427 research outputs found
Quantitative Phosphoproteomics of Proteasome Inhibition in Multiple Myeloma Cells
BACKGROUND: The proteasome inhibitor bortezomib represents an important advance in the treatment of multiple myeloma (MM). Bortezomib inhibits the activity of the 26S proteasome and induces cell death in a variety of tumor cells; however, the mechanism of cytotoxicity is not well understood. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the differential phosphoproteome upon proteasome inhibition by using stable isotope labeling by amino acids in cell culture (SILAC) in combination with phosphoprotein enrichment and LC-MS/MS analysis. In total 233 phosphoproteins were identified and 72 phosphoproteins showed a 1.5-fold or greater change upon bortezomib treatment. The phosphoproteins with expression alterations encompass all major protein classes, including a large number of nucleic acid binding proteins. Site-specific phosphopeptide quantitation revealed that Ser38 phosphorylation on stathmin increased upon bortezomib treatment, suggesting new mechanisms associated to bortezomib-induced apoptosis in MM cells. Further studies demonstrated that stathmin phosphorylation profile was modified in response to bortezomib treatment and the regulation of stathmin by phosphorylation at specific Ser/Thr residues participated in the cellular response induced by bortezomib. CONCLUSIONS/SIGNIFICANCE: Our systematic profiling of phosphorylation changes in response to bortezomib treatment not only advanced the global mechanistic understanding of the action of bortezomib on myeloma cells but also identified previously uncharacterized signaling proteins in myeloma cells
Multiple configurations of N-methylpyrrole binding on Si(111)-7×7
The adsorption configurations of N-methylpyrrole on Si(111)-7×7 were investigated using high-resolution electron energy-loss spectroscopy, x-ray photoelectron spectroscopy (XPS), scanning tunneling microscopy (STM), and density function theory calculations. Compared to physisorbed N-methylpyrrole, chemisorbed molecules present a different vibrational feature at 2886 cm-1 attributable to ν[(Si)Csp3-H] in addition to the vibrational features of (sp2)Cα-H (3106 cm-1), (sp2)Cβ-H (3050 cm-1), and C—H of CH3 (2944 cm-1) stretching modes, demonstrating the direct interaction between C=C bonds and Si(111)-7×7. The major change of N 1s XPS spectrum of N-methylpyrrole upon chemisorption strongly suggests the coexistence of two chemisorption states, further confirmed in the strong dependence of STM image features on the sample bias together with statistical analysis. The concurrent occurrence of [4+2] and [2+2] cycloadditions is proposed to account for these two adsorption configurations of N-methylpyrrole on Si(111)-7×
The Electron Pairing of KFeSe
We studied the pairing instabilities in KFeSe using a two
stage functional renormalization group (FRG) method. Our results suggest the
leading and subleading pairing symmetries are nodeless and nodal
extended respectively. In addition, despite having no Fermi surfaces we
find the buried hole bands make important contributions to the final effective
interaction. From the bandstructure, spin susceptibility and the FRG results we
conclude that the low energy effective interaction in KFeSe is
well described by a model with dominant nearest-neighbor
antiferromagnetic interaction (at least as far as the superconducting
pairing is concerned). In the end we briefly mention several obvious
experiments to test whether the pairing symmetry is indeed .Comment: typo in Eq.(7) corrected on top of published version, 15 pages, 7
figures, double line spacin
Size-Matched Radical Multivalency
Persistent π-radicals such as MV^+• (MV refers to methyl viologen, i.e., N,Nꞌ-dimethyl-4,4ꞌ-bipyridinum) engage in weak radical-radical interactions. This phenomenon has been utilized recently in supramolecular chemistry with the discovery that MV+• and [cyclobis(paraquat-p-phenylene)]2(+•) (CBPQT2(+•)) form a strong 1:1 host-guest complex [CBPQT⊂MV]3(+•). In this full paper, we describe the extension of radical-pairing-based molecular recognition to a larger, square-shaped diradical host, [cyclobis(paraquat-4,4ꞌ-biphenylene)]2(+•) (MS2(+•)). This molecular square was assessed for its ability to bind an isomeric series of possible diradical cyclophane guests, which consist of two radical viologen units that are linked by two ortho-, meta-, or para-xylylene bridges to provide different spacings between the planar radicals. UV-Vis-NIR measurements reveal that only the m-xylylene-linked isomer (m-CBPQT2(+•)) binds strongly inside of MS2(+•), resulting in the formation of a tetra-radical complex [MS⊂m-CBPQT]4(+•). Titration experiments and variable temperature UV-Vis-NIR and EPR spectroscopic data indicate that, relative to the smaller tris-radical complex [CBPQT⊂MV]3(+•), the new host-guest complex forms with a more favorable enthalpy change that is offset by a greater entropic penalty. As a result, the association constant (Ka = (1.12+/- 0.08) x 10^5 M^(-1)) for [MS⊂m-CBPQT]4(+•) is similar to that previously determined for [CBPQT⊂MV]3(+•). The (super)structures of MS2(+•), m-CBPQT2(+•), and [MS⊂m-CBPQT]4(+•) were examined by single-crystal X-ray diffraction measurements and DFT calculations. The solid-state and computational structural analyses reveal that m-CBPQT2(+•) is ideally sized to bind inside of MS2(+•). The solid-state superstructures also indicate that localized radical-radical interactions in m-CBPQT2(+•) and [MS⊂m-CBPQT]4(+•) disrupt the extended radical-pairing interactions that are common in crystals of other viologen radical cations. Lastly, the formation of [MS⊂m-CBPQT]4(+•) was probed by cyclic voltammetry, demonstrating that the radical states of the cyclophanes are stabilized by the radical-pairing interactions
Pairing symmetry and properties of iron-based high temperature superconductors
Pairing symmetry is important to indentify the pairing mechanism. The
analysis becomes particularly timely and important for the newly discovered
iron-based multi-orbital superconductors. From group theory point of view we
classified all pairing matrices (in the orbital space) that carry irreducible
representations of the system. The quasiparticle gap falls into three
categories: full, nodal and gapless. The nodal-gap states show conventional
Volovik effect even for on-site pairing. The gapless states are odd in orbital
space, have a negative superfluid density and are therefore unstable. In
connection to experiments we proposed possible pairing states and implications
for the pairing mechanism.Comment: 4 pages, 1 table, 2 figures, polished versio
Domain wall brane in squared curvature gravity
We suggest a thick braneworld model in the squared curvature gravity theory.
Despite the appearance of higher order derivatives, the localization of gravity
and various bulk matter fields is shown to be possible. The existence of the
normalizable gravitational zero mode indicates that our four-dimensional
gravity is reproduced. In order to localize the chiral fermions on the brane,
two types of coupling between the fermions and the brane forming scalar is
introduced. The first coupling leads us to a Schr\"odinger equation with a
volcano potential, and the other a P\"oschl-Teller potential. In both cases,
the zero mode exists only for the left-hand fermions. Several massive KK states
of the fermions can be trapped on the brane, either as resonant states or as
bound states.Comment: 18 pages, 5 figures and 1 table, references added, improved version
to be published in JHE
Prescribing patterns of antidepressants, antipsychotics and mood stabilizers in bipolar patients misdiagnosed with major depressive disorder in China
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94515/1/hup2262.pd
A simulation study on the measurement of D0-D0bar mixing parameter y at BES-III
We established a method on measuring the \dzdzb mixing parameter for
BESIII experiment at the BEPCII collider. In this method, the doubly
tagged events, with one decays to
CP-eigenstates and the other decays semileptonically, are used to
reconstruct the signals. Since this analysis requires good separation,
a likelihood approach, which combines the , time of flight and the
electromagnetic shower detectors information, is used for particle
identification. We estimate the sensitivity of the measurement of to be
0.007 based on a fully simulated MC sample.Comment: 6 pages, 7 figure
Effects of temperature on thick branes and the fermion (quasi-)localization
Following Campos's work [Phys. Rev. Lett. 88, 141602 (2002)], we investigate
the effects of temperature on flat, de Sitter (dS), and anti-de Following
Campos's work [Phys. Rev. Lett. \textbf{88}, 141602 (2002)], we investigate the
effects of temperature on flat, de Sitter (dS), and anti-de Sitter (AdS) thick
branes in five-dimensional (5D) warped spacetime, and on the fermion
(quasi-)localization. First, in the case of flat brane, when the critical
temperature reaches, the solution of the background scalar field and the warp
factor is not unique. So the thickness of the flat thick brane is uncertain at
the critical value of the temperature parameter, which is found to be lower
than the one in flat 5D spacetime. The mass spectra of the fermion Kaluza-Klein
(KK) modes are continuous, and there is a series of fermion resonances. The
number and lifetime of the resonances are finite and increase with the
temperature parameter, but the mass of the resonances decreases with the
temperature parameter. Second, in the case of dS brane, we do not find such a
critical value of the temperature parameter. The mass spectra of the fermion KK
modes are also continuous, and there is a series of fermion resonances. The
effects of temperature on resonance number, lifetime, and mass are the same
with the case of flat brane. Last, in the case of AdS brane, {the critical
value of the temperature parameter can less or greater than the one in the flat
5D spacetime.} The spectra of fermion KK modes are discrete, and the mass of
fermion KK modes does not decrease monotonically with increasing temperature
parameter.Comment: 24 pages, 15 figures, published versio
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