Characterization of a Differential Radio-Frequency Single-Electron Transistor

We have fabricated and characterized a new type of electrometer that couples two parallel single-electron transistors (SETs) to a radio-frequency tank circuit for use as a differential RF-SET. We demonstrate operation of this device in summing, differential, and single-SET operation modes, and use it to measure a Coulomb staircase from a differential single Cooper-pair box. In differential mode, the device is sensitive to uncorrelated input signals while screening out correlated ones.Comment: 3 pages, 3 figures, submitted to Applied Physics Letter

Asymptotic defectiveness of manufacturing plants: an estimate based on process learning curves

The paper describes a method for a preliminary estimation of asymptotic defectiveness of a manufacturing plant based on the prediction of its learning curve estimated during a p-chart setting up. The proposed approach provides process managers with the possibility of estimating the asymptotic variability of the process and the period of revision of p-chart control limits. An application of the method is also provided

Crossover from time-correlated single-electron tunneling to that of Cooper pairs

We have studied charge transport in a one-dimensional chain of small Josephson junctions using a single-electron transistor. We observe a crossover from time-correlated tunneling of single electrons to that of Cooper pairs as a function of both magnetic field and current. At relatively high magnetic field, single-electron transport dominates and the tunneling frequency is given by f=I/e, where I is the current through the chain and e is the electron's charge. As the magnetic field is lowered, the frequency gradually shifts to f=I/2e for I>200 fA, indicating Cooper-pair transport. For the parameters of the measured sample, we expect the Cooper-pair transport to be incoherent.Comment: 5 pages, 4 figures; v2: minor changes, clarifications, addition

Modulation of NF-κB-dependent gene transcription using programmable DNA minor groove binders

Nuclear factor κB (NF-κB) is a transcription factor that regulates various aspects of immune response, cell death, and differentiation as well as cancer. In this study we introduce the Py-Im polyamide 1 that binds preferentially to the sequences 5′-WGGWWW-3′ and 5′GGGWWW-3′. The compound is capable of binding to κB sites and reducing the expression of various NF-κB–driven genes including IL6 and IL8 by qRT-PCR. Chromatin immunoprecipitation experiments demonstrate a reduction of p65 occupancy within the proximal promoters of those genes. Genome-wide expression analysis by RNA-seq compares the DNA-binding polyamide with the well-characterized NF-κB inhibitor PS1145, identifies overlaps and differences in affected gene groups, and shows that both affect comparable numbers of TNF-α–inducible genes. Inhibition of NF-κB DNA binding via direct displacement of the transcription factor is a potential alternative to the existing antagonists

Top-transmon: hybrid superconducting qubit for parity-protected quantum computation

Qubits constructed from uncoupled Majorana fermions are protected from decoherence, but to perform a quantum computation this topological protection needs to be broken. Parity-protected quantum computation breaks the protection in a minimally invasive way, by coupling directly to the fermion parity of the system --- irrespective of any quasiparticle excitations. Here we propose to use a superconducting charge qubit in a transmission line resonator (a socalled transmon) to perform parity-protected rotations and read-out of a topological (top) qubit. The advantage over an earlier proposal using a flux qubit is that the coupling can be switched on and off with exponential accuracy, promising a reduced sensitivity to charge noise.Comment: 7 pages, 5 figure

Cardiopulmonary Exercise Testing Provides Additional Prognostic Information in Cystic Fibrosis

RATIONALE: The prognostic value of cardiopulmonary exercise testing (CPET) for survival in cystic fibrosis (CF) in the context of current clinical management, when controlling for other known prognostic factors, is unclear. OBJECTIVES: To determine the prognostic value of CPET-derived measures beyond peak oxygen uptake (V.o2peak) following rigorous adjustment for other predictors. METHODS: Data from 10 CF centers in Australia, Europe, and North America were collected retrospectively. A total of 510 patients completed a cycle CPET between January 2000 and December 2007, of which 433 fulfilled the criteria for a maximal effort. Time to death/lung transplantation was analyzed using Cox proportional hazards regression. In addition, phenotyping using hierarchical Ward clustering was performed to characterize high-risk subgroups. MEASUREMENTS AND MAIN RESULTS: Cox regression showed, even after adjustment for sex, FEV1% predicted, body mass index (z-score), age at CPET, Pseudomonas aeruginosa status, and CF-related diabetes as covariates in the model, that V.o2peak in % predicted (hazard ratio [HR], 0.964; 95% confidence interval [CI], 0.944–0.986), peak work rate (% predicted; HR, 0.969; 95% CI, 0.951–0.988), ventilatory equivalent for oxygen (HR, 1.085; 95% CI, 1.041–1.132), and carbon dioxide (HR, 1.060; 95% CI, 1.007–1.115) (all P < 0.05) were significant predictors of death or lung transplantation at 10-year follow-up. Phenotyping revealed that CPET-derived measures were important for clustering. We identified a high-risk cluster characterized by poor lung function, nutritional status, and exercise capacity. CONCLUSIONS: CPET provides additional prognostic information to established predictors of death/lung transplantation in CF. High-risk patients may especially benefit from regular monitoring of exercise capacity and exercise counseling

Betibeglogene Autotemcel Gene Therapy for Non-β⁰/β⁰ Genotype β-Thalassemia

BACKGROUND: Betibeglogene autotemcel (beti-cel) gene therapy for transfusion-dependent β-thalassemia contains autologous CD34+ hematopoietic stem cells and progenitor cells transduced with the BB305 lentiviral vector encoding the β-globin (βA-T87Q) gene. METHODS: In this open-label, phase 3 study, we evaluated the efficacy and safety of beti-cel in adult and pediatric patients with transfusion-dependent β-thalassemia and a non-β0/β0 genotype. Patients underwent myeloablation with busulfan (with doses adjusted on the basis of pharmacokinetic analysis) and received beti-cel intravenously. The primary end point was transfusion independence (i.e., a weighted average hemoglobin level of ≥9 g per deciliter without red-cell transfusions for ≥12 months). RESULTS: A total of 23 patients were enrolled and received treatment, with a median follow-up of 29.5 months (range, 13.0 to 48.2). Transfusion independence occurred in 20 of 22 patients who could be evaluated (91%), including 6 of 7 patients (86%) who were younger than 12 years of age. The average hemoglobin level during transfusion independence was 11.7 g per deciliter (range, 9.5 to 12.8). Twelve months after beti-cel infusion, the median level of gene therapy-derived adult hemoglobin (HbA) with a T87Q amino acid substitution (HbAT87Q) was 8.7 g per deciliter (range, 5.2 to 10.6) in patients who had transfusion independence. The safety profile of beti-cel was consistent with that of busulfan-based myeloablation. Four patients had at least one adverse event that was considered by the investigators to be related or possibly related to beti-cel; all events were nonserious except for thrombocytopenia (in 1 patient). No cases of cancer were observed. CONCLUSIONS: Treatment with beti-cel resulted in a sustained HbAT87Q level and a total hemoglobin level that was high enough to enable transfusion independence in most patients with a non-β0/β0 genotype, including those younger than 12 years of age. (Funded by Bluebird Bio; HGB-207 ClinicalTrials.gov number, NCT02906202.)