Practical quantum realization of the ampere from the electron charge

One major change of the future revision of the International System of Units (SI) is a new definition of the ampere based on the elementary charge \emph{e}. Replacing the former definition based on Amp\`ere's force law will allow one to fully benefit from quantum physics to realize the ampere. However, a quantum realization of the ampere from \emph{e}, accurate to within $10^{-8}$ in relative value and fulfilling traceability needs, is still missing despite many efforts have been spent for the development of single-electron tunneling devices. Starting again with Ohm's law, applied here in a quantum circuit combining the quantum Hall resistance and Josephson voltage standards with a superconducting cryogenic amplifier, we report on a practical and universal programmable quantum current generator. We demonstrate that currents generated in the milliampere range are quantized in terms of $ef_\mathrm{J}$ ($f_\mathrm{J}$ is the Josephson frequency) with a measurement uncertainty of $10^{-8}$. This new quantum current source, able to deliver such accurate currents down to the microampere range, can greatly improve the current measurement traceability, as demonstrated with the calibrations of digital ammeters. Beyond, it opens the way to further developments in metrology and in fundamental physics, such as a quantum multimeter or new accurate comparisons to single electron pumps.Comment: 15 pages, 4 figure

Experimental Test of the Numerical Renormalization Group Theory for Inelastic Scattering from Magnetic Impurities

We present measurements of the phase coherence time \tauphi in quasi one-dimensional Au/Fe Kondo wires and compare the temperature dependence of \tauphi with a recent theory of inelastic scattering from magnetic impurities (Phys. Rev. Lett. 93, 107204 (2004)). A very good agreement is obtained for temperatures down to 0.2 $T_K$. Below the Kondo temperature $T_K$, the inverse of the phase coherence time varies linearly with temperature over almost one decade in temperature.Comment: 5 pages, 3 figure

Quantum Hall effect in exfoliated graphene affected by charged impurities: metrological measurements

Metrological investigations of the quantum Hall effect (QHE) completed by transport measurements at low magnetic field are carried out in a-few-$\mu\mathrm{m}$-wide Hall bars made of monolayer (ML) or bilayer (BL) exfoliated graphene transferred on $\textrm{Si/SiO}_{2}$ substrate. From the charge carrier density dependence of the conductivity and from the measurement of the quantum corrections at low magnetic field, we deduce that transport properties in these devices are mainly governed by the Coulomb interaction of carriers with a large concentration of charged impurities. In the QHE regime, at high magnetic field and low temperature ($T<1.3 \textrm{K}$), the Hall resistance is measured by comparison with a GaAs based quantum resistance standard using a cryogenic current comparator. In the low dissipation limit, it is found quantized within 5 parts in $10^{7}$ (one standard deviation, $1 \sigma$) at the expected rational fractions of the von Klitzing constant, respectively $R_{\mathrm{K}}/2$ and $R_{\mathrm{K}}/4$ in the ML and BL devices. These results constitute the most accurate QHE quantization tests to date in monolayer and bilayer exfoliated graphene. It turns out that a main limitation to the quantization accuracy, which is found well above the $10^{-9}$ accuracy usually achieved in GaAs, is the low value of the QHE breakdown current being no more than $1 \mu\mathrm{A}$. The current dependence of the longitudinal conductivity investigated in the BL Hall bar shows that dissipation occurs through quasi-elastic inter-Landau level scattering, assisted by large local electric fields. We propose that charged impurities are responsible for an enhancement of such inter-Landau level transition rate and cause small breakdown currents.Comment: 14 pages, 9 figure

Risk Factors for Invasive Haemophilus influenzae Disease among Children 2-16 Years of Age in the Vaccine Era, Switzerland 1991-1993

Mūhlemann K (Institute of Medical Microbiology, Friedbūhistrasse 51, University of Berne, CH-3010 Berne, Switzerland), Alexander E R, Weiss N S, Pepe M, Schopfer K and the Swiss H.Influenzae Study Group. Risk factors for invasive Haemophilus influenzae disease among children aged 2-16 years of age in the vaccine era, Switzerland 1991-1993. International Journal of Epidemiology 1996; 25: 1280-1285. Background Continued surveillance, and detailed investigation of direct and indirect effects of conjugated vaccines and risk factors for invasive H. Influenzae serotype b (Hib) disease in the vaccine era are important Methods 143 cases with invasive disease between 1991 and 1993 aged 2-16 years were selected retrospectively from a large incidence trend study. Controls (n = 336) were recruited from local vital registries and matched to cases for age, gender, and residence. Hib vaccination histories among study subjects and their siblings and other sociodemographic variables were obtained by questionnaires completed by the parents of these children. Adjusted odds ratio (OR) estimates were calculated by conditional logistic regression analysis. Results Most vaccinated subjects had received the Polysacchande-Diphtheria Toxoid vaccine and estimated vaccine efficacy was high (95%; 95% confidence interval [Cl] 60-99%). Also, the results suggested that protection afforded by vaccination against Hib extended to the family members of vaccinated children. School attendance was found to be protective against invasive Hib disease (OR : 0.33; Cl : 0.14-0.75). Cases more often than controls reported sufferring from asthma and allergies (OR : 4.8; Cl: 1.2-19 4). Conclusions Post-licensure vaccine efficacy is high among children ≥2 years of age. The observed association between asthma and epiglottis is novel and deserves further investigatio

Impact of multiangular information on empirical models to estimate canopy nitrogen concentration in mixed forest

Directional effects in remotely sensed reflectance data can influence the retrieval of plant biophysical and biochemical estimates. Previous studies have demonstrated that directional measurements contain added information that may increase the accuracy of estimated plant structural parameters. Because accurate biochemistry mapping is linked to vegetation structure, also models to estimate canopy nitrogen concentration (CN) may be improved indirectly from using multiangular data. Hyperspectral imagery with five different viewing zenith angles was acquired by the spaceborne CHRIS sensor over a forest study site in Switzerland. Fifteen canopy reflectance spectra corresponding to subplots of field-sampled trees were extracted from the preprocessed CHRIS images and subsequently two-term models were developed by regressing CN on four datasets comprising either original or continuum-removed reflectances. Consideration is given to the directional sensitivity of the CN estimation by generating regression models based on various combinations (n=15) of observation angles. The results of this study show that estimating canopy CN with only nadir data is not optimal irrespective of spectral data processing. Moreover adding multiangular information improves significantly the regression model fits and thus the retrieval of forest canopy biochemistry. These findings support the potential of multiangular Earth observations also for application-oriented ecological monitoring

The ampere and the electrical units in the quantum era

By fixing two fundamental constants from quantum mechanics, the Planck constant $h$ and the elementary charge $e$, the revised Syst\`eme International (SI) of units endorses explicitly quantum mechanics. This evolution also highlights the importance of this theory which underpins the most accurate realization of the units. From 20 May 2019, the new definitions of the kilogram and of the ampere, based on fixed values of $h$ and $e$ respectively, will particularly impact the electrical metrology. The Josephson effect (JE) and the quantum Hall effect (QHE), used to maintain voltage and resistance standards with unprecedented reproducibility since 1990, will henceforth provide realizations of the volt and the ohm without the uncertainties inherited from the older electromechanical definitions. More broadly, the revised SI will sustain the exploitation of quantum effects to realize electrical units, to the benefit of end-users. Here, we review the state-of-the-art of these standards and discuss further applications and perspectives.Comment: 78 pages, 35 figure

Novel Roles for Peroxynitrite in Angiotensin II and CaMKII Signaling

Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) oxidation controls excitability and viability. While hydrogen peroxide (H2O2) affects Ca(2+)-activated CaMKII in vitro, Angiotensin II (Ang II)-induced CaMKIIδ signaling in cardiomyocytes is Ca(2+) independent and requires NADPH oxidase-derived superoxide, but not its dismutation product H2O2. To better define the biological regulation of CaMKII activation and signaling by Ang II, we evaluated the potential for peroxynitrite (ONOO(-)) to mediate CaMKII activation and downstream Kv4.3 channel mRNA destabilization by Ang II. In vitro experiments show that ONOO(-) oxidizes and modestly activates pure CaMKII in the absence of Ca(2+)/CaM. Remarkably, this apokinase stimulation persists after mutating known oxidation targets (M281, M282, C290), suggesting a novel mechanism for increasing baseline Ca(2+)-independent CaMKII activity. The role of ONOO(-) in cardiac and neuronal responses to Ang II was then tested by scavenging ONOO(-) and preventing its formation by inhibiting nitric oxide synthase. Both treatments blocked Ang II effects on Kv4.3, tyrosine nitration and CaMKIIδ oxidation and activation. Together, these data show that ONOO(-) participates in Ang II-CaMKII signaling. The requirement for ONOO(-) in transducing Ang II signaling identifies ONOO(-), which has been viewed as a reactive damaging byproduct of superoxide and nitric oxide, as a mediator of GPCR-CaMKII signaling

Electrophiles modulate glutathione reductase activity via alkylation and upregulation of glutathione biosynthesis

Cells evolved robust homeostatic mechanisms to protect against oxidation or alkylation by electrophilic species. Glutathione (GSH) is the most abundant intracellular thiol, protects cellular components from oxidation and is maintained in a reduced state by glutathione reductase (GR). Nitro oleic acid (NO2-OA) is an electrophilic fatty acid formed under digestive and inflammatory conditions that both reacts with GSH and induces its synthesis upon activation of Nrf2 signaling. The effects of NO2-OA on intracellular GSH homeostasis were evaluated. In addition to upregulation of GSH biosynthesis, we observed that NO2-OA increased intracellular GSSG in an oxidative stress-independent manner. NO2-OA directly inhibited GR in vitro by covalent modification of the catalytic Cys61, with kon of (3.45±0.04)×103 M−1 s−1, koff of (4.4±0.4)×10−4 s−1, and Keq of (1.3±0.1)×10−7 M. Akin to NO2-OA, the electrophilic Nrf2 activators bardoxolone-imidazole (CDDO-Im), bardoxolone-methyl (CDDO-Me) and dimethyl fumarate (DMF) also upregulated GSH biosynthesis while promoting GSSG accumulation, but without directly inhibiting GR activity. In vitro assays in which GR was treated with increasing GSH concentrations and GSH depletion experiments in cells revealed that GR activity is finely regulated via product inhibition, an observation further supported by theoretical (kinetic modeling of cellular GSSG:GSH levels) approaches. Together, these results describe two independent mechanisms by which electrophiles modulate the GSH/GSSG couple, and provide a novel conceptual framework to interpret experimentally determined values of GSH and GSSG

Characterization and quantifi cation of endogenous fatty acid nitroalkene metabolites in human urine

The oxidation and nitration of unsaturated fatty acids transforms cell membrane and lipoprotein constituents into mediators that regulate signal transduction. The formation of 9-NO2-octadeca-9,11-dienoic acid and 12-NO2-octadeca- 9,11-dienoic acid stems from peroxynitrite- and myeloperoxidase-derived nitrogen dioxide reactions as well as secondary to nitrite disproportionation under the acidic conditions of digestion. Broad anti-inflammatory and tissue-protective responses are mediated by nitro-fatty acids. It is now shown that electrophilic fatty acid nitroalkenes are present in the urine of healthy human volunteers (9.9 + 4.0 pmol/mg creatinine); along with electrophilic 16- and 14-carbon nitroalkenyl β-oxidation metabolites. High resolution mass determinations and co-elution with isotopically-labeled metabolites support renal excretion of cysteine-nitroalkene conjugates. These products of Michael addition are in equilibrium with the free nitroalkene pool in urine and are displaced by thiol reaction with HgCl2. This reaction increases the level of free nitroalkene fraction >10-fold and displays a KD of 7.5x10-6 M. In aggregate, the data indicates that formation of Michael adducts by electrophilic fatty acids is favored under biological conditions and that reversal of these addition reactions is critical for detecting both parent nitroalkenes and their metabolites. The measurement of this class of mediators can constitute a sensitive non-invasive index of metabolic and inflammatory status.Fil: Salvatore, Sonia Rosana. University of Pittsburgh; Estados UnidosFil: Vitturi, Dario A.. University of Pittsburgh; Estados UnidosFil: Baker, Paul R. S.. University of Pittsburgh; Estados UnidosFil: Bonacci, Gustavo Roberto. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Koenitzer, Jeffrey R.. University of Pittsburgh; Estados UnidosFil: Woodcock, Steven R.. University of Pittsburgh; Estados UnidosFil: Freeman, Bruce A.. University of Pittsburgh; Estados UnidosFil: Schopfer, Francisco J.. University of Pittsburgh; Estados Unido