Observation of a discrete time crystal.

Spontaneous symmetry breaking is a fundamental concept in many areas of physics, including cosmology, particle physics and condensed matter. An example is the breaking of spatial translational symmetry, which underlies the formation of crystals and the phase transition from liquid to solid. Using the analogy of crystals in space, the breaking of translational symmetry in time and the emergence of a 'time crystal' was recently proposed, but was later shown to be forbidden in thermal equilibrium. However, non-equilibrium Floquet systems, which are subject to a periodic drive, can exhibit persistent time correlations at an emergent subharmonic frequency. This new phase of matter has been dubbed a 'discrete time crystal'. Here we present the experimental observation of a discrete time crystal, in an interacting spin chain of trapped atomic ions. We apply a periodic Hamiltonian to the system under many-body localization conditions, and observe a subharmonic temporal response that is robust to external perturbations. The observation of such a time crystal opens the door to the study of systems with long-range spatio-temporal correlations and novel phases of matter that emerge under intrinsically non-equilibrium conditions.

Eliminating Leakage Errors in Hyperfine Qubits.

Population leakage outside the qubit subspace presents a particularly harmful source of error that cannot be handled by standard error correction methods. Using a trapped ^{171}Yb^{+} ion, we demonstrate an optical pumping scheme to suppress leakage errors in atomic hyperfine qubits. The selection rules and narrow linewidth of a quadrupole transition are used to selectively pump population out of leakage states and back into the qubit subspace. Each pumping cycle reduces the leakage population by a factor of ∼3, allowing for an exponential suppression in the number of cycles. We use interleaved randomized benchmarking on the qubit subspace to show that this pumping procedure has negligible side effects on the qubit subspace, bounding the induced qubit memory error by ≤2.0(8)×10^{-5} per cycle, and qubit population decay to ≤1.4(3)×10^{-7} per cycle. These results clear a major obstacle for implementations of quantum error correction and error mitigation protocols.

Erratum: Discrete Time Crystals: Rigidity, Criticality, and Realizations [Phys. Rev. Lett. 118, 030401 (2017)].

This corrects the article DOI: 10.1103/PhysRevLett.118.030401.

Discrete Time Crystals: Rigidity, Criticality, and Realizations.

Despite being forbidden in equilibrium, spontaneous breaking of time translation symmetry can occur in periodically driven, Floquet systems with discrete time-translation symmetry. The period of the resulting discrete time crystal is quantized to an integer multiple of the drive period, arising from a combination of collective synchronization and many body localization. Here, we consider a simple model for a one-dimensional discrete time crystal which explicitly reveals the rigidity of the emergent oscillations as the drive is varied. We numerically map out its phase diagram and compute the properties of the dynamical phase transition where the time crystal melts into a trivial Floquet insulator. Moreover, we demonstrate that the model can be realized with current experimental technologies and propose a blueprint based upon a one dimensional chain of trapped ions. Using experimental parameters (featuring long-range interactions), we identify the phase boundaries of the ion-time-crystal and propose a measurable signature of the symmetry breaking phase transition.

Floquet Symmetry-Protected Topological Phases in Cold-Atom Systems.

We propose and analyze two distinct routes toward realizing interacting symmetry-protected topological (SPT) phases via periodic driving. First, we demonstrate that a driven transverse-field Ising model can be used to engineer complex interactions which enable the emulation of an equilibrium SPT phase. This phase remains stable only within a parametric time scale controlled by the driving frequency, beyond which its topological features break down. To overcome this issue, we consider an alternate route based upon realizing an intrinsically Floquet SPT phase that does not have any equilibrium analog. In both cases, we show that disorder, leading to many-body localization, prevents runaway heating and enables the observation of coherent quantum dynamics at high energy densities. Furthermore, we clarify the distinction between the equilibrium and Floquet SPT phases by identifying a unique micromotion-based entanglement spectrum signature of the latter. Finally, we propose a unifying implementation in a one-dimensional chain of Rydberg-dressed atoms and show that protected edge modes are observable on realistic experimental time scales.

Nisin and lysostaphin activity against preformed biofilm of Staphylococcus aureus involved in bovine mastitis.

AIMS: The biofilm produced by Staphylococcus aureus isolates involved in clinical or subclinical bovine mastitis and the activity of nisin and lysostaphin against the preformed biofilm produced by these strains were investigated. METHODS AND RESULTS: Eighteen strains were tested and all produced biofilm. Eight strains with distinct biofilm composition were selected for the antimicrobial activity assays. The minimal inhibitory concentration of each bacteriocin was determined against the planktonic cells and ranged from 15·6 to 500 µg ml(-1) for nisin, and from 3·9 to 50 µg ml(-1) , for lysostaphin. Lysostaphin treatment (0·4 µg ml(-1) ) for 4 h caused a strong Staph. aureus 4181 biofilm detachment and death of the majority of the sessile cells, while nisin treatment (100 µg ml(-1) ) for the same time caused only a great reduction in cell viability. Additionally, combination of both bacteriocins for 4 h resulted in significant death of the sessile cells but no biofilm detachment. CONCLUSIONS: The treatment with lysostaphin alone or in combination with nisin was effective in killing most biofilm sessile cells. SIGNIFICANCE AND IMPACT OF THE STUDY: The action of lysostaphin, either alone or in combination with nisin, against established staphylococcal biofilm may represent an alternative to bovine mastitis control. However, the duration of the treatment should be considered for its application so that the best effectiveness can be achieved.

Quantum criticality of hot random spin chains.

We study the infinite-temperature properties of an infinite sequence of random quantum spin chains using a real-space renormalization group approach, and demonstrate that they exhibit nonergodic behavior at strong disorder. The analysis is conveniently implemented in terms of SU(2)_{k} anyon chains that include the Ising and Potts chains as notable examples. Highly excited eigenstates of these systems exhibit properties usually associated with quantum critical ground states, leading us to dub them "quantum critical glasses." We argue that random-bond Heisenberg chains self-thermalize and that the excited-state entanglement crosses over from volume-law to logarithmic scaling at a length scale that diverges in the Heisenberg limit k→∞. The excited state fixed points are generically distinct from their ground state counterparts, and represent novel nonequilibrium critical phases of matter.

Vaccination with the RSV fusion protein formulated with a combination adjuvant induces long-lasting protective immunity.

Respiratory syncytial virus (RSV) is one of the primary causative agents of upper and lower respiratory tract infections in young children, in particular infants. Recently, we reported the protective efficacy of a RSV vaccine formulation consisting of a truncated version of the fusion (F) protein formulated with a Toll-like receptor (TLR) agonist and an immunostimulatory peptide in a carrier system (ΔF/TriAdj). To evaluate the duration of immunity induced by this vaccine candidate, we carried out long-term trials. The ΔF was formulated with triple adjuvant (TriAdj) containing either polyinosinic : polycytidylic acid (polyI : C) or cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs) and administered intranasally to mice. One year after the second vaccination all mice were challenged with RSV. Both ΔF/TriAdj formulations mediated the induction of high levels of IgG1, IgG2a and virus-neutralizing antibodies, and IgA in the lungs. Based on the numbers of IFN-γ- and IL-5-secreting cells in the spleen, the immune response was slightly T-helper cell type 1 (Th1)-biased. This was confirmed by the presence of F85-93-specific CD8(+) effector T cells in the lungs of both ΔF/TriAdj(polyI : C)- and ΔF/TriAdj(CpG)-immunized mice. Both ΔF/TriAdj formulations induced RSV-specific CD8(+) T cells. However, ΔF/TriAdj(polyI : C) generated significantly higher IgG affinity maturation and higher numbers of RSV-specific CD8(+) effector memory T cells in lungs and CD8(+) central memory T cells in spleen and lymph nodes than ΔF/TriAdj(CpG). After RSV challenge, no virus replication and no evidence of vaccine-induced pathology were detected in mice immunized with either of the ΔF/TriAdj formulations, demonstrating that the duration of immunity induced with these vaccines is at least one year.

Induction of mucosal immunity and protection by intranasal immunization with a respiratory syncytial virus subunit vaccine formulation.

The majority of infections, including those caused by respiratory syncytial virus (RSV), occur at mucosal surfaces. As no RSV vaccine is available our goal is to produce an effective subunit vaccine with an adjuvant suitable for mucosal delivery and cross-presentation. A truncated secreted version of the RSV fusion (ΔF) protein formulated with polyI : C, an innate defence regulator peptide and polyphosphazene, induced local and systemic immunity, including affinity maturation of RSV F-specific IgG, IgA and virus-neutralizing antibodies, and F-specific CD8(+) T-cells in the lung, when delivered intranasally. Furthermore, this ΔF protein formulation promoted the production of CD8(+) central memory T-cells in the mediastinal lymph nodes and provided protection from RSV challenge. Formulation of ΔF protein with this adjuvant combination enhanced uptake by lung dendritic cells and trafficking to the draining lymph nodes. The ΔF protein formulation was confirmed to be highly efficacious and safe in cotton rats.

In vitro and in vivo studies with tetra-hydro-jasmonic acid (LR2412) reveal its potential to correct signs of skin ageing.

BACKGROUND: LR2412, a synthetic derivative of jasmonic acid, improved the reconstruction and homeostasis of our organotypic skin models. OBJECTIVES: The need for efficient 'anti-ageing' treatments, in particular for the management of photoaged skin, prompted us to investigate this new ingredient for its potential to correct signs of skin ageing in vitro and in vivo and to identify its mode of action. RESULTS: In vitro, penetration of LR2412 was evaluated using a Franz diffusion cell on excised human skin. Its exfoliating properties and interactions with the stratum corneum were studied using electron microscopy and X-ray diffraction. Experiments were performed on a human reconstructed skin model. In vivo, the effects of LR2412 on steroid-induced skin atrophy, a clinical skin ageing model, were assessed vs. vehicle. A patch test study evaluated its effect on deposition of fibrillin-rich microfibrils in the papillary dermis in clinically photoaged volunteers. A clinical study on the appearance of crow's feet wrinkles was conducted over 3 months of daily application. Penetration studies revealed that LR2412 reaches viable epidermis and superficial dermis, which are skin targets of anti-ageing actives. Within the upper layers of the stratum corneum LR2412 accelerates desquamation and improves the mechanical properties. At the dermal-epidermal junction of reconstructed skin, collagen IV, laminin-5 and fibrillin were stimulated. In vivo, LR2412 reversed steroid-induced atrophy. The patch test model confirms the deposition of fibrillin-rich microfibrils, then an in use clinical study revealed that it reduced facial wrinkles. CONCLUSIONS: The in vitro and in vivo data demonstrate that based on its multiple interactions within human skin, LR2412 has potential to partially correct the signs of ageing in intrinsically and photoaged skin.

A sustainable training strategy for improving health care following a catastrophic radiological or nuclear incident.

The detonation of a nuclear device in a US city would be catastrophic. Enormous loss of life and injuries would characterize an incident with profound human, political, social, and economic implications. Nevertheless, most responders have not received sufficient training about ionizing radiation, principles of radiation safety, or managing, diagnosing, and treating radiation-related injuries and illnesses. Members throughout the health care delivery system, including medical first responders, hospital first receivers, and health care institution support personnel such as janitors, hospital administrators, and security personnel, lack radiation-related training. This lack of knowledge can lead to failure of these groups to respond appropriately after a nuclear detonation or other major radiation incident and limit the effectiveness of the medical response and recovery effort. Efficacy of the response can be improved by getting each group the information it needs to do its job. This paper proposes a sustainable training strategy for spreading curricula throughout the necessary communities. It classifies the members of the health care delivery system into four tiers and identifies tasks for each tier and the radiation-relevant knowledge needed to perform these tasks. By providing education through additional modules to existing training structures, connecting radioactive contamination control to daily professional practices, and augmenting these systems with just-in-time training, the strategy creates a sustainable mechanism for giving members of the health care community improved ability to respond during a radiological or nuclear crisis, reducing fatalities, mitigating injuries, and improving the resiliency of the community.

Day-to-day reliability of basal heart rate and short-term and ultra short-term heart rate variability assessment by the Equivital eq02+ LifeMonitor in US Army soldiers.

INTRODUCTION: The present study determined the (1) day-to-day reliability of basal heart rate (HR) and HR variability (HRV) measured by the Equivital eq02+ LifeMonitor and (2) agreement of ultra short-term HRV compared with short-term HRV. METHODS: Twenty-three active-duty US Army Soldiers (5 females, 18 males) completed two experimental visits separated by >48 hours with restrictions consistent with basal monitoring (eg, exercise, dietary), with measurements after supine rest at minutes 20-21 (ultra short-term) and minutes 20-25 (short-term). HRV was assessed as the SD of R-R intervals (SDNN) and the square root of the mean squared differences between consecutive R-R intervals (RMSSD). RESULTS: The day-to-day reliability (intraclass correlation coefficient (ICC)) using linear-mixed model approach was good for HR (0.849, 95% CI: 0.689 to 0.933) and RMSSD (ICC: 0.823, 95% CI: 0.623 to 0.920). SDNN had moderate day-to-day reliability with greater variation (ICC: 0.689, 95% CI: 0.428 to 0.858). The reliability of RMSSD was slightly improved when considering the effect of respiration (ICC: 0.821, 95% CI: 0.672 to 0.944). There was no bias for HR measured for 1 min versus 5 min (p=0.511). For 1 min measurements versus 5 min, there was a very modest mean bias of -4 ms for SDNN and -1 ms for RMSSD (p≤0.023). CONCLUSION: When preceded by a 20 min stabilisation period using restrictions consistent with basal monitoring and measuring respiration, military personnel can rely on the eq02+ for basal HR and RMSSD monitoring but should be more cautious using SDNN. These data also support using ultra short-term measurements when following these procedures.

Skeletal muscle-specific expression of a utrophin transgene rescues utrophin-dystrophin deficient mice.

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease usually resulting in death of patients by their early twenties. In contrast, mice lacking dystrophin (Dmd(mdx)), appear physically normal despite their underlying muscle pathology. Mice deficient for both dystrophin and the dystrophin-related protein, utrophin, (Dmd(mdx);Utrn-/- mice) die between 6 and 20 weeks of age suffering from severe muscle weakness with joint contractures, pronounced growth retardation and kyphosis, suggesting that dystrophin and utrophin play complementary roles. The exact cause of death in these mice was not determined. Here we show that expression of a truncated utrophin transgene solely within the skeletal muscle of these mutants prevents premature death and the development of any clinical phenotype. In the absence of full-length dystrophin and utrophin, the presence of truncated utrophin also decreases muscle fibre regeneration, relocalizes the dystrophin protein complex to the sarcolemma and re-establishes a normal expression pattern of developmental muscle proteins. These data suggest that Dmd(mdx);Utrn-/- mice succumb to a skeletal muscle defect and that their reduced lifespan is not due to cardiac or neurogenic components. The phenotypic rescue observed demonstrates that the Dmd(mdx);Utrn-/- mice are an ideal model for testing gene delivery protocols for the expression of utrophin or dystrophin in skeletal muscle. To determine the cause of death of the Dmd(mdx):Utrn-/- mice.

The ABCD stop signal data: Response to Bissett et al.

This paper responds to a recent critique by Bissett et al. of the fMRI Stop task used in the Adolescent Brain Cognitive Development℠ Study (ABCD Study®). The critique focuses primarily on a task design feature related to race model assumptions (i.e., that the Go and Stop processes are fully independent). In response, we note that the race model is quite robust against violations of its assumptions. Most importantly, while Bissett raises conceptual concerns with the task we focus here on analyzes of the task data and conclude that the concerns appear to have minimal impact on the neuroimaging data (the validity of which do not rely on race model assumptions) and have far less of an impact on the performance data than the critique suggests. We note that Bissett did not apply any performance-based exclusions to the data they analyzed, a number of the trial coding errors they flagged were already identified and corrected in ABCD annual data releases, a number of their secondary concerns reflect sensible design decisions and, indeed, their own computational modeling of the ABCD Stop task suggests the problems they identify have just a modest impact on the rank ordering of individual differences in subject performance.

Modification of protein transfer across blood/cerebrospinal fluid barrier in response to altered plasma protein composition during development.

A developmentally regulated protein-specific transfer mechanism across choroid plexus epithelial cells has previously been proposed to contribute to the characteristically high concentration of protein in cerebrospinal fluid (CSF) in the immature brain. Here we demonstrate that this mechanism is sensitive to protein variations in plasma resulting in changed numbers of transferring cells for individual proteins and altered transfer into the CSF. Pups of Monodelphis domestica at postnatal day (P)9, P65 and P110 were injected intraperitoneally with either adult Monodelphis plasma or exogenous bovine fetuin. Samples of CSF, blood and brain were collected from terminally anaesthetized animals 3-48 h later. The concentration of total protein was measured and levels of albumin, hemopexin, α-fetoprotein and bovine fetuin were estimated by western blotting. Numbers of lateral ventricular choroid plexus cells positive for total and individual plasma proteins were counted in paraffin sections of brains stained with appropriate antibodies. Following intraperitoneal injections, the content of proteins in the CSF increased at all three ages, but the concentration increased only in the CSF of older animals. The total numbers of plexus cells positive for plasma protein did not change significantly, but cells positive for individual proteins did. Fetuin was detected in all protein-positive cells, but apparently displaced α-fetoprotein and, to a lesser degree, hemopexin. The results indicate that protein transfer across the blood/CSF barrier appears to be regulated by a molecular recognition mechanism that is probably saturable but may not be as specific for individual proteins as previously suggested.

FDG uptake in primary squamous cell carcinoma of the head and neck. The relationship between overexpression of glucose transporters and hexokinases, tumour proliferation and apoptosis.

AIM: This study aimed at assessing the relationship between over-expression of glucose transporters and hexokinases, tumour proliferation and apoptosis corrected for cellularity and partial volume corrected (pvc) FDG SUV values in primary squamous cell carcinoma of the head and neck (pSCCHN). PATIENTS, METHODS: In 27 consecutive patients suffering from pSCCHN, FDG SUVmax and mean pvc values of the primary tumour were derived from a pre-surgical routine staging FDG PET/CT examination. GLUT-1, GLUT-3, HK-1, HK-3 expression, tumour proliferation (Ki-67 staining) and the number of apoptotic cells (cleaved caspase-3 staining), corrected for tumour cellularity, were subsequently assessed on the corresponding post-surgically obtained biopsies and tumour specimens. FDG SUVmax and mean pvc values of pSCCHN were correlated with the corresponding histological findings. RESULTS: FDG SUV max and mean pvc values correlated significantly: with GLUT-1 scores r = 0.408 (p = 0.04) and r = 0.439 (p = 0.03) as well as with the number of apoptotic cells r = 0.529 (p = 0.008) and r = 0.484 (p = 0.017). The number of apoptotic cells also correlated to GLUT-3 scores: r = 0.62 (p = 0.001) and GLUT-1 scores r = 0.528 (p = 0.008). CONCLUSION: FDG SUV pvc proved significantly related to GLUT-1 expression by tumour cells and to the absolute number of apoptotic cells. The latter finding warrants further exploration and confirmation by additional studies.

Defining a standard medication kit for prehospital and retrieval physicians: a comprehensive review.

BACKGROUND: There is little consolidated evidence for which prehospital and retrieval drugs a given service should carry. OBJECTIVES: To suggest a core group of drugs based on the best evidence currently available. METHODS: This paper has reviewed documents from recognised evidence-based sources and put together an initial skeleton for an evidence-based drug pack. RESULTS: The resultant list of drugs is divided up into core agents with suggestions for regional variations. This may be of particular interest to de novo services. CONCLUSIONS: This review offers a starting point for services based on the evidence currently available. It is hoped that prehospital and retrieval clinicians will start to look analytically at what they carry and, through a process of audit, aim to improve the evidence in this area. Future reviews and comparisons of worldwide prehospital and retrieval databases are suggested.

Postsynaptic abnormalities at the neuromuscular junctions of utrophin-deficient mice.

Utrophin is a dystrophin-related cytoskeletal protein expressed in many tissues. It is thought to link F-actin in the internal cytoskeleton to a transmembrane protein complex similar to the dystrophin protein complex (DPC). At the adult neuromuscular junction (NMJ), utrophin is precisely colocalized with acetylcholine receptors (AChRs) and recent studies have suggested a role for utrophin in AChR cluster formation or maintenance during NMJ differentiation. We have disrupted utrophin expression by gene targeting in the mouse. Such mice have no utrophin detectable by Western blotting or immunocytochemistry. Utrophin-deficient mice are healthy and show no signs of weakness. However, their NMJs have reduced numbers of AChRs (alpha-bungarotoxin [alpha-BgTx] binding reduced to approximately 60% normal) and decreased postsynaptic folding, though only minimal electrophysiological changes. Utrophin is thus not essential for AChR clustering at the NMJ but may act as a component of the postsynaptic cytoskeleton, contributing to the development or maintenance of the postsynaptic folds. Defects of utrophin could underlie some forms of congenital myasthenic syndrome in which a reduction of postsynaptic folds is observed.