Nonpolar m-plane GaN/AlGaN heterostructures with intersubband transitions in the 5-10 THz band.

This paper assesses intersubband (ISB) transitions in the 1-10 THz frequency range in nonpolar m-plane GaN/AlGaN multi-quantum-wells deposited on free-standing semi-insulating GaN substrates. The quantum wells (QWs) were designed to contain two confined electronic levels, decoupled from the neighboring wells. Structural analysis reveals flat and regular QWs in the two perpendicular in-plane directions, with high-angle annular dark-field scanning transmission electron microscopy images showing inhomogeneities of the Al composition in the barriers along the growth axis. We do not observe extended structural defects (stacking faults or dislocations) introduced by the epitaxial process. Low-temperature ISB absorption from 1.5 to 9 THz (6.3-37.4 meV) is demonstrated, covering most of the 7-10 THz band forbidden to GaAs-based technologies.

Tunable spin-orbit coupling via strong driving in ultracold-atom systems.

Spin-orbit coupling is an essential ingredient in topological materials, conventional and quantum-gas-based alike. Engineered spin-orbit coupling in ultracold-atom systems-unique in their experimental control and measurement opportunities-provides a major opportunity to investigate and understand topological phenomena. Here we experimentally demonstrate and theoretically analyze a technique for controlling spin-orbit coupling in a two-component Bose-Einstein condensate using amplitude-modulated Raman coupling.

Intraband absorption in self-assembled Ge-doped GaN/AlN nanowire heterostructures.

We report the observation of transverse-magnetic-polarized infrared absorption assigned to the s-p(z) intraband transition in Ge-doped GaN/AlN nanodisks (NDs) in self-assembled GaN nanowires (NWs). The s-p(z) absorption line experiences a blue shift with increasing ND Ge concentration and a red shift with increasing ND thickness. The experimental results in terms of interband and intraband spectroscopy are compared to theoretical calculations of the band diagram and electronic structure of GaN/AlN heterostructured NWs, accounting for their three-dimensional strain distribution and the presence of surface states. From the theoretical analysis, we conclude that the formation of an AlN shell during the heterostructure growth applies a uniaxial compressive strain which blue shifts the interband optical transitions but has little influence on the intraband transitions. The presence of surface states with density levels expected for m-GaN plane charge-deplete the base of the NWs but is insufficient to screen the polarization-induced internal electric field in the heterostructures. Simulations show that the free-carrier screening of the polarization-induced internal electric field in the NDs is critical to predicting the photoluminescence behavior. The intraband transitions, on the other hand, are blue-shifted due to many-body effects, namely, the exchange interaction and depolarization shift, which exceed the red shift induced by carrier screening.

Raman-induced interactions in a single-component Fermi gas near an s-wave Feshbach resonance.

Ultracold gases of interacting spin-orbit-coupled fermions are predicted to display exotic phenomena such as topological superfluidity and its associated Majorana fermions. Here, we experimentally demonstrate a route to strongly interacting single-component atomic Fermi gases by combining an s-wave Feshbach resonance (giving strong interactions) and spin-orbit coupling (creating an effective p-wave channel). We identify the Feshbach resonance by its associated atomic loss feature and show that, in agreement with our single-channel scattering model, this feature is preserved and shifted as a function of the spin-orbit-coupling parameters.

The spin Hall effect in a quantum gas.

Electronic properties such as current flow are generally independent of the electron's spin angular momentum, an internal degree of freedom possessed by quantum particles. The spin Hall effect, first proposed 40 years ago, is an unusual class of phenomena in which flowing particles experience orthogonally directed, spin-dependent forces--analogous to the conventional Lorentz force that gives the Hall effect, but opposite in sign for two spin states. Spin Hall effects have been observed for electrons flowing in spin-orbit-coupled materials such as GaAs and InGaAs (refs 2, 3) and for laser light traversing dielectric junctions. Here we observe the spin Hall effect in a quantum-degenerate Bose gas, and use the resulting spin-dependent Lorentz forces to realize a cold-atom spin transistor. By engineering a spatially inhomogeneous spin-orbit coupling field for our quantum gas, we explicitly introduce and measure the requisite spin-dependent Lorentz forces, finding them to be in excellent agreement with our calculations. This 'atomtronic' transistor behaves as a type of velocity-insensitive adiabatic spin selector, with potential application in devices such as magnetic or inertial sensors. In addition, such techniques for creating and measuring the spin Hall effect are clear prerequisites for engineering topological insulators and detecting their associated quantized spin Hall effects in quantum gases. As implemented, our system realizes a laser-actuated analogue to the archetypal semiconductor spintronic device, the Datta-Das spin transistor.

Peierls substitution in an engineered lattice potential.

Artificial gauge fields open the possibility to realize quantum many-body systems with ultracold atoms, by engineering Hamiltonians usually associated with electronic systems. In the presence of a periodic potential, artificial gauge fields may bring ultracold atoms closer to the quantum Hall regime. Here, we describe a one-dimensional lattice derived purely from effective Zeeman shifts resulting from a combination of Raman coupling and radio-frequency magnetic fields. In this lattice, the tunneling matrix element is generally complex. We control both the amplitude and the phase of this tunneling parameter, experimentally realizing the Peierls substitution for ultracold neutral atoms.

Synthetic partial waves in ultracold atomic collisions.

Interactions between particles can be strongly altered by their environment. We demonstrate a technique for modifying interactions between ultracold atoms by dressing the bare atomic states with light, creating an effective interaction of vastly increased range that scatters states of finite relative angular momentum at collision energies where only s-wave scattering would normally be expected. We collided two optically dressed neutral atomic Bose-Einstein condensates with equal, and opposite, momenta and observed that the usual s-wave distribution of scattered atoms was altered by the appearance of d- and g-wave contributions. This technique is expected to enable quantum simulation of exotic systems, including those predicted to support Majorana fermions.

Adiabaticity and localization in one-dimensional incommensurate lattices.

We experimentally investigate the role of localization on the adiabaticity of loading a Bose-Einstein condensate into a one-dimensional optical potential comprised of a shallow primary lattice plus one or two perturbing lattice(s) of incommensurate period. We find that even a very weak perturbation causes dramatic changes in the momentum distribution and makes adiabatic loading of the combined lattice much more difficult than for a single period lattice. We interpret our results using a band-structure model and the one-dimensional Gross-Pitaevskii equation.

Comparison of methods for retroviral mediated transfer of glucocerebrosidase gene to CD34+ hematopoietic progenitor cells.

Gaucher disease is an excellent candidate for gene therapy by transduction of hematopoitic stem cells. In this study, we compared methods which allow an increase in transfer of the glucocerebrosidase gene to human hematopoietic progenitor cells. Several techniques were employed, including the use of cytokines, bone marrow stroma, fibronectin, centrifugal enhancement and in vitro long-term culture. The effect of prestimulation with cytokines interleukin-3 (IL-3), interleukin-6 (IL-6) and stem cell factor (SCF) on transduction of cord blood CD34+ cells was examined. The results suggest that 16-h prestimulation was sufficient for efficient transduction. We examined the effect of bone marrow stroma and fibronectin, both of which increased transduction efficiency up to 36% and 44%, respectively, as measured by PCR for the integrated GC-cDNA in clonogenic cells (9% without any support). Transduction efficiency of 83% was obtained using 2-h centrifugation. Combining centrifugation and in vitro culture in long-term bone marrow culture media containing cytokines (IL-3/IL-6/SCF), CD34+ cells from cord blood and peripheral blood of 3 Gaucher patients were transduced weekly for 21 d. The results of 6 separate experiments consistently demonstrated transduction efficiency of 100% after 7-d in vitro culture. This transduction protocol combining centrifugation and in vitro long-term culture is an attractive method and can be applied to clinical trials.

Gaucher's disease: studies of gene transfer to haematopoietic cells.

Transfer of the gene coding for glucocerebrosidase (GC) via a retroviral vector (MFG-GC) to haematopoietic progenitors results in engraftment and life-long expression of the human protein at high levels in transplanted mice. Studies of human CD34 cells were carried out to evaluate their potential use in a gene therapy approach to Gaucher's disease. High transduction efficiency and correction of the enzyme deficiency was possible in CD34 cells obtained from patients with Gaucher's disease. Based on these results, a clinical trial of gene therapy was designed and initiated. Preliminary results of this study indicate the persistence or engraftment of genetically corrected cells in the transplanted patients.

Efficient retroviral mediated transfer of the glucocerebrosidase gene in CD34+ enriched umbilical cord blood human hematopoietic progenitors.

Obtaining efficient transfer of a normal gene and its sustained expression in self-renewing hematopoietic stem cell populations is a central concern for gene therapy initiatives. Potentially, 10(8) to 10(9) CD34+ enriched cells per patient will be required for transduction and subsequent reimplantation. These studies present an efficient method for the transduction of human CD34+ cells that can be used in a clinical study of gene transfer. The method uses a centrifugation-enhanced technique for the retroviral-mediated transfer of the normal human glucocerebrosidase (GC) gene to human CD34+ enriched umbilical cord blood cells (CB). Previous studies had described high expression of GC in CD34+ enriched cells but had not reported transduction efficiency in the progenitor population specifically. The data demonstrate an average transduction efficiency in the progenitor cell population of 50% as measured by polymerase chain reaction (PCR) for the integrated GC-cDNA in clonogenic cells. Measurements of enzyme activity comparing transduced and nontransduced fractions at 6 days posttransduction indicate an average enzyme increase of six-fold over normal background levels. PCR of colony forming units-granulocyte/macrophage (CFU-GM) plated at 6 weeks from long-term culture-initiating cell (LTC-IC) cultures also indicates transfer of the transgene to early progenitor cells. Finally, experiments were carried out with the human erythroleukemia cell line, TF-1, to estimate the durable expression of the transgene. Enzymatic activities in transduced TF-1 cultures remained at 30-fold above the activity of nontransduced controls. The expression persisted for 6 weeks in culture. These studies demonstrate efficient transduction of early progenitor cells and sustained expression of the transgene in cell cultures.

Cytokine mobilization of peripheral blood stem cells in patients with Gaucher disease with a view to gene therapy.

As clinical trials for gene therapy in Gaucher disease (GD) begin, questions regarding the biology of the hematopoietic stem cell in this disease remain unanswered. This study demonstrates the ability to mobilize and collect CD34+ cells in three patients with the disorder. Our RAC/FDA-approved clinical trial utilizes mobilized peripheral blood stem cells (PBSC) as the target cells for gene transfer. In this approach, a white blood cell fraction is collected by apheresis, enriched for CD34+ cells, and transduced with a retroviral vector carrying the glucocerebrosidase (GC) gene. Transduced cells from the patient with activity corrected to at least normal levels will be returned to the patient without myelosuppressive therapy. We report here the effect of cytokines in mobilizing PBSC in three patients with GD. Two (patients 1 and 2) were given granulocyte colony-stimulating factor (G-CSF) at a dose of 5 micrograms/kg/d and one (patient 3) was given 10 micrograms/kg/d for 10 days. Leukaphereses were done daily for 5 days and the products enriched for CD34+ cells using the clinical Ceprate (CellPro) column. The CD34+ cells in all fractions were monitored daily during mobilization and leukaphereses. Subset analysis for the expression of Thy-1, CD38, HLA-DR, and CD33 on the CD34+ cells was performed. An increase in CD34+ cells in the peripheral blood was noted from day 5 onward (up to a six-fold increase). Up to a 625-fold enrichment in CD34+ cells in the apheresis product was noted using the clinical Ceprate column. Totals of 1.2, 3.5, and 2.1 x 10(6) CD34+ cells/kg were collected in the three patients. A diminution in the percent of CD34+/Thy-1+ cells was noted with enrichment. In vitro retroviral transduction of the CD34-enriched cells using centrifugation promoted transduction protocol previously described (Bahnson AB et al., Centrifugal enhancement of retroviral-mediated gene transfer. Journal of Virology Methods 54:131, 1995) and modified for clinical use, demonstrated a mean transduction efficiency of 37% (range 8.3-87.1%) in clonogenic cells and up to 50% in long-term culture-initiating cells (LTC-IC) at week 6. Significantly, we have been able to achieve up to a 50-fold increase in the level of GC above deficient levels in the patients' CD34+ enriched cells when maintained in vitro in culture. The study demonstrates that up to a six-fold increase in CD34+ cells in the PB can be achieved with cytokines in patients with GD. CD34+ cells can be collected in numbers sufficient for conventional transplantation and transduced efficiently in vitro. In gene therapy trials for genetic disorders to date, myelosuppressive therapy is not advocated. The clinical trial will demonstrate whether this number of transduced CD34+ cells will be adequate for competitive engraftment of genetically corrected PBSC.

Effect of anger on colon motor and myoelectric activity in irritable bowel syndrome.

The present investigation was designed to study the effect of anger on colon motor and myoelectric activity in irritable bowel syndrome. Patients with irritable bowel syndrome were compared with normal controls during resting and two anger stressors: criticism of performance on an intelligence test and during a delay of assistance for a diagnostic procedure. At rest patients with irritable bowel syndrome had higher motor and spike potential activity than normal subjects; however, the difference was only significant for spike activity. Anger significantly increased colon motor and spike potential activity in the groups compared with the resting state. Patients with irritable bowel syndrome produced significantly higher motor and spike potential activity when angered. They also reported themselves to be more hostile and appeared angrier than normal controls after the study. However, they did not report themselves to be more anxious or depressed, suggesting that the observed changes in colonic function of both groups were due to anger. Patients with irritable bowel syndrome scored significantly higher than controls on the Minnesota Multiphasic Personality Inventory scales of hypochondriasis, hysteria, and depression, but these personality factors did not significantly influence their anger level before the study. The results are discussed in terms of the role of learning in the colon and the abnormal reinforcement of bowel behavior in patients with irritable bowel syndrome.

Medical monitoring. What is it, how can it be improved?

Little has been published about optimizing medical monitoring protocols, although monitoring accounts for over half of all medical laboratory tests. Monitoring is a form of surveillance consisting of repeated testing intended to detect a specified change in a patient indicating a change in his prognosis, need for treatment or need for a change in treatment. The concept of monitoring overlaps with those of screening and diagnosis. One may monitor a physiologic or pathologic process, a therapeutic or noxious agent, comparing results with the patient's previous results or with a group reference range. Pertinent questions include: what are the indications, what is to be monitored, which tests are to be used, when to start, how frequently to test, when to stop. Preliminary improvement of monitoring protocols may be achieved by applying common sense guidelines for medical decision making; using best estimates of test characteristics, of possible risks and benefits of testing, not testing, treating and not treating. Sensitivity analysis may help determine when further clinical research is needed.