NDRG4 is a novel oncogenic protein and p53 associated regulator of apoptosis in malignant meningioma cells

Aggressive meningiomas exhibit high levels of recurrence, morbidity and mortality. When surgical and radiation options are exhausted, there is need for novel molecularly-targeted therapies. We have recently identified NDRG4 overexpression in aggressive meningiomas. NDRG4 is a member of the N-Myc Downstream Regulated Gene (NDRG) family of the alpha/beta hydrolase superfamily. We have demonstrated that NDRG4 downregulation results in decreased cell proliferation, migration and invasion. In follow up to our prior studies; here we demonstrate that the predominant form of cell death following NDRG4 silencing is apoptosis, utilizing Annexin-V flow cytometry assay. We show that apoptosis caused by p53 upregulation, phosphorylation at Ser15, BAX activation, Bcl-2 and BcL-xL downregulation, mitochondrial cytochrome c release and execution of caspases following NDRG4 depletion. Sub-cellular distribution of BAX and cytochrome c indicated mitochondrial-mediated apoptosis. In addition, we carried out the fluorescence cytochemical analysis to confirm mitochondrial-mediated apoptosis by changes in mitochondrial membrane potential (Ψm), using JC-1 dye. Immunoprecipitation and immunofluorescence confirmed binding of NDRG4 to p53. In addition, we demonstrate that apoptosis is mitochondrial and p53 dependent. The proapoptotic effect of p53 was verified by the results in which a small molecule compound PFT-α, an inhibitor of p53 phosphorylation, is greatly protected against targeting NDRG4 induced apoptosis. These findings bring novel insight to the roles of NDRG4 in meningioma progression. A better understanding of this pathway and its role in meningioma carcinogenesis and cell biology is promising for the development of novel therapeutic targets for the management of aggressive meningiomas

Group Equivariant Fourier Neural Operators for Partial Differential Equations

We consider solving partial differential equations (PDEs) with Fourier neural operators (FNOs), which operate in the frequency domain. Since the laws of physics do not depend on the coordinate system used to describe them, it is desirable to encode such symmetries in the neural operator architecture for better performance and easier learning. While encoding symmetries in the physical domain using group theory has been studied extensively, how to capture symmetries in the frequency domain is under-explored. In this work, we extend group convolutions to the frequency domain and design Fourier layers that are equivariant to rotations, translations, and reflections by leveraging the equivariance property of the Fourier transform. The resulting $G$-FNO architecture generalizes well across input resolutions and performs well in settings with varying levels of symmetry. Our code is publicly available as part of the AIRS library (https://github.com/divelab/AIRS).Comment: Proceedings of the 40th International Conference on Machine Learning https://icml.cc/virtual/2023/poster/2387

Exploring calibration algorithms to maximize the null depth in KPIC's vortex fiber nulling mode

Vortex fiber nulling (VFN) is a new interferometric technique with the potential to unlock the ability to detect and spectroscopically characterize exoplanets at angular separations smaller than the conventional diffraction limit of $\lambda$/D. In early 2022, a VFN mode was added to the Keck Planet Imager and Characterizer (KPIC) instrument suite on Keck II. VFN operates by adding an azimuthal phase ramp to the incident wavefront so that light from the star at the center of the field is prevented from coupling into a single-mode fiber. One of the key performance goals of VFN is to minimize the ratio of on-axis starlight coupling to off-axis planet coupling, which requires minimizing the wavefront aberrations of light being injected into the fiber. Non-common path aberrations can be calibrated during the daytime and compensated for with the KPIC deformable mirror during nighttime observing. By applying different amplitudes of low-order Zernike modes, we determine which combinations maximize the system performance. Here we present our work developing and testing different procedures to estimate the incident aberrations, both in simulation and on the Keck bench. The current iteration of this calibration algorithm has been used successfully for VFN observing, and there are several avenues for improvement.Comment: 14 pages, 10 figures, to be published in SPIE Proceedings associated with the 2023 SPIE Optics and Photonics Conferenc

As the Worlds Turn: Constraining Spin Evolution in the Planetary-Mass Regime

To understand how planetary spin evolves and traces planet formation processes, we measure rotational line broadening in eight planetary-mass objects (PMOs) of various ages (1--800 Myr) using near-infrared high-resolution spectra from NIRSPEC/Keck. Combining these with published rotation rates, we compile 27 PMO spin velocities, 16 of which derive from our NIRSPEC/Keck program. Our data are consistent with spin velocities $v$ scaling with planetary radius $R$ as $v \propto 1/R$. We conclude that spin angular momentum is conserved as objects cool and contract over the sampled age range. The PMOs in our sample spin at rates that are approximately an order of magnitude below their break-up values, consistent with the hypothesis that they were spun down by magnetized circum-PMO disks (CPDs) during the formation era at ages $\lesssim$ a few Myr. There is a factor of 4--5 variation in spin velocity that has yet to be understood theoretically. It also remains to be seen whether spin evolves on timescales $\gtrsim$ 1 Gyr for PMOs, as it does for stars and high-mass brown dwarfs emitting magnetized winds.Comment: accepted to Ap

Mutual inclinations between giant planets and their debris discs in HD 113337 and HD 38529

HD 113337 and HD 38529 host pairs of giant planets, a debris disc, and wide M-type stellar companions. We measure the disc orientation with resolved images from Herschel and constrain the three-dimensional orbits of the outer planets with Gaia DR2 and Hipparcos astrometry. Resolved disc modelling leaves degeneracy in the disc orientation, so we derive four separate planet-disc mutual inclination (∆I) solutions. The most aligned solutions give ∆I = 17°-32° for HD 113337 and ∆I = 21°-45○ for HD 38529 (both 1σ). In both systems, there is a small probability (<0.3 per cent) that the planet and disc are nearly aligned (∆I < 3○). The stellar and planetary companions cause the orbits of disc material to precess about a plane defined by the forced inclination. We determine this as well as the precession time-scale to interpret the mutual inclination results. We find that the debris discs in both systems could be warped via joint influences of the outer planet and stellar companion, potentially explaining the observed misalignments. However, this requires HD 113337 to be old (0.8-1.7 Gyr), whereas if young (14-21 Myr), the observed misalignment in HD 113337 could be inherited from the protoplanetary disc phase. For both systems, the inclination of the stellar spin axis is consistent with the disc and outer planet inclinations, which instead supports system-wide alignment or near alignment. High-resolution observations of the discs and improved constraints on the planetary orbits would provide firmer conclusions about the (mis)alignment status