High power DC and ns-pulsed 2 MV accelerator for light ions.

High Voltage Engineering developed, built, and tested a unique 2 MV single-ended accelerator (SingletronTM) for light ions. The system combines a beam current of up to 2 mA for protons and helium in direct-current mode with nanosecond-pulsing capability. Compared to other chopper-buncher applications with Tandem accelerators, the single-ended accelerator increases the charge per bunch by about a factor of 8. The all-solid-state Singletron 2 MV power supplyTM supports high-current operation and features a large dynamic range of the terminal voltage and good transient performance to support the high-current operation. The terminal accommodates an in-house developed 2.45 GHz electron cyclotron resonance ion source and a chopping-bunching system. The latter features phase-locked loop stabilization and temperature compensation of the excitation voltage and its phase. The chopping bunching system further features the selection of hydrogen, deuterium, and helium as well as a pulse repetition rate, ranging from 125 kHz to 4 MHz, that are fully computer controlled. In the testing phase, the system demonstrated smooth operation for 2 mA proton and helium beams at terminal voltages from 0.5 to 2.0 MV, and somewhat reduced current at a voltage down to 250 kV. In pulsing mode, pulses with a full width at half maximum of 2.0 ns reached a peak current of ∼10 and ∼5.0 mA for protons and helium, respectively. This is equivalent to a pulse charge of about 20 and 10 pC. Applications range from various fields requiring direct current at multi-mA levels and MV light ions, including nuclear astrophysics research, boron neutron capture therapy, and deep implantation for semiconductor applications.

Development of a variable-energy, high-intensity, pulsed-mode ion source for low-energy nuclear astrophysics studies.

The primary challenge in directly measuring nuclear reaction rates near stellar energies is their small cross sections. The signal-to-background ratio in these complex experiments can be significantly improved by employing high-current (mA-range) beams and novel detection techniques. Therefore, the electron cyclotron resonance ion source at the Laboratory for Experimental Nuclear Astrophysics underwent a complete upgrade of its acceleration column and microwave system to obtain high-intensity, pulsed proton beams. The new column uses a compression design with O-ring seals for vacuum integrity. Its voltage gradient between electrode sections is produced by the parallel resistance of channels of chilled, deionized water. It also incorporates alternating, transverse magnetic fields for electron suppression and an axially adjustable beam extraction system. Following this upgrade, the operational bremsstrahlung radiation levels and high-voltage stability of the source were vastly improved, over 3.5 mA of target beam current was achieved, and an order-of-magnitude increase in normalized brightness was measured. Beam optics calculations, structural design, and further performance results for this source are presented.

A LATS biosensor screen identifies VEGFR as a regulator of the Hippo pathway in angiogenesis.

The Hippo pathway is a central regulator of tissue development and homeostasis, and has been reported to have a role during vascular development. Here we develop a bioluminescence-based biosensor that monitors the activity of the Hippo core component LATS kinase. Using this biosensor and a library of small molecule kinase inhibitors, we perform a screen for kinases modulating LATS activity and identify VEGFR as an upstream regulator of the Hippo pathway. We find that VEGFR activation by VEGF triggers PI3K/MAPK signaling, which subsequently inhibits LATS and activates the Hippo effectors YAP and TAZ. We further show that the Hippo pathway is a critical mediator of VEGF-induced angiogenesis and tumor vasculogenic mimicry. Thus, our work offers a biosensor tool for the study of the Hippo pathway and suggests a role for Hippo signaling in regulating blood vessel formation in physiological and pathological settings.

Giant electron-hole transport asymmetry in ultra-short quantum transistors.

Making use of bipolar transport in single-wall carbon nanotube quantum transistors would permit a single device to operate as both a quantum dot and a ballistic conductor or as two quantum dots with different charging energies. Here we report ultra-clean 10 to 100 nm scale suspended nanotube transistors with a large electron-hole transport asymmetry. The devices consist of naked nanotube channels contacted with sections of tube under annealed gold. The annealed gold acts as an n-doping top gate, allowing coherent quantum transport, and can create nanometre-sharp barriers. These tunnel barriers define a single quantum dot whose charging energies to add an electron or a hole are vastly different (e-h charging energy asymmetry). We parameterize the e-h transport asymmetry by the ratio of the hole and electron charging energies ηe-h. This asymmetry is maximized for short channels and small band gap tubes. In a small band gap device, we demonstrate the fabrication of a dual functionality quantum device acting as a quantum dot for holes and a much longer quantum bus for electrons. In a 14 nm-long channel, ηe-h reaches up to 2.6 for a device with a band gap of 270 meV. The charging energies in this device exceed 100 meV.

Wiedemann-Franz relation and thermal-transistor effect in suspended graphene.

We extract experimentally the electronic thermal conductivity, Ke, in suspended graphene that we dope using a back-gate electrode. We make use of two-point dc electron transport at low bias voltages and intermediate temperatures (50-160 K), where the electron and lattice temperatures are decoupled. The thermal conductivity is proportional to the charge conductivity times the temperature, confirming that the Wiedemann-Franz relation is obeyed in suspended graphene. We extract an estimate of the Lorenz coefficient as 1.1-1.7 × 10(-8) W ΩK(-2). Ke shows a transistor effect and can be tuned with the back-gate by more than a factor of 2 as the charge carrier density ranges from ∼0.5 to 1.8 × 10(11) cm(-2).

Few-hundred GHz carbon nanotube nanoelectromechanical systems (NEMS).

We study 23-30 nm long suspended single-wall carbon nanotube quantum dots and observe both their stretching and bending vibrational modes. We use low-temperature DC electron transport to excite and measure the tubes' bending mode by making use of a positive feedback mechanism between their vibrations and the tunneling electrons. In these nanoelectromechanical systems (NEMS), we measure fundamental bending frequencies f(bend) ≈ 75-280 GHz and extract quality factors Q ∼ 10(6). The NEMS's frequencies can be tuned by a factor of 2 with tension induced by mechanical breakjunctions actuated by an electrostatic force or tension from bent suspended electrodes.

Mechanical control of spin states in spin-1 molecules and the underscreened Kondo effect.

The ability to make electrical contact to single molecules creates opportunities to examine fundamental processes governing electron flow on the smallest possible length scales. We report experiments in which we controllably stretched individual cobalt complexes having spin S = 1, while simultaneously measuring current flow through the molecule. The molecule's spin states and magnetic anisotropy were manipulated in the absence of a magnetic field by modification of the molecular symmetry. This control enabled quantitative studies of the underscreened Kondo effect, in which conduction electrons only partially compensate the molecular spin. Our findings demonstrate a mechanism of spin control in single-molecule devices and establish that they can serve as model systems for making precision tests of correlated-electron theories.

Evidence for a finite-temperature phase transition in a bilayer quantum Hall system.

We study the Josephson-like interlayer tunneling signature of the strongly correlated nuT=1 quantum Hall phase in bilayer two-dimensional electron systems as a function of the layer separation, temperature, and interlayer charge imbalance. Our results offer strong evidence that a finite temperature phase transition separates the interlayer coherent phase from incoherent phases which lack strong interlayer correlations. The transition temperature is dependent on both the layer spacing and charge imbalance between the layers.

New determination of the astrophysical S factor SE1 of the 12C(alpha,gamma)16O reaction.

A new measurement of the beta-delayed alpha decay of 16N has been performed using a set of high efficiency ionization chambers. Sources were made by implantation of a 16N beam, yielding very clean alpha spectra down to energies as low as 400 keV. Our data are in good agreement with earlier results. For the S factor S(E1), we obtain a value of 74 +/- 21 keV b. In spite of improvements in the measurement, the error in S(E1) remains relatively large because of the correlations among the fit parameters and the uncertainties inherent to the extrapolation.

Tuning the Kondo effect with a mechanically controllable break junction.

We study electron transport through C(60) molecules in the Kondo regime using a mechanically controllable break junction. By varying the electrode spacing, we are able to change both the width and the height of the Kondo resonance, indicating modification of the Kondo temperature and the relative strength of coupling to the two electrodes. The linear conductance as a function of T/T(K) agrees with the scaling function expected for the spin-1/2 Kondo problem. We are also able to tune finite-bias Kondo features which appear at the energy of the first C(60) intracage vibrational mode.

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.

Strength of the 18F(p,alpha)15O resonance at Ec.m. = 330 keV.

Production of the radioisotope 18F in novae is severely constrained by the rate of the 18F(p,alpha)15O reaction. A resonance at E(c.m.)=330 keV may strongly enhance the 18F(p,alpha)15O reaction rate, but its strength has been very uncertain. We have determined the strength of this important resonance by measuring the 18F(p,alpha)15O cross section on and off resonance using a radioactive 18F beam at the ORNL Holifield Radioactive Ion Beam Facility. We find that its resonance strength is 1.48+/-0.46 eV, and that it dominates the 18F(p,alpha)15O reaction rate over a significant range of temperatures characteristic of ONeMg novae.

[Management of lymphedema: experience of the Cognacq-Jay Hospital]. / Prise en charge des lymphoedèmes: l'expérience de l'hôpital Cognacq-Jay.

Treatment of lymphedema includes practical advices, manual lymph drainage, bandaging, self-bandaging, elastic compression garment, skin care and physical exercises. Weight loss may be useful if obesity. Surgery is indicated in genital lymphedema more than in limb lymphedema. In 2001, in Lymphology Unit, 248 women were treated for secondary upper limb lymphedema after breast cancer. Excess of volume of lymphedema was reduced by 31.3% after a mean time of 2.1 weeks. For lower limb lymphedema (primary or secondary), 136 patients were treated with a mean reduction of excess of lymphedema by 29.8% after a mean time of 2.2 weeks. After this treatment, long term follow-up is necessary to maintain results and the motivation of the patient.

Some hints concerning the shape of T-cell receptor structures.

Several models are proposed for T-cell antigen receptor (TCR) assembly and structure. However, there is little experimental data favouring directly either one or the other(s). The minimal complex appears to be composed of a TCRalphabeta/CD3deltaepsilon,gammaepsilon/zeta2 structure but at the cell membrane, multimers of this minimal structure may be formed. Quantitative cytofluometry has suggested three CD3epsilon chains for two TCRbeta (or TCRdelta) chains/complex. Such data should be repeated with monoclonal antibodies (MoAb) against extracellular (EC) parts of CD3delta or CD3gamma chains. In the present review, we have compared the TCR/CD3 assembly of pre-TCR, TCRgammadelta and TCRalphabeta containing complexes, and analysed the reactivity of antibodies (Abs) against the EC part of CD3delta chains. Our data suggest an alternative assembly pathway and structure of TCR/CD3 complexes.

Evolution of T cell receptor (TCR) alpha beta heterodimer assembly with the CD3 complex.

T cell antigen receptors (TCR) are composed of an antigen-recognizing unit, the TCRalpha beta heterodimer, and a signal transduction ensemble, the CD3 complex. Whereas mammals possess three CD3 dimers (delta epsilon, gamma epsilon, and zeta2), birds and amphibians have only two (delta/gamma-epsilon and zeta2). To understand evolutionary changes in TCR/CD3 assembly,a phylogenetic approach was employed to dissect the interaction of TCRalpha beta heterodimers with the CD3 components. While sheep and mouse TCRalpha and TCRbeta chains could replace the corresponding human chains in mutant human T cells to restore surface TCR/CD3 expression and function, chicken TCRalpha, TCRbeta and CD3delta/gamma chains were unable to replace the corresponding human chains in forming a chimeric TCR/CD3 complex. The inability of chicken TCR/CD3 components to replace the human molecules in T cells was found to result from the lack of interaction between chicken TCRalpha beta heterodimers and the human CD3 complex. In contrast, if no CD3 molecules are present (non-T cells), TCRalpha -TCRbeta chain pairing can take place in an apparently non-controlled way. Thus, the TCR-CD3 interactions have changed with the evolutionary divergence of two mammalian CD3gamma and CD3delta genes from a single prototypic chicken delta/gamma gene. Our data suggest that the structures in mammalian TCR.C regions, which distinguish between CD3delta and CD3gamma chains, have evolved with the appearance of two separate CD3delta and CD3gamma functions.

Lifetime of the 6793-keV state in 15O.

The energy derived from the CN cycle at low stellar temperatures is regulated by the 14N(p,gamma)15O reaction. A previous direct measurement of this reaction has been interpreted as showing evidence for a subthreshold resonance which makes a major contribution to the reaction rate at low temperatures. This resonance, at E(c.m.) = -504 keV would correspond to the known Ex = 6793-keV state in 15O. We have measured a mean lifetime of 1.60(+0.75)(-0.72) fs (90% C.L.) for this state using the Doppler-shift attenuation method. This lifetime is a factor of 15 longer than that inferred from the (p,gamma) data and implies that the contribution of the subthreshold resonance is negligible.

On the genetic mechanism of induction of CD3gamma-negative human T cell variants.

Invariant CD3gamma molecules are important components in TCR complex formation and function. Both CD3gamma alleles seem to be expressed co-dominantly. In the present report, we present experimental data which indicate that the induction of CD3gamma(-) Jurkat variants occurs with a frequency similar to that of TCRalpha(-) or TCRbeta(-) Jurkat cells. CD3delta(-), CD3epsilon(-) or CD3zeta(-) Jurkat variants were never obtained despite extensive efforts. Our data suggest a possible explanation for this genetic puzzle: the human CD3gamma gene has a mutational hot spot in a nucleotide sequence of nine adenosines (9A) in the exon 3 encoding most of the external CD3gamma domain. Thus, both CD3gamma alleles are easily mutated to either 8A or 10A sequences. Furthermore, absence of CD3gamma molecules in Jurkat T cells causes severe defects in TCR / CD3 assembly and function.

Molecular mechanisms in the TCR (TCR alpha beta-CD3 delta epsilon, gamma epsilon) interaction with zeta 2 homodimers: clues from a 'phenotypic revertant' clone.

The association between the TCRalphabeta-CD3gammaepsilondeltaepsilon hexamers and zeta2 homodimers in the endoplasmic reticulum (ER) constitutes a key step in TCR assembly and export to the T cell surface. Incompletely assembled TCR-CD3 complexes are degraded in the ER or the lysosomes. A previously described Jurkat variant (J79) has a mutation at position 195 on the TCR Calpha domain causing a phenylalanine to valine exchange. This results in a lack of association between TCRalphabeta-CD3gammaepsilondeltaepsilon hexamers and zeta2 homodimers. Two main hypotheses could explain this phenomenon in J79 cells: TCR-CD3 hexamers may be incapable of interacting with zeta2 due to a structural change in the TCR Calpha region; alternatively, TCR-CD3 hexamers may be incapable of interacting with zeta2 due to factors unrelated to either molecular complex. In order to assess these two possibilities, the TCR-CD3 membrane-negative J79 cells were treated with ethylmethylsulfonate and clones positive for TCR membrane expression were isolated. The characterization of the J79r58 phenotypic revertant cell line is the subject of this study. The main question was to assess the reason for the TCR re-expression. The TCR on J79r58 cells appears qualitatively and functionally equivalent to wild-type TCR complexes. Nucleotide sequence analysis confirmed the presence of the original mutation in the TCR Calpha region but failed to detect compensatory mutations in alpha, beta, gamma, delta, epsilon or zeta chains. Thus, mutated J79-TCR-CD3 complexes can interact with zeta2 homodimers. Possible mechanisms for the unsuccessful TCR-CD3 interaction with zeta2 homodimers are presented and discussed.