Neuroendocrine stress responsiveness in human obesity and non-obesity controls

BACKGROUND: Obesity is a leading health burden of the 21st century. Alterations of the individual endocrine stress response and the monoamine system may pathophysiologically contribute to the obesity pandemic and its metabolic and mental complications. OBJECTIVES: (i) to measure hypothalamic-pituitary-adrenal (HPA) axis responsiveness and its relation to serum concentrations of the arginine-vasopressin (AVP) surrogate copeptin in subjects with obesity (OB) compared to non-obesity controls (NOC), (ii) to test whether HPA axis responsiveness and copeptin are related to central noradrenaline (NA) transporter (NAT) availability, (iii) to assess brain serotonin transporter (SERT) binding potentials in OB compared to NOC. METHODS: 40 subjects with obesity (BMI > 35kg/m2) were compared to 25 non-obesity controls, matched for age and sex. (i) All individuals underwent the combined dexamethasone/corticotropin releasing hormone (dex/CRH) test. Plasma ACTH and cortisol curve parameters were derived, and copeptin was assessed in the 1500h sample. (ii) Positron emission tomography (PET) was applied in 10 OB and 10 NOC using the NAT-selective radiotracer S,S-[11C]O-methylreboxetine (MRB) and associated to curve indicators derived from the dex/CRH test as well as to copeptin. (iii) PET using the SERT selective radiotracer [11C] DASB was performed in 30 OB and 15 NOC for intergroup comparison. RESULTS: (i) OB subjects showed an increased HPA axis responsiveness as measured by cortisol concentrations after CRH stimulation. Correspondingly, the AVP surrogate copeptin was higher in OB along with being significantly associated to HPA axis reactivity. OB subjects had a higher adrenal sensitivity as measured by a lower ACTH/cortisol ratio. (ii) In NOC, the HPA response was related to NAT availability of the amygdala and the orbitofrontal cortex while in OB, this association was located in the hypothalamus. (iii) There were no differences in SERT availability between OB and NOC, but a higher inter-regional SERT connectivity was observed in OB. CONCLUSION: This work supports the notion of an increased endocrine stress response in human obesity, pointing to interacting alterations of the HPA and neurohypophyseal axes. Normally, these stress axes seem to be linked to prefrontal-limbic NA signaling, whereas a loss of this association in favor of a hypothalamic-centered relation is observed in OB. The SERT network pattern is more closely inter-related in OB, albeit central SERT concentrations per se do not differ between OB and NOC.:ABBREVIATIONS 4 LIST OF FIGURES 5 I. BIBLIOGRAPHIC DESCRIPTION 6 II. INTRODUCTION 7 2.1 Obesity as a global health burden 7 2.2 Neurobiology of stress 8 2.3 Stress and obesity 8 2.4 Neuroendocrine correlates of the stress response – The hypothalamic pituitary-adrenaland neurohypophyseal axes 9 2.4.1 Anatomy of the hypothalamic-pituitary-adrenal and neurohypophyseal axes 10 2.4.2 The role of CRH, ACTH and cortisol in the context of metabolism and obesity 11 2.4.3 The role of AVP in the context of metabolism and obesity 12 2.4.4 Measuring HPA axis responsiveness by means of the combined dexamethasonecorticotropin-releasing hormone (dex/CRH) test 12 2.4.5 Measuring AVP secretion by its equally-released surrogate copeptin 14 2.5 The noradrenergic system in the context of obesity and stress axis modulation 14 2.5.1 NA and its influence on feeding behavior16 2.5.2 The association of the noradrenergic system with the HPA and neurohypophyseal axes 16 2.5.3 Monoamine transporters as regulators of neurotransmitter signaling 17 2.5.4 Noradrenaline transporter imaging 18 2.6 The serotonergic system in obesity 19 2.6.1 Role of serotonin in the context of feeding behavior and metabolism 20 2.6.3 5-HTT imaging 21 2.7 Objectives and hypotheses 22 2.8 Study design 23 III. RESULTS 24 3. 1 Post-dexamethasone serum copeptin corresponds to HPA axis responsiveness in human obesity 24 3. 2 Central noradrenaline transporter availability is linked with HPA axis responsiveness and copeptin in human obesity and non-obese controls 34 3. 3 Central serotonin transporter availability in highly obese individuals compared with nonobese controls: A [11C] DASB positron emission tomography study 46 IV. SUMMARY 56 4.1 Subjects with obesity show an enhanced HPA axis responsiveness which correlates to serum concentrations of the AVP surrogate copeptin and abdominal fat distribution 56 4.2 HPA axis responsiveness and copeptin concentrations are differentially related to central NAT availability in subjects with obesity compared to non-obesity controls 58 4.3 Central serotonin transporter availability does not significantly differ in subjects with obesity compared to their non-obesity counterparts 59 4.4 Future direction 61 V. References 62 VI. APPENDICES 79 6.1 Curriculum vitae 79 6.2 Publications 81 6.3 Scientific contribution of the doctoral candidate to the publications 82 6.4 Declaration of the independent writing of this thesis 83 6.5 Acknowledgements 8

Uncertainty of the coefficient of band-to-band absorption of crystalline silicon at near-infrared wavelengths

We present data of the coefficient of band-to-band absorption of crystalline silicon at 295 K in the wavelength range from 950 to 1350 nm and analyze its uncertainty. The data is obtained from measurements of reflectance and transmittance as well as spectrally resolved photoluminescence measurements and spectral response measurements. A rigorous measurement uncertainty analysis based on an extensive characterization of our setups is carried out. We determine relative uncertainties of 4% at 1000 nm, increasing to 22% at 1200 nm and 160% at 1300 nm, and show that all methods yield comparable results. © 2014 AIP Publishing LLC

Impact of contacting geometries on measured fill factors

The fill factor determined from a measured current-voltage characteristic of a bare solar cell depends on the number and positions of the electrical contacting probes. Nine different geometries for contacting the front side busbars are used to measure the current-voltage (I-V) characteristics of a 5 busbar industrial-type passivated emitter and rear totally diffused (PERT) solar cell under standard testing conditions. The fill factors of the measured I-V characteristics vary from 78.5 %abs to 80.6 %abs. We further measure the contacting resistance of 3 different contacting probes to estimate the sensitivity of measurements with different contacting geometries on random resistance variations. The contacting resistance is 60 mΩ for nine-point probes and 80 mΩ for four- and single-point probes. We determine the magnitude of contacting resistance variations from measurements at different probe positions to be ±30 mΩ. Using this variation, we perform numerical simulations and find a larger sensitivity on random resistance variations for tandem- (pairs of current- and sense probes) compared to triplet (one sense- between two current probes) configurations. The corresponding fill factor deviation is approximately 0.1%abs for tandem configurations when the contacting resistances of up to two current probes are altered. The sensitivity for triplet configurations is negligible

Determination of the collection diffusion length by electroluminescence imaging

The electroluminescence emission of crystalline silicon solar cells at near-bandgap wavelengths is investigated. We show that the intensity of the emitted luminescence at near-bandgap wavelengths is directly proportional to the collection diffusion length Lc which is a measure of bulk and rear surface recombination properties and determines the short circuit current of a solar cell illuminated with light of near-bandgap wavelengths. We provide experimental evidence for the determination of Lc by carrying out electroluminescence measurements on a set of 15 specially prepared monocrystalline silicon solar cells with different thicknesses. Moreover, we demonstrate and discuss the applicability of the proposed method to obtain images of the collection diffusion length Lc of multicrystalline silicon solar cells. The values determined by electroluminescence imaging coincide with values obtained from spectrally resolved quantum efficiency measurements with a relative accuracy of 13 %.German Federal Environmental Foundation (Deutsche Bundesstiftung Umwelt

Identifying the location of recombination from voltage-dependent quantum efficiency measurements

This paper investigates process-induced variations of the open-circuit voltage (Voc) using voltage-dependent quantum efficiency measurements. By means of device modelling we show that this method is able to explain the Voc difference of two solar cells, even if they show identical electrical behaviour under short-circuit condition. This paper furthermore explains how the origin of Voc variations can be classified into emitter, base and rear of the solar cell. The simulation results have been experimentally verified with industrial-type passivated emitter and rear cells (PERC) cells made from p-type Czochralski wafers. The proposed analysis method is an attractive way for monitoring Voc variations of solar cells in industrial mass production since there is no need for specially prepared test structures. © 2017 The Authors. Published by Elsevier Ltd

Dataset for: Modeling chemotherapy induced neurotoxicity with human induced pluripotent stem cell (iPSC)-derived sensory neurons

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and potentially irreversible adverse event of cytotoxic chemotherapy. We evaluate whether sensory neurons derived from induced pluripotent stem cells (iPSC-DSN) can serve as human disease model system for chemotherapy induced neurotoxicity. Sensory neurons differentiated from two established induced pluripotent stem cell lines were used (s.c. BIHi005-A https://hpscreg.eu/cell- line/BIHi005-A and BIHi004-B https://hpscreg.eu/cell-line/BIHi004-B, Berlin Institute of Health Stem Cell Core Facility). Cell viability and cytotoxicity assays were performed, comparing susceptibility to four neurotoxic and two non-neurotoxic drugs. RNA sequencing analyses in paclitaxel vs. vehicle (DMSO)treated sensory neurons were performed. Treatment of iPSC-DSN for 24 h with the neurotoxic drugs paclitaxel, bortezomib, vincristine and cisplatin led to a dose dependent decline of cell viability in clinically relevant IC50 ranges, which was not the case for the non-neurotoxic compounds doxorubicin and 5-fluorouracil. RNA sequencing analyses at 24 h, i.e. before paclitaxel-induced cell death occurred, revealed the differential expression of genes of neuronal injury, cellular stress response, and sterol pathways in response to 1 mu M paclitaxel. Neuroprotective effects of lithium chloride co-incubation, which were previously shown in rodent dorsal root ganglia, could be replicated in human iPSC-DSN. Cell lines from the two different donors BIHi005-A and BIHi004-B showed different responses to the neurotoxic treatment in cell viability and cytotoxicity assays

Experimental Determination of the Uncertainty of the Absorption Coefficient of Crystalline Silicon

Based on a combined analysis of spectroscopic ellipsometry, reflectance and transmittance measurements as well as spectrally resolved luminescence measurements and spectral responsivity measurements, we present data of the coefficient of band-to-band absorption of crystalline silicon at 295 K in the wavelength range 250 - 1450 nm. A systematic measurement uncertainty analysis according to the "Guide to the Expression of Uncertainty in Measurements" (GUM) is carried out for each method, showing that the relative uncertainty of the absorption coefficient data so determined is of the order of 0.3% at 300 nm, 1% at 900 nm, 10% at 1200 nm and 180% at 1450 nm. The data are consolidated by comparison of measurements carried out independently at different institutions. The uncertainty of solar cell energy conversion predictions by means of simulations due to the uncertainty of the absorption coefficient data is shown to be of the order of 0.1% relative.Deutsche Bundesstiftung UmweltState of Lower Saxon

Instrumentation-related uncertainty of reflectance and transmittance measurements with a two-channel spectrophotometer

Spectrophotometers are operated in numerous fields of science and industry for a variety of applications. In order to provide confidence for the measured data, analyzing the associated uncertainty is valuable. However, the uncertainty of the measurement results is often unknown or reduced to sample-related contributions. In this paper, we describe our approach for the systematic determination of the measurement uncertainty of the commercially available two-channel spectrophotometer Agilent Cary 5000 in accordance with the Guide to the expression of uncertainty in measurements. We focus on the instrumentation-related uncertainty contributions rather than the specific application and thus outline a general procedure which can be adapted for other instruments. Moreover, we discover a systematic signal deviation due to the inertia of the measurement amplifier and develop and apply a correction procedure. Thereby we increase the usable dynamic range of the instrument by more than one order of magnitude. We present methods for the quantification of the uncertainty contributions and combine them into an uncertainty budget for the device. © 2017 Author(s)