Measurement Uncertainties in Fibre-coupled Spectrographs

The signal quality of fibre-coupled spectrographs can be limited by the inherent properties of the optical fibre. This is especially the case for applications that require high signal-to-noise performance and high spectral resolution. Examples include metallicity and age of star clusters, as well as investigations of Lyman-alpha absorbers. Extra-solar planet research in particular encounters its limitations due to the non-repeatability of the fibre response. Initially, a limited signal quality due to fibres seems counter-intuitive, since one of the most remarkable advantages of fibres is their signal stabilizing property, called image scrambling, which refers to the effect that the fibre output signal is largely insensitive to variations at the input side. However, the fibre photometric and barycentre response is sub ject to external parameters like stress, seeing and guiding variations. State-of-the-art instrumentation has attained a level of sensitivity where these effects will impact upon instrument performance, especially when advancing to a regime of spectral resolving powers where the quantized character of the standard optical fibre can be resolved, which manifests itself in modal noise. Unprecedented effort will be required in order to accomplish high resolving powers in the spectral and spatial domains with 40 m class telescopes. It is therefore essential to predict these fibre-related measurement uncertainties so that the performance of current and future instruments can be optimized. This thesis starts out with a phenomenological description of the different effects that give rise to fibre-related noise and its influence on the observables relevant to astrophysics, such as barycentre and photometric stability. Special emphasis is given to the photometric uncertainties related to modal noise, where first a theoretical model is outlined which in later chapters will be sub ject to experimental investigations. Subsequently, the barycentre repeatability due to incomplete scrambling is the subject of detailed investigation. The remaining sources of noise are estimated using experimental data as well as simulations and put in contrast with the other effects. Alongside the quantitative prediction of instrument instabilities, mitigation strategies will be presented and discussed. I conclude with a brief discussion of the impact of incomplete scrambling and modal noise on current instrumentation, the implications for future instrument pro jects as well as future work that will help to further understand and obviate the underlying mechanisms

The role of transcriptional repressor Hes-1 in glucocorticoid-mediated fatty liver development

Aberrant hepatic fat accumulation (“fatty liver”) represents a pathophysiological hallmark of obesity and is associated with extended glucocorticoid therapy, obesity, Type II diabetes, and starvation. Elevated glucocorticoid levels under these conditions are causative for the fatty liver phenotype, although the molecular mechanisms of their action remain largely unclear. This study demonstrates that glucocorticoids (GCs) promote fatty liver development through facilitated fat transport into the liver and not due to increased de novo fat synthesis. Transient knock-down of hepatic GR was associated with decreased hepatic gene expression of the fat transporters CD36 and caveolin 1 and with decreased expression of peroxisome proliferation-activating receptor gamma (PPARgamma) – a transcription factor promoting CD36 and caveolin expression. Moreover, glucocorticoids inhibited hepatic expression of transcriptional repressor Hairy and Enhancer of Split-1 (Hes-1) a previously identified anti-lipogenic factor. In fatty liver mouse models characterized by elevated GC levels diminished Hes-1 levels correlated with increased hepatic lipid stores. Genetic restoration of hepatic Hes-1 levels in obese mice normalized hepatic triglyceride levels and improved systemic insulin sensitivity. In mice injected with GCs for three weeks, genetically restored hepatic Hes-1 levels inhibited GC-induced liver fat accumulation. In both models, sustained Hes-1 was accompanied by increased oxidative consumption of triglycerides and decreased fat import into the liver. Hes-1 re-expression inhibited hepatic PPARgamma, CD36 and caveolin expression resembling effects in mice with transient GR knockdown. Loss of function analysis in primary hepatocytes confirmed PPARgamma and Cav1 as Hes-1 target genes. The data suggest that Hes-1 antagonizes GR-mediated transcriptional regulation of fat transport programs in the liver. Mechanistically, glucocorticoid exposure of hepatocytes lead to the disassembly of a cAMP-dependent CREB transactivator complex on the proximal Hes-1 gene promoter. The glucocorticoid receptor was shown here to decrease intracellular P-CREB levels and to interact with CREB via the bZIP domain of CREB. Furthermore, GR associated to glucocorticoid response elements in the proximal Hes-1 promoter region. Inhibition of hepatic Hes-1 provides a rationale for glucocorticoid-induced fatty liver development. Restoration of Hes-1 activity might, therefore, represent a new approach in the treatment of Non-Alcoholic Fatty Liver Disease and its associated complications such as hepatic insulin resistance

Promoting hearing and cognitive health in audiologic rehabilitation for the well-being of older adults

Objective: With our aging population, an increasing number of older adults with hearing loss have cognitive decline. Hearing care practitioners have an important role in supporting healthy aging and should be knowledgeable about cognitive decline and associated management strategies to maximize successful hearing intervention. Methods: A review of current research and expert opinion. Results: This article outlines the association between hearing loss and cognitive decline/dementia, hypothesized mechanisms underlying this, and considers current research into the effects of hearing intervention on cognitive decline. Cognition into old age, cognitive impairment, dementia, and how to recognize cognitive decline that is not part of normal aging are described. Screening of older asymptomatic adults for cognitive decline and practical suggestions for the delivery of person-centered hearing care are discussed. Holistic management goals, personhood, and person-centered care in hearing care management are considered for older adults with normal cognitive aging through to dementia. A case study illustrates important skills and potential management methods. Prevention strategies for managing hearing and cognitive health and function through to older age, and strategies to maximize successful hearing aid use are provided. Conclusion: This article provides evidence-based recommendations for hearing care professionals supporting older clients to maximize well-being through the cognitive trajectory

The Influence of IL-10 and TNFα on Chondrogenesis of Human Mesenchymal Stromal Cells in Three-Dimensional Cultures

Chondrogenic differentiated mesenchymal stromal cells (MSCs) are a promising cell source for articular cartilage repair. This study was undertaken to determine the effectiveness of two three-dimensional (3D) culture systems for chondrogenic MSC differentiation in comparison to primary chondrocytes and to assess the effect of Interleukin (IL)-10 and Tumor Necrosis Factor (TNF)α on chondrogenesis by MSCs in 3D high-density (H-D) culture. MSCs were isolated from femur spongiosa, characterized using a set of typical markers and introduced in scaffold-free H-D cultures or non-woven polyglycolic acid (PGA) scaffolds for chondrogenic differentiation. H-D cultures were stimulated with recombinant IL-10, TNFα, TNFα + IL-10 or remained untreated. Gene and protein expression of type II collagen, aggrecan, sox9 and TNFα were examined. MSCs expressed typical cell surface markers and revealed multipotency. Chondrogenic differentiated cells expressed cartilage-specific markers in both culture systems but to a lower extent when compared with articular chondrocytes. Chondrogenesis was more pronounced in PGA compared with H-D culture. IL-10 and/or TNFα did not impair the chondrogenic differentiation of MSCs. Moreover, in most of the investigated samples, despite not reaching significance level, IL-10 had a stimulatory effect on the type II collagen, aggrecan and TNFα expression when compared with the respective controls

Neural processing of emotional facial stimuli in specific phobia: An fMRI study

Background Patients with specific phobia (SP) show altered brain activation when confronted with phobia-specific stimuli. It is unclear whether this pathogenic activation pattern generalizes to other emotional stimuli. This study addresses this question by employing a well-powered sample while implementing an established paradigm using nonspecific aversive facial stimuli. Methods N = 111 patients with SP, spider subtype, and N = 111 healthy controls (HCs) performed a supraliminal emotional face-matching paradigm contrasting aversive faces versus shapes in a 3-T magnetic resonance imaging scanner. We performed region of interest (ROI) analyses for the amygdala, the insula, and the anterior cingulate cortex using univariate as well as machine-learning-based multivariate statistics based on this data. Additionally, we investigated functional connectivity by means of psychophysiological interaction (PPI). Results Although the presentation of emotional faces showed significant activation in all three ROIs across both groups, no group differences emerged in all ROIs. Across both groups and in the HC > SP contrast, PPI analyses showed significant task-related connectivity of brain areas typically linked to higher-order emotion processing with the amygdala. The machine learning approach based on whole-brain activity patterns could significantly differentiate the groups with 73% balanced accuracy. Conclusions Patients suffering from SP are characterized by differences in the connectivity of the amygdala and areas typically linked to emotional processing in response to aversive facial stimuli (inferior parietal cortex, fusiform gyrus, middle cingulate, postcentral cortex, and insula). This might implicate a subtle difference in the processing of nonspecific emotional stimuli and warrants more research furthering our understanding of neurofunctional alteration in patients with SP.Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659Peer Reviewe