15,547 research outputs found
The Hungarian Rhapsodies and the 15 Hungarian Peasant Songs: Historical and ideological parallels between Liszt and BartĂłk
While Liszt has been recognized as central to Hungaryâs place in Western music, BartĂłk has been credited with composing Hungaryâs authentic nationalistic music. Lisztâs role in Hungarian nationalistic music and his influence on BartĂłk have only recently been given serious attention. Musicologists are beginning to concede that Lisztâs ânationalisticâ sourceâthough a hybrid of stylesâconstituted a legitimate nationalistic style worthy of research. The author examines two transitional piano pieces composed by the respective composers: Lisztâs Hungarian Rhapsodies and BartĂłkâs Fifteen Hungarian Peasant Songs. He draws attention to similarities in the genesis of the works, in the role each work played in the respective composersâ compositional development, and in compositional elements of each work. He shows through correspondence, anecdotal accounts, and the implication of various biographical facts how each of the two composers was at least partially motivated by personal patriotism. He also notes the equally strong characteristic of musical progressiveness in evidence in the works of both composers. Finally, the author compares the two piano works, referencing examples of tonal, rhythmic, and idiomatic progressiveness in each
Harnessing autophagy to overcome mitogenâactivated protein kinase kinase inhibitorâinduced resistance in metastatic melanoma
Background
Patients with malignant melanoma often relapse after treatment with BRAF and/or mitogenâactivated protein kinase kinase (MEK) inhibitors (MEKi) owing to development of drug resistance.
Objectives
To establish the temporal pattern of CD271 regulation during development of resistance by melanoma to trametinib, and determine the association between development of resistance to trametinib and induction of prosurvival autophagy.
Methods
Immunohistochemistry for CD271 and p62 was performed on human naevi and primary malignant melanoma tumours. Western blotting was used to analyse expression of CD271, p62 and LC3 in melanoma subpopulations. Flow cytometry and immunofluorescence microscopy was used to evaluate trametinibâinduced cell death and CD271 expression. MTS viability assays and zebrafish xenografts were used to evaluate the effect of CD271 and autophagy modulation on trametinibâresistant melanoma cell survival and invasion, respectively.
Results
CD271 and autophagic signalling are increased in stage III primary melanomas vs. benign naevi. In vitro studies demonstrate MEKi of BRAFâmutant melanoma induced cytotoxic autophagy, followed by the emergence of CD271âexpressing subpopulations. Trametinibâinduced CD271 reduced autophagic flux, leading to activation of prosurvival autophagy and development of MEKi resistance. Treatment of CD271âexpressing melanoma subpopulations with RNA interference and smallâmolecule inhibitors to CD271 reduced the development of MEKi resistance, while clinically applicable autophagy modulatory agents â including Î9âtetrahydrocannabinol and Vps34 â reduced survival of MEKiâresistant melanoma cells. Combined MEK/autophagy inhibition also reduced the invasive and metastatic potential of MEKiâresistant cells in an in vivo zebrafish xenograft.
Conclusions
These results highlight a novel mechanism of MEKiâinduced drug resistance and suggest that targeting autophagy may be a translatable approach to resensitize drugâresistant melanoma cells to the cytotoxic effects of MEKi
Shock and Release Temperatures in Molybdenum
Shock and release temperatures in Mo were calculated, taking account of
heating from plastic flow predicted using the Steinberg-Guinan model. Plastic
flow was calculated self-consistently with the shock jump conditions: this is
necessary for a rigorous estimate of the locus of shock states accessible. The
temperatures obtained were significantly higher than predicted assuming ideal
hydrodynamic loading. The temperatures were compared with surface emission
spectrometry measurements for Mo shocked to around 60GPa and then released into
vacuum or into a LiF window. Shock loading was induced by the impact of a
planar projectile, accelerated by high explosive or in a gas gun. Surface
velocimetry showed an elastic wave at the start of release from the shocked
state; the amplitude of the elastic wave matched the prediction to around 10%,
indicating that the predicted flow stress in the shocked state was reasonable.
The measured temperatures were consistent with the simulations, indicating that
the fraction of plastic work converted to heat was in the range 70-100% for
these loading conditions
High Reynolds number tests of a Douglas DLBA 032 airfoil in the Langley 0.3-meter transonic cryogenic tunnel
A wind-tunnel investigation of a Douglas advanced-technology airfoil was conducted in the Langley 0.3-Meter Transonic Cryogenic Tunnel (0.3-m TCT). The temperature was varied from 227 K (409 R) to 100 K (180 R) at pressures ranging from about 159 kPa (1.57 atm) to about 514 kPa (5.07 atm). Mach number was varied from 0.50 to 0.78. These variables provided a Reynolds number range (based on airfoil chord) from 6.0 to 30.0 x 10 to the 6th power. This investigation was specifically designed to: (1) test a Douglas airfoil from moderately low to flight-equivalent Reynolds numbers, and (2) evaluate sidewall-boundary-layer effects on transonic airfoil performance characteristics by a systematic variation of Mach number, Reynolds number, and sidewall-boundary-layer removal. Data are included which demonstrate the effects of fixing transition, Mach number, Reynolds number, and sidewall-boundary-layer removal on the aerodynamic characteristics of the airfoil. Also included are remarks on model design and model structural integrity
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