Intersubband Polariton-Polariton Scattering in a Dispersive Microcavity.

The ultrafast scattering dynamics of intersubband polaritons in dispersive cavities embedding GaAs/AlGaAs quantum wells are studied directly within their band structure using a noncollinear pump-probe geometry with phase-stable midinfrared pulses. Selective excitation of the lower polariton at a frequency of ∼25 THz and at a finite in-plane momentum k_{‖} leads to the emergence of a narrowband maximum in the probe reflectivity at k_{‖}=0. A quantum mechanical model identifies the underlying microscopic process as stimulated coherent polariton-polariton scattering. These results mark an important milestone toward quantum control and bosonic lasing in custom-tailored polaritonic systems in the mid and far infrared.

Interferometric control of absorption in thin plasmonic metamaterials: general two port theory and broadband operation.

In order to extend the Coherent Perfect Absorption (CPA) phenomenology to broadband operation, the interferometric control of absorption is investigated in two-port systems without port permutation symmetry. Starting from the two-port theory of CPA treated within the Scattering Matrix formalism, we demonstrate that for all linear two-port systems with reciprocity the absorption is represented by an ellipse as function of the relative phase and intensity of the two input beams, and it is uniquely determined by the device single-beam reflectance and transmittance, and by the dephasing of the output beams. The basic properties of the phenomenon in systems without port permutation symmetry show that CPA conditions can still be found in such asymmetric devices, while the asymmetry can be beneficial for broadband operation. As experimental proof, we performed transmission measurements on a metal-semiconductor metamaterial, employing a Mach-Zehnder interferometer. The experimental results clearly evidence the elliptical feature of absorption and trace a route towards broadband operation.

Sub-cycle switch-on of ultrastrong light-matter interaction.

Controlling the way light interacts with material excitations is at the heart of cavity quantum electrodynamics (QED). In the strong-coupling regime, quantum emitters in a microresonator absorb and spontaneously re-emit a photon many times before dissipation becomes effective, giving rise to mixed light-matter eigenmodes. Recent experiments in semiconductor microcavities reached a new limit of ultrastrong coupling, where photon exchange occurs on timescales comparable to the oscillation period of light. In this limit, ultrafast modulation of the coupling strength has been suggested to lead to unconventional QED phenomena. Although sophisticated light-matter coupling has been achieved in all three spatial dimensions, control in the fourth dimension, time, is little developed. Here we use a quantum-well waveguide structure to optically tune light-matter interaction from weak to ultrastrong and turn on maximum coupling within less than one cycle of light. In this regime, a class of extremely non-adiabatic phenomena becomes observable. In particular, we directly monitor how a coherent photon population converts to cavity polaritons during abrupt switching. This system forms a promising laboratory in which to study novel sub-cycle QED effects and represents an efficient room-temperature switching device operating at unprecedented speed.

A ballistic quantum ring Josephson interferometer.

We report the realization of a ballistic Josephson interferometer. The interferometer is made from a quantum ring etched in a nanofabricated two-dimensional electron gas confined in an InAs-based heterostructure laterally contacted to superconducting niobium leads. The Josephson current flowing through the structure shows oscillations with h/e flux periodicity when threading the loop with a perpendicular magnetic field. This periodicity, in sharp contrast with the h/2e one observed in conventional dc superconducting quantum interference devices, confirms the ballistic nature of the device in agreement with theoretical predictions. This system paves the way for the implementation of interferometric Josephson π-junctions, and for the investigation of Majorana fermions.

Energy transport by neutral collective excitations at the quantum Hall edge.

We use the edge of the quantum Hall sample to study the possibility for counterpropagating neutral collective excitations. A novel sample design allows us to independently investigate charge and energy transport along the edge. We experimentally observe an upstream energy transfer with respect to the electron drift for the filling factors 1 and 1/3. Our analysis indicates that a neutral collective mode at the interaction-reconstructed edge is a proper candidate for the experimentally observed effect.

Phonon-mediated coupling of InGaAs/GaAs quantum-dot excitons to photonic crystal cavities.

We demonstrate that the emission characteristics of site-controlled InGaAs/GaAs single quantum dots embedded in photonic crystal slab cavities correspond to single confined excitons coupled to cavity modes, unlike previous reports of similar systems based on self-assembled quantum dots. By using polarization-resolved photoluminescence spectroscopy at different temperatures and a theoretical model, we show that the exciton-cavity interaction range is limited to the phonon sidebands. Photon-correlation and pump-power dependence experiments under nonresonant excitation conditions further establish that the cavity is fed only by a single exciton.

Ordered systems of site-controlled pyramidal quantum dots incorporated in photonic crystal cavities.

The coupling of a prescribed number of site-controlled pyramidal quantum dots (QDs) with photonic crystal (PhC) cavities was studied by polarization and power-dependent photoluminescence measurements. The energy of the cavity mode could be readily tuned, making use of the high spectral uniformity of the QDs and designing PhC cavities with different hole radii. Efficient coupling of the PhC cavity modes both to the ground state and to the excited state transitions of the QDs was observed, whereas no evidence for far off-resonant coupling was found.

Morphology and composition of InAs/GaAs quantum dots.

Surface compositional maps of self-organized InAs/GaAs quantum dots were obtained with laterally resolved photoemission spectroscopy. We found a surface In concentration of about 0.85 at the center of the islands which decreases to 0.75 on the wetting layer. Comparison with concentration values found in the core of similar dots suggests a strong In segregation on the topmost surface layers of the dots and on the surrounding wetting layer. Furthermore, the morphological properties of the dots such as size and density have been measured with plan-view transmission electron microscopy and low energy electron microscopy.

Conformational changes in the NS3 protease from hepatitis C virus strain Bk monitored by limited proteolysis and mass spectrometry.

Conformational changes occurring within the NS3 protease domain from the hepatitis C virus Bk strain (NS3(1-180)) under different physico-chemical conditions either in the absence or in the presence of its cofactor Pep4A were investigated by limited proteolysis experiments. Because the surface accessibility of the protein is affected by conformational changes, when comparative experiments were carried out on NS3(1-180) either at different glycerol concentrations or in the presence of Pep4A, differential peptide maps were obtained from which protein regions involved in the structural changes could be inferred. The surface topology of isolated NS3(1-180) in solution was essentially consistent with the crystal structure of the protein with the N-terminal segment showing a high conformational flexibility. At higher glycerol concentration, the protease assumed a more compact structure showing a decrease in the accessibility of the N-terminal segment that either was forced to interact with the protein or originate intermolecular interactions with neighboring molecules. Binding of the cofactor Pep4A caused the displacement of the N-terminal arm from the protein moiety, leading this segment to again adopt an open and flexible conformation, thus suggesting that the N-terminus of the protease contributes only marginally to the stability of the complex. The observed conformational changes might be directly correlated with the activation mechanism of the protease by either the cosolvent or the cofactor peptide because they lead to tighter packing of the substrate binding site.

Filling factor dependence of the fractional quantum Hall effect gap.

We directly measure the chemical potential jump in the low-temperature limit when the filling factor traverses the nu=1/3 and nu=2/5 fractional gaps in two-dimensional (2D) electron system in GaAs/AlGaAs single heterojunctions. In high magnetic fields B, both gaps are linear functions of B with slopes proportional to the inverse fraction denominator, 1/q. The fractional gaps close partially when the Fermi level lies outside. An empirical analysis indicates that the chemical potential jump for an ideal 2D electron system, in the highest accessible magnetic fields, is proportional to q(-1) B(1/2).

Direct measurements of fractional quantum Hall effect gaps.

We measure the chemical potential jump across the fractional gap in the low-temperature limit in the two-dimensional electron system of GaAs/AlGaAs single heterojunctions. In the fully spin-polarized regime, the gap for filling factor nu=1/3 increases linearly with the magnetic field and is coincident with that for nu=2/3, reflecting the electron-hole symmetry in the spin-split Landau level. In low magnetic fields, at the ground-state spin transition for nu=2/3, a correlated behavior of the nu=1/3 and nu=2/3 gaps is observed.

Role of charged residues in the catalytic mechanism of hepatitis C virus NS3 protease: electrostatic precollision guidance and transition-state stabilization.

Maturational cleavage of the hepatitis C virus polyprotein involves the viral chymotrypsin-like serine protease NS3. The substrate binding site of this enzyme is unusually flat and featureless. We here show that NS3 has a highly asymmetric charge distribution that is characterized by strong positive potentials in the vicinity of its active site and in the S5/S6 region. Using electrostatic potential calculations, we identified determinants of this positive potential, and the role of six different residues was explored by site-directed mutagenesis. Mutation of residues in the vicinity of the active site led to changes in k(cat) values of a peptide substrate indicating that basic amino acids play a role in the stabilization of the transition state. Charge neutralization in the S5/S6 region increased the K(m) values of peptide substrates in a manner that depended on the presence of negatively charged residues in the P5 and P6 positions. K(i) values of hexapeptide acids spanning P6-P1 (product inhibitors) were affected by charge neutralization in both the active site region and the S5/S6 region. Pre-steady-state kinetic data showed that the electrostatic surface potential is used by this enzyme to enhance collision rates between peptidic ligands and the active site. Calculations of the interaction energies of protease-substrate or protease-inhibitor complexes showed that electrostatic interaction energies oppose the formation of a tightly bound complex due to an unfavorable change in the desolvation energy. We propose that desolvation costs are minimized by avoiding the formation of individual ion pair interactions through the use of clusters of positively charged residues in the generation of local electrostatic potentials.

Complex formation between the hepatitis C virus serine protease and a synthetic NS4A cofactor peptide.

The NS3 protein of the hepatitis C virus contains a serine protease that, upon binding to its cofactor, NS4A, is responsible for maturational cleavages that occur in the nonstructural region of the viral polyprotein. We have studied in vitro complex formation between the NS3 protease domain expressed in Escherichia coli and a synthetic peptide spanning the minimal domain of the NS4A cofactor. Complex dissociation constants in the low micromolar range were measured using different techniques such as activity titration, fluorescence titration, and pre-equilibrium analysis of complex formation. Cofactor binding was strictly dependent on the glycerol content of buffer solutions and was not significantly influenced by substrate saturation of the enzyme. NS4A peptide binding to NS3 was accompanied by changes in the circular dichroism spectrum in the region between 270 and 290 nm, as well as by an enhancement of tryptophan fluorescence. Conversely, no changes in the far UV region of the circular dichroism spectrum were detectable. These data are indicative of induced tertiary structure changes and suggest that the secondary structure content of the uncomplexed enzyme does not differ significantly from that of the NS3-cofactor complex. Pre-equilibrium measurements of complex formation showed very low values for k(on), suggesting conformational transitions to be rate limiting for the association reaction.

Product inhibition of the hepatitis C virus NS3 protease.

The nonstructural protein NS3 of the hepatitis C virus (HCV) harbors a serine protease domain that is responsible for most of the processing events of the nonstructural region of the polyprotein. Its inhibition is presently regarded as a promising strategy for coping with the disease caused by HCV. In this work, we show that the NS3 protease undergoes inhibition by the N-terminal cleavage products of substrate peptides corresponding to the NS4A-NS4B, NS4B-NS5A, and NS5A-NS5B cleavage sites, whereas no inhibition is observed with a cleavage product of the intramolecular NS3-NS4A junction. The Ki values of the hexamer inhibitory products [Ki(NS4A) = 0.6 microM, Ki(NS5A) = 1.4 microM, and Ki(NS4B) = 180 microM] are lower than the Km values of the respective substrate peptides [Km(NS4A-NS4B) = 10 microM, Km(NS5A-NS5B) = 3.8 microM, and Km(NS4B-NS5A) > 1000 microM]. Mutagenesis experiments have identified Lys136 as an important determinant for product binding. The phenomenon of product inhibition can be exploited to optimize peptide inhibitors of NS3 protease activity that may be useful in drug development.

Activity of purified hepatitis C virus protease NS3 on peptide substrates.

The protease domain of the hepatitis C virus (HCV) protein NS3 was expressed in Escherichia coli, purified to homogeneity, and shown to be active on peptides derived from the sequence of the NS4A-NS4B junction. Experiments were carried out to optimize protease activity. Buffer requirements included the presence of detergent, glycerol, and dithiothreitol, pH between 7.5 and 8.5, and low ionic strength. C- and N-terminal deletion experiments defined a peptide spanning from the P6 to the P4' residue as a suitable substrate. Cleavage kinetics were subsequently measured by using decamer P6-P4' peptides corresponding to all intermolecular cleavage sites of the HCV polyprotein. The following order of cleavage efficiency, in terms of kcat/Km, was determined: NS5A-NS5B > NS4A-NS4B >> NS4B-NS5A. A 14-mer peptide containing residues 21 to 34 of the protease cofactor NS4A (Pep4A 21-34), when added in stoichiometric amounts, was shown to increase cleavage rates of all peptides, the largest effect (100-fold) being observed on the hydrolysis of the NS4B-NS5A decamer. From the kinetic analysis of cleavage data, we conclude that (i) primary structure is an important determinant of the efficiency with which each site is cleaved during polyprotein processing, (ii) slow cleavage of the NS4B-NS5A site in the absence of NS4A is due to low binding affinity of the enzyme for this site, and (iii) formation of a 1:1 complex between the protease and Pep4A 21-34 is sufficient and required for maximum activation.