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Search Results: 1 - 10 of 1331 matches for " Melanie Braig "
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Signs of Change? An Analysis of Taiwan’s December 2009 Local Elections
Stefan Braig
Journal of Current Chinese Affairs , 2010,
Abstract: Under special circumstances created by a government decision to partly merge and upgrade six counties and county-level cities to special municipality status, local elections took place on December 5, 2009 in areas covering less than half of Taiwan’s population. The results are generally seen as an important, though small, victory for the opposition Democratic Progressive Party (DPP). The ruling Kuomintang (KMT) (Guomindang), however, has remained in a stable position, while the DPP still has a long way to go towards a comeback.
Expression of Eukaryotic Initiation Factor 5A and Hypusine Forming Enzymes in Glioblastoma Patient Samples: Implications for New Targeted Therapies
Michael Preukschas, Christian Hagel, Alexander Schulte, Kristoffer Weber, Katrin Lamszus, Henning Sievert, Nora P?llmann, Carsten Bokemeyer, Joachim Hauber, Melanie Braig, Stefan Balabanov
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043468
Abstract: Glioblastomas are highly aggressive brain tumors of adults with poor clinical outcome. Despite a broad range of new and more specific treatment strategies, therapy of glioblastomas remains challenging and tumors relapse in all cases. Recent work demonstrated that the posttranslational hypusine modification of the eukaryotic initiation factor 5A (eIF-5A) is a crucial regulator of cell proliferation, differentiation and an important factor in tumor formation, progression and maintenance. Here we report that eIF-5A as well as the hypusine-forming enzymes deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH) are highly overexpressed in glioblastoma patient samples. Importantly, targeting eIF-5A and its hypusine modification with GC7, a specific DHS-inhibitor, showed a strong antiproliferative effect in glioblastoma cell lines in vitro, while normal human astrocytes were not affected. Furthermore, we identified p53 dependent premature senescence, a permanent cell cycle arrest, as the primary outcome in U87-MG cells after treatment with GC7. Strikingly, combined treatment with clinically relevant alkylating agents and GC7 had an additive antiproliferative effect in glioblastoma cell lines. In addition, stable knockdown of eIF-5A and DHS by short hairpin RNA (shRNA) could mimic the antiproliferative effects of GC7. These findings suggest that pharmacological inhibition of eIF-5A may represent a novel concept to treat glioblastomas and may help to substantially improve the clinical course of this tumor entity.
Separating soil respiration components with stable isotopes: natural abundance and labelling approaches
Braig E,Tupek B
iForest : Biogeosciences and Forestry , 2010, DOI: 10.3832/ifor0541-003
Abstract: Due to the potential of forest ecosystems contributing to CO2 increase as well as to climate change mitigation, forest-atmosphere CO2 exchange has been intensively studied over last decades. However, the contribution of individual components of belowground carbon pools is still poorly known. In particular, there is no unequivocal means to separate root respiration (autotrophic) from heterotrophic respiration by soil microflora and fauna. Most studies investigating soil respiration disturbed the soil and tried to exclude autrophic respiration. Here we review alternative non invasive methods to separate the two components. Those methods share the application of the stable carbon isotope 13C, using either local changes in natural abundance of 13CO2 or artificial labelling of trees with CO2 enriched or depleted in 13C. We conclude that the applicability of natural stable isotope methods is still limited in forest ecosystems because only in a few cases there are large enough differences in 13C among soil carbon pools (usually due to the earlier presence of a C4 canopy, which is seldom in forests). On the other hand, artificial labelling with CO2 either enriched or depleted in 13C is now in a widely used for partitioning soil respiration components. However, recent findings gave clear evidence that measurements of soil CO2 efflux can be substantially influenced by the return efflux of the abiotic label. Still, especially the combination of Free Air Carbon Enrichment (FACE) with dual δ13C and δ18O stable isotope approach has the potential to provide new answers on the response sensitivity of turnover dynamics of the largest belowground soil carbon storage to elevated temperature and CO2.
Vibrational sidebands and dissipative tunneling in molecular transistors
Stephan Braig,Karsten Flensberg
Physics , 2003, DOI: 10.1103/PhysRevB.68.205324
Abstract: Transport through molecular devices with strong coupling to a single vibrational mode is considered in the case where the vibration is damped by coupling to the environment. We focus on the weak tunneling limit, for which a rate equation approach is valid. The role of the environment can be characterized by a frictional damping term $\mysig(\omega)$ and corresponding frequency shift. We consider a molecule that is attached to a substrate, leading to frequency-dependent frictional damping of the single oscillator mode of the molecule, and compare it to a reference model with frequency-independent damping featuring a constant quality factor $Q$. For large values of $Q$, the transport is governed by tunneling between displaced oscillator states giving rise to the well-known series of the Frank-Condon steps, while at small $Q$, there is a crossover to the classical regime with an energy gap given by the classical displacement energy. Using realistic values for the elastic properties of the substrate and the size of the molecule, we calculate $I$-$V$ curves and find qualitative agreement between our theory and recent experiments on $C_{60}$ single-molecule devices.
Dissipative tunneling and orthogonality catastrophe in molecular transistors
Stephan Braig,Karsten Flensberg
Physics , 2004, DOI: 10.1103/PhysRevB.70.085317
Abstract: Transport through molecular devices with weak tunnel coupling to the leads but with strong coupling to a single vibrational mode is considered in the case where the vibration is damped by coupling to the environment. In particular, we investigate what influence the electrostatic coupling of the charge on the molecule to the vibrational modes of the environment has on the $I$-$V$ characteristics. We find that, for comparable characteristic length scales of the van-der-Waals and electrostatic interaction of the molecule with the environmental vibrational modes, the $I$-$V$ characteristics are qualitatively changed from what one would expect from orthogonality catastrophe and develop a steplike discontinuity at the onset of conduction. For the case of very different length scales, we recover dissipation consistent with modeling the electrostatic forces as an external influence on the system comprised of molecule and substrate, which implies the appearance of orthogonality catastrophe, in accord with previous results.
Abcg2 Overexpression Represents a Novel Mechanism for Acquired Resistance to the Multi-Kinase Inhibitor Danusertib in BCR-ABL-Positive Cells In Vitro
Stefan Balabanov,Artur Gontarewicz,Gunhild Keller,Laura Raddrizzani,Melanie Braig,Roberta Bosotti,Jürgen Moll,Edgar Jost,Christine Barett,Imke Rohe,Carsten Bokemeyer,Tessa L. Holyoake,Tim H. Brümmendorf
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0019164
Abstract: The success of Imatinib (IM) therapy in chronic myeloid leukemia (CML) is compromised by the development of IM resistance and by a limited IM effect on hematopoietic stem cells. Danusertib (formerly PHA-739358) is a potent pan-aurora and ABL kinase inhibitor with activity against known BCR-ABL mutations, including T315I. Here, the individual contribution of both signaling pathways to the therapeutic effect of Danusertib as well as mechanisms underlying the development of resistance and, as a consequence, strategies to overcome resistance to Danusertib were investigated. Starting at low concentrations, a dose-dependent inhibition of BCR-ABL activity was observed, whereas inhibition of aurora kinase activity required higher concentrations, pointing to a therapeutic window between the two effects. Interestingly, the emergence of resistant clones during Danusertib exposure in vitro occurred considerably less frequently than with comparable concentrations of IM. In addition, Danusertib-resistant clones had no mutations in BCR-ABL or aurora kinase domains and remained IM-sensitive. Overexpression of Abcg2 efflux transporter was identified and functionally validated as the predominant mechanism of acquired Danusertib resistance in vitro. Finally, the combined treatment with IM and Danusertib significantly reduced the emergence of drug resistance in vitro, raising hope that this drug combination may also achieve more durable disease control in vivo.
Ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) is a potential tumour suppressor in prostate cancer and is frequently silenced by promoter methylation
Ramesh Ummanni, Edgar Jost, Melanie Braig, Frithjof Lohmann, Frederike Mundt, Christine Barett, Thorsten Schlomm, Guido Sauter, Tina Senff, Carsten Bokemeyer, Holger Sültmann, Catherine Meyer-Schwesinger, Tim H Brümmendorf, Stefan Balabanov
Molecular Cancer , 2011, DOI: 10.1186/1476-4598-10-129
Abstract: Methylation specific PCR analysis results showed a highly methylated promoter region for UCHL1 in 90% (18/20) of tumor tissue compared to 15% (3/20) of normal tissues from PCa patients. Pyrosequencing results confirmed a mean methylation of 41.4% in PCa whereas only 8.6% in normal tissues. To conduct functional analysis of UCHL1 in PCa, UCHL1 is overexpressed in LNCaP cells whose UCHL1 expression is normally suppressed by promoter methylation and found that UCHL1 has the ability to decrease the rate of cell proliferation and suppresses anchorage-independent growth of these cells. In further analysis, we found evidence that exogenous expression of UCHL1 suppress LNCaP cells growth probably via p53-mediated inhibition of Akt/PKB phosphorylation and also via accumulation of p27kip1 a cyclin dependant kinase inhibitor of cell cycle regulating proteins. Notably, we also observed that exogenous expression of UCHL1 induced a senescent phenotype that was detected by using the SA-?-gal assay and might be due to increased p14ARF, p53, p27kip1 and decreased MDM2.From these results, we propose that UCHL1 downregulation via promoter hypermethylation plays an important role in various molecular aspects of PCa biology, such as morphological diversification and regulation of proliferation.Prostate cancer (PCa) is the most common type of cancer found in men and is among the leading causes of cancer death in the western world [1]. The specific causes of prostate cancer remain poorly understood [2]. Recently, our group identified differentially expressed proteins which are significantly deregulated in PCa predicting their role in initiation and progression of PCa [3]. Among those proteins several members of the ubiquitin system have shown an altered expression. Ubiquitination of proteins has emerged as one of the most versatile post-translational modifications, regulating a diverse arrays of cellular processes [4]. Ubiquitination plays a central role in degradation of proteins both th
Developing an educational framework for the teaching of simulation within nurse education  [PDF]
Melanie Humphreys
Open Journal of Nursing (OJN) , 2013, DOI: 10.4236/ojn.2013.34049
Abstract:

The use of simulations as a teaching and learning tool within health care has increasing importance; simulations are seen as the major teaching method for practicing and assessing developing skills, knowledge, attitudes and meaningful decision-making within the field of nursing. Certainly the utilisations of simulations feature widely within many aspects of health care; a greater understanding of the key conceptual notions will serve to benefit all of those engaged within their application. This literature review has enabled the construction of a conceptual model for the teaching of simulation and can serve to promote the continued positive development of simulations within education. Through a consistent and insightful approach to teaching, dynamic learning will be assured within this very important aspect of engaging the nursing student within the learning process.

Rate equations for Coulomb blockade with ferromagnetic leads
Stephan Braig,Piet W. Brouwer
Physics , 2004, DOI: 10.1103/PhysRevB.71.195324
Abstract: We present a density-matrix rate-equation approach to sequential tunneling through a metal particle weakly coupled to ferromagnetic leads. The density-matrix description is able to deal with correlations between degenerate many-electron states that the standard rate equation formalism in terms of occupation probabilities cannot describe. Our formalism is valid for an arbitrary number of electrons on the dot, for an arbitrary angle between the polarization directions of the leads, and with or without spin-orbit scattering on the metal particle. Interestingly, we find that the density-matrix description may be necessary even for metal particles with unpolarized leads if three or more single-electron levels contribute to the transport current and electron-electron interactions in the metal particle are described by the `universal interaction Hamiltonian'.
Conductance Peak Height Correlations for a Coulomb-Blockaded Quantum Dot in a Weak Magnetic Field
Stephan Braig,Shaffique Adam,Piet W. Brouwer
Physics , 2003, DOI: 10.1103/PhysRevB.68.035323
Abstract: We consider statistical correlations between the heights of conductance peaks corresponding to two different levels in a Coulomb-blockaded quantum dot. Correlations exist for two peaks at the same magnetic field if the field does not fully break time-reversal symmetry as well as for peaks at different values of a magnetic field that fully breaks time-reversal symmetry. Our results are also relevant to Coulomb-blockade conductance peak height statistics in the presence of weak spin-orbit coupling in a chaotic quantum dot.
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