158 research outputs found

    Aux Ouvrières!: socialist feminism in the Paris Commune

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    Feminist and socialist movements both aim at emancipation yet have often been at odds. The socialist feminists of the Paris Commune provide one of the few examples in late nineteenth-century Europe of a political movement combining the two. This article offers a new interpretation of the Commune feminists, focusing on the working-class women’s organisation the Union des femmes. We highlight how the Commune feminists articulated the specific form of oppression experienced by working-class women as both women and workers, which consequently required a joint, yet differentiated, struggle to overcome. We explore three aspects of this framework. First, the Commune feminists offered a vision of the transformation of the social through reforms to girls’ education, the family and women’s work. Second, they practised a politics of coalition building by connecting their struggle with those of other oppressed groups, such as male workers, peasants and workers of other nations. Third, these ideas were instantiated in the Union des femmes’ novel proposal for women’s worker co-operatives as part of a socialist re-organisation of the economy

    Meeting the Needs of Society and the Market

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    Notwithstanding the dramatic decline in law school enrollments over the past seven years, the number of law school graduates continues to significantly exceed the number of available entry-level bar-passage-required and J.D. advantage jobs. At the same time, millions of citizens have unmet legal needs because they cannot afford the cost of legal services. What does the future hold for law graduate employment? Will there be growth or contraction in particular areas of legal employment? Do we have a broad enough view of the law jobs of the future? What, if anything, can individual schools, or the legal academy as a whole, do to help bridge the justice gap? Should regulators do anything to respond to the changed environment, such as by adopting an employment rate accreditation standard or by tightening the bar passage standard

    Displaced geostationary orbit design using hybrid sail propulsion

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    Because of an increase in the number of geostationary spacecraft and the limits imposed by east–west spacing requirements, the geostationary orbit is becoming congested. To increase its capacity, this paper proposes to create new geostationary slots by displacing the geostationary orbit either out of or in the equatorial plane by means of hybrid solar sail and solar electric propulsion. To minimize propellant consumption, optimal steering laws for the solar sail and solar-electric-propulsion thrust vectors are derived and the performance in terms of mission lifetime is assessed. For comparison, similar analyses are performed for conventional propulsion, including impulsive and pure solar electric propulsion. It is shown that hybrid sails outperform these propulsion techniques and that out-of-plane displacements outperform in-plane displacements. The out-of-plane case is therefore further investigated in a spacecraft mass budget to determine the payload mass capacity. Finally, two transfers that enable a further improvement of the performance of hybrid sails for the out-of-plane case are optimized using a direct pseudospectral method: a seasonal transit between orbits displaced above and below the equatorial plane and a transit to a parking orbit when geostationary coverage is not needed. Both transfers are shown to require only a modest propellant budget, outweighing the improvements they can establish

    A reductive aminase from Aspergillus oryzae

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    Reductive amination is one of the most important methods for the synthesis of chiral amines. Here we report the discovery of an NADP(H)-dependent reductive aminase from Aspergillus oryzae (AspRedAm, Uniprot code Q2TW47) which can catalyse the reductive coupling of a broad set of carbonyl compounds with a variety of primary and secondary amines with up to >98% conversion and with up to >98% enantiomeric excess. In cases where both carbonyl and amine show high reactivity, it is possible to employ a 1:1 ratio of the substrates, forming amine products with up to 94% conversion. Steady-state kinetic studies establish that the enzyme is capable of catalysing imine formation as well as reduction. Crystal structures of AspRedAm in complex with NADP(H) and also with both NADP(H) and the pharmaceutical ingredient (R)-rasagiline are reported. We also demonstrate preparative scale reductive aminations with wild-type and Q240A variant biocatalysts displaying total turnover numbers of up to 32,000 and space time yields up to 3.73 g L-1 d-1

    Stereoselectivity and Structural Characterisation of an Imine Reductase (IRED) from Amycolatopsis orientalis

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    The imine reductase AoIRED from Amycolatopsis orientalis (Uniprot R4SNK4) catalyzes the NADPH-dependent reduction of a wide range of prochiral imines and iminium ions, predominantly with (S)-selectivity and with e.e.s of up to >99%. AoIRED displays up to 100-fold greater catalytic efficiency for 2-methyl-1-pyrroline (2MPN) compared to other IREDs, such as the enzyme from Streptomyces sp. GF3546, which also exhibits (S)-selectivity, and thus AoIRED is an interesting candidate for preparative synthesis. AoIRED exhibits unusual catalytic properties, with inversion of stereoselectivity observed between structurally similar substrates, and also, in the case of 1-methyl-3,4-dihydroisoquinoline, for the same substrate, dependent on the age of the enzyme after purification. The structure of AoIRED has been determined in an ‘open’ apo-form, revealing a canonical dimeric IRED fold in which the active site is formed between the N- and C-terminal domains of participating monomers. Co-crystallisation with NADPH gave a ‘closed’ form in complex with the cofactor, in which a relative closure of domains, and associated loop movements, has resulted in a much smaller active site. A ternary complex was also obtained by co-crystallization with NADPH and 1-methyl-1,2,3,4-tetrahydroisoquinoline [(MTQ], and reveals a binding site for the (R)-amine product which places the chiral carbon within 4 Å of the putative location of the C4 atom of NADPH that delivers hydride to the C=N bond of the substrate. The ternary complex has permitted structure-informed mutation of the active site, resulting in mutants including Y179A, Y179F and N241A, of altered activity and stereoselectivity

    Survey of highly non-Keplerian orbits with low-thrust propulsion

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    Celestial mechanics has traditionally been concerned with orbital motion under the action of a conservative gravitational potential. In particular, the inverse square gravitational force due to the potential of a uniform, spherical mass leads to a family of conic section orbits, as determined by Isaac Newton, who showed that Kepler‟s laws were derivable from his theory of gravitation. While orbital motion under the action of a conservative gravitational potential leads to an array of problems with often complex and interesting solutions, the addition of non-conservative forces offers new avenues of investigation. In particular, non-conservative forces lead to a rich diversity of problems associated with the existence, stability and control of families of highly non-Keplerian orbits generated by a gravitational potential and a non-conservative force. Highly non-Keplerian orbits can potentially have a broad range of practical applications across a number of different disciplines. This review aims to summarize the combined wealth of literature concerned with the dynamics, stability and control of highly non-Keplerian orbits for various low thrust propulsion devices, and to demonstrate some of these potential applications

    Genetic landscape of congenital insensitivity to pain and hereditary sensory and autonomic neuropathies

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    Congenital insensitivity to pain (CIP) and hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders exclusively or predominantly affecting the sensory and autonomic neurons. Due to the rarity of the diseases and findings based mainly on single case reports or small case series, knowledge about these disorders is limited. Here, we describe the molecular workup of a large international cohort of CIP/HSAN patients including patients from normally under-represented countries. We identify 80 previously unreported pathogenic or likely pathogenic variants in a total of 73 families in the >20 known CIP/HSAN-associated genes. The data expand the spectrum of disease-relevant alterations in CIP/HSAN, including novel variants in previously rarely recognized entities such as ATL3-, FLVCR1- and NGF-associated neuropathies and previously under-recognized mutation types such as larger deletions. In silico predictions, heterologous expression studies, segregation analyses and metabolic tests helped to overcome limitations of current variant classification schemes that often fail to categorize a variant as disease-related or benign. The study sheds light on the genetic causes and disease-relevant changes within individual genes in CIP/HSAN. This is becoming increasingly important with emerging clinical trials investigating subtype or gene-specific treatment strategies

    Post-translational modifications of voltage-gated sodium channels in chronic pain syndromes.

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    In the peripheral sensory nervous system the neuronal expression of voltage-gated sodium channels (Navs) is very important for the transmission of nociceptive information since they give rise to the upstroke of the action potential (AP). Navs are composed of nine different isoforms with distinct biophysical properties. Studying the mutations associated with the increase or absence of pain sensitivity in humans, as well as other expression studies, have highlighted Nav1.7, Nav1.8, and Nav1.9 as being the most important contributors to the control of nociceptive neuronal electrogenesis. Modulating their expression and/or function can impact the shape of the AP and consequently modify nociceptive transmission, a process that is observed in persistent pain conditions. Post-translational modification (PTM) of Navs is a well-known process that modifies their expression and function. In chronic pain syndromes, the release of inflammatory molecules into the direct environment of dorsal root ganglia (DRG) sensory neurons leads to an abnormal activation of enzymes that induce Navs PTM. The addition of small molecules, i.e., peptides, phosphoryl groups, ubiquitin moieties and/or carbohydrates, can modify the function of Navs in two different ways: via direct physical interference with Nav gating, or via the control of Nav trafficking. Both mechanisms have a profound impact on neuronal excitability. In this review we will discuss the role of Protein Kinase A, B, and C, Mitogen Activated Protein Kinases and Ca++/Calmodulin-dependent Kinase II in peripheral chronic pain syndromes. We will also discuss more recent findings that the ubiquitination of Nav1.7 by Nedd4-2 and the effect of methylglyoxal on Nav1.8 are also implicated in the development of experimental neuropathic pain. We will address the potential roles of other PTMs in chronic pain and highlight the need for further investigation of PTMs of Navs in order to develop new pharmacological tools to alleviate pain

    On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

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    A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)
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