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Alcohol use disorder (AUD) is the most common substance use disorder worldwide. Although dopamine-related findings were often observed in AUD, associated neurobiological mechanisms are still poorly understood. Therefore, in the present study, we investigate D2/3 receptor availability in healthy participants, participants at high risk (HR) to develop addiction (not diagnosed with AUD), and AUD patients in a detoxified stage, applying F-18-fallypride positron emission tomography (F-18-PET). Specifically, D2/3 receptor availability was investigated in (1) 19 low-risk (LR) controls, (2) 19 HR participants, and (3) 20 AUD patients after alcohol detoxification. Quality and severity of addiction were assessed with clinical questionnaires and (neuro)psychological tests. PET data were corrected for age of participants and smoking status. In the dorsal striatum, we observed significant reductions of D2/3 receptor availability in AUD patients compared with LR participants. Further, receptor availability in HR participants was observed to be intermediate between LR and AUD groups (linearly decreasing). Still, in direct comparison, no group difference was observed between LR and HR groups or between HR and AUD groups. Further, the score of the Alcohol Dependence Scale (ADS) was inversely correlated with D2/3 receptor availability in the combined sample. Thus, in line with a dimensional approach, striatal D2/3 receptor availability showed a linear decrease from LR participants to HR participants to AUD patients, which was paralleled by clinical measures. Our study shows that a core neurobiological feature in AUD seems to be detectable in an early, subclinical state, allowing more individualized alcohol prevention programs in the future.
White mica and tourmaline are the dominant hydrothermal alteration minerals at the world-class Panasqueira W-Sn-Cu deposit in Portugal. Thus, understanding the controls on their chemical composition helps to constrain ore formation processes at this deposit and determine their usefulness as pathfinder minerals for mineralization in general. We combine whole-rock geochemistry of altered and unaltered metasedimentary host rocks with in situ LA-ICP-MS measurements of tourmaline and white mica from the alteration halo. Principal component analysis (PCA) is used to better identify geochemical patterns and trends of hydrothermal alteration in the datasets. The hydrothermally altered metasediments are enriched in As, Sn, Cs, Li, W, F, Cu, Rb, Zn, Tl, and Pb relative to unaltered samples. In situ mineral analyses show that most of these elements preferentially partition into white mica over tourmaline (Li, Rb, Cs, Tl, W, and Sn), whereas Zn is enriched in tourmaline. White mica has distinct compositions in different settings within the deposit (greisen, vein selvages, wall rock alteration zone, late fault zone), indicating a compositional evolution with time. In contrast, tourmaline from different settings overlaps in composition, which is ascribed to a stronger dependence on host rock composition and also to the effects of chemical zoning and microinclusions affecting the LA-ICP-MS analyses. Hence, in this deposit, white mica is the better recorder of the fluid composition. The calculated trace-element contents of the Panasqueira mineralizing fluid based on the mica data and estimates of mica-fluid partition coefficients are in good agreement with previous fluid-inclusion analyses. A compilation of mica and tourmaline trace-element compositions from Panasqueira and other W-Sn deposits shows that white mica has good potential as a pathfinder mineral, with characteristically high Li, Cs, Rb, Sn, and W contents. The trace-element contents of hydrothermal tourmaline are more variable. Nevertheless, the compiled data suggest that high Sn and Li contents are distinctive for tourmaline from W-Sn deposits.
In nature, plants are constantly exposed to many transient, but recurring, stresses. Thus, to complete their life cycles, plants require a dynamic balance between capacities to recover following cessation of stress and maintenance of stress memory. Recently, we uncovered a new functional role for macroautophagy/autophagy in regulating recovery from heat stress (HS) and resetting cellular memory of HS inArabidopsis thaliana. Here, we demonstrated that NBR1 (next to BRCA1 gene 1) plays a crucial role as a receptor for selective autophagy during recovery from HS. Immunoblot analysis and confocal microscopy revealed that levels of the NBR1 protein, NBR1-labeled puncta, and NBR1 activity are all higher during the HS recovery phase than before. Co-immunoprecipitation analysis of proteins interacting with NBR1 and comparative proteomic analysis of annbr1-null mutant and wild-type plants identified 58 proteins as potential novel targets of NBR1. Cellular, biochemical and functional genetic studies confirmed that NBR1 interacts with HSP90.1 (heat shock protein 90.1) and ROF1 (rotamase FKBP 1), a member of the FKBP family, and mediates their degradation by autophagy, which represses the response to HS by attenuating the expression ofHSPgenes regulated by the HSFA2 transcription factor. Accordingly, loss-of-function mutation ofNBR1resulted in a stronger HS memory phenotype. Together, our results provide new insights into the mechanistic principles by which autophagy regulates plant response to recurrent HS.
Induced point mutations are important genetic resources for their ability to create hypo- and hypermorphic alleles that are useful for understanding gene functions and breeding. However, such mutant populations have only been developed for a few temperate maize varieties, mainly B73 and W22, yet no tropical maize inbred lines have been mutagenized and made available to the public to date. We developed a novel Ethyl Methanesulfonate (EMS) induced mutation resource in maize comprising 2050 independent M2 mutant families in the elite tropical maize inbred ML10. By phenotypic screening, we showed that this population is of comparable quality with other mutagenized populations in maize. To illustrate the usefulness of this population for gene discovery, we performed rapid mapping-by-sequencing to clone a fasciated-ear mutant and identify a causal promoter deletion in ZmCLE7 (CLE7). Our mapping procedure does not require crossing to an unrelated parent, thus is suitable for mapping subtle traits and ones affected by heterosis. This first EMS population in tropical maize is expected to be very useful for the maize research community. Also, the EMS mutagenesis and rapid mapping-by-sequencing pipeline described here illustrate the power of performing forward genetics in diverse maize germplasms of choice, which can lead to novel gene discovery due to divergent genetic backgrounds.
Increasingly fast development cycles and individualized products pose major challenges for today's smart production systems in times of industry 4.0. The systems must be flexible and continuously adapt to changing conditions while still guaranteeing high throughputs and robustness against external disruptions. Deep reinforcement learning (RL) algorithms, which already reached impressive success with Google DeepMind's AlphaGo, are increasingly transferred to production systems to meet related requirements. Unlike supervised and unsupervised machine learning techniques, deep RL algorithms learn based on recently collected sensorand process-data in direct interaction with the environment and are able to perform decisions in real-time. As such, deep RL algorithms seem promising given their potential to provide decision support in complex environments, as production systems, and simultaneously adapt to changing circumstances. While different use-cases for deep RL emerged, a structured overview and integration of findings on their application are missing. To address this gap, this contribution provides a systematic literature review of existing deep RL applications in the field of production planning and control as well as production logistics. From a performance perspective, it became evident that deep RL can beat heuristics significantly in their overall performance and provides superior solutions to various industrial use-cases. Nevertheless, safety and reliability concerns must be overcome before the widespread use of deep RL is possible which presumes more intensive testing of deep RL in real world applications besides the already ongoing intensive simulations.
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.
One for all, all for one
(2022)
We propose a conceptual model of acceptance of contact tracing apps based on the privacy calculus perspective. Moving beyond the duality of personal benefits and privacy risks, we theorize that users hold social considerations (i.e., social benefits and risks) that underlie their acceptance decisions. To test our propositions, we chose the context of COVID-19 contact tracing apps and conducted a qualitative pre-study and longitudinal quantitative main study with 589 participants from Germany and Switzerland. Our findings confirm the prominence of individual privacy calculus in explaining intention to use and actual behavior. While privacy risks are a significant determinant of intention to use, social risks (operationalized as fear of mass surveillance) have a notably stronger impact. Our mediation analysis suggests that social risks represent the underlying mechanism behind the observed negative link between individual privacy risks and contact tracing apps' acceptance. Furthermore, we find a substantial intention–behavior gap.
This article examines public service resilience during the COVID-19 pandemic and studies the switch to telework due to social distancing measures. We argue that the pandemic and related policies led to increasing demands on public organisations and their employees. Following the job demands-resources model, we argue that resilience only can arise in the presence of resources for buffering these demands. Survey data were collected from 1,189 German public employees, 380 participants were included for analysis. The results suggest that the public service was resilient against the crisis and that the shift to telework was not as demanding as expected.
Business incubators hatch start-ups, helping them to survive their early stage and to create a solid foundation for sustainable growth by providing services and access to knowledge. The great practical relevance led to a strong interest of researchers and a high output of scholarly publications, which made the field complex and scattered. To organize the research on incubators and provide a systematic overview of the field, we conducted bibliometric performance analyses and science mappings. The performance analyses depict the temporal development of the number of incubator publications and their citations, the most cited and most productive journals, countries, and authors, and the 20 most cited articles. The author keyword co-occurrence analysis distinguishes six, and the bibliographic coupling seven research themes. Based on a content analysis of the science mappings, we propose a research framework for future research on business incubators.