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Sökning: WFRF:(Hardwick R)

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1.
  • Niemi, MEK, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • 2017
  • Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
  • Tidskriftsartikel (refereegranskat)
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  • Galluzzi, L, et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes.
  • 2009
  • Ingår i: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 16:8, s. 1093-107
  • Forskningsöversikt (refereegranskat)abstract
    • Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies. It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios. Thus far, dozens of methods have been proposed to quantify cell death-related parameters. However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate. Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls. These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise. Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells.
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  • Ovaskainen, Otso, et al. (författare)
  • Global Spore Sampling Project: A global, standardized dataset of airborne fungal DNA
  • 2024
  • Ingår i: Scientific Data. - 2052-4463. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Novel methods for sampling and characterizing biodiversity hold great promise for re-evaluating patterns of life across the planet. The sampling of airborne spores with a cyclone sampler, and the sequencing of their DNA, have been suggested as an efficient and well-calibrated tool for surveying fungal diversity across various environments. Here we present data originating from the Global Spore Sampling Project, comprising 2,768 samples collected during two years at 47 outdoor locations across the world. Each sample represents fungal DNA extracted from 24 m3 of air. We applied a conservative bioinformatics pipeline that filtered out sequences that did not show strong evidence of representing a fungal species. The pipeline yielded 27,954 species-level operational taxonomic units (OTUs). Each OTU is accompanied by a probabilistic taxonomic classification, validated through comparison with expert evaluations. To examine the potential of the data for ecological analyses, we partitioned the variation in species distributions into spatial and seasonal components, showing a strong effect of the annual mean temperature on community composition.
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  • Winning, Tracey, et al. (författare)
  • Evidence-based care and the curriculum
  • 2008
  • Ingår i: European journal of dental education. - : Wiley. - 1396-5883 .- 1600-0579. ; 12:Suppl 1, s. 48-63
  • Forskningsöversikt (övrigt vetenskapligt/konstnärligt)abstract
    • An evidence-based (EB) approach has been a significant driver in reforming healthcare over the past two decades. This change has extended across a broad range of health professions, including oral healthcare. A key element in achieving an EB approach to oral healthcare is educating our practitioners, both current and future. This involves providing opportunities integrated within simulated and actual clinical settings for practitioners to learn and apply the principles and processes of evidence-based oral healthcare (EBOHC). Therefore, the focus of this discussion will be on ways in which EBOHC and associated research activities can be implemented into curricula, with the aim of improving patient care. This paper will initially define the scope of EBOHC and research, what these involve, why they are important, and issues that we need to manage when implementing EBOHC. This will be followed by a discussion of factors that enable successful implementation of EBOHC and research into curricula. The paper concludes with suggestions on the future of EBOHC and research in curricula. Key recommendations related to curricula include strengthening of the culture of a scientific approach to education and oral healthcare provision; complete integration of EBOHC into the curriculum at all levels; and faculty development to implement EBOHC based on their needs and evidence of effective approaches. Key recommendations to support implementation and maintenance of EBOHC include recognition and funding for high-quality systematic reviews and development of associated methodologies relevant for global environments; building global capacity of EBOHC researchers; research into improving translation of effective interventions into education and healthcare practice, including patient-reported outcomes, safety and harms, understanding and incorporation of patient values into EB decision-making, economic evaluation research specific to oral healthcare and effective methods for changing practitioner (faculty) behaviours; and extend access to synthesized research in 'user friendly' formats and languages tailored to meet users' needs. Realizing these recommendations may help to improve access to effective healthcare as a basic human right.
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  • Ruskin, J D, et al. (författare)
  • Alveolar ridge repair in a canine model using rhTGF-beta 1 with barrier membranes.
  • 2000
  • Ingår i: Clinical oral implants research. - 0905-7161. ; 11:2, s. 107-15
  • Tidskriftsartikel (refereegranskat)abstract
    • In both normal and membrane-assisted situations, healing events are modulated by the activity of endogenous protein molecules known as cytokines. Due to its mitogenic and chemotactic characteristics, the addition of rhTGF-beta 1 should increase the rate of osteogenesis or increase the potential for bone regeneration in oral osseous defects. This study evaluates the effects of an osteoconductive biodegradable matrix incorporating human recombinant transforming growth factor beta 1 (rhTGF-beta 1) in conjunction with barrier membranes on bone regeneration in canine alveolar ridge defects. A matrix of calcium carbonate and hydroxyethyl starch served as the carrier for test concentrations of 2.0 micrograms/0.8 ml and 20.0 micrograms/0.8 ml of rhTGF-beta 1. One surgically prepared site in each of 13 adult male fox-hounds received 1 of 4 experimental treatment regimens, with 6 sites utilizing barrier membranes. Four sites in each of 2 additional animals, two containing carrier matrix only and 2 with the additional barrier membrane, served as controls. Specimens were retrieved after 2 months of healing and processed for routine light microscopy. The quantity and composition of regenerated bone was examined. Analysis of variance revealed a statistically significant increase (P < 0.05) in the development of bone with the use of rhTGF-beta 1. Likewise, a statistically significant increase in regeneration was found in membrane-protected sites over nonmembrane-protected sites. No statistically significant difference was noted between the low and high dose treatments. The authors conclude that the use of rhTGF-beta 1 in conjunction with a barrier membrane greatly enhances bone regeneration in osseous oral defects.
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  • Tedersoo, L., et al. (författare)
  • Towards a co-crediting system for carbon and biodiversity
  • 2023
  • Ingår i: Plants People Planet. - 2572-2611. ; 6:1, s. 18-28
  • Tidskriftsartikel (refereegranskat)abstract
    • Societal Impact StatementHumankind is facing both climate and biodiversity crises. This article proposes the foundations of a scheme that offers tradable credits for combined aboveground and soil carbon and biodiversity. Multidiversity-as estimated based on high-throughput molecular identification of soil meiofauna, fungi, bacteria, protists, plants and other organisms shedding DNA into soil, complemented by acoustic and video analyses of aboveground macrobiota-offers a cost-effective method that captures much of the terrestrial biodiversity. Such a voluntary crediting system would increase the quality of carbon projects and contribute funding for delivering the Kunming-Montreal Global Biodiversity Framework. Carbon crediting and land offsets for biodiversity protection have been developed to tackle the challenges of increasing greenhouse gas emissions and the loss of global biodiversity. Unfortunately, these two mechanisms are not optimal when considered separately. Focusing solely on carbon capture-the primary goal of most carbon-focused crediting and offsetting commitments-often results in the establishment of non-native, fast-growing monocultures that negatively affect biodiversity and soil-related ecosystem services. Soil contributes a vast proportion of global biodiversity and contains traces of aboveground organisms. Here, we outline a carbon and biodiversity co-crediting scheme based on the multi-kingdom molecular and carbon analyses of soil samples, along with remote sensing estimation of aboveground carbon as well as video and acoustic analyses-based monitoring of aboveground macroorganisms. Combined, such a co-crediting scheme could help halt biodiversity loss by incentivising industry and governments to account for biodiversity in carbon sequestration projects more rigorously, explicitly and equitably than they currently do. In most cases, this would help prioritise protection before restoration and help promote more socially and environmentally sustainable land stewardship towards a 'nature positive' future.
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  • Baiocchi, Gian Luca, et al. (författare)
  • International consensus on a complications list after gastrectomy for cancer
  • 2019
  • Ingår i: Gastric Cancer. - : Springer Science and Business Media LLC. - 1436-3291 .- 1436-3305. ; 22:1, s. 172-189
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Perioperative complications can affect outcomes after gastrectomy for cancer, with high mortality and morbidity rates ranging between 10 and 40%. The absence of a standardized system for recording complications generates wide variation in evaluating their impacts on outcomes and hinders proposals of quality-improvement projects. The aim of this study was to provide a list of defined gastrectomy complications approved through international consensus. Methods: The Gastrectomy Complications Consensus Group consists of 34 European gastric cancer experts who are members of the International Gastric Cancer Association. A group meeting established the work plan for study implementation through Delphi surveys. A consensus was reached regarding a set of standardized methods to define gastrectomy complications. Results: A standardized list of 27 defined complications (grouped into 3 intraoperative, 14 postoperative general, and 10 postoperative surgical complications) was created to provide a simple but accurate template for recording individual gastrectomy complications. A consensus was reached for both the list of complications that should be considered major adverse events after gastrectomy for cancer and their specific definitions. The study group also agreed that an assessment of each surgical case should be completed at patient discharge and 90 days postoperatively using a Complication Recording Sheet. Conclusion: The list of defined complications (soon to be validated in an international multicenter study) and the ongoing development of an electronic datasheet app to record them provide the basic infrastructure to reach the ultimate goals of standardized international data collection, establishment of benchmark results, and fostering of quality-improvement projects.
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  • Di Sacco, A., et al. (författare)
  • Ten golden rules for reforestation to optimize carbon sequestration, biodiversity recovery and livelihood benefits
  • 2021
  • Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 27:7, s. 1328-1348
  • Tidskriftsartikel (refereegranskat)abstract
    • Urgent solutions to global climate change are needed. Ambitious tree-planting initiatives, many already underway, aim to sequester enormous quantities of carbon to partly compensate for anthropogenic CO2 emissions, which are a major cause of rising global temperatures. However, tree planting that is poorly planned and executed could actually increase CO2 emissions and have long-term, deleterious impacts on biodiversity, landscapes and livelihoods. Here, we highlight the main environmental risks of large-scale tree planting and propose 10 golden rules, based on some of the most recent ecological research, to implement forest ecosystem restoration that maximizes rates of both carbon sequestration and biodiversity recovery while improving livelihoods. These are as follows: (1) Protect existing forest first; (2) Work together (involving all stakeholders); (3) Aim to maximize biodiversity recovery to meet multiple goals; (4) Select appropriate areas for restoration; (5) Use natural regeneration wherever possible; (6) Select species to maximize biodiversity; (7) Use resilient plant material (with appropriate genetic variability and provenance); (8) Plan ahead for infrastructure, capacity and seed supply; (9) Learn by doing (using an adaptive management approach); and (10) Make it pay (ensuring the economic sustainability of the project). We focus on the design of long-term strategies to tackle the climate and biodiversity crises and support livelihood needs. We emphasize the role of local communities as sources of indigenous knowledge, and the benefits they could derive from successful reforestation that restores ecosystem functioning and delivers a diverse range of forest products and services. While there is no simple and universal recipe for forest restoration, it is crucial to build upon the currently growing public and private interest in this topic, to ensure interventions provide effective, long-term carbon sinks and maximize benefits for biodiversity and people.
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  • Gonzalez, Grecia M., et al. (författare)
  • Structure of the Escherichia coli ProQ RNA-binding protein
  • 2017
  • Ingår i: RNA. - : COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT. - 1355-8382 .- 1469-9001. ; 23:5, s. 696-711
  • Tidskriftsartikel (refereegranskat)abstract
    • The protein ProQ has recently been identified as a global small noncoding RNA-binding protein in Salmonella, and a similar role is anticipated for its numerous homologs in divergent bacterial species. We report the solution structure of Escherichia call ProQ, revealing an N-terminal FinO-like domain, a C-terminal domain that unexpectedly has a Tudor domain fold commonly found in eukaryotes, and an elongated bridging intradomain linker that is flexible but nonetheless incompressible. Structure-based sequence analysis suggests that the Tudor domain was acquired through horizontal gene transfer and gene fusion to the ancestral FinO-like domain. Through a combination of biochemical and biophysical approaches, we have mapped putative RNA-binding surfaces on all three domains of ProQ and modeled the protein's conformation in the apo and RNA-bound forms. Taken together, these data suggest how the FinO, Tudor, and linker domains of ProQ cooperate to recognize complex RNA structures and serve to promote RNA-mediated regulation.
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  • Hardwick, C., et al. (författare)
  • Low adhesion due to oxide formation in the presence of NaCl
  • 2012
  • Ingår i: 9th International Conference on Contact Mechanics and Wear of Rail/Wheel Systems, CM 2012. ; , s. 309-317
  • Konferensbidrag (refereegranskat)abstract
    • This paper outlines work carried out to assess how adhesion may be influenced by contamination of the rail head with salt/grit from level crossings during winter months when they are applied to the road surfaces as a preventative method to stop ice formation. Twin-disc testing was carried out in which a mechanically formed oxide layer was produced on the disc specimens prior to assessing adhesion levels under realistic contact pressures and slips in the following conditions: dry, wet, dry salt, and two salt-water solutions. Under dry conditions adhesion levels differ little from reference tests without an oxide layer, however, the presence of an oxide layer under wet conditions can be seen to further reduce adhesion from a reference level (0.2) to below 0.1. When NaCl is entrained into the contact it increases adhesion levels above that seen under wet conditions in the presence of an oxide layer, however, the presence of NaCl is most likely to affect the generation of rail head oxides in the first place and in turn influence adhesion.
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  • Noorani, A, et al. (författare)
  • A comparative analysis of whole genome sequencing of esophageal adenocarcinoma pre- and post-chemotherapy
  • 2017
  • Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 27:6, s. 902-912
  • Tidskriftsartikel (refereegranskat)abstract
    • The scientific community has avoided using tissue samples from patients that have been exposed to systemic chemotherapy to infer the genomic landscape of a given cancer. Esophageal adenocarcinoma is a heterogeneous, chemoresistant tumor for which the availability and size of pretreatment endoscopic samples are limiting. This study compares whole-genome sequencing data obtained from chemo-naive and chemo-treated samples. The quality of whole-genomic sequencing data is comparable across all samples regardless of chemotherapy status. Inclusion of samples collected post-chemotherapy increased the proportion of late-stage tumors. When comparing matched pre- and post-chemotherapy samples from 10 cases, the mutational signatures, copy number, and SNV mutational profiles reflect the expected heterogeneity in this disease. Analysis of SNVs in relation to allele-specific copy-number changes pinpoints the common ancestor to a point prior to chemotherapy. For cases in which pre- and post-chemotherapy samples do show substantial differences, the timing of the divergence is near-synchronous with endoreduplication. Comparison across a large prospective cohort (62 treatment-naive, 58 chemotherapy-treated samples) reveals no significant differences in the overall mutation rate, mutation signatures, specific recurrent point mutations, or copy-number events in respect to chemotherapy status. In conclusion, whole-genome sequencing of samples obtained following neoadjuvant chemotherapy is representative of the genomic landscape of esophageal adenocarcinoma. Excluding these samples reduces the material available for cataloging and introduces a bias toward the earlier stages of cancer.
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  • Wilson, L. F. L., et al. (författare)
  • The structure of EXTL3 helps to explain the different roles of bi-domain exostosins in heparan sulfate synthesis
  • 2022
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:3314
  • Tidskriftsartikel (refereegranskat)abstract
    • Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. Though quickly modified, it is initially synthesised as a polysaccharide of alternating β-d-glucuronosyl and N-acetyl-α-d-glucosaminyl residues by exostosins. These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)—each thought to add one type of monosaccharide unit to the backbone. Although previous structures of murine exostosin-like 2 (EXTL2) provide insight into the GT64 domain, the rest of the bi-domain architecture is yet to be characterised; hence, how the two domains co-operate is unknown. Here, we report the structure of human exostosin-like 3 (EXTL3) in apo and UDP-bound forms. We explain the ineffectiveness of EXTL3’s GT47 domain to transfer β-d-glucuronosyl units, and we observe that, in general, the bi-domain architecture would preclude a processive mechanism of backbone extension. We therefore propose that heparan sulfate backbone polymerisation occurs by a simple dissociative mechanism.
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