Exploring muonphilic ALPs at μ+μ−\mu^+\mu^- and μp\mu p colliders

Axion-like particles (ALPs) are new particles that extend beyond the standard model (SM) and are highly motivated. When considering ALPs within an effective field theory, their couplings with SM particles can be studied independently. It is a daunting task to search for GeV-scale ALPs coupled to muons in collider experiments because their coupling is proportional to the muon mass. However, a recent study by Altmannshofer, Dror, and Gori (2022) highlighted the importance of a four-point interaction, $W$-$\mu$-$\nu_{\mu}$-$a$, which coupling is not dependent on the muon mass. This interaction provides a new opportunity to explore muonphilic ALPs ($\mu$ALPs) at the GeV scale. We concentrate on $\mu$ALPs generated through this four-point interaction at future $\mu^+\mu^-$ and $\mu p$ colliders that subsequently decay into a pair of muons. This new channel for exploring $\mu$ALPs with $1$ GeV $\leq m_a\lesssim M_W$ can result in much stronger future constraints than the existing ones.Comment: 34 pages, 12 figures, 7 table

Hypoxia-Adenosine Axis As Therapeutic Targets for Acute Respiratory Distress Syndrome

The human respiratory and circulatory systems collaborate intricately to ensure oxygen delivery to all cells, which is vital for ATP production and maintaining physiological functions and structures. During limited oxygen availability, hypoxia-inducible factors (HIFs) are stabilized and play a fundamental role in maintaining cellular processes for hypoxia adaptation. First discovered during investigations of erythropoietin production regulation, HIFs influence physiological and pathological processes, including development, inflammation, wound healing, and cancer. HIFs promote extracellular adenosine signaling by enhancing adenosine generation and receptor signaling, representing an endogenous feedback mechanism that curbs excessive inflammation, supports injury resolution, and enhances hypoxia tolerance. This is especially important for conditions that involve tissue hypoxia, such as acute respiratory distress syndrome (ARDS), which globally poses significant health challenges without specific treatment options. Consequently, pharmacological strategies to amplify HIF-mediated adenosine production and receptor signaling are of great importance

Interplay of Hypoxia-Inducible Factors and Oxygen Therapy in Cardiovascular Medicine

Mammals have evolved to adapt to differences in oxygen availability. Although systemic oxygen homeostasis relies on respiratory and circulatory responses, cellular adaptation to hypoxia involves the transcription factor hypoxia-inducible factor (HIF). Given that many cardiovascular diseases involve some degree of systemic or local tissue hypoxia, oxygen therapy has been used liberally over many decades for the treatment of cardiovascular disorders. However, preclinical research has revealed the detrimental effects of excessive use of oxygen therapy, including the generation of toxic oxygen radicals or attenuation of endogenous protection by HIFs. In addition, investigators in clinical trials conducted in the past decade have questioned the excessive use of oxygen therapy and have identified specific cardiovascular diseases in which a more conservative approach to oxygen therapy could be beneficial compared with a more liberal approach. In this Review, we provide numerous perspectives on systemic and molecular oxygen homeostasis and the pathophysiological consequences of excessive oxygen use. In addition, we provide an overview of findings from clinical studies on oxygen therapy for myocardial ischaemia, cardiac arrest, heart failure and cardiac surgery. These clinical studies have prompted a shift from liberal oxygen supplementation to a more conservative and vigilant approach to oxygen therapy. Furthermore, we discuss the alternative therapeutic strategies that target oxygen-sensing pathways, including various preconditioning approaches and pharmacological HIF activators, that can be used regardless of the level of oxygen therapy that a patient is already receiving

The INTERSPEECH 2020 Far-Field Speaker Verification Challenge

The INTERSPEECH 2020 Far-Field Speaker Verification Challenge (FFSVC 2020) addresses three different research problems under well-defined conditions: far-field text-dependent speaker verification from single microphone array, far-field text-independent speaker verification from single microphone array, and far-field text-dependent speaker verification from distributed microphone arrays. All three tasks pose a cross-channel challenge to the participants. To simulate the real-life scenario, the enrollment utterances are recorded from close-talk cellphone, while the test utterances are recorded from the far-field microphone arrays. In this paper, we describe the database, the challenge, and the baseline system, which is based on a ResNet-based deep speaker network with cosine similarity scoring. For a given utterance, the speaker embeddings of different channels are equally averaged as the final embedding. The baseline system achieves minDCFs of 0.62, 0.66, and 0.64 and EERs of 6.27%, 6.55%, and 7.18% for task 1, task 2, and task 3, respectively.Comment: Submitted to INTERSPEECH 202

The Resurgence of the Adora2b Receptor as an Immunotherapeutic Target in Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense desmoplastic stroma that impedes drug delivery, reduces parenchymal blood flow, and suppresses the anti-tumor immune response. The extracellular matrix and abundance of stromal cells result in severe hypoxia within the tumor microenvironment (TME), and emerging publications evaluating PDAC tumorigenesis have shown the adenosine signaling pathway promotes an immunosuppressive TME and contributes to the overall low survival rate. Hypoxia increases many elements of the adenosine signaling pathway, resulting in higher adenosine levels in the TME, further contributing to immune suppression. Extracellular adenosine signals through 4 adenosine receptors (Adora1, Adora2a, Adora2b, Adora3). Of the 4 receptors, Adora2b has the lowest affinity for adenosine and thus, has important consequences when stimulated by adenosine binding in the hypoxic TME. We and others have shown that Adora2b is present in normal pancreas tissue, and in injured or diseased pancreatic tissue, Adora2b levels are significantly elevated. The Adora2b receptor is present on many immune cells, including macrophages, dendritic cells, natural killer cells, natural killer T cells, γδ T cells, B cells, T cells, CD