1,776 research outputs found

    Trading interactions for topology in scale-free networks

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    Scale-free networks with topology-dependent interactions are studied. It is shown that the universality classes of critical behavior, which conventionally depend only on topology, can also be explored by tuning the interactions. A mapping, γ=(γμ)/(1μ)\gamma' = (\gamma - \mu)/(1-\mu), describes how a shift of the standard exponent γ\gamma of the degree distribution P(q)P(q) can absorb the effect of degree-dependent pair interactions Jij(qiqj)μJ_{ij} \propto (q_iq_j)^{-\mu}. Replica technique, cavity method and Monte Carlo simulation support the physical picture suggested by Landau theory for the critical exponents and by the Bethe-Peierls approximation for the critical temperature. The equivalence of topology and interaction holds for equilibrium and non-equilibrium systems, and is illustrated with interdisciplinary applications.Comment: 4 pages, 5 figure

    Organ Donation: The Gift, the Weight and the Tyranny of Good Acts

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72413/1/j.1600-6143.2006.01731.x.pd

    Use of A Collagen/Elastin Matrix As Transport Carrier System to Transfer Proliferating Epidermal Cells to Human Dermis in Vitro

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    This in vitro study describes a novel cell culture, transport, and transfer protocol that may be highly suitable for delivering cultured proliferating keratinocytes and melanocytes to large open skin wounds (e.g., burns). We have taken into account previous limitations identified using other keratinocyte transfer techniques, such as regulatory issues, stability of keratinocytes during transport (single cell suspensions undergo terminal differentiation), ease of handling during application, and the degree of epidermal blistering resulting after transplantation (both related to transplanting keratinocyte sheets). Large numbers of proliferating epidermal cells (EC) (keratinocytes and melanocytes) were generated within 10-14 days and seeded onto a three-dimensional matrix composed of elastin and collagen types I, III, and V (Matriderm®), which enabled easy and stable transport of the EC for up to 24 h under ambient conditions. All culture conditions were in accordance with the regulations set by the Dutch Central Committee on Research Involving Human Subjects (CCMO). As an in vitro model system for clinical in vivo transfer, the EC were then transferred from Matriderm onto human acellular dermis during a period of 3 days. After transfer the EC maintained the ability to regenerate into a fully differentiated epidermis containing melanocytes on the human dermis. Proliferating keratinocytes were located in the basal layer and keratin-10 expression was located in differentiating suprabasal layers similar to that found in human epidermis. No blistering was observed (separation of the epidermis from the basement membrane). Keratin-6 expression was strongly upregulated in the regenerating epidermis similar to normal wound healing. In summary, we show that EC-Matriderm contains viable, metabolically active keratinocytes and melanocytes cultured in a manner that permits easy transportation and contains epidermal cells with the potential to form a pigmented reconstructed epidermis. This in vitro study has produced a robust protocol that is ready for clinical studies in the future

    Bisphosphonate-Associated Osteonecrosis of the Jaw: Are We Dealing with a Localized Non-Traditional Calciphylaxis?

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    The bisphosphonate (BP) family of drugs has been used as a vital component in cancer therapy and many other diseases. One of the main adverse effects related to (BP) is BP-associated osteonecrosis of the jaw (ONJ). Although this condition was first recognized in 2003, the pathophysiologic mechanism remains undefined. Our hypothesis is that ONJs clinical course and delayed wound healing is in part correlated to a localized non-traditional calciphylaxis. This effect is identified by the evidence of calcium deposition in the connective tissue and around small blood vessels in the soft tissues immediately adjacent to ONJ lesions. This phenomenon helps to fill gaps in the cascade of events which leads to soft tissue ischemia, necrosis, and non-healing ONJ lesions. Our finding adds to the current knowledge of the potential pathophysiologic mechanisms related to ONJ

    The precautions of clinical waste: disposable medical sharps in the United Kingdom

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    This article deals with recent changes in UK guidance on clinical waste, in particular a shift to disposable, single-use instruments and sharps. I use interviews conducted with nurses from a GP practice and two clinical waste managers at alternative treatment and incineration sites as a springboard for reflection on the relationship between the legislation on clinical waste management and its implementation. Scrutinizing the UK guidance, European legislation and World Health Organization principles, I draw out interviewees’ concerns that the changed practices lead to an expansion of the hazardous waste category, with an increased volume going to incineration. This raises questions regarding the regulations’ environmental and health effects, and regarding the precautionary approach embedded in the regulations. Tracing the diverse reverberations of the term ‘waste’ in different points along the journeys made by sharps in particular, and locating these questions in relation to existing literature on waste, I emphasize that public health rationales for the new practices are not made clear in the guidance. I suggest that this relative silence on the subject conceals both the uncertainties regarding the necessity for these means of managing the risks of infectious waste, and the tensions between policies of precautionary public health and environmental sustainability

    The spike generation processes: a case for low level computation

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    Over the last couple of years, it can be said that the focus of the computational aspects of neurons has moved from synaptic weight and firing rate encoding to temporal firing encoding. On the other hand, several elements of these models have been based on some conceptual assumptions that imply relative simple dynamic behaviour of neuronal membrane activity in an active-passive process. In line with recent advances that have produced a better understanding of the biochemical processes that occur within cells, it is proposed that the processes that are involved in a membrane depolarisation cascade are less static than have been assumed so far. In particular, the possibilities of low level computation at the membrane level need to be explored more extensively. In this chapter some computational properties of the spike generation processes are explored using phenomenological models

    Development of a Full-Thickness Human Skin Equivalent In Vitro Model Derived from TERT-Immortalized Keratinocytes and Fibroblasts

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    Currently, human skin equivalents (HSEs) used for in vitro assays (e.g., for wound healing) make use of primary human skin cells. Limitations of primary keratinocytes and fibroblasts include availability of donor skin and donor variation. The use of physiologically relevant cell lines could solve these limitations. The aim was to develop a fully differentiated HSE constructed entirely from human skin cell lines, which could be applied for in vitro wound-healing assays. Skin equivalents were constructed from human TERT-immortalized keratinocytes and fibroblasts (TERT-HSE) and compared with native skin and primary HSEs. HSEs were characterized by hematoxylin-eosin and immunohistochemical stainings with markers for epidermal proliferation and differentiation, basement membrane (BM), fibroblasts, and the extracellular matrix (ECM). Ultrastructure was determined with electron microscopy. To test the functionality of the TERT-HSE, burn and cold injuries were applied, followed by immunohistochemical stainings, measurement of reepithelialization, and determination of secreted wound-healing mediators. The TERT-HSE was composed of a fully differentiated epidermis and a fibroblast-populated dermis comparable to native skin and primary HSE. The epidermis consisted of proliferating keratinocytes within the basal layer, followed by multiple spinous layers, a granular layer, and cornified layers. Within the TERT-HSE, the membrane junctions such as corneosomes, desmosomes, and hemidesmosomes were well developed as shown by ultrastructure pictures. Furthermore, the BM consisted of a lamina lucida and lamina densa comparable to native skin. The dermal matrix of the TERT-HSE was more similar to native skin than the primary construct, since collagen III, an ECM marker, was present in TERT-HSEs and absent in primary HSEs. After wounding, the TERT-HSE was able to reepithelialize and secrete inflammatory wound-healing mediators. In conclusion, the novel TERT-HSE, constructed entirely from human cell lines, provides an excellent opportunity to study in vitro skin biology and can also be used for drug targeting and testing new therapeutics, and ultimately, for incorporating into skin-on-a chip in the future

    Porous Silicon-Based Aptasensors: Toward Cancer Protein Biomarker Detection

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    The anterior gradient homologue-2 (AGR2) protein is an attractive biomarker for various types of cancer. In pancreatic cancer, it is secreted to the pancreatic juice by premalignant lesions, which would be an ideal stage for diagnosis. Thus, designing assays for the sensitive detection of AGR2 would be highly valuable for the potential early diagnosis of pancreatic and other types of cancer. Herein, we present a biosensor for label-free AGR2 detection and investigate approaches for enhancing the aptasensor sensitivity by accelerating the target mass transfer rate and reducing the system noise. The biosensor is based on a nanostructured porous silicon thin film that is decorated with anti-AGR2 aptamers, where real-time monitoring of the reflectance changes enables the detection and quantification of AGR2, as well as the study of the diffusion and target-aptamer binding kinetics. The aptasensor is highly selective for AGR2 and can detect the protein in simulated pancreatic juice, where its concentration is outnumbered by orders of magnitude by numerous proteins. The aptasensor’s analytical performance is characterized with a linear detection range of 0.05-2 mg mL-1, an apparent dissociation constant of 21 ± 1 μM, and a limit of detection of 9.2 μg mL-1 (0.2 μM), which is attributed to mass transfer limitations. To improve the latter, we applied different strategies to increase the diffusion flux to and within the nanostructure, such as the application of isotachophoresis for the preconcentration of AGR2 on the aptasensor, mixing, or integration with microchannels. By combining these approaches with a new signal processing technique that employs Morlet wavelet filtering and phase analysis, we achieve a limit of detection of 15 nM without compromising the biosensor’s selectivity and specificity
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