HIL: designing an exokernel for the data center

We propose a new Exokernel-like layer to allow mutually untrusting physically deployed services to efficiently share the resources of a data center. We believe that such a layer offers not only efficiency gains, but may also enable new economic models, new applications, and new security-sensitive uses. A prototype (currently in active use) demonstrates that the proposed layer is viable, and can support a variety of existing provisioning tools and use cases.Partial support for this work was provided by the MassTech Collaborative Research Matching Grant Program, National Science Foundation awards 1347525 and 1149232 as well as the several commercial partners of the Massachusetts Open Cloud who may be found at http://www.massopencloud.or

NOTCH3 p.Arg1231Cys is markedly enriched in South Asians and associated with stroke

Acknowledgements: Supported by Regeneron Pharmaceuticals, Inc. This research has been conducted using the UK Biobank Resource (project 26041). The authors thank everyone who made this work possible, particularly the UK Biobank team, their funders, the professionals from the member institutions who contributed to and supported this work, and most especially the UK Biobank participants, without whom this research would not be possible. The exome sequencing was funded by the UK Biobank Exome Sequencing Consortium (Bristol Myers Squibb, Regeneron, Biogen, Takeda, Abbvie, Alnylam, AstraZeneca and Pfizer). Ethical approval for the UK Biobank was previously obtained from the North West Center for Research Ethics Committee (11/NW/0382). Disclosure forms provided by the authors are available with the full text of this article.The genetic factors of stroke in South Asians are largely unexplored. Exome-wide sequencing and association analysis (ExWAS) in 75 K Pakistanis identified NM_000435.3(NOTCH3):c.3691 C > T, encoding the missense amino acid substitution p.Arg1231Cys, enriched in South Asians (alternate allele frequency = 0.58% compared to 0.019% in Western Europeans), and associated with subcortical hemorrhagic stroke [odds ratio (OR) = 3.39, 95% confidence interval (CI) = [2.26, 5.10], p = 3.87 × 10−9), and all strokes (OR [CI] = 2.30 [1.77, 3.01], p = 7.79 × 10−10). NOTCH3 p.Arg231Cys was strongly associated with white matter hyperintensity on MRI in United Kingdom Biobank (UKB) participants (effect [95% CI] in SD units = 1.1 [0.61, 1.5], p = 3.0 × 10−6). The variant is attributable for approximately 2.0% of hemorrhagic strokes and 1.1% of all strokes in South Asians. These findings highlight the value of diversity in genetic studies and have major implications for genomic medicine and therapeutic development in South Asian populations