Andreev reflection of fractional quantum Hall quasiparticles.

Electron correlation in a quantum many-body state appears as peculiar scattering behaviour at its boundary, symbolic of which is Andreev reflection at a metal-superconductor interface. Despite being fundamental in nature, dictated by the charge conservation law, however, the process has had no analogues outside the realm of superconductivity so far. Here, we report the observation of an Andreev-like process originating from a topological quantum many-body effect instead of superconductivity. A narrow junction between fractional and integer quantum Hall states shows a two-terminal conductance exceeding that of the constituent fractional state. This remarkable behaviour, while theoretically predicted more than two decades ago but not detected to date, can be interpreted as Andreev reflection of fractionally charged quasiparticles. The observed fractional quantum Hall Andreev reflection provides a fundamental picture that captures microscopic charge dynamics at the boundaries of topological quantum many-body states.

Validation of impaired Transient Receptor Potential Melastatin 3 ion channel activity in natural killer cells from Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis patients.

BACKGROUND: Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS/ME) is a complex multifactorial disorder of unknown cause having multi-system manifestations. Although the aetiology of CFS/ME remains elusive, immunological dysfunction and more particularly reduced cytotoxic activity in natural killer (NK) cells is the most consistent laboratory finding. The Transient Receptor Potential (TRP) superfamily of cation channels play a pivotal role in the pathophysiology of immune diseases and are therefore potential therapeutic targets. We have previously identified single nucleotide polymorphisms in TRP genes in peripheral NK cells from CFS/ME patients. We have also described biochemical pathway changes and calcium signaling perturbations in NK cells from CFS/ME patients. Notably, we have previously reported a decrease of TRP cation channel subfamily melastatin member 3 (TRPM3) function in NK cells isolated from CFS/ME patients compared with healthy controls after modulation with pregnenolone sulfate and ononetin using a patch-clamp technique. In the present study, we aim to confirm the previous results describing an impaired TRPM3 activity in a new cohort of CFS/ME patients using a whole cell patch-clamp technique after modulation with reversible TRPM3 agonists, pregnenolone sulfate and nifedipine, and an effective TRPM3 antagonist, ononetin. Indeed, no formal research has commented on using pregnenolone sulfate or nifedipine to treat CFS/ME patients while there is evidence that clinicians prescribe calcium channel blockers to improve different symptoms. METHODS: Whole-cell patch-clamp technique was used to measure TRPM3 activity in isolated NK cells from twelve age- and sex-matched healthy controls and CFS/ME patients, after activation with pregnenolone sulfate and nifedipine and inhibition with ononetin. RESULTS: We confirmed a significant reduction in amplitude of TRPM3 currents after pregnenolone sulfate stimulation in isolated NK cells from another cohort of CFS/ME patients compared with healthy controls. The pregnenolone sulfate-evoked ionic currents through TRPM3 channels were again significantly modulated by ononetin in isolated NK cells from healthy controls compared with CFS/ME patients. In addition, we used nifedipine, another reversible TRPM3 agonist to support the previous findings and found similar results confirming a significant loss of the TRPM3 channel activity in CFS/ME patients. CONCLUSIONS: Impaired TRPM3 activity was validated in NK cells isolated from CFS/ME patients using different pharmacological tools and whole-cell patch-clamp technique as the gold standard for ion channel research. This investigation further helps to establish TRPM3 channels as a prognostic marker and/ or a potential therapeutic target for CFS/ME.

Detection and Control of Spin-Orbit Interactions in a GaAs Hole Quantum Point Contact.

We investigate the relationship between the Zeeman interaction and the inversion-asymmetry-induced spin-orbit interactions (Rashba and Dresselhaus SOIs) in GaAs hole quantum point contacts. The presence of a strong SOI results in the crossing and anticrossing of adjacent spin-split hole subbands in a magnetic field. We demonstrate theoretically and experimentally that the anticrossing energy gap depends on the interplay between the SOI terms and the highly anisotropic hole g tensor and that this interplay can be tuned by selecting the crystal axis along which the current and magnetic field are aligned. Our results constitute the independent detection and control of the Dresselhaus and Rashba SOIs in hole systems, which could be of importance for spintronics and quantum information applications.

Negative and positive cross-correlations of current noises in quantum Hall edge channels at bulk filling factor [Formula: see text].

Cross-correlation noise in electrical currents generated from a series connection of two quantum point contacts (QPCs), the injector and the detector, is described for investigating energy relaxation in quantum Hall edge channels at bulk filling factor [Formula: see text]. We address the importance of tuning the energy bias across the detector for this purpose. For a long channel with a macroscopic floating ohmic contact that thermalizes the electrons, the cross-correlation turns from negative values to the maximally positive value (identical noise in the two currents) by tuning the effective energy bias to zero. This can be understood by considering competition between the low-frequency charge fluctuation generated at the injector, which contributes positive correlation, and the partition noise at the detector, which gives negative correlation. Strikingly, even for a short channel without intentional thermalization, significantly large positive correlation is observed in contrast to negative values expected for coherent transport between the two QPCs.

Regulation of striatal dopamine responsiveness by Notch/RBP-J signaling.

Dopamine signaling is essential for reward learning and fear-related learning, and thought to be involved in neuropsychiatric diseases. However, the molecular mechanisms underlying the regulation of dopamine responsiveness is unclear. Here we show the critical roles of Notch/RBP-J signaling in the regulation of dopamine responsiveness in the striatum. Notch/RBP-J signaling regulates various neural cell fate specification, and neuronal functions in the adult central nervous system. Conditional deletion of RBP-J specifically in neuronal cells causes enhanced response to apomorphine, a non-selective dopamine agonist, and SKF38393, a D1 agonist, and impaired dopamine-dependent instrumental avoidance learning, which is corrected by SCH23390, a D1 antagonist. RBP-J deficiency drastically reduced dopamine release in the striatum and caused a subtle decrease in the number of dopaminergic neurons. Lentivirus-mediated gene transfer experiments showed that RBP-J deficiency in the striatum was sufficient for these deficits. These findings demonstrated that Notch/RBP-J signaling regulates dopamine responsiveness in the striatum, which may explain the mechanism whereby Notch/RBP-J signaling affects an individual's susceptibility to neuropsychiatric disease.

Exchange-Induced Spin Blockade in a Two-Electron Double Quantum Dot.

We have experimentally identified the exchange-induced spin blockade in a GaAs double quantum dot. The transport is suppressed only when the eigenstates are well-defined singlet and triplet states, and thus sensitive to dynamic nuclear-spin polarization that causes singlet-triplet mixing. This gives rise to unusual current spectra, such as a sharp current dip and an asymmetric current profile near the triplet resonance of a double quantum dot. Numerical simulations suggest that the current dip is a signature of identical nuclear-spin polarization in the two dots, which is attractive for coherent spin manipulations in a material with nuclear spins.

Enhanced electron-phonon coupling for a semiconductor charge qubit in a surface phonon cavity.

Electron-phonon coupling is a major decoherence mechanism, which often causes scattering and energy dissipation in semiconductor electronic systems. However, this electron-phonon coupling may be used in a positive way for reaching the strong or ultra-strong coupling regime in an acoustic version of the cavity quantum electrodynamic system. Here we propose and demonstrate a phonon cavity for surface acoustic waves, which is made of periodic metal fingers that constitute Bragg reflectors on a GaAs/AlGaAs heterostructure. Phonon band gap and cavity phonon modes are identified by frequency, time and spatially resolved measurements of the piezoelectric potential. Tunneling spectroscopy on a double quantum dot indicates the enhancement of phonon assisted transitions in a charge qubit. This encourages studying of acoustic cavity quantum electrodynamics with surface phonons.

Fractionalized wave packets from an artificial Tomonaga-Luttinger liquid.

The model of interacting fermion systems in one dimension known as a Tomonaga-Luttinger liquid (TLL) provides a simple and exactly solvable theoretical framework that predicts various intriguing physical properties. Evidence of a TLL has been observed as power-law behaviour in electronic transport on various types of one-dimensional conductor. However, these measurements, which rely on d.c. transport involving electron tunneling processes, cannot identify the long-awaited hallmark of charge fractionalization, in which an injection of elementary charge e from a non-interacting lead is divided into the non-trivial effective charge e* and the remainder, e-e* (refs 6, 7, 8). Here, we report time-resolved transport measurements on an artificial TLL composed of coupled integer quantum Hall edge channels, in which we successfully identify single charge fractionalization processes. A wave packet of charge q incident from a non-interacting region breaks up into several fractionalized charge wave packets at the edges of the artificial TLL, from which transport eigenmodes can be evaluated directly. These results are informative for elucidating the nature of TLLs and low-energy excitations in the edge channels.

Plasmon transport in graphene investigated by time-resolved electrical measurements.

Plasmons, which are collective charge oscillations, could provide a means of confining electromagnetic field to nanoscale structures. Recently, plasmonics using graphene have attracted interest, particularly because of the tunable plasmon dispersion, which will be useful for tunable frequency in cavity applications. However, the carrier density dependence of the dispersion is weak (proportional to n(1/4)) and it is difficult to tune the frequency over orders of magnitude. Here, by exploiting electronic excitation and detection, we carry out time-resolved measurements of a charge pulse travelling in a plasmon mode in graphene corresponding to the gigahertz range. We demonstrate that the plasmon velocity can be changed over two orders of magnitude by applying a magnetic field B and by screening the plasmon electric field with a gate metal; at high B, edge magnetoplasmons, which are plasmons localized at the sample edge, are formed and their velocity depends on B, n and the gate screening effect.

Selective overexpression of Comt in prefrontal cortex rescues schizophrenia-like phenotypes in a mouse model of 22q11 deletion syndrome.

The 22q11.2 microdeletion is one of the highest genetic risk factors for schizophrenia. It is not well understood which interactions of deleted genes in 22q11.2 regions are responsible for the pathogenesis of schizophrenia, but catechol-O-methytransferase (COMT) is among the candidates. Df1/+ mice are 22q11.2 deletion syndrome (22q11DS) model mice with a hemizygous deletion of 18 genes in the 22q11-related region. Df1/+ mice showed enhanced response to the dopamine D1 agonist, SKF38393, and the N-methyl-D-aspartate antagonist, MK801, which can be normalized by a GABA(A) receptor agonist, bretazenil, or a GABA(A) α2/α3 receptor agonist, SL651498. Here, we demonstrated the curing effects of virus-mediated reintroduction of Comt to the prefrontal cortex (PFC) in Df1/+ mice. In contrast, both Comt overexpression and Comt inhibition caused an abnormal responsiveness to Bretazenil, a GABA(A) receptor agonist in control mice. Comt overexpression increased MK801-induced interneuronal activation and GABA release in the PFC. The expression levels of GABA-related genes such as Gabrb2 (GABA(A)receptor ß2), Gad2 (glutamic acid decarboxylase 65 (Gad65)) and Reln (Reelin) correlate with a Comt expression level in PFC. Our data suggest that Comt-mediated regulation of GABAergic system might be involved in the behavioral pathogenesis of Df1/+ mice.

Magnetic-field dependence of tunnel couplings in carbon nanotube quantum dots.

By means of sequential and cotunneling spectroscopy, we study the tunnel couplings between metallic leads and individual levels in a carbon nanotube quantum dot. The levels are ordered in shells consisting of two doublets with strong- and weak-tunnel couplings, leading to gate-dependent level renormalization. By comparison to a one- and two-shell model, this is shown to be a consequence of disorder-induced valley mixing in the nanotube. Moreover, a parallel magnetic field is shown to reduce this mixing and thus suppress the effects of tunnel renormalization.

Unraveling the spin polarization of the ν = 5/2 fractional quantum Hall state.

The fractional quantum Hall (FQH) effect at filling factor ν = 5/2 has recently come under close scrutiny, as its ground state may possess quasi-particle excitations obeying nonabelian statistics, a property sought for topologically protected quantum operations. However, its microscopic origin remains unknown, and candidate model wave functions include those with undesirable abelian statistics. We report direct measurements of the electron spin polarization of the ν = 5/2 FQH state using resistively detected nuclear magnetic resonance. We find the system to be fully polarized, which unambiguously rules out the most likely abelian contender and lends strong support for the ν = 5/2 state being nonabelian. Our measurements reveal an intrinsically different nature of interaction in the first excited Landau level underlying the physics at ν = 5/2.

Gate-dependent orbital magnetic moments in carbon nanotubes.

We investigate how the orbital magnetic moments of electron and hole states in a carbon nanotube quantum dot depend on the number of carriers on the dot. Low temperature transport measurements are carried out in a setup where the device can be rotated in an applied magnetic field, thus enabling accurate alignment with the nanotube axis. The field dependence of the level structure is measured by excited state spectroscopy and excellent correspondence with a single-particle calculation is found. In agreement with band structure calculations we find a decrease of the orbital magnetic moment with increasing electron or hole occupation of the dot, with a scale given by the band gap of the nanotube.

Impact of valley polarization on the resistivity in two dimensions.

We examine the temperature dependence of resistivity in a two-dimensional electron system formed in a silicon-on-insulator quantum well. The device allows us to tune the valley splitting continuously in addition to the electron density. Our data provide a global picture of how the resistivity and its temperature dependence change with valley polarization. At the boundary between valley-polarized and partially polarized regions, we demonstrate that there is an insulating contribution from spin-degenerate electrons occupying the upper valley-subband edge.

Stereo-selective inhibition of transient receptor potential TRPC5 cation channels by neuroactive steroids.

BACKGROUND AND PURPOSE: Transient receptor potential canonical 5 (TRPC5) channels are widely expressed, including in the CNS, where they potentiate fear responses. They also contribute to other non-selective cation channels that are stimulated by G-protein-coupled receptor agonists and lipid and redox factors. Steroids are known to modulate fear and anxiety states, and we therefore investigated whether TRPC5 exhibited sensitivity to steroids. EXPERIMENTAL APPROACH: Human TRPC5 channels were conditionally expressed in HEK293 cells and studied using intracellular Ca2+ measurement, whole-cell voltage-clamp and excised patch techniques. For comparison, control experiments were performed with cells lacking TRPC5 channels or expressing another TRP channel, TRPM2. Native TRPC channel activity was recorded from vascular smooth muscle cells. KEY RESULTS: Extracellular application of pregnenolone sulphate, pregnanolone sulphate, pregnanolone, progesterone or dihydrotestosterone inhibited TRPC5 activity within 1-2min. Dehydroepiandrosterone sulphate or 17ß-oestradiol had weak inhibitory effects. Pregnenolone, and allopregnanolone, a progesterone metabolite and stereo-isomer of pregnanolone, all had no effects. Progesterone was the most potent of the steroids, especially against TRPC5 channel activity evoked by sphingosine-1-phosphate. In outside-out patch recordings, bath-applied progesterone and dihydrotestosterone had strong and reversible effects, suggesting relatively direct mechanisms of action. Progesterone inhibited native TRPC5-containing channel activity, evoked by oxidized phospholipid. CONCLUSIONS AND IMPLICATIONS: Our data suggest that TRPC5 channels are susceptible to relatively direct and rapid stereo-selective steroid modulation, leading to channel inhibition. The study adds to growing appreciation of TRP channels as non-genomic steroid sensors.

Carboplatin plus weekly paclitaxel treatment in non-small cell lung cancer patients with interstitial lung disease.

BACKGROUND: Since advanced non-small cell lung cancer (NSCLC) patients with the interstitial lung disease (ILD) have been excluded from clinical trials, it is uncertain whether chemotherapy really provides a benefit to these patients. PATIENTS AND METHODS: Fifteen advanced NSCLC patients with ILD that was detected on the chest X-rays were enrolled in this study. Carboplatin plus paclitaxel was administered by two methods (method A or method B). Method A: Carboplatin (AUC 6, day 1) and paclitaxel (70 mg/m(2), days 1, 8, 15) were administered every four weeks. Method B: Carboplatin (AUC 2, day 1, 8, 15) and paclitaxel (60 mg/m(2), days 1, 8, 15) were administered every four weeks. RESULTS: The response rate and the disease control rate were 33% and 53%. The median progression-free survival and the median overall survival time were 2.5 months and 7.0 months, respectively. The hematological toxicities were tolerable, but a grade 3 or higher pneumonitis was observed in 4 patients (27%). CONCLUSION: Carboplatin plus weekly paclitaxel must be administered carefully to advanced NSCLC patients with ILD that is detected on chest X-rays after a sufficient evaluation of the risks and the benefits.

Cis-isomerism and other chemical requirements of steroidal agonists and partial agonists acting at TRPM3 channels.

BACKGROUND AND PURPOSE: The transient receptor potential melastatin-3 (TRPM3) channel forms calcium-permeable, non-selective, cationic channels that are stimulated by pregnenolone sulphate (PregS). Here, we aimed to define chemical requirements of this acute steroid action and potentially reveal novel stimulators with physiological relevance. EXPERIMENTAL APPROACH: We used TRPM3 channels over-expressed in HEK 293 cells, with intracellular calcium measurement and whole-cell patch-clamp recording techniques. KEY RESULTS: The stimulation of TRPM3 channels was confined to PregS and closely related steroids and not mimicked by other major classes of steroids, including progesterone. Relatively potent stimulation of TRPM3-dependent calcium entry was observed. A sulphate group positioned at ring A was important for strong stimulation but more striking was the requirement for a cis (beta) configuration of the side group, revealing previously unrecognized stereo-selectivity and supporting existence of a specific binding site. A cis-oriented side group on ring A was not the only feature necessary for high activity because loss of the double bond in ring B reduced potency and loss of the acetyl group at ring D reduced efficacy and potency. Weak steroid stimulators of TRPM3 channels inhibited effects of PregS, suggesting partial agonism. In silico screening of chemical libraries for non-steroid modulators of TRPM3 channels revealed the importance of the steroid backbone for stimulatory effects. CONCLUSIONS AND IMPLICATIONS: Our data defined some of the chemical requirements for acute stimulation of TRPM3 channels by steroids, supporting the existence of a specific and unique steroid binding site. Epipregnanolone sulphate was identified as a novel TRPM3 channel stimulator.

Intrinsic gap and exciton condensation in the nu{T}=1 bilayer system.

We investigate the quasiparticle excitation of the bilayer quantum Hall (QH) system at a total filling factor nu{T}=1 in the limit of negligible interlayer tunneling under a tilted magnetic field. We show that the intrinsic quasiparticle excitation is of purely pseudospin origin and solely governed by the inter- and intralayer electron interactions. A model based on exciton formation successfully explains the quantitative behavior of the quasiparticle excitation gap, demonstrating the existence of a link between the excitonic QH state and the composite fermion liquid. Our results provide a new insight into the nature of the phase transition between the two states.

Spin-dependent phase diagram of the nuT=1 bilayer electron system.

We show that the spin degree of freedom plays a decisive role in the phase diagram of the nu(T)=1 bilayer electron system using an in-plane field B( parallel) in the regime of negligible tunneling. We observe that the phase boundary separating the quantum Hall and compressible states at d/l(B) = 1.90 for B(parallel) = 0 (d: interlayer distance, l(B): magnetic length) steadily shifts with B(parallel) before saturating at d/l(B) = 2.33 when the compressible state becomes fully polarized. Using a simple model for the energies of the competing phases, we can quantitatively describe our results. A new phase diagram as a function of d/l(B) and the Zeeman energy is established and its implications as to the nature of the phase transition are discussed.

NMR evidence for spin canting in a bilayer nu=2 quantum hall system.

We investigate the electron spin states in the bilayer quantum Hall system at total Landau level filling factor nu=2 exploiting current-pumped and resistively detected NMR. The measured Knight shift, K(S), of 75As nuclei reveals continuous variation of the out-of-plane electronic spin polarization between nearly full and zero as a function of density imbalance. Nuclear spin relaxation measurements indicate a concurrent development of an in-plane spin component. These results provide direct information on the spin configuration in this system and comprise strong evidence for the spin canting suggested by previous experiments.