Dependence of heat transport on the strength and shear rate of prescribed circulating flows

We study numerically the dependence of heat transport on the maximum velocity and shear rate of physical circulating flows, which are prescribed to have the key characteristics of the large-scale mean flow observed in turbulent convection. When the side-boundary thermal layer is thinner than the viscous boundary layer, the Nusselt number (Nu), which measures the heat transport, scales with the normalized shear rate to an exponent 1/3. On the other hand, when the side-boundary thermal layer is thicker, the dependence of Nu on the Peclet number, which measures the maximum velocity, or the normalized shear rate when the viscous boundary layer thickness is fixed, is generally not a power law. Scaling behavior is obtained only in an asymptotic regime. The relevance of our results to the problem of heat transport in turbulent convection is also discussed.Comment: 7 pages, 7 figures, submitted to European Physical Journal

Towards Transcervical Ultrasound Image Guidance for Transoral Robotic Surgery

Purpose: Trans-oral robotic surgery (TORS) using the da Vinci surgical robot is a new minimally-invasive surgery method to treat oropharyngeal tumors, but it is a challenging operation. Augmented reality (AR) based on intra-operative ultrasound (US) has the potential to enhance the visualization of the anatomy and cancerous tumors to provide additional tools for decision-making in surgery. Methods: We propose and carry out preliminary evaluations of a US-guided AR system for TORS, with the transducer placed on the neck for a transcervical view. Firstly, we perform a novel MRI-transcervical 3D US registration study. Secondly, we develop a US-robot calibration method with an optical tracker and an AR system to display the anatomy mesh model in the real-time endoscope images inside the surgeon console. Results: Our AR system reaches a mean projection error of 26.81 and 27.85 pixels for the projection from the US to stereo cameras in a water bath experiment. The average target registration error for MRI to 3D US is 8.90 mm for the 3D US transducer and 5.85 mm for freehand 3D US, and the average distance between the vessel centerlines is 2.32 mm. Conclusion: We demonstrate the first proof-of-concept transcervical US-guided AR system for TORS and the feasibility of trans-cervical 3D US-MRI registration. Our results show that trans-cervical 3D US is a promising technique for TORS image guidance.Comment: 12 pages, 8 figures. Accepted by Information Processing for Computer Assisted Interventions (IPCAI 2023

Interleukin-1β Produced in Response to Islet Autoantigen Presentation Differentiates T-Helper 17 Cells at the Expense of Regulatory T-Cells: Implications for the Timing of Tolerizing Immunotherapy

OBJECTIVE-The effectiveness of tolerizing immunotherapeutic strategies, such as anti-CD40L or dendritic cells (DCs), is greater when administered to young nonobese diabetic (NOD) mice than at peak insulitis. RelB(lo) DCs, generated in the presence of an nuclear factor-kappa B inhibitor, induce T-regulatory (Treg) cells and suppress inflammation in a model of rheumatoid arthritis. Interleukin (IL)-1 beta is overexpressed in humans and mice at risk of type 1 diabetes, dysregulates Treg cells, and accelerates diabetes in NOD mice. We investigated the relationship between IL-1 beta production and the response to RelB(lo) DCs in the prediabetic period

Neurexin Superfamily Cell Membrane Receptor Contactin-Associated Protein Like-4 (Cntnap4) Is Involved in Neural EGFL-Like 1 (Nell-1)-Responsive Osteogenesis

Contactin-associated protein-like 4 (Cntnap4) is a member of the neurexin superfamily of transmembrane molecules that have critical functions in neuronal cell communication. Cntnap4 knockout mice display decreased presynaptic gamma-aminobutyric acid (GABA) and increased dopamine release that is associated with severe, highly penetrant, repetitive, and perseverative movements commonly found in human autism spectrum disorder patients. However, no known function of Cntnap4 has been revealed besides the nervous system. Meanwhile, secretory protein neural EGFL-like 1 (Nell-1) is known to exert potent osteogenic effects in multiple small and large animal models without the off-target effects commonly found with bone morphogenetic protein 2. In this study, while searching for a Nell-1-specific cell surface receptor during osteogenesis, we identified and validated a ligand/receptor-like interaction between Nell-1 and Cntnap4 by demonstrating: 1) Nell-1 and Cntnap4 colocalization on the surface of osteogenic-committed cells; 2) high-affinity interaction between Nell-1 and Cntnap4; 3) abrogation of Nell-1-responsive Wnt and MAPK signaling transduction, as well as osteogenic effects, via Cntnap4 knockdown; and 4) replication of calvarial cleidocranial dysplasias-like defects observed in Nell-1-deficient mice in Wnt1-Cre-mediated Cntnap4-knockout transgenic mice. In aggregate, these findings indicate that Cntnap4 plays a critical role in Nell-1-responsive osteogenesis. Further, this is the first functional annotation for Cntnap4 in the musculoskeletal system. Intriguingly, Nell-1 and Cntnap4 also colocalize on the surface of human hippocampal interneurons, implicating Nell-1 as a potential novel ligand for Cntnap4 in the nervous system. This unexpected characterization of the ligand/receptor-like interaction between Nell-1 and Cntnap4 indicates a novel biological functional axis for Nell-1 and Cntnap4 in osteogenesis and, potentially, in neural development and function. © 2018 American Society for Bone and Mineral Research. © 2018 American Society for Bone and Mineral Researc

CDKN2B Upregulation Prevents Teratoma Formation in Multipotent Fibromodulin-Reprogrammed Cells

Tumorigenicity is a well-documented risk to overcome for pluripotent or multipotent cell applications in regenerative medicine. To address the emerging demand for safe cell sources in tissue regeneration, we established a novel, protein-based reprogramming method that does not require genome integration or oncogene activation to yield multipotent fibromodulin (FMOD)-reprogrammed (FReP) cells from dermal fibroblasts. When compared with induced pluripotent stem cells (iPSCs), FReP cells exhibited a superior capability for bone and skeletal muscle regeneration with markedly less tumorigenic risk. Moreover, we showed that the decreased tumorigenicity of FReP cells was directly related to an upregulation of cyclin-dependent kinase inhibitor 2B (CDKN2B) expression during the FMOD reprogramming process. Indeed, sustained suppression of CDKN2B resulted in tumorigenic, pluripotent FReP cells that formed teratomas in vivo that were indistinguishable from iPSC-derived teratomas. These results highlight the pivotal role of CDKN2B in cell fate determination and tumorigenic regulation and reveal an alternative pluripotent/multipotent cell reprogramming strategy that solely uses FMOD protein. © 2019, American Society for Clinical Investigation

Updated observing scenarios and multi-messenger implications for the International Gravitational-wave Network's O4 and O5

Advanced LIGO and Virgo's third observing run brought another binary neutron star merger (BNS) and the first neutron-star black-hole (NSBH) mergers. While no confirmed kilonovae (KNe) was identified in conjunction with any of these events, continued improvements of analyses surrounding GW170817 allow us to project constraints on the Hubble Constant ($H_0$), the Galactic enrichment from $r$-process nucleosynthesis, and ultra-dense matter possible from forthcoming events. Here, we describe the expected constraints based on the latest expected event rates from the international gravitational-wave network (IGWN) and analyses of GW170817. We show the expected detection rate of gravitational waves and their counterparts, as well as how sensitive potential constraints are to the observed numbers of counterparts. We intend this analysis as support for the community when creating scientifically-driven electromagnetic follow-up proposals. During the next observing run O4, we predict an annual detection rate of electromagnetic counterparts from BNS of $0.43^{+0.58}_{-0.26}$ ($1.97^{+2.68}_{-1.2}$) for the Zwicky Transient Facility (Rubin Observatory)