765 research outputs found
Nanosecond electric pulses penetrate the nucleus and enhance speckle formation
Nanosecond electric pulses generate nanopores in the interior membranes of cells and modulate cellular functions. Here, we used confocal microscopy and flow cytometry to observe Smith antigen antibody (Y12) binding to nuclear speckles, known as small nuclear ribonucleoprotein particles (snRNPs) or intrachromatin granule clusters (IGCs), in Jurkat cells following one or five 10 ns, 150 kV/cm pulses. Using confocal microscopy and flow cytometry, we observed changes in nuclear speckle labeling that suggested a disruption of pre-messenger RNA splicing mechanisms. Pulse exposure increased the nuclear speckled substructures by 2.5-fold above basal levels while the propidium iodide (PI) uptake in pulsed cells was unchanged. The resulting nuclear speckle changes were also cell cycle dependent. These findings suggest that 10 ns pulses directly influenced nuclear processes, such as the changes in the nuclear RNA–protein complexes
Efficiency of Energy Conversion in Thermoelectric Nanojunctions
Using first-principles approaches, this study investigated the efficiency of
energy conversion in nanojunctions, described by the thermoelectric figure of
merit . We obtained the qualitative and quantitative descriptions for the
dependence of on temperatures and lengths. A characteristic temperature:
was observed. When , . When , tends to a saturation value. The dependence of
on the wire length for the metallic atomic chains is opposite to that for
the insulating molecules: for aluminum atomic (conducting) wires, the
saturation value of increases as the length increases; while for
alkanethiol (insulating) chains, the saturation value of decreases as the
length increases. can also be enhanced by choosing low-elasticity bridging
materials or creating poor thermal contacts in nanojunctions. The results of
this study may be of interest to research attempting to increase the efficiency
of energy conversion in nano thermoelectric devices.Comment: 2 figure
Transition Between Ground State and Metastable States in Classical 2D Atoms
Structural and static properties of a classical two-dimensional (2D) system
consisting of a finite number of charged particles which are laterally confined
by a parabolic potential are investigated by Monte Carlo (MC) simulations and
the Newton optimization technique. This system is the classical analog of the
well-known quantum dot problem. The energies and configurations of the ground
and all metastable states are obtained. In order to investigate the barriers
and the transitions between the ground and all metastable states we first
locate the saddle points between them, then by walking downhill from the saddle
point to the different minima, we find the path in configurational space from
the ground state to the metastable states, from which the geometric properties
of the energy landscape are obtained. The sensitivity of the ground-state
configuration on the functional form of the inter-particle interaction and on
the confinement potential is also investigated
Highly Conducting pi-Conjugated Molecular Junctions Covalently Bonded to Gold Electrodes
We measure electronic conductance through single conjugated molecules bonded
to Au metal electrodes with direct Au-C covalent bonds using the scanning
tunneling microscope based break-junction technique. We start with molecules
terminated with trimethyltin end groups that cleave off in situ resulting in
formation of a direct covalent sigma bond between the carbon backbone and the
gold metal electrodes. The molecular carbon backbone used in this study consist
of a conjugated pi-system that has one terminal methylene group on each end,
which bonds to the electrodes, achieving large electronic coupling of the
electrodes to the pi-system. The junctions formed with the prototypical example
of 1,4-dimethylenebenzene show a conductance approaching one conductance
quantum (G0 = 2e2/h). Junctions formed with methylene terminated oligophenyls
with two to four phenyl units show a hundred-fold increase in conductance
compared with junctions formed with amine-linked oligophenyls. The conduction
mechanism for these longer oligophenyls is tunneling as they exhibit an
exponential dependence of conductance with oligomer length. In addition,
density functional theory based calculations for the Au-xylylene-Au junction
show near-resonant transmission with a cross-over to tunneling for the longer
oligomers.Comment: Accepted to the Journal of the American Chemical Society as a
Communication
Molecule-Electrode Interface Energetics in Molecular Junction: a Transition Voltage Spectroscopy Study
We assess the performances of the transition voltage spectroscopy (TVS)
method to determine the energies of the molecular orbitals involved in the
electronic transport though molecular junctions. A large number of various
molecular junctions made with alkyl chains but with different chemical
structure of the electrode-molecule interfaces are studied. In the case of
molecular junctions with clean, unoxidized electrode-molecule interfaces, i.e.
alkylthiols and alkenes directly grafted on Au and hydrogenated Si,
respectively, we measure transition voltages in the range 0.9 - 1.4 V. We
conclude that the TVS method allows estimating the onset of the tail of the
LUMO density of states, at energy located 1.0 - 1.2 eV above the electrode
Fermi energy. For oxidized interfaces (e.g. the same monolayer measured with Hg
or eGaIn drops, or monolayers formed on a slightly oxidized silicon substrate),
lower transition voltages (0.1 - 0.6 V) are systematically measured. These
values are explained by the presence of oxide-related density of states at
energies lower than the HOMO-LUMO of the molecules. As such, the TVS method is
a useful technique to assess the quality of the molecule-electrode interfaces
in molecular junctions.Comment: Accepted for publication in J. Phys. Chem C. One pdf file including
manuscript, figures and supporting informatio
Sensitivity of epidermal growth factor receptor and ErbB2 exon 20 insertion mutants to Hsp90 inhibition
The mature epidermal growth factor receptor (EGFR) neither associates with nor requires the molecular chaperone heat-shock protein 90 (Hsp90). Mutations in EGFR exons 18, 19, and 21 confer Hsp90 chaperone dependence. In non-small cell lung cancer (NSCLC), these mutations are associated with enhanced sensitivity to EGFR inhibitors in vitro and with clinical response in vivo. Although less prevalent, insertions in EGFR exon 20 have also been described in NSCLC. These mutations, however, confer resistance to EGFR inhibitors. In NSCLC, exon 20 insertions have also been identified in the EGFR family member ErbB2. Here, we examined the sensitivity of exon 20 insertion mutants to an Hsp90 inhibitor currently in the clinic. Our data demonstrate that both EGFR and ErbB2 exon 20 insertion mutants retain dependence on Hsp90 for stability and downstream-signalling capability, and remain highly sensitive to Hsp90 inhibition. Use of Hsp90 inhibitors should be considered in NSCLC harbouring exon 20 insertions in either EGFR or ErbB2
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