Calorimetric Observation of Single He 2 ∗ Excimers in a 100-mK He Bath.

We report the first calorimetric detection of individual He 2 ∗ excimers within a bath of superfluid 4 He . The detector used in this work is a single superconducting titanium transition edge sensor (TES) with an energy resolution of ∼ 1 eV , immersed directly in the helium bath. He 2 ∗ excimers are produced in the surrounding bath using an external gamma-ray source. These excimers exist either as short-lived singlet or long-lived triplet states. We demonstrate detection (and discrimination) of both states: In the singlet case the calorimeter records the absorption of a prompt ≈ 15 eV photon, and in the triplet case the calorimeter records a direct interaction of the molecule with the TES surface, which deposits a distinct fraction of the ≈ 15 eV , released upon decay, into the surface. We also briefly discuss the detector fabrication and characterization.

Ultrasensitive graphene far-infrared power detectors.

We describe the properties of ultrasensitive graphene photon detectors for use in the far-infrared/terahertz spectral region and present theoretical predictions for their power detection sensitivity. These predictions are based on two graphene contacting schemes with superconducting contacts: contacts with a thin insulating barrier, and direct superconducting contacts. To quantitatively assess these predictions, we perform thermal measurements of graphene at low temperatures and analyse them to extract information on electron-phonon cooling in graphene. These new results for the electron-phonon cooling channel allow reliable prediction of the noise equivalent power (NEP) that can be expected from an optimized graphene detector, using measurement of the Johnson noise emission as the thermometry method. We find that an NEP of 2 × 10(-19) W Hz(-1/2) should be achievable under certain biasing conditions with an ideal device.

Phase-preserving amplification near the quantum limit with a Josephson ring modulator.

Recent progress in solid-state quantum information processing has stimulated the search for amplifiers and frequency converters with quantum-limited performance in the microwave range. Depending on the gain applied to the quadratures of a single spatial and temporal mode of the electromagnetic field, linear amplifiers can be classified into two categories (phase sensitive and phase preserving) with fundamentally different noise properties. Phase-sensitive amplifiers use squeezing to reduce the quantum noise, but are useful only in cases in which a reference phase is attached to the signal, such as in homodyne detection. A phase-preserving amplifier would be preferable in many applications, but such devices have not been available until now. Here we experimentally realize a proposal for an intrinsically phase-preserving, superconducting parametric amplifier of non-degenerate type. It is based on a Josephson ring modulator, which consists of four Josephson junctions in a Wheatstone bridge configuration. The device symmetry greatly enhances the purity of the amplification process and simplifies both its operation and its analysis. The measured characteristics of the amplifier in terms of gain and bandwidth are in good agreement with analytical predictions. Using a newly developed noise source, we show that the upper bound on the total system noise of our device under real operating conditions is three times the quantum limit. We foresee applications in the area of quantum analog signal processing, such as quantum non-demolition single-shot readout of qubits, quantum feedback and the production of entangled microwave signal pairs.

Niobium direct detectors for fast and sensitive terahertz spectroscopy.

We report the performance of a niobium hot-electron bolometer designed for laboratory terahertz spectroscopy. The antenna-coupled detector can operate above 4.2 K and has fast (subnanosecond) response. Detailed microwave measurements of performance over a wide range of operating conditions were correlated with quantitative terahertz measurements. The maximum responsivity is 4 x 10(4) VW with a noise equivalent power at the detector of 2 x 10(-14) W/Hz(12), approaching the intrinsic thermal fluctuation limit for the device. This detector enables a variety of novel laboratory spectroscopy measurements.

Noise thermal impedance of a diffusive wire.

The current noise density S2 of a conductor in equilibrium, the Johnson noise, is determined by its temperature T: S2 = 4k(B)TG, with G the conductance. The sample's noise temperature T(N) = S2/(4k(B)G) generalizes T for a system out of equilibrium. We introduce the "noise thermal impedance" of a sample as the ratio deltaT(N)omega/deltaP(J)omega of the amplitude deltaT(N)omega of the oscillation of T(N) when heated by an oscillating power deltaP(J)omega at frequency omega. For a macroscopic sample, it is the usual thermal impedance. We show for a diffusive wire how this (complex) frequency-dependent quantity gives access to the electron-phonon interaction time in a long wire and to the diffusion time in a shorter one, and how its real part may also give access to the electron-electron inelastic time. These times are not simply accessible from the frequency dependence of S2 itself.

Environmental effects in the third moment of voltage fluctuations in a tunnel junction.

We present the first measurements of the third moment of the voltage fluctuations in a conductor. This technique can provide new and complementary information on the electronic transport in conducting systems. The measurement was performed on nonsuperconducting tunnel junctions as a function of voltage bias, for various temperatures and bandwidths up to 1 GHz. The data demonstrate the significant effect of the electromagnetic environment of the sample.

Phase sensitive shot noise in an Andreev interferometer.

We investigate nonequilibrium noise in a diffusive Andreev interferometer, in which currents emerging from two normal metal/superconductor (N-S) interfaces can interfere. We observe a modulation of the shot noise when the phase difference between the two N-S interfaces is varied by a magnetic flux. This is the signature of phase-sensitive fluctuations in the normal metal. The effective charge inferred from the shot noise measurement is close to q(eff) = 2e but shows phase-dependent deviations from 2e at finite energy, which we interpret as being due to pair correlations. Experimental data are in good agreement with predictions based on an extended Keldysh Green's function approach.

Time-resolved measurements of thermodynamic fluctuations of the particle number in a nondegenerate Fermi gas.

We report on time-resolved measurements of thermodynamic fluctuations in the number of particles in a nondegenerate Fermi gas. The gas is comprised of thermal quasiparticles, confined in a superconducting Al box by large-gap Ta leads. The average number of quasiparticles is about 10(5). This number fluctuates due to quasiparticle generation and recombination. The number is measured from the tunneling current through a barrier that bisects the box. The recombination time is independently measured by single-photon excitation and agrees with the frequency dependence of the fluctuations.

Pattern- and growth-linked cell cycles in Drosophila development.

During Drosophila development the cell cycle is subject to diverse regulatory inputs. In embryos, cells divide in stereotypic patterns that correspond to the cell fate map. There is little cell growth during this period, and cell proliferation is regulated at G2/M transitions by patterned transcription of the Cdk1-activator, Cdc25/String. The string locus senses pattern information via a > 40 kb cis-regulatory region composed of many cell-type specific transcriptional enhancers. Later, in differentiated larval tissues, the cell cycle responds to nutrition via mechanisms that sense cellular growth. These larval cell cycles lack mitoses altogether, and are regulated at G/S transitions. Cells in developing imaginal discs exhibit a cycle that is regulated at both G1/S and G2/M transitions. G2/M progression in disc cells is regulated, as in the embryo, by string transcription and is thus influenced by the many transcription factors that interact with string's 'pattern-sensing' control region. G1/S progression in disc cells is controlled, at least in part, by factors that regulate cell growth such as Myc, Ras and phosphatidylinositol-3-kinase. Thus G1/S progression appears to be growth-coupled, much as in the larval endocycles. The dual control mechanism used by imaginal disc cells allows integration of diverse inputs which operate in both cell specification and cell metabolism.

Growth regulation by oncogenes--new insights from model organisms.

A great deal of work has focused on how oncogenes regulate the cell cycle during normal development and in cancer, yet their roles in regulating cell growth have been largely unexplored. Recent work in several model organisms has demonstrated that homologs of several oncogenes regulate cell growth and has suggested that some of the effects of oncogenes on the cell cycle may be a result of growth promotion. These studies have also suggested how growth and cell-cycle progression may be coupled.

Identification and characterization of CKIP-1, a novel pleckstrin homology domain-containing protein that interacts with protein kinase CK2.

The catalytic subunits of protein kinase CK2, CK2alpha and CK2alpha', are closely related to each other but exhibit functional specialization. To test the hypothesis that specific functions of CK2alpha and CK2alpha' are mediated by specific interaction partners, we used the yeast two-hybrid system to identify CK2alpha- or CK2alpha'-binding proteins. We report the identification and characterization of a novel CK2-interacting protein, designated CKIP-1, that interacts with CK2alpha, but not CK2alpha', in the yeast two-hybrid system. CKIP-1 also interacts with CK2alpha in vitro and is co-immunoprecipitated from cell extracts with epitope-tagged CK2alpha and an enhanced green fluorescent protein fusion protein encoding CKIP-1 (i.e. EGFP-CKIP-1) when they are co-expressed. CK2 activity is detected in anti-CKIP-1 immunoprecipitates performed with extracts from non-transfected cells indicating that CKIP-1 and CK2 interact under physiological conditions. The CKIP-1 cDNA is broadly expressed and encodes a protein with a predicted molecular weight of 46,000. EGFP-CKIP-1 is localized within the nucleus and at the plasma membrane. The plasma membrane localization is dependent on the presence of an amino-terminal pleckstrin homology domain. We postulate that CKIP-1 is a non-enzymatic regulator of one isoform of CK2 (i.e. CK2alpha) with a potential role in targeting CK2alpha to a particular cellular location.

Ras1 promotes cellular growth in the Drosophila wing.

The Ras GTPase links extracellular mitogens to intracellular mechanisms that control cell proliferation. To understand how Ras regulates proliferation in vivo, we activated or inactivated Ras in cell clones in the developing Drosophila wing. Cells lacking Ras were smaller, had reduced growth rates, accumulated in G1, and underwent apoptosis due to cell competition. Conversely, activation of Ras increased cell size and growth rates and promoted G1/S transitions. Ras upregulated the growth driver dMyc, and both Ras and dMyc increased levels of cyclin E posttranscriptionally. We propose that Ras primarily promotes growth and that growth is coupled to G1/S progression via cyclin E. Interestingly, upregulation of growth by Ras did not deregulate G2/M progression or a developmentally regulated cell cycle exit.

Drosophila myc regulates cellular growth during development.

Transcription factors of the Myc proto-oncogene family promote cell division, but how they do this is poorly understood. Here we address the functions of Drosophila Myc (dMyc) during development. Using mosaic analysis in the fly wing, we show that loss of dMyc retards cellular growth (accumulation of cell mass) and reduces cell size, whereas dMyc overproduction increases growth rates and cell size. dMyc-induced growth promotes G1/S progression but fails to accelerate cell division because G2/M progression is independently controlled by Cdc25/String. We also show that the secreted signal Wingless patterns growth in the wing primordium by modulating dMyc expression. Our results indicate that dMyc links patterning signals to cell division by regulating primary targets involved in cellular growth and metabolism.

pp60(c-src) is required for cell locomotion regulated by the hyaluronanreceptor RHAMM.

The tyrosine kinase pp60(c-src) has been implicated as a regulator of focal adhesion formation and cell spreading. Here we show that c-src also regulates cell motility and is a key component in the signaling pathway triggered by the motogenic hyaluronan receptor RHAMM, which has been shown to regulate focal adhesion turnover and to regulate ras. Fibroblasts derived from mice lacking src, (src (-/-)), have a random locomotion rate that is significantly slower than the corresponding wild-type fibroblasts. Cell locomotion in these mutant cells is restored by the expression of c-src containing a functional kinase domain, but not by the expression of a kinase-deficient src or by a truncated src containing only functional SH2 and SH3 domains. RHAMM is also required for the restoration of src (-/-) cell locomotion. Thus, the motility of cells expressing c-src is reduced to src (-/-) levels by anti-RHAMM blocking antibodies while the cell locomotion of src (-/-) fibroblasts remains unaffected by anti-RHAMM antibodies. We predict that src acts downstream of RHAMM in the regulation of motility, since the expression of a dominant negative src significantly inhibits RHAMM-dependent ras and serum regulated cell locomotion, the expression of v-src enhances cell motility in a RHAMM independent fashion, and there is a physical and functional assocation between src and RHAMM in ras-transformed cells. However, we suggest that RHAMM regulates focal adhesion turnover via additional src-independent mechanisms. Thus, v-src is unable to turnover focal adhesions in the absence of RHAMM. These results directly demonstrate for the first time a role for src in the regulation of cell locomotion and confirm a key and complex role for src in the regulation of the actin cycle.

Simple bridge detector for use with a low-temperature capacitance thermometer, and thermometer performance limits.

A simple high-resolution bridge circuit for use with a glass-ceramic capacitance thermometer is described. This circuit allows a linear readout of capacitance changes and has better than 1 mK resolution and short-term stability. Performance limits of the thermometer itself are also reported. Irreproducibility of thermometer calibration upon thermal cycling can be as large as 0.3 K, and changes in the calibration slope dC/dT are also observed. The bridge circuit described partially compensates for these shifts in dC/dT.