bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Technology to Enhance the Student Experience in Large Cohort Settings: Evidence from a Journey of Innovation at the University of Manchester
Authors: Middleditch Paul , Moindrot William
Published: November 2015

The use of large cohorts in higher education poses significant challenges to institutions and lecturers required to convene in this setting. These challenges have been compounded by recent changes to higher education in the UK that have presented themselves in the form of a new fees structure, a push for student satisfaction and a technological tidal wave. This paper presents innovative approaches, from two large cohort economics courses running over three years at the University of Manchester, using methods of classroom interaction, peer instruction and social media to further engagement. We discuss data collected during this period of time through surveys and observations of how the students used these new learning tools. We have found that a move away from clickers toward utilisation of students’ own mobile devices, and in time the use of social media, meant that we were more able to adapt and evolve our teaching methods at a pace with the needs and interests of our students. We use this evidence to consider the implications and to provide advice to others teaching on large cohort courses whose ambition, like ours, is to make the large cohort class a more positive experience.
A Window to the World: Using Technology to Internationalise Entrepreneurship Education
Authors: McKinnon Sabine , Smith Anne MJ , Thomson Julie C
Published: November 2015

The discourse about internationalising higher education has often been dominated by discussions about the needs of international students in a UK classroom. These students have already taken the first step towards improving their international awareness and are still a minority in our classrooms. What about the vast majority of our home students who are often local and have not had the opportunity to study abroad? Given that the uptake of physical mobility schemes is still low in the UK using technology to connect students with their peers in other countries offers a cost effective way of enhancing their cultural awareness. This paper presents the results of a pilot study in entrepreneurship education which used the COIL (Collaborative Online International Learning) approach to internationalisation at home. Students at Glasgow Caledonian University (GCU) worked in teams with their peers at a Japanese institution using a Wiki, Skype and Facebook. During their six-week collaboration the Scottish students were monitored for their perceptions of their own intercultural sensitivity and their understanding of innovation and entrepreneurship in Japan and Scotland. Drawing on the results from an online evaluation survey this study makes a contribution to the pedagogical debate in entrepreneurship education which has not always paid sufficient attention to the relevance of intercultural skills in entrepreneurial activity. The data shows that students increased their awareness of the demands of cross-cultural team-working and improved their knowledge of entrepreneurship, innovation and trade across nations. On a more general note, this paper also reflects on the benefits and challenges for academic staff who collaborate with colleagues across national borders using internet based tools.
Comparison of the organization of teaching-learning process by different occupational seniority science teachers
Authors: Lal İzzet , Sarı Mediha
Published: November 2015

The aim of this study is to examine regulation of priority in the different teaching-learning process of science teachers format. Nine science teachers attendant in state schools with similar properties in Aksaray, constitute the working group's research. The data obtained through observation and interviews were analyzed descriptively. According to the results of teachers findings related to the preparation before the course examined three categories including content, learning environment, findings for students of different levels. All three groups of teachers said that they had made several preparations under this category before the course. The activities that took place in the introduction of class by teacher were examined in the form of reminders, class teacher attention, motivation, to notify the target and prerequisite information and it was determined that several variations based on priority in that category. According to the findings relating to the course of teacher workings, question-answer and lectures were used in three groups. The most diverse materials and teaching methods and techniques in the course belongs to teachers with priority between 11-20 years. While the priority of teachers increases student participation in the course decreases. 1-10 years from associating with everyday life; between the main and sub-points highlighting 11-20 years; making summaries are 21 and older teachers with seniority they left missing in the course of those points.
The production context of the Zeng State bronzes from Yejiashan Cemetery of the Western Zhou Dynasty
Authors: Zhang Changping
Published: November 2015

In 2011 and 2013, 65 Western Zhou tombs of the Zeng State were excavated at the Yejiashan Cemetery in Suizhou City, Hubei Province. Among them, M1, M28 and M27 and M65 and M2 are the tombs of the earliest three generations of rulers and spouses of the early Western Zhou Dynasty. The bronzes unearthed from the Yejiashan Cemetery exhibit not only the characteristics of the common Western Zhou style in typological morphology and assemblage, but also local features reflecting local production. In the technical sense, the bronzes from the Yejiashan Cemetery bear special traits in modeling and molding details: some are of the style other than that of the Zhou, and others are imitations of the same type of bronzes. The characteristics of the bronzes of the Zeng State indicate that in the early Western Zhou Dynasty, the Zeng State has the capability of producing bronzes as it does during the transitional period from the Western Zhou through the Eastern Zhou Period.
Lust, die glücklich macht
Authors: Espinet David
Published: November 2015

Against the still prevalent assumption according to which Kant’s moral philosophy does not, at least for sensuous rational agents, provide a satisfactory answer to the problem posed by their need of happiness, the present paper develops the following argument: The subject must be able to interrupt her pursuit of happiness - precisely in order not to game away her happiness. Within the horizon of Kant’s doctrine of moral incentives as well as in a secular reading of his conception of the highest good, one can see, first, that the possibility of a morally motivated interruption of the pursuit of happiness is a necessary condition precisely for the happiness of finite but rational agents; second, that sensuous satisfaction must be understood as an integrative component of the highest good and, as such, as a second necessary condition for happiness. Kant’s notion of the highest good, thus, conceptualizes the coincidence of virtue and lust as a sufficient condition of happiness, by which a morally mediated lust becomes possible that not only provides sensuous satisfaction, but also makes us happy.
The Structural Device of “Unsuccessful Repetition” in Two Ancient Greek Healing Narratives
Authors: Fariñas Óscar M. Bernao
Published: November 2015

Since the turn of the nineteenth into the twentieth century scholars have underscored the similarities between two ancient Greek healing accounts of miraculous cures ascribed to Asclepius, the Greek god of Medicine, and some modern narratives related to the international folktale known as ATU 753 A: Unsuccessful Repetition. This study analyses the narrative structure of these accounts in order to reassess the similarities pointed out by earlier researchers and also enquires into some compositional aspects of one of these narratives.
Involvement of loop 5 lysine residues and the N-terminal β-hairpin of the ribotoxin hirsutellin A on its insecticidal activity
Authors: Olombrada Miriam , García-Ortega Lucía , Lacadena Javier , Oñaderra Mercedes , Gavilanes José G. , Martínez-del-Pozo Álvaro
Published: November 2015

Ribotoxins are cytotoxic members of the family of fungal extracellular ribonucleases best represented by RNase T1. They share a high degree of sequence identity and a common structural fold, including the geometric arrangement of their active sites. However, ribotoxins are larger, with a well-defined N-terminal β-hairpin, and display longer and positively charged unstructured loops. These structural differences account for their cytotoxic properties. Unexpectedly, the discovery of hirsutellin A (HtA), a ribotoxin produced by the invertebrate pathogenHirsutella thompsonii, showed how it was possible to accommodate these features into a shorter amino acid sequence. Examination of HtA N-terminal β-hairpin reveals differences in terms of length, charge, and spatial distribution. Consequently, four different HtA mutants were prepared and characterized. One of them was the result of deleting this hairpin [Δ(8-15)] while the other three affected single Lys residues in its close spatial proximity (K115E, K118E, and K123E). The results obtained support the general conclusion that HtA active site would show a high degree of plasticity, being able to accommodate electrostatic and structural changes not suitable for the other previously known larger ribotoxins, as the variants described here only presented small differences in terms of ribonucleolytic activity and cytotoxicity against cultured insect cells.
Grautöne: Verleger und Zensurregime in Mitteleuropa 1800–1850
Authors: Brophy James M.
Published: November 2015

Das Ausmaß der staatlichen Intervention in Deutschlands Öffentlichkeit im frühen 19. Jahrhundert war erheblich. Die Korrespondenzen, Tagebücher oder andere Egodokumente der Intellektuellen geben dem Historiker eine Fülle von vorzüglichem Quellenmaterial an die Hand, um deren Rhetorik und Kritik herauszuarbeiten. Allerdings verblasst hinter jenen Textquellen die erstaunliche Leistung der Verleger, diese Texte als Drucke zu publizieren und zu verbreiten. Dieser Beitrag lenkt nun den Fokus auf jene Verleger und deren Auseinandersetzung mit der Zensur und modifiziert dabei die herkömmliche Interpretation. Anhand von Fallstudien aus Preußen, Sachsen und dem Deutschen Bund bildet die Studie den Umgang deutscher Verleger mit der Zensur ab, deren Aufgabe in einer sogenannten „Torhüterfunktion“ für eine staatlich sanktionierte Öffentlichkeit bestand. Trotz mancherlei Rückschlägen trugen die Verleger dazu bei, die neoabsolutistisch geprägte politische Öffentlichkeit aufzubrechen und eine neue, diskursive Qualität der politischen Kommunikation zu erreichen. Dabei verschafften die Dynamik einer liberalen Marktwirtschaft sowie das bürgerliche Rechtssystem, das Bücher als Ware und Privateigentum schützte, den Verlegern gewisse strategische Vorteile. Darüber hinaus gab es durchaus auch Zensoren, die mit Verlegern und Autoren mehr oder weniger informell kooperierten, um kontroverse Texte zu verlegen. Wenn man die auf diesem Wege erzielte beachtliche Verbreitung verbotener Schriften berücksichtigt, muss die Wirkung staatlicher Kontrolle neu eingeschätzt werden. Auf dieser revidierten Grundlage können somit auch der Transfer und die Verflechtung politischer Kompetenzen in West- und Mitteleuropa besser eingeordnet werden.
Un manuscrit mesconnëu de l’Estoire del Saint Graal: Bourg-en-Bresse, Médiathèque Vailland 55. Le programme paratextuel
Authors: Chase Carol J.
Published: November 2015

Bourg-en-Bresse, Médiathèque Vailland MS 55, which contains a copy of the Estoire del Saint Graal dated in the 1330s, is not very well known, for two reasons. First, the version of the text that it conserves is mixed; second, the codex is mutilated. Nevertheless, this witness deserves our attention, because a number of the rubrics have survived, as have some of the miniatures. The latter were realized by an artist working in Paris, known as the Master of the Vies de Saint Louis, or Mahiet. This article has a double goal: to present the manuscript and to study the rubrics and miniatures in order to explore their role and their relationship with the text and with other codices containing the Estoire del Saint Graal. A description of the manuscript is followed by a study of the paratextual programme; the article concludes with a section on the manuscript tradition.
The case of the ‘curious document’: Thomas Malory, William Matthews and Eugène Vinaver
Authors: Rayner Samantha
Published: November 2015

This article looks at the publication history of Eugène Vinaver’s Works of Sir Thomas Malory, examining letters and documents located in the Oxford University Press archive and exploring the part that correspondence between William Matthews and Press representatives played in the production of the Second Edition of 1967. These correspondences also expose new contexts for what has come to be known as ‘the Malory Debate’, after a book of the same name edited by Bonnie Wheeler, Robert L. Kindrick and Michael N. Salda (Cambridge: Brewer, 2000). The article uses the cultural production theories of Pierre Bourdieu to emphasise the important, but often hidden, part that publishers play in the development of scholarly texts and debates, helping to shape disciplinary fields and ensure a rigorous framework within which they can evolve and mature.
Learning the Condition of Satisfaction of an Elementary Behavior in Dynamic Field Theory
Authors: Luciw Matthew , Kazerounian Sohrob , Lahkman Konstantin , Richter Mathis , Sandamirskaya Yulia
Published: November 2015

In order to proceed along an action sequence, an autonomous agent has to recognize that the intended final condition of the previous action has been achieved. In previous work, we have shown how a sequence of actions can be generated by an embodied agent using a neural-dynamic architecture for behavioral organization, in which each action has an intention and condition of satisfaction. These components are represented by dynamic neural fields, and are coupled to motors and sensors of the robotic agent.Here,we demonstratehowthemappings between intended actions and their resulting conditions may be learned, rather than pre-wired.We use reward-gated associative learning, in which, over many instances of externally validated goal achievement, the conditions that are expected to result with goal achievement are learned. After learning, the external reward is not needed to recognize that the expected outcome has been achieved. This method was implemented, using dynamic neural fields, and tested on a real-world E-Puck mobile robot and a simulated NAO humanoid robot.
Functional Deficiencies in Fragile X Neurons Derived from Human Embryonic Stem Cells
Authors: Telias Michael , Kuznitsov-Yanovsky Liron , Segal Menahem , Ben-Yosef Dalit
Published: November 2015

Fragile X syndrome (FXS), the most common form of inherited mental retardation, is a neurodevelopmental disorder caused by silencing of the FMR1 gene, which in FXS becomes inactivated during human embryonic development. We have shown recently that this process is recapitulated byin vitroneural differentiation of FX human embryonic stem cells (FX-hESCs), derived from FXS blastocysts. In the present study, we analyzed morphological and functional properties of neurons generated from FX-hESCs. Human FX neurons can fire single action potentials (APs) to depolarizing current commands, but are unable to discharge trains of APs. Their APs are of a reduced amplitudes and longer durations than controls. These are reflected in reduced inward Na+and outward K+currents. In addition, human FX neurons contain fewer synaptic vesicles and lack spontaneous synaptic activity. Notably, synaptic activity in these neurons can be restored by coculturing them with normal rat hippocampal neurons, demonstrating a critical role for synaptic mechanisms in FXS pathology. This is the first extensive functional analysis of human FX neurons derivedin vitrofrom hESCs that provides a convenient tool for studying molecular mechanisms underlying the impaired neuronal functions in FXS.

SIGNIFICANCE STATEMENTFragile X syndrome (FXS), the most common form of inherited mental retardation, is caused by silencing of the FMR1 gene. In this study, we describe for the first time the properties of neurons developed from human embryonic stem cells (hESCs) that carry the FMR1 mutation and are grown in culture for extended periods. These neurons are retarded compared with controls in several morphological and functional properties.In vitroneural differentiation of FX hESCs can thus serve as a most relevant system for the analysis of molecular mechanisms underlying the impaired neuronal functions in FXS.
Head-Directional Tuning and Theta Modulation of Anatomically Identified Neurons in the Presubiculum
Authors: Tukker John J. , Tang Qiusong , Burgalossi Andrea , Brecht Michael
Published: November 2015

The presubiculum provides a major input to the medial entorhinal cortex (MEC) and contains cells that encode for the animal's head direction (HD), as well as other cells likely to be important for navigation and memory, including grid cells. To understand the mechanisms underlying HD cell firing and its effects on other parts of the circuit, it is important to determine the anatomical identity of these functionally defined cells. Therefore, we juxtacellularly recorded single cells in the presubiculum in freely moving rats, finding two classes of cells based on firing patterns and juxtacellular labeling (of a subset). Regular-firing cells had the anatomical characteristics of pyramidal cells and included most recorded HD cells. Therefore, HD cells are likely to be excitatory pyramidal cells. For one HD cell, we could follow an axon projecting directly to the MEC. Fast-spiking (FS) cells had the anatomical characteristics of interneurons and displayed weak HD tuning. Furthermore, FS cells displayed a surprising lack of theta-rhythmic firing, in strong contrast to the FS cells that we recorded in the MEC. Overall, we show that HD cells in the presubiculum are pyramidal cells, with FS interneurons only showing weak HD tuning; therefore, MEC may receive an excitatory HD input, as previously assumed by many models. The lack of theta rhythmicity in FS interneurons suggests that different mechanisms may underlie theta in different parts of the hippocampal formation.

SIGNIFICANCE STATEMENTIn freely moving rats, we recorded and labeled single neurons in the presubiculum, an area providing one of the major inputs to the medial entorhinal cortex and part of a network involved in spatial navigation and memory.Post hocidentification of labeled cells showed that (fast-spiking, FS) interneurons and pyramidal cells in the presubiculum can be distinguished based on physiological criteria. We found that both moderately and strongly tuned head-direction (HD) cells are pyramidal cells and therefore likely to provide an excitatory HD input to the entorhinal cortex. FS interneurons were weakly head directional and, surprisingly, showed no theta-rhythmic firing. Therefore, the presubiculum appears to encode HD information via excitatory pyramidal cells, possibly also involving FS interneurons, without using a theta-rhythmic temporal code.
Astroglial Connexin 43 Hemichannels Modulate Olfactory Bulb Slow Oscillations
Authors: Roux Lisa , Madar Antoine , Lacroix Marie Masako , Yi Chenju , Benchenane Karim , Giaume Christian
Published: November 2015

An emergent concept in neurosciences consists in considering brain functions as the product of dynamic interactions between neurons and glial cells, particularly astrocytes. Although the role played by astrocytes in synaptic transmission and plasticity is now largely documented, their contribution to neuronal network activity is only beginning to be appreciated. In mouse olfactory bulb slices, we observed that the membrane potential of mitral cells oscillates between UP and DOWN states at a low frequency (<1 Hz). Such slow oscillations are correlated with glomerular local field potentials, indicating spontaneous local network activity. Using a combination of genetic and pharmacological tools, we showed that the activity of astroglial connexin 43 hemichannels, opened in an activity-dependent manner, increases UP state amplitude and impacts mitral cell firing rate. This effect requires functional adenosine A1 receptors, in line with the observation that ATP is released via connexin 43 hemichannels. These results highlight a new mechanism of neuroglial interaction in the olfactory bulb, where astrocyte connexin hemichannels are both targets and modulators of neuronal circuit function.

SIGNIFICANCE STATEMENTAn emergent concept in neuroscience consists in considering brain function as the product of dynamic interactions between neurons and glial cells, particularly astrocytes. A typical feature of astrocytes is their high expression level of connexins, the molecular constituents of gap junction channels and hemichannels. Although hemichannels represent a powerful medium for intercellular communication between astrocytes and neurons, their function in physiological conditions remains largely unexplored. Our results show that in the olfactory bulb, connexin 43 hemichannel function is promoted by neuronal activity and, in turn, modulates neuronal network slow oscillations. This novel mechanism of neuroglial interaction could influence olfactory information processing by directly impacting the output of the olfactory bulb.
Layer-Specific fMRI Responses to Excitatory and Inhibitory Neuronal Activities in the Olfactory Bulb
Authors: Poplawsky Alexander John , Fukuda Mitsuhiro , Murphy Matthew , Kim Seong-Gi
Published: November 2015

High-resolution functional magnetic resonance imaging (fMRI) detects localized neuronal activity via the hemodynamic response, but it is unclear whether it accurately identifies neuronal activity specific to individual layers. To address this issue, we preferentially evoked neuronal activity in superficial, middle, and deep layers of the rat olfactory bulb: the glomerular layer by odor (5% amyl acetate), the external plexiform layer by electrical stimulation of the lateral olfactory tract (LOT), and the granule cell layer by electrical stimulation of the anterior commissure (AC), respectively. Electrophysiology, laser-Doppler flowmetry of cerebral blood flow (CBF), and blood oxygenation level-dependent (BOLD) and cerebral blood volume-weighted (CBV) fMRI at 9.4 T were performed independently. We found that excitation of inhibitory granule cells by stimulating LOT and AC decreased the spontaneous multi-unit activities of excitatory mitral cells and subsequently increased CBF, CBV, and BOLD signals. Odor stimulation also increased the hemodynamic responses. Furthermore, the greatest CBV fMRI responses were discretely separated into the same layers as the evoked neuronal activities for all three stimuli, whereas BOLD was poorly localized with some exception to the poststimulus undershoot. In addition, the temporal dynamics of the fMRI responses varied depending on the stimulation pathway, even within the same layer. These results indicate that the vasculature is regulated within individual layers and CBV fMRI has a higher fidelity to the evoked neuronal activity compared with BOLD. Our findings are significant for understanding the neuronal origin and spatial specificity of hemodynamic responses, especially for the interpretation of laminar-resolution fMRI.

SIGNIFICANCE STATEMENTFunctional magnetic resonance imaging (fMRI) is a noninvasive,in vivotechnique widely used to map function of the entire brain, including deep structures, in animals and humans. However, it measures neuronal activity indirectly by way of the vascular response. It is currently unclear how finely the hemodynamic response is regulated within single cortical layers and whether increased inhibitory neuronal activities affect fMRI signal changes. Both laminar specificity and the neural origins of fMRI are important to interpret functional maps properly, which we investigated by activating discrete rat olfactory bulb circuits.
Amperometric Monitoring of Sensory-Evoked Dopamine Release in Awake Larval Zebrafish
Authors: Shang Chun-feng , Li Xiao-quan , Yin Chen , Liu Bing , Wang Yu-fan , Zhou Zhuan , Du Jiu-lin
Published: November 2015

Dopamine plays crucial roles in a broad spectrum of brain functions, and neural circuit mechanisms underlying dopaminergic regulation have been intensively studied in the past decade. As larval zebrafish have relatively simple and highly conserved dopaminergic systems, it can serve as an ideal vertebrate animal model to tackle this issue at a whole-brain scale. For this purpose, it is important to develop methods for monitoring endogenous dopamine release in intact larval zebrafish. Here, we developed a real-time method to monitor dopamine release at high spatiotemporal resolution in the brain of awake larval zebrafish using carbon fiber microelectrodes. As an example for application, we combined this method with genetic tools andin vivocalcium imaging and found that food extract can activate pretectal dopaminergic neurons, which in turn release dopamine at the visual center through their projection, providing a dopaminergic circuit mechanism for olfactory modulation of visual functions. Thus, our study demonstrates, for the first time, the utility of carbon fiber microelectrodes for monitoring sensory-evoked dopamine release in the brain of an awake small organism.

SIGNIFICANCE STATEMENTWith carbon fiber microelectrodes, we have succeeded in monitoring sensory-evoked dopamine release in the brain of an awake small organism for the first time. By elucidating the circuitry origin of the dopamine release, we illustrated the potential application of this method in dissection of the neural circuitry mechanisms underlying dopaminergic neuromodulation.
Comprehensive Corticospinal Labeling withmu-crystallinTransgene Reveals Axon Regeneration after Spinal Cord Trauma inngr1−/−Mice
Authors: Fink Kathren L. , Strittmatter Stephen M. , Cafferty William B.J.
Published: November 2015

Spinal cord injury interrupts descending motor tracts and creates persistent functional deficits due to the absence of spontaneous axon regeneration. Of descending pathways, the corticospinal tract (CST) is thought to be the most critical for voluntary function in primates. Even with multiple tracer injections and genetic tools, the CST is visualized to only a minor degree in experimental studies. Here, we identify and validate the mu-crystallin (crym) gene as a high-fidelity marker of the CST. In transgenic mice expressing green fluorescent protein (GFP) undercrymregulatory elements (crym-GFP), comprehensive and near complete CST labeling is achieved throughout the spinal cord. Bilateral pyramidotomy eliminated the 17,000 GFP-positive CST axons that were reproducibly labeled in brainstem from the spinal cord. We show that CST tracing withcrym-GFP is 10-fold more efficient than tracing with biotinylated dextran amine (BDA). Usingcrym-GFP, we reevaluated the CST in mice lacking nogo receptor 1 (NgR1), a protein implicated in limiting neural repair. The number and trajectory of CST axons inngr1−/−mice without injury was indistinguishable fromngr1+/+mice. After dorsal hemisection in the midthoracic cord, CST axons did not significantly regenerate inngr1+/+mice, but an average of 162 of the 6000 labeled thoracic CST axons (2.68%) regenerated >100 μm past the lesion site incrym-GFPngr1−/−mice. Although traditional BDA tracing cannot reliably visualize regeneratingngr1−/−CST axons, their regenerative course is clear withcrym-GFP. Therefore thecrym-GFP transgenic mouse is a useful tool for studies of CST anatomy in experimental studies of motor pathways.

SIGNIFICANCE STATEMENTAxon regeneration fails in the adult CNS, resulting in permanent functional deficits. Traditionally, inefficient extrinsic tracers such a biotinylated dextran amine (BDA) are used to label regenerating fibers after therapeutic intervention. We introducecrym-green fluorescent protein (GFP) transgenic mice as a comprehensive and specific tool with which to study the primary descending motor tract, the corticospinal tract (CST). CST labeling withcrym-GFP is 10 times more efficient compared with BDA. The enhanced sensitivity afforded bycrym-GFP revealed significant CST regeneration in NgR1 knock-out mice. Therefore,crym-GFP can be used as a standardized tool for future CST spinal cord injury studies.
Automatic and Controlled Semantic Retrieval: TMS Reveals Distinct Contributions of Posterior Middle Temporal Gyrus and Angular Gyrus
Authors: Davey James , Cornelissen Piers L. , Thompson Hannah E. , Sonkusare Saurabh , Hallam Glyn , Smallwood Jonathan , Jefferies Elizabeth
Published: November 2015

Semantic retrieval involves both (1) automatic spreading activation between highly related concepts and (2) executive control processes that tailor this activation to suit the current context or goals. Two structures in left temporoparietal cortex, angular gyrus (AG) and posterior middle temporal gyrus (pMTG), are thought to be crucial to semantic retrieval and are often recruited together during semantic tasks; however, they show strikingly different patterns of functional connectivity at rest (coupling with the “default mode network” and “frontoparietal control system,” respectively). Here, transcranial magnetic stimulation (TMS) was used to establish a causal yet dissociable role for these sites in semantic cognition in human volunteers. TMS to AG disrupted thematic judgments particularly when the link between probe and target was strong (e.g., a picture of an Alsatian with a bone), and impaired the identification of objects at a specific but not a superordinate level (for the verbal label “Alsatian” not “animal”). In contrast, TMS to pMTG disrupted thematic judgments for weak but not strong associations (e.g., a picture of an Alsatian with razor wire), and impaired identity matching for both superordinate and specific-level labels. Thus, stimulation to AG interfered with the automatic retrieval of specific concepts from the semantic store while stimulation of pMTG impaired semantic cognition when there was a requirement to flexibly shape conceptual activation in line with the task requirements. These results demonstrate that AG and pMTG make a dissociable contribution to automatic and controlled aspects of semantic retrieval.

SIGNIFICANCE STATEMENTWe demonstrate a novel functional dissociation between the angular gyrus (AG) and posterior middle temporal gyrus (pMTG) in conceptual processing. These sites are often coactivated during neuroimaging studies using semantic tasks, but their individual contributions are unclear. Using transcranial magnetic stimulation and tasks designed to assess different aspects of semantics (item identity and thematic matching), we tested two alternative theoretical accounts. Neither site showed the pattern expected for a “thematic hub” (i.e., a site storing associations between concepts) since stimulation disrupted both tasks. Instead, the data indicated that pMTG contributes to the controlled retrieval of conceptual knowledge, while AG is critical for the efficient automatic retrieval of specific semantic information.
Bridging progestogens in pregnancy and pregnancy prevention
Authors: Micks Elizabeth , Raglan Greta B , Schulkin Jay
Published: November 2015

Steroid hormones have been in use for more than a half a century as contraceptive agents, and only now are researchers elucidating the biochemical mechanisms of action and non-target effects. Progesterone and synthetic progestins, critical for women's health in the US and internationally, appear to have important effects on immune functioning and other diverse systems. Apart from the contraceptive world is a separate field that is devoted to understanding progesterone in other contexts. Based on research following a development timeline parallel to hormonal contraception, progesterone and 17-hydroxyprogesterone caproate are now administered to prevent preterm birth in high-risk pregnant women. Preterm birth researchers are similarly working to determine the precise biochemical actions and immunological effects of progesterone. Progesterone research in both areas could benefit from increased collaboration and bringing these two bodies of literature together. Progesterone, through actions on various hormone receptors, has lifelong importance in different organ systems and researchers have much to learn about this molecule from the combination of existing literatures, and from future studies that build on this combined knowledge base.
Palliative treatment of uncontrollable hypercalcemia due to parathyrotoxicosis: denosumab as rescue therapy
Authors: von Schwartzenberg Reiner Jumpertz , Elbelt Ulf , Ventz Manfred , Mai Knut , Kienitz Tina , Maurer Lukas , Rose Thomas , Rückert Jens C , Strasburger Christian J , Spranger Joachim
Published: November 2015

Parathyroid carcinoma is a rare disease leading to severe hypercalcemia due to hyperparathyroidism. Surgery is the primary treatment option. A more progressive form of the disease is characterized by parathyrotoxicosis, and subsequent hypercalcemia is the most common cause of death. We report a case presenting with severe hypercalcemia due to parathyrotoxicosis from parathyroid carcinoma treated for the first time using the monoclonal antibody denosumab as a rescue therapy and present long-term follow-up data. The 71-year-old patient presented with severe hypercalcemia due to metastatic parathyroid carcinoma. Despite undergoing treatment with bisphosphonates, cinacalcet hydrochloride, and forced diuresis, the patient`s condition deteriorated rapidly due to resistant hypercalcemia. Surgery performed because of spinal metastasis and forced diuresis lowered calcium levels, albeit they remained in the hypercalcemic range and significantly increased when forced diuresis was stopped. Considering a palliative situation to overcome hypercalcemia, we decided to administer denosumab, a monoclonal antibody that binds to the receptor activator of nuclear factor-kappa B ligand. After a single subcutaneous administration of 60 mg denosumab, calcium levels normalized within one day. Subsequent denosumab injections led to permanent control of serum calcium for more than 2 years despite rising parathyroid hormone levels and repeated surgeries. Together with recent cases in the literature supporting our observation, we believe that denosumab is relevant for future trials and represents an effective tool to control hypercalcemia in patients with advanced stages of parathyroid cancer.

Learning points

Severe hypercalcemia is the most common cause of death in patients with parathyroid carcinoma.

The monoclonal antibody denosumab rapidly lowered severely elevated serum calcium levels due to parathyrotoxicosis.

Denosumab was effective in the long-term treatment of hypercalcemia despite progression of parathyroid carcinoma.
Predictive value of various Doppler-derived parameters of atrial conduction time for successful atrial fibrillation ablation
Authors: Shanks Miriam , Valtuille Lucas , Choy Jonathan B. , Becher Harald
Published: November 2015

Various Doppler-derived parameters of left atrial electrical remodeling have been demonstrated to predict recurrence of atrial fibrillation (AF) after AF ablation. The aim of this study was to compare three Doppler-derived measures of atrial conduction time in patients undergoing AF ablation, and to investigate their predictive value for successful procedure. In 32 prospectively enrolled patients undergoing the first AF ablation, atrial conduction time was estimated by measuring the time delay between the onset of P-wave on the surface ECG to the peak of the a′-wave on the pulsed-wave Doppler and color-coded tissue Doppler imaging of the left atrial lateral wall, and to the peak of the A-wave on the pulsed-wave Doppler of the mitral inflow. There was a significant difference in the baseline atrial conduction time measured by different echocardiographic techniques. Most (88%) patients had normal or only mildly dilated left atrium. At 6 months, 12 patients (38%) had recurrent AF/atrial tachycardia. The duration of history of AF was the only predictor of AF/atrial tachycardia recurrence following the first AF ablation (P=0.024; OR 1.023, CI 1.003–1.044). A combination of normal left atrial volume and history of paroxysmal AF of ≤48 months was associated with the best outcome. Predictive value of the Doppler derived parameters of atrial conduction time may be reduced in the early stages of left atrial remodeling. Future studies may determine which echocardiographic parameter correlates best with the extent of left atrial remodeling and is most predictive of successful AF ablation.
Key structural and functional differences between early and advanced glycation products
Authors: Paradela-Dobarro Beatriz , Rodiño-Janeiro Bruno K , Alonso Jana , Raposeiras-Roubín Sergio , González-Peteiro Mercedes , González-Juanatey José R , Álvarez Ezequiel
Published: November 2015

Most of the studies on advanced glycation end products (AGE) have been carried out with uncharacterized mixtures of AGE, so the observed effects cannot be linked to defined structures. Therefore, we analysed the structural differences between glycated human serum albumin (gHSA), a low glycated protein, and AGE-human serum albumin (AGE-HSA), a high glycated protein, and we compared their effects on endothelial functionality. Specifically, we characterized glycation and composition on both early and advanced stage glycation products of gHSA and AGE-HSA by using the MALDI-TOF-mass spectrometry assay. Furthermore, we studied the effects of both types of glycation products on reactive oxygen species (ROS) production and in the expression of vascular and intercellular cell adhesion molecules (VCAM-1 and ICAM-1) on human umbilical endothelial cells (HUVEC). We also measured the adhesion of peripheral blood mononuclear cells (PBMC) to HUVEC. Low concentrations of gHSA enhanced long-lasting ROS production in HUVEC, whereas lower concentrations of AGE-HSA caused the anticipation of the induced extracellular ROS production. Both gHSA and AGE-HSA up-regulated the expression of VCAM-1 and ICAM-1 at mRNA levels. Nevertheless, only AGE-HSA increased protein levels and enhanced the adhesion of PBMC to HUVEC monolayers. Functional differences were observed between gHSA and AGE-HSA, causing the latter an anticipation of the pro-oxidant effects in comparison to gHSA. Moreover, although both molecules induced genetic up-regulation of adhesion molecules in HUVEC, only the high glycated protein functionally increased mononuclear cell adhesion to endothelial monolayers. These observations could have important clinical consequences in the development of diabetic vascular complications.
El otro en la mirada etnográfica. Guatemala (1920-1950)
Authors: Alvarenga Patricia
Published: November 2015

Este artículo analiza diferentes representaciones de comunidades indígenas guatemaltecas durante la primera mitad del siglo XX. De igual forma, explora las perspectivas desde las cuales etnógrafos y antropólogos alemanes y estadounidenses explicaron las características culturas de estos pueblos.
Esta investigación concluye con la fiura de Antonio Goubaud Carrera, antropólogo guatemalteco vinculado con la antropología estadounidense y fiura clave del proyecto de la Revolución Guatemalteca de 1944, la cual se proponía la integración del mundo indígena a la ciudadanía. El trabajo se fundamenta en el análisis de los textos escritos por nuestros sujetos de estudio y pretende ofrecer una visión crítica a las valoraciones culturales que, en busca de la objetividad, fundamentan sus valoraciones de las otredades en posiciones de poder que generan distancias insalvables entre el observador y el observado
Messung kaniner und feliner PankreaslipaseImmunreaktivität – analytischer Vergleich neuer kommerzieller Tests mit etablierten Assays
Authors: Höfel E. , Suchodolski J. S. , Steiner J. M. , Burke K. , Rieker T.
Published: November 2015

Gegenstand und Ziel: Zur Messung der kaninen und felinen Pankreaslipase-Immunreaktivität gibt es seit mehreren Jahren kommerzielle Tests (Spec cPL®, Spec fPL®). Ziel der Studie war, neu verfügbare, bisher in der Literatur nicht validierte Assays mit den etablierten Assays zu vergleichen. Material und Methoden: Überschüssige Serumproben des GI-Labors der Texas A&M University wurden basierend auf verschiedenen Parametern (z. B. gute Probenqualität, hämolytische, lipämische, ikterische Proben) gesammelt und mit randomisierten ID-Nummern gekennzeichnet. Nach Durchführung der Tests Spec cPL® bzw. Spec fPL® wurden die Proben auf Trockeneis an die Kleintierklinik am Hochberg (Deutschland) versandt. Von dort ging ein Teil jeder Probe zur Untersuchung mit den neuen Assays verblindet an das Diagnostiklabor Laboklin (Deutschland). Ein weiterer Teil jeder Probe wurde zur erneuten Testung an das GI-Labor zurückgeschickt, um transportbedingte Veränderungen ausschließen zu können. Die Ergebnisse wurden mittels Wilcoxon-Vorzeichen-Rang-Tests, Rangkorrelationskoeffizienten, Bias Plots, Regressionsgleichung und Konkordanzkoeffizienten statistisch ausgewertet. Ergebnisse: Die Resultate des Spec cPL® und Spec fPL® im GI-Labor vor bzw. nach dem Transport differierten nicht signifikant (Wilcoxon-Rangsummentest: p = 0,581 bzw. 0,712). Zwischen den Ergebnissen der neuen Assays und der etablierten Assays bestanden signifikante Unterschiede (p = 0,0004 bzw. 0,025). Es zeigte sich zwar eine signifikante Assoziation zwischen den neuen und den etablierten Assays (Spearman r: 0,775 und 0,739), doch wurden signifikante systematische Abweichungen für die neuen Assays festgestellt. Konkordanzkoeffizienten der neuen Assays im Vergleich zu den etablierten Assays erwiesen sich als schwach (0,539 bzw. 0,465). Die klinische Interpretation der cPLund fPL-Ergebnisse stimmte in vielen Fällen nicht überein. Schlussfolgerung und klinische Relevanz: Die neuen Assays zur Bestimmung der cPL und fPL weisen statistisch signifikante Ungenauigkeiten auf und ergeben teilweise andere klinische Interpretationen. Deshalb sind weitere Studien zur Validierung der Tests nötig, bevor sie für den klinischen Gebrauch empfohlen werden können.
Computertomographische Untersuchungen mit computerassistierter Detektion von pulmonalen Rundherden bei Hund und Katze
Authors: Piesnack S. , Köhler C. , Ludewig E. , Alef M. , Kiefer I. , Niesterok C.
Published: November 2015

Ziel war, den diagnostischen Wert der computerassistierten Detektion (CAD) von pulmonalen Rundherden in der Tiermedizin zu überprüfen. Hierzu wurde die Detektionsrate der computerassistierten Methode mit der Detektionsrate zweier unabhängiger Untersucher in Bezug auf die Sensitivität und die Rate falsch positiver Befunde verglichen. Material und Methoden: In die Studie wurden 51 Hunde und 16 Katzen einbezogen, bei denen zuvor mittels computertomographischer Untersuchung pulmonale Rundherde diagnostiziert worden waren. Zwei unabhängige Untersucher erfassten bei jedem Patienten die Anzahl der Rundherde ≥ 3 mm und setzten anschließend das Programm zur automatischen Rundherddetektion ein. Im letzten Schritt wurde ein Konsensus der beiden Untersucher unter Kenntnis der CAD-Ergebnisse getroffen. Zur Rundherdauswertung diente ein kommerziell erhältliches Programm zur computerassistierten Detektion. Ergebnisse: Insgesamt wurden 586 pulmonale Rundherde diagnostiziert. Für Untersucher 1 ergab sich eine Sensitivität von 89,2%, für Untersucher 2 betrug sie 87,4%. Die CAD erreichte eine Sensitivität von 69,4%. Mithilfe der CAD ließ die Sensitivität von Untersucher 1 auf 94,7% und die Sensitivität von Untersucher 2 auf 90,8% steigern. Schlussfolgerung und klinische Relevanz: Das verwendete CAD-System wies eine moderate Sensitivität von 69,4% auf. Trotz gewichtiger Limitationen wie einer hohen Anzahl an falsch positiven und falsch negativen Befunden konnte die CAD die Sensitivität beider Untersucher erhöhen, sodass sie zumindest eine unterstützende Funktion besitzt.
HLA and skin cancer
Authors: Bonamigo Renan Rangel , Carvalho André Vicente Esteves de , Sebastiani Vanessa Raquel Zaleski , Silva Cristina Martino da , Pinto Angela Caroline de Zorzi
Published: November 2015

Skin cancer - melanoma and non melanoma - are common neoplasm with rising incidence over the last decades. It is an important public health problem. Its pathogenesis is not completely understood and the same happens with the genetic factors involved. The genes that encode the HLA are associated with some tumors and they may be responsible for one of the mechanisms that take part in the development of the before mentioned cancers. We have reviewed the literature on the subject of HLA antigens, melanoma and non melanoma skin cancer.
Comparative clinical evaluation of efficacy and safety of a formulation containing ciclopirox 8% in the form of a therapeutic nail lacquer in two different posologies for the treatment of onychomycosis of the toes
Authors: Schalka Sergio , Nunes Samanta , Gomes Neto Antonio
Published: November 2015

BACKGROUND: The use of topical antifungal agents in the treatment of onychomycosis is of great value in clinical practice as there are different limitations regarding the use of systemic treatment. OBJECTIVE: To evaluate the efficacy and safety of a nail lacquer formulation containing ciclopirox 8% in two different posologies: the traditional regimen (3/2/1) and a regimen of weekly use. METHODS: A blind, randomized, comparative trial which included 41 patients divided into 02 groups, with Group I using the nail lacquer once weekly and Group II using the traditional regimen (3/2/1). Both groups applied the medication for 06 months. RESULTS: The species most frequently found in groups I and II were Trichophyton rubrum (55% and 61.9%) and Trichophyton mentagrophytes (30% and 19%). There was a tendency to a higher level of treatment resistance by T. mentagrophytes infection in both groups, without any predilection for sex, age, proportion of the nail affected at the beginning of the study, duration of the clinical disease and quantity of nails affected per person. Both groups had significant levels of mycological cure, clinical response and therapeutic success and there was no statistically significant difference between groups I and II (p >0.05). CONCLUSION: The nail lacquer containing ciclopirox 8% was equally effective at a weekly dose when compared to the traditional dosing (3/2/1), allowing a more comfortable regimen.
Assessment of quality of life of patients with leprosy reactional states treated in a dermatology reference center
Authors: Costa Marina Dias , Terra Fábio de Souza , Costa Rosane Dias , Lyon Sandra , Costa Ana Maria Duarte Dias , Antunes Carlos Maurício de Figueiredo
Published: November 2015

BACKGROUND: Disabilities and deformities resulting from reactive outbreaks of leprosy can cause many problems for the patients, interfering with their quality of life. OBJECTIVES: To assess the quality of life of patients with leprosy reactional states identified at the Reference Center in Belo Horizonte - MG. METHODS: This was an epidemiological cross-sectional descriptive and analytical study, involving 120 patients in treatment for leprosy reactional states, from December 2007 to March 2008, held at the Dermatology outpatients clinic of the Hospital Eduardo de Menezes from FHEMIG, BH. We used two instruments for the socio-demographic, economic and clinical variables and a generic instrument WHOQOL WHO. The data were tabulated in SPSS and analyzed using the mean score with the application of statistical tests (p <0.05). RESULTS: We found that the median age of the patients was 48 years, most were males, married, from cities around BH, with incomplete elementary school, retired or pensioner, and with a family income of two minimum wages. Most of them reported that the disease interfered a great deal with their professional activities and leisure. In the assessment of QoL, the lowest rating was observed in the physical domain and the highest was observed in the psychological and social relations. The internal consistency of WHO-QOL-bref was acceptable to the facets and domains. CONCLUSIONS: Leprosy causes suffering that goes beyond the pain and discomfort strictly related to the physical damage, with great social and psychological impact.