The Evolution of Codification: A Principal-Agent Theory of the International Law Commission\u27s Influence

The International Law Commission has a mandate from the U.N. General Assembly to codify and progressively develop international law. For most of the ILC’s history, the lion’s share of its work took the form of draft articles adopted by the General Assembly as the basis for multilateral conventions. The ILC’s activities received their principal legal effect during this period through the United Nations treaty-making process, rather than directly on the basis of the ILC’s analysis of what customary international law does or should require. In recent decades, however, the ILC has turned to other outputs—such as principles, conclusions and draft articles that it does not recommend be turned into treaties. Significantly, the Commission often claims that these outputs reflect customary international law. In this chapter, we argue that increasing political gridlock in the General Assembly has led the Commission to modify the form of the work products it produces. We make three specific contributions to the literature. First, using principal-agent theory we argue that the ILC chooses the work product that maximizes its influence in shaping the evolution of custom. Our core claim is that, as gridlock has limited the General Assembly’s ability either to adopt treaties or decisively reject non-treaty outputs, the Commission has had both the incentive and the discretion to choose other outputs that do not require General Assembly approval. Second, we provide empirical support for this claim. Drawing upon a new data set that codes all ILC outputs since 1947, we show that the Commission began to favor non-treaty outputs beginning in the early 1990s. This followed a decade when ILC treaty recommendations were not adopted by the UNGA or, if adopted, did not garner sufficient ratifications for the treaties to enter into force. Third, we argue that the shift away from draft treaties increases the salience of the methodology that the ILC uses to prepare non-treaty outputs. Methodology functions as a de facto substitute for the political blessing that flows from the General Assembly’s adoption of draft treaty articles. Adherence to methodology increases the likelihood that a wider audience—government officials, international judges, national courts and non-state actors—will accept the ILC’s non-treaty work products as valid statements of custom. We thus expect the Commission to select a methodological approach that it expects will be supported by the audience(s) it hopes to persuade

Shear-melting of a hexagonal columnar crystal by proliferation of dislocations

A hexagonal columnar crystal undergoes a shear-melting transition above a critical shear rate or stress. We combine the analysis of the shear-thinning regime below the melting with that of synchrotron X-ray scattering data under shear and propose the melting to be due to a proliferation of dislocations, whose density is determined by both techniques to vary as a power law of the shear rate with a 2/3 exponent, as expected for a creep model of crystalline solids. Moreover, our data suggest the existence under shear of a line hexatic phase, between the columnar crystal and the liquid phase

Bridging Alone: Religious Conservatism, Marital Homogamy, and Voluntary Association Membership

This study characterizes social insularity of religiously conservative American married couples by examining patterns of voluntary associationmembership. Constructing a dataset of 3938 marital dyads from the second wave of the National Survey of Families and Households, the author investigates whether conservative religious homogamy encourages membership in religious voluntary groups and discourages membership in secular voluntary groups. Results indicate that couples’ shared affiliation with conservative denominations, paired with beliefs in biblical authority and inerrancy, increases the likelihood of religious group membership for husbands and wives and reduces the likelihood of secular group membership for wives, but not for husbands. The social insularity of conservative religious groups appears to be reinforced by homogamy—particularly by wives who share faith with husbands

A mechanism for the inhibition of DNA-PK-mediated DNA sensing by a virus

The innate immune system is critical in the response to infection by pathogens and it is activated by pattern recognition receptors (PRRs) binding to pathogen associated molecular patterns (PAMPs). During viral infection, the direct recognition of the viral nucleic acids, such as the genomes of DNA viruses, is very important for activation of innate immunity. Recently, DNA-dependent protein kinase (DNA-PK), a heterotrimeric complex consisting of the Ku70/Ku80 heterodimer and the catalytic subunit DNA-PKcs was identified as a cytoplasmic PRR for DNA that is important for the innate immune response to intracellular DNA and DNA virus infection. Here we show that vaccinia virus (VACV) has evolved to inhibit this function of DNA-PK by expression of a highly conserved protein called C16, which was known to contribute to virulence but by an unknown mechanism. Data presented show that C16 binds directly to the Ku heterodimer and thereby inhibits the innate immune response to DNA in fibroblasts, characterised by the decreased production of cytokines and chemokines. Mechanistically, C16 acts by blocking DNA-PK binding to DNA, which correlates with reduced DNA-PK-dependent DNA sensing. The C-terminal region of C16 is sufficient for binding Ku and this activity is conserved in the variola virus (VARV) orthologue of C16. In contrast, deletion of 5 amino acids in this domain is enough to knockout this function from the attenuated vaccine strain modified vaccinia virus Ankara (MVA). In vivo a VACV mutant lacking C16 induced higher levels of cytokines and chemokines early after infection compared to control viruses, confirming the role of this virulence factor in attenuating the innate immune response. Overall this study describes the inhibition of DNA-PK-dependent DNA sensing by a poxvirus protein, adding to the evidence that DNA-PK is a critical component of innate immunity to DNA viruses

ENCODE whole-genome data in the UCSC genome browser (2011 update)

The ENCODE project is an international consortium with a goal of cataloguing all the functional elements in the human genome. The ENCODE Data Coordination Center (DCC) at the University of California, Santa Cruz serves as the central repository for ENCODE data. In this role, the DCC offers a collection of high-throughput, genome-wide data generated with technologies such as ChIP-Seq, RNA-Seq, DNA digestion and others. This data helps illuminate transcription factor-binding sites, histone marks, chromatin accessibility, DNA methylation, RNA expression, RNA binding and other cell-state indicators. It includes sequences with quality scores, alignments, signals calculated from the alignments, and in most cases, element or peak calls calculated from the signal data. Each data set is available for visualization and download via the UCSC Genome Browser (http://genome.ucsc.edu/). ENCODE data can also be retrieved using a metadata system that captures the experimental parameters of each assay. The ENCODE web portal at UCSC (http://encodeproject.org/) provides information about the ENCODE data and links for access

Heterogeneity of variance components for preweaning growth in Romane sheep due to the number of lambs reared

<p>Abstract</p> <p>Background</p> <p>The pre-weaning growth rate of lambs, an important component of meat market production, is affected by maternal and direct genetic effects. The French genetic evaluation model takes into account the number of lambs suckled by applying a multiplicative factor (1 for a lamb reared as a single, 0.7 for twin-reared lambs) to the maternal genetic effect, in addition to including the birth*rearing type combination as a fixed effect, which acts on the mean. However, little evidence has been provided to justify the use of this multiplicative model. The two main objectives of the present study were to determine, by comparing models of analysis, 1) whether pre-weaning growth is the same trait in single- and twin-reared lambs and 2) whether the multiplicative coefficient represents a good approach for taking this possible difference into account.</p> <p>Methods</p> <p>Data on the pre-weaning growth rate, defined as the average daily gain from birth to 45 days of age on 29,612 Romane lambs born between 1987 and 2009 at the experimental farm of La Sapinière (INRA-France) were used to compare eight models that account for the number of lambs per dam reared in various ways. Models were compared using the Akaike information criteria.</p> <p>Results</p> <p>The model that best fitted the data assumed that 1) direct (maternal) effects correspond to the same trait regardless of the number of lambs reared, 2) the permanent environmental effects and variances associated with the dam depend on the number of lambs reared and 3) the residual variance depends on the number of lambs reared. Even though this model fitted the data better than a model that included a multiplicative coefficient, little difference was found between EBV from the different models (the correlation between EBV varied from 0.979 to 0.999).</p> <p>Conclusions</p> <p>Based on experimental data, the current genetic evaluation model can be improved to better take into account the number of lambs reared. Thus, it would be of interest to evaluate this model on field data and update the genetic evaluation model based on the results obtained.</p

Biomarker-Based HIV Incidence in a Community Sample of Men Who Have Sex with Men in Paris, France

BACKGROUND: Population-based estimates of HIV incidence in France have revealed that men who have sex with men (MSM) are the most affected population and contribute to nearly half of new infections each year. We sought to estimate HIV incidence among sexually active MSM in Paris gay community social venues. METHODOLOGY/ PRINCIPAL FINDINGS: A cross-sectional survey was conducted in 2009 in a sample of commercial venues such as bars, saunas and backrooms. We collected a behavioural questionnaire and blood sample. Specimens were tested for HIV infection and positive specimens then tested for recent infection by the enzyme immunoassay for recent HIV-1 infection (EIA-RI). We assessed the presence of antiretroviral therapy among infected individuals to rule out treated patients in the algorithm that determined recent infection. Biomarker-based cross-sectional incidence estimates were calculated. We enrolled 886 MSM participants among which 157 (18%) tested HIV positive. In positive individuals who knew they were infected, 75% of EIA-RI positive results were due to ART. Of 157 HIV positive specimens, 15 were deemed to be recently infected. The overall HIV incidence was estimated at 3.8% person-years (py) [95%CI: 1.5-6.2]. Although differences were not significant, incidence was estimated to be 3.5% py [0.1-6.1] in men having had a negative HIV test in previous year and 4.8% py [0.1-10.6] in men having had their last HIV test more than one year before the survey, or never tested. Incidence was estimated at 4.1% py [0-8.3] in men under 35 years and 2.5% py [0-5.4] in older men. CONCLUSIONS/ SIGNIFICANCE: This is the first community-based survey to estimate HIV incidence among MSM in France. It includes ART detection and reveals a high level of HIV transmission in sexually active individuals, despite a high uptake of HIV testing. These data call for effective prevention programs targeting MSM engaged in high-risk behaviours

Optimal Compensation for Temporal Uncertainty in Movement Planning

Motor control requires the generation of a precise temporal sequence of control signals sent to the skeletal musculature. We describe an experiment that, for good performance, requires human subjects to plan movements taking into account uncertainty in their movement duration and the increase in that uncertainty with increasing movement duration. We do this by rewarding movements performed within a specified time window, and penalizing slower movements in some conditions and faster movements in others. Our results indicate that subjects compensated for their natural duration-dependent temporal uncertainty as well as an overall increase in temporal uncertainty that was imposed experimentally. Their compensation for temporal uncertainty, both the natural duration-dependent and imposed overall components, was nearly optimal in the sense of maximizing expected gain in the task. The motor system is able to model its temporal uncertainty and compensate for that uncertainty so as to optimize the consequences of movement

Melanoma Chemotherapy Leads to the Selection of ABCB5-Expressing Cells

Metastatic melanoma is the most aggressive skin cancer. Recently, phenotypically distinct subpopulations of tumor cells were identified. Among them, ABCB5-expressing cells were proposed to display an enhanced tumorigenicity with stem cell-like properties. In addition, ABCB5+ cells are thought to participate to chemoresistance through a potential efflux function of ABCB5. Nevertheless, the fate of these cells upon drugs that are used in melanoma chemotherapy remains to be clarified. Here we explored the effect of anti-melanoma treatments on the ABCB5-expressing cells. Using a melanoma xenograft model (WM266-4), we observed in vivo that ABCB5-expressing cells are enriched after a temozolomide treatment that induces a significant tumor regression. These results were further confirmed in a preliminary study conducted on clinical samples from patients that received dacarbazine. In vitro, we showed that ABCB5-expressing cells selectively survive when exposed to dacarbazine, the reference treatment of metastatic melanoma, but also to vemurafenib, a new inhibitor of the mutated kinase V600E BRAF and other various chemotherapeutic drugs. Our results show that anti-melanoma chemotherapy might participate to the chemoresistance acquisition by selecting tumor cell subpopulations expressing ABCB5. This is of particular importance in understanding the relapses observed after anti-melanoma treatments and reinforces the interest of ABCB5 and ABCB5-expressing cells as potential therapeutic targets in melanoma