Interpretation and the Constraints on International Courts

This paper argues that methodologies of interpretation do not do what they promise – they do not constrain interpretation by providing neutral steps that one can follow in finding out a meaning of a text – but nevertheless do their constraining work by being part of what can be described as the legal practice

Cohesin Releases DNA through Asymmetric ATPase-Driven Ring Opening

Cohesin stably holds together the sister chromatids from S phase until mitosis. To do so, cohesin must be protected against its cellular antagonist Wapl. Eco1 acetylates cohesin's Smc3 subunit, which locks together the sister DNAs. We used yeast genetics to dissect how Wapl drives cohesin from chromatin and identified mutants of cohesin that are impaired in ATPase activity but remarkably confer robust cohesion that bypasses the need for the cohesin protectors Eco1 in yeast and Sororin in human cells. We uncover a functional asymmetry within the heart of cohesin's highly conserved ABC-like ATPase machinery and find that both ATPase sites contribute to DNA loading, whereas DNA release is controlled specifically by one site. We propose that Smc3 acetylation locks cohesin rings around the sister chromatids by counteracting an activity associated with one of cohesin's two ATPase sites. Tight regulation of DNA entrapment and release by the cohesin complex is crucial for its multiple cellular functions. Elbatsh et al. find that cohesin's release from DNA requires an activity associated with one of its ATPase sites, whereas both sites control cohesin's loading onto DNA

MICE: The muon ionization cooling experiment. Step I: First measurement of emittance with particle physics detectors

Copyright @ 2011 APSThe Muon Ionization Cooling Experiment (MICE) is a strategic R&D project intended to demonstrate the only practical solution to providing high brilliance beams necessary for a neutrino factory or muon collider. MICE is under development at the Rutherford Appleton Laboratory (RAL) in the United Kingdom. It comprises a dedicated beamline to generate a range of input muon emittances and momenta, with time-of-flight and Cherenkov detectors to ensure a pure muon beam. The emittance of the incoming beam will be measured in the upstream magnetic spectrometer with a scintillating fiber tracker. A cooling cell will then follow, alternating energy loss in Liquid Hydrogen (LH2) absorbers to RF cavity acceleration. A second spectrometer, identical to the first, and a second muon identification system will measure the outgoing emittance. In the 2010 run at RAL the muon beamline and most detectors were fully commissioned and a first measurement of the emittance of the muon beam with particle physics (time-of-flight) detectors was performed. The analysis of these data was recently completed and is discussed in this paper. Future steps for MICE, where beam emittance and emittance reduction (cooling) are to be measured with greater accuracy, are also presented.This work was supported by NSF grant PHY-0842798

Reference Array and Design Consideration for the next-generation Event Horizon Telescope

We describe the process to design, architect, and implement a transformative enhancement of the Event Horizon Telescope (ngEHT). This program - the next-generation Event Horizon Telescope (ngEHT) - will form a networked global array of radio dishes capable of making high-fidelity real-time movies of supermassive black holes (SMBH) and their emanating jets. This builds upon the EHT principally by deploying additional modest-diameter dishes to optimized geographic locations to enhance the current global mm/submm wavelength Very Long Baseline Interferometric (VLBI) array, which has, to date, utilized mostly pre-existing radio telescopes. The ngEHT program further focuses on observing at three frequencies simultaneously for increased sensitivity and Fourier spatial frequency coverage. Here, the concept, science goals, design considerations, station siting and instrument prototyping are discussed, and a preliminary reference array to be implemented in phases is described.Comment: Submitted to the journal Galaxie

A Systemic approach to scoping of factors influencing more sustainable land use in Herefordshire

Defining and putting into practice sustainable land use is a complex, systemic problem. Systems models and techniques were used in a study of Herefordshire to clarify the situation and identify the potential for a more locally focused, learning-based approach to land use. Issues included: (i) uncertainty about the boundary of a 'system of sustainable Herefordshire land use'; (ii) the complexity of economic flows in the county and the absence of some critical data; (iii) the importance of the Herefordshire landscape to tourism and the role of agriculture as a determinant of the state of that landscape; (iv) weakness of the institutional linkage between tourism and agriculture; (v) the current lack of inclusion of many relevant stakeholders in concerted action. Factors favouring a learning approach included a strong local identity, local food-related developments, and educational initiatives. Barriers to such an approach included questions of power and landholding, government policies, and attitudes and skills within organizations. These findings are considered in relation to the wider debate over approaches to sustainability

Studying black holes on horizon scales with space-VLBI

The Event Horizon Telescope (EHT) recently produced the first horizon-scale image of a supermassive black hole. Expanding the array to include a 3-meter space telescope operating at >200 GHz enables mass measurements of many black holes, movies of black hole accretion flows, and new tests of general relativity that are impossible from the ground

AChBP-targeted α-conotoxin correlates distinct binding orientations with nAChR subtype selectivity

Neuronal nAChRs are a diverse family of pentameric ion channels with wide distribution throughout cells of the nervous and immune systems. However, the role of specific subtypes in normal and pathological states remains poorly understood due to the lack of selective probes. Here, we used a binding assay based on acetylcholine-binding protein (AChBP), a homolog of the nicotinic acetylcholine ligand-binding domain, to discover a novel α-conotoxin (α-TxIA) in the venom of Conus textile. α-TxIA bound with high affinity to AChBPs from different species and selectively targeted the α3β2 nAChR subtype. A co-crystal structure of Ac-AChBP with the enhanced potency analog TxIA(A10L), revealed a 20° backbone tilt compared to other AChBP–conotoxin complexes. This reorientation was coordinated by a key salt bridge formed between Arg5 (TxIA) and Asp195 (Ac-AChBP). Mutagenesis studies, biochemical assays and electrophysiological recordings directly correlated the interactions observed in the co-crystal structure to binding affinity at AChBP and different nAChR subtypes. Together, these results establish a new pharmacophore for the design of novel subtype-selective ligands with therapeutic potential in nAChR-related diseases

Hydrodynamics of fossil fishes

Fromtheir earliest origins, fishes have developed a suite of adaptations for locomotion in water, which determine performance and ultimately fitness. Even without data from behaviour, soft tissue and extant relatives, it is possible to infer a wealth of palaeobiological and palaeoecological information. As in extant species, aspects of gross morphology such as streamlining, fin position and tail type are optimized even in the earliest fishes, indicating similar life strategies have been present throughout their evolutionary history. As hydrodynamical studies become more sophisticated, increasingly complex fluid movement can be modelled, including vortex formation and boundary layer control. Drag-reducing riblets ornamenting the scales of fast-moving sharks have been subjected to particularly intense research, but this has not been extended to extinct forms. Riblets are a convergent adaptation seen in many Palaeozoic fishes, and probably served a similar hydrodynamic purpose. Conversely, structures which appear to increase skin friction may act as turbulisors, reducing overall dragwhile serving a protective function. Here,we examine the diverse adaptions that contribute to drag reduction in modern fishes and review the few attempts to elucidate the hydrodynamics of extinct forms