42 research outputs found
Computational modeling and simulation of ligand-gated ion channels
No full textThe pentameric ligand-gated ion channel (pLGIC) superfamily, from bacteria to the brain, convert chemical signals into electric signals. These proteins are composed of two distinct domains; the extracellular domain (ECD), where the chemical compounds (ligands) bind, and the transmembrane domain (TMD), which contains the ion-permeation pore. With the ligand-binding sites and the ion channel gate almost 50 Å apart, an allosteric conformational transition in these proteins has been proposed as the underlying mechanism of signal transduction. Members of the pLGIC superfamily, have intrigued researchers from multiple scientific disciplines for more than a century. The muscle nicotinic acetylcholine receptor (nAChR), a member of the pLGIC superfamily, was the first ion channel to be extracted and thus became a model system not only for pLGICs but for all ligand-gated ion channels. Thanks to decades of electrophysiology experiments along with pharmacological, biochemical, and structural studies, enormous progress has been made in understanding the function and structure of pLGICs. However, relatively high-resolution structures of a small number of pLGICs have been obtained only in the last decade or two. The availability of these structures allows for asking and, hopefully, answering questions that were deemed impossible in the past. Only now, for example, molecular dynamics (MD) simulations can be utilized to probe the interactions between these proteins and different molecules at the atomic level. Another promising area for MD simulations is to investigate if and how the membrane physicochemical properties affect these proteins in different functional states. Moreover, enhanced sampling techniques can be used to characterize the conformational transitions between different functional states in these proteins.
In this work, after a brief introduction (Chapter 1), two studies --- each focused on a different mammalian pLGIC --- are discussed. The first project investigates the interaction between menthol, a small lipophilic molecule, and the human alpha4beta2 nAChR --- the most abundant nAChR type in the brain. Various computational methodologies were used to study menthol's interaction with and partitioning in organic phases and lipid bilayers representing cellular membranes (Chapter 2). Once menthol's behavior in the membrane was characterized, its interaction with a membrane-embedded human alpha4beta2 nAChR was studied (Chapter 3). The second project (Chapter 4) focuses on the structure of the human glycine receptor (GlyR), bound to full and partial agonists, in different functional states. In a collaborative work, MD simulations were used along with cryo-electron microscopy and electrophysiology to determine the structural models for the desensitized and open state GlyR bound to the full agonist glycine. More importantly, the structure of the primed/flipped state of GlyR bound to partial agonists, taurine and gamma-aminobutyric acid, were determined. I will focus on the computational part of the joint effort, where MD simulations were employed to establish the stability of different ion conducting states of the receptor in two membrane environments.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2022-05-01The student, Rezvan Shahoei, accepted the attached license on 2020-04-01 at 11:58.The student, Rezvan Shahoei, submitted this Dissertation for approval on 2020-04-01 at 12:24.This Dissertation was approved for publication on 2020-04-02 at 13:32.DSpace SAF Submission Ingestion Package generated from Vireo submission #14928 on 2020-08-25 at 17:39:17Made available in DSpace on 2020-08-27T00:49:51Z (GMT). No. of bitstreams: 4
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Low Energy Even Reconstruction in IceCube DeepCore
No full textThe reconstruction of event-level information, such as the direction or energy of a neutrino interacting in IceCube DeepCore, is a crucial ingredient to many physics analyses. Algorithms to extract this high level information from the detector�s raw data have been successfully developed and used for high energy events. In this work, we address unique challenges associated with the reconstruction of lower energy events in the range of a few to hundreds of GeV and present two separate, state-of-the-art algorithms. One algorithm focuses on the fast directional reconstruction of events based on unscattered light. The second algorithm is a likelihood-based multipurpose reconstruction offering superior resolutions, at the expense of larger computational cost
Searching for High-Energy Neutrino Emission from Galaxy Clusters with IceCube
No full textGalaxy clusters have the potential to accelerate cosmic rays (CRs) to ultrahigh energies via accretion shocks or embedded CR acceleration sites. The CRs with energies below the Hillas condition will be confined within the cluster and eventually interact with the intracluster medium gas to produce secondary neutrinos and gamma rays. Using 9.5 yr of muon neutrino track events from the IceCube Neutrino Observatory, we report the results of a stacking analysis of 1094 galaxy clusters with masses ?1014 Me and redshifts between 0.01 and ?1 detected by the Planck mission via the Sunyaev�Zel�dovich effect. We find no evidence for significant neutrino emission and report upper limits on the cumulative unresolved neutrino flux from massive galaxy clusters after accounting for the completeness of the catalog up to a redshift of 2, assuming three different weighting scenarios for the stacking and three different power-law spectra. Weighting the sources according to mass and distance, we set upper limits at a 90% confidence level that constrain the flux of neutrinos from massive galaxy clusters (?1014 Me) to be no more than 4.6% of the diffuse IceCube observations at 100 TeV, assuming an unbroken E?2.5 power-law spectrum
Electrochemical oceanic carbon capture: using bipolar membrane electrodialysis
No full textTo mitigate climate change, carbon capture is necessary. In addition to the energy transition towards renewable sources and green house gasses emission reduction, CO2 capture from flue gas and its sinks, including air and the ocean, must be promoted. By 2030, in less than 8 years, the global carbon capture capacity must increase 100 × (from the current ca. 40 MtCO2 yr−1 to 4 GtCO2 yr−1). To meet the net zero carbon goals of 2050, sustainable, scalable, inexpensive technologies that fit in an electrified industry and have a small footprint are needed for carbon capture. Currently, such technologies do not exist. In the framework of the necessary carbon capture, and the opportunities for electrochemical (ocean) CO2 capture, five research questions are defined and addressed in this thesis...ChemE/Transport Phenomen
Improved Characterization of the Astrophysical Muon-Neutrino Flux with 9.5 Years of IceCube Data
No full textWe present a measurement of the high-energy astrophysical muon�neutrino flux with the IceCube Neutrino Observatory. The measurement uses a high-purity selection of 650k neutrino-induced muon tracks from the northern celestial hemisphere, corresponding to 9.5 yr of experimental data. With respect to previous publications, the measurement is improved by the increased size of the event sample and the extended model testing beyond simple power-law hypotheses. An updated treatment of systematic uncertainties and atmospheric background fluxes has been implemented based on recent models. The best-fit single power-law parameterization for the astrophysical energy spectrum results in a normalization of � f = � n n + - m m + - - -- - @100TeV 1.44 10 GeV cm s sr 0.26 0.25 18 1 2 1 1 and a spectral index g = - + 2.37 SPL 0.09 0.09, constrained in the energy range from 15 TeV to 5 PeV. The model tests include a single power law with a spectral cutoff at high energies, a log-parabola model, several source-class-specific flux predictions from the literature, and a model-independent spectral unfolding. The data are consistent with a single power-law hypothesis, however, spectra with softening above one PeV are statistically more favorable at a twosigma leve
Detection of Astrophysical Tau Neutrino Candidates in IceCube
No full textHigh-energy tau neutrinos are rarely produced in atmospheric cosmic-ray showers or at cosmic particle accelerators, but are expected to emerge during neutrino propagation over cosmic distances due to flavor mixing. When high energy tau neutrinos interact inside the IceCube detector, two spatially separated energy depositions may be resolved, the first from the charged current interaction and the second from the tau lepton decay. We report a novel analysis of 7.5 years of IceCube data that identifies two candidate tau neutrinos among the 60 �High-Energy Starting Events� (HESE) collected during that period. The HESE sample offers high purity, all-sky sensitivity, and distinct observational signatures for each neutrino flavor, enabling a new measurement of the flavor composition. The measured astrophysical neutrino flavor composition is consistent with expectations, and an astrophysical tau neutrino flux is indicated at 2.8? significance
Search for Neutrino Emission from Cores of Active Galactic Nuclei
No full textThe sources of the majority of the high-energy astrophysical neutrinos observed with the IceCube neutrino telescope at the South Pole are unknown. So far, only a flaring gamma-ray blazar was compellingly associated with the emission of high-energy neutrinos. However, several studies suggest that the neutrino emission from the gamma-ray blazar population only accounts for a small fraction of the total astrophysical neutrino flux. In this work we probe the production of high-energy neutrinos in the cores of active galactic nuclei (AGN), induced by accelerated cosmic rays in the accretion disk region. We present a likelihood analysis based on eight years of IceCube data, searching for a cumulative neutrino signal from three AGN samples created for this work. The neutrino emission is assumed to be proportional to the accretion disk luminosity estimated from the soft x-ray flux. Next to the observed soft x-ray flux, the objects for the three samples have been selected based on their radio emission and infrared color properties. For the largest sample in this search, an excess of high-energy neutrino events with respect to an isotropic background of atmospheric and astrophysical neutrinos is found, corresponding to a post-trial significance of 2.60?. If interpreted as a genuine signal with the assumptions of a proportionality of x-ray and neutrino fluxes and a model for the subthreshold flux distribution, then this observation implies that at 100 TeV, 27%�100% of the observed neutrinos arise from particle acceleration in the core of AGN at 1? confidence interva
Searches for Neutrinos from Gamma-Ray Bursts Using the IceCube Neutrino Observatory
No full textGamma-ray bursts (GRBs) are considered as promising sources of ultra-high-energy cosmic rays (UHECRs) due to their large power output. Observing a neutrino flux from GRBs would offer evidence that GRBs are hadronic accelerators of UHECRs. Previous IceCube analyses, which primarily focused on neutrinos arriving in temporal coincidence with the prompt gamma-rays, found no significant neutrino excess. The four analyses presented in this paper extend the region of interest to 14 days before and after the prompt phase, including generic extended time windows and targeted precursor searches. GRBs were selected between 2011 May and 2018 October to align with the data set of candidate muon-neutrino events observed by IceCube. No evidence of correlation between neutrino events and GRBs was found in these analyses. Limits are set to constrain the contribution of the cosmic GRB population to the diffuse astrophysical neutrino flux observed by IceCube. Prompt neutrino emission from GRBs is limited to 1% of the observed diffuse neutrino flux, and emission on timescales up to 104 s is constrained to 24% of the total diffuse flux
Search for Unstable Sterile Neutrinos with the IceCube Neutrino Observatory
No full textWe present a search for an unstable sterile neutrino by looking for a resonant signal in eight years of atmospheric ?? data collected from 2011 to 2019 at the IceCube Neutrino Observatory. Both the (table)three-neutrino and the 3 � 1 sterile neutrino models are disfavored relative to the unstable sterile neutrino model, though with p values of 2.8% and 0.81%, respectively, we do not observe evidence for 3 � 1 neutrinos with neutrino decay. The best-fit parameters for the sterile neutrino with decay model from this study are ?m2 41 � 6.7�3.9 ?2.5 eV2, sin22?24 � 0.33�0.20 ?0.17 , and g2 � 2.5? 1.5?, where g is the decaymediating coupling. The preferred regions of the 3 � 1 � decay model from short-baseline oscillation searches are excluded at 90% C.
Graph Neural Networks for Low-Energy Event Classification & Reconstruction in IceCube
No full textIceCube, a cubic-kilometer array of optical sensors built to detect atmospheric and astrophysical neutrinos between 1 GeV and 1 PeV, is deployed 1.45 km to 2.45 km below the surface of the ice sheet at the South Pole. The classification and reconstruction of events from the in-ice detectors play a central role in the analysis of data from IceCube. Reconstructing and classifying events is a challenge due to the irregular detector geometry, inhomogeneous scattering and absorption of light in the ice and, below 100 GeV, the relatively low number of signal photons produced per event. To address this challenge, it is possible to represent IceCube events as point cloud graphs and use a Graph Neural Network (GNN) as the classification and reconstruction method. The GNN is capable of distinguishing neutrino events from cosmic-ray backgrounds, classifying different neutrino event types, and reconstructing the deposited energy, direction and interaction vertex. Based on simulation, we provide a comparison in the 1 GeV�100 GeV energy range to the current state-of-the-art maximum likelihood techniques used in current IceCube analyses, including the effects of known systematic uncertainties. For neutrino event classification, the GNN increases the signal efficiency by 18% at a fixed background rate, compared to current IceCube methods. Alternatively, the GNN offers a reduction of the background (i.e. false positive) rate by over a factor 8 (to below half a percent) at a fixed signal efficiency. For the reconstruction of energy, direction, and interaction vertex, the resolution improves by an average of 13%�20% compared to current maximum likelihood techniques in the energy range of 1 GeV�30 GeV. The GNN, when run on a GPU, is capable of processing IceCube events at a rate nearly double of the median IceCube trigger rate of 2.7 kHz, which opens the possibility of using low energy neutrinos in online searches for transient events
