Mediamusic (E-Journal)
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Magnetic field dependent cycloidal rotation in pristine and Ge-doped CoCr2O4
No full textWe report a soft x-ray resonant magnetic scattering study of the spin configuration in multiferroic thin films of Co0.975Ge0.025Cr2O4 (Ge-CCO) and CoCr2O4 (CCO) under low and high magnetic fields from 0.2 to 6.5 T. A characterization of Ge-CCO at a low magnetic field was performed, and the results were compared with those of pure CCO. The ferrimagnetic phase transition temperature T-C approximate to 95 K and the multiferroic transition temperature T-S approximate to 27 K in Ge-CCO are comparable with those observed in CCO. In Ge-CCO, the ordering wave vector (qq0) observed below T-S is slightly larger compared with that of CCO, and unlike CCO, the diffraction intensity consists of two contributions that show a dissimilar x-ray polarization dependence. In Ge-CCO, the coercive field observed at low temperatures was larger than the one reported for CCO. In both compounds, an unexpected reversal of the spiral helicity, and therefore the electric polarization, was observed on simply magnetic field cooling. In addition, we find a change in the helicity as a function of momentum transfer in the magnetic diffraction peak of Ge-CCO, indicative of the presence of multiple magnetic spirals.</p
Correction:First-line BRAF/MEK inhibitors versus anti-PD-1 monotherapy in BRAFV600-mutant advanced melanoma patients: a propensity-matched survival analysis
No full textA Correction to this paper has been published: https://doi.org/10.1038/s41416-021-01312-1</p
Diminished Feedback Evaluation and Knowledge Updating Underlying Age-Related Differences in Choice Behavior During Feedback Learning
No full textIn our daily lives, we continuously evaluate feedback information, update our knowledge, and adapt our behavior in order to reach desired goals. This ability to learn from feedback information, however, declines with age. Previous research has indicated that certain higher-level learning processes, such as feedback evaluation, integration of feedback information, and updating of knowledge, seem to be affected by age, and recent studieshave shown how the adaption of choice behavior following feedback can differ with age. The neural mechanisms underlying this age-related change in choice behavior during learning, however, remain unclear. The aim of this study is therefore to investigate the relation between learning-related neural processes and choice behavior during feedback learning in two age groups. Behavioral and fMRI data were collected, while a group of young (age 18–30) and older (age 60–75) adults performed a probabilistic learning task consisting of 10 blocks of 20 trials each. On each trial, the participants chose between a house and a face, after which they received visual feedback (loss vs. gain). In each block, either the house or the face image had a higher probability of yielding a reward (62.5 vs. 37.5%). Participants were instructed to try to maximize their gains. Our results showed that less successful learning in older adults, as indicated by a lower learning rate, corresponded with a higher tendency to switch to the other stimulus option, and with a reduced adaptation of this switch choice behavior following positive feedback. At the neural level, activation following positive and negative feedback was found to be less distinctive in the older adults, due to a smaller feedback-evaluation response to positive feedback in this group. Furthermore, whereas young adults displayed increased levels of knowledge updating prior to adapting choice behavior, we did not find this effect in older adults. Together, our results suggest that diminished learning performance with agecorresponds with diminished evaluation of positive feedback and reduced knowledgeupdating related to changes in choice behavior, indicating how such differences infeedback processing at the trial level in older adults might lead to reduced learningperformance across trials
Mapping Arginase Expression with <sup>18</sup>F-Fluorinated Late-Generation Arginase Inhibitors Derived from Quaternary α-Amino Acids
No full textArginase hydrolyzes L-arginine and influences levels of polyamines and nitric oxide. Arginase overexpression is associated with inflammation and tumorigenesis. Thus, radiolabeled arginase inhibitors may be suitable PET tracers for staging arginase-related pathophysiologies. We report the synthesis and evaluation of 2 radiolabeled arginase inhibitors, 18F-FMARS and 18F-FBMARS, developed from α-substituted-2-amino-6-boronohexanoic acid derivatives. Methods: Arylboronic ester-derived precursors were radiolabeled via copper-mediated fluorodeboronation. Binding assays using arginase-expressing PC3 and LNCaP cells were performed. Autoradiography of lung sections from a guinea pig model of asthma overexpressing arginase and dynamic small-animal PET imaging with PC3-xenografted mice evaluated the radiotracers' specific binding and pharmacokinetics. Results:18F-fluorinated compounds were obtained with radiochemical yields of up to 5% (decay-corrected) and an average molar activity of 53 GBq⋅μmol-1 Cell and lung section experiments indicated specific binding that was blocked up to 75% after pretreatment with arginase inhibitors. Small-animal PET studies indicated fast clearance of the radiotracers (7.3 ± 0.6 min), arginase-mediated uptake, and a selective tumor accumulation (SUV, 3.0 ± 0.7). Conclusion: The new 18F-fluorinated arginase inhibitors have the potential to map increased arginase expression related to inflammatory and tumorigenic processes. 18F-FBMARS showed the highest arginase-mediated uptake in PET imaging and a significant difference between uptake in control and arginase-inhibited PC3 xenografted mice. These results encourage further research to examine the suitability of 18F-FBMARS for selecting patients for treatments with arginase inhibitors
National Heart, Lung and Blood Institute and Building Respiratory Epithelium and Tissue for Health (BREATH) Consortium Workshop Report:Moving Forward in Lung Regeneration
No full textThe National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health, along with the Longfonds BREATH consortium convened a working group to review the field of lung regeneration and suggest avenues for future research. The meeting took place on May 22, 2019 at the American Thoracic Society 2019 conference in Dallas, Texas, USA, and brought together investigators studying lung development, adult stem cell biology, induced pluripotent stem cells, biomaterials and respiratory disease. The purpose of the working group was 1) to examine the present status of basic science approaches to tackling lung disease and promoting lung regeneration in patients and 2) to determine priorities for future research in the field.</p
Mitochondrial dysfunction in neurodegenerative diseases:A focus on iPSC-derived neuronal models
No full textProgressive neuronal loss is a hallmark of many neurodegenerative diseases, including Alzheimer's and Parkinson's disease. These pathologies exhibit clear signs of inflammation, mitochondrial dysfunction, calcium deregulation, and accumulation of aggregated or misfolded proteins. Over the last decades, a tremendous research effort has contributed to define some of the pathological mechanisms underlying neurodegenerative processes in these complex brain neurodegenerative disorders. To better understand molecular mechanisms responsible for neurodegenerative processes and find potential interventions and pharmacological treatments, it is important to have robust in vitro and pre-clinical animal models that can recapitulate both the early biological events undermining the maintenance of the nervous system and early pathological events. In this regard, it would be informative to determine how different inherited pathogenic mutations can compromise mitochondrial function, calcium signaling, and neuronal survival. Since post-mortem analyses cannot provide relevant information about the disease progression, it is crucial to develop model systems that enable the investigation of early molecular changes, which may be relevant as targets for novel therapeutic options. Thus, the use of human induced pluripotent stem cells (iPSCs) represents an exceptional complementary tool for the investigation of degenerative processes. In this review, we will focus on two neurodegenerative diseases, Alzheimer's and Parkinson's disease. We will provide examples of iPSC-derived neuronal models and how they have been used to study calcium and mitochondrial alterations during neurodegeneration.</p
The groovy TMEM16 family:Molecular mechanisms of lipid scrambling and ion conduction
No full textThe TMEM16 family of membrane proteins displays a remarkable functional dichotomy - while some family members function as Ca2+-activated anion channels, the majority of characterized TMEM16 homologs are Ca2+-activated lipid scramblases, which catalyze the exchange of phospholipids between the two membrane leaflets. Furthermore, some TMEM16 scramblases can also function as channels. Due to their involvement in important physiological processes, the family has been actively studied ever since their molecular identity was unraveled. In this review, we will summarize the recent advances in the field and how they influenced our view of TMEM16 family function and evolution. Structural, functional and computational studies reveal how relatively small rearrangements in the permeation pathway are responsible for the observed functional duality: while TMEM16 scramblases can adopt both ion- and lipid conductive conformations, TMEM16 channels can only populate the former. Recent data further provides the molecular details of a stepwise activation mechanism, which is initiated by Ca2+ binding and modulated by various cellular factors, including lipids. TMEM16 function and the surrounding membrane properties are inextricably intertwined, with the protein inducing bilayer deformations associated with scrambling, while the surrounding lipids modulate TMEM16 conformation and activity.</p
What Do Migrants Know About Their Childcare Rights? A First Exploration in West Germany
No full textAlthough an increasing number of studies emphasise migrants' lack of knowledge about their childcare rights as a crucial barrier to their childcare usage, almost none examines the conditions under which migrant families acquire this knowledge. This study contributes to the literature by exploring potential individual factors determining migrant families' knowledge about their childcare rights in Germany. I use unique data collected through the project Migrants' Welfare State Attitudes (MIFARE), in which nine different migrant groups in Germany were surveyed about their relation to the welfare state, including childcare. Analysing a total sample of 623 migrants living with children in their household and by using logistic regression analyses, I find that human and social capital play significant roles in explaining migrants' knowledge about their childcare rights. Migrants who speak the host language sufficiently are more likely to know about their childcare rights; however, it does not matter whether migrants are lower or higher educated. Moreover, I observe that migrants benefit from their co-ethnic relations only if childcare usage is high among their ethnic group. Based on these results, policy recommendations are discussed in order to increase migrants' knowledge about their childcare rights in Germany.</p
Does value-based management facilitate managerial decision-making? An analysis of divestiture decisions
No full textWhile recent studies indicate that value-based management (VBM) helps owners in aligning managerial interests (i.e., decision-influencing role), little evidence is provided for its support in managerial decision-making (i.e., decision-facilitating role). We investigate whether the depth of VBM implementation and contextual factors may determine VBM’s decision-facilitating role. We investigate our research question on a dataset of 1,774 divestitures by European firms between 2005 and 2016. Divestitures allow for the analysis of managerial decision-making in situations where managerial self-interest is less pronounced and, thus, where VBM’s decision-facilitating role can be differentiated from its decision-influencing role. Our empirical results indicate that VBM implementation down to the business-unit level is positively associated with divestiture returns, while we find no such effect if VBM implementation is limited to the corporate level. Further empirical tests indicate that this positive association is contingent on a high dispersion of the costs of capital across a firm’s business portfolio. In sum, our study indicates that VBM can facilitate managerial decision-making when firms consider its depth of implementation and firm-specific information needs
Integrating Diversity into Distance Research for Added Rigor, Parsimony, and Relevance
No full textThe management of cross-national differences is of central concern in international business (IB) and international management (IM). Thus, it is not surprising that the concept of distance which captures such differences has received much attention in this field. Lumineau, Hanisch, and Wurtz, in their Point article, seek to strengthen distance research by challenging one of its key assumptions - country level homogeneity - and advancing an alternative view of country differences based on the notion of diversity. We concur with their critique of the homogeneity assumption and with the general idea of bringing in the concept of diversity. However, our approach to this goal is substantially different. Instead of replacing distance with a diversity-based conceptualization, as they seem to propose, our emphasis is on integrating diversity into current distance research. Moving beyond critique and high-level conceptualizing, we provide a usable roadmap for incorporating diversity into distance research both theoretically and empirically. Specifically, we introduce a new construct of intra-country diversity that captures the condition of within-country differences, and then, explain how it can be used to enrich distance models, illustrating our approach with several key IB/IM topics. Empirically, we use available cross-cultural data to illustrate how to account for different degrees and patterns of intra-country diversity in distance research. Overall, our approach aims at building on, not negating, existing distance research, increasing its rigor and relevance through the concept of diversity, and helping scholars incorporate diversity into their work by providing concrete guidelines and examples.</p