Determination of the pre-exponential frequency factor for superparamagnetic maghemite particles in magnetoferritin

Magnetization and Mössbauer measurements on maghemite particles with an average particle diameter of 10 nm have been made in the temperature range from 5 K to 353 K spanning the superparamagnetic (SPM) and stable single domain (SD) regimes. The maghemite particles were produced within the iron-storage protein ferritin, resulting in a narrowly-sized, weakly interacting nanocomposite material called magnetoferritin. Experiments combining hysteresis measurements, low temperature remanence, and Mössbauer spectroscopy were used to characterize magnetoferritin and to provide experimental estimates of (1) the pre-exponential frequency factor ƒ0 in the Néel-Arhennius relaxation equation; (2) the SPM threshold size at room temperature for maghemite; and (3) the SD value of Hr/Hc at 0 K. The frequency factor was determined from the difference in blocking temperatures measured by dc magnetization and Mössbauer spectroscopy, yielding a value of f0≈109 Hz. This agrees well with the standard value and justifies the usually assumed superparamagnetic blocking condition of KV = 25 kT for remanence measurements. The SPM threshold size at room temperature for remanence measurements was estimated to be 20–27 nm and the extrapolated SD value at 0 K for Hr/Hc is 1.32. The latter value is slightly larger than the theoretical value of 1.09 but may be more appropriate for weakly interacting SD particles commonly found in sediments and soils. However, ƒ0 for ferrimagnetic magnetoferritin is a factor of 103 lower than was determined previously for native ferritin, which contains antiferromagnetic ferrihydrite cores. The difference in ƒ0 values between the two varieties of ferritin is probably related to the two different types of magnetic spin ordering of the core minerals and suggests that the higher value of ƒ0 is more appropriate for antiferromagnetic minerals like hematite and goethite, whereas the lower value is more appropriate for ferrimagnetic minerals like maghemite, magnetite, or greigite.R.B.F. was supported by NIH grant ROI DK36799-06A4. K.K.W.W. was supported by the BBSRC (U.K.). The Institute for Rock Magnetism (IRM) is supported by grants from the Keck Foundation and the NSF. IRM contribution 9704

Evolution of Models to Support Community and Policy Action with Science: Balancing Pastoral Livelihoods and Wildlife Conservation in Savannas of East Africa

We developed a “continual engagement” model to better integrate knowledge from policy makers, communities, and researchers with the goal of promoting more effective action to balance poverty alleviation and wildlife conservation in 4 pastoral ecosystems of East Africa. The model involved the creation of a core boundary-spanning team, including community facilitators, a policy facilitator, and transdisciplinary researchers, responsible for linking with a wide range of actors from local to global scales. Collaborative researcher–facilitator community teams integrated local and scientific knowledge to help communities and policy makers improve herd quality and health, expand biodiversity payment schemes, develop land-use plans, and fully engage together in pastoral and wildlife policy development. This model focused on the creation of hybrid scientific–local knowledge highly relevant to community and policy maker needs. The facilitation team learned to be more effective by focusing on noncontroversial livelihood issues before addressing more difficult wildlife issues, using strategic and periodic engagement with most partners instead of continual engagement, and reducing costs by providing new scientific information only when deemed essential. We conclude by examining the role of facilitation in redressing asymmetries in power in researcher–community–policy maker teams, the role of individual values and character in establishing trust, and how to sustain knowledge-action links when project funding ends

Identification of VEGF-regulated genes associated with increased lung metastatic potential: functional involvement of tenascin-C in tumor growth and lung metastasis

Metastasis is the primary cause of death in patients with breast cancer. Overexpression of c-myc in humans correlates with metastases, but transgenic mice only show low rates of micrometastases. We have generated transgenic mice that overexpress both c-myc and vascular endothelial growth factor (VEGF) (Myc/VEGF) in the mammary gland, which develop high rates of pulmonary macrometastases. Gene expression profiling revealed a set of deregulated genes in Myc/VEGF tumors compared to Myc tumors associated with the increased metastatic phenotype. Cross-comparisons between this set of genes with a human breast cancer lung metastasis gene signature identified five common targets: tenascin-C(TNC), matrix metalloprotease-2, collagen-6-A1, mannosidase-alpha-1A and HLA-DPA1. Signaling blockade or knockdown of TNC in MDA-MB-435 cells resulted in a significant impairment of cell migration and anchorage-independent cell proliferation. Mice injected with clonal MDA-MB-435 cells with reduced expression of TNC demonstrated a significant decrease (P<0.05) in (1) primary tumor growth; (2) tumor relapse after surgical removal of the primary tumor and (3) incidence of lung metastasis. Our results demonstrate that VEGF induces complex alterations in tissue architecture and gene expression. The TNC signaling pathway plays an important role in mammary tumor growth and metastases, suggesting that TNC may be a relevant target for therapy against metastatic breast cancer

The role of emotion, values, and beliefs in the construction of innovative work realities

Traditional approaches to requirements elicitation stress systematic and rational analysis and representation of organizational context and system requirements. This paper argues that (1) for an organization, a software system implements a shared vision of a future work reality and that (2) understanding the emotions, feelings, values, beliefs, and interests that drive organizational human action is needed in order to invent the requirements of such a software system. This paper debunks some myths about how organizations transform themselves through the adoption of Information and Communication Technology; describes the concepts of emotion, feeling, value, and belief; and presents some constructionist guidelines for the process of eliciting requirements for a software system that helps an organization to fundamentally change its work patterns.(undefined

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Roles of the matrix metalloproteinases in mammary gland development and cancer

Tissue remodeling is a key process involved in normal development, wound healing, bone remodeling, and embryonic implantation, as well as pathological conditions such as tumor invasion and metastasis, and angiogenesis. The degradation of the extracellular matrix that is associated with those processes is mediated by a number of families of extracellular proteinases. These families include the serine proteinases, such as the plasminogen-urokinase plasminogen activator system and leukocyte elastases, the cysteine proteinases, like cathepsin D and L, and the zinc-dependent matrix metalloproteinases (MMPs). Accumulating evidence has highlighted the central role of MMP-driven extracellular matrix remodeling in mammary gland development and breast cancer