Development of Josephson voltage standards

Neurology & clinical neurophysiolog

Ultrapure sinewave generation by combining Josephson systems

Peer Reviewe

Novel digital impedance bridges for the realization of the farad from graphene quantum standards

In the International System of Units, a realization of the impedance units is the quantum Hall effect, a macroscopic quantum phenomenon that produces quantized resistance values. Established experiments employ individual GaAs devices [1], but research is ongoing on novel materials such as graphene, which allows the realization of the units with relaxed experimental conditions. Furthermore, novel digital impedance bridges allow the implementation of simple traceability chains. In the framework of the European EMPIR project 18SIB07 GIQS (Graphene Impedance Quantum Standards), an affordable and easy-to-operate impedance standard combining novel digital impedance bridges and graphene quantum standards has been developed. An onsite comparison of an electronic and a Josephson impedance bridges developed at INRIM (Istituto Nazionale di Ricerca Metrologica, Italy) and PTB (Physikalisch-Technische Bundesanstalt, Germany), respectively, were organized for their mutual validation and to assess their performance in the realization of the farad.Measurements of temperature-controlled impedance standards and of a graphene quantized Hall resistance standard in the AC regime were performed with both INRIM’s and PTB’s bridges. The result of the comparison and the last progresses of the GIQS project are here presented

PTB-INRIM comparison of novel digital impedance bridges with graphene impedance quantum standards

This paper describes an onsite comparison of two different digital impedance bridges when performing measurements on a quantum Hall resistance standard with the purpose of realizing the SI unit of capacitance, the farad. In the EMPIR Joint Research Project 18SIB07 GIQS, graphene impedance quantum standards, the Physikalisch-Technische Bundesanstalt (PTB), Germany, developed a Josephson impedance bridge, and the Istituto Nazionale di Ricerca Metrologica (INRIM) and the Politecnico di Torino (POLITO), Italy, developed an electronic digital impedance bridge. The former is based on Josephson waveform generators and the latter on an electronic waveform synthesizer. The INRIM–POLITO impedance bridge was moved to PTB and the two bridges were compared by measuring both temperature-controlled standards and a graphene AC quantized Hall resistance (QHR) standard. The uncertainties for the calibration of 10 nF capacitance standards at 1233 Hz are within 1 × 10−8 for the PTB's bridge and around 1 × 10−7 for the INRIM–POLITO's bridge. The comparison mutually validates the two bridges within the combined uncertainty. The result confirms that digital impedance bridges allow the realization of the SI farad from the QHR with uncertainties comparable with the best calibration capabilities of the BIPM and the major National Metrology Institutes

Long-term effects of intravenous iloprost in patients with idiopathic pulmonary arterial hypertension deteriorating on non-parenteral therapy

Background: The majority of patients with idiopathic pulmonary arterial hypertension (IPAH) in functional classes II and III are currently being treated with non-parenteral therapies, including endothelin receptor antagonists (ERA), phosphodiesterase (PDE)-5 inhibitors, inhaled iloprost or combinations of these substances. If these treatments fail, current guidelines recommend the addition of parenteral prostanoid therapy. There is, however, limited evidence for the efficacy of parenteral prostanoids when added to combinations of non-parenteral therapies. Methods: In this retrospective, multicentre study we collected data from consecutive IPAH patients receiving intravenous iloprost in addition to optimized non-parenteral therapy between Jan 2002 and Dec 2009. Analyses included 6 min walk distance (6MWD), functional class, need for transplantation, and survival. Results: During the observation period, 50 patients were treated with intravenous iloprost in addition to non-parenteral therapy; 44% of the patients were on dual combination therapy and 52% on triple combination. Three months after initiation of iloprost, functional class had improved in 24% of the patients and the median 6MWD had increased from 289 m to 298 m (n.s.). During the observation period, 22 patients (44%) died and 14 (28%) underwent lung transplantation. The probabilities of LuTx-free survival at 1, 3 and 5 years following iloprost initiation were 38%, 17% and 17%, respectively. A 6MWD < 300 m and persistent functional class IV at 3 months after initiation of intravenous iloprost were predictors of an adverse outcome. Conclusion: In essence, late initiation of intravenous iloprost in IPAH patients who previously failed to respond to non-parenteral therapies appears to be of limited efficacy in the majority patients. Alternative therapeutic options are currently not available, underlying the need for the development of new drugs

Higher finiteness properties of reductive arithmetic groups in positive characteristic: the rank theorem

We show that the finiteness length of an $S$-arithmetic subgroup $\Gamma$ in a noncommutative isotropic absolutely almost simple group $G$ over a global function field is one less than the sum of the local ranks of $G$ taken over the places in $S$. This determines the finiteness properties for arithmetic subgroups in isotropic reductive groups, confirming the conjectured finiteness properties for this class of groups. Our main tool is Behr-Harder reduction theory which we recast in terms of the metric structure of euclidean buildings

The cytokine receptor CRLF3 is a human neuroprotective EV-3 (Epo) receptor

The evolutionary conserved orphan cytokine receptor-like factor 3 (CRLF3) has been implicated in human disease, vertebrate hematopoiesis and insect neuroprotection. While its specific functions are elusive, experimental evidence points toward a general role in cell homeostasis. Erythropoietin (Epo) is a major regulator of vertebrate hematopoiesis and a general cytoprotective cytokine. Erythropoietic functions mediated by classical Epo receptor are understood in great detail whereas Epo-mediated cytoprotective mechanisms are more complex due to involvement of additional Epo receptors and a non-erythropoietic splice variant with selectivity for certain receptors. In the present study, we show that the human CRLF3 mediates neuroprotection upon activation with the natural Epo splice variant EV-3. We generated CRLF3 knock-out iPSC lines and differentiated them toward the neuronal lineage. While apoptotic death of rotenone-challenged wild type iPSC-derived neurons was prevented by EV-3, EV-3-mediated neuroprotection was absent in CRLF3 knock-out neurons. Rotenone-induced apoptosis and EV-3-mediated neuroprotection were associated with differential expression of pro-and anti-apoptotic genes. Our data characterize human CRLF3 as a receptor involved in Epo-mediated neuroprotection and identify CRLF3 as the first known receptor for EV-3

Riociguat for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: Results from a phase II long-term extension study

Background: Riociguat was well tolerated and improved exercise and functional capacity in patients with pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH) in a 12 -week Phase II trial. We present final data from the long-term extension phase of this study. Methods: During this multicenter, open-label, uncontrolled long-term extension study, riociguat dose could be changed at the physician's discretion (range 0.5-2.5 mg three times daily). The primary outcome was long-term safety and tolerability of riociguat;secondary outcomes included 6-minute walking distance, World Health Organization functional class, survival, and clinical worsening-free survival. Results: Sixty-eight patients (inoperable CTEPH, n = 41;PAH, n = 27) entered the long-term extension. Median treatment duration at the final data cut-off was 77 months. The most common adverse events were nasopharyngitis (57%) and peripheral edema (37%). Three patients (4%) experienced serious adverse events of hemoptysis: two moderate, one severe, none fatal or considered drug-related. At Month 48, 6-minute walking distace increased from baseline by 69 +/- 105 m, and World Health Organization functional class improved/stabilized/worsened versus baseline in 50/45/5% of patients. Three-year survival and clinical worsening-free survival were 91% and 49%, respectively (with patients censored if they withdrew without experiencing an event). Starting a new PAH treatment was the most frequent clinical worsening event. Conclusions: Improvements in exercise and functional capacity were maintained at 4 years in patients remaining on treatment, with no new safety signals identified. These data support riociguat as a long-term treatment option for PAH and inoperable CTEPH. Trial registered at: ClinicalTrials.gov. Registration number: NCT00454558