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Striated muscle contraction is regulated by the translocation of troponin-tropomyosin strands over the thin filament surface. Relaxation relies partly on highly-favorable, conformation-dependent electrostatic contacts between actin and tropomyosin, which position tropomyosin such that it impedes actomyosin associations. Impaired relaxation and hypercontractile properties are hallmarks of various muscle disorders. The α-cardiac actin M305L hypertrophic cardiomyopathy-causing mutation lies near residues that help confine tropomyosin to an inhibitory position along thin filaments. Here, we investigate M305L actin in vivo, in vitro, and in silico to resolve emergent pathological properties and disease mechanisms. Our data suggest the mutation reduces actin flexibility and distorts the actin-tropomyosin electrostatic energy landscape that, in muscle, result in aberrant contractile inhibition and excessive force. Thus, actin flexibility may be required to establish and maintain interfacial contacts with tropomyosin as well as facilitate its movement over distinct actin surface features and is, therefore, likely necessary for proper regulation of contraction.
Background: 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD) is an autosomal recessive disorder of ketogenesis and leucine degradation due to mutations in HMGCL.
Method: We performed a systematic literature search to identify all published cases. Two hundred eleven patients of whom relevant clinical data were available were included in this analysis. Clinical course, biochemical findings and mutation data are highlighted and discussed. An overview on all published HMGCL variants is provided.
Results: More than 95% of patients presented with acute metabolic decompensation. Most patients manifested within the first year of life, 42.4% already neonatally. Very few individuals remained asymptomatic. The neurologic long-term outcome was favorable with 62.6% of patients showing normal development.
Conclusion: This comprehensive data analysis provides a systematic overview on all published cases with HMGCLD including a list of all known HMGCL mutations.
Computers can help us to trigger our intuition about how to solve a problem. But how does a computer take into account what a user wants and update these triggers? User preferences are hard to model as they are by nature vague, depend on the user’s background and are not always deterministic, changing depending on the context and process under which they were established. We pose that the process of preference discovery should be the object of interest in computer aided design or ideation. The process should be transparent, informative, interactive and intuitive. We formulate Hyper-Pref, a cyclic co-creative process between human and computer, which triggers the user’s intuition about what is possible and is updated according to what the user wants based on their decisions. We combine quality diversity algorithms, a divergent optimization method that can produce many, diverse solutions, with variational autoencoders to both model that diversity as well as the user’s preferences, discovering the preference hypervolume within large search spaces.
Until recently, studies regarding e-banking transactions have focused more on motivational factors that trigger the intention to accept and use the e-banking transaction, rather than the de-motivational factors that propel the action. However, in the developing countries like Sub-Sahara economies, the factors associated with the former have not been explored and are still rudimentary in the literature. Drawing from the Technology Threat Avoidance Theory (TTAT), the study seeks to examine the impact of online identity theft on customers’ willingness to engage in e-banking transactions in Ghana. A quantitative survey of 393 valid responses from retail bank customers amongst two leading commercial banks in Ghana for the analyses. Results from the PLS-SEM showed that the research constructs; perceived online identity theft’ positively and significantly predict “fear of financial loss”, “fear of reputational damage”, and “security and privacy concern” whilst the former has a negative mediated-relationship between perceived online identity theft and the intention to engage in e-banking transaction. This study is the first of its kind that has extended the application of the TTAT framework into the study of e-banking transactions. The study serves as a practical tool that will enable the banks in their quest to assess customers’ restriction/aversion towards the use of Fintech while ensuring sustainable growth of e-banking transactions in an emerging economy context. The study is limited to only banking institutions in Ghana without considering other players in the financial sub-sector. Future research direction has been suggested in the concluding part of the paper.
Do socio-economic factors impede the engagement in online banking transactions? Evidence from Ghana
(2020)
Researchers have long pondered on the online banking transaction adoption. Some of these studies focus primarily on the motivating factors that affect customers’ intention to adopt/accept these services (technologies). However, research into the constraining factors, in particular socio-economic factors, barely exist in the literature, especially in the context of sub-Saharan Africa. Against this background, the paper seeks to fill in this gap by: (1) assessing the socio-economic factors impeding the engagement of e-banking transactions among retail bank customers in Ghana, and (2) examining the moderating effect of ‘customer experience of Internet’ on the identified factors that inhibit the engagement in online banking in Ghana. The paper used a quantitative research approach to obtain data from two leading Ghanaian banks. Out of the 450 questionnaires distributed, 393 were valid for analysis. Data were analyzed with the aid of PLS-SEM (partial least squares and structural equation modeling). Findings revealed that perceived knowledge gap and the price of digital devices were directly important to the intention to disembark on e-banking transactions among Ghanaian bank customers. Whilst customer experience (frequent use of the Internet), as a moderator variable, has a significant effect on the interaction between perceived knowledge gap and the intent to disembark on e-banking transactions; and finance charges and the intent to disembark on e-banking transactions. Study implications and directions for future research are discussed in the paper.
4GREAT is an extension of the German Receiver for Astronomy at Terahertz frequencies (GREAT) operated aboard the Stratospheric Observatory for Infrared Astronomy (SOFIA). The spectrometer comprises four different detector bands and their associated subsystems for simultaneous and fully independent science operation. All detector beams are co-aligned on the sky. The frequency bands of 4GREAT cover 491-635, 890-1090, 1240-1525 and 2490-2590 GHz, respectively. This paper presents the design and characterization of the instrument, and its in-flight performance. 4GREAT saw first light in June 2018, and has been offered to the interested SOFIA communities starting with observing cycle 6.
Diese Studie untersucht die Aneignung und Nutzung von Sprachassistenten wie Google Assistant oder Amazon Alexa in Privathaushalten. Unsere Forschung basiert auf zehn Tiefeninterviews mit Nutzern von Sprachassistenten sowie der Evaluation bestimmter Interaktionen in der Interaktionshistorie. Unsere Ergebnisse illustrieren, zu welchen Anlässen Sprachassistenten im heimischen Umfeld genutzt werden, welche Strategien sich die Nutzer in der Interaktion mit Sprachassistenten angeeignet haben, wie die Interaktion abläuft und welche Schwierigkeiten sich bei der Einrichtung und Nutzung des Sprachassistenten ergeben haben. Ein besonderer Fokus der Studie liegt auf Fehlinteraktionen, also Situationen, in denen die Interaktion scheitert oder zu scheitern droht. Unsere Studie zeigt, dass das Nutzungspotenzial der Assistenten häufig nicht ausgeschöpft wird, da die Interaktion in komplexeren Anwendungsfällen häufig misslingt. Die Nutzer verwenden daher den Sprachassistenten eher in einfachen Anwendungsfällen und neue Apps und Anwendungsfälle werden gar nicht erst ausprobiert. Eine Analyse der Aneignungsstrategien, beispielsweise durch eine selbst erstellte Liste mit Befehlen, liefert Erkenntnisse für die Gestaltung von Unterstützungswerkzeugen sowie die Weiterentwicklung und Optimierung von sprachbasierten Mensch-Maschine-Interfaces.
2-methylacetoacetyl-coenzyme A thiolase (beta-ketothiolase) deficiency: one disease - two pathways
(2020)
Background: 2-methylacetoacetyl-coenzyme A thiolase deficiency (MATD; deficiency of mitochondrial acetoacetyl-coenzyme A thiolase T2/ “beta-ketothiolase”) is an autosomal recessive disorder of ketone body utilization and isoleucine degradation due to mutations in ACAT1.
Methods: We performed a systematic literature search for all available clinical descriptions of patients with MATD. Two hundred forty-four patients were identified and included in this analysis. Clinical course and biochemical data are presented and discussed.
Results: For 89.6% of patients at least one acute metabolic decompensation was reported. Age at first symptoms ranged from 2 days to 8 years (median 12 months). More than 82% of patients presented in the first 2 years of life, while manifestation in the neonatal period was the exception (3.4%). 77.0% (157 of 204 patients) of patients showed normal psychomotor development without neurologic abnormalities. Conclusion: This comprehensive data analysis provides a systematic overview on all cases with MATD identified in the literature. It demonstrates that MATD is a rather benign disorder with often favourable outcome, when compared with many other organic acidurias.
Intelligente Dialogsysteme – Chatbots – werden immer häufiger als virtuelle Ansprechpartner von Unternehmen und Institutionen eingesetzt. Auf Basis einer Wissensdatenbank können Chatbots einen größeren Anteil von Kundenanfragen automatisiert beantworten. Analog ist der Einsatz von Chatbots als digitaler Ansprechpartner öffentlicher Verwaltungen denkbar. Sie könnten Bürgern helfen, sich innerhalb der behördlichen Strukturen zu orientieren und Verwaltungsleistungen effizient und effektiv in Anspruch zu nehmen.
Diese Arbeit überprüft den Einsatz eines Chatbots in der öffentlichen Verwaltung hinsichtlich der entstehenden Kosten und des erwartbaren Nutzens. Auf Basis einer umfangreichen Literaturauswertung und der prototypischen Realisierung eines Chatbots für ein Stadtportal werden dabei Herausforderungen dieser Anwendungsdomäne herausgearbeitet, konkrete Funktionsweise und Implementierungsstrategien von Chatbots erörtert und einige Erfolgsfaktoren formuliert, die den Kern einer Handlungsempfehlung für Entscheidungsträger öffentlicher Verwaltungen bilden.