Diode effect in Josephson junctions with a single magnetic atom.

Current flow in electronic devices can be asymmetric with bias direction, a phenomenon underlying the utility of diodes1 and known as non-reciprocal charge transport2. The promise of dissipationless electronics has recently stimulated the quest for superconducting diodes, and non-reciprocal superconducting devices have been realized in various non-centrosymmetric systems3-10. Here we investigate the ultimate limits of miniaturization by creating atomic-scale Pb-Pb Josephson junctions in a scanning tunnelling microscope. Pristine junctions stabilized by a single Pb atom exhibit hysteretic behaviour, confirming the high quality of the junctions, but no asymmetry between the bias directions. Non-reciprocal supercurrents emerge when inserting a single magnetic atom into the junction, with the preferred direction depending on the atomic species. Aided by theoretical modelling, we trace the non-reciprocity to quasiparticle currents flowing by means of electron-hole asymmetric Yu-Shiba-Rusinov states inside the superconducting energy gap and identify a new mechanism for diode behaviour in Josephson junctions. Our results open new avenues for creating atomic-scale Josephson diodes and tuning their properties through single-atom manipulation.

Assessing the Usability of a Novel Wearable Remote Patient Monitoring Device for the Early Detection of In-Hospital Patient Deterioration: Observational Study.

BACKGROUND: Patients admitted to general wards are inherently at risk of deterioration. Thus, tools that can provide early detection of deterioration may be lifesaving. Frequent remote patient monitoring (RPM) has the potential to allow such early detection, leading to a timely intervention by health care providers. OBJECTIVE: This study aimed to assess the potential of a novel wearable RPM device to provide timely alerts in patients at high risk for deterioration. METHODS: This prospective observational study was conducted in two general wards of a large tertiary medical center. Patients determined to be at high risk to deteriorate upon admission and assigned to a telemetry bed were included. On top of the standard monitoring equipment, a wearable monitor was attached to each patient, and monitoring was conducted in parallel. The data gathered by the wearable monitors were analyzed retrospectively, with the medical staff being blinded to them in real time. Several early warning scores of the risk for deterioration were used, all calculated from frequent data collected by the wearable RPM device: these included (1) the National Early Warning Score (NEWS), (2) Airway, Breathing, Circulation, Neurology, and Other (ABCNO) score, and (3) deterioration criteria defined by the clinical team as a "wish list" score. In all three systems, the risk scores were calculated every 5 minutes using the data frequently collected by the wearable RPM device. Data generated by the early warning scores were compared with those obtained from the clinical records of actual deterioration among these patients. RESULTS: In total, 410 patients were recruited and 217 were included in the final analysis. The median age was 71 (IQR 62-78) years and 130 (59.9%) of them were male. Actual clinical deterioration occurred in 24 patients. The NEWS indicated high alert in 16 of these 24 (67%) patients, preceding actual clinical deterioration by 29 hours on average. The ABCNO score indicated high alert in 18 (75%) of these patients, preceding actual clinical deterioration by 38 hours on average. Early warning based on wish list scoring criteria was observed for all 24 patients 40 hours on average before clinical deterioration was detected by the medical staff. Importantly, early warning based on the wish list scoring criteria was also observed among all other patients who did not deteriorate. CONCLUSIONS: Frequent remote patient monitoring has the potential for early detection of a high risk to deteriorate among hospitalized patients, using both grouped signal-based scores and algorithm-based prediction. In this study, we show the ability to formulate scores for early warning by using RPM. Nevertheless, early warning scores compiled on the basis of these data failed to deliver reasonable specificity. Further efforts should be directed at improving the specificity and sensitivity of such tools. TRIAL REGISTRATION: ClinicalTrials.gov NCT04220359; https://clinicaltrials.gov/ct2/show/NCT04220359.

Shot-noise measurements of single-atom junctions using a scanning tunneling microscope.

Current fluctuations related to the discreteness of charge passing through small constrictions are termed shot noise. This unavoidable noise provides both advantages-being a direct measurement of the transmitted particles' charge-and disadvantages-a main noise source in nanoscale devices operating at low temperature. While better understanding of shot noise is desired, the technical difficulties in measuring it result in relatively few experimental works, especially in single-atom structures. Here, we describe a local shot-noise measurement apparatus and demonstrate successful noise measurements through single-atom junctions. Our apparatus, based on a scanning tunneling microscope, operates at liquid helium temperatures. It includes a broadband commercial amplifier mounted in close proximity to the tunnel junction, thus reducing both the thermal noise and input capacitance that limit traditional noise measurements. The full capabilities of the microscope are maintained in the modified system, and a quick transition between different measurement modes is possible.

Potentio-tunable FET sensor having a redox-polarizable single electrode for the implementation of a wearable, continuous multi-analyte monitoring device.

The emerging field of wearable devices for monitoring bioanalytes calls for the miniaturization of biochemical sensors. The only commercially available electrochemical wearable monitoring medical devices for bioanalytes are the amperometric continuous glucose monitoring (CGM) systems. The use of such amperometric methods to monitor glucose levels requires a relatively large electrode surface area for sufficient redox species collection, allowing accurate measurements to be made. Consequently, miniaturization of such sensors bearing large electrodes is challenging. Furthermore, it is difficult to introduce and deploy more than one electrode-based sensor per device, thereby limiting the number of analytes that can be monitored in parallel. To address these limitations, we have employed a non-referenced, single polarizable electrode coupled to a fin-shaped field-effect transistor (Fin-FET). We have discovered that by passivating the FET area by a relatively thick oxide and/or polytetrafluoroethylene (PTFE) polymer, leaving only the polarizable working electrode (WE) exposed, we can monitor redox analytes at the micromolar to millimolar concentration range. We attribute this effect to the WE polarization by the solution redox species. We have exploited the superior sensitivity of the adjacent silicon-based Fin-FET to detect changes in sensor electrode potentials induced by the redox species. Furthermore, we demonstrated the correlation between a specific analyte and the biasing WE potential on the accumulation/depletion of the coupled Fin-FET channel as manifested by the transistor source-drain current. Moreover, we utilized the analyte-electrode potential interaction, which is analyte-specific, to tune the specificity of the sensor towards an analyte of choice. In addition, we demonstrated the use of a single-electrode potentiometric sweep to assist in identifying the accumulation/depletion as a result of analyte-WE state. Collectively, the tiny potentio-tunable electrochemical sensor (PTEchem sensor) area is ~50 × 50 µm, and dedicated wireless transducer facilitates the use of this sensor for wearable continuous, multi-metabolite monitoring.

Safety and efficacy of a novel ureteral occlusion device.

OBJECTIVE: To evaluate the safety of a novel ureteral occlusion device and compare its performance with that of other devices and guidewires. METHODS: The XenX (Xenolith Medical) was tested in an ex vivo porcine model to determine the percentage of denuded urothelium because of manipulation within the ureter, the capacity to prevent stone migration during laser lithotripsy, stent compatibility, and the ability to be used for stent placement. Comparative evaluations of the insertion forces and maneuverability were conducted in an in vitro ureter model with the XenX, Stone Cone (Boston Scientific), NTrap (Cook Urological), HiWire (Cook Urological), Roadrunner (Cook Urological), and Sensor (Boston Scientific). Stone migration efficacy was measured using a controlled distribution of stones in 4- and 10-mm silicone tubing with the XenX, NTrap, and Stone Cone. RESULTS: The XenX was safely manipulated within the ureter, prevented significant particle migration during laser lithotripsy, and effectively placed stents. The NTrap required the greatest force when attempting to navigate past a stone (P = .0003), followed by the Stone Cone (P = .009), with little difference among the other devices (P > .72). No differences were found for the passing forces (P = .061), interval to pass (P = .30), or number of attempts to pass the stone (P = .68). The XenX prevented stone migration the most, with more notable differences in the 10- than in the 4-mm tubing. CONCLUSION: Ex vivo evaluations hold promise for the XenX to be safely and effectively used during ureteroscopic procedures. Clinical evaluations are warranted to confirm the safety and performance of the XenX relative to the other ureteral occlusion devices.

Monophosphorylation of CD79a and CD79b ITAM motifs initiates a SHIP-1 phosphatase-mediated inhibitory signaling cascade required for B cell anergy.

Anergic B cells are characterized by impaired signaling and activation after aggregation of their antigen receptors (BCR). The molecular basis of this impairment is not understood. In studies reported here, Src homology-2 (SH2)-containing inositol 5-phosphatase SHIP-1 and its adaptor Dok-1 were found to be constitutively phosphorylated in anergic B cells, and activation of this inhibitory circuit was dependent on Src-family kinase activity and consequent to biased BCR immunoreceptor tyrosine-based activation motif (ITAM) monophosphorylation. B cell-targeted deletion of SHIP-1 caused severe lupus-like disease. Moreover, absence of SHIP-1 in B cells led to loss of anergy as indicated by restoration of BCR signaling, loss of anergic surface phenotype, and production of autoantibodies. Thus, chronic BCR signals maintain anergy in part via ITAM monophosphorylation-directed activation of an inhibitory signaling circuit involving SHIP-1 and Dok-1.

Downstream of kinase, p62(dok), is a mediator of Fc gamma IIB inhibition of Fc epsilon RI signaling.

The low-affinity receptor for IgG, Fc gamma RIIB, is expressed widely in the immune system and functions to attenuate Ag-induced immune responses. In mast cells, coaggregation of Fc gamma RIIB with the high-affinity IgE receptor, Fc epsilon RI, leads to inhibition of Ag-induced degranulation and cytokine production. Fc gamma RIIB inhibitory activity requires a conserved motif within the Fc gamma RIIB cytoplasmic domain termed the immunoreceptor tyrosine-based inhibition motif. When coaggregated with an activating receptor (e.g., Fc epsilon RI, B cell Ag receptor), Fc gamma RIIB is rapidly phosphorylated on tyrosine and recruits the SH2 domain-containing inositol 5-phosphatase (SHIP). However, the mechanisms by which SHIP mediates Fc gamma RIIB inhibitory function in mast cells remain poorly defined. In this report we demonstrate that Fc gamma RIIB coaggregation with Fc epsilon RI stimulates enhanced SHIP tyrosine phosphorylation and association with Shc and p62(dok). Concurrently, enhanced p62(dok) tyrosine phosphorylation and association with RasGAP are observed, suggesting that SHIP may mediate Fc gamma RIIB inhibitory function in mast cells via recruitment of p62(dok) and RasGAP. Supporting this hypothesis, recruitment of p62(dok) to Fc epsilon RI is sufficient to inhibit Fc epsilon RI-induced calcium mobilization and extracellular signal-regulated kinase 1/2 activation. Interestingly, both the amino-terminal pleckstrin homology and phosphotyrosine binding domains and the carboxyl-terminal proline/tyrosine-rich region of p62(dok) can mediate inhibition, suggesting activation of parallel downstream signaling pathways that converge at extracellular signal-regulated kinase 1/2 activation. Finally, studies using gene-ablated mice indicate that p62(dok) is dispensable for Fc gamma RIIB inhibitory signaling in mast cells. Taken together, these data suggest a role for p62(dok) as a mediator of Fc gamma RIIB inhibition of Fc epsilon RI signal transduction in mast cells.