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

Examination of change factor methodologies for climate change impact assessment

Citation: Anandhi, A., Frei, A., Pierson, D. C., Schneiderman, E. M., Zion, M. S., Lounsbury, D., and Matonse, A. H. ( 2011), Examination of change factor methodologies for climate change impact assessment, Water Resour. Res., 47, W03501, doi:10.1029/2010WR009104.A variety of methods are available to estimate values of meteorological variables at future times and at spatial scales that are appropriate for local climate change impact assessment. One commonly used method is Change Factor Methodology (CFM), sometimes referred to as delta change factor methodology. Although more sophisticated methods exist, CFM is still widely applicable and used in impact analysis studies. While there are a number of different ways by which change factors (CFs) can be calculated and used to estimate future climate scenarios, there are no clear guidelines available in the literature to decide which methodologies are most suitable for different applications. In this study several categories of CFM (additive versus multiplicative and single versus multiple) for a number of climate variables are compared and contrasted. The study employs several theoretical case studies, as well as a real example from Cannonsville watershed, which supplies water to New York City, USA. Results show that in cases when the frequency distribution of Global Climate Model (GCM) baseline climate is close to the frequency distribution of observed climate, or when the frequency distribution of GCM future climate is close to the frequency distribution of GCM baseline climate, additive and multiplicative single CFMs provide comparable results. Two options to guide the choice of CFM are suggested. The first option is a detailed methodological analysis for choosing the most appropriate CFM. The second option is a default method for use under circumstances in which a detailed methodological analysis is too cumbersome

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

The design-by-adaptation approach to universal access: learning from videogame technology

This paper proposes an alternative approach to the design of universally accessible interfaces to that provided by formal design frameworks applied ab initio to the development of new software. This approach, design-byadaptation, involves the transfer of interface technology and/or design principles from one application domain to another, in situations where the recipient domain is similar to the host domain in terms of modelled systems, tasks and users. Using the example of interaction in 3D virtual environments, the paper explores how principles underlying the design of videogame interfaces may be applied to a broad family of visualization and analysis software which handles geographical data (virtual geographic environments, or VGEs). One of the motivations behind the current study is that VGE technology lags some way behind videogame technology in the modelling of 3D environments, and has a less-developed track record in providing the variety of interaction methods needed to undertake varied tasks in 3D virtual worlds by users with varied levels of experience. The current analysis extracted a set of interaction principles from videogames which were used to devise a set of 3D task interfaces that have been implemented in a prototype VGE for formal evaluation

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.)

Response vs. Perception

Three experiments were conducted in which college students read, and then attempted to match, a series of written descriptive passages with the referent photographs on which they were based; the photographs sho wed the face of an actor, representing a variety of emotional expressions. In Experiment I, subjects provided with a series of context passages depicting a narrow range of emotions (neither pleasant nor unpleasant) chose “matches” having more extreme pleasantness values than did subjects provided with context passages depicting a wide range of descriptions on the pleasantness dimension when responding to test descriptions embedded within the context series. In Experiments II and III, contrast effects were obtained; subjects who had read mostly unpleasant context passages chose more pleasant referents in response to neutral test descriptions than did those who had read mostly pleasant descriptions. The results of all three experiments suggested that these effects were mediated in large part by a response bias, the tendency to use each response alternative with roughly equal frequency. In Experiments II and III, there was suggestive evidence for the possibility that a more central (or perceptual) mechanism may also have contributed to the observed results.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45367/1/11031_2004_Article_BF00992590.pd

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

TTFields alone and in combination with chemotherapeutic agents effectively reduce the viability of MDR cell sub-lines that over-express ABC transporters

<p>Abstract</p> <p>Background</p> <p>Exposure of cancer cells to chemotherapeutic agents may result in reduced sensitivity to structurally unrelated agents, a phenomenon known as multidrug resistance, MDR. The purpose of this study is to investigate cell growth inhibition of wild type and the corresponding MDR cells by Tumor Treating Fields - TTFields, a new cancer treatment modality that is free of systemic toxicity. The TTFields were applied alone and in combination with paclitaxel and doxorubicin.</p> <p>Methods</p> <p>Three pairs of wild type/MDR cell lines, having resistivity resulting from over-expression of ABC transporters, were studied: a clonal derivative (C11) of parental Chinese hamster ovary AA8 cells and their emetine-resistant sub-line Emt^R1; human breast cancer cells MCF-7 and their mitoxantrone-resistant sub lines MCF-7/Mx and human breast cancer cells MDA-MB-231 and their doxorubicin resistant MDA-MB-231/Dox cells. TTFields were applied for 72 hours with and without the chemotherapeutic agents. The numbers of viable cells in the treated cultures and the untreated control groups were determined using the XTT assay. Student t-test was applied to asses the significance of the differences between results obtained for each of the three cell pairs.</p> <p>Results</p> <p>TTFields caused a similar reduction in the number of viable cells of wild type and MDR cells. Treatments by TTFields/drug combinations resulted in a similar increased reduction in cell survival of wild type and MDR cells. TTFields had no effect on intracellular doxorubicin accumulation in both wild type and MDR cells.</p> <p>Conclusions</p> <p>The results indicate that TTFields alone and in combination with paclitaxel and doxorubicin effectively reduce the viability of both wild type and MDR cell sub-lines and thus can potentially be used as an effective treatment of drug resistant tumors.</p

NAFTA Chapter 11 as Supraconstitution

More and more legal scholars are turning to constitutional law to make sense of the growth of transnational and international legal orders. They often employ constitutional terminology loosely, in a bewildering variety of ways, with little effort to clarify their analytical frameworks or acknowledge the normative presuppositions embedded in their analysis. The potential of constitutional analysis as an instrument of critique of transnational legal orders is frequently lost in methodological confusion and normative controversy. An effort at clarification is necessary. We propose a functional approach to supraconstitutional analysis that applies across issue areas, accommodates variation in kinds and degrees of supraconstitutionalization, recognizes its simultaneously domestic and transnational character, and reflects its uneven incidence and impacts. We apply this framework to NAFTA to consider whether and how it superimposes a supraconstitutional legal order on member states\u27 domestic constitutional orders. We show that the main thrust of this contemporary supraconstitutional project is to restructure state and international political forms to promote market efficiency and discipline, enable free capital movement, confer privileged rights of citizenship and representation on corporate capital, insulate key aspects of the economy from state interference, and constrain democratic decision-making