bluuebunny/crossref_metadata_2025 huggingface dataset:
Pouvoir et impouvoir du langage : Introduction
Authors: Plante Maxime
Published: June 2018

Ce dossier interroge les rapports intimes entre langage et politique en partant de
l’hypothèse que le pouvoir du langage ou sa performativité est inséparable d’un
investissement du langage par le pouvoir. Un tel questionnement sémiopolitique ne serait pas
complet s’il ne venait pas à affronter la question de la limite où il semble remis en
question. C’est l’expérience de la littérature, prise entre le pouvoir et l’impouvoir, la
mobilisation et l’épuisement, du langage, qui apparaît comme cette frontière à interroger.
Les textes rassemblés dans ce dossier abordent l’un ou l’autre de ces deux axes de réflexion
selon des perspectives riches et variées qui laissent peut-être suggérer qu’entre pouvoir et
impouvoir du langage, il n’est pas certain qu’il en aille d’une alternative.
La question du fondement discursif des discours nationalistes : Le problème de
Münchhausen
Authors: Melekevik Åsbjørn
Published: June 2018

Le présent article examine la question des fondements du nationalisme par rapport au
trilemme de Münchhausen, en tentant d’établir la dimension discursive du nationalisme qui se
réalise idéalement dans un espace public ouvert. Nous critiquons le « nationalisme
ontologique » et sa fâcheuse tendance à proclamer la « déjà-nation », soit une nation sans
possibilité de connaissance pour les sujets, les discours individuels sur la nation étant
alors immédiatement bloqués par une interprétation déjà-vraie de la nation. Une telle
interprétation de la déjà-nation fait fi de la distinction entre le cadre interprétatif
général qu’est le nationalisme et les propositions qui en découlent, ces propositions étant
de la seule responsabilité des individus. La nation est en fait la représentation même du
pouvoir du langage, n’existant qu’à l’intérieur d’un filet de sens créé par les discours
nationalistes dans la sphère publique.
Le selfie
Authors: B. Daphné
Published: June 2018

Cet article traite du néologisme "égoportrait", inventé par le journaliste Fabien Deglise, et montre en quoi ce dernier reconduit un discours sexiste et une conception étroite de la pratique culturelle. En effet, la traduction francophone du terme anglais "selfie" consolide des stéréotypes sexistes, associés à la pratique du selfie. Cet article tente ensuite de brosser un portrait plus rigoureux du selfie, une pratique culturelle qui peut être saine et valorisante. Finalement, cet article examine le selfie dans un contexte littéraire. En analysant le travail de deux poètes contemporains, il montre en quoi le selfie peut être un procédé littéraire.
Le fait littéraire au temps du numérique
Authors: Monjour Servanne , Vitali-Rosati Marcello , Wormser Gérard
Published: June 2018

Souvent conçues comme le vecteur de changements majeurs, les pratiques numériques constituent une occasion de mieux comprendre le fait littéraire en faisant apparaître de manière plus explicite que jamais des aspects ontologiques qui, en tant que tels, ont une valeur atemporelle. En particulier, et c’est l’objet de cet article, le fait numérique donne l’occasion de réinvestir une problématique qui parcourt l’ensemble de la réflexion sur le statut de la littérature depuis Platon et Aristote : celle du rapport entre littérature et réalité, dont Sartre et Derrida avaient déjà œuvré à déconstruire l’opposition au XXe siècle. Selon nous, le numérique souligne l’absence de séparation entre symbolique et non-symbolique, nous empêchant de penser une rupture entre imaginaire et réel. Pour rendre compte de cette structure, nous nous appuierons sur le concept d’éditorialisation, qui vient désigner l’ensemble des dispositifs permettant la production de contenus dans l’espace numérique en tenant compte de la fusion entre espace numérique et espace non numérique. À travers des exemples littéraires – Traque Traces de Cécile Portier et Laisse venir d’Anne Savelli et Pierre Ménard – nous démontrerons comment la littérature participe aujourd’hui à l’éditorialisation du monde, enterrant ainsi définitivement le dualisme imaginaire-réel pour lui préférer une structure anamorphique.
La sociabilité numérique comme ressort de la fiction
Authors: Marcotte Sophie
Published: June 2018

Cet article interroge la manière dont le roman contemporain intègre les nouvelles
formes de sociabilités découlant de l’usage des dispositifs numériques permettant des
échanges textuels (courriels et textos, par exemple). Les représentations des nouvelles
habitudes d’interaction avec autrui, examinées dans Scrapbook de Nadine Bismuth et dans Les
Charmes de l’impossible de Karine Glorieux, montrent que l’utilisation des dispositifs
technologiques comme le téléphone cellulaire, la tablette et l’ordinateur ne contribuent pas
à créer de la proximité, comme on pourrait le supposer de prime abord, mais bien de la
distance et du vide. On remarque que si ces dispositifs agissent comme des médiateurs dans
l’établissement et l’évolution des liens sociaux et affectifs entre les personnages, ils
représentent aussi des éléments perturbateurs qui empêchent ces relations de se développer
de manière harmonieuse et de durer.
Se réinventer with a new tab
Authors: Savoie-Bernard Chloé
Published: June 2018

Cet article s’intéresse au roman New Tab (2014, 2016 pour la traduction française), de
l’écrivain montréalais Guillaume Morissette. Né francophone, ce dernier écrit en anglais et
est actif sur la scène littéraire anglophone. Son œuvre thématise Internet, et nous verrons
comment l’utilisation de la langue anglaise est d’abord liée aux liens qu’entretient
l’écrivain avec l’alt lit, courant littéraire américain, plutôt qu’à une revendication
politique.
Ouvrir le livre et voir l’écran : pratiques littéraires et pratiques numériques
Authors: Thériault Jean-François , Savoie-Bernard Chloé
Published: June 2018

Ce dossier s’intéresse à la manière dont s’entrelacent littérature et numérique dans
la littérature contemporaine. Puisque le numérique teinte l’ensemble des pratiques humaines,
la littérature fait partie des lieux qu’elle investit. Ainsi, la question autour de laquelle
s’articulent les textes de ce dossier est donc la suivante : comment pratiques littéraires
et pratiques numériques peuvent-elles dialoguer aujourd’hui, et que peut-on dire des
interactions qui découlent de ces échanges ? Il ne s’agit pas d’affirmer que toute la
production littéraire contemporaine développe un discours sur le numérique, mais bien que
les nouvelles possibilités de lecture et d’analyse qui nous sont offertes méritent d’être
analysées et mises à l’épreuve.
Viral GPCR US28 can signal in response to chemokine agonists of nearly unlimited structural degeneracy
Authors: Miles Timothy F , Spiess Katja , Jude Kevin M , Tsutsumi Naotaka , Burg John S , Ingram Jessica R , Waghray Deepa , Hjorto Gertrud M , Larsen Olav , Ploegh Hidde L , Rosenkilde Mette M , Garcia K Christopher
Published: June 2018

Human cytomegalovirus has hijacked and evolved a human G-protein-coupled receptor into US28, which functions as a promiscuous chemokine 'sink’ to facilitate evasion of host immune responses. To probe the molecular basis of US28’s unique ligand cross-reactivity, we deep-sequenced CX3CL1 chemokine libraries selected on ‘molecular casts’ of the US28 active-state and find that US28 can engage thousands of distinct chemokine sequences, many of which elicit diverse signaling outcomes. The structure of a G-protein-biased CX3CL1-variant in complex with US28 revealed an entirely unique chemokine amino terminal peptide conformation and remodeled constellation of receptor-ligand interactions. Receptor signaling, however, is remarkably robust to mutational disruption of these interactions. Thus, US28 accommodates and functionally discriminates amongst highly degenerate chemokine sequences by sensing the steric bulk of the ligands, which distort both receptor extracellular loops and the walls of the ligand binding pocket to varying degrees, rather than requiring sequence-specific bonding chemistries for recognition and signaling.
Soft-bottom fishes and spatial protection: findings from a temperate marine protected area
Authors: Sousa Inês , Gonçalves Jorge M.S. , Claudet Joachim , Coelho Rui , Gonçalves Emanuel J. , Erzini Karim
Published: June 2018

Numerous studies over the last decades have focused on marine protected areas (MPAs) and their effects on fish communities. However, there is a knowledge gap regarding how species that live associated with soft-substrates (e.g., sand, mud) respond to spatial protection. We analyzed abundance, biomass and total lengths of the soft-bottom fishes in a multiple-use MPA in the north-eastern Atlantic, the Luiz Saldanha Marine Park (Portugal), during and after the implementation of its management plan. Data were collected by experimental fishing in areas with three different levels of protection, during the implementation period and for three years after full implementation of the MPA. Univariate analysis detected significant biomass increases between the two periods. Fish assemblages were mainly structured by depth and substrate, followed by protection level. Community composition analyses revealed significant differences between protection levels and between the two periods. Species exhibited a broad variation in their response to protection, and we hypothesize that factors such as species habitat preferences, body size and late maturity might be underlying determinants. Overall, this study provides some evidence of protection effectiveness in soft-bottom fish communities, supported by the significant increase in biomass in the protected areas and the positive trends of some species.
­Characterization of pyruvate kinase from the anoxia tolerant turtle, Trachemys scripta elegans: a potential role for enzyme methylation during metabolic rate depression
Authors: Mattice Amanda M.S. , MacLean Isabelle A. , Childers Christine L. , Storey Kenneth B.
Published: June 2018

Background

Pyruvate kinase (PK) is responsible for the final reaction in glycolysis. As PK is a glycolytic control point, the analysis of PK posttranslational modifications (PTM) and kinetic changes reveals a key piece of the reorganization of energy metabolism in an anoxia tolerant vertebrate.

Methods

To explore PK regulation, the enzyme was isolated from red skeletal muscle and liver of aerobic and 20-hr anoxia-exposed red eared-slider turtles (Trachemys scripta elegans). Kinetic analysis and immunoblotting were used to assess enzyme function and the corresponding covalent modifications to the enzymes structure during anoxia.

Results

Both muscle and liver isoforms showed decreased affinity for phosphoenolpyruvate substrate during anoxia, and muscle PK also had a lower affinity for ADP. I50 values for the inhibitors ATP and lactate were lower for PK from both tissues after anoxic exposure while I50 L-alanine was only reduced in the liver. Both isozymes showed significant increases in threonine phosphorylation (by 42% in muscle and 60% in liver) and lysine methylation (by 43% in muscle and 70% in liver) during anoxia which have been linked to suppression of PK activity in other organisms. Liver PK also showed a 26% decrease in tyrosine phosphorylation under anoxia.

Discussion

Anoxia responsive changes in turtle muscle and liver PK coordinate with an overall reduced activity state. This reduced affinity for the forward glycolytic reaction is likely a key component of the overall metabolic rate depression that supports long term survival in anoxia tolerant turtles. The coinciding methyl- and phospho- PTM alterations present the mechanism for tissue specific enzyme modification during anoxia.
MipLAAO, a new L-amino acid oxidase from the redtail coral snake Micrurus mipartitus
Authors: Rey-Suárez Paola , Acosta Cristian , Torres Uday , Saldarriaga-Córdoba Mónica , Lomonte Bruno , Núñez Vitelbina
Published: June 2018

L-amino acid oxidases (LAAOs) are ubiquitous enzymes in nature. Bioactivities described for these enzymes include apoptosis induction, edema formation, induction or inhibition of platelet aggregation, as well as antiviral, antiparasite, and antibacterial actions. With over 80 species, Micrurus snakes are the representatives of the Elapidae family in the New World. Although LAAOs in Micrurus venoms have been predicted by venom gland transcriptomic studies and detected in proteomic studies, no enzymes of this kind have been previously purified from their venoms. Earlier proteomic studies revealed that the venom of M. mipartitus from Colombia contains ∼4% of LAAO. This enzyme, here named MipLAAO, was isolated and biochemically and functionally characterized. The enzyme is found in monomeric form, with an isotope-averaged molecular mass of 59,100.6 Da, as determined by MALDI-TOF. Its oxidase activity shows substrate preference for hydrophobic amino acids, being optimal at pH 8.0. By nucleotide sequencing of venom gland cDNA of mRNA transcripts obtained from a single snake, six isoforms of MipLAAO with minor variations among them were retrieved. The deduced sequences present a mature chain of 483 amino acids, with a predicted pI of 8.9, and theoretical masses between 55,010.9 and 55,121.0 Da. The difference with experimentally observed mass is likely due to glycosylation, in agreement with the finding of three putative N-glycosylation sites in its amino acid sequence. A phylogenetic analysis of MmipLAAO placed this new enzyme within the clade of homologous proteins from elapid snakes, characterized by the conserved Serine at position 223, in contrast to LAAOs from viperids. MmipLAAO showed a potent bactericidal effect on S. aureus (MIC: 2 µg/mL), but not on E. coli. The former activity could be of interest to future studies assessing its potential as antimicrobial agent.
Process-based allometry describes the influence of management on orchard tree aboveground architecture
Authors: Brym Zachary T. , Ernest S.K. Morgan
Published: June 2018

We evaluated allometric relationships in length, diameter, and mass of branches for two variably managed orchard tree species (tart cherry,Prunus cerasus; apple,Malusspp.). The empirically estimated allometric exponents (a) of the orchard trees were described in the context of two processed-based allometry models that make predictions fora: the West, Brown and Enquist fractal branching model (WBE) and the recently introduced Flow Similarity model (FS). These allometric models make predictions about relationships in plant morphology (e.g., branch mass, diameter, length, volume, surface area) based on constraints imposed on plant growth by physical and physiological processes. We compared our empirical estimates ofato the model predictions to interpret the physiological implications of pruning and management in orchard systems. Our study found strong allometric relationships among the species and individuals studied with limited agreement with the expectations of either model. The 8/3-power law prediction of the mass ∼ diameter relationship by the WBE, indicative of biomechanical limitations, was marginally supported by this study. Length-including allometric relationships deviated from predictions of both models, but shift toward the expectation of flow similarity. In this way, managed orchard trees deviated from strict adherence to the idealized expectations of the models, but still fall within the range of model expectations in many cases despite intensive management.
Gorgonopsian therapsids (Nochnitsa gen. nov. and Viatkogorgon) from the Permian Kotelnich locality of Russia
Authors: Kammerer Christian F. , Masyutin Vladimir
Published: June 2018

The early evolution of gorgonopsians is poorly understood. New material from the Kotelnich locality in Russia expands our knowledge of middle/earliest late Permian gorgonopsians from Laurasia. Two gorgonopsian taxa are recognized from Kotelnich: Viatkogorgon ivakhnenkoi Tatarinov, 1999 and Nochnitsa geminidens gen. et sp. nov. Nochnitsa can be distinguished from all known gorgonopsians by its unique upper postcanine tooth row, composed of pairs of teeth (a small anterior and larger posterior) separated by diastemata. Both Viatkogorgon and Nochnitsa are relatively small gorgonopsians, comparable in size to the South African middle Permian taxon Eriphostoma. Inclusion of Viatkogorgon and Nochnitsa in a phylogenetic analysis of gorgonopsians recovers them in basal positions, with Nochnitsa representing the earliest-diverging gorgonopsian genus. All other sampled gorgonopsians fall into two major subclades: one made up entirely of Russian taxa (Inostrancevia, Pravoslavlevia, Sauroctonus, and Suchogorgon) and the other containing only African gorgonopsians. The high degree of endemism indicated in this analysis for gorgonopsians is remarkable, especially given the extensive intercontinental dispersal inferred for coeval therapsid groups.
Estudio sobre la posibilidad de mediación con menores y sus familias en situaciones de violencia de género bajo la perspectiva de profesionales del ámbito sociojurídico de Almería
Authors: Ibáñez López Andrea , García-Longoria María Paz
Published: June 2018

El objetivo principal de este artículo es estudiar la viabilidad del uso de la mediación en casos de violencia de género donde se dé la presencia de menores, conocer la opinión de los profesionales en relación a este tipo de mediación, comprobar cómo afecta al desarrollo del menor la presencia de violencia de género en su entorno familiar, así como conocer qué particularidades deben tener este tipo de procesos de mediación para aplicarse con éxito. Para comenzar, se realiza una fundamentación teórica que sirva de base para situar y centrar el objeto de estudio. A continuación, se describenlos distintos pasos seguidos para llevar a cabo la realización de la investigación mediante la metodología elegida. Finalmente se presentarán los resultados de la investigación con la elaboración de unas conclusiones finales que nos permitan confirmar la tesis central de esta investigación.
Participación política de las mujeres en Chile y sus oportunidades, en la percepción de estudiantes de primer año de universidad. El caso de la Universidad de Concepción
Authors: Gauché Marchetti Ximena Andrea , Muñoz Labraña Carlos , Bustos Ibarra Cecilia , Alvez Marín Amaya
Published: June 2018

Esta investigación da cuenta de algunas concepciones y actitudes que posee el estudiantado de carreras de las áreas de educación, ciencias sociales y ciencias jurídicas de la Universidad de Concepción, sobre algunos aspectos vinculados a la participación política de las mujeres en Chile. Ello se ha obtenido a partir de los resultados de una encuesta aplicada aestudiantes de primer año. Tales resultados demostraron que al iniciar sus estudios universitarios valoran positivamente la consagración formal de la participación política de las mujeres, consideran un deber del Estado garantizar la igualdad de oportunidades y manifiestan desconfianza en los partidos políticos y en el Congreso Nacional. Sin embargo, a la hora de lasoportunidades, la confianza tiende a ser mayor en los hombres para depositar responsabilidades de carácter político, lo que introduce la necesidad de avanzar desde la formalidad del buen discurso sobre igualdad a la acción práctica en política.
Procedimiento Inspector y proceso penal. Problemas no resueltos en la doble instrucción de delítos contra la hacienda pública en el Reino de España
Authors: López Martinez Juan
Published: June 2018

En el presente estudio se analizan las relaciones existentes en el derecho positivo español entre la articulación de las instrucciones del procedimiento de regularización de la deuda y el proceso por delito contra la Hacienda Pública. En él se pone de manifiesto que en la normativa que resulta aplicable no se establecen el conjunto de técnicas que de forma precisa articulen los derechos, deberes y garantías que han de observarse en ambos órdenes. En este sentido se analiza el concepto y efectos de la «noticia criminis» en el procedimiento de Inspección tributaria vigente en España; la naturaleza, el contenido y el alcance del traslado del «tanto de culpa» y, la operatividad y sus límites, del derecho a no autoinculparse en el procedimiento de regularización de deudas. Problemas que resultan nucleares en cualquier regulación que se establezca para la articulación de las relaciones entre procedimiento y proceso.
¿Por qué se aprobó el voto voluntario en Chile? Razones y argumentos que impulsaron la reforma
Authors: Morales Quiroga Mauricio
Published: June 2018

Teóricamente, con voto voluntario baja la participación electoral y tienden a votar más los ricos que los pobres, generando lo que la literatura denomina como sesgo de clase. Entonces, ¿qué lleva a los políticos a optar por un régimen de voto voluntario? Considerando el caso de Chile, nuestro objetivo es identificar las razones que impulsaron la reforma. Metodológicamente, utilizamos tres fuentes de información: discusión legislativa, encuestas de opinión y una inédita encuesta aplicada al 100% de los diputados luego de aprobada la reforma. Nuestros resultados indican que la reforma se aprobó producto de la interacción entre intereses estratégicos de la coalición de gobierno (de centro-izquierda) y de la oposición. Mientras el gobierno impulsó la reforma creyendo que los nuevos votantes serían principalmente de centro-izquierda, la derecha lo hizo pensando en que sus nuevos electores tendrían mayor probabilidad de votar dado su mayor nivel de ingresos. A esto se sumó un amplio apoyo ciudadano a la reforma expresado en las encuestas, lo que pudo presionar a los diputados. Constatamos que en la centro-izquierda hubo rápidas señales de arrepentimiento, pues el 70% de los diputados –en una encuesta hecha a meses de la reforma– se mostró partidario del voto obligatorio.
Informados y confiados: el efecto del consumo de medios de comunicación tradicional y digital sobre la confianza de los chilenos en 2015
Authors: Espinoza-Bianchini Gonzalo
Published: June 2018

La confianza de las personas, interpersonal o institucional, ayuda a explicar interacciones entre individuos y otros fenómenos sociales, resulta clave tratar de entender por qué la gente confía. El consumo de medios de comunicación ha sido considerado como un factor importante para entender en el comportamiento de los individuos. Pero el efecto entre el consumo de medios tradicionales sobre la confianza de las personas es considerada positiva por algunos y negativa por otros. Además, existe menos evidencia sobre el efecto del consumo de medios de comunicación digitales sobre la confianza de las personas. Utilizando la encuesta del Programa de Naciones Unidas para el Desarrollo – Índice de Desarrollo Humano 2015 (PNUD-IDH 2015), evalúo el efecto del consumo de medios tradicionales y digitales sobre la confianza interpersonal e institucional de los chilenos en 2015. Reporto que consumir distintos tipos de medios de comunicación motiva diferentes tipos de confianza. Así, mientras el consumo de medios tradicionales aumenta la confianza en las instituciones, el consumo de medios digitales fomenta la confianza interpersonal de los chilenos en 2015
Partidos políticos y producción legislativa en el Perú: 2006 - 2011
Authors: García Marín Ignacio
Published: June 2018

La presente investigación analiza la producción legislativa llevada a cabo durante el segundo mandato de Alan García desde un punto de vista cuantitativo. Para ello, se exponen las principales potestades del ejecutivo y congreso así como el sistema partidario peruano en el quinquenio 2006-2011 y su evolución. Posteriormente se analizan las tasas de éxito de los proyectos de ley presentados en dicho período. Aparentemente, la elevada y creciente fragmentación partidaria dificultó la aprobación de proyectos de ley tanto los provenientes del oficialismo como de la oposición. Asimismo, el ejecutivo tendió al empleo elevado del decreto, práctica no obstante frecuente en el Perú. Todo ello, enmarcado en un sistema partidario altamente fragmentado y con escasa institucionalización, lo que estaría propiciando un rol secundario para las organizaciones partidarias en el sistema político respecto al papel que quizá debieran desempeñar en otras circunstancias.
Stamen and Pollen Development
Authors: Muñoz‐Sanz Juan V , McClure Bruce
Published: June 2018

Stamens are the male sexual organs in flowers. Their function is to produce and disperse pollen, which carries the plant's sperm cells to the pistil. Mature stamens consist of a filament and an anther. They are initiated on floral meristems and form the third of four concentric organ whorls. The sterile filament provides a vascular connection and positions the anther for pollen dispersal. The anther sits at the tip of the filament and is the site of pollen production. Diploid germ‐line cells in the anther interior undergo meiosis to produce haploid microspores. These microspores, in turn, undergo one or two mitotic divisions, making pollen either bicellular or tricellular at the time of anthesis. Surrounding layers of nonsexual cells are essential for pollen development and also contribute to the external pollen coat. At anthesis, the mature anther splits open, and pollen is available for transfer to the pistil.

Key Concepts

A canonical flower contains four concentric organ whorls.

Stamens comprise the third whorl and function to produce and disperse pollen, which contains the male gametes.

Stamens are specified by the combined action of B‐ and C‐class floral homeotic genes in a floral meristem.

A mature stamen consists of a nonsexual filament and a four‐lobed anther that is the site of pollen production.

Positional information and cell–cell signalling are crucial for specifying the germ‐line pollen mother cells and surrounding somatic tissues.

Cells in the interior of the developing anther differentiate into germ‐line archesporial cells and then induce somatic fates in surrounding cells.

After meiosis, the germ‐line archesporial cells develop into pollen, and the surrounding somatic cells support pollen development.

At anthesis, the mature anther splits and desiccates to allow pollen dispersal.
Adeno‐associated Viral Vectors in Gene Therapy
Authors: Ling Chen , Zhong Li , Srivastava Arun
Published: June 2018

Recombinant vectors based on a nonpathogenic human parvovirus, the
adeno‐associated virus
(AAV), have gained attention as a potentially safe and useful alternative to the more commonly used retroviral and adenoviral vectors. The past decade has witnessed the use of AAV vectors in the potential gene therapy of an ever‐increasing number of human diseases. The safety of AAV vectors in 165 Phase I/II and 1 Phase III clinical trials in humans to date and clinical efficacy in at least 8 human diseases have now been well documented. The availability of a vast repertoire of AAV serotype vectors, both naturally occurring and genetically engineered, and the availability of promising results with animal models of human diseases provide further impetus to the optimism that their use in the potential gene therapy of a wide variety of human diseases, both genetic and acquired, will continue in the foreseeable future.

Key Concepts

The first‐generation recombinant AAV vectors have shown efficacy in a number of Phase I/II clinical trials targeting various human diseases.

The host immune response to AAV vectors, especially at high doses, remains a challenging problem.

The presence of preexisting antibodies to AAV is also a challenge as a significant proportion of the human population is sero‐positive for one or more of the AAV serotypes.

The next‐generation AAV vectors have been developed that promise to circumvent most, if not all, of the problems associated with the first generation of AAV vectors.

The next generation of AAV vectors, which are more efficacious at lower doses, are likely to prove safe and effective in the potential gene therapy of a wide variety of human diseases in the not‐too‐distant future.
Cystathionine β‐Synthase (CBS) Deficiency: Genetics
Authors: Kožich Viktor , Kraus Jan P , Majtan Tomas
Published: June 2018

Cystathionine β‐synthase (CBS) catalyses condensation of homocysteine and serine to cystathionine, and by alternative reactions also synthesis of hydrogen sulfide. CBS deficiency, an autosomal recessive trait with estimated worldwide frequency of 0.82–1.09 per 100 000 births, manifests usually by thromboembolism, and in severe forms also by lens dislocation, marfanoid features, osteoporosis and neuropsychiatric complications. Laboratory findings include grossly elevated plasma total homocysteine and mildly to grossly elevated blood methionine, which is analysed in neonatal screening. CBS binds three cofactors: pyridoxal‐5′‐phosphate, an allosteric activatorS‐adenosylmethionine and haem with as‐yet‐unresolved function. In theCBSgene, more than 160 different mutations have been described to date. Most of the mutations are missense yielding misfolded enzymes, which can potentially be rescued by chaperones. CBS deficiency is efficiently treated by combination of large doses of pyridoxine, methionine‐restricted diet and betaine; experimental enzyme replacement therapy is efficient in mouse models of disease.

Key Concepts

Cystathionine β‐synthase catalyses the first step in the transsulfuration of homocysteine to cysteine, and also synthesis of hydrogen sulfide from cysteine.

Cystathionine β‐synthase is a modular enzyme composed of a haem‐bindingN‐terminal domain, the active core with pyridoxal‐5′‐phosphate involved in catalysis and theC‐terminal autoinhibitory domain, which bindsS‐adenosylmethionine.

More than 160 different pathogenic mutations have been described in theCBSgene, almost 90% of all mutantCBSalleles carry missense mutations.

Mutant CBS subunits often misfold, and their conformation and activity may be rescued by chaperones.

Deficient CBS activity leads to gross elevation of plasma total homocysteine, often to elevated blood methionine levels, and decreased blood cystathionine.

Phenotypic consequences of mutations in theCbsgene include thromboembolism and vascular occlusion, which is accompanied in severe forms of the disease by lens dislocation, marfanoid features, osteoporosis and neuropsychiatric involvement.

CBS deficiency can be managed by administration of pyridoxine, low‐methionine diet and betaine; treatment is efficient when started early after birth.

Population frequency of patients with CBS deficiency ascertained clinically and by newborn screening is one to two orders of magnitude lower than the frequency calculated from the prevalence of heterozygotes for pathogenic mutations; this observation indicates an ascertainment bias or lack of symptoms in many CBS‐deficient individuals.

Various murine models of CBS deficiency recapitulate the organ involvement observed in human patients, and experimental enzyme replacement therapy corrects efficiently these complications.
The Origin of the
A
cheulian
Authors: Domínguez‐Rodrigo Manuel
Published: June 2018

Current evidence shows that the origin of the Acheulian dates back to at least 1.7 Ma in Africa. Although only three sites exist before 1.5 Ma, this complex technology seems to coexist for substantial time with small core and flake tools, typical of the Oldowan. While animal butchery has been widely documented at Oldowan sites, this activity remains marginal at Acheulian sites. There is a wide diversity of predominant tool types at Acheulian sites. This, together with spatial and palaeoecological patterning, is suggestive of a diversity of activities carried out at these sites according to ecological location. Acheulian sites are bigger than Oldowan sites, but their functions remain unknown. The complexity of the Acheulian has been exhaustively studied from a technological perspective, but not so much from a behavioural point of view. Understanding what activities were carried out at Acheulian sites is crucial to understand this crucial phase of the evolution of
Homo erectus/ergaster
.

Key Concepts

The Acheulian is the oldest human complex technology.

It consists of large intentionally shaped tools.

The Acheulian emerges 1.7 Ma.

The oldest symmetrical bifacial handaxes show that complex neurophysiology existed at the beginning of the Acheulian.

The diversity of tools and reduction sequences at Acheulian sites show that hominins had complex behaviours and adaptations in the early Pleistocene.
Combined transcranial magnetic stimulation in the treatment of chronic tinnitus
Authors: Formánek Martin , Migaľová Petra , Krulová Petra , Bar Michal , Jančatová Debora , Zakopčanová‐Srovnalová Hana , Tomášková Hana , Zeleník Karol , Komínek Pavel
Published: June 2018

Objective

Repetitive transcranial magnetic stimulation (rTMS) is currently being tested for suppressing the symptoms of subjective chronic primary tinnitus, although its effect is controversial. The aim of this randomized double‐blinded controlled trial was to determine the effect of rTMS with unique settings for tinnitus treatment.

Methods

Fifty‐three adult patients suffering from chronic subjective unilateral or bilateral nonpulsatile primary tinnitus for at least 6 months were randomly assigned to rTMS (group 1, n = 20), sham stimulation (group 2, n = 12), or medicament therapy only (group 3, n = 21). The dorsolateral prefrontal cortex (frequency 25 Hz, 300 pulses, and 80% resting motor threshold [RMT]) on the left side and primary auditory cortex (1 Hz, 1000 pulses, 110% RMT) were stimulated on both sides in patients in group 1 for 5 consecutive days. The Tinnitus Reaction Questionnaire (TRQ), Tinnitus Handicap Questionnaire (THQ), Tinnitus Handicap Inventory (THI), Beck Depression Inventory (BDI), pure‐tone audiometry with Fowler scoring of hearing loss, and tinnitus analysis were used to evaluate tinnitus in all patients. Data were recorded the day the patient was included in the study and at 1‐ and 6‐month follow‐up.

Results

The study groups were homogenous. No significant effect of rTMS was found at 1 or 6 months based on the BDI, THQ, and TRQ scores or tinnitus masking. There was a significant but clinically irrelevant effect on the THI score after 1 and 6 months.

Interpretation

No significant effect of bilateral low‐frequency rTMS of the primary auditory cortex and high‐frequency stimulation of the left dorsolateral prefrontal cortex was demonstrated.
Using automated electrode localization to guide stimulation management in DBS
Authors: Petersen Mikkel V. , Husch Andreas , Parsons Christine E. , Lund Torben E. , Sunde Niels , Østergaard Karen
Published: June 2018

Deep Brain Stimulation requires extensive postoperative testing of stimulation parameters to achieve optimal outcomes. Testing is typically not guided by neuroanatomical information on electrode contact locations. To address this, we present an automated reconstruction of electrode locations relative to the treatment target, the subthalamic nucleus, comparing different targeting methods: atlas‐, manual‐, or tractography‐based subthalamic nucleus segmentation. We found that most electrode contacts chosen to deliver stimulation were closest or second closest to the atlas‐based subthalamic nucleus target. We suggest that information on each electrode contact's location, which can be obtained using atlas‐based methods, might guide clinicians during postoperative stimulation testing.
Lateral‐Polarity Structure of AlGaN Quantum Wells: A Promising Approach to Enhancing the Ultraviolet Luminescence
Authors: Guo Wei , Sun Haiding , Torre Bruno , Li Junmei , Sheikhi Moheb , Jiang Jiean , Li Hongwei , Guo Shiping , Li Kuang‐Hui , Lin Ronghui , Giugni Andrea , Di Fabrizio Enzo , Li Xiaohang , Ye Jichun
Published: June 2018

Aluminum‐gallium‐nitride alloys (Al
x
Ga1–

x
N, 0 ≤ x ≤ 1) can emit light covering the ultraviolet spectrum from 210 to 360 nm. However, these emitters have not fulfilled their full promise to replace the toxic and fragile mercury UV lamps due to their low efficiencies. This study demonstrates a promising approach to enhancing the luminescence efficiency of AlGaN multiple quantum wells (MQWs) via the introduction of a lateral‐polarity structure (LPS) comprising both III and N‐polar domains. The enhanced luminescence in LPS is attributed to the surface roughening, and compositional inhomogeneities in the N‐polar domain. The space‐resolved internal quantum efficiency (IQE) mapping shows a higher relative IQE in N‐polar domains and near inversion domain boundaries, providing strong evidence of enhanced radiative recombination efficiency in the LPS. These experimental observations are in good agreement with the theoretical calculations, where both lateral and vertical band diagrams are investigated. This work suggests that the introduction of the LPS in AlGaN‐based MQWs can provide unprecedented tunability in achieving higher luminescence performance in the development of solid state light sources.
3D‐Printed, Superelastic Polypyrrole–Graphene Electrodes with Ultrahigh Areal Capacitance for Electrochemical Energy Storage
Authors: Qi Zhen , Ye Jianchao , Chen Wen , Biener Juergen , Duoss Eric B. , Spadaccini Christopher M. , Worsley Marcus A. , Zhu Cheng
Published: June 2018

Disruptive custom electronics require a transformation in energy storage systems from traditional thin‐film units to shape conformable 3D components. However, current thick electrodes suffer from uncontrollable geometries and architectures, which lead to ion diffusion limitations, and poor mechanical properties. Here, designed, superelastic polypyrrole (PPy)‐coated graphene aerogel (GA) electrodes are fabricated via 3D printing and polymer self‐assembly methods. This resilient GA template (up to 90% compression) can be printed into any desired shape including engineered 3D architectures with periodic macropores, which promote the uniform deposition and adhesion of PPy onto the support. The coated PPy thin film increases the specific gravimetric capacitance of the GA electrode from 14 to 395 F g−1 with 90% retention after 5000 charging–discharging cycles. The capacitance remains the same value after 100 times compression cycles. It also improves the compressive strength by one order of magnitude from 0.14 to 2.4 MPa. Areal capacitance and energy density of the PPy–GA electrode are 2 F cm−2 and 0.78 mWh cm−2, respectively, which to the best of the knowledge break the record for compressible electrodes, respectively. This approach enables the fabrication of complex architectured energy storage modules with enhanced compressibility, ultrahigh areal electrochemical performance, and excellent cyclability.
Rapid Response Fluorescence Probe Enabled In Vivo Diagnosis and Assessing Treatment Response of Hypochlorous Acid‐Mediated Rheumatoid Arthritis
Authors: Feng Huan , Zhang Zhiqiang , Meng Qingtao , Jia Hongmin , Wang Yue , Zhang Run
Published: June 2018

Diagnosis and early assessment of the treatment response of rheumatoid arthritis (RA) necessitates a reliable bioanalytical method for rapid, sensitive, and specific detection of the hypochlorous acid (HOCl) biomarker in inflammatory diseases. Herein, two fluorescence probes, Probe‐1 and Probe‐2 are developed for quantitative monitoring and visualization of inflammatory response–related HOCl levels in vitro and in vivo. In the presence of HOCl, fluorescence “OFF–ON” response is obtained for both the probes as a result of specific HOCl‐triggered CN bond cleavage reaction. Probe‐1 and Probe‐2 feature rapid response (<4 s), a high degree of sensitivity and selectivity toward HOCl, which allow them to be used for quantification of HOCl in a simulated physiological condition. Using Probe‐2 as the probe, fluorescence imaging and flow cytometry analysis of HOCl levels in lysosome of inflammatory mimic cells, visualization of HOCl generation in endotoxin‐induced inflammation of adult zebrafish and RA of mice are possible. Probe‐2 exhibits high effectiveness for early assessment of the treatment response of HOCl‐mediated RA in mice with an antiarthritic drug, methotrexate (MTX). The results demonstrate that Probe‐2 is a powerful tool for future studies on diagnosis and monitoring treatment efficiency in a broad range of inflammatory diseases, including RA.
One‐Pot Gram‐Scale, Eco‐Friendly, and Cost‐Effective Synthesis of CuGaS2/ZnS Nanocrystals as Efficient UV‐Harvesting Down‐Converter for Photovoltaics
Authors: Jalalah Mohammed , Al‐Assiri M. S. , Park Jea‐Gun
Published: June 2018

It is presented for the first time nontoxic CuGaS2/ZnS quantum dots (QDs) with free‐self‐reabsorption losses and large Stokes shift (>190 nm) synthesized on an industrially gram‐scale as an alternative for Cd‐based energy‐downshift (EDS)‐QD layers. The QDs exhibit a typical EDS that absorbs only UV light (<407 nm) and emits the whole range of visible light (400–800 nm) with a high photoluminescence‐quantum yield of ≈76%. The straightforward application of these EDS‐QDs on the front surface of a monocrystalline p‐type silicon solar cell significantly enhances the short‐circuit current density by ≈1.64 mA cm−2 (+4.20%); thereby, improving the power‐conversion‐efficiency by ≈4.11%. The significant improvement in the external quantum efficiency increases by ≈35.7% and that in the surface reflectance decreases by ≈14.1% in the UV region (300–450 nm) clearly manifest the photovoltaic enhancement. Such promising results together with the simple (one‐pot core/shell synthesis), cost‐effective (reduction in a bill of material–system by ≈2.62%), and scalable (2000 mL three‐neck flask, 11 g of QDs) preparation process might encourage the manufacturers of solar cells and other optoelectronic applications to apply these EDS‐QDs to different broader eco‐friendly applications.
Implementation of genomic medicine for gastrointestinal tumors
Authors: Furukawa Yoichi
Published: June 2018

Genomic medicine is an approach to take advantage of genomic data in medical practice and health care. The advancement of sequencing technologies has enabled the determination of individual genomes as well as the genome in neoplasms. In the field of human cancer, understanding genomic alterations in tumors and variations associated with drug responses has paved the way towards the development of new drugs and personalized medicine. International collaborations of cancer genome analyses have accumulated a huge body of information about somatic mutations, and identified new driver mutations and pathways in a wide range of cancers. In particular, a growing body of evidence has shown that information about mutations in neoplasms helps to assess the efficacy and resistance of anti‐cancer drugs. Information about germline mutations associated with hereditary cancer has been shown to benefit patients by enabling early detection of their tumors and disease‐specific treatment, as well as reducing the risk for those at risk. To promote personalized medicine in a more cost‐effective and personalized way, further inter‐institutional, nationwide, and international collaboration is needed. This article summarizes the background and current situation of genomic medicine in the field of gastrointestinal tumors to help physicians and medical coworkers by assisting their better understanding of genomic medicine and strengthening their confidence of its clinical use.
Team Science, Justice, and the Co‐Production of Knowledge
Authors: Tebes Jacob Kraemer
Published: June 2018

Science increasingly consists of interdisciplinary team‐based research to address complex social, biomedical, public health, and global challenges through a practice known as team science. In this article, I discuss the added value of team science, including participatory team science, for generating scientific knowledge. Participatory team science involves the inclusion of public stakeholders on science teams as co‐producers of knowledge. I also discuss how constructivism offers a common philosophical foundation for both community psychology and team science, and how this foundation aligns well with contemporary developments in science that emphasize the co‐production of knowledge. I conclude with a discussion of how the co‐production of knowledge in team science can promote justice.
Nature Inspired Molecular Design: Stereoselective Synthesis of Bicyclic and Polycyclic Ethers for Potent HIV‐1 Protease Inhibitors
Authors: Ghosh Arun K. , Brindisi Margherita
Published: June 2018

We have developed a conceptually new generation of non‐peptidic HIV‐1 protease inhibitors incorporating novel structural templates inspired by nature. This has resulted in protease inhibitors with exceptional potency and excellent pharmacological and drug‐resistance profiles. The design of a stereochemically defined bis‐tetrahydrofuran (bis‐THF) scaffold followed by modifications to promote hydrogen bonding interactions with the backbone atoms of HIV‐1 protease led to darunavir, the first clinically approved drug for treatment of drug resistant HIV. Subsequent X‐ray crystal structure‐based design efforts led us to create a range of exceptionally potent inhibitors incorporating other intriguing molecular templates possessing fused ring polycyclic ethers with multiple stereocenters. These structural templates are critical to inhibitors’ exceptional potency and drug‐like properties. Herein, we will highlight the synthetic strategies that provided access to these complex scaffolds in a stereoselective and optically active form, enabling our medicinal chemistry and drug development efforts.
Metal‐Free [3+2]‐Cycloaddition of Thiiranes with Isothiocyanates, Isoselenocyanates and Carbodiimides: Synthesis of 2‐Imino‐Dithiolane/Thiaselenolane/Thiazolidines
Authors: Satheesh Vanaparthi , Kumar Sundaravel Vivek , Vijay Murugan , Barik Debashis , Punniyamurthy Tharmalingam
Published: June 2018

Metal‐free regioselective [3+2]‐cycloaddition of 2‐aryl/alkylthiiranes with isothiocyanates, isoselenocyanates and carbodiimides is developed using BF2OTf⋅OEt2 to produce 2‐imino‐dithiolane/‐thiaselenolane/‐thiazolidine frameworks at room temperature. The selectivity, substrate scope and scale up are the important practical features.
Rhodium(II)‐Catalyzed C−H Bond Carboxylation of Heteroarenes with CO2
Authors: Huang Raolin , Li Shangda , Fu Lei , Li Gang
Published: June 2018

A method of RhII‐catalyzed C−H carboxylation of 2‐(imidazo[1,2‐a]pyridin‐2‐yl)phenols via CO2 fixation under redox‐neutral conditions was reported, providing an access to a range of coumarin derivatives. A suitable diphosphine ligand was crucial for this reaction. This reaction could be performed under relatively lower temperature or in a shorter time than the alternative base‐promoted protocol.