High-fidelity initialization and control of electron and nuclear spins in a four-qubit register.

Single electron spins bound to multi-phosphorus nuclear spin registers in silicon have demonstrated fast (0.8 ns) two-qubit SWAP gates and long spin relaxation times (~30 s). In these spin registers, when the donors are ionized, the nuclear spins remain weakly coupled to their environment, allowing exceptionally long coherence times. When the electron is present, the hyperfine interaction allows coupling of the spin and charge degrees of freedom for fast qubit operation and control. Here we demonstrate the use of the hyperfine interaction to enact electric dipole spin resonance to realize high-fidelity ( F = 10 0 - 6 + 0 %) initialization of all the nuclear spins within a four-qubit nuclear spin register. By controllably initializing the nuclear spins to ⇓ ⇓ ⇓ , we achieve single-electron qubit gate fidelities of F = 99.78 ± 0.07% (Clifford gate fidelities of 99.58 ± 0.14%), above the fault-tolerant threshold for the surface code with a coherence time of T 2 * = 12 µ s .

Engineering topological states in atom-based semiconductor quantum dots.

The realization of controllable fermionic quantum systems via quantum simulation is instrumental for exploring many of the most intriguing effects in condensed-matter physics1-3. Semiconductor quantum dots are particularly promising for quantum simulation as they can be engineered to achieve strong quantum correlations. However, although simulation of the Fermi-Hubbard model4 and Nagaoka ferromagnetism5 have been reported before, the simplest one-dimensional model of strongly correlated topological matter, the many-body Su-Schrieffer-Heeger (SSH) model6-11, has so far remained elusive-mostly owing to the challenge of precisely engineering long-range interactions between electrons to reproduce the chosen Hamiltonian. Here we show that for precision-placed atoms in silicon with strong Coulomb confinement, we can engineer a minimum of six all-epitaxial in-plane gates to tune the energy levels across a linear array of ten quantum dots to realize both the trivial and the topological phases of the many-body SSH model. The strong on-site energies (about 25 millielectronvolts) and the ability to engineer gates with subnanometre precision in a unique staggered design allow us to tune the ratio between intercell and intracell electron transport to observe clear signatures of a topological phase with two conductance peaks at quarter-filling, compared with the ten conductance peaks of the trivial phase. The demonstration of the SSH model in a fermionic system isomorphic to qubits showcases our highly controllable quantum system and its usefulness for future simulations of strongly interacting electrons.

A two-qubit gate between phosphorus donor electrons in silicon.

Electron spin qubits formed by atoms in silicon have large (tens of millielectronvolts) orbital energies and weak spin-orbit coupling, giving rise to isolated electron spin ground states with coherence times of seconds1,2. High-fidelity (more than 99.9 per cent) coherent control of such qubits has been demonstrated3, promising an attractive platform for quantum computing. However, inter-qubit coupling-which is essential for realizing large-scale circuits in atom-based qubits-has not yet been achieved. Exchange interactions between electron spins4,5 promise fast (gigahertz) gate operations with two-qubit gates, as recently demonstrated in gate-defined silicon quantum dots6-10. However, creating a tunable exchange interaction between two electrons bound to phosphorus atom qubits has not been possible until now. This is because it is difficult to determine the atomic distance required to turn the exchange interaction on and off while aligning the atomic circuitry for high-fidelity, independent spin readout. Here we report a fast (about 800 picoseconds) [Formula: see text] two-qubit exchange gate between phosphorus donor electron spin qubits in silicon using independent single-shot spin readout with a readout fidelity of about 94 per cent on a complete set of basis states. By engineering qubit placement on the atomic scale, we provide a route to the realization and efficient characterization of multi-qubit quantum circuits based on donor qubits in silicon.

Essential Oil Emulsions as Postharvest Sanitizers To Mitigate Salmonella Cross-Contamination on Peppers.

Alternative postharvest sanitizers to chlorine are of increasing interest for many organic growers and consumers. An emulsion of clove bud oil (CBO; 0.2 and 0.5%) or thyme oil (0.2 and 0.5%) was evaluated as a sanitizer for produce washing against a five-serovar cocktail of Salmonella on snacking peppers and compared for antimicrobial efficacy with sodium hypochlorite (200 ppm). To further evaluate these compounds, the sanitation efficacy of an emulsion was examined after the addition of 1% organic load (OL). Emulsion treatments at 0.2 and 0.5% thyme oil and 0.5% CBO were the least effected by OL and effectively reduced cross-contamination of Salmonella on clean peppers, in many cases to below the limit of detection (1 CFU/10 g; P < 0.05). Chlorine and 0.2% CBO were rendered ineffective by the addition of OL in preventing cross-contamination and performed similarly to the water control. For surface-inoculated peppers, none of the evaluated treatments performed better than a water-only wash. The antimicrobial efficacy of the essential oil emulsions in the presence of OL indicates these emulsions may be suitable replacements for chlorine in postharvest produce wash systems.

Two-electron spin correlations in precision placed donors in silicon.

Substitutional donor atoms in silicon are promising qubits for quantum computation with extremely long relaxation and dephasing times demonstrated. One of the critical challenges of scaling these systems is determining inter-donor distances to achieve controllable wavefunction overlap while at the same time performing high fidelity spin readout on each qubit. Here we achieve such a device by means of scanning tunnelling microscopy lithography. We measure anti-correlated spin states between two donor-based spin qubits in silicon separated by 16 ± 1 nm. By utilising an asymmetric system with two phosphorus donors at one qubit site and one on the other (2P-1P), we demonstrate that the exchange interaction can be turned on and off via electrical control of two in-plane phosphorus doped detuning gates. We determine the tunnel coupling between the 2P-1P system to be 200 MHz and provide a roadmap for the observation of two-electron coherent exchange oscillations.

Quantifying the radiant exposure and effective dose in patients treated for actinic keratoses with topical photodynamic therapy using daylight and LED white light.

Daylight photodynamic therapy (dl-PDT) is as effective as conventional PDT (c-PDT) for treating actinic keratoses but has the advantage of reducing patient discomfort significantly. Topical dl-PDT and white light-PDT (wl-PDT) differ from c-PDT by way of light sources and methodology. We measured the variables associated with light dose delivery to skin surface and influence of geometry using a radiometer, a spectral radiometer and an illuminance meter. The associated errors of the measurement methods were assessed. The spectral and spatial distribution of the radiant energy from the LED white light source was evaluated in order to define the maximum treatment area, setup and treatment protocol for wl-PDT. We compared the data with two red LED light sources we use for c-PDT. The calculated effective light dose is the product of the normalised absorption spectrum of the photosensitizer, protoporphyrin IX (PpIX), the irradiance spectrum and the treatment time. The effective light dose from daylight ranged from 3 ± 0.4 to 44 ± 6 J cm-2due to varying weather conditions. The effective light dose for wl-PDT was reproducible for treatments but it varied across the treatment area between 4 ± 0.1 J cm-2 at the edge and 9 ± 0.1 J cm-2 centrally. The effective light dose for the red waveband (615-645 nm) was 0.42 ± 0.05 J cm-2 on a clear day, 0.05 ± 0.01 J cm-2 on an overcast day and 0.9 ± 0.01 J cm-2 using the white light. This compares with 0.95 ± 0.01 and 0.84 ± 0.01 J cm-2 for c-PDT devices. Estimated errors associated with indirect determination of daylight effective light dose were very significant, particularly for effective light doses less than 5 J cm-2 (up to 83% for irradiance calculations). The primary source of error is in establishment of the relationship between irradiance or illuminance and effective dose. Use of the O'Mahoney model is recommended using a calibrated logging illuminance meter with the detector in the plane of the treatment area.

Shiitake Flagellate Dermatitis: the First Case Reported in Ireland.

Shiitake (Lentinula edodes) is the second most commonly consumed mushroom worldwide. The first case of shiitake mushroom flagellate dermatitis was described in Japan in 1977 and it is now being reported in the western world. We describe the first reported case in Ireland.

Alpha-1-antitrypsin deficiency-related panniculitis: two cases with diverse clinical courses.

Alpha-1-antitrypsin deficiency (AATD)-related panniculitis is an extremely rare and underdiagnosed entity, and there is a paucity of data on its treatment. We report two cases of AATD-related panniculitis. The first was a 24-year-old woman with known AATD who presented with painful leg ulcers refractory to treatment with corticosteroids and colchicine. She had a good response to α1-antitrypsin infusions but required dose adjustment due to flares in disease activity. The second case was a 38-year-old woman who presented with painful nodules on the legs refractory to corticosteroid therapy. Laboratory investigations revealed severe AATD. She had an excellent response to colchicine therapy. In both these cases of AATD, panniculitis was the first clinical manifestation of the disease. AATD-related panniculitis may have none of the typical clinical clues for AATD, such as a family history, cirrhosis or emphysema. Early identification may help prevent these complications from developing.

High-Fidelity Single-Shot Singlet-Triplet Readout of Precision-Placed Donors in Silicon.

In this work we perform direct single-shot readout of the singlet-triplet states in exchange coupled electrons confined to precision-placed donor atoms in silicon. Our method takes advantage of the large energy splitting given by the Pauli-spin blockaded (2,0) triplet states, from which we can achieve a single-shot readout fidelity of 98.4±0.2%. We measure the triplet-minus relaxation time to be of the order 3 s at 2.5 T and observe its predicted decrease as a function of magnetic field, reaching 0.5 s at 1 T.

Validation of high-performance liquid chromatography-tandem mass spectrometry assays quantifying omacetaxine mepesuccinate and its 4'­des-methyl and cephalotaxine metabolites in human plasma and urine.

Omacetaxine mepesuccinate (hereafter called omacetaxine) is a modified cephalotaxine and is registered (Synribo(®)) for the treatment of adult patients with chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKIs). To evaluate the pharmacokinetics of omacetaxine, sensitive high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays for the quantification of omacetaxine and its inactive 4'-des-methyl (4'-DMHHT) and cephalotaxine metabolites in human plasma and urine were developed and validated. Since omacetaxine is mainly metabolised by esterases, the plasma samples were immediately stabilised after collection with an esterase inhibitor and stored at a nominal temperature of -80°C. Urine samples were stored at -80°C immediately after collection. Protein precipitation was applied as the sample pretreatment method for the plasma samples, and urine samples were processed using solid-phase extraction (SPE). For both assays, the dried and reconstituted extracts were injected on a XBridge BEH Phenyl column for analysis of all analytes. Gradient elution was applied with 0.1% formic acid in water and methanol as mobile phases. Analytes were ionised using a turbospray ionisation source in positive mode and detected with a triple quadrupole mass spectrometer. The validated plasma assay quantifies all analytes in the concentration range of 0.1-100ng/mL and the urine assay in the range of 0.1-50ng/mL. At all concentrations, the accuracies were within ±15% of the nominal concentrations and precisions were ≤15%. The developed methods have successfully been applied in a human mass balance study of omacetaxine.

An uncommon dermatophyte infection: two cases of cutaneous infection with Trichophyton verrucosum.

Zoophilic dermatophytes can cause highly inflammatory cutaneous infections. Cattle represent the largest reservoir for the zoophilic dermatophyte Trichophyton verrucosum. Effective vaccination programmes have contributed to a low rate of livestock infection in central and northern Europe, and T. verrucosum infection is relatively more common in southern Europe and in Arabic countries. Transmission to humans typically results from direct contact with infected livestock. It may also be transmitted from person to person. We report two cases of T. verrucosum skin infections in Irish farmers. In both cases, effective treatment was delayed due to misdiagnosis of the condition as a bacterial infection in the primary care setting. Both cases responded rapidly to treatment with oral terbinafine. Culture of T. verrucosum can take 3 weeks or longer to grow, therefore a high index of clinical suspicion is necessary, and skin scrapings for potassium hydroxide microscopy and culture are essential for accurate diagnosis.

Atmospheric pressure, nonthermal plasma inactivation of MS2 bacteriophage: effect of oxygen concentration on virucidal activity.

AIMS: The main aim of this study was to determine the virucidal inactivation efficacy of an in-house-designed atmospheric pressure, nonthermal plasma jet operated at varying helium/oxygen feed gas concentrations against MS2 bacteriophage, widely employed as a convenient surrogate for human norovirus. METHODS AND RESULTS: The effect of variation of percentage oxygen concentration in the helium (He) carrier gas was studied and found to positively correlate with MS2 inactivation rate, indicating a role for reactive oxygen species (ROS) in viral inactivation. The inactivation rate constant increased with increasing oxygen concentrations up to 0·75% O2 . 3 log10 (99·9%) reductions in MS2 viability were achieved after 3 min of exposure to the plasma source operated in a helium/oxygen (99·25% : 0·75%) gas mixture, with >7 log10 reduction after 9 min exposure. CONCLUSIONS: Atmospheric pressure, nonthermal plasmas may have utility in the rapid disinfection of virally contaminated surfaces for infection control applications. SIGNIFICANCE AND IMPACT OF STUDY: The atmospheric pressure, nonthermal plasma jet employed in this study exhibits rapid virucidal activity against a norovirus surrogate virus, the MS2 bacteriophage, which is superior to previously published inactivation rates for chemical disinfectants.

Development and validation of LC-MS/MS assays for the quantification of bendamustine and its metabolites in human plasma and urine.

A sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) assay is described for the quantification of the anti-cancer agent bendamustine and its phase I metabolites γ-hydroxy-bendamustine (M3) and N-des-methylbendamustine (M4) and for its product of two-fold hydrolysis, dihydroxy-bendamustine (HP2), in human plasma and urine. Like most alkylating nitrogen mustards, bendamustine is prone to chemical hydrolysis in aqueous solution. To minimize degradation of bendamustine, urine samples were stabilized by a 100-fold dilution with human plasma and then processed identically to plasma samples. Sample aliquots of 200 µL were mixed with an internal standard solution and acidified before separation of the analytes from the biomatrix with solid phase extraction. Dried and reconstituted extracts were injected on a Synergi Hydro RP column for the analysis of bendamustine, M3 and M4 or a Synergi Polar RP column for the analysis of HP2. Gradient elution was applied using 5mM ammonium formate with 0.1% formic acid in water and methanol as mobile phases. Analytes were ionized using an electrospray ionisation source in positive mode and detected with a triple quadrupole mass spectrometer. The quantifiable range for bendamustine, M3 and M4 was 0.5-500 ng/mL in plasma and 0.5-50 µg/mL in urine, and that for HP2 was 1-500 ng/mL in plasma and 0.1-50 µg/mL in urine. The assays were accurate and precise, with inter-assay and intra-assay accuracies within ± 20% of nominal and CV values below 20% at the lower limit of quantification and within ± 15% of nominal and below 15% at the other concentration levels tested. These methods were successfully applied to evaluate the pharmacokinetic profile of bendamustine and its metabolites in cancer patients treated with bendamustine.

UV inhibits allergic airways disease in mice by reducing effector CD4 T cells.

BACKGROUND: In human asthma, and experimental allergic airways disease in mice, antigen-presenting cells and CD4(+) effector cells at the airway mucosa orchestrate, and CD4(+)CD25(+) regulatory T cells attenuate, allergen immunity. UV irradiation of skin before sensitization with ovalbumin (OVA) causes significantly reduced asthma-like responses in respiratory tissues. OBJECTIVE: To determine whether UV-induced changes in CD11c(+) cells, CD4(+)CD25(+) effector cells or CD4(+)CD25(+) regulatory cells in the trachea and airway draining lymph nodes (ADLNs) were responsible for reduced allergic airways disease. METHODS: The phenotype and function of CD11c(+) cells and CD4(+)CD25(+) cells in the trachea and ADLNs of UV- and non-irradiated, OVA-sensitized mice was examined 24 h after a single exposure to aerosolized OVA. RESULTS: No changes in the function of CD11c(+) cells from UV-irradiated mice were observed. CD4(+)CD25(+) cells from UV-irradiated, OVA-sensitized mice harvested 24 h after OVA aerosol proliferated less in response to OVA in vitro and were unable to suppress the proliferation of OVA-sensitized responder cells. This result suggested reduced activation of effector T cells in the airway mucosa of UV-irradiated, OVA-sensitized mice. To exclude regulatory cells of any type, there was similar proliferation in vivo to aerosolized OVA by CFSE-loaded, OVA-TCR-specific CD4(+) cells adoptively transferred into UV- and non-irradiated, OVA-sensitized mice. In addition, there was no difference in the expression of regulatory T cell markers (Foxp3, IL-10, TGF-beta mRNA). To examine effector T cells, ADLN cells from UV-irradiated, OVA-sensitized and -challenged mice were cultured with OVA. There was reduced expression of the early activation marker CD69 by CD4(+)CD25(+) cells, and reduced proliferation in the absence of the regulatory cytokine, IL-10. CONCLUSION: Reduced allergic airways disease in UV-irradiated mice is due to fewer effector CD4(+)CD25(+) cells in the trachea and ADLNs, and not due to UV-induced regulatory cells.

Cellular senescence induced by aberrant MAD2 levels impacts on paclitaxel responsiveness in vitro.

BACKGROUND: The mitotic arrest deficiency protein 2 (MAD2) is a key component of the mitotic spindle assembly checkpoint, monitoring accurate chromosomal alignment at the metaphase plate before mitosis. MAD2 also has a function in cellular senescence and in a cell's response to microtubule inhibitory (MI) chemotherapy exemplified by paclitaxel. METHODS: Using an siRNA approach, the impact of MAD2 down-regulation on cellular senescence and paclitaxel responsiveness was investigated. The endpoints of senescence, cell viability, migration, cytokine expression, cell cycle analysis and anaphase bridge scoring were carried out using standard approaches. RESULTS: We show that MAD2 down-regulation induces premature senescence in the MCF7 breast epithelial cancer cell line. These MAD2-depleted (MAD2) cells are also significantly replicative incompetent but retain viability. Moreover, they show significantly higher levels of anaphase bridges and polyploidy compared to controls. In addition, these cells secrete higher levels of IL-6 and IL-8 representing key components of the senescence-associated secretory phenotype (SASP) with the ability to impact on neighbouring cells. In support of this, MAD2 cells show enhanced migratory ability. At 72 h after paclitaxel, MAD2 cells show a significant further induction of senescence compared with paclitaxel naive controls. In addition, there are significantly more viable cells in the MAD2 MCF7 cell line after paclitaxel reflecting the observed increase in senescence. CONCLUSION: Considering that paclitaxel targets actively dividing cells, these senescent cells will evade cytotoxic kill. In conclusion, compromised MAD2 levels induce a population of senescent cells resistant to paclitaxel.

Stockpiling antiviral drugs for the next influenza pandemic.

The threat of an influenza pandemic has been at the forefront of public health preparedness for more than 5 years. The national planning effort has included stockpiling antiviral drugs in the Centers for Disease Control and Prevention's Strategic National Stockpile (SNS). This article highlights the composition of the SNS before the 2009 H1N1 pandemic and includes considerations for future antiviral stockpile purchases, focusing on emergence of oseltamivir resistance and the need for additional pediatric supplies.