Das IceCube Neutrino Observatory, das größte Neutrino-Observatorium der Welt, entdeckte 2013 erstmals einen Fluss hochenergetischer Neutrinos. Diese Neutrinos müssen von astrophysikalischen Beschleunigern erzeugt werden, aber ihr genauer Ursprung ist bisher unbekannt. Vorgeschlagene Neutrinoquellen sind Gezeitenkatastrophen (Tidal Disruption Events, TDEs), Ereignisse bei denen Sterne zerfallen, wenn sie supermassiven Schwarzen Löchern zu nahe kommen. In dieser Doktorarbeit wurde erstmals nach Korrelationen zwischen Neutrinos und TDEs gesucht, wobei eine Zusammenstellung veröffentlichter TDEs und ein IceCube-Datensatz von einer Million Myon-Neutrinos mit GeV-PeV-Energien von verwendet wurde. Es wurde keine signifikante Korrelation gefunden, sodass der Beitrag von TDEs ohne relativistische Jets auf 0-38,0% des gesamten astrophysikalischen Neutrinoflusses begrenzt werden kann. Der Beitrag von TDEs mit relativistischen Jets wurde auf 0-3,0% des Gesamtflusses begrenzt. IceCube veröffentlicht auch hochenergetische (>100 TeV) Myon-Neutrino-Ereignisse in Form von automatischen, öffentlichen Echtzeit-‘Neutrinoalerts’. Im Rahmen dieser Arbeit wurde die Lokalisierung von 22 solcher Neutrinoalerts mit dem optischen Zwicky Transient Facility (ZTF) Teleskop beobachtet, um nach möglichen elektromagnetischen Gegenstücken zu Neutrinos zu suchen. Mit diesem Neutrino-Nachfolgebeobachtungsprogramm wurde die helle TDE AT2019dsg als mutmaßliche Neutrinoquelle identifiziert. Die Wahrscheinlichkeit, solch eine helle TDE zufällig zu finden, beträgt 0,2%. Die Assoziation bedeutet, dass TDEs 3-100% der astrophysikalischen Neutrino-Alerts von IceCube ausmachen. Zusammengenommen deuten diese beiden Ergebnisse darauf hin, dass TDEs einen subdominanten Anteil des astrophysikalischen Neutrinoflusses bei hohen Energien emittieren. Die Assoziation des Neutrinoalerts IC191001A mit AT2019dsg ist erst das zweite Mal, dass ein hochenergetisches Neutrino mit einer mutmaßlichen astrophysikalischen Quelle in Verbindung gebracht werden konnte. / The IceCube Neutrino Observatory, the world’s largest neutrino observatory, first discovered a flux of high-energy neutrinos in 2013. These neutrinos must be produced by astrophysical accelerators, but their exact origin remains unknown. One proposed source of neutrinos are Tidal Disruption Events (TDEs), which occur when stars disintegrate after passing sufficiently close to supermassive black holes. In this thesis, the first search for neutrino-TDE correlations was performed, using a compilation of published TDEs and a dataset of one million muon neutrino events of GeV-PeV energies from IceCube. No significant correlation was found, limiting the contribution of TDEs without relativistic jets to 0-38.0% of the total astrophysical neutrino flux. The contribution of TDEs with relativistic jets was limited to 0-3.0% of the total flux. IceCube also publishes high-energy (>100 TeV) probable astrophysical muon neutrino events automatically, in the form of public realtime alerts. As part of this thesis, the location of 22 such neutrino alerts were observed by the Zwicky Transient Facility (ZTF), an optical telescope, in order to search for possible electromagnetic counterparts to neutrinos. With this neutrino follow-up program, the bright TDE AT2019dsg was identified as a probable neutrino source. The probability of finding such a bright TDE by chance is 0.2%. The association implies that TDEs contribute 3-100% of the astrophysical neutrino alerts issued by IceCube. Taken together, these two results suggest that TDEs emit a subdominant fraction of the astrophysical neutrino flux at high energies. The association of neutrino alert IC191001A with AT2019dsg represents only the second time that a high-energy neutrino has been matched to a probable astrophysical source.

Typ Ia Supernovae (SNe) können verwendet werden, um Bulk-Flows zu messen, die durchschnittliche Bewegung von Materie relativ zur kosmischen Mikrowellenhintergrundstrahlung (CMB). Bulk-Flow-Studien ermöglichen Tests der Behauptung des Kosmologischen Prinzips von Homogenität und Isotropie für ausreichend große Distanzen. Im letzten Jahrzehnt wurden mehrere hohe Bulk-Geschwindigkeiten in großen Skalen gemeldet, die schwer mit den Vorhersagen des ΛCDM-Kosmologiemodells zu vereinbaren sind. In dieser Arbeit schätze ich Bulk-Flows auf der Grundlage einer neuen Probe von SNe aus einer Next-Generation-Sky-Survey namens Zwicky Transient Facility (ZTF). Die Auswahl und Analyse der großen Anzahl von astrophysikalischen Transienten, die jede Nacht von dieser Survey erfasst werden, ist komplex. Ich habe eine flexible Analysis Software namens AMPEL entwickelt, um diese Aufgaben zu erfüllen. Ein neuer ZTF-Datensatz, der aus etwa 850 Typ Ia SNe besteht, wurde für diese Forschung zusammengestellt. Simulationen zeigen, dass die nicht-sphärische Surveygeometrie von ZTF, die aktuellen Stichprobengrößenbeschränkungen und der Malmquist-Bias zusammen systematische Effekte ergeben, die kleiner sind als die aktuellen statistischen Unsicherheiten. Ich habe die ZTF-Probe zusammen mit zwei anderen kosmologischen SNe-Proben im heliozentrischen Inertialsystem verwendet, um das kosmische Ruhesystem unabhängig vom CMB zu etablieren. Der gemessene Beobachter-Dipol innerhalb der Rotverschiebungsschale 0,06 < z < 0,1 zeigt eine Konvergenz mit dem CMB-Temperaturdipol. Im CMB-Inertialsystem im gleichen Skala wird kein signifikanter Bulk-Flow gemessen. / Type Ia supernovae (SNe) can be used to measure bulk flows, the average motion of matter relative to the Cosmic Microwave Background (CMB). Bulk-flow studies enable tests of the Cosmological Principle’s assertion of large-scale homogeneity and isotropy. Over the past decade, several high bulk-velocities at large scales have been reported, which are difficult to unify with constraints from the ΛCDM cosmological model. In this work, I estimate bulk-flows based on a new sample of SNe from a next-generation sky survey called the Zwicky Transient Facility (ZTF). Selecting and analyzing the large number of astrophysical transients detected each night by this survey is complex. I developed a flexible analysis framework called AMPEL to address these challenges. A new ZTF dataset comprising roughly 850 type Ia SNe was assembled for this research. Simulations show that the non-spherical survey geometry of ZTF, the current sample size limitations, and the Malmquist bias together yield systematic effects smaller than current statistical uncertainties. I used the ZTF sample along with two cosmological-grade SNe samples in heliocentric inertial frame to establish the cosmic rest frame independently from the CMB. The measured observer-dipole within the redshift shell 0.06 < z < 0.1 shows convergence with the CMB temperature dipole. In the CMB inertial frame at the same scale, no significant bulk-flow is detected.

The gene lin-42 is an ortholog of the mammalian period gene, a component of the circadian pathway that converts environmental stimuli into behavioral and physiological outputs over 24 hours. Mammalian period also regulates adult stem cell differentiation, although this function is poorly understood. The structure, function and expression of lin-42 are all similar to period. Therefore, we are studying lin-42 regulation and function during C. elegans larval development as a model for understanding period control of mammalian stem/progenitor cell development. Previous work has shown that ZTF-16 is a regulator of lin-42 transcription. The lin-42 locus encodes three isoforms, and we have characterized lin-42 isoform specific regulation by ZTF-16 through phenotypic assays and analysis of transcriptional reporter strains. Our data show that ZTF-16 regulates the cyclic expression of lin-42A and lin-42B during larval development. However, ztf-16 is not expressed during the adult stage and does not regulate lin-42C, which is expressed only in adults and may be responsible for the circadian functions of lin-42. We also show that ztf-16 reduction-of-function mutations phenocopy loss-of- function phenotypes of the lin-42A/B isoforms. Finally, we have found that deletion of a putative ZTF-16 transcription factor binding site within the lin-42BC promoter abolishes tissue-specific expression patterns. Together, these data indicate that ZTF-16 is required to regulate the expression of lin-42A/B during C. elegans development, and may do this by direct binding to the lin-42BC promoter. Our  findings pave the way for testing the possible regulation of period expression by HIL-family transcription factors in mammalian tissues. / Master of Science

Period, which is broadly conserved in metazoans, regulates circadian timing of neurophysiology as well as cell fate specification. Studies in mouse and humans indicate that period functions as a tumor suppressor and controls adult stem cell differentiation. However, regulation of period function in developmental pathways has not been characterized and appears to be different from its regulation and function in circadian pathways. lin-42 is the Caenorhabditis elegans ortholog of period and has both circadian and developmental timing functions. During post-embryonic larval development, cyclic expression and function of lin-42 controls stage-specific and reiterative cell fate choices of a subset of epidermal stem cells called seam cells. We are studying lin-42 regulation of seam cell fate during C. elegans larval development as a model for understanding the mechanisms of period regulation of adult stem cell fate in mammals. This dissertation describes the research undertaken to characterize the cis-regulatory elements and the trans-regulatory factors that control lin-42 expression. We used direct molecular interaction assays (Electrophoretic Mobility Shift Assay, EMSA) (Chapter 2) followed by an RNA interference (RNAi)-based genetic screen (Chapter 3) to identify lin-42 transcriptional regulators. Using the EMSA, we identified three 50 to 100 base pair regions (binding regions, BR1-3) in the lin-42 5â noncoding sequences that were bound with specificity by C. elegans nuclear proteins. These binding regions represent putative cis-regulatory elements that may serve as transcription factor binding sites (TFBSs). We attempted to identify by mass spectrometry the proteins that bind to the BR sequences. We also used Phylogenetic Footprinting and bioinformatics screens to identify candidate C. elegans transcription factors (TFs) that may bind to putative TFBSs within the BR sequences. Using an RNAi-based screen, we tested the candidate TF genes for potential genetic interactions with lin-42. We identified ZTF-16, a member of the Hunchback/Ikaros zinc-finger transcription factor family, as a potential lin-42 activator and, using quantitative real-time PCR, confirmed that ztf-16 mutation results in down-regulation and loss of cycling expression of lin-42. We further determined that loss of ztf-16 results in seam cell development defects that phenocopy lin-42 loss-of-function, thus validating ZTF-16 as a transcriptional activator of lin-42. / Ph. D.