Two-level systems in superconducting quantum devices due to trapped quasiparticles.

A major issue for the implementation of large-scale superconducting quantum circuits is the interaction with interfacial two-level system (TLS) defects that lead to qubit parameter fluctuations and relaxation. Another major challenge comes from nonequilibrium quasiparticles (QPs) that result in qubit relaxation and dephasing. Here, we reveal a previously unexplored decoherence mechanism in the form of a new type of TLS originating from trapped QPs, which can induce qubit relaxation. Using spectral, temporal, thermal, and magnetic field mapping of TLS-induced fluctuations in frequency tunable resonators, we identify a highly coherent subset of the general TLS population with a low reconfiguration temperature ∼300 mK and a nonuniform density of states. These properties can be understood if the TLS are formed by QPs trapped in shallow subgap states formed by spatial fluctutations of the superconducting order parameter. This implies that even very rare QP bursts will affect coherence over exponentially long time scales.

Suppression of low-frequency charge noise in superconducting resonators by surface spin desorption.

Noise and decoherence due to spurious two-level systems located at material interfaces are long-standing issues for solid-state quantum devices. Efforts to mitigate the effects of two-level systems have been hampered by a lack of knowledge about their chemical and physical nature. Here, by combining dielectric loss, frequency noise and on-chip electron spin resonance measurements in superconducting resonators, we demonstrate that desorption of surface spins is accompanied by an almost tenfold reduction in the charge-induced frequency noise in the resonators. These measurements provide experimental evidence that simultaneously reveals the chemical signatures of adsorbed magnetic moments and highlights their role in generating charge noise in solid-state quantum devices.

Enhancing quantitative approaches for assessing community resilience.

Scholars from many different intellectual disciplines have attempted to measure, estimate, or quantify resilience. However, there is growing concern that lack of clarity on the operationalization of the concept will limit its application. In this paper, we discuss the theory, research development and quantitative approaches in ecological and community resilience. Upon noting the lack of methods that quantify the complexities of the linked human and natural aspects of community resilience, we identify several promising approaches within the ecological resilience tradition that may be useful in filling these gaps. Further, we discuss the challenges for consolidating these approaches into a more integrated perspective for managing social-ecological systems.

Associations of carboxypeptidase 4 with ALDH1A1 expression and their prognostic value in esophageal squamous cell carcinoma.

Esophageal cancer is an aggressive disease with poor prognosis because of early metastasis when diagnosed and recurrence after surgery. This study is aimed at investigating the expression of carboxypeptidaseA4 (CPA4) and aldehyde dehydrogenase 1A1 (ALDH1A1) in esophageal squamous cell carcinoma (ESCC) tumor tissues and analyzed their association and clinical significance. The expression of CPA4 and ALDH1A1 was determined by immunohistochemistry using the corresponding primary antibodies on two commercial tissue arrays. High level of CPA4 was observed in 87/150 (58%) ESCC samples and was significantly associated with histologic grade, lymph node metastasis, and TNM Classification of Esophageal cancer stage. The expression level of ALDH1A1 was much higher in ESCC than their corresponding normal epithelial tissues, with 66% positive rate. And, high levels of ALDH1A1 were significantly associated with lymph nodes metastasis (P < 0.05) and TNM stage (P < 0.05). Correlation analysis showed the expression level of CPA4 positively correlated with that of ALDH1A1 (r = 0.416, P < 0.01). In Kaplan-Meier survival analysis, either CPA4 or ALDH1A1 was significantly correlated with poor overall survival of ESCC patients. Multivariate Cox regression model showed that high expression of CPA4 was an independent prognostic factor for ESCC patients. In conclusion, our present study demonstrated for the first time that CPA4 might be used as an independent poor prognostic factor in ESCC. This study demonstrated for the first time that CPA4 was aberrantly expressed in ESCC tissues. Overexpression of CPA4 was closely associated with the putative cancer stem cell marker ALDH1A1 and might be used as an independent prognostic factor in ESCC.

The potential detection of low-level aerosol isotopes from new civilian nuclear processes.

As the world faces a challenging future in maintaining the commercial availability of radioactive isotopes for medical use, new methods of medical isotope production are being pursued. Many of these are small in size and could effectively operate continuously. With the potential for much shorter retention times, a new suite of isotopes may soon be found in the environment. The authors estimate that many more aerosols containing low-level isotopes of gas/volatile origin could be detectable at short range and times, and a few at longer ranges and times as compared to those released in more common nuclear reactor operations.

Low-background gamma-ray spectrometry for the international monitoring system.

PNNL has developed two low-background gamma-ray spectrometers in a new shallow underground laboratory, thereby significantly improving its ability to detect low levels of gamma-ray emitting fission or activation products in airborne particulate in samples from the IMS (International Monitoring System). The combination of cosmic veto panels, dry nitrogen gas to reduce radon and low background shielding results in a reduction of the background count rate by about a factor of 100 compared to detectors operating above ground at our laboratory.

Effect of omega-3 fatty acid supplementation on arterial elasticity in patients with familial hypercholesterolaemia on statin therapy.

BACKGROUND AND AIMS: Increased arterial stiffness is closely linked with raised blood pressure that contributes substantially to enhanced risk of coronary heart disease in high risk individuals with familial hypercholesterolaemia (FH). Omega-3 fatty acid (ω3-FA) supplementation has been demonstrated to lower blood pressure in subjects with a high cardiovascular disease risk. Whether ω3-FA supplementation improves arterial stiffness in FH subjects, on background statin therapy, has yet to be investigated. METHOD AND RESULTS: We carried out an 8-week randomized, crossover intervention trial to test the effect of 4 g/d ω3-FA supplementation (46% eicosapentaenoic acid and 38% docosahexaenoic acid) on arterial elasticity in 20 adults with FH on optimal cholesterol-lowering therapy. Large and small artery elasticity were measured by pulse contour analysis of the radial artery. ω3-FA supplementation significantly (P < 0.05 in all) increased large artery elasticity (+9%) and reduced systolic blood pressure (-6%) and diastolic blood pressure (-6%), plasma triglycerides (-20%), apoB concentration (-8%). In contrast, ω3-FAs had no significant effect on small artery elasticity. The change in large artery elasticity was not significantly associated with changes in systolic blood pressure or plasma triglyceride concentration. CONCLUSIONS: ω3-FA supplementation improves large arterial elasticity and arterial blood pressure independent of statin therapy in adults with FH. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.com/NCT01577056.

Insulin/glucose induces natriuretic peptide clearance receptor in human adipocytes: a metabolic link with the cardiac natriuretic pathway.

Cardiac natriuretic peptides (NP) are involved in cardiorenal regulation and in lipolysis. The NP activity is largely dependent on the ratio between the signaling receptor NPRA and the clearance receptor NPRC. Lipolysis increases when NPRC is reduced by starving or very-low-calorie diet. On the contrary, insulin is an antilipolytic hormone that increases sodium retention, suggesting a possible functional link with NP. We examined the insulin-mediated regulation of NP receptors in differentiated human adipocytes and tested the association of NP receptor expression in visceral adipose tissue (VAT) with metabolic profiles of patients undergoing renal surgery. Differentiated human adipocytes from VAT and Simpson-Golabi-Behmel Syndrome (SGBS) adipocyte cell line were treated with insulin in the presence of high-glucose or low-glucose media to study NP receptors and insulin/glucose-regulated pathways. Fasting blood samples and VAT samples were taken from patients on the day of renal surgery. We observed a potent insulin-mediated and glucose-dependent upregulation of NPRC, through the phosphatidylinositol 3-kinase pathway, associated with lower lipolysis in differentiated adipocytes. No effect was observed on NPRA. Low-glucose medium, used to simulate in vivo starving conditions, hampered the insulin effect on NPRC through modulation of insulin/glucose-regulated pathways, allowing atrial natriuretic peptide to induce lipolysis and thermogenic genes. An expression ratio in favor of NPRC in adipose tissue was associated with higher fasting insulinemia, HOMA-IR, and atherogenic lipid levels. Insulin/glucose-dependent NPRC induction in adipocytes might be a key factor linking hyperinsulinemia, metabolic syndrome, and higher blood pressure by reducing NP effects on adipocytes.

A high-efficiency HPGe coincidence system for environmental analysis.

The Comprehensive Nuclear-Test-Ban Treaty (CTBT) is supported by a network of certified laboratories which must meet certain sensitivity requirements for CTBT relevant radionuclides. At the UK CTBT Radionuclide Laboratory (GBL15), a high-efficiency, dual-detector gamma spectroscopy system has been developed to improve the sensitivity of measurements for treaty compliance, greatly reducing the time required for each sample. Utilising list-mode acquisition, each sample can be counted once, and processed multiple times to further improve sensitivity. For the 8 key radionuclides considered, Minimum Detectable Activities (MDA's) were improved by up to 37% in standard mode (when compared to a typical CTBT detector system), with the acquisition time required to achieve the CTBT sensitivity requirements reduced from 6 days to only 3. When utilising the system in coincidence mode, the MDA for (60) Co in a high-activity source was improved by a factor of 34 when compared to a standard CTBT detector, and a factor of 17 when compared to the dual-detector system operating in standard mode. These MDA improvements will allow the accurate and timely quantification of radionuclides that decay via both singular and cascade γ emission, greatly enhancing the effectiveness of CTBT laboratories.

Quantification and genotyping of lipoprotein lipase in patients with diabetic lipaemia.

AIMS: To determine if diabetic lipaemia is caused by loss of function mutations in the lipoprotein lipase gene, LPL. METHODS: We conducted a case-control study over 2 years in two tertiary care hospitals in South Australia. Six patients with a history of diabetic lipaemia and 12 control subjects, with previous diabetic ketoacidosis and peak triglyceride concentrations < 2.4 mmol/l were included. Participants were well at the time of study investigations. RESULTS: Only one patient with lipaemia had a loss of function mutation in LPL and no functional mutations in APOC2 or GPIHBP1 were identified. The mean lipoprotein lipase concentration was lower in patients with diabetic lipaemia than in control subjects (306 vs. 484 µg/l, P = 0.04). The mean fasting C-peptide concentration was higher in patients with diabetic lipaemia than in control subjects (771 vs. 50 pmol/l; P = 0.001). CONCLUSIONS: Lipoprotein lipase deficiency in patients with a history of diabetic lipaemia was predominantly quantitative, rather than secondary to mutations in LPL, APOC2 or GPIHBP1. The majority of patients with severe hypertriglyceridaemia in diabetic ketoacidosis may have ketosis-prone Type 2, rather than Type 1, diabetes.

Evidence for interacting two-level systems from the 1/f noise of a superconducting resonator.

The performance of a great variety of electronic devices--ranging from semiconductor transistors to superconducting qubits--is hampered by low-frequency noise with spectra proportional to 1/f. The ubiquity and negative impact of 1/f noise has motivated intensive research into its cause, and it is now believed to originate from a bath of fluctuating two-level defect states (TLSs) embedded in the material. This phenomenon is commonly described by the long-established standard tunnelling model (STM) of independent TLS. A key prediction of STM is that the noise should vanish at low temperatures. Here we report measurements on superconducting microresonators over previously unattainable, very long time scales that show an increase in 1/f noise at low temperatures and low microwave power, contrary to the STM. We propose a new generalised tunnelling model that includes significant interaction between multiple TLSs, which fully describes these observations, as well as recent studies of individual TLS lifetimes in superconducting qubits.

PTH: Potential role in management of heart failure.

Biomarkers play an important role for the diagnosis and prognosis of heart failure (HF), a disease with high morbidity and mortality as well as a huge impact on healthcare budgets. Parathyroid hormone (PTH) is a major systemic calcium-regulating hormone and an important regulator of bone and mineral homeostasis. PTH testing is important for differential diagnosis of calcemia related disorders and for the management of patients with chronic kidney disease. As secondary hyperparathyroidism has been evidenced in HF patients, PTH testing might be relevant in HF patients for risk stratification and more personalized selection of treatment.

Maximising the sensitivity of a γ spectrometer for low-energy, low-activity radionuclides using Monte Carlo simulations.

Monte-Carlo simulations have been utilised to determine the optimum material and thickness for a γ spectrometer to be used for the assay of radionuclides that emit radiation in the 50-300 keV energy range. Both HPGe and LaBr3(Ce) materials were initially considered for use, however the additional background radiation and lack of resolution in the latter drove the selection of HPGe for further optimisation. Multiple thicknesses were considered for the HPGe detector, with the aim of improving the sensitivity of the system by maximising the efficiency for low energy emissions, and reducing the probability of interaction with (and therefore the continuum from) higher energy photons. The minimum amount of material needed to achieve this was found to be 15 mm for a source that is dominated by high energy (>2.614 MeV) photons, and 20-30 mm for a typical reference source (with photons of energy 59.54 keV-2.614 MeV).

TGF-ß and NF-κB signal pathway cross-talk is mediated through TAK1 and SMAD7 in a subset of head and neck cancers.

Transforming growth factor-beta (TGF-ß) has a dual role in epithelial malignancies, including head and neck squamous cell carcinoma (HNSCC). Attenuation of canonical TGF-ß signaling enhances de novo tumor development, whereas TGF-ß overexpression and signaling paradoxically promotes malignant progression. We recently observed that TGF-ß-induced growth arrest response is attenuated, in association with aberrant activation of nuclear factor-κB (NF-κB), a transcription factor, which promotes malignant progression in HNSCC. However, what role cross-talk between components of the TGF-ß and NF-κB pathways plays in altered activation of these pathways has not been established. Here, we show TGF-ß receptor II and TGF-ß-activated kinase 1 (TAK1) are predominantly expressed in a subset of HNSCC tumors with nuclear activation of NF-κB family member RELA (p65). Further, TGF-ß1 treatment induced sequential phosphorylation of TAK1, IKK, IκBα and RELA in human HNSCC lines. TAK1 enhances TGF-ß-induced NF-κB activation, as TAK1 siRNA knockdown decreased TGF-ß1-induced phosphorylation of IKK, IκB and RELA, degradation of IκBα, RELA nuclear translocation and DNA binding, and NF-κB-induced reporter and target gene transcription. Functionally, TAK1 siRNA inhibited cell proliferation, migration and invasion. Celastrol, a TAK1 inhibitor and anti-inflammatory compound used in traditional Chinese medicine, also decreased TGF-ß1-induced phosphorylation of TAK1 and RELA, and suppressed basal, TGF-ß1- and tumor necrosis factor-alpha (TNF-α)-induced NF-κB reporter gene activity. Celastrol also inhibited cell proliferation, while increasing sub-G0 DNA fragmentation and Annexin V markers of apoptosis. Furthermore, TGF-ß and RELA activation promoted SMAD7 expression. In turn, SMAD7 preferentially suppressed TGF-ß-induced SMAD and NF-κB reporters when compared with constitutive or TNF-α-induced NF-κB reporter gene activation. Thus, cross-talk by TGF-ß via TAK1 and NF-κB promotes the malignant phenotype of HNSCC. Moreover, NF-κB may contribute to the downstream attenuation of canonical TGF-ß signaling through increased SMAD7 expression. Celastrol highlights the therapeutic potential of agents targeting TAK1 as a key node in this pro-oncogenic TGF-ß-NF-κB signal pathway.

Pound-locking for characterization of superconducting microresonators.

We present a new application and implementation of the Pound-locking technique for the interrogation of superconducting microresonators. We discuss how by comparing against stable frequency sources this technique can be used to characterize properties of resonators that cannot be accessed using traditional methods. Specifically, by analyzing the noise spectra and the Allan deviation, we obtain valuable information about the nature of the noise in superconducting planar resonators. This technique also greatly improves the read-out accuracy and measurement throughput compared to conventional methods.

Supercritical fluid chromatography in research laboratories: design, development and implementation of an efficient generic screening for exploiting this technique in the achiral environment.

A new strategy for exploiting SFC in the achiral arena has been designed, developed and successfully implemented in our Analytical Technologies laboratories, in support of Drug Discovery. The development of a generic analytical SFC/MS screening protocol, following extensive evaluation of different stationary phase, modifier and gradient elution combinations, has enabled fast analytical method development for structurally diverse compounds within both specialised and high-throughput purification environments. Application of this approach into the daily routine has provided data on a large number and a wide variety of reaction mixtures. The results confirm the scope and generality of the strategy with more than 85% of targets being successfully resolved from their impurities.

Pre-concentration of naturally occurring radionuclides and the determination of (212)Pb from fresh waters.

A novel technique has been developed for determining the (212)Pb activity of fresh waters. This is of interest to environmental monitoring programmes that utilise gross α-activity methods to screen for anthropogenic radionuclides. The contribution from (212)Pb varies, and is difficult to experimentally measure due to its relatively short half-life (t(½) = 10.6 h) and low environmental activity (<0.1 Bq l(-1)). The use of a three-stage technique that encompasses a unique form of pre-concentration, separation and analysis by liquid scintillation counting allows a lower detection limit of 0.006 Bq l(-1) with a chemical yield of 92.5 ± 5.6%. The measurement can be obtained within 7 h of sample collection, and is calculated using the radioactive decay of (212)Bi. Other naturally occurring radionuclides may also be extracted using the pre-concentration stage of the technique, with efficiencies above 90% at a range of pH values.

Short-lived variations in the background gamma-radiation dose.

Sudden increases in the background gamma-radiation dose may occur due to the removal of (222)Rn and (220)Rn progeny from the atmosphere by wet deposition mechanisms. This contribution has been measured using a Geiger-Muller detector at the Atomic Weapons Establishment (Aldermaston, UK) during July 2005-April 2006. The results are approximated by a log-normal distribution and there were nine separate occurrences of the gamma-radiation dose exceeding 125% of the geometric mean value. The increases were associated with periods of heavy rainfall, although no correlation was evident between the dose rate and the amount of rainfall, as increased rainfall dilutes the activity further rather than increasing its atmospheric removal. The events were preceded by periods of fine weather and atmospheric stability that allow for the build-up of (222)Rn and (220)Rn progeny. Similar increases in gamma-radiation dose have been measured at a nearby monitoring station situated approximately 11 miles from Aldermaston. Increases in gamma-radiation dose during heavy rainfall have also been observed throughout the UK, that followed the trajectory of an air mass. All events decreased to typical values within 1-2 h as the water permeated into the ground below and the radioactivity decayed away.

Feather lead concentrations and (207)Pb/(206)Pb ratios reveal lead exposure history of California Condors (Gymnogyps californianus).

Lead poisoning is a primary factor impeding the survival and recovery of the critically endangered California Condor (Gymnogyps californianus). However, the frequency and magnitude of lead exposure in condors is not well-known in part because most blood lead monitoring occurs biannually, and biannual blood samples capture only approximately 10% of a bird's annual exposure history. We investigated the use of growing feathers from free-flying condors in California to establish a bird's lead exposure history. We show that lead concentration and stable lead isotopic composition analyses of sequential feather sections and concurrently collected blood samples provided a comprehensive history of lead exposure over the 2-4 month period of feather growth. Feather analyses identified exposure events not evident from blood monitoring efforts, and by fitting an empirically derived timeline to actively growing feathers, we were able to estimate the time frame for specific lead exposure events. Our results demonstrate the utility of using sequentially sampled feathers to reconstruct lead exposure history. Since exposure risk in individuals is one determinant of population health, our findings should increase the understanding of population-level effects from lead poisoning in condors; this information may also be helpful for other avian species potentially impacted by lead poisoning.

A serological study of Dirofilaria immitis in feral cats in Grenada, West Indies.

A study to determine the seroprevalence of Dirofilaria immitis was carried out in feral cats in Grenada. Of the 137 feral cats tested for circulating antibodies (IgG; lateral-flow immunoassay) and circulating antigens (Ag; enzyme-linked immunosorbent assay), 8% (95% confidence interval (CI) 3.5-12.5%) were antibody positive and 5.1% (95% CI 1.4-8.8%) were antigen positive. No significant difference between cats aged>1 to 4 years and cats less than 1 year of age was found (P>0.05, χ²). There was also no significant difference (P>0.05, χ²) between male and female cats. Dirofilaria immitis prevalence is relatively high in the feral cat population of Grenada. Evidence of D. immitis infection in feral cats coupled with the endemic nature of heartworm disease in dogs in Grenada leads us to suggest the introduction of heartworm prophylaxis in cats. To the authors' knowledge, this serological evidence of heartworm infection in feral cats in Grenada is the first report from the Caribbean region.