Interaction-based quantum metrology showing scaling beyond the Heisenberg limit

Quantum metrology aims to use entanglement and other quantum resources to improve precision measurement. An interferometer using N independent particles to measure a parameter χ can achieve at best the standard quantum limit of sensitivity, δχ?∝?N(-1/2). However, using N entangled particles and exotic states, such an interferometer can in principle achieve the Heisenberg limit, δχ?∝?N(-1). Recent theoretical work has argued that interactions among particles may be a valuable resource for quantum metrology, allowing scaling beyond the Heisenberg limit. Specifically, a k-particle interaction will produce sensitivity δχ?∝?N(-k) with appropriate entangled states and δχ?∝?N(-(k-1/2)) even without entanglement. Here we demonstrate 'super-Heisenberg' scaling of δχ?∝?N(-3/2) in a nonlinear, non-destructive measurement of the magnetization of an atomic ensemble. We use fast optical nonlinearities to generate a pairwise photon-photon interaction (corresponding to k = 2) while preserving quantum-noise-limited performance. We observe super-Heisenberg scaling over two orders of magnitude in N, limited at large numbers by higher-order nonlinear effects, in good agreement with theory. For a measurement of limited duration, super-Heisenberg scaling allows the nonlinear measurement to overtake in sensitivity a comparable linear measurement with the same number of photons. In other situations, however, higher-order nonlinearities prevent this crossover from occurring, reflecting the subtle relationship between scaling and sensitivity in nonlinear systems. Our work shows that interparticle interactions can improve sensitivity in a quantum-limited measurement, and experimentally demonstrates a new resource for quantum metrology.     

Fault lubrication during earthquakes

The determination of rock friction at seismic slip rates (about 1?m?s(-1)) is of paramount importance in earthquake mechanics, as fault friction controls the stress drop, the mechanical work and the frictional heat generated during slip. Given the difficulty in determining friction by seismological methods, elucidating constraints are derived from experimental studies. Here we review a large set of published and unpublished experiments (～300) performed in rotary shear apparatus at slip rates of 0.1-2.6?m?s(-1). The experiments indicate a significant decrease in friction (of up to one order of magnitude), which we term fault lubrication, both for cohesive (silicate-built, quartz-built and carbonate-built) rocks and non-cohesive rocks (clay-rich, anhydrite, gypsum and dolomite gouges) typical of crustal seismogenic sources. The available mechanical work and the associated temperature rise in the slipping zone trigger a number of physicochemical processes (gelification, decarbonation and dehydration reactions, melting and so on) whose products are responsible for fault lubrication. The similarity between (1) experimental and natural fault products and (2) mechanical work measures resulting from these laboratory experiments and seismological estimates suggests that it is reasonable to extrapolate experimental data to conditions typical of earthquake nucleation depths (7-15?km). It seems that faults are lubricated during earthquakes, irrespective of the fault rock composition and of the specific weakening mechanism involved.     

FAS and NF-κB signalling modulate dependence of lung cancers on mutant EGFR

Human lung adenocarcinomas with activating mutations in EGFR (epidermal growth factor receptor) often respond to treatment with EGFR tyrosine kinase inhibitors (TKIs), but the magnitude of tumour regression is variable and transient. This heterogeneity in treatment response could result from genetic modifiers that regulate the degree to which tumour cells are dependent on mutant EGFR. Through a pooled RNA interference screen, we show that knockdown of FAS and several components of the NF-κB pathway specifically enhanced cell death induced by the EGFR TKI erlotinib in EGFR-mutant lung cancer cells. Activation of NF-κB through overexpression of c-FLIP or IKK (also known as CFLAR and IKBKB, respectively), or silencing of IκB (also known as NFKBIA), rescued EGFR-mutant lung cancer cells from EGFR TKI treatment. Genetic or pharmacologic inhibition of NF-κB enhanced erlotinib-induced apoptosis in erlotinib-sensitive and erlotinib-resistant EGFR-mutant lung cancer models. Increased expression of the NF-κB inhibitor IκB predicted for improved response and survival in EGFR-mutant lung cancer patients treated with EGFR TKI. These data identify NF-κB as a potential companion drug target, together with EGFR, in EGFR-mutant lung cancers and provide insight into the mechanisms by which tumour cells escape from oncogene dependence.     

Prion propagation and toxicity in vivo occur in two distinct mechanistic phases

Mammalian prions cause fatal neurodegenerative conditions including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. Prion infections are typically associated with remarkably prolonged but highly consistent incubation periods followed by a rapid clinical phase. The relationship between prion propagation, generation of neurotoxic species and clinical onset has remained obscure. Prion incubation periods in experimental animals are known to vary inversely with expression level of cellular prion protein. Here we demonstrate that prion propagation in brain proceeds via two distinct phases: a clinically silent exponential phase not rate-limited by prion protein concentration which rapidly reaches a maximal prion titre, followed by a distinct switch to a plateau phase. The latter determines time to clinical onset in a manner inversely proportional to prion protein concentration. These findings demonstrate an uncoupling of infectivity and toxicity. We suggest that prions themselves are not neurotoxic but catalyse the formation of such species from PrP(C). Production of neurotoxic species is triggered when prion propagation saturates, leading to a switch from autocatalytic production of infectivity (phase 1) to a toxic (phase 2) pathway.     

Programming the magnitude and persistence of antibody responses with innate immunity

Many successful vaccines induce persistent antibody responses that can last a lifetime. The mechanisms by which they do so remain unclear, but emerging evidence indicates that they activate dendritic cells via Toll-like receptors (TLRs). For example, the yellow fever vaccine YF-17D, one of the most successful empiric vaccines ever developed, activates dendritic cells via multiple TLRs to stimulate proinflammatory cytokines. Triggering specific combinations of TLRs in dendritic cells can induce synergistic production of cytokines, which results in enhanced T-cell responses, but its impact on antibody responses remain unknown. Learning the critical parameters of innate immunity that program such antibody responses remains a major challenge in vaccinology. Here we demonstrate that immunization of mice with synthetic nanoparticles containing antigens plus ligands that signal through TLR4 and TLR7 induces synergistic increases in antigen-specific, neutralizing antibodies compared to immunization with nanoparticles containing antigens plus a single TLR ligand. Consistent with this there was enhanced persistence of germinal centres and of plasma-cell responses, which persisted in the lymph nodes for >1.5 years. Surprisingly, there was no enhancement of the early short-lived plasma-cell response relative to that observed with single TLR ligands. Molecular profiling of activated B cells, isolated 7 days after immunization, indicated that there was early programming towards B-cell memory. Antibody responses were dependent on direct triggering of both TLRs on B cells and dendritic cells, as well as on T-cell help. Immunization protected completely against lethal avian and swine influenza virus strains in mice, and induced robust immunity against pandemic H1N1 influenza in rhesus macaques.     

A Pluto-like radius and a high albedo for the dwarf planet Eris from an occultation

The dwarf planet Eris is a trans-Neptunian object with an orbital eccentricity of 0.44, an inclination of 44 degrees and a surface composition very similar to that of Pluto. It resides at present at 95.7 astronomical units (1?AU is the Earth-Sun distance) from Earth, near its aphelion and more than three times farther than Pluto. Owing to this great distance, measuring its size or detecting a putative atmosphere is difficult. Here we report the observation of a multi-chord stellar occultation by Eris on 6 November 2010 UT. The event is consistent with a spherical shape for Eris, with radius 1,163?±?6?kilometres, density 2.52?±?0.05 grams per cm(3) and a high visible geometric albedo, Pv = 0.96(+0.09)(-0.04). No nitrogen, argon or methane atmospheres are detected with surface pressure larger than ～1?nanobar, about 10,000 times more tenuous than Pluto's present atmosphere. As Pluto's radius is estimated to be between 1,150 and 1,200 kilometres, Eris appears as a Pluto twin, with a bright surface possibly caused by a collapsed atmosphere, owing to its cold environment. We anticipate that this atmosphere may periodically sublimate as Eris approaches its perihelion, at 37.8 astronomical units from the Sun.     

Role of sulphuric acid, ammonia and galactic cosmic rays in atmospheric aerosol nucleation

Atmospheric aerosols exert an important influence on climate through their effects on stratiform cloud albedo and lifetime and the invigoration of convective storms. Model calculations suggest that almost half of the global cloud condensation nuclei in the atmospheric boundary layer may originate from the nucleation of aerosols from trace condensable vapours, although the sensitivity of the number of cloud condensation nuclei to changes of nucleation rate may be small. Despite extensive research, fundamental questions remain about the nucleation rate of sulphuric acid particles and the mechanisms responsible, including the roles of galactic cosmic rays and other chemical species such as ammonia. Here we present the first results from the CLOUD experiment at CERN. We find that atmospherically relevant ammonia mixing ratios of 100 parts per trillion by volume, or less, increase the nucleation rate of sulphuric acid particles more than 100-1,000-fold. Time-resolved molecular measurements reveal that nucleation proceeds by a base-stabilization mechanism involving the stepwise accretion of ammonia molecules. Ions increase the nucleation rate by an additional factor of between two and more than ten at ground-level galactic-cosmic-ray intensities, provided that the nucleation rate lies below the limiting ion-pair production rate. We find that ion-induced binary nucleation of H(2)SO(4)-H(2)O can occur in the mid-troposphere but is negligible in the boundary layer. However, even with the large enhancements in rate due to ammonia and ions, atmospheric concentrations of ammonia and sulphuric acid are insufficient to account for observed boundary-layer nucleation.