magnitude below the requirements for XENON1T and even sufficient for future dark matter experiments using liquid xenon, such as XENONnT and DARWIN

Search for Two-Neutrino Double Electron Capture of 124^{124}Xe with XENON100

Two-neutrino double electron capture is a rare nuclear decay where two electrons are simultaneously captured from the atomic shell. For $^{124}$Xe this process has not yet been observed and its detection would provide a new reference for nuclear matrix element calculations. We have conducted a search for two-neutrino double electron capture from the K-shell of $^{124}$Xe using 7636 kg$\cdot$d of data from the XENON100 dark matter detector. Using a Bayesian analysis we observed no significant excess above background, leading to a lower 90 % credibility limit on the half-life $T_{1/2}>6.5\times10^{20}$ yr. We also evaluated the sensitivity of the XENON1T experiment, which is currently being commissioned, and find a sensitivity of $T_{1/2}>6.1\times10^{22}$ yr after an exposure of 2 t$\cdot$yr.Comment: 6 pages, 4 figure

Lowering the radioactivity of the photomultiplier tubes for the XENON1T dark matter experiment

The low-background, VUV-sensitive 3-inch diameter photomultiplier tube R11410 has been developed by Hamamatsu for dark matter direct detection experiments using liquid xenon as the target material. We present the results from the joint effort between the XENON collaboration and the Hamamatsu company to produce a highly radio-pure photosensor (version R11410-21) for the XENON1T dark matter experiment. After introducing the photosensor and its components, we show the methods and results of the radioactive contamination measurements of the individual materials employed in the photomultiplier production. We then discuss the adopted strategies to reduce the radioactivity of the various PMT versions. Finally, we detail the results from screening 216 tubes with ultra-low background germanium detectors, as well as their implications for the expected electronic and nuclear recoil background of the XENON1T experiment.Comment: 10 pages, 5 figure

Search for Event Rate Modulation in XENON100 Electronic Recoil Data

We have searched for periodic variations of the electronic recoil event rate in the (2-6) keV energy range recorded between February 2011 and March 2012 with the XENON100 detector, adding up to 224.6 live days in total. Following a detailed study to establish the stability of the detector and its background contributions during this run, we performed an un-binned profile likelihood analysis to identify any periodicity up to 500 days. We find a global significance of less than 1 sigma for all periods suggesting no statistically significant modulation in the data. While the local significance for an annual modulation is 2.8 sigma, the analysis of a multiple-scatter control sample and the phase of the modulation disfavor a dark matter interpretation. The DAMA/LIBRA annual modulation interpreted as a dark matter signature with axial-vector coupling of WIMPs to electrons is excluded at 4.8 sigma.Comment: 6 pages, 4 figure

Zinc transporter gene expression is regulated by pro-inflammatory cytokines: a potential role for zinc transporters in beta-cell apoptosis?

<p>Abstract</p> <p>Background</p> <p>β-cells are extremely rich in zinc and zinc homeostasis is regulated by zinc transporter proteins. β-cells are sensitive to cytokines, interleukin-1β (IL-1β) has been associated with β-cell dysfunction and -death in both type 1 and type 2 diabetes. This study explores the regulation of zinc transporters following cytokine exposure.</p> <p>Methods</p> <p>The effects of cytokines IL-1β, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) on zinc transporter gene expression were measured in INS-1-cells and rat pancreatic islets. Being the more sensitive transporter, we further explored ZnT8 (Slc30A8): the effect of ZnT8 over expression on cytokine induced apoptosis was investigated as well as expression of the insulin gene and two apoptosis associated genes, BAX and BCL2.</p> <p>Results</p> <p>Our results showed a dynamic response of genes responsible for β-cell zinc homeostasis to cytokines: IL-1β down regulated a number of zinc-transporters, most strikingly ZnT8 in both islets and INS-1 cells. The effect was even more pronounced when mixing the cytokines. TNF-α had little effect on zinc transporter expression. IFN-γ down regulated a number of zinc transporters. Insulin expression was down regulated by all cytokines. ZnT8 over expressing cells were more sensitive to IL-1β induced apoptosis whereas no differences were observed with IFN-γ, TNF-α, or a mixture of cytokines.</p> <p>Conclusion</p> <p>The zinc transporting system in β-cells is influenced by the exposure to cytokines. Particularly ZnT8, which has been associated with the development of diabetes, seems to be cytokine sensitive.</p

Unlocking legal validity. Some remarks on the artificial ontology of law

Following Kelsen’s influential theory of law, the concept of validity has been used in the literature to refer to different properties of law (such as existence, membership, bindingness, and more) and so it is inherently ambiguous. More importantly, Kelsen’s equivalence between the existence and the validity of law prevents us from accounting satisfactorily for relevant aspects of our current legal practices, such as the phenomenon of ‘unlawful law’. This chapter addresses this ambiguity to argue that the most important function of the concept of validity is constituting the complex ontological paradigm of modern law as an institutional-normative practice. In this sense validity is an artificial ontological status that supervenes on that of existence of legal norms, thus allowing law to regulate its own creation and creating the logical space for the occurrence of ‘unlawful law’. This function, I argue in the last part, is crucial to understanding the relationship between the ontological and epistemic dimensions of the objectivity of law. For given the necessary practice-independence of legal norms, it is the epistemic accessibility of their creation that enables the law to fulfill its general action-guiding (and thus coordinating) function