University of Duisburg-Essen
  • Essen, NRW, Germany
Recent publications
The use of ultrasonic waves in the context of SHM offers methods to analyze materials and systems. Both Acoustic Emission-based approaches (passive, active) are limited by the propagation characteristics of ultrasonic waves, especially in inhomogeneous materials like carbon fiber reinforced polymers (CFRP). The use of the piezoelectric and inverse piezoelectric effect is a very accurate method of sensing and exciting ultrasonic waves. However, the transducers resonance characteristics affect the waveforms. For illustration in this contribution different excitation signals are experimentally compared in frequency domain by fast Fourier transform (FFT) and in time-frequency domain by continuous wavelet transform (CWT). Then transducers effects along the propagation path of the wave are investigated. Frequency and fiber direction dependent damping factors of ultrasonic waves in CFRP as well as the influence of the transducers are determined. The distance between sensors in a sensor network is limited by attenuation, so fiber direction must be considered. Finally, by analyzing the frequency response of the transducer, a filtering method is developed to compensate for the resonance characteristics of the transducers. Finally, a more accurate estimate of the energy released and therefore a more accurate estimate of the severity of damages/failures is proposed.
This is a comprehensive, critical, and pedagogical review of volumetric emission tomography for combustion processes. Many flames that are of interest to scientists and engineers are turbulent and thus inherently three-dimensional, especially in practical combustors, which often contain multiple interacting flames. Fortunately, combustion leads to the emission of light, both spontaneously and in response to laser-based stimulation. Therefore, images of a flame convey path-integrated information about the source of light, and a tomography algorithm can be used to reconstruct the spatial distribution of the light source, called emission tomography. In a carefully designed experiment, reconstructions can be post-processed using chemical kinetic, spectroscopic, and/or transport models to extract quantitative information. This information can be invaluable for benchmarking numerical solutions, and volumetric emission tomography is increasingly relied upon to paint a more complete picture of combustion than point, linear, or planar tools. Steady reductions in the cost of optical equipment and computing power, improvements in imaging technology, and advances in reconstruction algorithms have enabled a suite of three-dimensional sensors that are regularly used to characterize combustion. Four emission modalities are considered in this review: chemiluminescence, laser-induced fluorescence, passive incandescence, and laser-induced incandescence. The review covers the reconstruction algorithms, imaging models, camera calibration techniques, signal physics, instrumentation, and post-processing methods needed to conduct volumetric emission tomography and interpret the results. Limitations of each method are discussed and a survey of key applications is presented. The future of volumetric combustion diagnostics is considered, with special attention paid to the advent and promise of machine learning as well as spectrally-resolved volumetric measurement techniques.
Species distribution models (SDMs) are key tools in biodiversity and conservation, but assessing their reliability in unsampled locations is difficult, especially where there are sampling biases. We present a spatially-explicit sensitivity analysis for SDMs – SDM profiling – which assesses the leverage that unsampled locations have on the overall model by exploring the interaction between the effect on the variable response curves and the prevalence of the affected environmental conditions. The method adds a ‘pseudo-presence’ and ‘pseudo-absence’ to unsampled locations, re-running the SDM for each, and measuring the difference between the probability surfaces of the original and new SDMs. When the standardised difference values are plotted against each other (a ‘profile plot’), each point's location can be summarized by four leverage measures, calculated as the distances to each corner. We explore several applications: visualization of model certainty; identification of optimal new sampling locations and redundant existing locations; and flagging potentially erroneous occurrence records.
The recent push for renewable electrical energy sources has resulted in a significant increase in the installation of the offshore wind farms. These farms become much bigger than their earlier counterparts and the generated power is much larger. This puts additional performance requirements on the export cables. Long submarine export cables are not only subjected to changing laying conditions along the route, including depth and seabed material variations, but also the loading patterns vary significantly over time. Additionally, applied reactive power compensation measures and the time-dependent grid situation change the distribution of the current along the route. These unique features of long submarine power cables necessitate a new type of approach to their design and construction optimization. This paper introduces a new approach for ampacity calculations of long submarine power cables. As the ampacity calculations form a basis for the design of a cable route, it is of paramount importance that they are performed as accurately as possible. The approach can be applied to general-purpose circuit solvers, and this paper describes how to implement it using the ATP-EMTP software, which is extended to the consideration of concurrent electrical and thermal effects. The approach permits considering all the important local and time-dependent parameters of the analysis simultaneously. In particular, the approach allows simultaneous analysis of the varying laying conditions along the route including changes in the depth of burial and thermal resistivity of the soil together with the temporal variations of the cable loading. Additionally, current characteristics in long AC cable conductors are strongly affected by the reactive power flow, which in turn depends on the location of the reactive power compensation, the reactive power demand for grid operation, and the wind farm voltage reactive power control strategy. Such analysis cannot be performed with any existing analytical tool. Also, numerical tools cannot handle such problems because a 3-dimensional time-dependent analysis of a cable route which is 100 km long would encounter convergence problems as the size of such model would be prohibitive. Hence, at present, the proposed approach is the only one available to solve this complex electro-thermal problem. Several numerical examples illustrate an application of the proposed methodology.
The LC 50 values of cigarette butts (CBs) leachates for the P. waltoni were evaluated. • Smoked CBs leachates with tobacco (SCB) were more toxic than other CBs leachates. • Significant difference among LC 50 values of leachates at different exposure times. • SCB leachate had higher heavy metals and PAHs levels than other CBs leachates. • All CBs leachates were acutely toxic for P. waltoni. A B S T R A C T Cigarette butts (CBs) are one of the most commonly found types of litter contaminating the aquatic environment. However, the environmental risks posed by CBs need further investigation. In this study, the in-vivo toxic effects of various concentrations of CB leachates on juvenile (5.45 ± 1.36 gr and 7.08 ± 1.12 cm) fish (Periophthalmus waltoni) were evaluated. The LC 50 values of CB leachate from smoked cigarette butts with tobacco (SCB) were 3.75, 3.0, 1.94, and 1.37 CBs/L in 24, 48, 72, and 96 h exposure times, respectively. The LC 50 values for leachate of smoked CBs without tobacco (SF) were 7.58, 6.22, 4.73, and 2.9 CBs/L at 24, 48, 72, and 96 h exposure times, 2 The Persian gulf Toxicity respectively. In the case of leachate from unsmoked filters (USF), LC 50 values were 14.68, 12.44, 10.19, and 7.46 CBs/L in 24, 48, 72, and 96 h exposure time, respectively. The mean concentrations of heavy metals and polycyclic aromatic hydrocarbons in SCBs leachates were higher than in SF and USF leachates. Our findings report that even low concentrations of CBs leachates can led to lethality of P. waltoni and may pose a threat to their population density.
The battery electric vehicle’s environmental impacts are highly influenced by the emissions attributed to the electricity used to recharge the battery. The electricity generation’s environmental assessment, however, is mainly based on static yearly mean shares of primary energy sources. To overcome this uncertainty, we develop a mixed-integer linear programming model to couple variable, hourly environmental impacts of electricity generation with representative user behavior in Germany. The model is then used to quantify and optimize the mitigation potential of environmental impacts for 2019, 2025, 2030, and 2050. Focusing on one method that minimizes the overarching environmental impacts could lead to ambiguous results. Instead, we aim to optimize charging behavior regarding each midpoint category and reveal the conflicting objectives among all the environmental categories that arise when aiming to minimize environmental impacts holistically. Considering greenhouse gas emissions, a reduction of 38% can be achieved through optimized demand timing for 2019. This charging strategy, however, increases the depletion of material resources by 72% compared to an optimal reference charging profile. The results for the future energy generation scenarios show that deviation between environmental impact categories can deviate and differences increase over the investigated time horizon. Nevertheless, by analyzing the differences between all impact category pairs, we found six categories, including climate change, within which differences are found to be less than 10%.
Background Unloading knee braces represent a conservative treatment option for non-pharmalogical management of unicompartmental osteoarthritis of the knee. Though there is consensus on the clinical effectiveness of unloading, the effect mechanism of bracing remains part of a debate. Our study was designed to assess the effect of unloader bracing on damaged cartilage via MRI cartilage mappings. Methods Fourteen patients (7 female, 7 male, mean age 43.1 ± 9.4 years) with unicompartmental cartilage wear in knees with varus or valgus malalignment were enrolled. Clinical scores, radiographs and MR-graphic properties (T2/T2* mapping, T1 Delayed Gadolinium Enhanced MRI of the cartilage (dGEMRIC) mapping, high-resolution PDw sequences) of knee cartilage were recorded before and three months after brace use. Results Bracing the knees for a mean of 14.4 ± 2.0 weeks (range 11 to 18 weeks) resulted in significant pain reduction (VAS changed from 5.9 ± 2.0 to 2.0 ± 1.3, p < 0.001) and improvement in knee function (KOOS increased from 42.1 ± 22.7 to 64.8 ± 18.7, p < 0.001). In the affected cartilage regions T2 relaxation times significantly decreased from 56.1 ± 11.4 ms to 46.5 ± 11.2 ms (p < 0.05). No changes in T1-dGEMRIC and T2* relaxation times, thickness or the extent of the damaged cartilage area could be detected. Conclusions Our results suggest, that unloader bracing improves the biochemical properties of the damaged cartilage by increasing collagen and proteoglycan concentration as well as decreasing the cartilage edema.
Antibody-mediated cancer immunotherapy targets inhibitory surface molecules, such as PD1, PD-L1, and CTLA-4, aiming to re-invigorate dysfunctional T cells. We purified and characterized tumor-infiltrating lymphocytes (TILs) and their patient-matched non-tumor counterparts from treatment-naïve NSCLC patient biopsies to evaluate the effect of PD1 expression on the functional and molecular profiles of tumor-resident T cells. We show that PD1+ CD8+ TILs have elevated expression of the transcriptional regulator ID3 and that the cytotoxic potential of CD8 T cells can be improved by knocking down ID3, defining it as a potential regulator of T cell effector function. PD1+ CD4+ memory TILs display transcriptional patterns consistent with both helper and regulator function, but can robustly facilitate B cell activation and expansion. Furthermore, we show that expanding ex vivo-prepared TILs in vitro broadly preserves their functionality with respect to tumor cell killing, B cell help, and TCR repertoire. Although purified PD1+ CD8+ TILs generally maintain an exhausted phenotype upon expansion in vitro, transcriptional analysis reveals a downregulation of markers of T-cell dysfunction, including the co-inhibitory molecules PD1 and CTLA-4 and transcription factors ID3, TOX and TOX2, while genes involved in cell cycle and DNA repair are upregulated. We find reduced expression of WNT signaling components to be a hallmark of PD1+ CD8+ exhausted T cells in vivo and in vitro and demonstrate that restoring WNT signaling, by pharmacological blockade of GSK3β, can improve effector function. These data unveil novel targets for tumor immunotherapy and have promising implications for the development of a personalized TIL-based cell therapy for lung cancer.
Immune checkpoint molecule B7-H1 plays a decisive immune regulatory role in different pathologies including cancer, and manipulation of B7-H1 expression became an attractive approach in cancer immunotherapy. Pancreatic cancer (PDAC) is characterized by pronounced immunosuppressive environment and B7-H1 expression correlates with PDAC prognosis. However, the first attempts to diminish B7-H1 expression in patients were not so successful. This points the complicity of PDAC immunosuppressive network and requires further examinations. We investigated the effect of B7-H1 deficiency in PDAC. Our results clearly show that partial or complete B7-H1 inhibition in vivo let to reduced tumor volume and improved survival of PDAC-bearing mice. This oncological benefit is due to the abrogation of immunosuppression provided by MDSC, macrophages, DC and Treg, which resulted in simultaneous restoration of anti-tumor immune response, namely improved accumulation and functionality of effector-memory CD4 and CD8 T cells. Our results underline the potential of B7-H1 molecule to control immunosuppressive network in PDAC and provide new issues for further clinical investigations.
Muscular dystrophies are a group of rare and severe inherited disorders mainly affecting the muscle tissue. Duchene Muscular Dystrophy, Myotonic Dystrophy types 1 and 2, Limb Girdle Muscular Dystrophy and Facioscapulohumeral Muscular Dystrophy are some of the members of this family of disorders. In addition to the current diagnostic tools, there is an increasing interest for the development of novel non-invasive biomarkers for the diagnosis and monitoring of these diseases. miRNAs are small RNA molecules characterized by high stability in blood thus making them ideal biomarker candidates for various diseases. In this study, we present the first genome-wide next-generation small RNA sequencing in serum samples of five different types of muscular dystrophy patients and healthy individuals. We identified many small RNAs including miRNAs, lncRNAs, tRNAs, snoRNAs and snRNAs, that differentially discriminate the muscular dystrophy patients from the healthy individuals. Further analysis of the identified miRNAs showed that some miRNAs can distinguish the muscular dystrophy patients from controls and other miRNAs are specific to the type of muscular dystrophy. Bioinformatics analysis of the target genes for the most significant miRNAs and the biological role of these genes revealed different pathways that the dysregulated miRNAs are involved in each type of muscular dystrophy investigated. In conclusion, this study shows unique signatures of small RNAs circulating in five types of muscular dystrophy patients and provides a useful resource for future studies for the development of miRNA biomarkers in muscular dystrophies and for their involvement in the pathogenesis of the disorders.
We hereby provide the first documented data on the occurrence of a viable Procambarus virginalis population in a nature reserve in Poland and the steps that were taken to prevent further introductions of the species in the country. To date, Poland represents the most north-eastward distribution area in Europe, where the species occurs in ecosystems with natural water temperature regimes. The ecological plasticity of P. virginalis and its obligate parthenogenetic reproduction make this crayfish an exceptional invader. The crayfish may have detrimental effects on the native invertebrates, amphibians, and fish, and alter the state of the entire ecosystem. Therefore, we investigated the presence of the species in the nature reserve of Pojezierze Łęczyńskie Landscape Park after a suspected P. virginalis individual was found by a local citizen. The nature reserve also includes an area designated to protect native amphibians and turtles. Our study revealed the presence of a thriving population of P. virginalis in the protected area and clear indications of its impact on native and invasive species, both in aquatic and terrestrial environments. If no action is taken, the species will likely expand to other water bodies across the country. An extensive sensibilization campaign allowed us to find additional invaded areas and significantly contribute to the effective ban of this and other invasive crayfish species from private and commercial online trade. Raising public awareness and banning invasive crayfish species trade is essential for successfully detecting and preventing further introductions.
Heart failure is a clinical syndrome where cardiac output is not sufficient to sustain adequate perfusion and normal bodily functions, initially during exercise and in more severe forms also at rest. The two most frequent forms are heart failure of ischemic origin and of non-ischemic origin. In heart failure of ischemic origin, reduced coronary blood flow is causal to cardiac contractile dysfunction, and this is true for stunned and hibernating myocardium, coronary microembolization, myocardial infarction and post-infarct remodeling, possibly also for the takotsubo syndrome. The most frequent form of non-ischemic heart failure is dilated cardiomyopathy, caused by genetic mutations, myocarditis, toxic agents or sustained tachyarrhythmias, where alterations in coronary blood flow result from and contribute to cardiac contractile dysfunction. Hypertrophic cardiomyopathy is caused by genetic mutations but can also result from increased pressure and volume overload (hypertension, valve disease). Heart failure with preserved ejection fraction is characterized by pronounced coronary microvascular dysfunction, the causal contribution of which is however not clear. The present review characterizes the alterations of coronary blood flow which are causes or consequences of heart failure in its different manifestations. Apart from any potentially accompanying coronary atherosclerosis, all heart failure entities share common features of impaired coronary blood flow, but to a different extent: enhanced extravascular compression, impaired nitric oxide-mediated, endothelium-dependent vasodilation and enhanced vasoconstriction to mediators of neurohumoral activation. Impaired coronary blood flow contributes to the progression of heart failure and is thus a valid target for established and novel treatment regimens.
Background: Oncogenic KRAS mutations are prevalent in human cancers, but effective treatment of KRAS-mutant malignancies remains a major challenge in the clinic. Increasing evidence suggests that aberrant metabolism plays a central role in KRAS-driven oncogenic transformation. The aim of this study is to identify selective metabolic dependency induced by mutant KRAS and to exploit it for the treatment of the disease. Method: We performed an integrated analysis of RNAi- and CRISPR-based functional genomic datasets (n = 5) to identify novel genes selectively required for KRAS-mutant cancer. We further screened a customized library of chemical inhibitors for candidates that are synthetic lethal with NOP56 depletion. Functional studies were carried out by genetic knockdown using siRNAs and shRNAs, knockout using CRISPR/Cas9, and/or pharmacological inhibition, followed by cell viability and apoptotic assays. Protein expression was determined by Western blot. Metabolic ROS was measured by flow cytometry-based quantification. Results: We demonstrated that nucleolar protein 5A (NOP56), a core component of small nucleolar ribonucleoprotein complexes (snoRNPs) with an essential role in ribosome biogenesis, confers a metabolic dependency by regulating ROS homeostasis in KRAS-mutant lung cancer cells and that NOP56 depletion causes synthetic lethal susceptibility to inhibition of mTOR. Mechanistically, cancer cells with reduced NOP56 are subjected to higher levels of ROS and rely on mTOR signaling to balance oxidative stress and survive. We also discovered that IRE1α-mediated unfolded protein response (UPR) regulates this process by activating mTOR through p38 MAPK. Consequently, co-targeting of NOP56 and mTOR profoundly enhances KRAS-mutant tumor cell death in vitro and in vivo. Conclusions: Our findings reveal a previously unrecognized mechanism in which NOP56 and mTOR cooperate to play a homeostatic role in the response to oxidative stress and suggest a new rationale for the treatment of KRAS-mutant cancers.
Background Goltz syndrome (GS) is a X-linked disorder defined by defects of mesodermal- and ectodermal-derived structures and caused by PORCN mutations. Features include striated skin-pigmentation, ocular and skeletal malformations and supernumerary or hypoplastic nipples. Generally, GS is associated with in utero lethality in males and most of the reported male patients show mosaicism (only three non-mosaic surviving males have been described so far). Also, precise descriptions of neurological deficits in GS are rare and less severe phenotypes might not only be caused by mosaicism but also by less pathogenic mutations suggesting the need of a molecular genetics and functional work-up of these rare variants. Results We report two cases: one girl suffering from typical skin and skeletal abnormalities, developmental delay, microcephaly, thin corpus callosum, periventricular gliosis and drug-resistant epilepsy caused by a PORCN nonsense-mutation (c.283C > T, p.Arg95Ter). Presence of these combined neurological features indicates that CNS-vulnerability might be a guiding symptom in the diagnosis of GS patients. The other patient is a boy with a supernumerary nipple and skeletal anomalies but also, developmental delay, microcephaly, cerebral atrophy with delayed myelination and drug-resistant epilepsy as predominant features. Skin abnormalities were not observed. Genotyping revealed a novel PORCN missense-mutation (c.847G > C, p.Asp283His) absent in the Genome Aggregation Database (gnomAD) but also identified in his asymptomatic mother. Given that non-random X-chromosome inactivation was excluded in the mother, fibroblasts of the index had been analyzed for PORCN protein-abundance and -distribution, vulnerability against additional ER-stress burden as well as for protein secretion revealing changes. Conclusions Our combined findings may suggest incomplete penetrance for the p.Asp283His variant and provide novel insights into the molecular etiology of GS by adding impaired ER-function and altered protein secretion to the list of pathophysiological processes resulting in the clinical manifestation of GS.
Background The optimal duration of immune checkpoint blockade (ICB) therapy is not well established. Active residual disease is considered prohibitive for treatment discontinuation and its detection by diagnostic CT imaging is limited. Here, we set out to determine the potential added value of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) to identify patients at higher risk of relapse following discontinuation of ICB in advanced melanoma. Methods Metastatic melanoma patients who discontinued ICB were identified retrospectively. Eligible patients received FDG-PET and diagnostic CT within four months of ICB discontinuation. We defined morphologic response using RECIST v1.1. Complete metabolic response (CMR) was defined as uptake in tumor lesions below background, whereas any site of residual, FDG-avid disease was rated as non-CMR. The primary endpoint was time to progression (TTP) after therapy discontinuation stratified by morphologic and metabolic imaging response using Kaplan–Meier estimates and log-rank test. Results Thiry-eight patients were eligible for this analysis. Median follow-up was 37.3 months since ICB discontinuation. Median TTP in the overall cohort was not reached. A greater proportion of patients were rated as CMR in PET ( n = 34, 89.5%) as compared to complete response (CR) in CT ( n = 13, 34.2%). Median TTP was reached in patients with non-CMR (12.7 months, 95%CI 4.4-not reached) but not for patients with CMR (log-rank: p < 0.001). All patients with complete response by CT had CMR by PET. In a subset of patients excluding those with complete response by CT, TTP remained significantly different between CMR and non-CMR (log-rank: p < 0.001). Conclusion Additional FDG-PET at time of discontinuation of ICB therapy helps identify melanoma patients with a low risk of recurrence and favourable prognosis compared to CT imaging alone. Results may have clinical relevance especially for patients with residual tumor burden.
Background In pediatric hereditary cystic kidney diseases, epithelial cell defects mostly result from rare, autosomal recessively inherited pathogenic variants in genes encoding proteins of the cilia-centrosome complex. Consequences of individual gene variants on epithelial function are often difficult to predict and can furthermore depend on the patient’s genetic background. Here, we studied urine-derived renal tubular epithelial cells (URECs) from genetically determined, pediatric cohorts of different hereditary cystic kidney diseases, comprising autosomal recessive polycystic kidney disease, nephronophthisis (NPH) and the Bardet Biedl syndrome (BBS). UREC characteristics and behavior in epithelial function-related 3D cell culture were compared in order to identify gene and variant-specific properties and to determine aspects of epithelial (cell) dysfunction. Results UREC preparations from patients (19) and healthy controls (39) were studied in a qualitative and quantitative manner using primary cells cultured for up-to 21 days. In patients with biallelic pathogenic variants in PKHD1 or NPHP genes, we were able to receive satisfactory amounts of URECs of reproducible quality. In BBS patients, UREC yield was lower and more dependent on the individual genotype. In contrast, in UREC preparations derived from healthy controls, no predictable and satisfactory outcome could be established. Considering cell proliferation, tubular origin and epithelial properties in 2D/3D culture conditions, we observed distinct and reproducible epithelial properties of URECs. In particular, the cells from patients carrying PKHD1 variants were characterized by a high incidence of defective morphogenesis of monolayered spheroids—a property proposed to be suitable for corrective intervention. Furthermore, we explored different ways to generate reference cell lines for both—patients and healthy controls—in order to eliminate restrictions in cell number and availability of primary URECs. Conclusions Ex vivo 3D cell culture of primary URECs represents a valuable, non-invasive source to evaluate epithelial cell function in kidney diseases and as such helps to elucidate the functional consequences of rare genetic disorders. In combination with genetically defined control cell lines to be generated in the future, the cultivation of primary URECs could become a relevant tool for testing personalized treatment of epithelial dysfunction in patients with hereditary cystic kidney disease.
Extracellular vesicle (EV) secretion is a highly conserved evolutionary trait in all organisms in the three domains of life. The packaging and release of EVs appears to be a bulk-flow process which takes place mainly under extreme conditions. EVs participate in horizontal gene transfer, which supports the survival of prokaryotic and eukaryotic microbes. In higher eukaryotes, almost all cells secrete a heterogeneous population of EVs loaded with various biomolecules. EV secretion is typically higher in cancer microenvironments, promoting tumor progression and metastasis. EVs are now recognized as additional mediators of autocrine and paracrine communication in health and disease. In this context, proteins and RNAs have been studied the most, but extracellular vesicle DNA (EV-DNA) has started to gain in importance in the last few years. In this review, we summarize new findings related to the loading mechanism(s), localization, and post-shedding function of EV-DNA. We also discuss the feasibility of using EV-DNA as a biomarker when performing a liquid biopsy, at the same time emphasizing the lack of data from clinical trials in this regard. Finally, we outline the potential of EV-DNA uptake and its interaction with the host genome as a promising tool for understanding the mechanisms of cancer evolution.
Neuroblastoma (NB) accounts for 15% of cancer-related deaths in childhood despite considerable therapeutic improvements. While several risk factors, including MYCN amplification and alterations in RAS and p53 pathway genes, have been defined in NB, the clinical outcome is very variable and difficult to predict. Since genes of the mechanistic target of rapamycin (mTOR) pathway are upregulated in MYCN -amplified NB, we aimed to define the predictive value of the mTOR substrate-encoding gene eukaryotic translation initiation factor 4E-binding protein 1 ( EIF4EBP1 ) expression in NB patients. Using publicly available data sets, we found that EIF4EBP1 mRNA expression is positively correlated with MYCN expression and elevated in stage 4 and high-risk NB patients. In addition, high EIF4EBP1 mRNA expression is associated with reduced overall and event-free survival in the entire group of NB patients in three cohorts, as well as in stage 4 and high-risk patients. This was confirmed by monitoring the clinical value of 4EBP1 protein expression, which revealed that high levels of 4EBP1 are significantly associated with prognostically unfavorable NB histology. Finally, functional analyses revealed that EIF4EBP1 expression is transcriptionally controlled by MYCN binding to the EIF4EBP1 promoter in NB cells. Our data highlight that EIF4EBP1 is a direct transcriptional target of MYCN whose high expression is associated with poor prognosis in NB patients. Therefore, EIF4EBP1 may serve to better stratify patients with NB.
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12,099 members
Stefan Stieglitz
  • Abteilung Informatik und Angewandte Kognitionswissenschaft
Stephan Barcikowski
  • Group of Technical Chemistry
Sascha Kriewel
  • Abteilung Informatik und Angewandte Kognitionswissenschaft
Wolfgang Sand
  • Biofilm Centre
Essen, NRW, Germany