196 research outputs found
Role of Dicer Enzyme in the Regulation of Store Operated Calcium Entry (SOCE) in CD4+ T Cells
Background/Aims: Activation of T cell receptors (TCRs) in CD4+ T cells leads to a cascade of signalling reactions including increase of intracellular calcium (Ca2+) levels with subsequent Ca2+ dependent stimulation of gene expression, proliferation, cell motility and cytokine release. The increase of cytosolic Ca2+ results from intracellular Ca2+ release with subsequent activation of store-operated Ca2+ entry (SOCE). Previous studies suggested miRNAs are required for the development and functions of CD4+ T cells. An enzyme called Dicer is required during the process of manufacturing mature miRNAs from the precursor miRNAs. In this study, we explored whether loss of Dicer in CD4+ T cells affects SOCE and thus Ca2+ dependent regulation of cellular functions. Methods: We tested the expression of Orai1 by q-RT-PCR and flow cytometry. Further, we measured SOCE by an inverted phase-contrast microscope with the Incident-light fluorescence illumination system using Fura-2. Intracellular Ca2+ was also measured by flow cytometry using Ca2+ sensitive dye Fluo-4. Results: We found that in Dicer deficient (DicerΔ/Δ) mice Orai1 was downregulated at mRNA and protein level in CD4+ T cells. Further, SOCE was significantly smaller in DicerΔ/Δ CD4+ T cells than in CD4+ T cells isolated from wild-type (Dicerfl/fl) mice. Conclusion: Our data suggest that miRNAs are required for adequate Ca2+ entry into CD4+ T cells and thus triggering of Ca2+ sensitive immune functions
Targeting lyn kinase in chorea-acanthocytosis: A translational treatment approach in a rare disease
Background: Chorea-acanthocytosis (ChAc) is a neurodegenerative disease caused by mutations in the VPS13A gene. It is characterized by several neurological symptoms and the appearance of acanthocytes. Elevated tyrosine kinase Lyn activity has been recently identified as one of the key pathophysiological mechanisms in this disease, and therefore represents a promising drug target. Methods: We evaluated an individual off-label treatment with the tyrosine kinase inhibitor dasatinib (100 mg/d, 25.8–50.4 weeks) of three ChAc patients. Alongside thorough safety monitoring, we assessed motor and non-motor scales (e.g., MDS-UPDRS, UHDRS, quality of life) as well as routine and experimental laboratory parameters (e.g., serum neurofilament, Lyn kinase activity, actin cytoskeleton in red blood cells). Results: Dasatinib appeared to be reasonably safe. The clinical parameters remained stable without significant improvement or deterioration. Regain of deep tendon reflexes was observed in one patient. Creatine kinase, serum neurofilament levels, and acanthocyte count did not reveal consistent effects. However, a reduction of initially elevated Lyn kinase activity and accumulated autophagy markers, as well as a partial restoration of the actin cytoskeleton, was found in red blood cells. Conclusions: We report on the first treatment approach with disease-modifying intention in ChAc. The experimental parameters indicate target engagement in red blood cells, while clinical effects on the central nervous system could not be proven within a rather short treatment time. Limited knowledge on the natural history of ChAc and the lack of appropriate biomarkers remain major barriers for “clinical trial readiness”. We suggest a panel of outcome parameters for future clinical trials in ChA
Laser modulated optical reflectance of thin semiconductor films on glass
Semiconductor films, deposited by reactive magnetron sputtering on glass substrates have been analyzed with the help of laser-modulated optical reflectance. The results are discussed with respect to the thermal and charge carrier transport properties. Semiconductor properties have been identified both for micro-crystalline and amorphous film
Theory of Banana Liquid Crystal Phases and Phase Transitions
We study phases and phase transitions that can take place in the newly
discovered banana (bow-shaped or bent-core) liquid crystal molecules. We show
that to completely characterize phases exhibited by such bent-core molecules a
third-rank tensor order parameter is necessary in addition to the
vector and the nematic (second-rank) tensor order parameters. We present an
exhaustive list of possible liquid phases, characterizing them by their
space-symmetry group and order parameters, and catalog the universality classes
of the corresponding phase transitions that we expect to take place in such
bent-core molecular liquid crystals. In addition to the conventional
liquid-crystal phases such as the nematic phase, we predict the existence of
novel liquid phases, including the spontaneously chiral nematic
and chiral polar phases, the orientationally-ordered but
optically isotropic tetrahedratic phase, and a novel nematic phase
with symmetry that is neither uniaxial nor biaxial. Interestingly, the
Isotropic-Tetrahedratic transition is {\em continuous} in mean-field theory,
but is likely driven first-order by thermal fluctuations. We conclude with a
discussion of smectic analogs of these phases and their experimental
signatures.Comment: 28 pgs. RevTex, 32 eps figures, submitted to Phys. Rev.
Mathematical Properties of a New Levin-Type Sequence Transformation Introduced by \v{C}\'{\i}\v{z}ek, Zamastil, and Sk\'{a}la. I. Algebraic Theory
\v{C}\'{\i}\v{z}ek, Zamastil, and Sk\'{a}la [J. Math. Phys. \textbf{44}, 962
- 968 (2003)] introduced in connection with the summation of the divergent
perturbation expansion of the hydrogen atom in an external magnetic field a new
sequence transformation which uses as input data not only the elements of a
sequence of partial sums, but also explicit estimates
for the truncation errors. The explicit
incorporation of the information contained in the truncation error estimates
makes this and related transformations potentially much more powerful than for
instance Pad\'{e} approximants. Special cases of the new transformation are
sequence transformations introduced by Levin [Int. J. Comput. Math. B
\textbf{3}, 371 - 388 (1973)] and Weniger [Comput. Phys. Rep. \textbf{10}, 189
- 371 (1989), Sections 7 -9; Numer. Algor. \textbf{3}, 477 - 486 (1992)] and
also a variant of Richardson extrapolation [Phil. Trans. Roy. Soc. London A
\textbf{226}, 299 - 349 (1927)]. The algebraic theory of these transformations
- explicit expressions, recurrence formulas, explicit expressions in the case
of special remainder estimates, and asymptotic order estimates satisfied by
rational approximants to power series - is formulated in terms of hitherto
unknown mathematical properties of the new transformation introduced by
\v{C}\'{\i}\v{z}ek, Zamastil, and Sk\'{a}la. This leads to a considerable
formal simplification and unification.Comment: 41 + ii pages, LaTeX2e, 0 figures. Submitted to Journal of
Mathematical Physic
THERMAL-WAVE MEASUREMENTS OF MULTI-LAYER SUPERINSULATION FOILS
Abstract Thermal wave measurements rely on modulated laser heating and IR detection of the thermal response, using a MCT detector with IR optics and lock-in amplifier. Both, the amplitude and the phase retardation of the thermal wave response with respect to the heating modu-lation, provide information on the effective thermal transport properties of the measured samples. Here we apply this method to determine the shielding properties of multilayer superinsulation foils, used for the thermal insulation of superconducting magnetic coils in particle accelerators, e.g. in LHC at CERN. The measurements, performed at ambient temperature and ambient and reduced pressure, have been interpreted using a theoreti-cal model, including both conductive and radiative heat transport. The results show that the radiative heat transport can be well identified, although the conductive heat transport is dominant across multi-layer samples. At reduced pressures, the conductive heat transport decrea-ses considerably and, depending on the number of spacer layers, the radiative heat transport can become dominant. Applying this new photothermal technique, the shielding efficiencies of multi-layer superinsulation foils have been compared in this work for the first time
Detection of crenosoma spp., angiostrongylus vasorum and aelurostrongylus abstrusus in gastropods in Eastern Austria
Canine and feline cardiorespiratory parasites are of utmost relevance in veterinary medicine. Key epizootiological information on major pet metastrongyloids, i.e., Angiostrongylus vasorum and Crenosoma vulpis infecting dogs, and Aelurostrongylus abstrusus and Troglostrongylus brevior infecting cats, is missing from Austria. This study investigated their occurrence in 1320 gastropods collected in the Austrian provinces of Styria, Burgenland, Lower Austria, and in metropolitan Vienna. Metastrongyloid larvae were microscopically detected in 25 samples, and sequence analysis confirmed the presence of metastrongyloids in nine samples, i.e., A. vasorum in one slug (Arion vulgaris) (0.07%), C. vulpis in five slugs (one Limax maximus and four A. vulgaris) (0.4%), A. abstrusus in two A. vulgaris (0.17%), and the hedgehog lungworm Crenosoma striatum was detected in one A. vulgaris. The present study confirms the enzooticity of major cardiorespiratory nematodes in Austria and that canine and feline populations are at risk of infection
QED Effective Action Revisited
The derivation of a convergent series representation for the quantum
electrodynamic effective action obtained by two of us (S.R.V. and D.R.L.) in
[Can. J. Phys. vol. 71, p. 389 (1993)] is reexamined. We present more details
of our original derivation. Moreover, we discuss the relation of the
electric-magnetic duality to the integral representation for the effective
action, and we consider the application of nonlinear convergence acceleration
techniques which permit the efficient and reliable numerical evaluation of the
quantum correction to the Maxwell Lagrangian.Comment: 20 pages, LaTeX, 1 table; minor additions and adjustments; to appear
in Can. J. Phy
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