1,509 research outputs found
Dynamical Coulomb Blockade Observed in Nano-Sized Electrical Contacts
Electrical contacts between nano-engineered systems are expected to
constitute the basic building blocks of future nano-scale electronics. However,
the accurate characterization and understanding of electrical contacts at the
nano-scale is an experimentally challenging task. Here we employ
low-temperature scanning tunneling spectroscopy to investigate the conductance
of individual nano-contacts formed between flat Pb islands and their supporting
substrates. We observe a suppression of the differential tunnel conductance at
small bias voltages due to dynamical Coulomb blockade effects. The differential
conductance spectra allow us to determine the capacitances and resistances of
the electrical contacts which depend systematically on the island--substrate
contact area. Calculations based on the theory of environmentally assisted
tunneling agree well with the measurements.Comment: 5 pages, 3 figures, to appear in PR
Albumin-coupled methotrexate (MTX-HSA) is a new anti-arthritic drug which acts synergistically to MTX
Objective. To evaluate the anti-arthritic effects of the new inflammation-targeted drug MTX-HSA and to investigate whether peripheral blood mononuclear cells (PBMC) are potential target cells for albumin-mediated drug delivery. Methods. The murine model of collagen-induced arthritis (CIA) was used to measure the anti-arthritic effect of MTX, MTX-HSA or a combination of both (n = 30 to 35 per group). In addition, the uptake of fluorescence-labelled albumin (AFLc-HSA) in PBMC of 14 patients with RA was measured by fluorescence-activated cell sorting (FACS). Results. In equivalent doses of 7.5 mg/kg intravenously (IV) twice a week, MTX-HSA is significantly (P<0.02) superior to MTX in inhibiting the development of CIA and reducing the joint count as well as the number of affected paws. When given in lower doses as combination therapy, both drugs act synergistically (P<0.03). A mean of 96, 72 and 64% of the CD14-, CD16- and CD20-positive cells from peripheral blood of rheumatoid arthritis (RA) patients showed an uptake of albumin after incubation with AFLc-HSA in vitro. This finding was not significantly different in comparison to healthy controls. In contrast, the number of CD3-positive cells taking up albumin is increased significantly in RA patients in comparison to controls (26.3 ± 12.9% s.d. vs 11.6 ± 7.3% s.d.; P = 0.005). Conclusion. The data show that the effectiveness of MTX-HSA in CIA is superior to MTX and that both drugs act synergistically. In addition, albumin appears to be taken up by peripheral blood cells, suggesting that they might be one of the potential target cells of this novel anti-arthritic treatment approac
Measuring the proton spectrum in neutron decay - latest results with aSPECT
The retardation spectrometer aSPECT was built to measure the shape of the
proton spectrum in free neutron decay with high precision. This allows us to
determine the antineutrino electron angular correlation coefficient a. We aim
for a precision more than one order of magnitude better than the present best
value, which is Delta_a /a = 5%.
In a recent beam time performed at the Institut Laue-Langevin during April /
May 2008 we reached a statistical accuracy of about 2% per 24 hours measurement
time. Several systematic effects were investigated experimentally. We expect
the total relative uncertainty to be well below 5%.Comment: Accepted for publication in the Conference Proceedings of the
International Workshop on Particle Physics with Slow Neutrons 2008 held at
the ILL, France. To be published in Nuclear Instruments and Methods in
Physics Research, Section
Immunolocalization of dually phosphorylated MAPKs in dividing root meristem cells of Vicia faba, Pisum sativum, Lupinus luteus and Lycopersicon esculentum
Key message In plants, phosphorylated MAPKs display
constitutive nuclear localization; however, not all
studied plant species show co-localization of activated
MAPKs to mitotic microtubules.
Abstract The mitogen-activated protein kinase (MAPK)
signaling pathway is involved not only in the cellular
response to biotic and abiotic stress but also in the regulation
of cell cycle and plant development. The role of
MAPKs in the formation of a mitotic spindle has been
widely studied and the MAPK signaling pathway was
found to be indispensable for the unperturbed course of cell
division. Here we show cellular localization of activated
MAPKs (dually phosphorylated at their TXY motifs) in
both interphase and mitotic root meristem cells of Lupinus
luteus, Pisum sativum, Vicia faba (Fabaceae) and Lycopersicon esculentum (Solanaceae). Nuclear localization
of activated MAPKs has been found in all species. Colocalization
of these kinases to mitotic microtubules was
most evident in L. esculentum, while only about 50 % of
mitotic cells in the root meristems of P. sativum and V.
faba displayed activated MAPKs localized to microtubules
during mitosis. Unexpectedly, no evident immunofluorescence
signals at spindle microtubules and phragmoplast
were noted in L. luteus. Considering immunocytochemical
analyses and studies on the impact of FR180204 (an
inhibitor of animal ERK1/2) on mitotic cells, we hypothesize
that MAPKs may not play prominent role in the
regulation of microtubule dynamics in all plant species
Разработка мероприятий по улучшению условий труда на примере предприятия ООО "Юргинский машиностроительный завод"
Abstract
IL-6 is known to play a crucial role in the pathogenesis of chronic intestinal inflammation by modulating T cell functions. In this study, we investigated the role of gp130, the common signal transducer for all IL-6 cytokines, in a murine model of acute T cell independent colitis to better characterize the impact of gp130 on innate immune cells and the early stages of inflammation. Experimental colitis was induced by dextran sulfate sodium treatment of mice with inducible systemic deletion of gp130 (MxCre/gp130−/−), macrophage/neutrophil-specific gp130-deficiency (LysCre/gp130−/−), or bone marrow chimeric mice and compared with wild-type controls (gp130f/f). Systemic deletion of gp130 (MxCre/gp130−/−) protected mice from severe colitis and wasting and attenuated the mucosal inflammatory infiltrate as well as local cytokine, chemokine, and adhesion molecule expression. Experiments in newly generated macrophage/neutrophil-specific gp130-deleted animals (LysCre/gp130−/−) and gp130 bone marrow chimeric mice, revealed a dual mechanism of proinflammatory effects mediated by gp130. Leukocyte recruitment was impaired in gp130-deleted animals and gp130-deleted recipients of wild-type bone marrow, demonstrating a central role of gp130-dependent signals in nonmyeloid cells for directing leukocytes to sites of inflammation, which was further confirmed in a model of sterile peritonitis. In contrast, macrophage/neutrophil-specific gp130 deficiency delayed and attenuated the disease but only marginally affected the inflammatory infiltrate, indicating a defective activation of mucosal leukocytes. We provide evidence that IL-6 cytokines acting via gp130 are required in the acute stages of intestinal inflammation by modulating the dynamics of innate immune cell recruitment and activation.</jats:p
Single-molecule experiments in biological physics: methods and applications
I review single-molecule experiments (SME) in biological physics. Recent
technological developments have provided the tools to design and build
scientific instruments of high enough sensitivity and precision to manipulate
and visualize individual molecules and measure microscopic forces. Using SME it
is possible to: manipulate molecules one at a time and measure distributions
describing molecular properties; characterize the kinetics of biomolecular
reactions and; detect molecular intermediates. SME provide the additional
information about thermodynamics and kinetics of biomolecular processes. This
complements information obtained in traditional bulk assays. In SME it is also
possible to measure small energies and detect large Brownian deviations in
biomolecular reactions, thereby offering new methods and systems to scrutinize
the basic foundations of statistical mechanics. This review is written at a
very introductory level emphasizing the importance of SME to scientists
interested in knowing the common playground of ideas and the interdisciplinary
topics accessible by these techniques. The review discusses SME from an
experimental perspective, first exposing the most common experimental
methodologies and later presenting various molecular systems where such
techniques have been applied. I briefly discuss experimental techniques such as
atomic-force microscopy (AFM), laser optical tweezers (LOT), magnetic tweezers
(MT), biomembrane force probe (BFP) and single-molecule fluorescence (SMF). I
then present several applications of SME to the study of nucleic acids (DNA,
RNA and DNA condensation), proteins (protein-protein interactions, protein
folding and molecular motors). Finally, I discuss applications of SME to the
study of the nonequilibrium thermodynamics of small systems and the
experimental verification of fluctuation theorems. I conclude with a discussion
of open questions and future perspectives.Comment: Latex, 60 pages, 12 figures, Topical Review for J. Phys. C (Cond.
Matt
Linkage between fitness of yeast cells and adenylate kinase catalysis
Enzymes have evolved with highly specific values of their catalytic parameters kcat and KM. This poses fundamental biological questions about the selection pressures responsible for evolutionary tuning of these parameters. Here we are address these questions for the enzyme adenylate kinase (Adk) in eukaryotic yeast cells. A plasmid shuffling system was developed to allow quantification of relative fitness (calculated from growth rates) of yeast in response to perturbations of Adk activity introduced through mutations. Biophysical characterization verified that all variants studied were properly folded and that the mutations did not cause any substantial differences to thermal stability. We found that cytosolic Adk is essential for yeast viability in our strain background and that viability could not be restored with a catalytically dead, although properly folded Adk variant. There exist a massive overcapacity of Adk catalytic activity and only 12% of the wild type kcat is required for optimal growth at the stress condition 20°C. In summary, the approach developed here has provided new insights into the evolutionary tuning of kcat for Adk in a eukaryotic organism. The developed methodology may also become useful for uncovering new aspects of active site dynamics and also in enzyme design since a large library of enzyme variants can be screened rapidly by identifying viable colonies
Genomic deletion and promoter methylation status of Hypermethylated in Cancer 1 (HIC1) in mantle cell lymphoma
Mantle cell lymphomas (MCL), characterized by the t(11;14)(q13;q32), frequently carry secondary genetic alterations such as deletions in chromosome 17p involving the TP53 locus. Given that the association between TP53-deletions and concurrent mutations of the remaining allele is weak and based on our recent report that the Hypermethylated in Cancer 1 (HIC1) gene, that is located telomeric to the TP53 gene, may be targeted by deletions in 17p in diffuse large B-cell lymphoma (DLBCL), we investigated whether HIC1 inactivations might also occur in MCL. Monoallelic deletions of the TP53 locus were detected in 18 out of 59 MCL (31%), while overexpression of p53 protein occurred in only 8 out of 18 of these MCL (44%). In TP53-deleted MCL, the HIC1 gene locus was co-deleted in 11 out of 18 cases (61%). However, neither TP53 nor HIC1 deletions did affect survival of MCL patients. In most analyzed cases, no hypermethylation of the HIC1 exon 1A promoter was observed (17 out of 20, 85%). However, in MCL cell lines without HIC1-hypermethylation, the mRNA expression levels of HIC1 were nevertheless significantly reduced, when compared to reactive lymph node specimens, pointing to the occurrence of mechanisms other than epigenetic or genetic events for the inactivation of HIC1 in this entity
Learning to Think Iconically in the Human and Social Sciences: Iconic Standards of Understanding as a Pivotal Challenge for Method Development
Theoretically as well as alongside an empirical research idea, this paper outlines conditions for the development of social scientific empirical methods able to further exploit the iconic potential of the image. Reconstructing the role of formal pictorial elements for the standards of understanding within the medium “image” is considered pivotal in this endeavor. Within the context of language, standards of communication have already been extensively researched. The linguistic format of the narrative, for instance, is well studied. Up to now, though, comparable formal vehicles of iconic semantics have only been examined in aesthetics and art history. Nevertheless, standards of iconic understanding are part of our implicit knowledge, are incessantly in use in everyday practice and, thus, the basis of everyday identity formation. With the help of empirical methods based on an iconic logos we can deepen our understanding of orientations, longings, and anxieties of our time that are often silently conveyed by images. Fashion will be outlined as a prototypical field, in which an empirically based development of such methods might start off
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