1,514 research outputs found

    Local Data Spaces: Leveraging trusted research environments for secure location-based policy research in the age of coronavirus disease-2019

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    This work explores the use of Trusted Research Environments for the secure analysis of sensitive, record-level data on local coronavirus disease-2019 (COVID-19) inequalities and economic vulnerabilities. The Local Data Spaces (LDS) project was a targeted rapid response and cross-disciplinary collaborative initiative using the Office for National Statistics’ Secure Research Service for localized comparison and analysis of health and economic outcomes over the course of the COVID-19 pandemic. Embedded researchers worked on co-producing a range of locally focused insights and reports built on secure secondary data and made appropriately open and available to the public and all local stakeholders for wider use. With secure infrastructure and overall data governance practices in place, accredited researchers were able to access a wealth of detailed data and resources to facilitate more targeted local policy analysis. Working with data within such infrastructure as part of a larger research project involved advanced planning and coordination to be efficient. As new and novel granular data resources become securely available (e.g., record-level administrative digital health records or consumer data), a range of local policy insights can be gained across issues of public health or local economic vitality. Many of these new forms of data however often come with a large degree of sensitivity around issues of personal identifiability and how the data is used for public-facing research and require secure and responsible use. Learning to work appropriately with secure data and research environments can open up many avenues for collaboration and analysis

    Amino Acids Are an Ineffective Fertilizer for Dunaliella spp. Growth

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    Autotrophic microalgae are a promising bioproducts platform. However, the fundamental requirements these organisms have for nitrogen fertilizer severely limit the impact and scale of their cultivation. As an alternative to inorganic fertilizers, we investigated the possibility of using amino acids from deconstructed biomass as a nitrogen source in the genus Dunaliella. We found that only four amino acids (glutamine, histidine, cysteine, and tryptophan) rescue Dunaliella spp. growth in nitrogen depleted media, and that supplementation of these amino acids altered the metabolic profile of Dunaliella cells. Our investigations revealed that histidine is transported across the cell membrane, and that glutamine and cysteine are not transported. Rather, glutamine, cysteine, and tryptophan are degraded in solution by a set of oxidative chemical reactions, releasing ammonium that in turn supports growth. Utilization of biomass-derived amino acids is therefore not a suitable option unless additional amino acid nitrogen uptake is enabled through genetic modifications of these algae

    Paths and partitions: combinatorial descriptions of the parafermionic states

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    The Z_k parafermionic conformal field theories, despite the relative complexity of their modes algebra, offer the simplest context for the study of the bases of states and their different combinatorial representations. Three bases are known. The classic one is given by strings of the fundamental parafermionic operators whose sequences of modes are in correspondence with restricted partitions with parts at distance k-1 differing at least by 2. Another basis is expressed in terms of the ordered modes of the k-1 different parafermionic fields, which are in correspondence with the so-called multiple partitions. Both types of partitions have a natural (Bressoud) path representation. Finally, a third basis, formulated in terms of different paths, is inherited from the solution of the restricted solid-on-solid model of Andrews-Baxter-Forrester. The aim of this work is to review, in a unified and pedagogical exposition, these four different combinatorial representations of the states of the Z_k parafermionic models. The first part of this article presents the different paths and partitions and their bijective relations; it is purely combinatorial, self-contained and elementary; it can be read independently of the conformal-field-theory applications. The second part links this combinatorial analysis with the bases of states of the Z_k parafermionic theories. With the prototypical example of the parafermionic models worked out in detail, this analysis contributes to fix some foundations for the combinatorial study of more complicated theories. Indeed, as we briefly indicate in ending, generalized versions of both the Bressoud and the Andrews-Baxter-Forrester paths emerge naturally in the description of the minimal models.Comment: 53 pages (v2: minor modifications,v3: 3 typos corrected); to appear in the special issue of J. Math. Phys. on "Integrable Quantum Systems and Solvable Statistical Mechanics Models.

    Mineral Composition of Serial Slaughter Holstein Carcasses

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    Carcasses of 115 Holstein steers were divided into lean, bone, internal cavity, hide, and fat tissues for analysis of P, Ca, K, Mg, and S retention. Every 28 days, five steers from each of two treatments, fed Zilmax for 20 days prior to harvest or not fed Zilmax, were harvested. There were no differences due to treatment or days on feed when mineral retention was expressed as g/100 g of protein gain. Expressing mineral retention relative to protein gain reduced variation due to rate of gain and animal size

    Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling

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    Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα(Thr172) and CREB-1(Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65(Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs

    Viral Superantigen Drives Extrafollicular and Follicular B Cell Differentiation Leading to Virus-specific Antibody Production

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    Mouse mammary tumor virus (MMTV[SW]) encodes a superantigen expressed by infected B cells. It evokes an antibody response specific for viral envelope protein, indicating selective activation of antigen-specific B cells. The response to MMTV(SW) in draining lymph nodes was compared with the response to haptenated chicken gamma globulin (NP-CGG) using flow cytometry and immunohistology. T cell priming occurs in both responses, with T cells proliferating in association with interdigitating dendritic cells in the T zone. T cell proliferation continues in the presence of B cells in the outer T zone, and B blasts then undergo exponential growth and differentiation into plasma cells in the medullary cords. Germinal centers develop in both responses, but those induced by MMTV(SW) appear later and are smaller. Most T cells activated in the T zone and germinal centers in the MMTV(SW) response are superantigen specific and these persist for weeks in lymph nodes draining the site MMTV(SW) injection; this contrasts with the selective loss of superantigen-specific T cells from other secondary lymphoid tissues. The results indicate that this viral superantigen, when expressed by professional antigen-presenting cells, drives extrafollicular and follicular B cell differentiation leading to virus-specific antibody production

    JWST/NIRCam Transmission Spectroscopy of the Nearby Sub-Earth GJ 341b

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    We present a JWST/NIRCam transmission spectrum from 3.95.03.9-5.0 μ\mum of the recently-validated sub-Earth GJ 341b (RP=0.92\mathrm{R_P} = 0.92 R\mathrm{R_{\oplus}}, Teq=540\mathrm{T_{eq}} = 540 K) orbiting a nearby bright M1 star (d=10.4\mathrm{d} = 10.4 pc, Kmag=5.6\mathrm{K_{mag}}=5.6). We use three independent pipelines to reduce the data from the three JWST visits and perform several tests to check for the significance of an atmosphere. Overall, our analysis does not uncover evidence of an atmosphere. Our null hypothesis tests find that none of our pipelines' transmission spectra can rule out a flat line, although there is weak evidence for a Gaussian feature in two spectra from different pipelines (at 2.3 and 2.9σ2.9\sigma). However, the candidate features are seen at different wavelengths (4.3 μ\mum vs 4.7 μ\mum), and our retrieval analysis finds that different gas species can explain these features in the two reductions (CO2_2 at 3.1σ3.1\sigma compared to O3_3 at 2.9σ2.9\sigma), suggesting that they are not real astrophysical signals. Our forward model analysis rules out a low mean molecular weight atmosphere (<350×< 350\times solar metallicity) to at least 3σ3\sigma, and disfavors CH4_4-dominated atmospheres at 13σ1-3\sigma, depending on the reduction. Instead, the forward models find our transmission spectra are consistent with no atmosphere, a hazy atmosphere, or an atmosphere containing a species that does not have prominent molecular bands across the NIRCam/F444W bandpass, such as a water-dominated atmosphere. Our results demonstrate the unequivocal need for two or more transit observations analyzed with multiple reduction pipelines, alongside rigorous statistical tests, to determine the robustness of molecular detections for small exoplanet atmospheres.Comment: 25 pages, 18 figures, 6 tables. Accepted for publication in A

    Disease acceptance and adherence to imatinib in Taiwanese chronic myeloid leukaemia outpatients

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    Background The launch of imatinib has turned chronic myeloid leukaemia (CML) into a chronic illness due to the dramatic improvement in survival. Several recent studies have demonstrated that poor adherence to imatinib may hamper the therapeutic outcomes and result in increased medical expenditures, whilst research on exploring the reasons for non-adherence to imatinib is still limited. Objective This study aimed to explore the experience of patients as they journey through their CML treatments and associated imatinib utilisation in order to understand the perceptions, attitudes and concerns that may influence adherence to imatinib treatment. Setting This study was conducted at oncology outpatient clinics in a medical centre in southern Taiwan. Methods CML patients who regularly attended the oncology outpatient clinics to receive imatinib treatment from October 2011 to March 2012 were invited to participate in the study. Semi-structured face-to-face interviews were used to explore patients’ experiences and views of their treatment, their current CML status and CML-related health conditions, their concerns about imatinib treatment and imatinib-taking behaviours. Patient interviews were recorded, transcribed verbatim and thematically analysed using the constant comparison approach. Main outcome measure Themes related to patients’ views of the disease and health conditions, worries and concerns influencing imatinib utilisation behaviours are reported. Results Forty-two CML patients participated in the interviews. The emerging themes included: acceptance of current disease and health status, misconceptions about disease progression, factors associated with adherence to imatinib, concerns and management of adverse drug effects. Participants regarded CML as a chronic disease but had misconceptions about disease progression, therapeutic monitoring, resistance to imatinib and symptoms of side effects. Participants were generally adherent to imatinib and favoured long-term prescriptions to avoid regular outpatient visits for medication refills. Experiencing adverse effect was the main reason influencing adherence and led to polypharmacy. Most participants altered medicine-taking behaviours to maintain long-term use of imatinib. Conclusion Taiwanese CML patients are adherent to imatinib but report changing their medication-taking behaviour due to adverse drug effects and associated polypharmacy. Patients’ misconceptions of the disease and medication suggests that it is necessary to improve communication between patients and healthcare professionals. Routinely providing updated information as part of the patient counselling process should be considered as a means of improving this communication

    Double Trouble: Two Transits of the Super-Earth GJ 1132 b Observed with JWST NIRSpec G395H

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    The search for rocky planet atmospheres with JWST has focused on planets transiting M dwarfs. Such planets have favorable planet-to-star size ratios, enhancing the amplitude of atmospheric features. Since the expected signal strength of atmospheric features is similar to the single-transit performance of JWST, multiple observations are required to confirm any detection. Here, we present two transit observations of the rocky planet GJ 1132 b with JWST NIRSpec G395H, covering 2.8-5.2 μ\mum. Previous HST WFC3 observations of GJ 1132 b were inconclusive, with evidence reported for either an atmosphere or a featureless spectrum based on analyses of the same dataset. Our JWST data exhibit substantial differences between the two visits. One transit is consistent with either a H2_2O-dominated atmosphere containing ~1% CH4_4 and trace N2_2O (χν2\chi^{2}_{\nu} = 1.13) or stellar contamination from unocculted starspots (χν2\chi^{2}_{\nu} = 1.36). However, the second transit is consistent with a featureless spectrum. Neither visit is consistent with a previous report of HCN. Atmospheric variability is unlikely to explain the scale of the observed differences between the visits. Similarly, our out-of-transit stellar spectra show no evidence of changing stellar inhomogeneity between the two visits - observed 8 days apart, only 6.5% of the stellar rotation rate. We further find no evidence of differing instrumental systematic effects between visits. The most plausible explanation is an unlucky random noise draw leading to two significantly discrepant transmission spectra. Our results highlight the importance of multi-visit repeatability with JWST prior to claiming atmospheric detections for these small, enigmatic planets.Comment: 22 pages, 10 figures, 2 tables. Accepted for publication in ApJ Letters. Co-First Authors. Bonus materials and spectral data: https://doi.org/10.5281/zenodo.1000208
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