Not Fade Away: The International Criminal Court and the State of Sovereignty

Sovereignty concerns were central to the negotiations over the ICC Statute. To be sure, the future court will relate to individuals and States, as well as inter-governmental and non-governmental organizations, in a way that differs from the international institutions created at mid-century. But by designing an institution that must work through and with sovereign States in crucial aspects of its functioning, the ICC Statute presupposes the continued existence of a system based on sovereign States. The Statute\u27s details reinforce the notion that [d]irectly or indirectly, the entire edifice of international human-rights law is built on state sovereignty. Seen in this light, there seems little basis for predicting that the ICC will cause the sovereign State to fade away. Moreover, the ICC may actually strengthen individual States by acting both as a judicial model for effective domestic institutions, where they do not now exist, and as a prod for states to deal domestically with crimes within the court\u27s subject matter jurisdiction. To that extent, it is consistent with a growing realization that weak states can be as much of a threat to human rights as strong states. This does not mean, however, that the relationship between the future ICC and sovereign States is one that will be accepted by the U.S. political system through the process of advice and consent to ratification. That judgment remains to be made

Causal distributed breakpoints

The authors define a causal distributed breakpoint, which is initiated by a sequential breakpoint in one process of a distributed computation and restores each process in the computation to its earliest state that reflects all events that happened before the breakpoint. An algorithm for finding the causal distributed breakpoint, given a sequential breakpoint in one of the processes, is presented. Approximately consistent checkpoint sets are used for efficiently restoring each process to its state in a causal distributed breakpoint. Causal distributed breakpoints assume deterministic processes that communicate solely by messages. The dependencies that arise from communication between processes are logged. Dependency logging and approximately consistent checkpoint sets are implemented on a network of SUN workstations running the V-System. Overhead on the message-passing primitives varies between 1% and 14% for dependency logging. Execution time overhead for a 200×200 Gaussian elimination is less than 4% and generates a dependency log of 288 kbyte

Chromosomal Imbalances Detected via RNA-Sequencing in 28 Cancers

Motivation: RNA-sequencing (RNA-seq) of tumor tissue is typically only used to measure gene expression. Here, we present a statistical approach that leverages existing RNA-seq data to also detect somatic copy number alterations (SCNAs), a pervasive phenomenon in human cancers, without a need to sequence the corresponding DNA. Results: We present an analysis of 4942 participant samples from 28 cancers in The Cancer Genome Atlas (TCGA), demonstrating robust detection of SCNAs from RNA-seq. Using genotype imputation and haplotype information, our RNA-based method had a median sensitivity of 85% to detect SCNAs defined by DNA analysis, at high specificity (∼95%). As an example of translational potential, we successfully replicated SCNA features associated with breast cancer subtypes. Our results credential haplotype-based inference based on RNA-seq to detect SCNAs in clinical and population-based settings. Availability and implementation: The analyses presented use the data publicly available from TCGA Research Network (http://cancergenome.nih.gov/). See Methods for details regarding data downloads. hapLOHseq software is freely available under The MIT license and can be downloaded from http://scheet.org/software.html. Supplementary information: Supplementary data are available at Bioinformatics online

A Whole-Exome Case-Control Association Study To Characterize the Contribution of Rare Coding Variation to Pancreatic Cancer Risk

Pancreatic cancer is a deadly disease that accounts for approximately 5% of cancer deaths worldwide, with a dismal 5-year survival rate of 10%. Known genetic risk factors explain only a modest proportion of the heritable risk of pancreatic cancer. We conducted a whole-exome case-control sequencing study in 1,591 pancreatic cancer cases and 2,134 cancer-free controls of European ancestry. In our gene-based analysis, ATM ranked first, with a genome-wide significant p value of 1 × 10-8. The odds ratio for protein-truncating variants in ATM was 24, which is substantially higher than prior estimates, although ours includes a broad 95% confidence interval (4.0-1000). SIK3 was the second highest ranking gene (p = 3.84 × 10-6, false discovery rate or FDR = 0.032). We observed nominally significant association signals in several genes of a priori interest, including BRCA2 (p = 4.3 × 10-4), STK11 (p = 0.003), PALB2 (p = 0.019), and TP53 (p = 0.037), and reported risk estimates for known pathogenic variants and variants of uncertain significance (VUS) in these genes. The rare variants in established susceptibility genes explain approximately 24% of log familial relative risk, which is comparable to the contribution from established common susceptibility variants (17%). In conclusion, this study provides new insights into the genetic susceptibility of pancreatic cancer, refining rare variant risk estimates in known pancreatic cancer susceptibility genes and identifying SIK3 as a novel candidate susceptibility gene. This study highlights the prominent importance of ATM truncating variants and the underappreciated role of VUS in pancreatic cancer etiology

Utilizing a Global Network of Telescopes to Update the Ephemeris for the Highly Eccentric Planet HD 80606 b and to Ensure the Efficient Scheduling of JWST

The transiting planet HD 80606 b undergoes a 1000 fold increase in insolation during its 111 days orbit due to it being highly eccentric (e = 0.93). The planet's effective temperature increases from 400 to over 1400 K in a few hours as it makes a rapid passage to within 0.03 au of its host star during periapsis. Spectroscopic observations during the eclipse (which is conveniently oriented a few hours before periapsis) of HD 80606 b with the James Webb Space Telescope (JWST) are poised to exploit this highly variable environment to study a wide variety of atmospheric properties, including composition, chemical and dynamical timescales, and large scale atmospheric motions. Critical to planning and interpreting these observations is an accurate knowledge of the planet's orbit. We report on observations of two full-transit events: 2020 February 7 as observed by the TESS spacecraft and 2021 December 7-8 as observed with a worldwide network of small telescopes. We also report new radial velocity observations which, when analyzed with a coupled model to the transits, greatly improves the planet's orbital ephemeris. Our new orbit solution reduces the uncertainty in the transit and eclipse timing of the JWST era from tens of minutes to a few minutes. When combined with the planned JWST observations, this new precision may be adequate to look for non-Keplerian effects in the orbit of HD 80606 b

Preparation of radioactive rare earth targets for neutron capture study

The understanding of thc details of nucleosynthesis in stars remains a great challenge. Though the basic mechanisms governing the processes have been known since the pioneering work of Burbidge, Burbidge, Fowler and Hoyle (l), we are now evolving into a condition where we can ask more specific questions. Of particular interest are the dynamics of the s ('slow') process. In this process the general condition is one in which sequential neutron captures occur at time scales long compared with the beta decay half lives of the capturing nuclides. The nucleosynthesis period for C or Ne burning stellar shells is believed to be in the year to few year time frame (2). This means that radionuclides with similar half lives to this burning period serve as 'branch point' nuclides. That is, there will be a competition between a capture to the next heavier isotope and a beta decay to the element of nexl higher atomic number. By understanding the abundances of these competing reactions we can learn about the dynamics of the nucleosynthesis process in the stellar medium. Crucial to this understanding is that we have a knowledge of the underlying neutron reaction cross sections on these unstable nuclides in the relevant stellar energy regions (neutrons of 0.1-100 KeV). Tm (1.9 years) and ls'Sm (90 ycws) have decay properties that permit their handling in an open fume hood. These Iwo were therefore selected to be the first radionuclides for neutron capture study in what will be an ongoing effort