In a superconductor, absorption of photons with an energy below the superconducting gap leads to redistribution of quasiparticles over energy and thus induces a strong nonequilibrium quasiparticle ...energy distribution. We have measured the electrodynamic response, quality factor, and resonant frequency of a superconducting aluminium microwave resonator as a function of microwave power and temperature. Below 200 mK, both the quality factor and resonant frequency decrease with increasing microwave power, consistent with the creation of excess quasiparticles due to microwave absorption. Counterintuitively, above 200 mK, the quality factor and resonant frequency increase with increasing power. We demonstrate that the effect can only be understood by a nonthermal quasiparticle distribution.
Parkinson's disease, the most common age-related movement disorder, is a progressive neurodegenerative disease with unclear etiology. Key neuropathological hallmarks are Lewy bodies and Lewy ...neurites: neuronal inclusions immunopositive for the protein α-synuclein. In-depth ultrastructural analysis of Lewy pathology is crucial to understanding pathogenesis of this disease. Using correlative light and electron microscopy and tomography on postmortem human brain tissue from Parkinson's disease brain donors, we identified α-synuclein immunopositive Lewy pathology and show a crowded environment of membranes therein, including vesicular structures and dysmorphic organelles. Filaments interspersed between the membranes and organelles were identifiable in many but not all α-synuclein inclusions. Crowding of organellar components was confirmed by stimulated emission depletion (STED)-based super-resolution microscopy, and high lipid content within α-synuclein immunopositive inclusions was corroborated by confocal imaging, Fourier-transform coherent anti-Stokes Raman scattering infrared imaging and lipidomics. Applying such correlative high-resolution imaging and biophysical approaches, we discovered an aggregated protein-lipid compartmentalization not previously described in the Parkinsons' disease brain.
We discuss how reactive and dissipative nonlinearities affect the intrinsic response of superconducting thin-film resonators. We explain how most, if not all, of the complex phenomena commonly seen ...can be described by a model in which the underlying resonance is a single-pole Lorentzian, but whose centre frequency and quality factor change as external parameters, such as readout power and frequency, are varied. What is seen during a vector-network-analyser measurement is series of samples taken from an ideal Lorentzian that is shifting and spreading as the readout frequency is changed. According to this model, it is perfectly proper to refer to, and measure, the resonant frequency and quality factor of the underlying resonance, even though the swept-frequency curves appear highly distorted and hysteretic. In those cases where the resonance curve is highly distorted, the specific shape of the trajectory in the Argand plane gives valuable insights into the second-order physical processes present. We discuss the formulation and consequences of this approach in the case of nonlinear kinetic inductance, two-level-system loss, quasiparticle generation, and a generic model based on a power-law form. The generic model captures the key features of specific dissipative nonlinearities, but additionally leads to insights into how general dissipative processes create characteristic forms in the Argand plane. We provide detailed formulations in each case, and indicate how they lead to the wide variety of phenomena commonly seen in experimental data. We also explain how the properties of the underlying resonance can be extracted from this data. Overall, our paper provides a self-contained compendium of behaviour that will help practitioners interpret and determine important parameters from distorted swept-frequency measurements.
In this study, we evaluate the suitability of using DC-biased aluminium resonators as low-frequency kinetic inductance detectors capable of operating in the frequency range of 50-120 GHz. Our ...analysis routine for supercurrent-biased resonators is based on the Usadel equations and gives outputs including density of states, complex conductivities, transmission line properties, and quasiparticle lifetimes. Results from our analysis confirm previous experimental observations on resonant frequency tuneability and retention of high quality factor. Crucially, our analysis suggests that DC-biased resonators demonstrate significantly suppressed superconducting density of states gap. Consequently these resonators have lower frequency detection threshold and are suitable materials for low-frequency kinetic inductance detectors.
Genotypic sequencing for drug-resistant strains of HIV can guide the choice of antiretroviral therapy.
To assess the cost-effectiveness of genotypic resistance testing for patients acquiring drug ...resistance through failed treatment (secondary resistance) and those infected with resistant virus (primary resistance).
Cost-effectiveness analysis with an HIV simulation model incorporating CD4 cell count and HIV RNA level as predictors of disease progression.
Published randomized trials and data from the Multicenter AIDS Cohort Study, the national AIDS Cost and Services Utilization Survey, the Red Book, and an institutional cost-accounting system.
HIV-infected patients in the United States with baseline CD4 counts of 0.250 x 10(9) cells/L.
Lifetime.
Societal.
Genotypic resistance testing and clinical judgment, compared with clinical judgment alone, in two contexts: after initial treatment failure (secondary resistance testing) and before initiation of antiretroviral therapy (primary resistance testing).
Life expectancy, quality-adjusted life expectancy, and cost-effectiveness in dollars per quality-adjusted life-year (QALY) gained.
Secondary resistance testing increased life expectancy by 3 months, at a cost of $17 900 per QALY gained. The cost-effectiveness of primary resistance testing was $22 300 per QALY gained with a 20% prevalence of primary resistance but increased to $69 000 per QALY gained with 4% prevalence.
The cost-effectiveness ratio for secondary resistance testing remained under $25 000 per QALY gained, even when effectiveness and cost of testing and antiretroviral therapy, quality-of-life weights, and discount rate were varied.
Genotypic antiretroviral resistance testing following antiretroviral failure is cost-effective. Primary resistance testing also seems to be reasonably cost-effective and will become more so as the prevalence of primary resistance increases.
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