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Search Results: 1 - 10 of 287241 matches for " W. R. Falk "
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Absence of Leucine Zipper in the Natural FOXP3Δ2Δ7 Isoform Does Not Affect Dimerization but Abrogates Suppressive Capacity
Reiner K. W. Mailer, Kirsten Falk, Olaf R?tzschke
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006104
Abstract: Background Phenotype and function of regulatory T cells (Treg) largely depend on the presence of the transcription factor FOXP3. In contrast to mice, human Treg cells express isoforms of this protein. Besides the full length version (FOXP3fl), an isoform lacking the exon 2 (FOXP3Δ2) is co-expressed in comparable amounts. Recently, a third splice variant has been described that in addition to exon 2 also misses exon 7 (FOXP3Δ2Δ7). Exon 7 encodes for a leucine zipper motif commonly used as structural dimerization element. Mutations in exon 7 have been linked to IPEX, a severe autoimmune disease suggested to be caused by impaired dimerization of the FOXP3 protein. Principal Findings This study shows that the lack of exon 7 does not affect (homo-) dimerization. Moreover, the interaction of FOXP3Δ2Δ7 to RUNX1, NFAT and NF-kB appeared to be unchanged in co-immunoprecipitation experiments and reporter gene assays, when compared to FOXP3fl and FOXP3Δ2. Nevertheless, retroviral transduction with FOXP3Δ2Δ7 failed to induce the typical Treg-associated phenotype. The expression of FOXP3-induced surface molecules such as CD25 and CTLA-4 were not enhanced in FOXP3Δ2Δ7 transduced CD4+ T cells, which also failed to exhibit any suppressive capacity. Notably, however, co-expression of FOXP3fl with FOXP3Δ2Δ7 resulted in a reduction of CD25 expression by a dominant negative effect. Conclusions The leucine zipper of FOXP3 does not mediate dimerization or interaction with NFAT, NF-kB and RUNX1, but is indispensable for the characteristic phenotype and function in Treg cells. FOXP3Δ2Δ7 could play a role in regulating the function of the other FOXP3 isoforms and may be involved in cancer pathogenesis, as it is overexpressed by certain malignant cells.
1/f noise of Josephson-junction-embedded microwave resonators at single photon energies and millikelvin temperatures
K. W. Murch,S. J. Weber,E. M. Levenson-Falk,R. Vijay,I. Siddiqi
Physics , 2011, DOI: 10.1063/1.3700964
Abstract: We present measurements of 1/f frequency noise in both linear and Josephson-junction-embedded superconducting aluminum resonators in the low power, low temperature regime - typical operating conditions for superconducting qubits. The addition of the Josephson junction does not result in additional frequency noise, thereby placing an upper limit for fractional critical current fluctuations of $10^{-8}$ (Hz$^{-1/2}$) at 1 Hz for sub-micron, shadow evaporated junctions. These values imply a minimum dephasing time for a superconducting qubit due to critical current noise of 40 -- 1400 $\mu$s depending on qubit architecture. Occasionally, at temperatures above 50 mK, we observe the activation of individual fluctuators which increase the level of noise significantly and exhibit Lorentzian spectra.
RNA Interference towards the Potato Psyllid, Bactericera cockerelli, Is Induced in Plants Infected with Recombinant Tobacco mosaic virus (TMV)
Hada Wuriyanghan, Bryce W. Falk
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0066050
Abstract: The potato/tomato psyllid, Bactericera cockerelli (B. cockerelli), is an important plant pest and the vector of the phloem-limited bacterium Candidatus Liberibacter psyllaurous (solanacearum), which is associated with the zebra chip disease of potatoes. Previously, we reported induction of RNA interference effects in B. cockerelli via in vitro-prepared dsRNA/siRNAs after intrathoracic injection, and after feeding of artificial diets containing these effector RNAs. In order to deliver RNAi effectors via plant hosts and to rapidly identify effective target sequences in plant-feeding B. cockerelli, here we developed a plant virus vector-based in planta system for evaluating candidate sequences. We show that recombinant Tobacco mosaic virus (TMV) containing B. cockerelli sequences can efficiently infect and generate small interfering RNAs in tomato (Solanum lycopersicum), tomatillo (Physalis philadelphica) and tobacco (Nicotiana tabacum) plants, and more importantly delivery of interfering sequences via TMV induces RNAi effects, as measured by actin and V-ATPase mRNA reductions, in B. cockerelli feeding on these plants. RNAi effects were primarily detected in the B. cockerelli guts. In contrast to our results with TMV, recombinant Potato virus X (PVX) and Tobacco rattle virus (TRV) did not give robust infections in all plants and did not induce detectable RNAi effects in B. cockerelli. The greatest RNA interference effects were observed when B. cockerelli nymphs were allowed to feed on leaf discs collected from inoculated or lower expanded leaves from corresponding TMV-infected plants. Tomatillo plants infected with recombinant TMV containing B. cockerelli actin or V-ATPase sequences also showed phenotypic effects resulting in decreased B. cockerelli progeny production as compared to plants infected by recombinant TMV containing GFP. These results showed that RNAi effects can be achieved in plants against the phloem feeder, B. cockerelli, and the TMV-plant system will provide a faster and more convenient method for screening of suitable RNAi target sequences in planta.
Oral Delivery of Double-Stranded RNAs and siRNAs Induces RNAi Effects in the Potato/Tomato Psyllid, Bactericerca cockerelli
Hada Wuriyanghan,Cristina Rosa,Bryce W. Falk
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0027736
Abstract: The potato/tomato psyllid, Bactericerca cockerelli (B. cockerelli), and the Asian citrus psyllid, Diaphorina citri (D. citri), are very important plant pests, but they are also vectors of phloem-limited bacteria that are associated with two devastating plant diseases. B. cockerelli is the vector of Candidatus Liberibacter psyllaurous (solanacearum), which is associated with zebra chip disease of potatoes, and D. citri is the vector of Ca. Liberibacter asiaticus, which is associated with the Huanglongbing (citrus greening) disease that currently threatens the entire Florida citrus industry. Here we used EST sequence information from D. citri to identify potential targets for RNA interference in B. cockerelli. We targeted ubiquitously expressed and gut-abundant mRNAs via injection and oral acquisition of double-stranded RNAs and siRNAs and were able to induce mortality in recipient psyllids. We also showed knockdown of target mRNAs, and that oral acquisition resulted primarily in mRNA knockdown in the psyllid gut. Concurrent with gene knockdown was the accumulation of target specific ~ 21 nucleotide siRNAs for an abundant mRNA for BC-Actin. These results showed that RNAi can be a powerful tool for gene function studies in psyllids, and give support for continued efforts for investigating RNAi approaches as possible tools for psyllid and plant disease control.
Conformal measures associated to ends of hyperbolic n-manifolds
James W. Anderson,Kurt Falk,Pekka Tukia
Mathematics , 2004,
Abstract: Let Gamma be a non-elementary Kleinian group acting on the closed n-dimensional unit ball and assume that its Poincare series converges at the exponent alpha. Let M_Gamma be the Gamma-quotient of the open unit ball. We consider certain families E = {E_1,...,E_p} of open subsets of M_Gamma such that M_Gamma minus the union of all E_i is compact. The sets E_i are called ends of M_Gamma and E is called a complete collection of ends for M_Gamma. We show that we can associate to each end in E a conformal measure of dimension alpha such that the two measures corresponding to different ends are mutually singular if non-trivial. Each conformal measure for Gamma of dimension alpha on the limit set Lambda(Gamma) of Gamma can be written as a sum of such conformal measures associated to ends in E. In dimension 3, our results overlap with some results of Bishop and Jones.
Origin, Spread and Demography of the Mycobacterium tuberculosis Complex
Thierry Wirth ,Falk Hildebrand,Caroline Allix-Béguec,Florian W?lbeling,Tanja Kubica,Kristin Kremer,Dick van Soolingen,Sabine Rüsch-Gerdes,Camille Locht,Sylvain Brisse,Axel Meyer,Philip Supply equal contributor ,Stefan Niemann equal contributor
PLOS Pathogens , 2008, DOI: 10.1371/journal.ppat.1000160
Abstract: The evolutionary timing and spread of the Mycobacterium tuberculosis complex (MTBC), one of the most successful groups of bacterial pathogens, remains largely unknown. Here, using mycobacterial tandem repeat sequences as genetic markers, we show that the MTBC consists of two independent clades, one composed exclusively of M. tuberculosis lineages from humans and the other composed of both animal and human isolates. The latter also likely derived from a human pathogenic lineage, supporting the hypothesis of an original human host. Using Bayesian statistics and experimental data on the variability of the mycobacterial markers in infected patients, we estimated the age of the MTBC at 40,000 years, coinciding with the expansion of “modern” human populations out of Africa. Furthermore, coalescence analysis revealed a strong and recent demographic expansion in almost all M. tuberculosis lineages, which coincides with the human population explosion over the last two centuries. These findings thus unveil the dynamic dimension of the association between human host and pathogen populations.
Electric Field Controlled Magnetic Anisotropy in a Single Molecule
Alexander S. Zyazin,Johan W. G. van den Berg,Edgar A. Osorio,Herre S. J. van der Zant,Nikolaos P. Konstantinidis,Martin Leijnse,Maarten R. Wegewijs,Falk May,Walter Hofstetter,Chiara Danieli,Andrea Cornia
Physics , 2010, DOI: 10.1021/nl1009603
Abstract: We have measured quantum transport through an individual Fe$_4$ single-molecule magnet embedded in a three-terminal device geometry. The characteristic zero-field splittings of adjacent charge states and their magnetic field evolution are observed in inelastic tunneling spectroscopy. We demonstrate that the molecule retains its magnetic properties, and moreover, that the magnetic anisotropy is significantly enhanced by reversible electron addition / subtraction controlled with the gate voltage. Single-molecule magnetism can thus be electrically controlled.
Interaction of spin and vibrations in transport through single-molecule magnets
Falk May,Maarten R. Wegewijs,Walter Hofstetter
Beilstein Journal of Nanotechnology , 2011, DOI: 10.3762/bjnano.2.75
Abstract: We study electron transport through a single-molecule magnet (SMM) and the interplay of its anisotropic spin with quantized vibrational distortions of the molecule. Based on numerical renormalization group calculations we show that, despite the longitudinal anisotropy barrier and small transverse anisotropy, vibrational fluctuations can induce quantum spin-tunneling (QST) and a QST-Kondo effect. The interplay of spin scattering, QST and molecular vibrations can strongly enhance the Kondo effect and induce an anomalous magnetic field dependence of vibrational Kondo side-bands.
A Rate-Dependent Effective-Temperature Model of Shear Band Formation During Flow
Adam R. Hinkle,Michael L. Falk
Physics , 2015,
Abstract: Recent shear experiments of carbopol gels have revealed the formation of a transient shear band before reaching the steady state, which is characterized by homogeneous flow. Analysis of this phenomenon using a time-evolving effective temperature in the shear transformation zone (STZ) theory predicts that the observed fluidization proceeds via two distinct processes. A shear band nucleates and gradually broadens via disordering at the interface of the band. Simultaneously, spatially homogeneous fluidization is induced outside of the shear band where the disorder of the gel grows uniformly. Experimental data are used to determine the physical parameters of the theory, and direct, quantitative comparison is made to measurements of the structural evolution of the gel.
DO3SE modelling of soil moisture to determine ozone flux to forest trees
P. Büker, T. Morrissey, A. Briolat, R. Falk, D. Simpson, J.-P. Tuovinen, R. Alonso, S. Barth, M. Baumgarten, N. Grulke, P. E. Karlsson, J. King, F. Lagergren, R. Matyssek, A. Nunn, R. Ogaya, J. Pe uelas, L. Rhea, M. Schaub, J. Uddling, W. Werner,L. D. Emberson
Atmospheric Chemistry and Physics (ACP) & Discussions (ACPD) , 2012,
Abstract: The DO3SE (Deposition of O3 for Stomatal Exchange) model is an established tool for estimating ozone (O3) deposition, stomatal flux and impacts to a variety of vegetation types across Europe. It has been embedded within the EMEP (European Monitoring and Evaluation Programme) photochemical model to provide a policy tool capable of relating the flux-based risk of vegetation damage to O3 precursor emission scenarios for use in policy formulation. A key limitation of regional flux-based risk assessments has been the assumption that soil water deficits are not limiting O3 flux due to the unavailability of evaluated methods for modelling soil water deficits and their influence on stomatal conductance (gsto), and subsequent O3 flux. This paper describes the development and evaluation of a method to estimate soil moisture status and its influence on gsto for a variety of forest tree species. This DO3SE soil moisture module uses the Penman-Monteith energy balance method to drive water cycling through the soil-plant-atmosphere system and empirical data describing gsto relationships with pre-dawn leaf water status to estimate the biological control of transpiration. We trial four different methods to estimate this biological control of the transpiration stream, which vary from simple methods that relate soil water content or potential directly to gsto, to more complex methods that incorporate hydraulic resistance and plant capacitance that control water flow through the plant system. These methods are evaluated against field data describing a variety of soil water variables, gsto and transpiration data for Norway spruce (Picea abies), Scots pine (Pinus sylvestris), birch (Betula pendula), aspen (Populus tremuloides), beech (Fagus sylvatica) and holm oak (Quercus ilex) collected from ten sites across Europe and North America. Modelled estimates of these variables show consistency with observed data when applying the simple empirical methods, with the timing and magnitude of soil drying events being captured well across all sites and reductions in transpiration with the onset of drought being predicted with reasonable accuracy. The more complex methods, which incorporate hydraulic resistance and plant capacitance, perform less well, with predicted drying cycles consistently underestimating the rate and magnitude of water loss from the soil. A sensitivity analysis showed that model performance was strongly dependent upon the local parameterisation of key model drivers such as the maximum gsto, soil texture, root depth and leaf area index. The results suggest that the simple modelling methods that relate gsto directly to soil water content and potential provide adequate estimates of soil moisture and influence on gsto such that they are suitable to be used to assess the potential risk posed by O3 to forest trees across Europe.
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