A hermetic on-cryostat helium source for low temperature experiments.

We describe a helium source cell for use in cryogenic experiments that is hermetically sealed in situ on the cold plate of a cryostat. The source cell is filled with helium gas at room temperature and, subsequently, sealed using a cold weld crimping tool before the cryostat is closed and cooled down. At low temperatures, the helium condenses and collects in a connected experimental volume, as monitored via the frequency response of a planar superconducting resonator device sensitive to small amounts of liquid helium. This on-cryostat helium source negates the use of a filling tube between the cryogenic volumes and room temperature, thereby preventing unwanted effects such as temperature instabilities that arise from the thermomechanical motion of helium within the system. This helium source can be used in experiments investigating the properties of quantum fluids or to better thermalize quantum devices.

Phononic bath engineering of a superconducting qubit.

Phonons, the ubiquitous quanta of vibrational energy, play a vital role in the performance of quantum technologies. Conversely, unintended coupling to phonons degrades qubit performance and can lead to correlated errors in superconducting qubit systems. Regardless of whether phonons play an enabling or deleterious role, they do not typically admit control over their spectral properties, nor the possibility of engineering their dissipation to be used as a resource. Here we show that coupling a superconducting qubit to a bath of piezoelectric surface acoustic wave phonons enables a novel platform for investigating open quantum systems. By shaping the loss spectrum of the qubit via the bath of lossy surface phonons, we demonstrate preparation and dynamical stabilization of superposition states through the combined effects of drive and dissipation. These experiments highlight the versatility of engineered phononic dissipation and advance the understanding of mechanical losses in superconducting qubit systems.

Piezoacoustics for precision control of electrons floating on helium.

Piezoelectric surface acoustic waves (SAWs) are powerful for investigating and controlling elementary and collective excitations in condensed matter. In semiconductor two-dimensional electron systems SAWs have been used to reveal the spatial and temporal structure of electronic states, produce quantized charge pumping, and transfer quantum information. In contrast to semiconductors, electrons trapped above the surface of superfluid helium form an ultra-high mobility, two-dimensional electron system home to strongly-interacting Coulomb liquid and solid states, which exhibit non-trivial spatial structure and temporal dynamics prime for SAW-based experiments. Here we report on the coupling of electrons on helium to an evanescent piezoelectric SAW. We demonstrate precision acoustoelectric transport of as little as ~0.01% of the electrons, opening the door to future quantized charge pumping experiments. We also show SAWs are a route to investigating the high-frequency dynamical response, and relaxational processes, of collective excitations of the electronic liquid and solid phases of electrons on helium.

Unconventional field-effect transistor composed of electrons floating on liquid helium.

We report on an unconventional macroscopic field effect transistor composed of electrons floating above the surface of superfluid helium. With this device unique transport regimes are realized in which the charge density of the electron layer can be controlled in a manner not possible in other material systems. In particular, we are able to manipulate the collective behavior of the electrons to produce a highly non-uniform, but precisely controlled, charge density to reveal a negative source-drain current. This behavior can be understood by considering the propagation of damped charge oscillations along a transmission line formed by the inhomogeneous sheet of two-dimensional electrons above, and between, the source and drain electrodes of the transistor.

Anisotropic phases of superfluid

It has been shown that the relative stabilities of various superfluid states of ^{3}He can be influenced by anisotropy in a silica aerogel framework. We prepared a suite of aerogel samples compressed up to 30% for which we performed pulsed NMR on ^{3}He imbibed within the aerogel. We identified A and B phases and determined their magnetic field-temperature phase diagrams as a function of strain. From these results, we infer that the B phase is distorted by negative strain forming an anisotropic superfluid state more stable than the A phase.

Stability of superfluid 3He-B in compressed aerogel.

In recent work, it was shown that new anisotropic p-wave states of superfluid (3)He can be stabilized within high-porosity silica aerogel under uniform positive strain. In contrast, the equilibrium phase in an unstrained aerogel is the isotropic superfluid B phase. Here we report that this phase stability depends on the sign of the strain. For a negative strain of ∼ 20% achieved by compression, the B phase can be made more stable than the anisotropic A phase, resulting in a tricritical point for A, B, and normal phases with a critical field of ∼ 100 mT. From pulsed NMR measurements, we identify these phases and the orientation of the angular momentum.

Identification of superfluid phases of 3He in uniformly isotropic 98.2% aerogel.

Superfluid ^{3}He confined to high porosity silica aerogel is the paradigm system for understanding impurity effects in unconventional superconductors. However, a crucial first step has been elusive: exact identification of the microscopic states of the superfluid in the presence of quenched disorder. Using a new class of highly uniform aerogel materials, we report pulsed nuclear magnetic resonance experiments that demonstrate definitively that the two observed superfluid states in aerogel are impure versions of the isotropic and axial p-wave states. The theoretically predicted destruction of long-range orbital order (Larkin-Imry-Ma effect) in the impure axial state is not observed.

Modification of the 3He phase diagram by anisotropic disorder.

Motivated by the recent prediction that uniaxially compressed aerogel can stabilize the anisotropic A phase over the isotropic B phase, we measure the pressure dependent superfluid fraction of (3)He entrained in 10% axially compressed, 98% porous aerogel. We observe that a broad region of the temperature-pressure phase diagram is occupied by the metastable A phase. The reappearance of the A phase on warming from the B phase, before superfluidity is extinguished at T(c), is in contrast to its absence in uncompressed aerogel. The phase diagram is modified from that of pure (3)He, with the disappearance of the polycritical point (PCP) and the appearance of a region of A phase extending below the PCP of bulk (3)He, even in zero applied magnetic field. The expected alignment of the A phase texture by compression is not observed.

Anomalous attenuation of transverse sound in 3He.

We present the first measurements of the attenuation of transverse sound in superfluid 3He-B. We use fixed path length interferometry combined with the magnetoacoustic Faraday effect to vary the effective path length by a factor of 2, resulting in absolute values of the attenuation. We find that attenuation is significantly larger than expected from the theoretical dispersion relation, in contrast with the phase velocity of transverse sound. We suggest that the anomalous attenuation can be explained by surface Andreev bound states.

Magnetoacoustic spectroscopy in superfluid 3He-B.

We have used the acoustic Faraday effect in superfluid 3He to perform high resolution spectroscopy of an excited state of the superfluid condensate, called the imaginary squashing mode. With acoustic cavity interferometry we measure the rotation of the plane of polarization of a transverse sound wave propagating in the direction of the magnetic field from which we determine the Zeeman energy of the mode. We interpret the Landé g factor, combined with the zero-field energies of this excited state, using the theory of Sauls and Serene, to calculate the strength of f-wave interactions in 3He.

Collective modes and f-wave pairing interactions in superfluid (3)He.

Precision measurements of collective mode frequencies in superfluid (3)He-B are sensitive to quasiparticle and f-wave pairing interactions. Measurements were performed at various pressures using interference of transverse sound in an acoustic cavity. We fit the measured collective mode frequencies, which depend on the strength of f-wave pairing and the Fermi liquid parameter F(2)(s), to theoretical predictions and discuss what implications these values have for observing new order parameter collective modes.

Surface specific heat of 3He and Andreev bound states.

High resolution measurements of the specific heat of liquid 3He in the presence of a silver surface have been performed at temperatures near the superfluid transition in the pressure range of 1-29 bar. The surface contribution to the heat capacity is identified with Andreev bound states of quasiparticles that have a range of half a coherence length.

Biological treatment in rheumatic diseases: results from a longitudinal surveillance: adverse events.

The objective of this study was to assess the long-term safety and tolerability of biologicals in a clinical setting. Data on adverse events (AEs) have been collected over a 5-year period by means of detailed reports sent in to the National Register of Biological Treatment in Finland (ROB-FIN) and validated by information collected by the National Agency for Medicines. Three hundred and eight reports on AEs were filed, concerning a total of 248 patients; this corresponds to 17% of all patients in the ROB-FIN register who started biological treatments. Skin reactions and infections comprised 35 and 28% of the AEs, respectively. Some cases of tuberculosis and other infections, heart failure and demyelinating conditions were seen. Our work demonstrates no unexpected AEs in a Finnish patient cohort consisting of rheumatoid arthritis and spondylarthropathy patients, although many of them were treated with combination treatments in common use in Finland. Biological treatment appears safe in the hands of the Finnish rheumatologists.

Direct measurement of the 14N(p,gamma)15O S factor.

The 14N(p,gamma)15O reaction regulates the rate of energy generation in the stellar CN cycle. Because discrepancies have been found in the analysis and interpretation of previous capture data, we have measured the 14N(p,gamma)15O excitation function for energies in the range E(lab)(p)=155-524 keV. Fits of these data using R-matrix theory yield a value for the S factor at zero energy of 1.68+/-0.09(stat)+/-0.16(syst) keV b, which is significantly smaller than the previous result. The corresponding reduction in the stellar reaction rate for 14N(p,gamma)15O has a number of interesting consequences, including an impact on estimates for the age of the Galaxy derived from globular clusters.

Explosive hydrogen burning of 17O in classical novae.

We report on the observation of a new resonance at E(lab)(R)=190 keV in the 17O(p,gamma)18F reaction. The measured resonance strength amounts to omegagamma(pgamma)=(1.2+/-0.2)x10(-6) eV. With this new value, the uncertainties in the 17O(p,gamma)18F and 17O(p,alpha)14N thermonuclear reaction rates are reduced by orders of magnitude at nova temperatures. Our significantly improved reaction rates have major implications for the galactic synthesis of 17O, the stellar production of the radioisotope 18F, and the predicted oxygen isotopic ratios in nova ejecta.

The N-terminal domain of human urokinase receptor contains two distinct regions critical for ligand recognition.

The high-affinity receptor that binds human urokinase-type plasminogen activator (hu-PAR) is a glycosyl-phosphatidylinositol (GPI)-anchored cell-surface glycoprotein that belongs to the Ly-6 superfamily of T-cell-activating receptors. Binding of urokinase (u-PA) to u-PAR is species-specific, since neither murine (mu-PAR) nor hu-PAR binds u-PA from the other species. I designed and analyzed a series of exchanges between hu-PAR and mu-PAR in the N-terminal first domain to which ligand-binding function had been independently mapped. Introduction of as few as 13 murine residues (six of 13 variables) into the N-terminal region of hu-PAR abrogated binding to recombinant human pro-u-PA, whereas the opposite chimera, a mu-PAR carrying six of 13 human residues, was positive for binding. Within this region, the mu-PAR domain 1 could be minimally humanized to bind human pro-u-PA by a substitution of as few as four of the six nonconserved residues, thereby identifying the residues arginine-2, lysine-7, threonine-8, and glycine-10 as important in determining binding specificity. By alanine-scanning mutagenesis, a second recognition site within domain 1 was discovered between residues 47 and 53, a segment that is fully conserved between the human and the mouse receptors. Taken together, these results provide identification of two confined subregions within the N-terminal domain of hu-PAR critically involved in pro-u-PA recognition.

N-linked glycosylation of the ligand-binding domain of the human urokinase receptor contributes to the affinity for its ligand.

Variations in glycosylation exist among urokinase plasminogen activator receptors (u-PARs) from different cell types. We have studied the functional role of N-linked carbohydrate within the ligand-binding domain of u-PAR. Treatment with glycosidases demonstrated that all the N-linked carbohydrates on u-PAR are complex-type oligosaccharides. Substitution of a single Asn (Asn52) to Gln by means of site-directed mutagenesis led to an active receptor mutant with a ligand-binding domain devoid of carbohydrate. The cellular distribution, the glycosyl-phosphatidylinositol anchoring, and the conformational stability after solubilization were unaffected by this single substitution. However, ligand binding analysis demonstrated a 4- 5-fold decrease in affinity as compared with the wild type receptor. Two different strategies were used in order to obtain a u-PAR type completely devoid of N-linked carbohydrates. 1) Tunicamycin treatment of wild type u-PAR-expressing cells. 2) Mutation of all glycosylation sites (Hu-PARN5-mut). In neither case, unglycosylated receptors with ligand binding activity were identified. However, immunofluorescence studies demonstrated that the Hu-PARN5-mut was retained inside the cells in the endoplasmic reticulum. The same result was found for Hu-PARN4-mut, where only the glycosylation sites outside the binding domain were mutated. These results demonstrate that some extent of glycosylation of u-PAR is necessary for cellular transport and for molecular maturation events leading to ligand binding activity. Glycosylation of the binding domain per se affects only the affinity of the receptor. The positive modulation of the Asn52 carbohydrate side chain on ligand affinity suggests that the u-PAR glycosylation variants observed in various cell types may have different functional roles.

Internalization of the urokinase-plasminogen activator inhibitor type-1 complex is mediated by the urokinase receptor.

The role of the urokinase receptor (uPAR) in the internalization of the urokinase-plasminogen activator inhibitor type-1 (uPA.PAI-1) complex has been investigated. First, exploiting the species specificity of uPA binding, we show that mouse LB6 cells (that express a mouse uPAR) were unable to bind or degrade the human uPA.PAI-1 complex. On the other hand, LB6 clone 19 cells, which express a transfected human uPAR, degraded uPA.PAI-1 complexes with kinetics identical to the human monocytic U937 cells. We also show by immunofluorescence experiments with anti-uPA antibodies that in LB6 clone 19 cells, the uPA.PAI-1 complex is indeed internalized. While at 4 degrees C uPA fluorescence was visible at the cell surface, shift of the temperature to 37 degrees C caused a displacement of the immunoreactivity to the cytoplasmic compartment, with a pattern indicating lysosomal localization. If uPA.PAI-1 internalization/degradation is mediated by uPAR, inhibition of uPA.PAI-1 binding to uPAR should block degradation. Three different treatments, competition with the agonist amino-terminal fragment of uPA, treatment with a monoclonal antibody directed toward the binding domain of uPAR or release of uPAR from the cell surface with phosphatidylinositol-specific phospholipase C completely prevented uPA.PAI-1 degradation. The possibility that a serpin-enzyme complex receptor might be primarily or secondarily involved in the internalization process was excluded since a serpin-enzyme complex peptide failed to inhibit uPA.PAI-1 binding and degradation. Similarly, complexes of PAI-1 with low molecular mass uPA (33 kDa uPA), which lacks the uPAR binding domain, were neither bound nor degraded. Finally we also show that treatment of cells with uPA.PAI-1 complex caused a specific but partial down-regulation of uPAR. A similar result was obtained when PAI-1 was allowed to complex to uPA that had been previously bound to the receptor. The possibility therefore exists that the entire complex uPA.PAI-1-uPAR is internalized. All these data allow us to conclude that internalization of the uPA.PAI-1 complex is mediated by uPAR.

Stimulation of cell surface plasminogen activation by heparin and related polyionic substances.

The functional operation of the cell surface pro-u-PA and plasminogen activating system has previously been shown to depend on the assembly of u-PA receptors, plasminogen binding sites, and their respective ligands at the focal adhesions of cell extensions. We now show that additional factors operate that affect the persistence of functional activity and that evidently involve charge interactions mediated by polyanions, such as those found in the cell surface proteoglycans. Heparin-like compounds and protamine were identified as fast-acting stimulators of cell surface plasminogen activation. Heparin stabilized surface u-PA activity during plasminogen activation, and we propose that a heparin binding site exists in the kringle structure of u-PA. Heparin at 40 micrograms/ml could reduce u-PA loss to only 20% compared with 60% on control cells activating plasminogen. Protamine (25 micrograms/ml) exerted a strong stimulatory effect on the level of generated bound plasmin and notably prolonged the persistence of this activity, so that 100 minutes after addition of plasminogen the level of plasmin on protamine-treated cells was five times higher than on control-treated cells. The effect of protamine on plasmin clearance suggests that an unknown plasmin inhibitor may be produced by rhabdomyosarcoma cells, whose action is accelerated by endogenous polyanions, in an analogous manner to thrombin inactivation by antithrombin III and protease nexin on endothelial cells and fibroblasts, respectively. The stimulatory effects of heparin and protamine do not affect the inactivation of cell surface u-PA by recombinant PAI-2.