Trading interactions for topology in scale-free networks

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, $\gamma' = (\gamma - \mu)/(1-\mu)$, describes how a shift of the standard exponent $\gamma$ of the degree distribution $P(q)$ can absorb the effect of degree-dependent pair interactions $J_{ij} \propto (q_iq_j)^{-\mu}$. 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

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

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?

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

Functional detection of MDR1/P170 and MRP/P190-mediated multidrug resistance in tumour cells by flow cytometry.

Multidrug resistance (MDR) in tumour cells is often caused by the overexpression of the plasma membrane drug transporter P-glycoprotein (P-gp) or the recently discovered multidrug resistance-associated protein (MRP). In this study we investigated the specificity and sensitivity of the fluorescent probes rhodamine 123 (R123), daunorubicin (DNR) and calcein acetoxymethyl ester (calcein-AM) in order to detect the function of the drug transporters P-gp and MRP, using flow cytometry. The effects of modulators on the accumulation and retention of these probes were compared in several pairs of sensitive and P-gp- as well as MRP-overexpressing cell lines. R123, in combination with the modulator PSC833, provided the most sensitive test for detecting P-gp-mediated resistance. Moreover, in a 60 min drug accumulation assay R123 can be regarded as a P-gp-specific probe, since R123 is not very efficiently effluxed by MRP. In contrast to R123, a 60 min DNR or calcein-AM accumulation test could be used to detect MRP-mediated resistance. The MRP-specific modulator genistein could be used in combination with DNR, but not with calcein-AM. Vincristine (VCR) can be used to increase the cellular uptake of calcein-AM in MDR cells, but is not specific for MRP. Thus, although the combination of DNR with genistein appeared to be as sensitive as the combination of calcein-AM with VCR, the former may be used to probe specific MRP activity whereas the latter provides a combined (P-gp + MRP) functional MDR parameter. With these functional assays the role and relative importance of P-gp and MRP can be studied in, for example, haematological malignancies

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

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