An Understanding of The Diffuse Supernova Neutrino Background

Neutrinos, some of the most elusive particles in the universe are emitted in copious numbers by core-collapse supernovae. Over the course of time, these particles create a faint cosmic background known as the Diffuse Supernova Neutrino Background(DSNB). The DSNB, if detected, can prove to be a powerful tool to constrain the cosmic star formation history and place significant constraints on the core-collapse supernova physics. In this work, we model this background field and estimate the DSNB flux in the energy range from 19 MeV to 100 MeV. We investigate the change of the spectral shape of the DSNB as the redshift increases. We also predict the core collapse supernova rates of galaxies in the local volume (LV),i.e. distances less than 10 Mpc and predict the number of neutrinos released from individual supernova events from galaxies within the LV. This prediction will not only help us resolve the DSNB but also guide the development of future neutrino surveys

Cosmic Diffuse Neutrino and Gamma-Ray Backgrounds in the MeV Regime

Cosmic Multi-Messenger backgrounds include relic diffuse components created in the early Universe and contributions from individual sources. In this dissertation, I present the work done in Anandagoda (2019); Anandagoda et al. (2020, 2023) where type Ia (SNe Ia) and core-collapse supernovae (CCSNe) contributions to the diffuse neutrino and gamma-ray backgrounds in the MeV regime are studied. These backgrounds are referred to as DSNB and DSGB respectively. Based on this work, the diffuse SN Ia background is ~106 times lower (for electron antineutrinos) than the CCSN background making it negligible. The predicted DSNB electron antineutrino flux at earth in the 19.3-32 MeV regime is 0.36 ν cm-2s-1. We also find that the DSNB flux in the energy range from 11.3 - 32 MeV varies by ≈+29\% with a change in the SFRD model from Madau and Fragos (2017) which yielded a minimum predicted flux, to EBL reconstruction model (Fermi-LAT Collaboration et al., 2018) (maximum predicted flux). The diffuse SN Ia gamma-ray background and its dependence on the progenitor-supernova delay time distribution (DTD) is also evaluated. Furthermore, we address the origin of the CGB (Cosmic Gamma-ray Background) in the 0.1-7 MeV regime by adding contributions from sources such as SNe Ia, CCSNe, radio-quiet Active Galactic Nuclei (AGN), Flat spectrum radio quasars (FSRQs) and Neutron star - neutron star (NS-NS) mergers. We find that our modeled background (including uncertainties) matches the observed CGB above 1.0 MeV, but is a factor ≈2 lower than the observed flux in the 0.1 MeV to 1.0 MeV range, highlighting the need for future MeV missions to establish the CGB spectrum more reliably, and to possibly identify additional sources or even source classes in the under-explored MeV band. While solar neutrino spectra have been studied extensively, neutrino spectra from other stars have not been the subject of detailed studies. In this work, the change in the electron neutrino spectra for various stars of different masses and ages are evaluated using stellar models evolved using Modules for Experiments in Stellar Astrophysics (MESA) simulation software. Based on these results, the electron neutrino spectrum from the Milky Way galaxy is modeled

microRNA-142-mediated repression of phosphodiesterase 3B critically regulates peripheral immune tolerance

Tregs play a fundamental role in immune tolerance via control of self-reactive effector T cells (Teffs). This function is dependent on maintenance of a high intracellular cAMP concentration. A number of microRNAs are implicated in the maintenance of Tregs. In this study, we demonstrate that peripheral immune tolerance is critically dependent on posttranscriptional repression of the cAMP-hydrolyzing enzyme phosphodiesterase-3b (Pde3b) by microRNA-142-5p (miR-142-5p). In this manner, miR-142-5p acts as an immunometabolic regulator of intracellular cAMP, controlling Treg suppressive function. Mir142 was associated with a super enhancer bound by the Treg lineage-determining transcription factor forkhead box P3 (FOXP3), and Treg-specific deletion of miR-142 in mice (TregΔ142) resulted in spontaneous, lethal, multisystem autoimmunity, despite preserved numbers of phenotypically normal Tregs. Pharmacological inhibition and genetic ablation of PDE3B prevented autoimmune disease and reversed the impaired suppressive function of Tregs in TregΔ142 animals. These findings reveal a critical molecular switch, specifying Treg function through the modulation of a highly conserved, cell-intrinsic metabolic pathway. Modulation of this pathway has direct relevance to the pathogenesis and treatment of autoimmunity and cancer

Mir142 loss unlocks IDH2R140-dependent leukemogenesis through antagonistic regulation of HOX genes

AML is a genetically heterogeneous disease and understanding how different co-occurring mutations cooperate to drive leukemogenesis will be crucial for improving diagnostic and therapeutic options for patients. MIR142 mutations have been recurrently detected in IDH-mutated AML samples. Here, we have used a mouse model to investigate the interaction between these two mutations and demonstrate a striking synergy between Mir142 loss-of-function and IDH2R140Q, with only recipients of double mutant cells succumbing to leukemia. Transcriptomic analysis of the non-leukemic single and leukemic double mutant progenitors, isolated from these mice, suggested a novel mechanism of cooperation whereby Mir142 loss-of-function counteracts aberrant silencing of Hoxa cluster genes by IDH2R140Q. Our analysis suggests that IDH2R140Q is an incoherent oncogene, with both positive and negative impacts on leukemogenesis, which requires the action of cooperating mutations to alleviate repression of Hoxa genes in order to advance to leukemia. This model, therefore, provides a compelling rationale for understanding how different mutations cooperate to drive leukemogenesis and the context-dependent effects of oncogenic mutations

MicroRNA-142 Critically Regulates Group 2 Innate Lymphoid Cell Homeostasis and Function

Innate lymphoid cells are central to the regulation of immunity at mucosal barrier sites, with group 2 innate lymphoid cells (ILC2s) being particularly important in type 2 immunity. In this study, we demonstrate that microRNA(miR)-142 plays a critical, cell-intrinsic role in the homeostasis and function of ILC2s. Mice deficient for miR-142 expression demonstrate an ILC2 progenitor_biased development in the bone marrow, and along with peripheral ILC2s at mucosal sites, these cells display a greatly altered phenotype based on surface marker expression. ILC2 proliferative and effector functions are severely dysfunctional following Nippostrongylus brasiliensis infection, revealing a critical role for miR-142 isoforms in ILC2-mediated immune responses. Mechanistically, Socs1 and Gfi1 expression are regulated by miR-142 isoforms in ILC2s, impacting ILC2 phenotypes as well as the proliferative and effector capacity of these cells. The identification of these novel pathways opens potential new avenues to modulate ILC2-dependent immune functions

SNuGGY: v0.1

<p>Software to simulate point like neutrino and gamma-ray emissions from our Galaxy. See https://arxiv.org/pdf/2306.17305.pdf for more details regarding usage of the code. </p><p>If you use this software, please cite using the zenodo and ApJ/arxiv links. Feel free to message us if you want us to add more functionalty to the software or collaborate.</p&gt

Boosting translational research in the U.K.

Investment in national infrastructure is critical for growth in early-phase translational research and experimental medicine.</jats:p