Formation of robust bound states of interacting microwave photons.

Systems of correlated particles appear in many fields of modern science and represent some of the most intractable computational problems in nature. The computational challenge in these systems arises when interactions become comparable to other energy scales, which makes the state of each particle depend on all other particles1. The lack of general solutions for the three-body problem and acceptable theory for strongly correlated electrons shows that our understanding of correlated systems fades when the particle number or the interaction strength increases. One of the hallmarks of interacting systems is the formation of multiparticle bound states2-9. Here we develop a high-fidelity parameterizable fSim gate and implement the periodic quantum circuit of the spin-½ XXZ model in a ring of 24 superconducting qubits. We study the propagation of these excitations and observe their bound nature for up to five photons. We devise a phase-sensitive method for constructing the few-body spectrum of the bound states and extract their pseudo-charge by introducing a synthetic flux. By introducing interactions between the ring and additional qubits, we observe an unexpected resilience of the bound states to integrability breaking. This finding goes against the idea that bound states in non-integrable systems are unstable when their energies overlap with the continuum spectrum. Our work provides experimental evidence for bound states of interacting photons and discovers their stability beyond the integrability limit.

Accurately computing the electronic properties of a quantum ring.

A promising approach to study condensed-matter systems is to simulate them on an engineered quantum platform1-4. However, the accuracy needed to outperform classical methods has not been achieved so far. Here, using 18 superconducting qubits, we provide an experimental blueprint for an accurate condensed-matter simulator and demonstrate how to investigate fundamental electronic properties. We benchmark the underlying method by reconstructing the single-particle band structure of a one-dimensional wire. We demonstrate nearly complete mitigation of decoherence and readout errors, and measure the energy eigenvalues of this wire with an error of approximately 0.01 rad, whereas typical energy scales are of the order of 1 rad. Insight into the fidelity of this algorithm is gained by highlighting the robust properties of a Fourier transform, including the ability to resolve eigenenergies with a statistical uncertainty of 10-4 rad. We also synthesize magnetic flux and disordered local potentials, which are two key tenets of a condensed-matter system. When sweeping the magnetic flux we observe avoided level crossings in the spectrum, providing a detailed fingerprint of the spatial distribution of local disorder. By combining these methods we reconstruct electronic properties of the eigenstates, observing persistent currents and a strong suppression of conductance with added disorder. Our work describes an accurate method for quantum simulation5,6 and paves the way to study new quantum materials with superconducting qubits.

Perceived relevance mediates the relationship between professional identity and attitudes towards interprofessional education in first-year university students.

The strength of health science students' identification with their chosen profession is associated with their attitudes towards interprofessional education (IPE). However, little is known about the factors that might mediate this relationship. In this article, we examine the relationships between professional identification, communication and teamwork skills, perceived relevance of IPE, and positive and negative attitudes towards IPE. A sample of 444 first-year university students from 25 health science professions enrolled in a first-year interprofessional program participated in this research by completing a questionnaire. Data were analysed using path analysis. Positive IPE attitudes were more strongly endorsed than negative IPE attitudes. Perceived relevance of IPE to future careers was the strongest predictor of both positive and negative attitudes to IPE, and fully mediated the effect of professional identity. Self-reported communication and teamwork skills were a significant negative predictor of negative attitudes to IPE only, and the effect was not mediated by perceived relevance. These findings indicate that IPE may be particularly challenging for students who do not have confidence in their abilities to communicate and work effectively in teams. Building these skills through alternative communication technologies may decrease negative attitudes. In order to maintain or increase positive attitudes towards IPE in introductory programs that span professions, the curriculum needs to be designed to demonstrate relevance to the future careers of participating students.

Dynamics of magnetization at infinite temperature in a Heisenberg spin chain.

Understanding universal aspects of quantum dynamics is an unresolved problem in statistical mechanics. In particular, the spin dynamics of the one-dimensional Heisenberg model were conjectured as to belong to the Kardar-Parisi-Zhang (KPZ) universality class based on the scaling of the infinite-temperature spin-spin correlation function. In a chain of 46 superconducting qubits, we studied the probability distribution of the magnetization transferred across the chain's center, [Formula: see text]. The first two moments of [Formula: see text] show superdiffusive behavior, a hallmark of KPZ universality. However, the third and fourth moments ruled out the KPZ conjecture and allow for evaluating other theories. Our results highlight the importance of studying higher moments in determining dynamic universality classes and provide insights into universal behavior in quantum systems.

Stable quantum-correlated many-body states through engineered dissipation.

Engineered dissipative reservoirs have the potential to steer many-body quantum systems toward correlated steady states useful for quantum simulation of high-temperature superconductivity or quantum magnetism. Using up to 49 superconducting qubits, we prepared low-energy states of the transverse-field Ising model through coupling to dissipative auxiliary qubits. In one dimension, we observed long-range quantum correlations and a ground-state fidelity of 0.86 for 18 qubits at the critical point. In two dimensions, we found mutual information that extends beyond nearest neighbors. Lastly, by coupling the system to auxiliaries emulating reservoirs with different chemical potentials, we explored transport in the quantum Heisenberg model. Our results establish engineered dissipation as a scalable alternative to unitary evolution for preparing entangled many-body states on noisy quantum processors.

Artificial ionospheric layers during pump frequency stepping near the 4th gyroharmonic at HAARP.

We report on artificial descending plasma layers created in the ionosphere F region by high-power high-frequency (HF) radio waves from High-frequency Active Auroral Research Program at frequencies f(0) near the fourth electron gyroharmonic 4f(ce). The data come from concurrent measurements of the secondary escaping radiation from the HF-pumped ionosphere, also known as stimulated electromagnetic emission, reflected probing signals at f(0), and plasma line radar echoes. The artificial layers appeared only for injections along the magnetic field and f(0)>4f(ce) at the nominal HF interaction altitude in the background ionosphere. Their average downward speed ~0.5 km/s holds until the terminal altitude where the local fourth gyroharmonic matches f(0). The total descent increases with the nominal offset f(0)-4f(ce).

Noise-resilient edge modes on a chain of superconducting qubits.

Inherent symmetry of a quantum system may protect its otherwise fragile states. Leveraging such protection requires testing its robustness against uncontrolled environmental interactions. Using 47 superconducting qubits, we implement the one-dimensional kicked Ising model, which exhibits nonlocal Majorana edge modes (MEMs) with [Formula: see text] parity symmetry. We find that any multiqubit Pauli operator overlapping with the MEMs exhibits a uniform late-time decay rate comparable to single-qubit relaxation rates, irrespective of its size or composition. This characteristic allows us to accurately reconstruct the exponentially localized spatial profiles of the MEMs. Furthermore, the MEMs are found to be resilient against certain symmetry-breaking noise owing to a prethermalization mechanism. Our work elucidates the complex interplay between noise and symmetry-protected edge modes in a solid-state environment.

Realizing topologically ordered states on a quantum processor.

The discovery of topological order has revised the understanding of quantum matter and provided the theoretical foundation for many quantum error­correcting codes. Realizing topologically ordered states has proven to be challenging in both condensed matter and synthetic quantum systems. We prepared the ground state of the toric code Hamiltonian using an efficient quantum circuit on a superconducting quantum processor. We measured a topological entanglement entropy near the expected value of ­ln2 and simulated anyon interferometry to extract the braiding statistics of the emergent excitations. Furthermore, we investigated key aspects of the surface code, including logical state injection and the decay of the nonlocal order parameter. Our results demonstrate the potential for quantum processors to provide insights into topological quantum matter and quantum error correction.

Distinctive organization of genes for light-harvesting proteins in the cryptophyte alga Rhodomonas.

Cryptophyte algae contain two kinds of light-harvesting protein, phycobiliproteins and chlorophyll a,c-binding proteins. The beta subunit of the phycobiliprotein phycoerythrin (PE) is encoded in the chloroplast. Genes for the other PE polypeptides are located in the nucleus but little is known of their organization. We cloned and sequenced six cpeA genes encoding the phycoerythrin alpha subunit from a genomic library of the cryptophyte Rhodomonas CS24. Derived peptide sequences of the cpeA genes show that alpha subunits occur in at least two forms, a longer alpha1 form and a shorter alpha2 form. Remarkably, all six cpeA genes occur in divergent pairs encoding one alpha1 and one alpha2 subunit. Four cac genes encoding chlorophyll a,c-binding proteins were cloned and sequenced and also found to occur in divergent pairs comprising one cac1 and one cac2 gene. Inspection of the predicted targeting sequences of the alpha1 and alpha2 phycoerythrin polypeptides shows that only the alpha1 polypeptides have a thylakoid lumen targeting sequence, corresponding to the TAT pathway. Given the previously reported lack of a lumen-targeting sequence on the beta subunit, we propose a novel import mechanism in which the entire alpha1alpha2 betabeta phycoerythrin complex is assembled in the stroma and transported into the thylakoid under the direction of the single targeting sequence on the alpha1 protein. The FAP motif implicated in plastid targeting in diatoms appears to be conserved in this cryptophyte.

Cloning and analysis of the spinosad biosynthetic gene cluster of Saccharopolyspora spinosa.

BACKGROUND: Spinosad is a mixture of novel macrolide secondary metabolites produced by Saccharopolyspora spinosa. It is used in agriculture as a potent insect control agent with exceptional safety to non-target organisms. The cloning of the spinosyn biosynthetic gene cluster provides the starting materials for the molecular genetic manipulation of spinosad yields, and for the production of novel derivatives containing alterations in the polyketide core or in the attached sugars. RESULTS: We cloned the spinosad biosynthetic genes by molecular probing, complementation of blocked mutants, and cosmid walking, and sequenced an 80 kb region. We carried out gene disruptions of some of the genes and analyzed the mutants for product formation and for the bioconversion of intermediates in the spinosyn pathway. The spinosyn gene cluster contains five large open reading frames that encode a multifunctional, multi-subunit type I polyketide synthase (PKS). The PKS cluster is flanked on one side by genes involved in the biosynthesis of the amino sugar forosamine, in O-methylations of rhamnose, in sugar attachment to the polyketide, and in polyketide cross-bridging. Genes involved in the early common steps in the biosynthesis of forosamine and rhamnose, and genes dedicated to rhamnose biosynthesis, were not located in the 80 kb cluster. CONCLUSIONS: Most of the S. spinosa genes involved in spinosyn biosynthesis are found in one 74 kb cluster, though it does not contain all of the genes required for the essential deoxysugars. Characterization of the clustered genes suggests that the spinosyns are synthesized largely by mechanisms similar to those used to assemble complex macrolides in other actinomycetes. However, there are several unusual genes in the spinosyn cluster that could encode enzymes that generate the most striking structural feature of these compounds, a tetracyclic polyketide aglycone nucleus.

Conjugal transfer of cosmid DNA from Escherichia coli to Saccharopolyspora spinosa: effects of chromosomal insertions on macrolide A83543 production.

Cosmid pOJ436, containing large inserts of Saccharopolyspora spinosa (Ss) DNA, was transferred by conjugation from Escherichia coli to Ss an integrated into the chromosome, apparently by homologous recombination, at high frequencies (10(-5) to 10(-4) per recipient). Transfer was mediated by the plasmid RP4 (RK2) transfer functions in E. coli, and the RK2 oriT function located on pOJ436 [Bierman et al., Gene 116 (1992) 43-49]. pOJ436 lacking Ss DNA, or containing a small insert (approx. 2 kb) of Ss DNA, conjugated from E. coli and integrated at either of two bacteriophage phi C31 attB sites at low frequency (approx. 10(-7) per recipient). Exconjugants containing homologous inserts or inserts at the phi C31 attB sites were stable in the absence of antibiotic selection, and most produced control levels of tetracyclic macrolide A83543 factors. Some exconjugants contained similar kinds of large deletions and were defective in macrolide production.

Vitamin A supplementation reduces measles morbidity in young African children: a randomized, placebo-controlled, double-blind trial.

The effects of vitamin A supplementation on measles morbidity are unclear. Sixty hospitalized children aged 4-24 mo with complicated measles received a World Health Organization--(WHO) recommended dose of vitamin A or placebo. The two groups were comparable in known covariants of measles severity: weight-for-age percentiles, overcrowding, rash, total lymphocytes, and serum concentrations of zinc, albumin, prealbumin, retinol-binding protein, and vitamins A and E. Ninety percent of the patients had hyporetinemia. Integrated morbidity scores, determined by severity of condition (eg, diarrhoea, herpes, and respiratory-tract infection) were assigned on day 8 and 6 wk and 6 mo; these were reduced by 82%, 61%, and 85%, respectively, in the supplemented group, which was mainly due to reduced respiratory-tract infection. There was one death in the placebo group. At 6 wk weight gain was significant in the supplemented group. Despite the selected sample, attention to multiple covariates enhances the validity of the data obtained and supports the current WHO recommendations for vitamin A supplementation during measles.

Vitamin A supplementation enhances specific IgG antibody levels and total lymphocyte numbers while improving morbidity in measles.

The effect of vitamin A supplementation on selected factors of immunity was tested in African children (ages 4 to 24 months with complicated measles) during a randomized double-blind intervention trial. Placebo (n = 31) and treated groups (n = 29) had similar baseline characteristics. The supplemented group had significant reductions in morbidity (expressed as integrated morbidity scores) during the acute (Day 8, P = 0.006) and chronic (Day 42, P = 0.02; 6 months; P = 0.002) phases. In the treated group there was an increase in total number of lymphocytes (Day 42, P = 0.05) and measles IgG antibody concentrations (Day 8, P = 0.02), both of which have consistently been previously shown to correlate more closely with outcome in measles than other immunologic, clinical and radiologic factors. Interleukin 2 and plasma complement values were unaffected by vitamin A supplementation. These findings reinforce results from animal studies that show that the pathways of vitamin A activity in decreasing morbidity and mortality are partly founded on selective immunopotentiation.

Membrane fluidity alterations in a cytochrome P-450-deficient mutant of Candida albicans.

A cytochrome P450-deficient mutant of the pathogenic fungus, Candida albicans, which accumulates exclusively 14 alpha-methylsterols in place of the normal end product sterol, ergosterol, was examined for alterations in membrane fluidity by electron paramagnetic resonance. The results using four nitroxyl spin labels indicated that exponential phase cultures of the mutant strain, D10, had a uniformly more rigid membrane than similarly grown wild type. Since D10 shows a sterol spectrum similar to that of wild type cells treated with imidazole and triazole antifungal agents, many of the physiological effects reported as the result of azole application may be the result of alterations in membrane fluidity.

Micronutrient utilisation during measles treated with vitamin A or placebo.

Micronutrients (zinc, vitamins A and E) and related proteins (retinol binding protein (RBP), prealbumin, albumin) were measured in the serum of African children with measles, and the changes induced in these by vitamin A supplementation (offered in a randomised, double blind, placebo controlled trial) were studied. All these substances were significantly reduced early in the exanthem in measles patients as compared to controls; they attained control values by day 8 after the rash, except for serum albumin which became normal by day 42. Vitamin A and prealbumin levels on day 8 were significantly increased in the supplemented over the placebo group. Vitamin A levels in serum correlated with those of RBP, prealbumin and zinc. These findings strengthen the hypothesis that hyporetinemia during measles is the consequence of impaired mobilisation. Our results indicate that our patients did not have pre-existing low liver stores. Accordingly, the results obtained here provide rational support for the recommendation that vitamin A should be given to all children with severe measles, even in communities where vitamin A deficiency is not a recognised public health problem.

The superficial musculoaponeurotic system of the face: a model explored.

Regional differences in the integument of the body are explained, at least in part, by differences in fascial arrangements. In the face, where the skin is more mobile due to the action of the underlying facial muscles, fascial organisation is important for support and separation of muscle groups. This study used bequeathed cadaver material to investigate a current model of the SMAS proposed by Macchi et al., the original boundaries of which were explored and extended using both histology and gross dissection. As a clearly identifiable structure spanning the lateral and midface, the SMAS in the specimen supported the model proposed by Macchi et al. The three main findings that support the model were the layered morphological appearance of the SMAS, its progression from fibrous to aponeurotic in a lateral to medial direction, and the enveloping of the zygomaticus musculature. Extension beyond the proposed model into the temporal region was observed, but nasal and forehead regions showed no evidence of SMAS, while its presence in the cervical platysma region remained inconclusive. Fascial and soft tissue variability was considerable within facial regions of the examined specimen, helping to explain the debate around the SMAS in the literature.

Curative resection for low rectal adenocarcinoma: abdomino-perineal vs anterior resection.

OBJECTIVE: Local recurrence after abdomino-perineal excision of the rectum for tumours has been reported to occur in up to a third of patients in contrast to 4% after restorative anterior resection. METHOD: Low rectal tumours were defined as tumours within 8 cm of the anal verge and were treated by either stapled low anterior resection (SLAR) or abdomino-perineal excision of the rectum (APER). One hundred and seventy-eight patients with tumours in the lower third of the rectum (30% of 591 rectal cancers) underwent surgical resection between 1980 and 2001. Data were collected prospectively; 68 (38%) had SLAR and 110 (62%) had APER with median follow up of approximately 12 years; 54 SLAR (79%) and 76 APER (69%) had curative procedures on clinical and pathological criteria. RESULTS: Local and distant recurrence occurred in seven (13%) and eight (15%) patients in the SLAR group and six (8%) and 14 (18%) patients in the APER group, respectively. Overall 5-year survival was 63% and 60% in the SLAR and APER groups, respectively CONCLUSION: For rectal cancers within 8 cm of the anal verge, both procedures achieved equivalent results measured by low local recurrence rates and overall survival.

Pneumocystis carinii dihydrofolate reductase used to screen potential antipneumocystis drugs.

Pneumocystis carinii was obtained in high yield from the lungs of immunosuppressed rats by rupturing mammalian host cells, washing away the soluble mammalian dihydrofolate reductase, and harvesting intact organisms in association with the mammalian plasma membranes. P. carinii dihydrofolate reductase, measured in the 100,000 x g supernatant from sonicated organisms, was obtained in yields ranging up to 62 IU per rat. The enzyme prepared in the presence of protease inhibitors was stable when frozen in liquid nitrogen. P. carinii dihydrofolate reductase differed from the mammalian enzyme in that the former was slightly inhibited by 150 mM KCl, whereas the latter was stimulated over twofold by 150 mM KCl. The standard assay for P. carinii dihydrofolate reductase contained 0.12 mM NADPH and 92 microM dihydrofolic acid. Under these conditions, the 50% inhibitory concentrations of the known inhibitors trimethoprim, trimetrexate, and pyrimethamine were 12 microM, 42 nM, and 3.8 microM, respectively. These standard compounds were also tested against dihydrofolate reductase from rat liver to allow an assessment of the selectivity of the drugs. Although it was the least potent, trimethoprim was the most selective. Pyrimethamine was more potent but was nonselective. Trimetrexate was extremely potent but was selective for mammalian dihydrofolate reductase. A series of experimental compounds was obtained from the National Cancer Institute and other sources through the Developmental Therapeutics Branch of the Division of AIDS at the National Institute of Allergy and Infectious Diseases. Among the first 87 compounds tested, 11 had 50% inhibitory concentrations below that of trimetrexate and 3 were more selective than trimethoprim. The most promising compounds in this original group were chemically related to methotrexate.

How can experiences of patients and carers influence the clinical care of large bowel cancer?

A qualitative project was designed to investigate the care of large bowel cancer from patients' and carers' perspectives using semi-structured interviews; tape-recorded, transcribed and analysed; to identify recurrent themes. Forty-nine patients treated surgically for bowel cancer from three hospital trusts in West Surrey were visited at home, and eight of their carers attended a focus group from a choice of three geographical locations. Five main themes identified: experience of symptoms; general practitioner (GP) management; impact of diagnosis; perceptions of clinical care and treatment; information needs. Results showed that patients and carers were ignorant of the symptoms and signs of large bowel cancer and wanted more information. They were satisfied when the GP took symptoms seriously and referred promptly. Three groups of patients were particularly vulnerable: those requiring stomas (25), those diagnosed with polyps initially (11) and patients admitted as an emergency (7). Specialist nurses were seen as the main source of written information and support, which was most needed at the time of diagnosis and discharge. The public needs more accessible information about the symptoms and signs of bowel cancer. Referral to multiprofessional bowel cancer teams is essential to provide appropriate support and clear information from the time of diagnosis throughout the care pathway. Recommended strategies for improving clinical care are outlined.