Electronic Transport and Possible Superconductivity at Van Hove Singularities in Carbon Nanotubes.

Van Hove singularities (VHSs) are a hallmark of reduced dimensionality, leading to a divergent density of states in one and two dimensions and predictions of new electronic properties when the Fermi energy is close to these divergences. In carbon nanotubes, VHSs mark the onset of new subbands. They are elusive in standard electronic transport characterization measurements because they do not typically appear as notable features and therefore their effect on the nanotube conductance is largely unexplored. Here we report conductance measurements of carbon nanotubes where VHSs are clearly revealed by interference patterns of the electronic wave functions, showing both a sharp increase of quantum capacitance, and a sharp reduction of energy level spacing, consistent with an upsurge of density of states. At VHSs, we also measure an anomalous increase of conductance below a temperature of about 30 K. We argue that this transport feature is consistent with the formation of Cooper pairs in the nanotube.

Bursting activity of substantia nigra pars reticulata neurons in mouse parkinsonism in awake and anesthetized states.

Electrophysiological changes in basal ganglia neurons are hypothesized to underlie motor dysfunction in Parkinson's disease (PD). Previous results in head-restrained MPTP-treated non-human primates have suggested that increased bursting within the basal ganglia and related thalamic and cortical areas may be a hallmark of pathophysiological activity. In this study, we investigated whether there is increased bursting in substantia nigra pars reticulata (SNpr) output neurons in anesthetized and awake, head-restrained unilaterally lesioned 6-OHDA mice when compared to control mice. Confirming previous studies, we show that there are significant changes in the firing rate and pattern in SNpr neuron activity under urethane anesthesia. The regular firing pattern of control urethane-anesthetized SNpr neurons was not present in the 6-OHDA-lesioned group, as the latter neurons instead became phase locked with cortical slow wave activity (SWA). Next, we examined whether such robust electrophysiological changes between groups carried over to the awake state. SNpr neurons from both groups fired at much higher frequencies in the awake state than in the anesthetized state and surprisingly showed only modest changes between awake control and 6-OHDA groups. While there were no differences in firing rate between groups in the awake state, an increase in the coefficient of variation (CV) was observed in the 6-OHDA group. Contrary to the bursting hypothesis, this increased CV was not due to changes in bursting but was instead due to a mild increase in pausing. Together, these results suggest that differences in SNpr activity between control and 6-OHDA lesioned mice may be strongly influenced by changes in network activity during different arousal and behavioral states.

Resistive flow in a weakly interacting Bose-Einstein condensate.

We report the direct observation of resistive flow through a weak link in a weakly interacting atomic Bose-Einstein condensate. Two weak links separate our ring-shaped superfluid atomtronic circuit into two distinct regions, a source and a drain. Motion of these weak links allows for creation of controlled flow between the source and the drain. At a critical value of the weak link velocity, we observe a transition from superfluid flow to superfluid plus resistive flow. Working in the hydrodynamic limit, we observe a conductivity that is 4 orders of magnitude larger than previously reported conductivities for a Bose-Einstein condensate with a tunnel junction. Good agreement with zero-temperature Gross-Pitaevskii simulations and a phenomenological model based on phase slips indicate that the creation of excitations plays an important role in the resulting conductivity. Our measurements of resistive flow elucidate the microscopic origin of the dissipation and pave the way for more complex atomtronic devices.

In vivo electrophysiology of nigral and thalamic neurons in alpha-synuclein-overexpressing mice highlights differences from toxin-based models of parkinsonism.

Numerous studies have suggested that alpha-synuclein plays a prominent role in both familial and idiopathic Parkinson's disease (PD). Mice in which human alpha-synuclein is overexpressed (ASO) display progressive motor deficits and many nonmotor features of PD. However, it is unclear what in vivo pathophysiological mechanisms drive these motor deficits. It is also unknown whether previously proposed pathophysiological features (i.e., increased beta oscillations, bursting, and synchronization) described in toxin-based, nigrostriatal dopamine-depletion models are also present in ASO mice. To address these issues, we first confirmed that 5- to 6-mo-old ASO mice have robust motor dysfunction, despite the absence of significant nigrostriatal dopamine degeneration. In the same animals, we then recorded simultaneous single units and local field potentials (LFPs) in the substantia nigra pars reticulata (SNpr), the main basal ganglia output nucleus, and one of its main thalamic targets, the ventromedial nucleus, as well as LFPs in the primary motor cortex in anesthetized ASO mice and their age-matched, wild-type littermates. Neural activity was examined during slow wave activity and desynchronized cortical states, as previously described in 6-hydroxydopamine-lesioned rats. In contrast to toxin-based models, we found a small decrease, rather than an increase, in beta oscillations in the desynchronized state. Similarly, synchronized burst firing of nigral neurons observed in toxin-based models was not observed in ASO mice. Instead, we found more subtle changes in pauses of SNpr firing compared with wild-type control mice. Our results suggest that the pathophysiology underlying motor dysfunction in ASO mice is distinctly different from striatal dopamine-depletion models of parkinsonism.

Bulk and surface tunneling hydrogen defects in alumina.

We perform ab initio calculations of hydrogen-based tunneling defects in alumina to identify deleterious two-level systems (TLS) in superconducting qubits. The defects analyzed include bulk hydrogenated Al vacancies, bulk hydrogen interstitial defects, and a surface OH rotor. The formation energies of the defects are first computed for an Al- and O-rich environment to give the likelihood of defect occurrence during growth. The potential energy surfaces are then computed and the corresponding dipole moments are evaluated to determine the coupling of the defects to an electric field. Finally, the tunneling energy is computed for the hydrogen defect and the analogous deuterium defect, providing an estimate of the TLS energy and the corresponding frequency for photon absorption. We predict that hydrogenated cation vacancy defects will form a significant density of GHz frequency TLSs in alumina.

Driving phase slips in a superfluid atom circuit with a rotating weak link.

We have observed well-defined phase slips between quantized persistent current states around a toroidal atomic (23Na) Bose-Einstein condensate. These phase slips are induced by a weak link (a localized region of reduced superfluid density) rotated slowly around the ring. This is analogous to the behavior of a superconducting loop with a weak link in the presence of an external magnetic field. When the weak link is rotated more rapidly, well-defined phase slips no longer occur, and vortices enter into the bulk of the condensate. A noteworthy feature of this system is the ability to dynamically vary the current-phase relation of the weak link, a feature which is difficult to implement in superconducting or superfluid helium circuits.

Superflow in a toroidal Bose-Einstein condensate: an atom circuit with a tunable weak link.

We have created a long-lived (≈40 s) persistent current in a toroidal Bose-Einstein condensate held in an all-optical trap. A repulsive optical barrier across one side of the torus creates a tunable weak link in the condensate circuit, which can affect the current around the loop. Superflow stops abruptly at a barrier strength such that the local flow velocity at the barrier exceeds a critical velocity. The measured critical velocity is consistent with dissipation due to the creation of vortex-antivortex pairs. This system is the first realization of an elementary closed-loop atom circuit.

Contact resistance and phase slips in mesoscopic superfluid atom transport.

We have experimentally measured transport of superfluid, bosonic atoms in a mesoscopic system: a small channel connecting two large reservoirs. Starting far from equilibrium (superfluid in a single reservoir), we observe first resistive flow transitioning at a critical current into superflow, characterized by oscillations. We reproduce this full evolution with a simple electronic circuit model. We compare our fitted conductance to two different microscopic phenomenological models. We also show that the oscillations are consistent with LC oscillations as estimated by the kinetic inductance and effective capacitance in our system. Our experiment provides an attractive platform to begin to probe the mesoscopic transport properties of a dilute, superfluid, Bose gas.

Covalent structure and affinity of channel catfish anti-dinitrophenyl antibodies.

Serum antibody (Ab) of channel catfish, Ictalurus punctatus, is predominantly a tetrameric, approximately 700,000-dalton protein. This tetrameric Ab dissociates into 8 distinctive subpopulations, each composed of equimolar heavy and light chains, when in the presence of denaturing solvents. The present studies utilizing purified anti-DNP Abs obtained from catfish monitored for either short (1-2 months) or long (1-2 years) periods post-primary immunization with dinitrophenylated horse serum albumin showed no demonstrable differences in the ratio of the covalent Ab subpopulations. Although significant humoral Ab levels were sustained during the 1-2 year monitoring period, there were no significant changes in the binding affinities or heterogeneity of the induced Ab.

Organization of immunoglobulin heavy chain constant and joining region genes in the channel catfish.

A channel catfish genomic lambda library was screened with CH and JH probes which were derived from our earlier sequence analyses on different full-length heavy chain cDNA clones. One clone, designated C7, contained a genomic insert of about 18 kb and hybridized with specific probes for each of the four domains of the known C region gene as well as with different oligonucleotides specific for JH gene segments. Southern blot hybridization analysis identified a cluster of JH gene segments which are closely linked to the CH gene. Sequence analysis of the CH-proximal JH element, located about 1.9 kb upstream from the CH1 domain, showed that this element contains 5'-recombination signals typical of JH elements defined in higher vertebrates, i.e. a nonamer, a 24 bp spacer, and a heptamer. The coding region of this JH element was identical to that contained in the variable region sequence of a cDNA clone previously reported. Sequence analysis of the catfish JH-CH intron suggests that several sequences are present which appear similar to important transcriptional regulatory elements found within JH-CH introns of higher vertebrates. These features include sequences similar to higher vertebrate enhancer elements and regulatory octamers. An additional feature reminiscent of some higher vertebrate heavy chain switch regions is a repetitive sequence area composed of tandemly repeated simple sequences. Lastly, several restriction length polymorphisms were identified and mapped within a 1 kb region located immediately upstream from the JH cluster. This finding suggests that polymorphisms within the IgH locus should be useful in the analyses of channel catfish populations. These combined studies provide further evidence that the genomic organization of heavy chain genes in bony fish shares common organizational features with those known from higher vertebrates.

Distinctive subpopulations of catfish serum antibody and immunoglobulin.

High molecular weight antibodies and immunoglobulin of the channel catfish were found to be composed of heterogeneous mixtures of covalent subpopulations. Although these proteins appeared tetrameric in physiological buffers (mol. wt approximately 700,000), molecular weight estimates in the presence of the detergent sodium dodecyl sulfate indicated that they dissociated into eight distinct subpopulations. Each dissociative subpopulation was found to be stable under the conditions of electrophoretic analysis, and furthermore each was apparently composed of equimolar H and L chains. Based upon relative mobilities it seems probable that the catfish antibody was composed of various combinations of covalent linkages between covalently-linked H-L chain pairs, i.e. 8, 7, 6, 5, 4, 3, 2 and 1. Further studies suggest the presence of size heterogeneity in catfish light chains. Whether or not this distinction represents isotypic L chain differences is not yet known but these findings coupled with the complex architecture of the physiological tetramer suggest an unusual and previously unappreciated level of complexity present in fish antibody.

Activation of complement by different immunoglobulin heavy chain isotypes of the channel catfish (Ictalurus punctatus).

The approximately 750,000 mol. wt tetrameric Ab population from catfish immunized with sheep erythrocytes (E) was purified and shown to sensitize E to the hemolytic activity of catfish serum complement. Catfish complement was heat-labile at 45 degrees C and was hemolytically inactivated by both EGTA and EDTA. Hemolytic activity of EDTA treated serum was restored by the addition of both Ca+ and Mg2+ ions. In comparative assays, the CH50 titers of catfish sera were similar to the CH50 titers of human sera. Catfish complement was hemolytically active at incubation temps ranging from 3 to 40 degrees C, which suggests that complement should be functional throughout the catfish's normal environmental temps. Human complement exhibited considerable cross-reactivity when assayed on catfish Ab sensitized E at 25 degrees C; however, at 3 degrees C, no hemolytic activity was observed. They findings suggest that there may be structural differences between the complement component(s) of these two systems. Mouse mAbs to the recently described H chain isotypes of catfish Ig were used to fractionate catfish anti-sheep E antisera. Each of the purified isotypes contained Ab which sensitized E to the hemolytic activity of catfish complement. Dose-response analysis of the average number of hemolytic sites per cell, as a function of relative Ab concn, predicts that the catfish tetramer conforms to the one-hit theory of immune hemolysis. Purified catfish anti-fluorescein Ab of each isotype was also reacted with fluorescein-labeled sheep E and the level of complement-mediated hemolysis determined. Dose-response analysis indicated that similar numbers of Ab molecules bound to haptenated E resulted in similar levels of complement-mediated lysis. Lastly, the effect of cell surface hapten density of target cells was examined. These studies, similar to those reported with human IgM, showed that the binding of the catfish tetramer to a cell surface hapten may not be sufficient to activate lytic complement.

Structure and genomic organization of VH gene segments in the channel catfish: members of different VH gene families are interspersed and closely linked.

To determine the structure and organization of germline VH gene segments in the channel catfish, genomic lambda libraries were screened with cDNA probes representing different catfish VH gene families. Thirty-six VH positive genomic clones were isolated and four of these were characterized by restriction mapping and Southern blot analysis with probes specific for each known VH gene family. The four clones, representing about 65 kb of DNA, contained 21 VH segments. The average distance between segments was about 3 kb and gene segments representing different VH gene families were interspersed with each other. Dot-blot hybridization analysis of all 36 genomic clones (average insert size 16-18 kb) indicated that the average clone contained gene segments representing four different VH families. In addition, these analyses indicated that VH segments representing each VH family could be found closely linked to gene segments representing each of the other VH families. Genomic restriction fragments containing a VH segment of each gene family were sequenced. These analyses showed that the general structure of VH segments is conserved in catfish. These structural features include the presence of a leader sequence split by a short intron, an uninterrupted open reading frame encoding readily identified framework and complementarity determining regions, and a downstream recombination signal sequence represented by a consensus heptamer, a 22-24 bp spacer, and an A-rich nonamer. Upstream of the VH segments was an octamer sequence. These analyses indicate that the organization and structure of VH segments typically associated with VH loci of higher vertebrates evolved early in phylogeny at the level of the bony fishes.

Secretory immunity induced in catfish, Ictalurus punctatus, following bath immunization.

Individual adult channel catfish were immunized by immersion in an antigen bath containing dinitrophenylated-horse serum albumin. Anti-DNP hemagglutination titers of serum and cutaneous mucus were determined following both primary and secondary bath immunization. The results showed that five of the six fish had a cutaneous mucosal anti-DNP titer following the bath immunizations. In contrast, only one of the six catfish was shown to have any demonstrable change in its serum anti-DNP titer following the bath immunizations. The mucous anti-DNP hemagglutinin was shown to be antibody (Ab). The affinity-purified mucous Ab was found to have the same complex tetrameric architecture as well as the same molecular weight heavy and light chains as serum anti-DNP Ab. Histological studies showed that the catfish epidermis was richly vascularized. Within the epidermis there were numerous lymphocytes which were predominantly associated with the basal layer. These studies indicate that the secretory immune system of catfish can be stimulated by external antigens. Secondly, these studies show that bath immunization can differentially effect the relative antibody response of the catfish secretory and systemic immune systems.

Immunoglobulin in the eggs of the channel catfish (Ictalurus punctatus).

Egg yolk proteins obtained from 2-3-day-old fertilized channel catfish eggs were analyzed to determine if immunoglobulin (Ig) was present. Using both monoclonal and polyclonal antibodies to catfish Ig, egg Ig was isolated and structurally characterized. The egg Ig when analyzed in SDS-gels under nonreducing conditions dissociated into eight distinct subpopulations with relative mobilities identical to that previously described for the serum Ig of the channel catfish. In addition, the component heavy (H) and light (L) chains of the egg Ig had similar relative mobilities as the H and L chains identified in serum Ig. Immunocytological studies using both polyclonal and monoclonal anti-catfish Ig showed that Ig was dispersed throughout the yolk of the egg. In addition these analyses indicated that Ig was localized within the external membranes (eggshell) of the egg.

Fish lymphocytes differ in the expression of surface immunoglobulin.

Catfish peripheral blood and splenic lymphocytes were assayed for surface immunoglobulin using fifteen different mouse hybridoma antibodies to catfish immunoglobulin (Ig). These studied showed that this battery of monoclonal antibodies did not detect significant amounts of Ig on all lymphocytes. Unlike polyclonal antisera which demonstrated nearly 100% surface Ig+ cells, the monoclonal antibodies detected approximately 40% surface Ig+ cells. Furthermore, the percentage of Ig+ cells reactive with two of these monoclonals, tentatively shown to react with two different types of catfish light chains, was found to be nearly additive when the two antibodies were mixed. Thus it seems that fish lymphocytes, like their mammalian counterparts, have two different populations of lymphocytes; one which contains abundant surface Ig and one which does not. Whether these two types of cells represent the fish equivalents of B and T cells remains to be determined.

Characterization of anti-hapten antibodies generated in vitro by channel catfish peripheral blood lymphocytes.

Secondary in vitro stimulation of channel catfish peripheral blood lymphocytes with haptenated T-dependent antigen (TNP-KLH) elicited large numbers of hapten-specific Ab-producing cells and relatively high levels (10-96 micrograms/mL) of TNP-specific Ab in the culture medium. These in vitro generated Abs were compared to in vivo generated Abs from the serum of the same fish with respect to covalent structure, affinity, and isotypic composition of heavy and light chains. SDS-PAGE analysis under both reducing and nonreducing conditions revealed that the in vitro Abs were structurally similar to the serum Abs. Similarly, in vitro pulse-labeled Abs also exhibited the eight band profile characteristic of channel catfish serum Abs when run under nonreducing denaturing conditions. Scatchard analysis of equilibrium dialysis data revealed that the affinities of the culture- and serum-derived Abs were quite similar, that is, exhibited association constants of approximately 2.0 x 10(6) M-1. However, it was routinely observed that the in vitro generated Abs exhibited somewhat fewer binding sites per molecule than those derived from serum. The use of murine monoclonal Abs specifically for different isotypes of channel catfish heavy and light chains demonstrated that the isotypic composition of the culture- and serum-derived fish anti-TNP Abs were similar; exceptions occurred with cultures producing lower levels of Abs. These results strongly suggest that channel catfish in vitro Ab responses closely reflect what normally occurs in vivo.

Temperature-mediated processes in teleost immunity: differential effects of in vitro and in vivo temperatures on mitogenic responses of channel catfish lymphocytes.

The in vitro mitogenic responses of channel catfish peripheral blood leucocytes to ConA and LPS were differentially affected by both in vitro and in vivo temperatures. The magnitude of the response to LPS was relatively independent of both in vitro culture temperature and in vivo acclimation temperature. The magnitude of the response to ConA was suppressed at lower in vitro temperatures although this suppression could be reduced by lower in vivo acclimation temperatures. In vitro temperature-shift experiments indicated that channel catfish PBL could respond to ConA at a lower in vitro temperature if first stimulated with ConA at a higher in vitro temperature. The converse, however was not true in that channel catfish PBL did not respond at a higher in vitro temperature after an initial stimulation with ConA at a lower in vitro temperature. This latter failure to respond could not be attributed to the induction of a suppressor cell (or factor) by exposure to ConA at a lower temperature. These studies, when coupled with other available data on channel catfish PBL subpopulations, are interpreted as supporting the hypothesis that low temperature immunosuppression in fish may result from preferential inhibitory effects on T cells rather than B cells.

Structural diversity of channel catfish immunoglobulins.

This paper describes a number of observations which show that the covalent structure of catfish Ig is heterogeneous and secondly that different Ig L chain classes are present.

A 30 mK, 13.5 T scanning tunneling microscope with two independent tips.

We describe the design, construction, and performance of an ultra-low temperature, high-field scanning tunneling microscope (STM) with two independent tips. The STM is mounted on a dilution refrigerator and operates at a base temperature of 30 mK with magnetic fields of up to 13.5 T. We focus on the design of the two-tip STM head, as well as the sample transfer mechanism, which allows in situ transfer from an ultra high vacuum preparation chamber while the STM is at 1.5 K. Other design details such as the vibration isolation and rf-filtered wiring are also described. Their effectiveness is demonstrated via spectral current noise characteristics and the root mean square roughness of atomic resolution images. The high-field capability is shown by the magnetic field dependence of the superconducting gap of CuxBi2Se3. Finally, we present images and spectroscopy taken with superconducting Nb tips with the refrigerator at 35 mK that indicate that the effective temperature of our tips/sample is approximately 184 mK, corresponding to an energy resolution of 16 µeV.