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Hermanussen, Michael ; Scheffler, Christiane ; Pulungan, Aman B. ; Batubara, Jose R. L. ; Julia, Madarina ; Bogin, Barry
Wang, Wei-shi ; Oswald, Sascha Eric ; Gräff, Thomas ; Lensing, Hermann-Josef ; Liu, Tie ; Strasser, Daniel ; Munz, Matthias
Raoufi, Meysam ; Hörmann, Ulrich ; Ligorio, Giovanni ; Hildebrandt, Jana ; Pätzel, Michael ; Schultz, Thorsten ; Perdigon, Lorena ; Koch, Norbert ; List-Kratochvil, Emil ; Hecht, Stefan ; Neher, Dieter
The combined effect of ultraviolet (UV) light soaking and self-assembled monolayer deposition on the work function (WF) of thin ZnO layers and on the efficiency of hole injection into the prototypical conjugated polymer poly(3-hexylthiophen-2,5-diyl) (P3HT) is systematically investigated. It is shown that the WF and injection efficiency depend strongly on the history of UV light exposure. Proper treatment of the ZnO layer enables ohmic hole injection into P3HT, demonstrating ZnO as a potential anode material for organic optoelectronic devices. The results also suggest that valid conclusions on the energy-level alignment at the ZnO/organic interfaces may only be drawn if the illumination history is precisely known and controlled. This is inherently problematic when comparing electronic data from ultraviolet photoelectron spectroscopy (UPS) measurements carried out under different or ill-defined illumination conditions.
Background:
Anti-TNFα monoclonal antibodies (mAbs) are a well-established treatment for patients with Crohn’s disease (CD). However, subtherapeutic concentrations of mAbs have been related to a loss of response during the first year of therapy1. Therefore, an appropriate dosing strategy is crucial to prevent the underexposure of mAbs for those patients. The aim of our study was to assess the impact of different dosing strategies (fixed dose or body size descriptor adapted) on drug exposure and the target concentration attainment for two different anti-TNFα mAbs: infliximab (IFX, body weight (BW)-based dosing) and certolizumab pegol (CZP, fixed dosing). For this purpose, a comprehensive pharmacokinetic (PK) simulation study was performed.
Methods:
A virtual population of 1000 clinically representative CD patients was generated based on the distribution of CD patient characteristics from an in-house clinical database (n = 116). Seven dosing regimens were investigated: fixed dose and per BW, lean BW (LBW), body surface area, height, body mass index and fat-free mass. The individual body size-adjusted doses were calculated from patient generated body size descriptor values. Then, using published PK models for IFX and CZP in CD patients2,3, for each patient, 1000 concentration–time profiles were simulated to consider the typical profile of a specific patient as well as the range of possible individual profiles due to unexplained PK variability across patients. For each dosing strategy, the variability in maximum and minimum mAb concentrations (Cmax and Cmin, respectively), area under the concentration-time curve (AUC) and the per cent of patients reaching target concentration were assessed during maintenance therapy.
Results:
For IFX and CZP, Cmin showed the highest variability between patients (CV ≈110% and CV ≈80%, respectively) with a similar extent across all dosing strategies. For IFX, the per cent of patients reaching the target (Cmin = 5 µg/ml) was similar across all dosing strategies (~15%). For CZP, the per cent of patients reaching the target average concentration of 17 µg/ml ranged substantially (52–71%), being the highest for LBW-adjusted dosing.
Conclusion:
By using a PK simulation approach, different dosing regimen of IFX and CZP revealed the highest variability for Cmin, the most commonly used PK parameter guiding treatment decisions, independent upon dosing regimen. Our results demonstrate similar target attainment with fixed dosing of IFX compared with currently recommended BW-based dosing. For CZP, the current fixed dosing strategy leads to comparable percentage of patients reaching target as the best performing body size-adjusted dosing (66% vs. 71%, respectively).
The termprocess modelis widely used, but rarely agreed upon. This paper proposes a framework for characterizing and building cognitive process models. Process models model not only inputs and outputs but also model the ongoing information transformations at a given level of abstraction. We argue that the following dimensions characterize process models: They have a scope that includes different levels of abstraction. They specify a hypothesized mental information transformation. They make predictions not only for the behavior of interest but also for processes. The models' predictions for the processes can be derived from the input, without reverse inference from the output data. Moreover, the presumed information transformation steps are not contradicting current knowledge of human cognitive capacities. Lastly, process models require a conceptual scope specifying levels of abstraction for the information entering the mind, the proposed mental events, and the behavior of interest. This framework can be used for refining models before testing them or after testing them empirically, and it does not rely on specific modeling paradigms. It can be a guideline for developing cognitive process models. Moreover, the framework can advance currently unresolved debates about which models belong to the category of process models.
Ben Dor, Yoav ; Neugebauer, Ina ; Enzel, Yehouda ; Schwab, Markus J. ; Tjallingii, Rik ; Erel, Yigal ; Brauer, Achim
In the comment on "Varves of the Dead Sea sedimentary record." Quaternary Science Reviews 215 (Ben Dor et al., 2019): 173-184. by R. Bookman, two recently published papers are suggested to prove that the interpretation of the laminated sedimentary sequence of the Dead Sea, deposited mostly during MIS2 and Holocene pluvials, as annual deposits (i.e., varves) is wrong. In the following response, we delineate several lines of evidence which coalesce to demonstrate that based on the vast majority of evidence, including some of the evidence provided in the comment itself, the interpretation of these sediments as varves is the more likely scientific conclusion. We further discuss the evidence brought up in the comment and its irrelevance and lack of robustness for addressing the question under discussion.
Aldehyde oxidases (AOXs) are a small group of enzymes belonging to the larger family of molybdo-flavoenzymes, along with the well-characterized xanthine oxidoreductase. The two major types of reactions that are catalyzed by AOXs are the hydroxylation of heterocycles and the oxidation of aldehydes to their corresponding carboxylic acids. Different animal species have different complements of AOX genes. The two extremes are represented in humans and rodents; whereas the human genome contains a single active gene (AOX1), those of rodents, such as mice, are endowed with four genes (Aox1-4), clustering on the same chromosome, each encoding a functionally distinct AOX enzyme. It still remains enigmatic why some species have numerous AOX enzymes, whereas others harbor only one functional enzyme. At present, little is known about the physiological relevance of AOX enzymes in humans and their additional forms in other mammals. These enzymes are expressed in the liver and play an important role in the metabolisms of drugs and other xenobiotics. In this review, we discuss the expression, tissue-specific roles, and substrate specificities of the different mammalian AOX enzymes and highlight insights into their physiological roles.
Kunstmann, Ruth Sonja ; Engström, Olof ; Wehle, Marko ; Widmalm, Göran ; Santer, Mark ; Barbirz, Stefanie
Broad and unspecific use of antibiotics accelerates spread of resistances. Sensitive and robust pathogen detection is thus important for a more targeted application. Bacteriophages contain a large repertoire of pathogen-binding proteins. These tailspike proteins (TSP) often bind surface glycans and represent a promising design platform for specific pathogen sensors. We analysed bacteriophage Sf6 TSP that recognizes the O-polysaccharide of dysentery-causing Shigella flexneri to develop variants with increased sensitivity for sensor applications. Ligand polyrhamnose backbone conformations were obtained from 2D H-1,H-1-trNOESY NMR utilizing methine-methine and methine-methyl correlations. They agreed well with conformations obtained from molecular dynamics (MD), validating the method for further predictions. In a set of mutants, MD predicted ligand flexibilities that were in good correlation with binding strength as confirmed on immobilized S. flexneri O-polysaccharide (PS) with surface plasmon resonance. In silico approaches combined with rapid screening on PS surfaces hence provide valuable strategies for TSP-based pathogen sensor design.
Do all roads lead to Rome?
(2020)
Content website providers have two main goals: They seek to attract consumers and to keep them on their websites as long as possible. To reach potential consumers, they can utilize several online channels, such as paid search results or advertisements on social media, all of which usually require a substantial marketing budget. However, with rising user numbers of online communication tools, website providers increasingly integrate social sharing buttons on their websites to encourage existing consumers to facilitate referrals to their social networks. While little is known about this social form of guiding consumers to a content website, the study proposes that the way in which consumers reach a website is related to their stickiness to the website and their propensity to refer content to others. By using a unique clickstream data set of a video-on-demand website, the study compares consumers referred by their social network to those consumers arriving at the website via organic search or social media advertisements in terms of stickiness to the website (e.g., visit length, number of page views, video starts) and referral likelihood. The results show that consumers referred through social referrals spend more time on the website, view more pages, and start more videos than consumers who respond to social media advertisements, but less than those coming through organic search. Concerning referral propensity, the results indicate that consumers attracted to a website through social referrals are more likely to refer content to others than those who came through organic search or social media advertisements. The study offers direct insights to managers and recommends an increase in their efforts to promote social referrals on their websites.
Do all roads lead to Rome?
(2020)
Content website providers have two main goals: They seek to attract consumers and to keep them on their websites as long as possible. To reach potential consumers, they can utilize several online channels, such as paid search results or advertisements on social media, all of which usually require a substantial marketing budget. However, with rising user numbers of online communication tools, website providers increasingly integrate social sharing buttons on their websites to encourage existing consumers to facilitate referrals to their social networks. While little is known about this social form of guiding consumers to a content website, the study proposes that the way in which consumers reach a website is related to their stickiness to the website and their propensity to refer content to others. By using a unique clickstream data set of a video-on-demand website, the study compares consumers referred by their social network to those consumers arriving at the website via organic search or social media advertisements in terms of stickiness to the website (e.g., visit length, number of page views, video starts) and referral likelihood. The results show that consumers referred through social referrals spend more time on the website, view more pages, and start more videos than consumers who respond to social media advertisements, but less than those coming through organic search. Concerning referral propensity, the results indicate that consumers attracted to a website through social referrals are more likely to refer content to others than those who came through organic search or social media advertisements. The study offers direct insights to managers and recommends an increase in their efforts to promote social referrals on their websites.
This article explores the structural diversity of intraministerial organization over time. Based on organization theory, it proposes a generic typology for intraministerial units applicable to any hierarchically structured government organization. We empirically investigate the critical case of the German federal bureaucracy. By classifying its subunits, we analyze the longitudinal development of structural differentiation and its correspondence to denominational variety. The data stem from a novel international dataset, covering all ministries between 1980 and 2015. We find that intraministerial structure differentiates over time, across and within ministries. A stable core of traditional Weberian structure is complemented by structurally innovative intraministerial units. We conclude that the German federal bureaucracy is more diverse than suggested in previous literature. Our findings indicate that less Weberian bureaucracies are at least as structurally diverse and that more reform-driven bureaucracies will have experienced at least as many changes in structural diversity.
Digitale Plattformen
(2020)
Obwohl digitale Plattformen vornehmlich von Großunternehmen betrieben werden, bieten sie klein- und mittelständischen Unternehmen (KMU) Potenziale zur Verbreitung innovativer Technologien und für den Ausbau ihres Geschäftsmodells. Für die Umsetzung digitaler Plattformen stehen Unternehmen mehrere Strategien zur Verfügung. Der Beitrag vergleicht und bewertet grundlegende Strategien am Beispiel eines Maschinenbauunternehmens. Die Ergebnisse dienen als Grundlage für die Entscheidungsfindung von KMU.
Birds of a feather?
(2020)
Heinzel, Mirko Noa ; Richter, Jonas ; Busch, Per-Olof ; Feil, Hauke ; Herold, Jana ; Liese, Andrea Margit
The International Monetary Fund and the World Bank ascribe to impartiality in their mandates. At the same time, scholarship indicates that their decisions are disproportionately influenced by powerful member states. Impartiality is seen as crucial in determining International Organizations' (IOs) effectiveness and legitimacy in the literature. However, we know little about whether key interlocutors in national governments perceive the International Financial Institutions as biased actors who do the bidding for powerful member states or as impartial executors of policy. In order to better understand these perceptions, we surveyed high-level civil servants who are chiefly responsible for four policy areas from more than 100 countries. We found substantial variations in impartiality perceptions. What explains these variations? By developing an argument of selective awareness, we extend rationalist and ideational perspectives on IO impartiality to explain domestic perceptions. Using novel survey data, we test whether staffing underrepresentation, voting underrepresentation, alignment to the major shareholders and overlapping economic policy paradigms are associated with impartiality perceptions. We find substantial evidence that shared economic policy paradigms influence impartiality perceptions. The findings imply that by diversifying their ideational culture, IOs can increase the likelihood that domestic stakeholders view them as impartial.
The COVID-19 virus has hit Germany as unexpectedly as other European countries. For a few weeks, Germans thought that COVID-19 was an issue for Asian states and not for their country. Although Germany continues to be affected by the coronavirus, the situation is nowhere as dire as it was in Britain, Italy or Spain. The race to lift restrictions in Germany began in May, and by early June, the country may be back to normal. Germany, with its enormous financial resources and a well-equipped medical sector, appears to be better placed than other economies to weather the storm.
Scholars have long recognised the importance of contexts of reception in shaping the integration of immigrants and refugees in a host society. Studies of refugees, in particular, have examined groups where the different dimensions of reception (government, labour market, and ethnic community) have been largely positive. How important is this merging of positive contexts across dimensions of reception? We address this through a comparative study of Vietnamese refugees to West Germany beginning in 1979 and contract workers to East Germany beginning in 1980. These two migration streams converged when Germany reunified in 1990. Drawing on mixed qualitative methods, this paper offers a strategic case for understanding factors that shape the resettlement experiences of Vietnamese refugees and immigrants in Germany. By comparing two migration streams from the same country of origin, but with different backgrounds and contexts of reception, we suggest that ethnic networks may, in time, offset the disadvantages of a negative government reception.
Value research has a long and extensive history of theoretical definitions and empirical investigations using large scale quantitative surveys. However, the way the general population understands, defines, and relates to the concept of values, and how these views vary across individuals is seldom addressed. The present study examined subjective interpretations of the term through focus group interviews, and reports on the development of a Value Conceptualisation Scale (VCS) that distinguishes six dimensions of different views on values: normativity, relevance, validity, stability, consistency, and awareness. Focus group interviews (n = 38) as well as several surveys (n = 100, n = 1519, n = 903, n = 94) were used to develop, refine, and test the scale in terms of response variety, temporal stability, as well as convergent and discriminant validity. These systematic results show that views on values do indeed vary significantly between participants. Correlations with dogmatism, preference for consistency, and metacognition were found for corresponding dimensions. The VCS provides an original measure, which enables future research to explore this variation on the conceptualisation of values.
Griscom, Bronson W. ; Busch, Jonah ; Cook-Patton, Susan C. ; Ellis, Peter W. ; Funk, Jason ; Leavitt, Sara M. ; Lomax, Guy ; Turner, Will R. ; Chapman, Melissa ; Streck, Charlotte
Better land stewardship is needed to achieve the Paris Agreement's temperature goal, particularly in the tropics, where greenhouse gas emissions from the destruction of ecosystems are largest, and where the potential for additional land carbon storage is greatest. As countries enhance their nationally determined contributions (NDCs) to the Paris Agreement, confusion persists about the potential contribution of better land stewardship to meeting the Agreement's goal to hold global warming below 2 degrees C. We assess cost-effective tropical country-level potential of natural climate solutions (NCS)-protection, improved management and restoration of ecosystems-to deliver climate mitigation linked with sustainable development goals (SDGs). We identify groups of countries with distinctive NCS portfolios, and we explore factors (governance, financial capacity) influencing the feasibility of unlocking national NCS potential. Cost-effective tropical NCS offers globally significant climate mitigation in the coming decades (6.56 Pg CO(2)e yr(-1) at less than 100 US$ per Mg CO(2)e). In half of the tropical countries, cost-effective NCS could mitigate over half of national emissions. In more than a quarter of tropical countries, cost-effective NCS potential is greater than national emissions. We identify countries where, with international financing and political will, NCS can cost-effectively deliver the majority of enhanced NDCs while transforming national economies and contributing to SDGs. This article is part of the theme issue 'Climate change and ecosystems: threats, opportunities and solutions'.