3,791 research outputs found

    Backup Tapes, You Can’t Live With Them And You Can’t Toss Them: Strategies For Dealing With The Litigation Burdens Associated With Backup Tapes Under The Amended Federal Rules Of Civil Procedure

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    The law in the federal courts governing whether litigants must disclose their backup tapes just changed. Faced with the cost, burdens and uncertainties of mining backup tapes, as well as other sources of data that are difficult to reach, most litigants have simply been ignoring their backup tapes. No more. The amendments to the Federal Rules of Civil Procedure adopt a new standard that embraces the Zubulake I distinction between “accessible” and “inaccessible” data, and requires the disclosing party to identify all its sources of data

    Portaria nÂş 22/2018/EMB/CJ

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    Designação de banca de processo seletivo simplificado

    Giant Impacts and Debris Disk Morphology

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    Certain debris disks have non-axisymmetric shapes in scattered light which are unexplained. The appearance of a disk depends on how its constituent Keplerian ellipses are arranged. The more the ellipses align apsidally, the more non-axisymmetric the disk. Apsidal alignment is automatic for fragments released from a catastrophic collision between solid bodies. We synthesize scattered light images, and thermal emission images, of such giant impact debris. Depending on the viewing geometry, and if and how the initial apsidal alignment is perturbed, the remains of a giant impact can appear in scattered light as a one-sided or two-sided "fork", a lopsided "needle", or a set of "double wings". Double wings are difficult to reproduce in other scenarios involving gravitational forcing or gas drag, which do not align orbits as well. We compare our images with observations and offer a scorecard assessing whether the scattered light asymmetries in HD 15115, HD 32297, HD 61005, HD 111520, HD 106906, beta Pic, and AU Mic are best explained by giant impacts, gravitational perturbations, or sculpting by the interstellar medium.Comment: Final ApJ-proofed version with updated references to summary Table 1. Animations available at https://github.com/joshwajones/jones_etal_animations

    CHCHD4 regulates tumour proliferation and EMT-related phenotypes, through respiratory chain-mediated metabolism

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    Abstract: Background: Mitochondrial oxidative phosphorylation (OXPHOS) via the respiratory chain is required for the maintenance of tumour cell proliferation and regulation of epithelial to mesenchymal transition (EMT)-related phenotypes through mechanisms that are not fully understood. The essential mitochondrial import protein coiled-coil helix coiled-coil helix domain-containing protein 4 (CHCHD4) controls respiratory chain complex activity and oxygen consumption, and regulates the growth of tumours in vivo. In this study, we interrogate the importance of CHCHD4-regulated mitochondrial metabolism for tumour cell proliferation and EMT-related phenotypes, and elucidate key pathways involved. Results: Using in silico analyses of 967 tumour cell lines, and tumours from different cancer patient cohorts, we show that CHCHD4 expression positively correlates with OXPHOS and proliferative pathways including the mTORC1 signalling pathway. We show that CHCHD4 expression significantly correlates with the doubling time of a range of tumour cell lines, and that CHCHD4-mediated tumour cell growth and mTORC1 signalling is coupled to respiratory chain complex I (CI) activity. Using global metabolomics analysis, we show that CHCHD4 regulates amino acid metabolism, and that CHCHD4-mediated tumour cell growth is dependent on glutamine. We show that CHCHD4-mediated tumour cell growth is linked to CI-regulated mTORC1 signalling and amino acid metabolism. Finally, we show that CHCHD4 expression in tumours is inversely correlated with EMT-related gene expression, and that increased CHCHD4 expression in tumour cells modulates EMT-related phenotypes. Conclusions: CHCHD4 drives tumour cell growth and activates mTORC1 signalling through its control of respiratory chain mediated metabolism and complex I biology, and also regulates EMT-related phenotypes of tumour cells

    CHCHD4 confers metabolic vulnerabilities to tumour cells through its control of the mitochondrial respiratory chain.

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    BACKGROUND: Tumour cells rely on glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) to survive. Thus, mitochondrial OXPHOS has become an increasingly attractive area for therapeutic exploitation in cancer. However, mitochondria are required for intracellular oxygenation and normal physiological processes, and it remains unclear which mitochondrial molecular mechanisms might provide therapeutic benefit. Previously, we discovered that coiled-coil-helix-coiled-coil-helix domain-containing protein 4 (CHCHD4) is critical for regulating intracellular oxygenation and required for the cellular response to hypoxia (low oxygenation) in tumour cells through molecular mechanisms that we do not yet fully understand. Overexpression of CHCHD4 in human cancers correlates with increased tumour progression and poor patient survival. RESULTS: Here, we show that elevated CHCHD4 expression provides a proliferative and metabolic advantage to tumour cells in normoxia and hypoxia. Using stable isotope labelling with amino acids in cell culture (SILAC) and analysis of the whole mitochondrial proteome, we show that CHCHD4 dynamically affects the expression of a broad range of mitochondrial respiratory chain subunits from complex I-V, including multiple subunits of complex I (CI) required for complex assembly that are essential for cell survival. We found that loss of CHCHD4 protects tumour cells from respiratory chain inhibition at CI, while elevated CHCHD4 expression in tumour cells leads to significantly increased sensitivity to CI inhibition, in part through the production of mitochondrial reactive oxygen species (ROS). CONCLUSIONS: Our study highlights an important role for CHCHD4 in regulating tumour cell metabolism and reveals that CHCHD4 confers metabolic vulnerabilities to tumour cells through its control of the mitochondrial respiratory chain and CI biology

    Constraints on the architecture of the HD 95086 planetary system with the Gemini Planet Imager

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    We present astrometric monitoring of the young exoplanet HD 95086 b obtained with the Gemini Planet Imager between 2013 and 2016. A small but significant position angle change is detected at constant separation; the orbital motion is confirmed with literature measurements. Efficient Monte Carlo techniques place preliminary constraints on the orbital parameters of HD 95086 b. With 68% confidence, a semimajor axis of 61.7^{+20.7}_{-8.4} au and an inclination of 153.0^{+9.7}_{-13.5} deg are favored, with eccentricity less than 0.21. Under the assumption of a co-planar planet-disk system, the periastron of HD 95086 b is beyond 51 au with 68% confidence. Therefore HD 95086 b cannot carve the entire gap inferred from the measured infrared excess in the SED of HD 95086. We use our sensitivity to additional planets to discuss specific scenarios presented in the literature to explain the geometry of the debris belts. We suggest that either two planets on moderately eccentric orbits or three to four planets with inhomogeneous masses and orbital properties are possible. The sensitivity to additional planetary companions within the observations presented in this study can be used to help further constrain future dynamical simulations of the planet-disk system.Comment: Accepted for publication in ApJ
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