418 research outputs found

    A technique for optimal temperature estimation for modeling sunrise/sunset thermal snap disturbance torque

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    A predictive temperature estimation technique which can be used to drive a model of the Sunrise/Sunset thermal 'snap' disturbance torque experienced by low Earth orbiting spacecraft is described. The twice per orbit impulsive disturbance torque is attributed to vehicle passage in and out of the Earth's shadow cone (umbra), during which large flexible appendages undergo rapidly changing thermal conditions. Flexible members, in particular solar arrays, experience rapid cooling during umbra entrance (Sunset) and rapid heating during exit (Sunrise). The thermal 'snap' phenomena has been observed during normal on-orbit operations of both the LANDSAT-4 satellite and the Communications Technology Satellite (CTS). Thermal 'snap' has also been predicted to be a dominant source of error for the TOPEX satellite. The fundamental equations used to model the Sunrise/Sunset thermal 'snap' disturbance torque for a typical solar array like structure will be described. For this derivation the array is assumed to be a thin, cantilevered beam. The time varying thermal gradient is shown to be the driving force behind predicting the thermal 'snap' disturbance torque and therefore motivates the need for accurate estimates of temperature. The development of a technique to optimally estimate appendage surface temperature is highlighted. The objective analysis method used is structured on the Gauss-Markov Theorem and provides an optimal temperature estimate at a prescribed location given data from a distributed thermal sensor network. The optimally estimated surface temperatures could then be used to compute the thermal gradient across the body. The estimation technique is demonstrated using a typical satellite solar array

    Coping with multiple enemies : pairwise interactions do not predict evolutionary change in complex multitrophic communities

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    Predicting the ecological and evolutionary trajectories of populations in multispecies communities is one of the fundamental challenges in ecology. Many of these predictions are made by scaling patterns observed from pairwise interactions. Here, we show that the coupling of ecological and evolutionary outcomes is likely to be weaker in increasingly complex communities due to greater chance of life-history trait correlations. Using model microbial communities comprising a focal bacterial species (Bacillus subtilis), a bacterial competitor, protist predator and phage parasite, we found that increasing the number of enemies in a community had an overall negative effect on B. subtilis population growth. However, only the competitor imposed direct selection for B. subtilis trait evolution in pairwise cultures and this effect was weakened in the presence of other antagonists that had a negative effect on the competitor. In contrast, adaptation to parasites was driven indirectly by correlated selection where competitors had a positive and predators a negative effect. For all measured traits, selection in pairwise communities was a poor predictor of B. subtilis evolution in more complex communities. Together, our results suggest that coupling of ecological and evolutionary outcomes is interaction-specific and weakly coupled in more complex communities. We conclude that understanding 2 the ecological and evolutionary mechanisms underpinning trait correlations is crucial to predict species response to global change in complex microbial communitie

    Efficacy of the Pentavalent Rotavirus Vaccine, RotaTeq (RV5), Between Doses of a 3-Dose Series and With Less Than 3 Doses (Incomplete Regimen)

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    Post-hoc analyses of the Rotavirus Efficacy and Safety Trial (RES T) were conducted to determine whether the pentavalent rotavirus vaccine (RV5) confers early protection against rotavirus gastroenteritis (RVGE) before completion of the 3-dose regimen. To evaluate the efficacy of RV5 between doses in reducing the rates of RVGE-related hospitalizations and emergency department (ED) visits in infants who ultimately received all 3 doses of RV5/placebo, events occurring from 2 weeks after the first and second doses to receipt of the subsequent dose (Analysis A) and events occurring from 2 weeks after the first and second doses to 2 weeks after the subsequent dose (Analysis B) were analyzed. In Analysis A, RV5 reduced the rates of combined hospitalizations and ED visits for G1-G4 RVGE or RVGE regardless of serotype between doses 1 and 2 by 100% [95% confidence interval (CI): 72-100%] or 82% (95% CI: 39-97%), respectively, and between doses 2 and 3, RV5 reduced the rates of combined hospitalizations and ED visits for G1-G4 RVGE or RVGE regardless of serotype by 91% (95% CI: 63-99%) or 84% (95% CI: 54-96%), respectively. Similar rate reductions were observed in Analysis B. These data suggest that RV5 provides a high level of protection between doses against hospitalizations and ED visits for RVGE starting as early as 14 days after the first dose

    Temporal control of gene deletion in sensory ganglia using a tamoxifen-inducible Advillin-Cre-ERT2 recombinase mouse

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    <p>Abstract</p> <p>Background</p> <p>Tissue-specific gene deletion has proved informative in the analysis of pain pathways. <it>Advillin </it>has been shown to be a pan-neuronal marker of spinal and cranial sensory ganglia. We generated BAC transgenic mice using the <it>Advillin </it>promoter to drive a tamoxifen-inducible CreERT2 recombinase construct in order to be able to delete genes in adult animals. We used a floxed stop <it>ROSA26LacZ </it>reporter mouse to examine functional Cre expression, and analysed the behaviour of mice expressing Cre recombinase.</p> <p>Results</p> <p>We used recombineering to introduce a CreERT2 cassette in place of exon 2 of the <it>Advillin </it>gene into a BAC clone (RPCI23-424F19) containing the 5' region of the <it>Advillin </it>gene. Transgenic mice were generated using pronuclear injection. The resulting <it>AvCreERT2 </it>transgenic mice showed a highly specific expression pattern of Cre activity after tamoxifen induction. Recombinase activity was confined to sensory neurons and no expression was found in other organs. Less than 1% of neurons showed Cre expression in the absence of tamoxifen treatment. Five-day intraperitoneal treatment with tamoxifen (2 mg per day) induced Cre recombination events in ≈90% of neurons in dorsal root and cranial ganglia. Cell counts of dorsal root ganglia (DRG) from transgenic animals with or without tamoxifen treatment showed no neuronal cell loss. Sensory neurons in culture showed ≈70% induction after 3 days treatment with tamoxifen. Behavioural tests showed no differences between wildtype, <it>AvCreERT2 </it>and tamoxifen-treated animals in terms of motor function, responses to light touch and noxious pressure, thermal thresholds as well as responses to inflammatory agents.</p> <p>Conclusions</p> <p>Our results suggest that the inducible pan-DRG <it>AvCreERT2 </it>deleter mouse strain is a useful tool for studying the role of individual genes in adult sensory neuron function. The pain phenotype of the Cre-induced animal is normal; therefore any alterations in pain processing can be unambiguously attributed to loss of the targeted gene.</p

    Acupuncture for chronic neck pain: a pilot for a randomised controlled trial

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    Background: Acupuncture is increasingly being used for many conditions including chronic neck pain. However the evidence remains inconclusive, indicating the need for further well-designed research. The aim of this study was to conduct a pilot randomised controlled parallel arm trial, to establish key features required for the design and implementation of a large-scale trial on acupuncture for chronic neck pain. Methods: Patients whose GPs had diagnosed neck pain were recruited from one general practice, and randomised to receive usual GP care only, or acupuncture ( up to 10 treatments over 3 months) as an adjunctive treatment to usual GP care. The primary outcome measure was the Northwick Park Neck Pain Questionnaire (NPQ) at 3 months. The primary analysis was to determine the sample size for the full scale study. Results: Of the 227 patients with neck pain identified from the GP database, 28 (12.3%) consenting patients were eligible to participate in the pilot and 24 (10.5%) were recruited to the trial. Ten patients were randomised to acupuncture, receiving an average of eight treatments from one of four acupuncturists, and 14 were randomised to usual GP care alone. The sample size for the full scale trial was calculated from a clinically meaningful difference of 5% on the NPQ and, from this pilot, an adjusted standard deviation of 15.3%. Assuming 90% power at the 5% significance level, a sample size of 229 would be required in each arm in a large-scale trial when allowing for a loss to follow-up rate of 14%. In order to achieve this sample, one would need to identify patients from databases of GP practices with a total population of 230,000 patients, or approximately 15 GP practices roughly equal in size to the one involved in this study (i.e. 15,694 patients). Conclusion: This pilot study has allowed a number of recommendations to be made to facilitate the design of a large-scale trial, which in turn will help to clarify the existing evidence base on acupuncture for neck pain

    Comparison of the development of SARS-Coronavirus-2-specific cellular immunity, and central memory CD4+ T-Cell responses following infection versus vaccination

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    Memory T-cell responses following infection with coronaviruses are reportedly long-lived and provide long-term protection against severe disease. Whether vaccination induces similar long-lived responses is not yet clear since, to date, there are limited data comparing memory CD4+ T-cell responses induced after SARS-CoV-2 infection versus following vaccination with BioNTech/Pfizer BNT162b2. We compared T-cell immune responses over time after infection or vaccination using ELISpot, and memory CD4+ T-cell responses three months after infection/vaccination using activation-induced marker flow cytometric assays. Levels of cytokine-producing T-cells were remarkably stable between three and twelve months after infection, and were comparable to IFNγ+ and IFNγ+IL-2+ T-cell responses but lower than IL-2+ T-cell responses at three months after vaccination. Consistent with this finding, vaccination and infection elicited comparable levels of SARS-CoV-2 specific CD4+ T-cells after three months in addition to comparable proportions of specific central memory CD4+ T-cells. By contrast, the proportions of specific effector memory CD4+ T-cells were significantly lower, whereas specific effector CD4+ T-cells were higher after infection than after vaccination. Our results suggest that T-cell responses—as measured by cytokine expression—and the frequencies of SARS-CoV-2-specific central memory CD4+T-cells—indicative of the formation of the long-lived memory T-cell compartment—are comparably induced after infection and vaccination

    Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'.

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    Innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. Dectin-1 (also known as CLEC7A) is a pattern-recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects β-glucans in fungal cell walls and triggers direct cellular antimicrobial activity, including phagocytosis and production of reactive oxygen species (ROS). In contrast to inflammatory responses stimulated upon detection of soluble ligands by other pattern-recognition receptors, such as Toll-like receptors (TLRs), these responses are only useful when a cell comes into direct contact with a microbe and must not be spuriously activated by soluble stimuli. In this study we show that, despite its ability to bind both soluble and particulate β-glucan polymers, Dectin-1 signalling is only activated by particulate β-glucans, which cluster the receptor in synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 (also known as PTPRC and PTPRJ, respectively) are excluded (Supplementary Fig. 1). The 'phagocytic synapse' now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular antimicrobial responses only when they are required

    Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

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    Funding: The authors thank the Wellcome Trust (102705) and the Universities of Aberdeen and Cape Town for funding. This research was also supported, in part, by National Institutes of Health GM53522 and GM083016 to DLW. KF and BNL are funded by the Fonds Wetenschappelijk Onderzoek, BNL is the recipient of an European Research Commission consolidator grant and participates in the European Union FP7 programs EUBIOPRED and MedALL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

    Synthesis and Spectroscopic Characterization of Two New Thiosaccharinate Salts : Molecular Structure of Bis(triphenylphosphine)iminium thiosaccharinate, PNP(tsac)

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    We report the synthesis, FTIR, Raman and NMR spectroscopic features of bis(triphenylphosphine)iminium and tetrabutylammonium thiosaccharinates, PNP(tsac) and NBu₄(tsac) (tsac: thiosaccharinate anion, PNP: bis(triphenylphosphine)iminium). The molecular structure of the former compound was determined by X-ray diffraction methods. The salt crystallizes in the monoclinic P2₁/n space group with a = 9.6481(9), b = 29.258(3), c = 13.177(2) Å, β = 97.53(1)°, and Z = 4 molecules per unit cell. Slight but significant changes in the bonding structure of the thiosaccharinate anion as compared with those reported for the neutral molecule are observed.Centro de Química InorgánicaInstituto de Física La Plat
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