1,578 research outputs found
Theory of pressure acoustics with boundary layers and streaming in curved elastic cavities
The acoustic fields and streaming in a confined fluid depend strongly on the
acoustic boundary layer forming near the wall. The width of this layer is
typically much smaller than the bulk length scale set by the geometry or the
acoustic wavelength, which makes direct numerical simulations challenging.
Based on this separation in length scales, we extend the classical theory of
pressure acoustics by deriving a boundary condition for the acoustic pressure
that takes boundary-layer effects fully into account. Using the same
length-scale separation for the steady second-order streaming, and combining it
with time-averaged short-range products of first-order fields, we replace the
usual limiting-velocity theory with an analytical slip-velocity condition on
the long-range streaming field at the wall. The derived boundary conditions are
valid for oscillating cavities of arbitrary shape and wall motion as long as
the wall curvature and displacement amplitude are both sufficiently small.
Finally, we validate our theory by comparison with direct numerical simulation
in two examples of two-dimensional water-filled cavities: The well-studied
rectangular cavity with prescribed wall actuation, and the more generic
elliptical cavity embedded in an externally actuated rectangular elastic glass
block.Comment: 18 pages, 5 figures, pdfLatex, RevTe
Dirac Magnons, Nodal Lines, and Nodal Plane in Elemental Gadolinium
We investigate the magnetic excitations of elemental gadolinium (Gd) using inelastic neutron scattering, showing that Gd is a Dirac magnon material with nodal lines at K and nodal planes at half integer l. We find an anisotropic intensity winding around the K-point Dirac magnon cone, which is interpreted to indicate Berry phase physics. Using linear spin wave theory calculations, we show the nodal lines have nontrivial Berry phases, and topological surface modes. We also discuss the origin of the nodal plane in terms of a screw-axis symmetry, and introduce a topological invariant characterizing its presence and effect on the scattering intensity. Together, these results indicate a highly nontrivial topology, which is generic to hexagonal close packed ferromagnets. We discuss potential implications for other such systems
Spin-exchange Hamiltonian and topological degeneracies in elemental gadolinium
We present a comprehensive study of the magnetic exchange Hamiltonian of elemental gadolinium. We use neutron scattering to measure the magnon spectrum over the entire Brillouin zone and fit the excitations to a spin wave model to extract the first 26 nearest-neighbor magnetic exchange interactions with rigorously defined uncertainty. We find these exchange interactions to follow RKKY behavior, oscillating from ferromagnetic to antiferromagnetic as a function of distance. Finally, we discuss the topological features and degeneracies in Gd, and HCP ferromagnets in general. We show theoretically how, with asymmetric exchange, topological properties could be tuned with a magnetic field
Decreased resistin expression in mice with different sensitivities to a high-fat diet
The regulation of resistin, a new adipose-derived circulating factor, is the subject of controversy. In particular, the question of its modulation in obesity led to opposite results reported by two different groups. In the current study, we assayed adipocyte resistin mRNA using fluorescent real-time RT-PCR. We studied the expression of resistin in mice which are differently sensitive to diet-induced obesity: the FVB/n strain, which poorly responds to high-fat diet and transgenic mice that express human alpha 2A-AR in adipose tissue in the absence of beta 3-adrenergic receptor (AR) under the FVB genetic background which are highly sensitive to high-fat diet and develop hyperplastic obesity. We observed that FVB mice, which have no significant increased body weight after an 8-week high-fat diet period, exhibited no alteration of resistin expression. In contrast, the transgenic mice developing high-fat diet-induced obesity exhibited markedly downregulated adipocyte resistin mRNA. We also showed that obesity induced by gold thioglucose injection in FVB/n mice reduces the expression of resistin in isolated adipocytes. This argues for decreased expression of resistin as a hallmark of obesity. Moreover, our data show that feeding a high-fat diet is not a primary determinant of resistin regulation
Demonstration of astrocytes in cultured amniotic fluid cells of three cases with neural-tube defect
We have investigated the origin of rapidly adhering (RA) cells in three cases of neural tube defects (two anencephali, one encephalocele). We were able to demonstrate the presence of glial fibrillary acidic (GFA) protein in variable percentages (4–80%) of RA cells cultured for 4–6 days by use of indirect immunofluorescence with GFA antiserum. Cells cultured from amniotic fluids of normal pregnancies and fetal fibroblasts were completely GFA protein negative. GFA protein is well established as a highly specific marker for astrocytes. Demonstration of astrocytes may prove to be a criterion of high diagnostic value for neural tube defects. The percentage of astrocytes decreased with increasing culture time, while the percentage of fibronectin positive cells increased both in amniotic fluid cell cultures from neural tube defects and normal pregnancies
Correction of RT–qPCR data for genomic DNA-derived signals with ValidPrime
Genomic DNA (gDNA) contamination is an inherent problem during RNA purification that can lead to non-specific amplification and aberrant results in reverse transcription quantitative PCR (RT—qPCR). Currently, there is no alternative to RT(−) controls to evaluate the impact of the gDNA background on RT–PCR data. We propose a novel method (ValidPrime) that is more accurate than traditional RT(−) controls to test qPCR assays with respect to their sensitivity toward gDNA. ValidPrime measures the gDNA contribution using an optimized gDNA-specific ValidPrime assay (VPA) and gDNA reference sample(s). The VPA, targeting a non-transcribed locus, is used to measure the gDNA contents in RT(+) samples and the gDNA reference is used to normalize for GOI-specific differences in gDNA sensitivity. We demonstrate that the RNA-derived component of the signal can be accurately estimated and deduced from the total signal. ValidPrime corrects with high precision for both exogenous (spiked) and endogenous gDNA, contributing ∼60% of the total signal, whereas substantially reducing the number of required qPCR control reactions. In conclusion, ValidPrime offers a cost-efficient alternative to RT(−) controls and accurately corrects for signals derived from gDNA in RT–qPCR
Cisplatin and Oxaliplatin Toxicity: Importance of Cochlear Kinetics as a Determinant for Ototoxicity
Background
Cisplatin is a commonly used platinum anti-cancer drug. Regrettably cisplatin
has dose-limiting ototoxic side effects, e.g. the drug can induce an irreversible
hearing loss. The ototoxic mechanisms of cisplatin have not been
elucidated in the human ear and no clinically useful oto-protectors are yet
available. Cisplatin is a necessary part of many treatment regimes. Its beneficial
therapeutic effects might be reduced if cisplatin was excluded from the
treatment in order to protect the hearing function. In this work the ototoxic
effects of cisplatin are studied with the aim to better understand the mechanisms
behind the irreversible hearing loss induced by this drug. Oxaliplatin is
a second generation platinum-derivative anti-cancer drug, free from ototoxic
side effects in clinical practice. The effects of oxaliplatin on the inner ear have
been studied in this work and the results are compared with cisplatin treatment.
The two drugs differ regarding both anti-cancer effects and side effects,
which could be attributed to differences in pharmacokinetic factors, cellular
uptake and apoptotic mechanisms. The thioredoxin redox system with the
enzyme thioredoxin reductase (TrxR) was studied in cochleae due to a suggested
DNA-independent apoptotic mechanism of the hair cells. The cochlear
pharmacokinetics of cisplatin was assessed and the transport protein organic
cation transporter 2 (OCT2) was studied in relation to the ototoxic effect of
cisplatin.
Material and methods
Cultured human colon carcinoma cells and cell cultures of rat organ of Corti
were used for apoptosis studies in vitro following exposure to cisplatin and
oxaliplatin. Cisplatin and oxaliplatin were administered i.v. to guinea pigs,
followed by in vivo sampling of blood, cerebrospinal fluid (CSF) and scala
tympani (ST) perilymph. Liquid chromatography with post-column derivatization
was used to determine the concentration of parent drug in the samples.
Electrophysiological hearing thresholds and the loss of hair cells were assessed
to evaluate their ototoxic effects. Phenformin, a potential blocker of
OCT2 was administered and the ototoxic side effect of cisplatin was evaluated.
For immunohistochemical studies, cochlea from rat, guinea pig and pig
were used, where TrxR and OCT2 were evaluated in the cochlea. TrxR-assays
were used to measure the TrxR activity in cochlear tissue, both in vivo and in
vitro.
Results
The results from the in vitro studies showed that addition of either cisplatin
or oxaliplatin to the culture medium in organ of Corti cell cultures caused a
similar amount of outer hair cell loss and inhibition of TrxR activity. Cisplatin
exposure to cultured human colon carcinoma cells also reduced the activity
of TrxR. The results from the in vivo studies showed that a considerable concentration
of cisplatin was present in ST perilymph as compared with weak
concentrations of oxaliplatin after high dose oxaliplatin i.v. Ten minutes after
cisplatin administration, its concentration in ST perilymph was 4-fold higher
in the basal turn of the cochlea as compared to the apex. Cisplatin could be
analysed in ST perilymph for up to 120 min. Phenformin i.v. did not reduce
the ototoxic side-effect of cisplatin. Positive immunoreactivity to TrxR was
evident in both hair cells and spiral ganglion cells. Futhermore, OCT2 was
expressed in the supporting cells of organ of Corti and in the spiral ganglion
cells.
Conclusion
The transport of cisplatin to the vulnerable cells of hearing seems to be of major
importance for the ototoxic effects. An early high concentration of cisplatin
in the base of the cochlea and delayed elimination of cisplatin from ST perilymph
may be related to the cisplatin-induced loss of outer hair cells in the
basal turn of the cochlea. Cisplatin and oxaliplatin both cause similar ototoxic
effects when the organ of Corti is directly exposed in vitro. The thioredoxin
redox system with the TrxR enzyme may well play a critical role in cisplatininduced
ototoxicity. The presence of OCT2 in the supporting cells indicates
that this transport protein is primarily not involved in the uptake of cisplatin
from the systemic circulation but rather from the deeper compartments of
the cochlea. The knowledge elicited in this work will hopefully suggest objectives
for further studies in order to develop oto-protective treatments to
preserve the hearing of cisplatin treated patients
Human alpha 2A-adrenergic receptor gene expressed in transgenic mouse adipose tissue under the control of its regulatory elements.
Catecholamines regulate white adipose tissue function and development by acting through beta- and alpha2-adrenergic receptors (ARs). Human adipocytes express mainly alpha 2A- but few or no beta 3-ARs while the reverse is true for rodent adipocytes. Our aim was to generate a mouse model with a human-like alpha2/beta-adrenergic balance in adipose tissue by creating transgenic mice harbouring the human alpha 2A-AR gene under the control of its own regulatory elements in a combined mouse beta 3-AR-/- and human beta 3-AR+/+ background. Transgenic mice exhibit functional human alpha 2A-ARs only in white fat cells. Interestingly, as in humans, subcutaneous adipocytes expressed higher levels of alpha2-AR than perigonadal fat cells, which are associated with a better antilipolytic response to epinephrine. High-fat-diet-induced obesity was observed in transgenic mice in the absence of fat cell size modifications. In addition, analysis of gene expression related to lipid metabolism in isolated adipocytes suggested reduced lipid mobilization and no changes in lipid storage capacity of transgenic mice fed a high-fat diet. Finally, the development of adipose tissue in these mice was not associated with significant modifications of glucose and insulin blood levels. Thus, these transgenic mice constitute an original model of diet-induced obesity for in vivo physiological and pharmacological studies with respect to the alpha2/beta-AR balance in adipose tissue
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