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In the context of persistent images of self-perpetuated technologies, we discuss the interplay of digital technologies and organisational dynamics against the backdrop of systems theory. Building on the case of an international corporation that, during an agile reorganisation, introduced an AI-based personnel management platform, we show how technical systems produce a form of algorithmic contingency that subsequently leads to the emergence of formal and informal interaction systems. Using the concept of datafication, we explain how these interactions are barriers to the self-perpetuation of data-based decision-making, making it possible to take into consideration further decision factors and complementing the output of the platform. The research was carried out within the scope of the research project ‘Organisational Implications of Digitalisation: The Development of (Post-)Bureaucratic Organisational Structures in the Context of Digital Transformation’ funded by the German Research Foundation (DFG).
Cells are built from a variety of macromolecules and metabolites. Both, the proteome and the metabolome are highly dynamic and responsive to environmental cues and developmental processes. But it is not their bare numbers, but their interactions that enable life. The protein-protein (PPI) and protein-metabolite interactions (PMI) facilitate and regulate all aspects of cell biology, from metabolism to mitosis. Therefore, the study of PPIs and PMIs and their dynamics in a cell-wide context is of great scientific interest. In this dissertation, I aim to chart a map of the dynamic PPIs and PMIs across metabolic and cellular transitions. As a model system, I study the shift from the fermentative to the respiratory growth, known as the diauxic shift, in the budding yeast Saccharomyces cerevisiae. To do so, I am applying a co-fractionation mass spectrometry (CF-MS) based method, dubbed protein metabolite interactions using size separation (PROMIS). PROMIS, as well as comparable methods, will be discussed in detail in chapter 1.
Since PROMIS was developed originally for Arabidopsis thaliana, in chapter 2, I will describe the adaptation of PROMIS to S. cerevisiae. Here, the obtained results demonstrated a wealth of protein-metabolite interactions, and experimentally validated 225 previously predicted PMIs. Applying orthogonal, targeted approaches to validate the interactions of a proteogenic dipeptide, Ser-Leu, five novel protein-interactors were found. One of those proteins, phosphoglycerate kinase, is inhibited by Ser-Leu, placing the dipeptide at the regulation of glycolysis.
In chapter 3, I am presenting PROMISed, a novel web-tool designed for the analysis of PROMIS- and other CF-MS-datasets. Starting with raw fractionation profiles, PROMISed enables data pre-processing, profile deconvolution, scores differences in fractionation profiles between experimental conditions, and ultimately charts interaction networks. PROMISed comes with a user-friendly graphic interface, and thus enables the routine analysis of CF-MS data by non-computational biologists.
Finally, in chapter 4, I applied PROMIS in combination with the isothermal shift assay to the diauxic shift in S. cerevisiae to study changes in the PPI and PMI landscape across this metabolic transition. I found a major rewiring of protein-protein-metabolite complexes, exemplified by the disassembly of the proteasome in the respiratory phase, the loss of interaction of an enzyme involved in amino acid biosynthesis and its cofactor, as well as phase and structure specific interactions between dipeptides and enzymes of central carbon metabolism.
In chapter 5, I am summarizing the presented results, and discuss a strategy to unravel the potential patterns of dipeptide accumulation and binding specificities. Lastly, I recapitulate recently postulated guidelines for CF-MS experiments, and give an outlook of protein interaction studies in the near future.
Die Arbeit gibt einen Einblick in die Verständigungspraxen bei Stadtführungen mit (ehemaligen) Obdachlosen, die in ihrem Selbstverständnis auf die Herstellung von Verständnis, Toleranz und Anerkennung für von Obdachlosigkeit betroffene Personen zielen. Zunächst wird in den Diskurs des Slumtourismus eingeführt und, angesichts der Vielfalt der damit verbundenen Erscheinungsformen, Slumming als organisierte Begegnung mit sozialer Ungleichheit definiert. Die zentralen Diskurslinien und die darin eingewobenen moralischen Positionen werden nachvollzogen und im Rahmen der eigenommenen wissenssoziologischen Perspektive als Ausdruck einer per se polykontexturalen Praxis re-interpretiert. Slumming erscheint dann als eine organisierte Begegnung von Lebensformen, die sich in einer Weise fremd sind, als dass ein unmittelbares Verstehen unwahrscheinlich erscheint und genau aus diesem Grund auf der Basis von gängigen Interpretationen des Common Sense ausgehandelt werden muss. Vor diesem Hintergrund untersucht die vorliegende Arbeit, wie sich Teilnehmer und Stadtführer über die Erfahrung der Obdachlosigkeit praktisch verständigen und welcher Art das hierüber erzeugte Verständnis für die im öffentlichen Diskurs mit vielfältigen stigmatisierenden Zuschreibungen versehenen Obdachlosen ist. Dabei interessiert besonders, in Bezug auf welche Aspekte der Erfahrung von Obdachlosigkeit ein gemeinsames Verständnis möglich wird und an welchen Stellen dieses an Grenzen gerät. Dazu wurden die Gesprächsverläufe auf neun Stadtführungen mit (ehemaligen) obdachlosen Stadtführern unterschiedlicher Anbieter im deutschsprachigen Raum verschriftlicht und mit dem Verfahren der Dokumentarischen Methode ausgewertet. Die vergleichende Betrachtung der Verständigungspraxen eröffnet nicht zuletzt eine differenzierte Perspektive auf die in den Prozessen der Verständigung immer schon eingewobenen Anerkennungspraktiken. Mit Blick auf die moralische Debatte um organisierte Begegnungen mit sozialer Ungleichheit wird dadurch eine ethische Perspektive angeregt, in deren Zentrum Fragen zur Vermittlungsarbeit stehen.
Language processing requires memory retrieval to integrate current input with previous context and making predictions about upcoming input. We propose that prediction and retrieval are two sides of the same coin, i.e. functionally the same, as they both activate memory representations. Under this assumption, memory retrieval and prediction should interact: Retrieval interference can only occur at a word that triggers retrieval and a fully predicted word would not do that. The present study investigated the proposed interaction with event-related potentials (ERPs) during the processing of sentence pairs in German. Predictability was measured via cloze probability. Memory retrieval was manipulated via the position of a distractor inducing proactive or retroactive similarity-based interference. Linear mixed model analyses provided evidence for the hypothesised interaction in a broadly distributed negativity, which we discuss in relation to the interference ERP literature. Our finding supports the proposal that memory retrieval and prediction are functionally the same.
Hantaviruses are emerging pathogens that occasionally cause deadly outbreaks in the human population. While the structure of the viral envelope has been characterized with high precision, protein-protein interactions leading to the formation of new virions in infected cells are not fully understood. We used quantitative fluorescence microscopy (i.e., number and brightness analysis and fluorescence fluctuation spectroscopy) to monitor the interactions that lead to oligomeric spike complex formation in the physiological context of living cells. To this aim, we quantified protein-protein interactions for the glycoproteins Gn and Gc from Puumala and Hantaan orthohantaviruses in several cellular models. The oligomerization of each protein was analyzed in relation to subcellular localization, concentration, and the concentration of its interaction partner. Our results indicate that, when expressed separately, Gn and Gc form, respectively, homo-tetrameric and homo-dimeric complexes, in a concentration-dependent manner. Site-directed mutations or deletion mutants showed the specificity of their homotypic interactions. When both glycoproteins were coexpressed, we observed in the Golgi apparatus clear indication of GnGc interactions and the formation of Gn-Gc multimeric protein complexes of different sizes, while using various labeling schemes to minimize the influence of the fluorescent tags. Such large glycoprotein multimers may be identified as multiple Gn viral spikes interconnected via Gc-Gc contacts. This observation provides the possible first evidence for the initial assembly steps of the viral envelope within this organelle, and does so directly in living cells. <br /> IMPORTANCE In this work, we investigate protein-protein interactions that drive the assembly of the hantavirus envelope. These emerging pathogens have the potential to cause deadly outbreaks in the human population. Therefore, it is important to improve our quantitative understanding of the viral assembly process in infected cells, from a molecular point of view. By applying advanced fluorescence microscopy methods, we monitored the formation of viral spike complexes in different cell types. Our data support a model for hantavirus assembly according to which viral spikes are formed via the clustering of hetero-dimers of the two viral glycoproteins Gn and Gc. Furthermore, the observation of large Gn-Gc hetero-multimers provide the possible first evidence for the initial assembly steps of the viral envelope, directly in the Golgi apparatus of living cells.
Deliberative and paternalistic interaction styles for conversational agents in digital health
(2021)
Background:
Recent years have witnessed a constant increase in the number of people with chronic conditions requiring ongoing medical support in their everyday lives. However, global health systems are not adequately equipped for this extraordinarily time-consuming and cost-intensive development. Here, conversational agents (CAs) can offer easily scalable and ubiquitous support. Moreover, different aspects of CAs have not yet been sufficiently investigated to fully exploit their potential. One such trait is the interaction style between patients and CAs. In human-to-human settings, the interaction style is an imperative part of the interaction between patients and physicians. Patient-physician interaction is recognized as a critical success factor for patient satisfaction, treatment adherence, and subsequent treatment outcomes. However, so far, it remains effectively unknown how different interaction styles can be implemented into CA interactions and whether these styles are recognizable by users.
Objective:
The objective of this study was to develop an approach to reproducibly induce 2 specific interaction styles into CA-patient dialogs and subsequently test and validate them in a chronic health care context.
Methods:
On the basis of the Roter Interaction Analysis System and iterative evaluations by scientific experts and medical health care professionals, we identified 10 communication components that characterize the 2 developed interaction styles: deliberative and paternalistic interaction styles. These communication components were used to develop 2 CA variations, each representing one of the 2 interaction styles. We assessed them in a web-based between-subject experiment. The participants were asked to put themselves in the position of a patient with chronic obstructive pulmonary disease. These participants were randomly assigned to interact with one of the 2 CAs and subsequently asked to identify the respective interaction style. Chi-square test was used to assess the correct identification of the CA-patient interaction style.
Results:
A total of 88 individuals (42/88, 48% female; mean age 31.5 years, SD 10.1 years) fulfilled the inclusion criteria and participated in the web-based experiment. The participants in both the paternalistic and deliberative conditions correctly identified the underlying interaction styles of the CAs in more than 80% of the assessments (X-1(,8)8(2)=38.2; P<.001; phi coefficient r(phi)=0.68). The validation of the procedure was hence successful.
Conclusions:
We developed an approach that is tailored for a medical context to induce a paternalistic and deliberative interaction style into a written interaction between a patient and a CA. We successfully tested and validated the procedure in a web-based experiment involving 88 participants. Future research should implement and test this approach among actual patients with chronic diseases and compare the results in different medical conditions. This approach can further be used as a starting point to develop dynamic CAs that adapt their interaction styles to their users.
Küstennahe Niedermoore wurden durch den Menschen verändert, bspw. durch das Anlegen von Entwässerungsgräben, dem Bau von Küstenschutzdeichen oder aktuell einer Renaturierung. Außerdem ist es wichtig die komplexe Interaktion mit der See zu verstehen, um Aussagen über die zukünftige Entwicklung treffen zu können. In der vorliegenden Studie wurde die ober- und unterirdische Strömung in einem Feuchtgebiet an der mecklenburgischen Ostseeküste nahe Warnemünde
(Deutschland) untersucht, um dessen wechselseitigen Austausch mit der Ostsee zu quantifizieren und zu analysieren, wie sich ein Sturmhochwasserereignis auf den Salzeintrag ins Gebiet auswirkt. Hierfür wurde ein dreidimensionales
instationäres Grundwassermodell erstellt, mit einem eindimensionalen Modell des Grabensystems gekoppelt und mit Messungen im Gebiet kalibriert und verglichen. Die Ergebnisse zeigen, dass neben der oberirdischen Entwässerung auch der
Grundwasserabstrom in Richtung Ostsee eine wesentliche Komponente der Wasserbilanz darstellt. Das Verhalten entlang der Küste wird deutlich durch die Dynamik der Ostseewasserstände geprägt, wobei ein Grundwasserabstrom mit einem
Zustrom von Ostseewasser bei hohen Küstenwasserständen innerhalb täglicher bis wöchentlicher Zeitskalen wechselt.
Differentially-charged liposomes interact with alphaherpesviruses and interfere with virus entry
(2020)
Exposure of phosphatidylserine (PS) in the outer leaflet of the plasma membrane is induced by infection with several members of the Alphaherpesvirinae subfamily. There is evidence that PS is used by the equine herpesvirus type 1 (EHV-1) during entry, but the exact role of PS and other phospholipids in the entry process remains unknown. Here, we investigated the interaction of differently charged phospholipids with virus particles and determined their influence on infection. Our data show that liposomes containing negatively charged PS or positively charged DOTAP (N-[1-(2,3-Dioleoyloxy)propyl]-N,N,N-trimethylammonium) inhibited EHV-1 infection, while neutral phosphatidylcholine (PC) had no effect. Inhibition of infection with PS was transient, decreased with time, and was dose dependent. Our findings indicate that both cationic and anionic phospholipids can interact with the virus and reduce infectivity, while, presumably, acting through different mechanisms. Charged phospholipids were found to have antiviral effects and may be used to inhibit EHV-1 infection.
In his seminal works, Endel Tulving argued that functionally distinct memory systems give rise to subjective experiences of remembering and knowing (i.e., recollection- vs. familiarity-based memory, respectively). Evidence shows that emotion specifically enhances recollection, and this effect is subserved by a synergistic mechanism involving the amygdala (AMY) and hippocampus (HC). In extreme circumstances, however, uncontrolled recollection of highly distressing memories may lead to symptoms of affective disorders. Therefore, it is important to understand the factors that can diminish such detrimental effects. Here, we investigated the effects of Focused Attention (FA) on emotional recollection. FA is an emotion regulation strategy that has been proven quite effective in reducing the impact of emotional responses associated with the recollection of distressing autobiographical memories, but its impact during emotional memory encoding is not known. Functional MRI and eye-tracking data were recorded while participants viewed a series of composite negative and neutral images with distinguishable foreground (FG) and background (BG) areas. Participants were instructed to focus either on the FG or BG content of the images and to rate their emotional responses. About 4 days later, participants' memory was assessed using the R/K procedure, to indicate whether they Recollected specific contextual details about the encoded images or the images were just familiar to them - i.e., participants only Knew that they saw the pictures without being able to remember specific contextual details. First, results revealed that FA was successful in decreasing memory for emotional pictures viewed in BG Focus condition, and this effect was driven by recollection-based retrieval. Second, the BG Focus condition was associated with decreased activity in the AMY, HC, and anterior parahippocampal gyrus for subsequently recollected emotional items. Moreover, correlation analyses also showed that reduced activity in these regions predicted greater reduction in emotional recollection following FA. These results demonstrate the effectiveness of FA in mitigating emotional experiences and emotional recollection associated with unpleasant emotional events.
This paper analyses the interaction of domestic political elites and external donors against the backdrop of Mozambique’s decentralisation process. The empirical research at national and local levels supports the hypothesis that informal power structures influence the dynamics of this interaction. Consequently, this contributes to an outcome of externally induced democratisation different to what was intended by external actors. The decentralisation process has been utilised by ruling domestic elites for political purposes. Donors have rather focused on the technical side and ignored this informal dimension. By analysing the diverging objectives and perceptions of external and internal actors, as well as the instrumentalisation of formal democratic structures, it becomes clear, that the ‘informal has to be seen as normal’. At a theoretical level, the analysis contributes to elite-oriented approaches of post-conflict democratisation by adding ‘the informal’ as an additional factor for the dynamics of external-internal interaction. At a policy level, external actors need to take more into account informal power structures and their ambivalence for state-building and democratisation.