788 research outputs found
The Band Excitation Method in Scanning Probe Microscopy for Rapid Mapping of Energy Dissipation on the Nanoscale
Mapping energy transformation pathways and dissipation on the nanoscale and
understanding the role of local structure on dissipative behavior is a
challenge for imaging in areas ranging from electronics and information
technologies to efficient energy production. Here we develop a novel Scanning
Probe Microscopy (SPM) technique in which the cantilever is excited and the
response is recorded over a band of frequencies simultaneously rather than at a
single frequency as in conventional SPMs. This band excitation (BE) SPM allows
very rapid acquisition of the full frequency response at each point (i.e.
transfer function) in an image and in particular enables the direct measurement
of energy dissipation through the determination of the Q-factor of the
cantilever-sample system. The BE method is demonstrated for force-distance and
voltage spectroscopies and for magnetic dissipation imaging with sensitivity
close to the thermomechanical limit. The applicability of BE for various SPMs
is analyzed, and the method is expected to be universally applicable to all
ambient and liquid SPMs.Comment: 32 pages, 9 figures, accepted for publication in Nanotechnolog
Resting respiratory tract dendritic cells preferentially stimulate T helper cell Type 2(Th2) responses and require obligatory cytokine signals for induction of Th1 immunity
Consistent with their role in host defense, mature dendritic cells (DCs) from central lymphoid organs preferentially prime for T helper cell type 1 (Th1)-polarized immunity. However, the “default” T helper response at mucosal surfaces demonstrates Th2 polarity, which is reflected in the cytokine profiles of activated T cells from mucosal lymph nodes. This study on rat respiratory tract DCs (RTDCs) provides an explanation for this paradox. We demonstrate that freshly isolated RTDCs are functionally immature as defined in vitro, being surface major histocompatibility complex (MHC) II lo, endocytosishi, and mixed lymphocyte reactionlo, and these cells produce mRNA encoding interleukin (IL)-10. After ovalbumin (OVA)-pulsing and adoptive transfer, freshly isolated RTDCs preferentially stimulated Th2-dependent OVA-specific immunoglobulin (Ig)G1 responses, and antigen-stimulated splenocytes from recipient animals produced IL-4 in vitro. However, preculture with granulocyte/macrophage colony stimulating factor increased their in vivo IgG priming capacity by 2–3 logs, inducing production of both Th1- and Th2-dependent IgG subclasses and high levels of IFN-γ by antigen-stimulated splenocytes. Associated phenotypic changes included upregulation of surface MHC II and B7 expression and IL-12 p35 mRNA, and downregulation of endocytosis, MHC II processing– associated genes, and IL-10 mRNA expression. Full expression of IL-12 p40 required additional signals, such as tumor necrosis factor α or CD40 ligand. These results suggest that the observed Th2 polarity of the resting mucosal immune system may be an inherent property of the resident DC population, and furthermore that mobilization of Th1 immunity relies absolutely on the provision of appropriate microenvironmental costimuli
Bioavailability, Antipsoriatic Efficacy and Tolerability of a New Light Cream with Mometasone Furoate 0.1%
Mometasone furoate, a potent glucocorticoid (class III) with a favorable benefit/risk ratio, has emerged as a standard medication for the treatment of inflammatory skin disorders. The purpose of the investigation presented here was to determine the noninferiority of a topical mometasone formulation, a light cream (O/W 60/40 emulsion) with mometasone furoate 0.1% (water content of 33%) versus marketed comparators. Using the vasoconstrictor assay, a strong blanching effect of the new cream (called Mometasone cream) comparable to that of a mometasone comparator, a fatty cream with mometasone furoate 0.1%, could be demonstrated. Thus, the topical bioavailability of the active ingredient mometasone furoate (0.1%) was regarded to be similar for Mometasone cream and the mometasone comparator. Using the psoriasis plaque test, a strong antipsoriatic effect comparable to that of the mometasone comparator was found for Mometasone cream after 12 days of occlusive treatment. A nearly identical reduction in the mean infiltrate thickness and similar mean AUC values were noted with both formulations confirmed by clinical assessment data. The noninferiority of Mometasone cream to its active comparator with re-spect to the AUC of change to baseline in infiltrate thickness was demonstrated. Both medications were well tolerated. Overall, Mometasone cream and the mometasone comparator showed similar efficacy and tolerability. Mometasone cream, in addition to its high potency and good tolerability, provides the properties of a light cream, which might make this new medication particularly suitable for application on acutely inflamed and sensitive skin. Copyright (C) 2012 S. Karger AG, Base
The mycotoxin phomoxanthone A disturbs the form and function of the inner mitochondrial membrane.
Mitochondria are cellular organelles with crucial functions in the generation and distribution of ATP, the buffering of cytosolic Ca2+ and the initiation of apoptosis. Compounds that interfere with these functions are termed mitochondrial toxins, many of which are derived from microbes, such as antimycin A, oligomycin A, and ionomycin. Here, we identify the mycotoxin phomoxanthone A (PXA), derived from the endophytic fungus Phomopsis longicolla, as a mitochondrial toxin. We show that PXA elicits a strong release of Ca2+ from the mitochondria but not from the ER. In addition, PXA depolarises the mitochondria similarly to protonophoric uncouplers such as CCCP, yet unlike these, it does not increase but rather inhibits cellular respiration and electron transport chain activity. The respiration-dependent mitochondrial network structure rapidly collapses into fragments upon PXA treatment. Surprisingly, this fragmentation is independent from the canonical mitochondrial fission and fusion mediators DRP1 and OPA1, and exclusively affects the inner mitochondrial membrane, leading to cristae disruption, release of pro-apoptotic proteins, and apoptosis. Taken together, our results suggest that PXA is a mitochondrial toxin with a novel mode of action that might prove a useful tool for the study of mitochondrial ion homoeostasis and membrane dynamics
Calibration of multi-layered probes with low/high magnetic moments
We present a comprehensive method for visualisation and quantification of the magnetic stray field of magnetic force microscopy (MFM) probes, applied to the particular case of custom-made multi-layered probes with controllable high/low magnetic moment states. The probes consist of two decoupled magnetic layers separated by a non-magnetic interlayer, which results in four stable magnetic states: ±ferromagnetic (FM) and ±antiferromagnetic (A-FM). Direct visualisation of the stray field surrounding the probe apex using electron holography convincingly demonstrates a striking difference in the spatial distribution and strength of the magnetic flux in FM and A-FM states. In situ MFM studies of reference samples are used to determine the probe switching fields and spatial resolution. Furthermore, quantitative values of the probe magnetic moments are obtained by determining their real space tip transfer function (RSTTF). We also map the local Hall voltage in graphene Hall nanosensors induced by the probes in different states. The measured transport properties of nanosensors and RSTTF outcomes are introduced as an input in a numerical model of Hall devices to verify the probe magnetic moments. The modelling results fully match the experimental measurements, outlining an all-inclusive method for the calibration of complex magnetic probes with a controllable low/high magnetic moment
Constructing living buildings: a review of relevant technologies for a novel application of biohybrid robotics
Biohybrid robotics takes an engineering approach to the expansion and exploitation of biological behaviours for application to automated tasks. Here, we identify the construction of living buildings and infrastructure as a high-potential application domain for biohybrid robotics, and review technological advances relevant to its future development. Construction, civil infrastructure maintenance and building occupancy in the last decades have comprised a major portion of economic production, energy consumption and carbon emissions. Integrating biological organisms into automated construction tasks and permanent building components therefore has high potential for impact. Live materials can provide several advantages over standard synthetic construction materials, including self-repair of damage, increase rather than degradation of structural performance over time, resilience to corrosive environments, support of biodiversity, and mitigation of urban heat islands. Here, we review relevant technologies, which are currently disparate. They span robotics, self-organizing systems, artificial life, construction automation, structural engineering, architecture, bioengineering, biomaterials, and molecular and cellular biology. In these disciplines, developments relevant to biohybrid construction and living buildings are in the early stages, and typically are not exchanged between disciplines. We, therefore, consider this review useful to the future development of biohybrid engineering for this highly interdisciplinary application.publishe
Magnetic force microscopy of single crystal magnetite (Fe3O4)(abstract)
The micromagnetic domain structure of a magnetite (Fe3O4) single crystal has been studied using a magnetic force microscope (MFM). The MFM responds to the perpendicular component of the stray field above the magnetite surface. The sample was polished in the (011) plane. In this case, there are two easy magnetic axes parallel to the surface. Surface domains observed near cracks and edges have a complex closure structure (see Fig. 1), while walls seen far from such boundaries have a sinusoidal structure. Of particular interest is the presence of walls with either even or odd symmetry of the perpendicular stray field component across the transition. These can be conventionally modeled as Bloch or Neel walls, respectively. Both types of walls have been modeled and compared with the experimentally observed structures. We find the Bloch domain walls to be about 300 nm wide, nearly twice the value expected from bulk wall calculations. This distinction is consistent with a surface broadening of the domain wall due to magnetostatic effects.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70207/2/JAPIAU-75-10-6892-1.pd
Dual-Frequency Resonance-Tracking Atomic Force Microscopy
A dual-excitation method for resonant-frequency tracking in scanning probe
microscopy based on amplitude detection is developed. This method allows the
cantilever to be operated at or near resonance for techniques where standard
phase locked loops are not possible. This includes techniques with non-acoustic
driving where the phase of the driving force is frequency and/or position
dependent. An example of the later is Piezoresponse Force Microscopy (PFM),
where the resonant frequency of the cantilever is strongly dependent on the
contact stiffness of the tip-surface junction and the local mechanical
properties, but the spatial variability of the drive phase rules out the use of
a phase locked loop. Combined with high-voltage switching and imaging,
dual-frequency, resonance-tracking PFM allows reliable studies of
electromechanical and elastic properties and polarization dynamics in a broad
range of inorganic and biological systems, and is illustrated using lead
zirconate-titanate, rat tail collagen, and native and switched ferroelectric
domains in lithium niobate
ADAM17/EGFR axis promotes transglutaminase-dependent skin barrier formation through phosholipase C gamma 1 and protein kinase C pathways
This work was supported by the German Research Foundation DFG (SFB 850/B6) and by the Fritz-Thyssen
foundation (Az.10.14.2.150) to C.-W.F and the Medical Research Council (MR/L010402/1) to D.P.K
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