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Bakiri L.,National Cancer Research Center | Reschke M.O.,National Cancer Research Center | Reschke M.O.,Beth Israel Deaconess Medical Center | Gefroh H.A.,National Cancer Research Center | And 9 more authors.
Oncogene | Year: 2011

Mice lacking c-fos develop osteopetrosis due to a block in osteoclast differentiation. Carboxy-terminal phosphorylation of Fos on serine 374 by ERK1/2 and serine 362 by RSK1/2 regulates Fos stability and transactivation potential in vitro. To assess the physiological relevance of Fos phosphorylation in vivo, serine 362 and/or serine 374 was replaced by alanine (Fos362A, Fos374A and FosAA) or by phospho-mimetic aspartic acid (FosDD). Homozygous mutants were healthy and skeletogenesis was largely unaffected. Fos C-terminal phosphorylation, predominantly on serine 374, was found important for osteoclast differentiation in vitro and affected lipopolysaccharide (LPS)-induced cytokine response in vitro and in vivo. Importantly, skin papilloma development was delayed in FosAA, Fos362A and Rsk2-deficient mice, accelerated in FosDD mice and unaffected in Fos374A mutants. Furthermore, the related Fos protein and putative RSK2 target Fra1 failed to substitute for Fos in papilloma development. This indicates that phosphorylation of serines 362 and 374 exerts context-dependent roles in modulating Fos activity in vivo. Inhibition of Fos C-terminal phosphorylation on serine 362 by targeting RSK2 might be of therapeutic relevance for skin tumours. © 2011 Macmillan Publishers Limited All rights reserved.


Jha H.,Hokkaido University | Jha H.,University of Erlangen Nurenberg | Kikuchi T.,Hokkaido University | Sakairi M.,Hokkaido University | Takahashi H.,Hokkaido University
ACS Applied Materials and Interfaces | Year: 2010

The paper demonstrates simple methods for the fabrication of aluminum microstructures on the anodic oxide film of aluminum. The aluminum sheets were first engraved (patterned) either by laser beam or by embossing to form deep grooves on the surface. One side of the sheet was then anodized, blocking the other side by using polymer mask to form the anodic alumina. Because of the lower thickness at the bottom part of the grooves, the part was completely anodized before the complete oxidation of the other parts. Such selectively complete anodizing resulted in the patterns of metallic aluminum on anodic alumina. Using the technique, we fabricated microstructures such as line patterns and a simple wiring circuit-board-like structure on the anodic alumina. The aluminum microstructures fabricated by the techniques were embedded in anodic alumina/aluminum sheet, and this technique is promising for applications in electronic packaging and devices. © 2010 American Chemical Society.


Kanseri B.,Max Planck Institute for the Science of Light | Iskhakov T.,Max Planck Institute for the Science of Light | Rytikov G.,Moscow State University of Printing Arts | Chekhova M.,Max Planck Institute for the Science of Light | And 3 more authors.
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2013

Photon-number correlation measurements are performed on bright squeezed vacuum states using a standard Bell-test setup, and quantum correlations are observed for conjugate polarization-frequency modes. We further test the entanglement witnesses for these states and demonstrate the violation of the separability criteria, which infers that all of the macroscopic Bell states, containing typically 106 photons per pulse, are polarization entangled. The study also reveals the symmetry of macroscopic Bell states with respect to local polarization transformations. © 2013 American Physical Society.


Weih M.,University of Erlangen Nurenberg | Degirmenci U.,University of Erlangen Nurenberg | Kreil S.,University of Erlangen Nurenberg | Suttner G.,University of Erlangen Nurenberg | And 4 more authors.
Journal of Alzheimer's Disease | Year: 2011

Nuclear medicine techniques were the first functional imaging techniques used to support the clinical diagnosis of Alzheimers Disease (AD). Perfusion-SPECT allows registration of regional cerebral blood flow (rCBF) which is altered in a characteristic temporal-parietal pattern in AD. Numerous studies have shown the diagnostic value of reduced CBF and metabolic changes using perfusion-SPECT and FDG-PET in AD diagnosis as well as in differential diagnosis against frontotemporal dementia (FTD), dementia with Lewy-Bodies (DLB), and vascular cognitive disorders. This renders perfusion-SPECT an important piece of the puzzle (together with other diagnostic tests) by the clinician is often faced when making a final etiologic dementia diagnosis especially between AD and FTD. A similar diagnostic value can be expected when arterial spin labeling (ASL) MRI sequence is used, but the diagnostic value has yet to be confirmed in lager studies. Recently, more pathophysiology-based biomarkers in CSF and Amyloid-PET tracers have been developed that probably have a higher diagnostic accuracy than the more indirect rCBF changes seen in perfusion-SPECT. In the current review, we describe recent advances in AD biomarkers as well as improvements in the SPECT technique. © 2011 IOS Press and the authors. All rights reserved.


Treuter S.,Research Unit | Schuh A.,Research Unit | Schuh A.,Teaching Hospital of the University of Erlangen Nurenberg | Honle W.,Musculoskeletal Center Neumarkt | And 3 more authors.
International Orthopaedics | Year: 2012

Purpose: There is relatively little information available about the long-term results of total knee arthroplasty (TKA) following high tibial osteotomy. The aim of our study was to share our experiences and long-term results of TKA after a previous closing wedge high tibial osteotomy according to Wagner. Methods: In a retrospective study we identified 48 consecutive patients who had undergone TKA after a previous closing wedge high tibial osteotomy according to Wagner with a follow-up of over ten years. The average duration of follow-up after the TKA was 13.3 years (min 10.0, max 15.5). X-rays were taken in two planes before TKA, one week after TKA and at the latest follow-up. Tibio-femoral alignment was measured on weightbearing long-leg anteroposterior radiographs. Radiolucent lines at the latest follow-up were documented. Functional evaluations were performed preoperatively and postoperatively (at the time of latest follow-up). Results: The mean Knee Society function score increased from 63.1 points preoperatively to 90.0 points postoperatively. The mean overall Knee Society score increased from 93.2 points preoperatively to 160.8 points postoperatively. The mean average femoro-tibial angle was corrected from varus 0.8° (varus 14°-valgus 8.0°) preoperatively to valgus 7.6° (valgus 2-9°) at the last follow-up. Conclusions: The closing wedge high tibial osteotomy according to Wagner does not compromise subsequent total knee replacement and leads to good clinical and radiological results. © 2011 Springer-Verlag.


Vogel T.,University of Erlangen Nurenberg | Riess S.,University of Erlangen Nurenberg | Fluegel A.,University of Erlangen Nurenberg | Wensing M.,University of Erlangen Nurenberg
SAE Technical Papers | Year: 2013

Differences in thermo-physical parameters of fuels have high impact on the ignition, combustion and emission. Pure rapeseed FAME and diesel fuel with a cetane number of 60 have been compared to reference fuel. In an optical accessible vessel the fuels have been injected in order to investigate the spray, the ignition and soot formation. The high cetane number fuel showed similar behavior in spray phase to the reference fuel but the FAME fuel is more present at all operating points due to low volatile fuel components. The ignition and combustion process was investigated via chemical luminescence (CL) and laser induced incandescence (LII). In engine investigations a reduced ignition delay is detected in case of high cetane-number. The more sensitive optical techniques show differences in the combustion process. The ignition behavior of the reference fuel and the increased cetane number fuel were similar until the cetane increaser of the high cetane fuel came into effect. The FAME showed a shortened ignition delay but was found to be slower in combustion propagation. For the LII investigation a Nd:YAG pulsed laser with a wavelength of 532 nm was used. The light sheet excited the soot particles up to temperatures where the black body radiation is shifted towards the UV-spectra. The soot formation of the reference fuel is equal to the soot formation of the high cetane number fuel until the cetane increaser affected the flame and increased soot production. The soot production of the FAME is advanced in time but overall significantly lower. Copyright © 2013 SAE International and Copyright © 2013 KSAE.


Schmidt D.,University of Erlangen Nurenberg | Zimmermann R.,University of Erlangen Nurenberg | Lewczuk P.,University of Erlangen Nurenberg | Schaller G.,University of Erlangen Nurenberg | And 7 more authors.
Journal of Neural Transmission | Year: 2010

In Alzheimer disease, CSF biomarkers and nuclear imaging are of particular interest. Many studies investigated only one technique, limiting comparison. Here, in 76 patients blinded 99mTc-SPECT was compared to CSF. Sensitivity of CSF was 92%; and 51% for SPECT. Specificity favored SPECT (90 vs. 80%). Both techniques showed no coherence (p = 0.17-0.47). Our results confirm that CSF biomarkers show higher sensitivity. SPECT has higher specificity and can also be used for other dementias without established CSF biomarkers. © 2010 Springer-Verlag.


Sierra S.,University of Cologne | Lubke N.,University of Cologne | Walter H.,University of Erlangen Nurenberg | Schulter E.,University of Cologne | And 6 more authors.
Medical Microbiology and Immunology | Year: 2011

The SnoB study analysed the variability of the integrase (IN) gene of non-B viruses from treatment-naïve patients to determine whether non-B subtypes carry natural resistance mutations to raltegravir (RAL). Plasma viral RNA from 427 patients was gained, and IN sequences were subtyped and screened for subtype-speciWc highly-variable residues. Seven viruses of diVerent subtypes were phenotypically tested for RAL susceptibility; 359/427 samples could be sequenced. One hundred and seventy samples (47%) were classiWed as non-B subtypes. No primary RAL resistance-associated mutations (RRAMs) were detected. Certain secondary mutations were found, mostly related to speciWc non-B subtypes. L74 M was signiWcantly more prevalent in subtype 02°AG, T97A in A and 06°cpx, V151I in 06°cpx, and G163R in 12°BF. Various additional mutations were also detected and could be associated with the subtype too. While K156 N and S230 N were correlated with B subtype, V72I, L74I, T112I, T125A, V201I and T206S were more frequent in certain non-B subtypes. The resistance factors (RF) of 7 viral strains of diVerent subtypes ranged from 1.0 to 1.9. No primary or secondary but subtype-associated additional RRAMs were present. No correlation between RF and additional RRAMs was found. The prevalence of RRAMs was higher in non-B samples. However, the RFs for the analysed non-B subtypes showed lower values to those reported relevant to clinical failure. As the role of baseline secondary and additional mutations on RAL therapy failure is actually not known, baseline IN screening is necessary. © Springer-Verlag 2011.


PubMed | University of Erlangen Nurenberg
Type: Comparative Study | Journal: Journal of neural transmission (Vienna, Austria : 1996) | Year: 2010

In Alzheimer disease, CSF biomarkers and nuclear imaging are of particular interest. Many studies investigated only one technique, limiting comparison. Here, in 76 patients blinded 99mTc-SPECT was compared to CSF. Sensitivity of CSF was 92%; and 51% for SPECT. Specificity favored SPECT (90 vs. 80%). Both techniques showed no coherence (p = 0.17-0.47). Our results confirm that CSF biomarkers show higher sensitivity. SPECT has higher specificity and can also be used for other dementias without established CSF biomarkers.


PubMed | University of Erlangen Nurenberg
Type: | Journal: Journal of Alzheimer's disease : JAD | Year: 2011

Nuclear medicine techniques were the first functional imaging techniques used to support the clinical diagnosis of Alzheimers Disease (AD). Perfusion-SPECT allows registration of regional cerebral blood flow (rCBF) which is altered in a characteristic temporal-parietal pattern in AD. Numerous studies have shown the diagnostic value of reduced CBF and metabolic changes using perfusion-SPECT and FDG-PET in AD diagnosis as well as in differential diagnosis against frontotemporal dementia (FTD), dementia with Lewy-Bodies (DLB), and vascular cognitive disorders. This renders perfusion-SPECT an important piece of the puzzle (together with other diagnostic tests) by the clinician is often faced when making a final etiologic dementia diagnosis especially between AD and FTD. A similar diagnostic value can be expected when arterial spin labeling (ASL) MRI sequence is used, but the diagnostic value has yet to be confirmed in lager studies. Recently, more pathophysiology-based biomarkers in CSF and Amyloid-PET tracers have been developed that probably have a higher diagnostic accuracy than the more indirect rCBF changes seen in perfusion-SPECT. In the current review, we describe recent advances in AD biomarkers as well as improvements in the SPECT technique.

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