Remote and reversible inhibition of neurons and circuits by small molecule induced potassium channel stabilization

Manipulating the function of neurons and circuits that translate electrical and chemical signals into behavior represents a major challenges in neuroscience. In addition to optogenetic methods using light-activatable channels, pharmacogenetic methods with ligand induced modulation of cell signaling and excitability have been developed. However, they are largely based on ectopic expression of exogenous or chimera proteins. Now, we describe the remote and reversible expression of a Kir2.1 type potassium channel using the chemogenetic technique of small molecule induced protein stabilization. Based on shield1-mediated shedding of a destabilizing domain fused to a protein of interest and inhibition of protein degradation, this principle has been adopted for biomedicine, but not in neuroscience so far. Here, we apply this chemogenetic approach in brain research for the first time in order to control a potassium channel in a remote and reversible manner. We could show that shield1-mediated ectopic Kir2.1 stabilization induces neuronal silencing in vitro and in vivo in the mouse brain. We also validated this novel pharmacogenetic method in different neurobehavioral paradigms. The DD-Kir2.1 may complement the existing portfolio of pharmaco- and optogenetic techniques for specific neuron manipulation, but it may also provide an example for future applications of this principle in neuroscience research

Adapting mark-recapture methods to estimating accepted species-level diversity: a case study with terrestrial Gastropoda.

We introduce a new method of estimating accepted species diversity by adapting mark-recapture methods to comparisons of taxonomic databases. A taxonomic database should become more complete over time, so the error bar on an estimate of its completeness and the known diversity of the taxon it treats will decrease. Independent databases can be correlated, so we use the time course of estimates comparing them to understand the effect of correlation. If a later estimate is significantly larger than an earlier one, the databases are positively correlated, if it is significantly smaller, they are negatively correlated, and if the estimate remains roughly constant, then the correlations have averaged out. We tested this method by estimating how complete MolluscaBase is for accepted names of terrestrial gastropods. Using random samples of names from an independent database, we determined whether each name led to a name accepted in MolluscaBase. A sample tested in August 2020 found that 16.7% of tested names were missing; one in July 2021 found 5.3% missing. MolluscaBase grew by almost 3,000 accepted species during this period, reaching 27,050 species. The estimates ranged from 28,409 ± 365 in 2021 to 29,063 ± 771 in 2020. All estimates had overlapping 95% confidence intervals, indicating that correlations between the databases did not cause significant problems. Uncertainty beyond sampling error added 475 ± 430 species, so our estimate for accepted terrestrial gastropods species at the end of 2021 is 28,895 ± 630 species. This estimate is more than 4,000 species higher than previous ones. The estimate does not account for ongoing flux of species into and out of synonymy, new discoveries, or changing taxonomic methods and concepts. The species naming curve for terrestrial gastropods is still far from reaching an asymptote, and combined with the additional uncertainties, this means that predicting how many more species might ultimately be recognized is presently not feasible. Our methods can be applied to estimate the total number of names of Recent mollusks (as opposed to names currently accepted), the known diversity of fossil mollusks, and known diversity in other phyla

Constraints on the Ultra-High Energy Neutrino Flux from Gamma-Ray Bursts from a Prototype Station of the Askaryan Radio Array

We report on a search for ultra-high-energy (UHE) neutrinos from gamma-ray bursts (GRBs) in the data set collected by the Testbed station of the Askaryan Radio Array (ARA) in 2011 and 2012. From 57 selected GRBs, we observed no events that survive our cuts, which is consistent with 0.12 expected background events. Using NeuCosmA as a numerical GRB reference emission model, we estimate upper limits on the prompt UHE GRB neutrino fluence and quasi-diffuse flux from $10^{7}$ to $10^{10}$ GeV. This is the first limit on the prompt UHE GRB neutrino quasi-diffuse flux above $10^{7}$ GeV.Comment: 14 pages, 8 figures, Published in Astroparticle Physics Journa

First Constraints on the Ultra-High Energy Neutrino Flux from a Prototype Station of the Askaryan Radio Array

The Askaryan Radio Array (ARA) is an ultra-high energy ($>10^{17}$ eV) cosmic neutrino detector in phased construction near the South Pole. ARA searches for radio Cherenkov emission from particle cascades induced by neutrino interactions in the ice using radio frequency antennas ($\sim150-800$ MHz) deployed at a design depth of 200 m in the Antarctic ice. A prototype ARA Testbed station was deployed at $\sim30$ m depth in the 2010-2011 season and the first three full ARA stations were deployed in the 2011-2012 and 2012-2013 seasons. We present the first neutrino search with ARA using data taken in 2011 and 2012 with the ARA Testbed and the resulting constraints on the neutrino flux from $10^{17}-10^{21}$ eV.Comment: 26 pages, 15 figures. Since first revision, added section on systematic uncertainties, updated limits and uncertainty band with improvements to simulation, added appendix describing ray tracing algorithm. Final revision includes a section on cosmic ray backgrounds. Published in Astropart. Phys.

Frequency spectra of cosmic ray air shower radio emission measured with LOPES

Aims. We wish to study the spectral dependence of the radio emission from cosmic-ray air showers around .Methods. We observe short radio pulses in a broad frequency band with the dipole-interferometer LOPES (LOFAR Prototype Station), which is triggered by a particle detector array named Karlsruhe Shower Core and Array Detector (KASCADE). LOFAR is the Low Frequency Array. For this analysis, 23 strong air shower events are selected using parameters from KASCADE. The radio data are digitally beam-formed before the spectra are determined by sub-band filtering and fast Fourier transformation.Results. The resulting electric field spectra fall off to higher frequencies. An average electric field spectrum is fitted with an exponential and , or alternatively, with a power law and a spectral index of . The spectral slope obtained is not consistent within uncertainties and it is slightly steeper than the slope obtained from Monte Carlo simulations based on air showers simulated with CORSIKA (Cosmic Ray Simulations for KASCADE). For the analyzed sample of LOPES events, we do not find any significant dependence of the spectral slope on the electric field amplitude, the azimuth angle, the zenith angle, the curvature radius, nor on the average distance of the antennae from the shower core position. But one of the strongest events was measured during thunderstorm activity in the vicinity of LOPES and shows the longest pulse length measured of and a spectral slope of .Conclusions. We show with two different methods that frequency spectra from air shower radio emission can be reconstructed on event-by-event basis, with only two dozen dipole antennae simultaneously over a broad range of frequencies. According to the obtained spectral slopes, the maximum power is emitted below 40 MHz. Furthermore, the decrease in power to higher frequencies indicates a loss in coherence determined by the shower disc thickness. We conclude that a broader bandwidth, larger collecting area, and longer baselines, as will be provided by LOFAR, are necessary to further investigate the relation of the coherence, pulse length, and spectral slope of cosmic ray air showers

Velocity independent constraints on spin-dependent DM-nucleon interactions from IceCube and PICO

[EN] Adopting the Standard Halo Model (SHM) of an isotropic Maxwellian velocity distribution for dark matter (DM) particles in the Galaxy, the most stringent current constraints on their spin-dependent scattering cross-section with nucleons come from the IceCube neutrino observatory and the PICO-60 C3F8 superheated bubble chamber experiments. The former is sensitive to high energy neutrinos from the self-annihilation of DM particles captured in the Sun, while the latter looks for nuclear recoil events from DM scattering off nucleons. Although slower DM particles are more likely to be captured by the Sun, the faster ones are more likely to be detected by PICO. Recent N-body simulations suggest significant deviations from the SHM for the smooth halo component of the DM, while observations hint at a dominant fraction of the local DM being in substructures. We use the method of Ferrer et al. (JCAP 1509: 052, 2015) to exploit the complementarity between the two approaches and derive conservative constraints on DM-nucleon scattering. Our results constrain sigma SD less than or similar to 3x10-39cm2 (6x10-38cm2) at greater than or similar to 90% C.L. for a DM particle of mass 1 TeV annihilating into tau+tau- (bb) with a local density of rho DM=0.3GeV/cm3. The constraints scale inversely with rho DM and are independent of the DM velocity distribution.Aartsen, MG.; Ackermann, M.; Adams, J.; Aguilar, JA.; Ahlers, M.; Ahrens, M.; Alispach, C.... (2020). Velocity independent constraints on spin-dependent DM-nucleon interactions from IceCube and PICO. The European Physical Journal C. 80(9):1-8. https://doi.org/10.1140/epjc/s10052-020-8069-5S18809F. Ferrer, A. Ibarra, S. Wild, JCAP 1509(09), 052 (2015). arXiv:1506.03386 [hep-ph]S. van den Bergh, Publ. Astron. Soc. Pac. 111, 657 (1999). arXiv:astro-ph/9904251G. Bertone, D. Hooper, J. Silk, Phys. Rept. 405, 279 (2005). arXiv:hep-ph/0404175A.K. Drukier, K. Freese, D.N. Spergel, Phys. Rev. D 33, 3495 (1986)M. Kuhlen, N. Weiner, J. Diemand, P. Madau, B. Moore, D. Potter, J. Stadel, M. Zemp, JCAP 1002, 030 (2010). arXiv:0912.2358 [astro-ph.GA]M. Lisanti, L.E. Strigari, J.G. Wacker, R.H. Wechsler, Phys. Rev. D 83, 023519 (2011). arXiv:1010.4300 [astro-ph.CO]Y.Y. Mao, L.E. Strigari, R.H. Wechsler, H.Y. Wu, O. Hahn, Astrophys. J. 764, 35 (2013). arXiv:1210.2721 [astro-ph.CO]L. Necib, M. Lisanti, V. Belokurov, arXiv:1807.02519 [astro-ph.GA]N.W. Evans, C.A.J. O’Hare, C. McCabe, Phys. Rev. D 99(2), 023012 (2019). arXiv:1810.11468 [astro-ph.GA]M.G. Aartsen et al. [IceCube Collaboration], Eur. Phys. J. C 77, no. 3, 146 (2017) arXiv:1612.05949 [astro-ph.HE]C. Amole et al., [PICO Collaboration]. Phys. Rev. Lett. 118(25), 251301 (2017). arXiv:1702.07666 [astro-ph.CO]M.T. Frandsen, F. Kahlhoefer, C. McCabe, S. Sarkar, K. Schmidt-Hoberg, JCAP 1201, 024 (2012). arXiv:1111.0292 [hep-ph]K. Choi, C. Rott, Y. Itow, JCAP 1405, 049 (2014). arXiv:1312.0273 [astro-ph.HE]A. Achterberg et al., [IceCube Collaboration]. Astropart. Phys. 26, 155 (2006). arXiv:astro-ph/0604450R. Abbasi et al. [IceCube Collaboration], Nucl. Instrum. Meth. A 601, 294 (2009) arXiv:0810.4930 [physics.ins-det]M.G. Aartsen et al. [IceCube Collaboration], JINST 12, no. 03, P03012 (2017) arXiv:1612.05093 [astro-ph.IM]R. Abbasi et al., [IceCube Collaboration]. Astropart. Phys. 35, 615 (2012). arXiv:1109.6096 [astro-ph.IM]G.J. Feldman, R.D. Cousins, Phys. Rev. D 57, 3873 (1998). https://doi.org/10.1103/PhysRevD.57.3873. arXiv:physics/9711021 [physics.data-an]M. Tanabashi et al. [Particle Data Group], Phys. Rev. D 98, no. 3, 030001 (2018)C. Amole et al. [PICO Collaboration], arXiv:1905.12522 [physics.ins-det]C. Amole et al. [PICO Collaboration], Phys. Rev. D 93, no. 5, 052014 (2016) arXiv:1510.07754 [hep-ex]E. Tollerud et al. [ERFA] Computational Science and Discovery, no 8, 1 (2015) https://doi.org/10.5281/zenodo.1021149J.N. Bahcall, R.K. Ulrich, Rev. Mod. Phys. 60, 297 (1988)T. Mumford et al. [SunPy Community] Computational Science and Discovery, no 8, 1 (2015) arXiv:1505.02563 [astro-ph]V. Gluscevic, M.I. Gresham, S.D. McDermott, A.H.G. Peter, K.M. Zurek, JCAP 1512(12), 057 (2015). arXiv:1506.04454 [hep-ph]A.L. Fitzpatrick, W. Haxton, E. Katz, N. Lubbers, Y. Xu, ‘, JCAP 1302, 004 (2013). https://doi.org/10.1088/1475-7516/2013/02/004. arXiv:1203.3542 [hep-ph]A. Ibarra, A. Rappelt, JCAP 1708(08), 039 (2017). arXiv:1703.09168 [hep-ph

Frequency spectra of cosmic ray air shower radio emission measured with LOPES

AIMS: We wish to study the spectral dependence of the radio emission from cosmic-ray air showers around 100 PeV (1017 eV). METHODS: We observe short radio pulses in a broad frequency band with the dipole-interferometer LOPES (LOFAR Prototype Station), which is triggered by a particle detector array named Karlsruhe Shower Core and Array Detector (KASCADE). LOFAR is the Low Frequency Array. For this analysis, 23 strong air shower events are selected using parameters from KASCADE. RESULTS: The resulting electric field spectra fall off to higher frequencies. An average electric field spectrum is fitted with an exponential, or alternatively, with a power law. The spectral slope obtained is not consistent within uncertainties and it is slightly steeper than the slope obtained from Monte Carlo simulations based on air showers simulated with CORSIKA (Cosmic Ray Simulations for KASCADE). One of the strongest events was measured during thunderstorm activity in the vicinity of LOPES and shows the longest pulse length measured of 110 ns and a spectral slope of -3.6. CONCLUSIONS: We show with two different methods that frequency spectra from air shower radio emission can be reconstructed on event-by-event basis, with only two dozen dipole antennae simultaneously over a broad range of frequencies. According to the obtained spectral slopes, the maximum power is emitted below 40 MHz. Furthermore, the decrease in power to higher frequencies indicates a loss in coherence determined by the shower disc thickness. We conclude that a broader bandwidth, larger collecting area, and longer baselines, as will be provided by LOFAR, are necessary to further investigate the relation of the coherence, pulse length, and spectral slope of cosmic ray air showers.Comment: 13 pages, 21 figures. Nigl, A. et al. (LOPES Collaboration), Frequency spectra of cosmic ray air shower radio emission measured with LOPES, accepted by A&A on 17/06/200