3,676 research outputs found

    Decoherence Rates in Large Scale Quantum Computers and Macroscopic Systems

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    Markovian regime decoherence effects in quantum computers are studied in terms of the fidelity for the situation where the number of qubits N becomes large. A general expression giving the decoherence time scale in terms of Markovian relaxation elements and expectation values of products of system fluctuation operators is obtained, which could also be applied to study decoherence in other macroscopic systems such as Bose condensates and superconductors. A standard circuit model quantum computer involving three-state lambda system ionic qubits is considered, with qubits localised around well-separated positions via trapping potentials. The centre of mass vibrations of the qubits act as a reservoir. Coherent one and two qubit gating processes are controlled by time dependent localised classical electromagnetic fields that address specific qubits, the two qubit gating processes being facilitated by a cavity mode ancilla, which permits state interchange between qubits. With a suitable choice of parameters, it is found that the decoherence time can be made essentially independent of N.Comment: Minor revisions. To be published in J Mod Opt. One figur

    Palaeoecological assessment of freshwaters in SACs and ASSIs in Northern Ireland

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    This is the final report to the Environment and Heritage Service (EHS) in Northern Ireland on the ‘Palaeoecological investigation of the past biological structure and function in Freshwaters in SACs and ASSIs

    P20-16. Ultra-deep pyrosequencing detects complex patterns of CD8+ T-lymphocyte escape in SIV-infected macaques

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    Background A complex population of viral variants exists within each individual infected with immunodeficiency virus. Deciphering the breadth and frequency of accruing viral mutations provides insight into immune responses, drug resistance, and potential vaccine targets. Contemporary sequencing methods are limited to detection of high frequency variants, leading to an incomplete assessment of the overall viral population. Here, we use ultra-deep pyrosequencing to create a comprehensive picture of CD8+ T-lymphocyte (CD8-TL) escape in two epitopes in SIV-infected rhesus and cynomolgus macaques, revealing a complex pattern of viral variants previously undetected. Methods Plasma was collected from SIV-infected rhesus and cynomolgus macaques at multiple timepoints between weeks 1 and 20 post-infection. Viral RNA was isolated and amplicons spanning the epitopes of interest were generated by RT-PCR, using primers that incorporated a unique 10 bp molecular barcode into each sample. Amplicons were pooled and sequenced on a Roche Genome Sequencer FLX instrument and analyzed using Roche Amplicon Variant Analyzer software. Results The increased sensitivity of ultra-deep pyrosequencing enabled detection of acute CD8-TL escape as early as 17 days post-infection, representing the earliest published example of CD8-TL escape in intrarectally infected macaques. Conversely, we observed the continued presence of a complex viral population well into chronic infection, indicating that viral mutations deemed ''fixed'' by Sanger sequencing are instead complemented by a broad array of viral variants. Additionally, we show that these methods can be applied to sequencing of the entire SIVmac239 genome, supporting the continued use of pyrosequencing in comprehensive SIV infection studies. Conclusion Overall, these findings demonstrate that pyrosequencing can be used to study viral evolution during HIV/SIV infection with an unprecedented degree of sensitivity. Utilizing newly emerging molecular tools is essential and will further our understanding of how viral pathogens evade the immune system

    Skeletal muscle-derived interstitial progenitor cells (PICs) display stem cell properties, being clonogenic, self-renewing and multi-potent in vitro and in vivo.

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    European Research Council, European Community 7th Framework project ENDOSTEM (contract number FP7-Health-2009-ENDOSTEM 241440 (Activation of vasculature-associated stem cells and muscle stem cells for the repair and maintenance of muscle tissue)

    Management of imatinib-resistant CML patients

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    Imatinib has had marked impact on outcomes in chronic myelogenous leukemia (CML) patients for all stages of the disease and is endorsed by international treatment guidelines as the first line option. Although imatinib is highly effective and well tolerated, the development of resistance represents a clinical challenge. Since the most frequently identified mechanism of acquired imatinib resistance is bcr-abl kinase domain point mutations, periodic hematologic, cytogenetic, and molecular monitoring is critical throughout imatinib therapy. Once cytogenetic remission is achieved, residual disease can be monitored by bcr-abl transcript levels as assayed by reverse transcription polymerase chain reaction (RT-PCR). Detection of bcr-abl mutants prior to and during imatinib therapy can aid in risk stratification as well as in determining therapeutic strategies. Thus, mutation screening is indicated in patients lacking or losing hematologic response. Moreover, search for mutations should also be performed when a 3-log reduction of bcr-abl transcripts is not achieved or there is a reproducible increase of transcript levels. In patients harboring mutations which confer imatinib resistance, novel second line tyrosine kinase inhibitors have demonstrated encouraging efficacy with low toxicity. Only the T315I bcr-abl mutant has proved totally resistant to all clinically available bcr-abl inhibitors. Strategies to further increase the rates of complete molecular remissions represent the next frontier in the targeted therapy of CML patients

    The cost of promiscuity: sexual transmission of Nosema microsporidian parasites in polyandrous honey bees

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    Multiple mating (and insemination) by females with different males, polyandry, is widespread across animals, due to material and/or genetic benefits for females. It reaches particularly high levels in some social insects, in which queens can produce significantly fitter colonies by being polyandrous. It is therefore a paradox that two thirds of eusocial hymenopteran insects appear to be exclusively monandrous, in spite of the fitness benefits that polyandry could provide. One possible cost of polyandry could be sexually transmitted parasites, but evidence for these in social insects is extremely limited. Here we show that two different species of Nosema microsporidian parasites can transmit sexually in the honey bee Apis mellifera. Honey bee males that are infected by the parasite have Nosema spores in their semen, and queens artificially inseminated with either Nosema spores or the semen of Nosema-infected males became infected by the parasite. The emergent and more virulent N. ceranae achieved much higher rates of infection following insemination than did N. apis. The results provide the first quantitative evidence of a sexually transmitted disease (STD) in social insects, indicating that STDs may represent a potential cost of polyandry in social insects

    Genetic imprint of vaccination on simian/human immunodeficiency virus type 1 transmitted viral genomes in rhesus macaques.

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    Understanding the genetic, antigenic and structural changes that occur during HIV-1 infection in response to pre-existing immunity will facilitate current efforts to develop an HIV-1 vaccine. Much is known about HIV-1 variation at the population level but little with regard to specific changes occurring in the envelope glycoprotein within a host in response to immune pressure elicited by antibodies. The aim of this study was to track and map specific early genetic changes occurring in the viral envelope gene following vaccination using a highly controlled viral challenge setting in the SHIV macaque model. We generated 449 full-length env sequences from vaccinees, and 63 from the virus inoculum. Analysis revealed a different pattern in the distribution and frequency of mutations in the regions of the envelope gene targeted by the vaccine as well as different patterns of diversification between animals in the naïve control group and vaccinees. Given the high stringency of the model it is remarkable that we were able to identify genetic changes associated with the vaccination. This work provides insight into the characterization of breakthrough viral populations in less than fully efficacious vaccines and illustrates the value of HIV-1 Env SHIV challenge model in macaques to unravel the mechanisms driving HIV-1 envelope genetic diversity in the presence of vaccine induced-responses.Evolutionary analysis was supported by a Wellcome Intermediate Clinical Fellowship while the animal work by National Institutes of Health (NIH) grant 1P01AI06628. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    Equipping for risk: Lessons learnt from the UK shale-gas experience on assessing environmental risks for the future geoenergy use of the deep subsurface

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    \ua9 2024 The Authors. Summary findings are presented from an investigation to improve understanding of the environmental risks associated with developing an unconventional-hydrocarbons industry in the UK. The EQUIPT4RISK project, funded by UK Research Councils, focused on investigations around Preston New Road (PNR), Fylde, Lancashire, and Kirby Misperton Site A (KMA), North Yorkshire, where operator licences to explore for shale gas by hydraulic fracturing (HF) were issued in 2016, although exploration only took place at PNR. EQUIPT4RISK considered atmospheric (greenhouse gases, air quality), water (groundwater quality) and solid-earth (seismicity) compartments to characterise and model local conditions and environmental responses to HF activities. Risk assessment was based on the source-pathway-receptor approach. Baseline monitoring of air around the two sites characterised the variability with meteorological conditions, and isotopic signatures were able to discriminate biogenic methane (cattle) from thermogenic (natural-gas) sources. Monitoring of a post-HF nitrogen-lift (well-cleaning) operation at PNR detected the release of atmospheric emissions of methane (4.2 \ub1 1.4 t CH4). Groundwater monitoring around KMA identified high baseline methane concentrations and detected ethane and propane at some locations. Dissolved methane was inferred from stable-isotopic evidence as overwhelmingly of biogenic origin. Groundwater-quality monitoring around PNR found no evidence of HF-induced impacts. Two approaches for modelling induced seismicity and associated seismic risk were developed using observations of seismicity and operational parameters from PNR in 2018 and 2019. Novel methodologies developed for monitoring include use of machine learning to identify fugitive atmospheric methane, Bayesian statistics to assess changes to groundwater quality, a seismicity forecasting model seeded by the HF-fluid injection rate and high-resolution monitoring of soil-gas methane. The project developed a risk-assessment framework, aligned with ISO 31000 risk-management principles, to assess the theoretical combined and cumulative environmental risks from operations over time. This demonstrated the spatial and temporal evolution of risk profiles: seismic and atmospheric impacts from the shale-gas operations are modelled to be localised and short-lived, while risk to groundwater quality is longer-term
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