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Sökning: WFRF:(Frenzel S)

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  • Han, L. K. M., et al. (författare)
  • Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group
  • 2020
  • Ingår i: Molecular Psychiatry. - 1359-4184 .- 1476-5578.
  • Tidskriftsartikel (refereegranskat)abstract
    • Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18–75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen’s d = 0.14, 95% CI: 0.08–0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates. © 2020, The Author(s).
  • Ainsbury, Elizabeth, et al. (författare)
  • Integration of new biological and physical retrospective dosimetry methods into EU emergency response plans - joint RENEB and EURADOS inter-laboratory comparisons
  • 2017
  • Ingår i: International Journal of Radiation Biology. - : Taylor & Francis. - 0955-3002 .- 1362-3095. ; 93:1, s. 99-109
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: RENEB, 'Realising the European Network of Biodosimetry and Physical Retrospective Dosimetry,' is a network for research and emergency response mutual assistance in biodosimetry within the EU. Within this extremely active network, a number of new dosimetry methods have recently been proposed or developed. There is a requirement to test and/or validate these candidate techniques and inter-comparison exercises are a well-established method for such validation. Materials and methods: The authors present details of inter-comparisons of four such new methods: dicentric chromosome analysis including telomere and centromere staining; the gene expression assay carried out in whole blood; Raman spectroscopy on blood lymphocytes, and detection of radiation induced thermoluminescent signals in glass screens taken from mobile phones. Results: In general the results show good agreement between the laboratories and methods within the expected levels of uncertainty, and thus demonstrate that there is a lot of potential for each of the candidate techniques. Conclusions: Further work is required before the new methods can be included within the suite of reliable dosimetry methods for use by RENEB partners and others in routine and emergency response scenarios.
  • Zirath, Hanna, et al. (författare)
  • MYC inhibition induces metabolic changes leading to accumulation of lipid droplets in tumor cells
  • 2013
  • Ingår i: Proceedings of the National Academy of Sciences. - : National Acad Sciences. - 1091-6490. ; 110:25, s. 10258-10263
  • Tidskriftsartikel (refereegranskat)abstract
    • The MYC genes are the most frequently activated oncogenes in human tumors and are hence attractive therapeutic targets. MYCN amplification leads to poor clinical outcome in childhood neuroblastoma, yet strategies to modulate the function of MYCN do not exist. Here we show that 10058-F4, a characterized c-MYC/Max inhibitor, also targets the MYCN/Max interaction, leading to cell cycle arrest, apoptosis, and neuronal differentiation in MYCN-amplified neuroblastoma cells and to increased survival of MYCN transgenic mice. We also report the discovery that inhibition of MYC is accompanied by accumulation of intracellular lipid droplets in tumor cells as a direct consequence of mitochondrial dysfunction. This study expands on the current knowledge of how MYC proteins control the metabolic reprogramming of cancer cells, especially highlighting lipid metabolism and the respiratory chain as important pathways involved in neuroblastoma pathogenesis. Together our data support direct MYC inhibition as a promising strategy for the treatment of MYC-driven tumors.
  • Schriever, V. A., et al. (författare)
  • Olfactory speed - Temporal odor processing of paired stimuli
  • 2015
  • Ingår i: Neuroscience. - 0306-4522. ; 295, s. 72-9
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Compared to other senses, temporal perception of odors seems fairly slow. In addition it has been shown in previous studies that even not consciously perceived odors could influence our behavior. Aim of the current study therefore was to study the interstimulus interval (ISI) length, which is necessary between two repetitive stimuli to be able to perceive them separately. The additional aim focused on observing central odor processing of not perceived odorous stimuli. MATERIALS AND METHODS: The study was divided into three parts. In each part healthy, normosmic volunteers were included. In part I and II stimulus pairs (CO2, H2S, orange and phenyl ethyl alcohol (PEA)) were presented to the subjects via a computer-controlled olfactometer with short ISI of 0.6-9s. The decision whether one or two stimuli were perceived was recorded. In addition the influence of odor valence, trigeminallity and concentrations was observed. In part III olfactory event-related potentials (OERPs) to perceived and not-perceived odors were recorded. RESULTS: The two stimuli of a stimulus pair were perceived separately more often with increasing ISI length. This increase was significant until an ISI between the stimuli of 4s. Odor intensity, pleasantness, trigeminallity and sex had no major influence on this. In addition we were able to observe that OERPs are less often detected in response to not perceived olfactory stimuli. However, the presence of OERP in response to not perceived stimuli in more than half of the cases indicated that even not perceived stimuli are centrally processed.
  • Wilhelms, Frank, et al. (författare)
  • The EPICA Dronning Maud Land deep drilling operation
  • 2014
  • Ingår i: Annals of Glaciology. - 0260-3055 .- 1727-5644. ; 55:68, s. 355-366
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on the EPICA Dronning Maud Land (East Antarctica) deep drilling operation. Starting with the scientific questions that led to the outline of the EPICA project, we introduce the setting of sister drillings at NorthGRIP and EPICA Dome C within the European ice-coring community. The progress of the drilling operation is described within the context of three parallel, deep-drilling operations, the problems that occurred and the solutions we developed. Modified procedures are described, such as the monitoring of penetration rate via cable weight rather than motor torque, and modifications to the system (e.g. closing the openings at the lower end of the outer barrel to reduce the risk of immersing the drill in highly concentrated chip suspension). Parameters of the drilling (e.g. corebreak force, cutter pitch, chips balance, liquid level, core production rate and piece number) are discussed. We also review the operational mode, particularly in the context of achieved core length and piece length, which have to be optimized for drilling efficiency and core quality respectively. We conclude with recommendations addressing the design of the chip-collection openings and strictly limiting the cable-load drop with respect to the load at the start of the run.
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