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  1. Free, publicly-accessible full text available June 1, 2023
  2. Abstract Tumor necrosis factor-α-induced protein 8 (TNFAIP8) is a member of the TIPE/TNFAIP8 family which regulates tumor growth and survival. Our goal is to delineate the detailed oncogenic role of TNFAIP8 in skin cancer development and progression. Here we demonstrated that higher expression of TNFAIP8 is associated with basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma development in patient tissues. Induction of TNFAIP8 expression by TNFα or by ectopic expression of TNFAIP8 in SCC or melanoma cell lines resulted in increased cell growth/proliferation. Conversely, silencing of TNFAIP8 decreased cell survival/cell migration in skin cancer cells. We also showedmore »that miR-205-5p targets the 3′UTR of TNFAIP8 and inhibits TNFAIP8 expression. Moreover, miR-205-5p downregulates TNFAIP8 mediated cellular autophagy, increased sensitivity towards the B-RAF V600E mutant kinase inhibitor vemurafenib, and induced cell apoptosis in melanoma cells. Collectively our data indicate that miR-205-5p acts as a tumor suppressor in skin cancer by targeting TNFAIP8.« less
    Free, publicly-accessible full text available December 1, 2022
  3. Free, publicly-accessible full text available October 1, 2022
  4. Monte Carlo (MC) methods are widely used in many research areas such as physical simulation, statistical analysis, and machine learning. Application of MC methods requires drawing fast mixing samples from a given probability distribution. Among existing sampling methods, the Hamiltonian Monte Carlo (HMC) utilizes gradient information during Hamiltonian simulation and can produce fast mixing samples at the highest efficiency. However, without carefully chosen simulation parameters for a specific problem, HMC generally suffers from simulation locality and computation waste. As a result, the No-U-Turn Sampler (NUTS) has been proposed to automatically tune these parameters during simulation and is the current state-of-the-artmore »sampling algorithm. However, application of NUTS requires frequent gradient calculation of a given distribution and high-volume vector processing, especially for large-scale problems, leading to drawing an expensively large number of samples and a desire of hardware acceleration. While some hardware acceleration works have been proposed for traditional Markov Chain Monte Carlo (MCMC) and HMC methods, there is no existing work targeting hardware acceleration of the NUTS algorithm. In this paper, we present the first NUTS accelerator on FPGA while addressing the high complexity of this state-of-the-art algorithm. Our hardware and algorithm co-optimizations include an incremental resampling technique which leads to a more memory efficient architecture and pipeline optimization for multi-chain sampling to maximize the throughput. We also explore three levels of parallelism in the NUTS accelerator to further boost performance. Compared with optimized C++ NUTS package: RSTAN, our NUTS accelerator can reach a maximum speedup of 50.6X and an energy improvement of 189.7X.« less
    Free, publicly-accessible full text available July 7, 2022
  5. Free, publicly-accessible full text available September 22, 2022
  6. Two-dimensional van der Waals (vdWs) materials have gathered a lot of attention recently. However, the majority of these materials have Curie temperatures that are well below room temperature, making it challenging to incorporate them into device applications. In this work, we synthesized a room-temperature vdW magnetic crystal Fe5GeTe2 with a Curie temperature T$_c = 332$ K, and studied its magnetic properties by vibrating sample magnetometry (VSM) and broadband ferromagnetic resonance (FMR) spectroscopy. The experiments were performed with external magnetic fields applied along the c-axis (H$\parallel$c) and the ab-plane (H$\parallel$ab), with temperatures ranging from 300 to 10 K. We have foundmore »a sizable Landé g-factor difference between the H$\parallel$c and H$\parallel$ab cases. In both cases, the Landé g-factor values deviated from g = 2. This indicates contribution of orbital angular momentum to the magnetic moment. The FMR measurements reveal that Fe5GeTe2 has a damping constant comparable to Permalloy. With reducing temperature, the linewidth was broadened. Together with the VSM data, our measurements indicate that Fe5GeTe2 transitions from ferromagnetic to ferrimagnetic at lower temperatures. Our experiments highlight key information regarding the magnetic state and spin scattering processes in Fe5GeTe2, which promote the understanding of magnetism in Fe5GeTe2, leading to implementations of Fe5GeTe2 based room-temperature spintronic devices.« less
    Free, publicly-accessible full text available September 13, 2022
  7. Abstract Mitochondria play important roles in ovarian follicle development. Mitochondrial dysfunction, including mitochondrial gene deficiency, impairs ovarian development. Here, we explored the role and mechanism of mitochondrial inner membrane gene Immp2l in ovarian follicle growth and development. Our results revealed that female Immp2l-/- mice were infertile, whereas Immp2l+/- mice were normal. Body and ovarian weights were reduced in the female Immp2l-/- mice, ovarian follicle growth and development were stunted in the secondary follicle stage. Although a few ovarian follicles were ovulated, the oocytes were not fertilized because of mitochondrial dysfunction. Increased oxidative stress, decreased estrogen levels, and altered genes expressionmore »of Wnt/β-catenin and steroid hormone synthesis pathways were observed in 28-day-old Immp2l-/- mice. The Immp2l mutation accelerated ovarian aging process, as no ovarian follicles were detected by age 5 months in Immp2l-/- mice. All the aforementioned changes in the Immp2l-/- mice were reversed by administration of antioxidant melatonin to the Immp2l-/- mice. Furthermore, our in vitro study using Immp2l knockdown granulosa cells confirmed that the Immp2l downregulation induced granulosa cell aging by enhancing reactive oxygen species (ROS) levels, suppressing Wnt16, increasing β-catenin, and decreasing steroid hormone synthesis gene cyp19a1 and estrogen levels, accompanied by an increase in the aging phenotype of granulosa cells. Melatonin treatment delayed granulosa cell aging progression. Taken together, Immp2l causes ovarian aging through the ROS-Wnt/β-catenin-estrogen (cyp19a1) pathway, which can be reversed by melatonin treatment.« less