Abstract This article challenges four basic and intertwining assumptions informing orthodox comparative law: that a comparatist can exactly represent foreign law; that he can write about foreign law ...objectively; that he can state the truth regarding foreign law; and that he enjoys the subjective agency to overcome the obstacles on the way to the achievement of these goals. Comparatists-at-law being oblivious to their structural cognitive weakness, which makes the pursuit of these realizations irredeemably preposterous, a strong contrarian programme is necessary so as to bring comparative law to its epistemological senses and, in the process, to heighten the scholarly integrity and reliability of comparative interventions. This article succinctly formulates such an oppositional stance.
Abstract While much legal research involves foreign law and much of foreign law exists in a foreign language, the issue of translation has attracted limited theoretical attention only. In particular, ...few lawyers are aware of the work issuing from fields like literary criticism, philosophy, or translation studies. Urging acknowledgment and redress of such a serious epistemic deficit, basing itself on a critical approach to foreignness, this article offers a constructive guide to the making of just translations. A noteworthy feature of the argument concerns the formulation of conclusions that can fairly be expected to run counter-intuitively to a lawyer’s unexamined assumptions. Indeed, much of what is received as conventional wisdom about the translation of foreign law is either ill-considered or plain wrong.
The field of comparative law prioritizes the ascertainment of universals or commonalities across laws, two chimerical pursuits. In the process, comparative research abides significant distortion of ...information, not always in good faith, and a correlative loss of intellectual warrant. This article urges acknowledgment of such serious epistemic deficit, of its detrimental impact on comparative law, and of the need to restore intellectual integrity to comparative research in law through a radically different approach to foreignness.
Vesicular stomatitis virus (VSV) is an oncolytic rhabdovirus and its glycoprotein G is widely used to pseudotype other viruses for gene therapy. Low-density lipoprotein receptor (LDL-R) serves as a ...major entry receptor for VSV. Here we report two crystal structures of VSV G in complex with two distinct cysteine-rich domains (CR2 and CR3) of LDL-R, showing that their binding sites on G are identical. We identify two basic residues on G, which are essential for its interaction with CR2 and CR3. Mutating these residues abolishes VSV infectivity even though VSV can use alternative receptors, indicating that all VSV receptors are members of the LDL-R family. Collectively, our data suggest that VSV G has specifically evolved to interact with receptor CR domains. These structural insights into the interaction between VSV G and host cell receptors provide a basis for the design of recombinant viruses with an altered tropism.
Essential tremor is a movement disorder characterized by tremor during voluntary movements, mainly affecting the upper limbs. The cerebellum and its connections to the cortex are known to be involved ...in essential tremor, but no task-free intrinsic signatures of tremor related to structural cerebellar defects have so far been found in the cortical motor network. Here we used voxel-based morphometry, tractography and resting-state functional MRI at 3 T to compare structural and functional features in 19 patients with essential tremor and homogeneous symptoms in the upper limbs, and 19 age- and gender-matched healthy volunteers. Both structural and functional abnormalities were found in the patients' cerebellum and supplementary motor area. Relative to the healthy controls, the essential tremor patients' cerebellum exhibited less grey matter in lobule VIII and less effective connectivity between each cerebellar cortex and the ipsilateral dentate nucleus. The patient's supplementary motor area exhibited (i) more grey matter; (ii) a lower amplitude of low-frequency fluctuation of the blood oxygenation level-dependent signal; (iii) less effective connectivity between each supplementary motor area and the ipsilateral primary motor hand area, and (iv) a higher probability of connection between supplementary motor area fibres and the spinal cord. Structural and functional changes in the supplementary motor area, but not in the cerebellum, correlated with clinical severity. In addition, changes in the cerebellum and supplementary motor area were interrelated, as shown by a correlation between the lower amplitude of low-frequency fluctuation in the supplementary motor area and grey matter loss in the cerebellum. The structural and functional changes observed in the supplementary motor area might thus be a direct consequence of cerebellar defects: the supplementary motor area would attempt to reduce tremor in the motor output by reducing its communication with M1 hand areas and by directly modulating motor output via its corticospinal projections.See Raethjen and Muthuraman (doi:10.1093/brain/awv238) for a scientific commentary on this article.
Human members of the solute carrier 1 (SLC1) family of transporters take up excitatory neurotransmitters in the brain and amino acids in peripheral organs. Dysregulation of the function of SLC1 ...transporters is associated with neurodegenerative disorders and cancer. Here we present crystal structures of a thermostabilized human SLC1 transporter, the excitatory amino acid transporter 1 (EAAT1), with and without allosteric and competitive inhibitors bound. The structures reveal architectural features of the human transporters, such as intra- and extracellular domains that have potential roles in transport function, regulation by lipids and post-translational modifications. The coordination of the allosteric inhibitor in the structures and the change in the transporter dynamics measured by hydrogen-deuterium exchange mass spectrometry reveal a mechanism of inhibition, in which the transporter is locked in the outward-facing states of the transport cycle. Our results provide insights into the molecular mechanisms underlying the function and pharmacology of human SLC1 transporters.
Bacteriophages have long been known to use modified bases in their DNA to prevent cleavage by the host's restriction endonucleases. Among them, cyanophage S-2L is unique because its genome has all ...its adenines (A) systematically replaced by 2-aminoadenines (Z). Here, we identify a member of the PrimPol family as the sole possible polymerase of S-2L and we find it can incorporate both A and Z in front of a T. Its crystal structure at 1.5 Å resolution confirms that there is no structural element in the active site that could lead to the rejection of A in front of T. To resolve this contradiction, we show that a nearby gene is a triphosphohydolase specific of dATP (DatZ), that leaves intact all other dNTPs, including dZTP. This explains the absence of A in S-2L genome. Crystal structures of DatZ with various ligands, including one at sub-angstrom resolution, allow to describe its mechanism as a typical two-metal-ion mechanism and to set the stage for its engineering.
The 14 essays that make up this 2003 volume are written by leading international scholars to provide an authoritative survey of the state of comparative legal studies. Representing such varied ...disciplines as the law, political science, sociology, history and anthropology, the contributors review the intellectual traditions that have evolved within the discipline of comparative legal studies, explore the strengths and failings of the various methodologies that comparatists adopt and, significantly, explore the directions that the subject is likely to take in the future. No previous work had examined so comprehensively the philosophical and methodological foundations of comparative law. This is quite simply a book with which anyone embarking on comparative legal studies will have to engage.
•New methods for computerized spiral analysis are proposed, which outperform the usual velocity method.•They provide new insight into tremor amplitude and frequency variations.•They were implemented ...on a computer via a digitized tablet.
Spiral drawing is one of the standard tests used to assess tremor severity for the clinical evaluation of medical treatments. Tremor severity is estimated through visual rating of the drawings by movement disorders experts. Different approaches based on the mathematical signal analysis of the recorded spiral drawings were proposed to replace this rater dependent estimate. The objective of the present study is to propose new numerical methods and to evaluate them in terms of agreement with visual rating and reproducibility.
Series of spiral drawings of patients with essential tremor were visually rated by a board of experts. In addition to the usual velocity analysis, three new numerical methods were tested and compared, namely static and dynamic unraveling, and empirical mode decomposition. The reproducibility of both visual and numerical ratings was estimated, and their agreement was evaluated.
The statistical analysis demonstrated excellent agreement between visual and numerical ratings, and more reproducible results with numerical methods than with visual ratings.
The velocity method and the new numerical methods are in good agreement. Among the latter, static and dynamic unravelling both display a smaller dispersion and are easier for automatic analysis.
The reliable scores obtained through the proposed numerical methods allow considering that their implementation on a digitized tablet, be it connected with a computer or independent, provides an efficient automatic tool for tremor severity assessment.
The promising drug target N-myristoyltransferase (NMT) catalyses an essential protein modification thought to occur exclusively at N-terminal glycines (Gly). Here, we present high-resolution human ...NMT1 structures co-crystallised with reactive cognate lipid and peptide substrates, revealing high-resolution snapshots of the entire catalytic mechanism from the initial to final reaction states. Structural comparisons, together with biochemical analysis, provide unforeseen details about how NMT1 reaches a catalytically competent conformation in which the reactive groups are brought into close proximity to enable catalysis. We demonstrate that this mechanism further supports efficient and unprecedented myristoylation of an N-terminal lysine side chain, providing evidence that NMT acts both as N-terminal-lysine and glycine myristoyltransferase.
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