Umwelteinflüsse auf Werkstoffe

The corrosion behavior of different metals commonly used in civil engineering and construction was investigated under outdoor exposure conditions. The exposure sites were chosen at locations of the Swiss National Air Pollution Monitoring Network (NABEL) in different regions of Switzerland, where the concentrations of different air pollutants and climate data are registered continuously. After different exposure times, a set of test specimens is taken back for gravimetric evaluation of material loss and chemical characterization of corrosion products and deposits. Transmission and scanning electron microscopy, X-ray diffraction (XRD), and X-ray fluorescence (XRF) were used to characterize corrosion products. Water soluble compounds on the metal surfaces have also been analyzed quantitatively. First results for the exposure period of six months are presented. They show large differences in corrosion rate and in the amount of corrosive species on the metal surfaces for the different test sites. In some cases a very good correlation to the specific pollution and climate conditions at the particular locations is possible

Optical interferometer in space

The present design concepts for a Laser Gravitational Wave Observatory in Space are described. Laser heterodyne distance measurements are made between test masses located in three spacecraft separated by roughly 10(exp 6) km. The major technology issues are: the reduction of spurious acceleration noise for the test masses to below 2 x 10(exp -15) cm/sq sec/Hz(0.5) from 10(exp -5) to 10(exp -3) Hz; and the measurement of changes in the difference of the antenna arm lengths to 5 x 10(exp -11) cm/Hz(0.5) from 10(exp -3) to 1 Hz with high reliability. The science objectives are: to measure discrete sinusoidal gravitational wave signals from individual sources with periods of 1 second to 1 day; to measure the stochastic background due to unresolved binaries; and to search for gravitational wave pulses with periods longer than 1 sec from possible exotic sources such as gravitational collapse of very massive objects

Chasing the elusive "in-between" state of the copper-amyloid β complex by X-ray absorption through partial thermal relaxation after photoreduction

The redox activity of Cu ions bound to the amyloid-β (Aβ) peptide is implicated as a source of oxidative stress in the context of Alzheimer's disease. In order to explain the efficient redox cycling between CuII -Aβ (distorted square-pyramidal) and CuI -Aβ (digonal) resting states, the existence of a low-populated "in-between" state, prone to bind Cu in both oxidation states, has been postulated. Here, we exploited the partial X-ray induced photoreduction at 10 K, followed by a thermal relaxation at 200 K, to trap and characterize by X-ray Absorption Spectroscopy (XAS) a partially reduced Cu-Aβ1-16 species different from the resting states. Remarkably, the XAS spectrum is well-fitted by a previously proposed model of the "in-between" state, hence providing the first direct spectroscopic characterization of an intermediate state. The present approach could be used to explore and identify the catalytic intermediates of other relevant metal complexes

Opposing function of MYBBP1A in proliferation and migration of head and neck squamous cell carcinoma cells

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent and lethal cancers worldwide and mortality mostly results from loco-regional recurrence and metastasis. Despite its significance, our knowledge on molecular, cellular and environmental mechanisms that drive disease pathogenesis remains largely elusive, and there are limited therapeutic options, with only negligible clinical benefit. METHODS: We applied global gene expression profiling with samples derived from a recently established mouse model for oral cancer recurrence and identified a list of genes with differential expression between primary and recurrent tumors. RESULTS: One differentially expressed gene codes for Myb-binding protein 1a (MYBBP1A), which is known as a transcriptional co-regulator that physically interacts with nuclear transcription factors, such as NFκB and p53. We confirmed significantly reduced MYBBP1A protein levels on tissue sections of recurrent mouse tumors compared to primary tumors by immunohistochemistry, and found aberrant MYBBP1A protein levels also in tumor samples of HNSCC patients. Interestingly, silencing of MYBBP1A expression in murine SCC7 and in human HNSCC cell lines elicited increased migration but decreased cell growth. CONCLUSION: We provide experimental evidence that MYBBP1A is an important molecular switch in the regulation of tumor cell proliferation versus migration in HNSCC and it will be a major challenge for the future to proof the concept whether regulation MYBBP1A expression and/or function could serve as a novel option for anti-cancer therapy

Renal pathology in a mouse model of severe Spinal Muscular Atrophy is associated with downregulation of Glial Cell-Line Derived Neurotrophic Factor (GDNF)

Acknowledgements: We would like to acknowledge the Microscopy and Histology Core Facility members; Kevin Mackenzie, Debbie Wilkinson, Gillian Milne and Lucy Wight at the University of Aberdeen, and Margaret Mullin at the Glasgow Imaging Facility, University of Glasgow, for their support, assistance and use of the facilities. Funding: SMA Europe and an Anatomical Society PhD Studentship to S.H.P. and H.A.; the Deutsche Muskelstiftung (E-2019-01 to P.C.)Peer reviewedPostprin

A Self-administered version of the functioning assessment short test for use in population-based studies: A pilot study

Background: The Functioning Assessment Short Test (FAST) is an interviewer-administered scale assessing functional impairment originally developed for psychiatric patients. Objectives: To adapt the FAST for the general population, we developed a self-administered version of the scale and assessed its properties in a pilot study. Methods: The original FAST scale was translated into German via forward and backward translation. Afterwards, we adjusted the scale for self-administered application and inquired participants from two ongoing studies in Germany, 'STAAB' (Würzburg) and 'BiDirect' (Münster), both recruiting subjects from the general population across a wide age range (STAAB: 30-79 years, BiDirect: 35-65 years). To assess reliability, agreement of self-assessment with proxy-assessment by partners was measured via intraclass correlation coefficient (ICC) over the FAST score. Construct validity was estimated by conducting correlations with validated scales of depression (PHQ-9), anxiety (GAD-7), and health-related quality of life (SF-12) and regression analyses using these scales besides potentially disabling comorbidities (e.g. Chronic Back Pain (CBP)). Results: Participants (n=54) had a median age of 57.0 years (quartiles: 49.8, 65.3), 46.3% were female. Reliability was moderate: ICC 0.50 (95% CI 0.46-0.54). The FAST score significantly correlated with PHQ-9, GAD-7, and the mental sub-scale of SF-12. In univariable linear regression, all three scales and chronic back pain explained variance of the FAST score. In multivariable analysis, only CBP and the SF-12 remained significant predictors. Conclusion: The German self-administered version of the FAST yielded moderate psychometric properties in this pilot study, indicating its applicability to assess functional impairment in the general population

A Prospective Study of the Association of Metacognitive Beliefs and Processes with Persistent Emotional Distress After Diagnosis of Cancer

Two hundred and six patients, diagnosed with primary breast or prostate cancer completed self-report questionnaires on two occasions: before treatment (T1) and 12 months later (T2). The questionnaires included: the Hospital Anxiety and Depression Scale; Impact of Events Scale; the Metacognitions Questionnaire-30 (MCQ-30) and the Illness Perceptions Questionnaire-revised. A series of regression analyses indicated that metacognitive beliefs at T1 predicted between 14 and 19 % of the variance in symptoms of anxiety, depression and trauma at T2 after controlling for age and gender. For all three outcomes, the MCQ-30 subscale ‘negative beliefs about worry’ made the largest individual contribution with ‘cognitive confidence’ also contributing in each case. For anxiety, a third metacognitive variable, ‘positive beliefs about worry’ also predicted variance in T2 symptoms. In addition, hierarchical analyses indicated that metacognitive beliefs explained a small but significant amount of variance in T2 anxiety (2 %) and T2 depression (4 %) over and above that explained by demographic variables, T1 symptoms and T1 illness perceptions. The findings suggest that modifying metacognitive beliefs and processes has the potential to alleviate distress associated with cancer

Revisiting the pro-oxidant activity of copper: interplay of ascorbate, cysteine and glutathione

Copper (Cu) is essential for most organisms, but it can be poisonous in excess, through mechanisms such as protein aggregation, trans-metallation and oxidative stress. Latter could implicate the formation of potentially harmful Reactive Oxygen Species (ROS: O2•–, H2O2 and HO•) via the redox cycling between Cu(II)/Cu(I) states in the presence of dioxygen and physiological reducing agents such as ascorbate (AscH), cysteine (Cys) and the tripeptide glutathione (GSH). Although the reactivity of Cu with these reductants has been previously investigated, the reactions taking place in a more physiologically-relevant mixture of these biomolecules are not known. Hence, we report here on the reactivity of Cu with binary and ternary mixtures of AscH, Cys and GSH. By measuring ascorbate and thiol oxidation, as well as HO• formation, we show that Cu reacts preferentially with GSH and Cys, halting AscH oxidation and also HO• release. This could be explained by the formation of Cu-thiolate clusters with both GSH and, as we first demonstrate here, Cys. Moreover, we observed a remarkable acceleration of Cu-catalysed GSH oxidation in the presence of Cys. We provide evidence that both thiol-disulfide exchange and the generated H2O2 contribute to this effect. Based on these findings, we speculate that Cu-induced oxidative stress may be mainly driven by GSH depletion and/or protein disulfide formation rather than by HO• and envision a synergistic effect of Cys on Cu toxicity