Measles virus glycoprotein-based lentiviral targeting vectors that avoid neutralizing antibodies

Lentiviral vectors (LVs) are potent gene transfer vehicles frequently applied in research and recently also in clinical trials. Retargeting LV entry to cell types of interest is a key issue to improve gene transfer safety and efficacy. Recently, we have developed a targeting method for LVs by incorporating engineered measles virus (MV) glycoproteins, the hemagglutinin (H), responsible for receptor recognition, and the fusion protein into their envelope. The H protein displays a single-chain antibody (scFv) specific for the target receptor and is ablated for recognition of the MV receptors CD46 and SLAM by point mutations in its ectodomain. A potential hindrance to systemic administration in humans is pre-existing MV-specific immunity due to vaccination or natural infection. We compared transduction of targeting vectors and non-targeting vectors pseudotyped with MV glycoproteins unmodified in their ectodomains (MV-LV) in presence of α-MV antibody-positive human plasma. At plasma dilution 1:160 MV-LV was almost completely neutralized, whereas targeting vectors showed relative transduction efficiencies from 60% to 90%. Furthermore, at plasma dilution 1:80 an at least 4-times higher multiplicity of infection (MOI) of MV-LV had to be applied to obtain similar transduction efficiencies as with targeting vectors. Also when the vectors were normalized to their p24 values, targeting vectors showed partial protection against α-MV antibodies in human plasma. Furthermore, the monoclonal neutralizing antibody K71 with a putative epitope close to the receptor binding sites of H, did not neutralize the targeting vectors, but did neutralize MV-LV. The observed escape from neutralization may be due to the point mutations in the H ectodomain that might have destroyed antibody binding sites. Furthermore, scFv mediated cell entry via the target receptor may proceed in presence of α-MV antibodies interfering with entry via the natural MV receptors. These results are promising for in vivo applications of targeting vectors in humans

The adoption of algorithmic decision-making agents over time: algorithm aversion as a temporary effect?

Many individuals encounter algorithmic decision-making agents with algorithm aversion – the irrational discounting of superior algorithmic advice. So far, we know little about how algorithm adoption develops over time and how people may overcome algorithm aversion. In response, we explore the factors that foster the adoption of algorithmic decision-making agents – initially and over time. Based on an experiment with incentive-compatible awards over several rounds, we find that one’s knowledge about peers successfully using the technology as well as low transaction costs serve as strong initial motivators to foster initial algorithm adoption. Further, by revealing that adoption rates increase and initial difference in adoption rates become smaller over time, we find evidence that despite the technology’s particularities, algorithm aversion seems to have a temporary effect only

Fearless but anxious?: A systematic review on the utility of fear and anxiety levels to classify subtypes of psychopathy

Abstract Psychopathic traits have been linked to anomalies in experiencing fear and anxiety. It remains unclear, however, to what extent fear and anxiety levels are useful parameters to effectively distinguish between subtypes of psychopathy. Therefore, we aimed to elucidate whether different psychopathic phenotypes (primary and secondary psychopathy) can be delineated based on fear/anxiety levels. To investigate associations between psychopathic traits and conscious experiences of fear and/or anxiety a systematic qualitative review of studies was conducted following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Seventeen studies were included in the review. We found some evidence for attenuated fear/anxiety levels in primary psychopathy. In secondary psychopathy, the experience of fear/anxiety seemed rather intact. Moreover, primary psychopathy might be associated with a more positive appraisal of the conscious feeling of fear. We reason that consciously experienced fear and anxiety are distinctly related to primary and secondary psychopathy. Due to a lack of consistent and comprehensive operationalizations of fear and anxiety, however, conclusions about their potential to differentiate psychopathic subtypes should be drawn with caution

Digital Work: A Conceptual Clarification

This paper provides a typology of digital work – a popular term still lacking a clear meaning. We show how previous attempts to capture the essence of digital work struggle to provide a meaningful yet comprehensive understanding of what differentiates traditional from digital work. We draw on prior literature to argue that digital work requires three rationales to be fulfilled: process (How?), outcome (What?), and objective (Why?). Based on this, we highlight three variations – digital enabled work, digital engaged work, and digital embedded work. This typology allows us to define digital work more clearly and enables future research to adequately study and theorize digital work. Furthermore, this typology permits considering alternate classifications for activities and actors in work that traditional work conceptualizations fail to include

Ditadura militar e literatura “parajornalística”:: desconstruindo relações

Este artigo busca rever a abordagem do romance-reportagem brasileiro da década de 1970 pela crítica literária acadêmica. Entende-se que, na apreciação dessas obras, considerou-se apenas a repercussão da situação política nacional ”“ ditadura militar ”“, tomando-se as narrativas de jornalistas como meras substitutas do jornal censurado. Foi desconsiderada, portanto, a diferença entre notícia, produto do jornalismo informativo diário, e reportagem, gênero jornalístico que não tem lugar na grande imprensa. Na primeira não há narração, ao passo que, na segunda, a construção de personagens e a configuração da intriga garantem a instauração do universo ficcional, como querem autores como Paul Ricoeur, Mikhail Bakhtin e Käte Hamburger

Verbal and nonverbal communication in schizophrenia - New insights from uni- and multimodal brain imaging

Socio-cognitive symptoms represent prominent and often strongly impairing deficits in patients with schizophrenia and they are tightly intertwined with dysfunctional communicative representations or systems. In particular, deficient verbal and nonverbal social information processing is associated with decreased functional outcome and prominent difficulties in everyday social interactions. Some specific aspects of verbal and nonverbal communication in schizophrenia have been thoroughly assessed by previous studies, particularly semantic priming at word level (verbal-cognitive domain) as well as face and facial emotion recognition (nonverbal-affective domain) and rather broad sociocognitive functions including Theory of Mind (ToM). However, only very little is known about disease-related alterations in more complex language functions, such as pragmatic (e.g. non-literal) language comprehension, or emotion processing from social cues other than the face, such as human body language. To this end, the present dissertation intended to investigate neurophysiological correlates of verbal and nonverbal socio-communicative (dys)functions in schizophrenia that have so far been rarely investigated using functional imaging, namely pragmatic language (verbalcognitive domain, 2 studies) and emotional body language (nonverbal-affective domain, 2 studies) processing. Neurophysiological activity was assessed by means of functional nearinfrared spectroscopy (fNIRS) measurements, either applied alone (unimodal imaging) or combined with electroencephalography (EEG; multimodal imaging). These specific neuroimaging methods have been chosen because they are characterised by high ecological validity and a relatively high flexibility regarding their applicability in varying contexts, implying a great potential of these techniques to assess social communicative functions in schizophrenia that are highly relevant for everyday social interactions. Taken together, the results obtained in the four studies revealed 1) that fNIRS measurements – either unimodally applied or combined with EEG – are useful to detect cortical activation associated with verbal-cognitive and nonverbal-affective information processing. 2) Patients with schizophrenia show significant alterations in these neurophysiological processes along with impaired recognition of pragmatic language (verbal-cognitive domain) and emotional body language (nonverbal-affective domain). The findings complement previous studies on more commonly assessed sociocommunicative dysfunctions in schizophrenia (altered semantic priming and facial expression perception). The present work provides a holistic overview over different social communication dysfunctions that may be apparent in patients suffering from schizophrenia and their accessibility via fNIRS and EEG-fNIRS measurements, respectively. Hereby, all project parts focused on an innovative implementation of neuroimaging methods that may be particularly promising for future directions in neuropsychiatric research. The findings are discussed in the light of contemporary models of pragmatic language comprehension as well as nonverbal social information processing. Moreover, they are integrated into current concepts of schizophrenia, particularly with respect to etiological models and neurocognitive frameworks as well as the endophenotype concept.Sozial-kognitive Symptome stellen ein markantes und häufig stark beeinträchtigendes Defizit von Patienten mit schizophrener Erkrankung dar, welches eng mit Dysfunktionen in Kommunikation und Interaktion verknüpft ist. Hierbei sind insbesondere Einschränkungen in der Verarbeitung verbal und nonverbal dargebotener sozialer Information mit einem verminderten generellen Funktionsniveau sowie deutlichen Schwierigkeiten bei alltäglichen sozialen Interaktionen assoziiert. Einige spezifische Teilbereiche verbaler und nonverbaler Kommunikation bei Schizophrenie wurden bereits in früheren Studien zum Teil ausführlich untersucht, wie beispielsweise semantische Bahnung (Priming) auf Wortebene (verbalkognitive Ebene), (emotionale) Gesichtsverarbeitung (nonverbal-affektive Ebene) sowie weniger scharf umgrenzte sozial-kognitive Funktionen einschließlich Theory of Mind (ToM). Bislang ist jedoch wenig bekannt über störungsbezogene Veränderungen komplexer Sprachverarbeitung, wie pragmatisches (z. B. nicht-wörtlich gemeintes) Sprachverstehen, oder der Verarbeitung von Emotionen auf Basis sozialer Reize, die nicht auf Gesichter beschränkt sind, wie beispielsweise menschliche Körpersprache. Die vorliegende Dissertation befasst sich daher mit der Untersuchung neurophysiologischer Korrelate solcher verbaler und nonverbaler kommunikativer (Dys-)Funktionen bei Schizophrenie, die bislang nur wenig mittels funktioneller Bildgebung untersucht worden sind. Hierbei werden zum einen pragmatische Sprache (verbal-kognitive Ebene) und zum anderen emotionale Körpersprache (nonverbal-affektive Ebene) fokussiert. Die Erfassung neurophysiologischer Aktivität erfolgt mithilfe der Methode der funktionellen Nahinfrarot-Spektroskopie (fNIRS), welche hierbei entweder allein (unimodale Messungen) oder in Kombination mit Elektroenzephalographie (EEG, multimodale Messungen) zum Einsatz kommt. Diese bildgebenden Verfahren wurden insbesondere aufgrund ihrer hohen ökologischen Validität und flexiblen Anwendbarkeit in verschiedensten Untersuchungs-Situationen ausgewählt, welche ein hohes Potential beider Methoden zur validen und ökonomischen Untersuchung alltagsrelevanter kommunikativer Funktionen bei Schizophrenie nahe legen. Zusammengefasst ergaben die in den vier Studien erbrachten Ergebnisse folgendes Bild: (1) fNIRS Messungen, sowohl uni- als auch multimodal (hier: in Kombination mit EEG) angewendet, bilden eine nützliche Methode zur realitätsnahen Erfassung kortikaler Aktivierung, die mit verbal-kognitiver und nonverbal-affektiver Informationsverarbeitung in Zusammenhang stehen. (2) Patienten mit Schizophrenie zeigen signifikante Veränderungen dieser neurophysiologischen Prozesse, welche behavioral mit einem verminderten pragmatischem Sprachverstehen (verbal-kognitive Ebene) sowie Einschränkungen im Erkennen emotionaler Körpersprache (nonverbal-affektive Ebene) einhergehen. Diese Befunde ergänzen frühere Studien zu weniger komplexen, aber bislang häufiger untersuchten sozio-kommunikativen Dysfunktionen bei Schizophrenie (z. B. verändertes semantisches Priming sowie beeinträchtigte Verarbeitung von Gesichtsausdrücken). Die Befunde werden vor dem Hintergrund theoretischer Modelle zum pragmatischen Sprachverstehen sowie der Verarbeitung nonverbaler sozialer Information diskutiert. Darüber hinaus werden die Ergebnisse in aktuelle Konzepte der Schizophrenie integriert, insbesondere im Hinblick auf äthiologische Modelle und neurokognitive Erklärungsansätze der Erkrankung. Zudem wird eine Einordnung der hier untersuchten kommunikativen Funktionen in das Endophänotypenkonzept versucht

A escuta da fala marginalizada em ancestral na voz ascendente

Neste trabalho de conclusão desejo mostrar a importância das narrativas orais e discutir o seu valor, uma vez que elas trazem a paixão que vai além dos documentos oficiais da escrita da História, bem como propor um espaço na academia para a discussão a partir de Poéticas marginalizadas. O vídeo Ancestral na Voz Ascendente, traz a história de mulheres, retratando as sociedades machistas nas quais elas viveram, cada uma a seu tempo e espaço. Nele, estabelece-se um diálogo entre duas formas distintas de narração de histórias (ZUMTHOR, 2005). Uma narrativa é feita por Anita, que está em casa e, de forma espontânea, relembra a história de sua mãe, uma pastora de ovelhas. A outra é constituída por uma performance feita por Gilda, na qual a artista recupera a história de suas antepassadas indígenas: a bisavó retirada da aldeia para ser escravizada em uma fazenda, e a avó vendida para uma família da cidade para exercer atividades domésticas. Pensando numa tradição contínua, passada pela oralidade, busca-se valorizar as vozes subalternizadas das mulheres entrevistadas, registrando suas narrativas como forma de resistência ao poder do colonizador. O conteúdo do vídeo e a sua análise no texto são, além de tudo, questionamentos sobre a forma ocidental de narrar a história e a poesia da humanidade, cujo discurso oficial esquece a parte que cabe aos marginalizados e às mulheres, inscrevendo, geralmente, a perspectiva patriarcal como única. Dessa forma, trata-se de um trabalho sobre e de resistência da mulher e dos subalternizados.En esta monografía deseo mostrar la importancia de las narrativas orales, ya que muestran una pasión que va más allá de los documentos oficiales de la historia escrita. Igualmente propongo un espacio dentro de la academia para discutir su valor a partir de poemas marginalizados. El video ancestral en la voz ascendente, contiene la historia de mujeres retratando las sociedades machistas en las cuales viven, cada una en su tiempo y espacio. En el video se establece un dialogo entre dos formas distintas de narración de historias (ZUMTHOR, 2005): Una de las narraciones es hecha por Anita de manera espontanea recordando la historia de su madre la cual fue una pastora de ovejas. La otra historia está constituida por una performance hecha por Gilda, en la cual se recupera la historia de sus antepasadas indígenas: la bisabuela que fue extirpada de su aldea para convertirse en esclava en una hacienda y la abuela vendida para una familia de la ciudad para transformarse en empleada doméstica. Pensando en una tradición continua, pasada oralmente, se pretende valorizar las voces de las mujeres entrevistadas, registrando sus narraciones como forma de resistencia al poder del colonizador. El contenido del video y su análisis en el texto son, más que todo, cuestionamientos sobre la forma occidental de narrar la historia y poesías humanas, cuyo discurso oficial se olvida de la parte que corresponde a marginales y mujeres, inscribiendo generalmente la perspectiva patriarcal como única. De esta forma se trata de un trabajo sobre y la resistencia de la mujer e de los subalternos

Studying eParticipation in Government Innovation Programmes: Lessons from a Survey

While eGovernment is a well-established field in research and practice, eParticipation trails behind with only a low number of programmes and strategies at the moment. With the lessons learnt from a survey for studying eParticipation in Government Innovation Programmes and Strategies, the contribution at hand analyses the degree of integration of eParticipation in ICT and eGovernment research and implementation programmes and strategies. It sets out the types of approach necessary to accelerate progress. Together with insights from two projects that analysed eGovernment innovation strategies, the synthesis and comparison of the survey data led to recommendations for activities and measures for innovation programme managers to include eParticipation in future programmes and strategies. The work was performed in the context of DEMO_net1, the Network of Excellence on eParticipation

Heat adaptation measures in private households: an application and adaptation of the protective action decision model

Extreme heatwaves will occur more frequently and with higher intensity in future. Their consequences for human health can be fatal if adaptation measures will not be taken. This study analyses factors related to heat adaptation measures in private households in Germany. During the summer months of 2019, indoor temperatures were measured in over 500 private households in the City of Augsburg, Germany, accompanied by a survey to find out about heat perception and adaptation measures. Hypotheses deducted from the Protective Action Decision Model were tested using one-way ANOVAs, regression analysis and in the end a multiple hierarchical regression model. The results of the hypotheses tested imply an influence of knowledge and heat risk perception of heat adaptation behaviour and an influence of age on heat risk perception. The results of the regression model show an influence of the efficacy-related attribute, of age, indoor temperature, subjective heat stress and health implications to heat adaptation behaviour. In the end, this study proposes adjustments to the PADM according to the results of the hierarchical regression analysis