Autophagy gene haploinsufficiency drives chromosome instability, increases migration, and promotes early ovarian tumors.

Autophagy, particularly with BECN1, has paradoxically been highlighted as tumor promoting in Ras-driven cancers, but potentially tumor suppressing in breast and ovarian cancers. However, studying the specific role of BECN1 at the genetic level is complicated due to its genomic proximity to BRCA1 on both human (chromosome 17) and murine (chromosome 11) genomes. In human breast and ovarian cancers, the monoallelic deletion of these genes is often co-occurring. To investigate the potential tumor suppressor roles of two of the most commonly deleted autophagy genes in ovarian cancer, BECN1 and MAP1LC3B were knocked-down in atypical (BECN1+/+ and MAP1LC3B+/+) ovarian cancer cells. Ultra-performance liquid chromatography mass-spectrometry metabolomics revealed reduced levels of acetyl-CoA which corresponded with elevated levels of glycerophospholipids and sphingolipids. Migration rates of ovarian cancer cells were increased upon autophagy gene knockdown. Genomic instability was increased, resulting in copy-number alteration patterns which mimicked high grade serous ovarian cancer. We further investigated the causal role of Becn1 haploinsufficiency for oncogenesis in a MISIIR SV40 large T antigen driven spontaneous ovarian cancer mouse model. Tumors were evident earlier among the Becn1+/- mice, and this correlated with an increase in copy-number alterations per chromosome in the Becn1+/- tumors. The results support monoallelic loss of BECN1 as permissive for tumor initiation and potentiating for genomic instability in ovarian cancer

Detector dead-time effects and paralyzability in high-speed quantum key distribution

Recent advances in quantum key distribution (QKD) have given rise to systems that operate at transmission periods significantly shorter than the dead times of their component single-photon detectors. As systems continue to increase in transmission rate, security concerns associated with detector dead times can limit the production rate of sifted bits. We present a model of high-speed QKD in this limit that identifies an optimum transmission rate for a system with given link loss and detector response characteristics

A simulation-calibrated limit on the H i power spectrum from the GMRT Epoch of Reionization experiment

The Giant Metrewave Radio Telescope Epoch of Reionization experiment is an ongoing effort to measure the power spectrum from neutral hydrogen at high redshift. We have previously reported an upper limit of (70 mK)^2 at wavenumbers of k ≈ 0.65 h Mpc^(−1) using a basic piecewise-linear foreground subtraction. In this paper, we explore the use of a singular value decomposition to remove foregrounds with fewer assumptions about the foreground structure. Using this method, we also quantify, for the first time, the signal loss due to the foreground filter and present new power spectra adjusted for this loss, providing a revised measurement of a 2σ upper limit at (248 mK)^2 for k = 0.50 h Mpc^(−1). While this revised limit is larger than previously reported, we believe it to be more robust and still represents the best current constraint on reionization at z ≈ 8.6

Salvage therapies for radiation-relapsed isocitrate dehydrogenase-mutant astrocytoma and 1p/19q codeleted oligodendroglioma

BACKGROUND: Optimal management for recurrent IDH-mutant glioma after radiation therapy (RT) is not well-defined. This study assesses practice patterns for managing recurrent IDH-mutant astrocytoma (Astro) and 1p/19q codeleted oligodendroglioma (Oligo) after RT and surveys their clinical outcomes after different salvage approaches. METHODS: Ninety-four recurrent Astro or Oligo patients after RT who received salvage systemic therapy (SST) between 2001 and 2019 at a tertiary cancer center were retrospectively analyzed. SST was defined as either alkylating chemotherapy (AC) or nonalkylating therapy (non-AC). Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method from the start of SST. Multivariable analysis (MVA) was conducted using Cox regression analysis. RESULTS: Recurrent Oligo (n = 35) had significantly higher PFS (median: 3.1 vs 0.8 years, respectively, CONCLUSIONS: Recurrent radiation-relapsed IDH-mutant gliomas represent a heterogeneous group with variable treatment approaches. Surgery, AC, and reirradiation remain the mainstay of salvage options for retreatment

Strain Engineering a 4a×3a4a\times\sqrt{3}a Charge Density Wave Phase in Transition Metal Dichalcogenide 1T-VSe2_2

We report a rectangular charge density wave (CDW) phase in strained 1T-VSe$_2$ thin films synthesized by molecular beam epitaxy on c-sapphire substrates. The observed CDW structure exhibits an unconventional rectangular 4a{\times}{\sqrt{3a}} periodicity, as opposed to the previously reported hexagonal $4a\times4a$ structure in bulk crystals and exfoliated thin layered samples. Tunneling spectroscopy shows a strong modulation of the local density of states of the same $4a\times\sqrt{3}a$ CDW periodicity and an energy gap of $2\Delta_{CDW}=(9.1\pm0.1)$ meV. The CDW energy gap evolves into a full gap at temperatures below 500 mK, indicating a transition to an insulating phase at ultra-low temperatures. First-principles calculations confirm the stability of both $4a\times4a$ and $4a\times\sqrt{3}a$ structures arising from soft modes in the phonon dispersion. The unconventional structure becomes preferred in the presence of strain, in agreement with experimental findings

Weak Lensing with SDSS Commissioning Data: The Galaxy-Mass Correlation Function To 1/h Mpc

(abridged) We present measurements of galaxy-galaxy lensing from early commissioning imaging data from the Sloan Digital Sky Survey (SDSS). We measure a mean tangential shear around a stacked sample of foreground galaxies in three bandpasses out to angular radii of 600'', detecting the shear signal at very high statistical significance. The shear profile is well described by a power-law. A variety of rigorous tests demonstrate the reality of the gravitational lensing signal and confirm the uncertainty estimates. We interpret our results by modeling the mass distributions of the foreground galaxies as approximately isothermal spheres characterized by a velocity dispersion and a truncation radius. The velocity dispersion is constrained to be 150-190 km/s at 95% confidence (145-195 km/s including systematic uncertainties), consistent with previous determinations but with smaller error bars. Our detection of shear at large angular radii sets a 95% confidence lower limit $s>140^{\prime\prime}$, corresponding to a physical radius of $260h^{-1}$ kpc, implying that galaxy halos extend to very large radii. However, it is likely that this is being biased high by diffuse matter in the halos of groups and clusters. We also present a preliminary determination of the galaxy-mass correlation function finding a correlation length similar to the galaxy autocorrelation function and consistency with a low matter density universe with modest bias. The full SDSS will cover an area 44 times larger and provide spectroscopic redshifts for the foreground galaxies, making it possible to greatly improve the precision of these constraints, measure additional parameters such as halo shape, and measure the properties of dark matter halos separately for many different classes of galaxies.Comment: 28 pages, 11 figures, submitted to A

Characterization of the genomic and immunologic diversity of malignant brain tumors through multisector analysis

Despite some success in secondary brain metastases, targeted or immune-based therapies have shown limited efficacy against primary brain malignancies such as glioblastoma (GBM). Although the intratumoral heterogeneity of GBM is implicated in treatment resistance, it remains unclear whether this diversity is observed within brain metastases and to what extent cancer cell-intrinsic heterogeneity sculpts the local immune microenvironment. Here, we profiled the immunogenomic state of 93 spatially distinct regions from 30 malignant brain tumors through whole-exome, RNA, and T-cell receptor sequencing. Our analyses identified differences between primary and secondary malignancies, with gliomas displaying more spatial heterogeneity at the genomic and neoantigen levels. In addition, this spatial diversity was recapitulated in the distribution of T-cell clones in which some gliomas harbored highly expanded but spatially restricted clonotypes. This study defines the immunogenomic landscape across a cohort of malignant brain tumors and contains implications for the design of targeted and immune-based therapies against intracranial malignancies. SIGNIFICANCE: This study describes the impact of spatial heterogeneity on genomic and immunologic characteristics of gliomas and brain metastases. The results suggest that gliomas harbor significantly greater intratumoral heterogeneity of genomic alterations, neoantigens, and T-cell clones than brain metastases, indicating the importance of multisector analysis for clinical or translational studies