82 research outputs found
A cortical motor nucleus drives the basal ganglia-recipient thalamus in singing birds
The pallido-recipient thalamus transmits information from the basal ganglia to the cortex and is critical for motor initiation and learning. Thalamic activity is strongly inhibited by pallidal inputs from the basal ganglia, but the role of nonpallidal inputs, such as excitatory inputs from cortex, remains unclear. We simultaneously recorded from presynaptic pallidal axon terminals and postsynaptic thalamocortical neurons in a basal ganglia–recipient thalamic nucleus that is necessary for vocal variability and learning in zebra finches. We found that song-locked rate modulations in the thalamus could not be explained by pallidal inputs alone and persisted following pallidal lesion. Instead, thalamic activity was likely driven by inputs from a motor cortical nucleus that is also necessary for singing. These findings suggest a role for cortical inputs to the pallido-recipient thalamus in driving premotor signals that are important for exploratory behavior and learning.National Institutes of Health (U.S.) (Grant R01DC009183)National Institutes of Health (U.S.) (Grant K99NS067062)Damon Runyon Cancer Research Foundation (Postdoctoral Fellowship)Charles A. King Trust (Postdoctoral Fellowship
Shot noise in mesoscopic systems
This is a review of shot noise, the time-dependent fluctuations in the
electrical current due to the discreteness of the electron charge, in small
conductors. The shot-noise power can be smaller than that of a Poisson process
as a result of correlations in the electron transmission imposed by the Pauli
principle. This suppression takes on simple universal values in a symmetric
double-barrier junction (suppression factor 1/2), a disordered metal (factor
1/3), and a chaotic cavity (factor 1/4). Loss of phase coherence has no effect
on this shot-noise suppression, while thermalization of the electrons due to
electron-electron scattering increases the shot noise slightly. Sub-Poissonian
shot noise has been observed experimentally. So far unobserved phenomena
involve the interplay of shot noise with the Aharonov-Bohm effect, Andreev
reflection, and the fractional quantum Hall effect.Comment: 37 pages, Latex, 10 figures (eps). To be published in "Mesoscopic
Electron Transport," edited by L. P. Kouwenhoven, G. Schoen, and L. L. Sohn,
NATO ASI Series E (Kluwer Academic Publishing, Dordrecht
Juvenile Hormone (JH) Esterase of the Mosquito Culex quinquefasciatus Is Not a Target of the JH Analog Insecticide Methoprene
Juvenile hormones (JHs) are essential sesquiterpenes that control insect development and reproduction. JH analog (JHA) insecticides such as methoprene are compounds that mimic the structure and/or biological activity of JH. In this study we obtained a full-length cDNA, cqjhe, from the southern house mosquito Culex quinquefasciatus that encodes CqJHE, an esterase that selectively metabolizes JH. Unlike other recombinant esterases that have been identified from dipteran insects, CqJHE hydrolyzed JH with specificity constant (kcat/KM ratio) and Vmax values that are common among JH esterases (JHEs). CqJHE showed picomolar sensitivity to OTFP, a JHE-selective inhibitor, but more than 1000-fold lower sensitivity to DFP, a general esterase inhibitor. To our surprise, CqJHE did not metabolize the isopropyl ester of methoprene even when 25 pmol of methoprene was incubated with an amount of CqJHE that was sufficient to hydrolyze 7,200 pmol of JH to JH acid under the same assay conditions. In competition assays in which both JH and methoprene were available to CqJHE, methoprene did not show any inhibitory effects on the JH hydrolysis rate even when methoprene was present in the assay at a 10-fold higher concentration relative to JH. Our findings indicated that JHE is not a molecular target of methoprene. Our findings also do not support the hypothesis that methoprene functions in part by inhibiting the action of JHE
Drug Discovery Using Chemical Systems Biology: Weak Inhibition of Multiple Kinases May Contribute to the Anti-Cancer Effect of Nelfinavir
Nelfinavir is a potent HIV-protease inhibitor with pleiotropic effects in cancer cells. Experimental studies connect its anti-cancer effects to the suppression of the Akt signaling pathway, but the actual molecular targets remain unknown. Using a structural proteome-wide off-target pipeline, which integrates molecular dynamics simulation and MM/GBSA free energy calculations with ligand binding site comparison and biological network analysis, we identified putative human off-targets of Nelfinavir and analyzed the impact on the associated biological processes. Our results suggest that Nelfinavir is able to inhibit multiple members of the protein kinase-like superfamily, which are involved in the regulation of cellular processes vital for carcinogenesis and metastasis. The computational predictions are supported by kinase activity assays and are consistent with existing experimental and clinical evidence. This finding provides a molecular basis to explain the broad-spectrum anti-cancer effect of Nelfinavir and presents opportunities to optimize the drug as a targeted polypharmacology agent
First-principles quantum transport modeling of spin-transfer and spin-orbit torques in magnetic multilayers
We review a unified approach for computing: (i) spin-transfer torque in
magnetic trilayers like spin-valves and magnetic tunnel junction, where
injected charge current flows perpendicularly to interfaces; and (ii)
spin-orbit torque in magnetic bilayers of the type
ferromagnet/spin-orbit-coupled-material, where injected charge current flows
parallel to the interface. Our approach requires to construct the torque
operator for a given Hamiltonian of the device and the steady-state
nonequilibrium density matrix, where the latter is expressed in terms of the
nonequilibrium Green's functions and split into three contributions. Tracing
these contributions with the torque operator automatically yields field-like
and damping-like components of spin-transfer torque or spin-orbit torque
vector, which is particularly advantageous for spin-orbit torque where the
direction of these components depends on the unknown-in-advance orientation of
the current-driven nonequilibrium spin density in the presence of spin-orbit
coupling. We provide illustrative examples by computing spin-transfer torque in
a one-dimensional toy model of a magnetic tunnel junction and realistic
Co/Cu/Co spin-valve, both of which are described by first-principles
Hamiltonians obtained from noncollinear density functional theory calculations;
as well as spin-orbit torque in a ferromagnetic layer described by a
tight-binding Hamiltonian which includes spin-orbit proximity effect within
ferromagnetic monolayers assumed to be generated by the adjacent monolayer
transition metal dichalcogenide.Comment: 22 pages, 9 figures, PDFLaTeX; prepared for Springer Handbook of
Materials Modeling, Volume 2 Applications: Current and Emerging Material
Quantum Rings in Electromagnetic Fields
This is the author accepted manuscript. The final version is available from Springer via the DOI in this recordThis chapter is devoted to optical properties of so-called Aharonov-Bohm
quantum rings (quantum rings pierced by a magnetic flux resulting in AharonovBohm
oscillations of their electronic spectra) in external electromagnetic fields.
It studies two problems. The first problem deals with a single-electron AharonovBohm
quantum ring pierced by a magnetic flux and subjected to an in-plane (lateral)
electric field. We predict magneto-oscillations of the ring electric dipole moment.
These oscillations are accompanied by periodic changes in the selection rules for
inter-level optical transitions in the ring allowing control of polarization properties
of the associated terahertz radiation. The second problem treats a single-mode microcavity
with an embedded Aharonov-Bohm quantum ring which is pierced by a
magnetic flux and subjected to a lateral electric field. We show that external electric
and magnetic fields provide additional means of control of the emission spectrum
of the system. In particular, when the magnetic flux through the quantum ring is
equal to a half-integer number of the magnetic flux quanta, a small change in the
lateral electric field allows for tuning of the energy levels of the quantum ring into
resonance with the microcavity mode, thus providing an efficient way to control
the quantum ring-microcavity coupling strength. Emission spectra of the system are
discussed for several combinations of the applied magnetic and electric fields
More turán-type theorems for triangles in convex point sets
We study the following family of problems: Given a set of n points in convex position, what is the maximum number triangles one can create having these points as vertices while avoiding certain sets of forbidden configurations. As forbidden configurations we consider all 8 ways in which a pair of triangles in such a point set can interact. This leads to 256 extremal Turán-type questions. We give nearly tight (within a log n factor) bounds for 248 of these questions and show that the remaining 8 questions are all asymptotically equivalent to Stein’s longstanding tripod packing problem.SCOPUS: ar.jDecretOANoAutActifinfo:eu-repo/semantics/publishe
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