Introducción. El presente trabajo analiza los orígenes del gimnasio moderno durante el siglo XIX, período de edificación de los sistemas gimnásticos. Durante este período, la mujer occidental accede ...gradualmente al uso de las prácticas gimnásticas, ya desde la apariencia educativa, higiénica o recreativa. Objetivos. El objeto de estudio es el de descubrir, en el caso concreto de España, los discursos expresados por los poderes de la masculinidad que hicieron del gimnasio y de las prácticas gimnásticas un dispositivo de feminización. Metodología. La metodología utilizada es de base historicista y se concreta por un tratamiento documentalista, el análisis de contenido de los textos y, además, la revisión de otros estudios que facilitan la interpretación contextual. Resultados. Se concluye argumentando que el proceso de incorporación de la mujer decimonónica en las prácticas gimnásticas estuvo condicionado por los discursos subyacentes del patriarcado de la masculinidad, que ocultaban los temores de una sociedad que creían en decadencia. Discusión. En el gimnasio del siglo XIX el cuerpo femenino se convertía en un ente vigilado por el dominio del hombre que buscaba la salud de la mujer para proteger la descendencia. Con lo cual, el gimnasio se configuró como un centro de dominación facultativo en donde el cuerpo femenino se sometía al examen articulándose una perversión ontológica de la realidad femenina.
Abstract
Quantum mechanics is well known to accelerate statistical sampling processes over classical techniques. In quantitative finance, statistical samplings arise broadly in many use cases. Here ...we focus on a particular one of such use cases, credit valuation adjustment (CVA), and identify opportunities and challenges towards quantum advantage for practical instances. To build a NISQ-friendly quantum circuit able to solve such problem, we draw on various heuristics that indicate the potential for significant improvement over well-known techniques such as reversible logical circuit synthesis. In minimizing the resource requirements for amplitude amplification while maximizing the speedup gained from the quantum coherence of a noisy device, we adopt a recently developed Bayesian variant of quantum amplitude estimation using engineered likelihood functions. We perform numerical analyses to characterize the prospect of quantum speedup in concrete CVA instances over classical Monte Carlo simulations.
ResumenAnte la escasez de una auténtica historia del deporte para las personas con discapacidad o deporte adaptado en España, se aborda un estudio inédito, cuyo objeto es el de ofrecer visibilidad y ...aclaraciones a uno de los temas más ignorados del deporte español. Mediante una revisión documental de la prensa histórica, localizada en plataformas digitales, y el análisis de otros estudios relativos se esboza un relato sobre los inicios del deporte adaptado para personas con discapacidad física. El estudio se inicia a partir de las primeras noticias durante la dictadura franquista y termina en el año 1972, momento en el que se puede dar por finalizado un primer proceso en la institucionalización del deporte adaptado. Se concluye que las iniciativas institucionales emprendías durante este periodo surgieron por las presiones de los organismos internacionales y, también, de ciertas voluntades personales vinculadas con el poder. AbstractGiven the scarcity of an authentic history of sport for people with disabilities or adapted sport in Spain, an unpublished study is undertaken, the aim of which is to offer visibility and clarification to one of the most ignored subjects in Spanish sport. Through a documentary review of the historical press, located on digital platforms, and the analysis of other related studies, an account of the beginnings of adapted sport for people with physical disabilities is sketched out. The study starts from the first news during Franco's dictatorship and ends in 1972, when a first process in the institutionalisation of adapted sport can be considered to have been completed. It is concluded that the institutional initiatives undertaken during this period arose from the pressures of international organisations and also from certain personal wills linked to those in power.
Summary Background Friedreich's ataxia is a progressive degenerative disorder caused by deficiency of the frataxin protein. Expanded GAA repeats within intron 1 of the frataxin ( FXN ) gene lead to ...its heterochromatinisation and transcriptional silencing. Preclinical studies have shown that the histone deacetylase inhibitor nicotinamide (vitamin B3) can remodel the pathological heterochromatin and upregulate expression of FXN . We aimed to assess the epigenetic and neurological effects and safety of high-dose nicotinamide in patients with Friedreich's ataxia. Methods In this exploratory, open-label, dose-escalation study in the UK, male and female patients (aged 18 years or older) with Friedreich's ataxia were given single doses (phase 1) and repeated daily doses of 2–8 g oral nicotinamide for 5 days (phase 2) and 8 weeks (phase 3). Doses were gradually escalated during phases 1 and 2, with individual maximum tolerated doses used in phase 3. The primary outcome was the upregulation of frataxin expression. We also assessed the safety and tolerability of nicotinamide, used chromatin immunoprecipitation to investigate changes in chromatin structure at the FXN gene locus, and assessed the effect of nicotinamide treatment on clinical scales for ataxia. This study is registered with ClinicalTrials.gov , number NCT01589809. Findings Nicotinamide was generally well tolerated; the main adverse event was nausea, which in most cases was mild, dose-related, and resolved spontaneously or after dose reduction, use of antinausea drugs, or both. Phase 1 showed a dose-response relation for proportional change in frataxin protein concentration from baseline to 8 h post-dose, which increased with increasing dose (p=0·0004). Bayesian analysis predicted that 3·8 g would result in a 1·5-times increase and 7·5 g in a doubling of frataxin protein concentration. Phases 2 and 3 showed that daily dosing at 3·5–6 g resulted in a sustained and significant (p<0·0001) upregulation of frataxin expression, which was accompanied by a reduction in heterochromatin modifications at the FXN locus. Clinical measures showed no significant changes. Interpretation Nicotinamide was associated with a sustained improvement in frataxin concentrations towards those seen in asymptomatic carriers during 8 weeks of daily dosing. Further investigation of the long-term clinical benefits of nicotinamide and its ability to ameliorate frataxin deficiency in Friedreich's ataxia is warranted. Funding Ataxia UK, Ataxia Ireland, Association Suisse de l'Ataxie de Friedreich, Associazione Italiana per le Sindromi Atassiche, UK National Institute for Health Research, European Friedreich's Ataxia Consortium for Translational Studies, and Imperial Biomedical Research Centre.
We introduce NetKet, a comprehensive open source framework for the study of many-body quantum systems using machine learning techniques. The framework is built around a general and flexible ...implementation of neural-network quantum states, which are used as a variational ansatz for quantum wavefunctions. NetKet provides algorithms for several key tasks in quantum many-body physics and quantum technology, namely quantum state tomography, supervised learning from wavefunction data, and ground state searches for a wide range of customizable lattice models. Our aim is to provide a common platform for open research and to stimulate the collaborative development of computational methods at the interface of machine learning and many-body physics.
Abstract Generative modeling has seen a rising interest in both classical and quantum machine learning, and it represents a promising candidate to obtain a practical quantum advantage in the near ...term. In this study, we build over an existing framework for evaluating the generalization performance of generative models, and we establish the first quantitative comparative race towards practical quantum advantage (PQA) between classical and quantum generative models, namely Quantum Circuit Born Machines (QCBMs), Transformers (TFs), Recurrent Neural Networks (RNNs), Variational Autoencoders (VAEs), and Wasserstein Generative Adversarial Networks (WGANs). After defining four types of PQAs scenarios, we focus on what we refer to as potential PQA, aiming to compare quantum models with the best-known classical algorithms for the task at hand. We let the models race on a well-defined and application-relevant competition setting, where we illustrate and demonstrate our framework on 20 variables (qubits) generative modeling task. Our results suggest that QCBMs are more efficient in the data-limited regime than the other state-of-the-art classical generative models. Such a feature is highly desirable in a wide range of real-world applications where the available data is scarce.
Protein Glycan Coupling Technology (PGCT) uses purposely modified bacterial cells to produce recombinant glycoconjugate vaccines. This vaccine platform holds great potential in this context, namely ...due to its modular nature, the simplified production process in comparison to traditional chemical conjugation methods, and its amenability to scaled-up operations. As a result, a considerable reduction in production time and cost is expected, making PGCT-made vaccines a suitable vaccine technology for low-middle income countries, where vaccine coverage remains predominantly low and inconsistent. This work aims to develop an integrated whole-process automated platform for the screening of PGCT-made glycoconjugate vaccine candidates. The successful translation of a bench scale process for glycoconjugate production to a microscale automated setting was achieved. This was integrated with a numerical computational software that allowed hands-free operation and a platform adaptable to biological variation over the course of a production process. Platform robustness was proven with both technical and biological replicates and subsequently the platform was used to screen for the most favourable conditions for production of a pneumococcal serotype 4 vaccine candidate. This work establishes an effective automated platform that enabled the identification of the most suitable E. coli strain and genetic constructs to be used in ongoing early phase research and be further brought into preclinical trials.
Glycoengineering, in the biotechnology workhorse bacterium, Escherichia coli, is a rapidly evolving field, particularly for the production of glycoconjugate vaccine candidates (bioconjugation). ...Efficient production of glycoconjugates requires the coordinated expression within the bacterial cell of three components: a carrier protein, a glycan antigen and a coupling enzyme, in a timely fashion. Thus, the choice of a suitable E. coli host cell is of paramount importance. Microbial chassis engineering has long been used to improve yields of chemicals and biopolymers, but its application to vaccine production is sparse.
In this study we have engineered a family of 11 E. coli strains by the removal and/or addition of components rationally selected for enhanced expression of Streptococcus pneumoniae capsular polysaccharides with the scope of increasing yield of pneumococcal conjugate vaccines. Importantly, all strains express a detoxified version of endotoxin, a concerning contaminant of therapeutics produced in bacterial cells. The genomic background of each strain was altered using CRISPR in an iterative fashion to generate strains without antibiotic markers or scar sequences.
Amongst the 11 modified strains generated in this study, E. coli Falcon, Peregrine and Sparrowhawk all showed increased production of S. pneumoniae serotype 4 capsule. Eagle (a strain without enterobacterial common antigen, containing a GalNAc epimerase and PglB expressed from the chromosome) and Sparrowhawk (a strain without enterobacterial common antigen, O-antigen ligase and chain length determinant, containing a GalNAc epimerase and chain length regulators from Streptococcus pneumoniae) respectively produced an AcrA-SP4 conjugate with 4 × and 14 × more glycan than that produced in the base strain, W3110. Beyond their application to the production of pneumococcal vaccine candidates, the bank of 11 new strains will be an invaluable resource for the glycoengineering community.
Our current knowledge about the mechanisms of miRNA silencing is restricted to few lineages such as vertebrates, arthropods, nematodes and land plants. miRNA-mediated silencing in bilaterian animals ...is dependent on the proteins of the GW182 family. Here, we dissect the function of GW182 protein in the cnidarian Nematostella, separated by 600 million years from other Metazoa. Using cultured human cells, we show that Nematostella GW182 recruits the CCR4-NOT deadenylation complexes via its tryptophan-containing motifs, thereby inhibiting translation and promoting mRNA decay. Further, similarly to bilaterians, GW182 in Nematostella is recruited to the miRNA repression complex via interaction with Argonaute proteins, and functions downstream to repress mRNA. Thus, our work suggests that this mechanism of miRNA-mediated silencing was already active in the last common ancestor of Cnidaria and Bilateria.
Campylobacter is an animal and zoonotic pathogen of global importance, and a pressing need exists for effective vaccines, including those that make use of conserved polysaccharide antigens. To this ...end, we adapted Protein Glycan Coupling Technology (PGCT) to develop a versatile Escherichia coli strain capable of generating multiple glycoconjugate vaccine candidates against Campylobacter jejuni.
We generated a glycoengineering E. coli strain containing the conserved C. jejuni heptasaccharide coding region integrated in its chromosome as a model glycan. This methodology confers three advantages: (i) reduction of plasmids and antibiotic markers used for PGCT, (ii) swift generation of many glycan-protein combinations and consequent rapid identification of the most antigenic proteins or peptides, and (iii) increased genetic stability of the polysaccharide coding-region. In this study, by using the model glycan expressing strain, we were able to test proteins from C. jejuni, Pseudomonas aeruginosa (both Gram-negative), and Clostridium perfringens (Gram-positive) as acceptors. Using this pgl integrant E. coli strain, four glycoconjugates were readily generated. Two glycoconjugates, where both protein and glycan are from C. jejuni (double-hit vaccines), and two glycoconjugates, where the glycan antigen is conjugated to a detoxified toxin from a different pathogen (single-hit vaccines). Because the downstream application of Live Attenuated Vaccine Strains (LAVS) against C. jejuni is to be used in poultry, which have a higher body temperature of 42 °C, we investigated the effect of temperature on protein expression and glycosylation in the E. coli pgl integrant strain.
We determined that glycosylation is temperature dependent and that for the combination of heptasaccharide and carriers used in this study, the level of PglB available for glycosylation is a step limiting factor in the glycosylation reaction. We also demonstrated that temperature affects the ability of PglB to glycosylate its substrates in an in vitro glycosylation assay independent of its transcriptional level.
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