Constitutional Analogies in the International Legal System

This Article explores issues at the frontier of international law and constitutional law. It considers five key structural and systemic challenges that the international legal system now faces: (1) decentralization and disaggregation; (2) normative and institutional hierarchies; (3) compliance and enforcement; (4) exit and escape; and (5) democracy and legitimacy. Each of these issues raises questions of governance, institutional design, and allocation of authority paralleling the questions that domestic legal systems have answered in constitutional terms. For each of these issues, I survey the international legal landscape and consider the salience of potential analogies to domestic constitutions, drawing upon and extending the writings of international legal scholars and international relations theorists. I also offer some preliminary thoughts about why some treaties and institutions, but not others, more readily lend themselves to analysis in constitutional terms. And I distinguish those legal and political issues that may generate useful insights for scholars studying the growing intersections of international and constitutional law from other areas that may be more resistant to constitutional analogies

Dynamical Behaviour of Low Autocorrelation Models

We have investigated the nature of the dynamical behaviour in low autocorrelation binary sequences. These models do have a glass transition $T_G$ of a purely dynamical nature. Above the glass transition the dynamics is not fully ergodic and relaxation times diverge like a power law $\tau\sim (T-T_G)^{-\gamma}$ with $\gamma$ close to $2$. Approaching the glass transition the relaxation slows down in agreement with the first order nature of the dynamical transition. Below the glass transition the system exhibits aging phenomena like in disordered spin glasses. We propose the aging phenomena as a precise method to determine the glass transition and its first order nature.Comment: 19 pages + 14 figures, LateX, figures uuencoded at the end of the fil

Is it the boundaries or disorder that dominates electron transport in semiconductor `billiards'?

Semiconductor billiards are often considered as ideal systems for studying dynamical chaos in the quantum mechanical limit. In the traditional picture, once the electron's mean free path, as determined by the mobility, becomes larger than the device, disorder is negligible and electron trajectories are shaped by specular reflection from the billiard walls alone. Experimental insight into the electron dynamics is normally obtained by magnetoconductance measurements. A number of recent experimental studies have shown these measurements to be largely independent of the billiards exact shape, and highly dependent on sample-to-sample variations in disorder. In this paper, we discuss these more recent findings within the full historical context of work on semiconductor billiards, and offer strong evidence that small-angle scattering at the sub-100 nm length-scale dominates transport in these devices, with important implications for the role these devices can play for experimental tests of ideas in quantum chaos.Comment: Submitted to Fortschritte der Physik for special issue on Quantum Physics with Non-Hermitian Operator

Molecular features associated with response to enasidenib plus azacitidine in newly diagnosed IDH2-mutated acute myeloid leukemia

IDH2 gene mutations, typically at residues R140 and R172, occur in 8–19% of patients with acute myeloid leukemia (AML). These mutations induce production of 2-hydroxyglutarate (2-HG), an oncometabolite that causes DNA and histone hypermethylation, and subsequent blockade of hematopoietic cell differentiation. In a phase 1b/2 trial (NCT02677922), combination therapy with azacitidine + enasidenib significantly improved overall response rate compared with azacitidine only therapy (74% vs 36%; P<0.001) in patients with newly diagnosed IDH2-mutated AML not eligible for intensive chemotherapy. We investigated the association between molecular features and clinical outcomes from that trial. In all, 101 patients were randomized to enasidenib + azacitidine (n=68) or azacitidine only (n=33); 74% of patients had IDH2-R140. Baseline 2-HG levels and IDH2 variant allele frequency (VAF) were similar between treatment arms and IDH2 variants, and were not significantly different between clinical response categories. Significant 2-HG and IDH2 VAF reductions from baseline were observed with combination therapy compared with azacitidine only. Molecular profiling revealed SRSF2 preferentially co-mutated with IDH2-R140, and DNMT3A co-mutated with IDH2-R172. IDH2 VAF was reduced to <1% in 50% of patients who achieved CR with combination therapy (18/36) and azacitidine only (2/4). VAFs of genes in the DNA methylation, receptor-tyrosine-kinase, and RAS canonical pathways were reduced in patients achieving CR. Of note, combination therapy improved event-free survival in patients with RAS-pathway mutations, which have been associated with resistance to enasidenib monotherapy