An elementary quantum network operation involves storing a qubit state in an atomic quantum memory node, and then retrieving and transporting the information through a single photon excitation to a ...remote quantum memory node for further storage or analysis. Implementations of quantum network operations are thus conditioned on the ability to realize matter-to-light and/or light-to-matter quantum state mappings. Here we report the generation, transmission, storage and retrieval of single quanta using two remote atomic ensembles. A single photon is generated from a cold atomic ensemble at one site , and is directed to another site through 100 metres of optical fibre. The photon is then converted into a single collective atomic excitation using a dark-state polariton approach. After a programmable storage time, the atomic excitation is converted back into a single photon. This is demonstrated experimentally, for a storage time of 0.5 microseconds, by measurement of an anti-correlation parameter. Storage times exceeding ten microseconds are observed by intensity cross-correlation measurements. This storage period is two orders of magnitude longer than the time required to achieve conversion between photonic and atomic quanta. The controlled transfer of single quanta between remote quantum memories constitutes an important step towards distributed quantum networks.
In this Phase 2b study, 331 low‐to‐moderate risk de novo kidney transplant patients (approximately 60% deceased donors) were randomized to a more intensive (MI) or less intensive (LI) regimen of ...tofacitinib (CP‐690, 550), an oral Janus kinase inhibitor or cyclosporine (CsA). All patients received basiliximab induction, mycophenolic acid and corticosteroids. Primary endpoints were: incidence of biopsy‐proven acute rejection (BPAR) with a serum creatinine increase of ≥0.3 mg/dL and ≥20% (clinical BPAR) at Month 6 and measured GFR at Month 12. Similar 6‐month incidences of clinical BPAR (11%, 7% and 9%) were observed for MI, LI and CsA. Measured GFRs were higher (p < 0.01) at Month 12 for MI and LI versus CsA (65 mL/min, 65 mL/min vs. 54 mL/min). Fewer (p < 0.05) patients in MI or LI developed chronic allograft nephropathy at Month 12 compared with CsA (25%, 24% vs. 48%). Serious infections developed in 45%, 37% and 25% of patients in MI, LI and CsA, respectively. Anemia, neutropenia and posttransplant lymphoproliferative disorder occurred more frequently in MI and LI compared with CsA. Tofacitinib was equivalent to CsA in preventing acute rejection, was associated with improved renal function and less chronic allograft histological injury, but had side‐effects at the doses evaluated.
The authors present the results of a phase 2b trial of tofacitinib in renal transplantation.
Phytoplankton subsumes the great variety of unicellular photoautotrophs that perform roughly half of Earth's primary production. They achieve this despite their challenging oceanic habitat, with ...opposing vertical gradients of nutrients (which often limit their growth near the surface) and light (which becomes limiting with increasing depth). Most phytoplankton species are commonly assumed to be incapable of moving actively between the zones of light and nutrient availability, which are separated vertically by from 30-120 m. Here we propose that a considerable fraction of phytoplankton vertically traverse these gradients over time scales from hours to weeks, employing variations of a common migration strategy to acquire multiple resources. We present a mechanistic Lagrangian model resolving phytoplankton growth linked to optimal migration behaviour and demonstrate unprecedented agreement of its calculated vertical CHL-a distributions with 773 profiles observed at five prominent marine time-series stations. Our simulations reveal that vertically cycling phytoplankton can pump up enough nutrient to sustain as much as half of oceanic Net Primary Production (NPP). Active locomotion is therefore a plausible mechanism enabling relatively high NPP in the oligotrophic surface ocean. Our simulations also predict similar fitness for a variety of very different migration strategies, which helps to explain the puzzling diversity of phytoplankton observed in the ocean.
Autonomic nervous system activation can induce significant and heterogeneous changes of atrial electrophysiology and induce atrial tachyarrhythmias, including atrial tachycardia and atrial ...fibrillation (AF). The importance of the autonomic nervous system in atrial arrhythmogenesis is also supported by circadian variation in the incidence of symptomatic AF in humans. Methods that reduce autonomic innervation or outflow have been shown to reduce the incidence of spontaneous or induced atrial arrhythmias, suggesting that neuromodulation may be helpful in controlling AF. In this review, we focus on the relationship between the autonomic nervous system and the pathophysiology of AF and the potential benefit and limitations of neuromodulation in the management of this arrhythmia. We conclude that autonomic nerve activity plays an important role in the initiation and maintenance of AF, and modulating autonomic nerve function may contribute to AF control. Potential therapeutic applications include ganglionated plexus ablation, renal sympathetic denervation, cervical vagal nerve stimulation, baroreflex stimulation, cutaneous stimulation, novel drug approaches, and biological therapies. Although the role of the autonomic nervous system has long been recognized, new science and new technologies promise exciting prospects for the future.
Rather than spatial means of biomass, observed overlap in the intermittent spatial distributions of aquatic predators and prey is known to be more important for determining the flow of nutrients and ...energy up the food chain. A few previous studies have separately suggested that such intermittency enhances phytoplankton growth and trophic transfer to sustain zooplankton and ultimately fisheries. Recent observations have revealed that phytoplankton distributions display consistently high degrees of mm scale patchiness, increasing along a gradient from estuarine to open ocean waters. Using a generalized framework of plankton ecosystem models with different trophic configurations, each accounting for this intermittency, we show that it consistently enhances trophic transfer efficiency (TE), i.e. the transfer of energy up the food chain, and expands the model stability domain. Our results provide a new explanation for observation-based estimates of unexpectedly high TE in the vast oligotrophic ocean and suggest that by enhancing the viable trait space, micro-scale variability may potentially sustain plankton biodiversity.
Summary
Background
Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis.
Objectives
To determine the 16‐week efficacy and safety of two oral tofacitinib doses vs. placebo in ...patients with moderate‐to‐severe chronic plaque psoriasis.
Methods
Patients in two similarly designed phase III studies (OPT Pivotal 1, NCT01276639, n = 901; OPT Pivotal 2, NCT01309737, n = 960) were initially randomized 2 : 2 : 1 to tofacitinib 10 or 5 mg or placebo, twice daily. Coprimary efficacy end points (week 16) included the proportion of patients achieving Physician's Global Assessment (PGA) of ‘clear’ or ‘almost clear’ (PGA response) and the proportion achieving ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75).
Results
Across OPT Pivotal 1 and OPT Pivotal 2, 745 patients received tofacitinib 5 mg, 741 received tofacitinib 10 mg and 373 received placebo. At week 16, a greater proportion of patients achieved PGA responses with tofacitinib 5 and 10 mg twice daily vs. placebo (OPT Pivotal 1, 41·9% and 59·2% vs. 9·0%; OPT Pivotal 2, 46·0% and 59·1% vs. 10·9%; all P < 0·001). Higher PASI 75 rates were observed with tofacitinib vs. placebo (OPT Pivotal 1, 39·9%, 59·2% and 6·2%, respectively, for tofacitinib 5 and 10 mg twice daily and placebo; OPT Pivotal 2, 46·0%, 59·6% and 11·4%; all P < 0·001 vs. placebo). Adverse event (AE) rates appeared generally similar across groups; rates of serious AEs, infections, malignancies and discontinuations due to AEs were low. Twelve patients reported herpes zoster across the tofacitinib treatment groups in both studies vs. none in the respective placebo groups. The most common AE across groups was nasopharyngitis.
Conclusions
Oral tofacitinib demonstrated significant efficacy vs. placebo during the initial 16 weeks of treatment in patients with moderate‐to‐severe psoriasis. Safety findings were consistent with prior studies.
What's already known about this topic?
The management of moderate‐to‐severe chronic plaque psoriasis has benefited from the introduction of biological therapies, but unmet needs still remain.
Tofacitinib is an oral Janus kinase inhibitor that is being investigated for psoriasis.
A phase IIb study demonstrated that oral tofacitinib is efficacious and well tolerated in the treatment of patients with plaque psoriasis over a 12‐week period.
What does this study add?
These phase III studies demonstrated that oral tofacitinib 5 and 10 mg twice daily is efficacious and well tolerated in the treatment of plaque psoriasis in a large, global patient population over a 16‐week period.
These studies provide support for tofacitinib as an innovative oral systemic option for the treatment of patients with psoriasis in the future.
The effects of microstructure on crack resistance and toughening mechanism of an ultra-low carbon steel were investigated. The microstructures were controlled via thermal-mechanical control ...processing (TMCP) and heat-treatments. Distribution of stress concentration, microcracks formation and propagation during Charpy impacting were investigated in detail. The results indicate that the lath martensitic structure provided a higher yield stress together with a better impact property, compared to the polygonal ferritic structure. The high strength can be attributed to the high density of dislocations in the lath martensitic structure introduced by quenching. The instrumented Charpy impact results indicated that the crack initiation energy in the lath martensitic structure was similar to that in the ferritic structure while the crack propagation energy was significantly greater than that in the ferritic structure, leading to the high toughness of the steel with the lath martensitic structure. Local stress concentration distributed uniformly in lath martensitic structure, leading to the homogeneous nucleation of microcrack. The high crack propagation energy in the lath martensitic structure can be attributed to the high fraction of high angle grain boundaries and fine effective grains, which deflected the cleavage crack propagation direction.
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•60 °C decrement in DBTT was obtained through controlling microstructure.•The lath martensite provides a good combination of strength and toughness.•The high crack propagation energy of lath martensite benefits to the good toughness.•HAGB and EGS deflect the cleavage crack propagation direction.
An anomaly in differential scanning calorimetry has been reported in a number of metallic glass materials in which a broad exothermal peak was observed between the glass and crystallization ...temperatures. The mystery surrounding this calorimetric anomaly is epitomized by four decades long studies of Pd-Ni-P metallic glasses, arguably the best glass-forming alloys. Here we show, using a suite of in situ experimental techniques, that Pd-Ni-P alloys have a hidden amorphous phase in the supercooled liquid region. The anomalous exothermal peak is the consequence of a polyamorphous phase transition between two supercooled liquids, involving a change in the packing of atomic clusters over medium-range length scales as large as 18 Å. With further temperature increase, the alloy reenters the supercooled liquid phase, which forms the room-temperature glass phase on quenching. The outcome of this study raises a possibility to manipulate the structure and hence the stability of metallic glasses through heat treatment.
•The optimal PAHLOW model predicts different patterns of N:C and Chl:C ratios with the MONOD model.•The PAHLOW model fits the laboratory date qualitatively better than the MONOD model.•The PAHLOW ...model overestimates phytoplankton growth rate and Chl:C ratios in the DCM layer.•The PAHLOW model costs two times computation time than the MONOD model.
To increase the efficiency of computing phytoplankton growth rate (μ), chlorophyll-to-carbon (θ) and nitrogen-to-carbon ratios (QN) in three-dimensional ocean circulation models, it is preferable to directly calculate θ and QN from ambient environmental factors instead of treating them as independent tracers. Optimality-based modeling has emerged as a novel and efficient approach to fulfill this task. However, it is still unclear precisely how the response of optimality-based models differs from conventional models. We compare a recent optimality-based phytoplankton model (PAHLOW model), based on which the familiar Droop function can be derived, to a commonly used Monod-type (MONOD) model. The two models generate similar patterns of μ with some important differences. Compared to the MONOD model, the PAHLOW model predicts higher μ under light limitation. The PAHLOW model also predicts that θ decreases with decreasing light under dim light and predicts decreasing QN with increasing light even at constant nutrient levels. Compared to the MONOD model, these features of the PAHLOW model qualitatively agree better with laboratory data. The PAHLOW model also suffers from a few shortcomings including the underestimation of θ under very low light and two times of computation time compared to the MONOD model. The two models generate striking differences of QN and θ in a one-dimensional implementation. Validation of such patterns will require more direct in situ measurements of μ, θ and QN.