First Insights into Human Fingertip Regeneration by Echo-Doppler Imaging and Wound Microenvironment Assessment.

Fingertip response to trauma represents a fascinating example of tissue regeneration. Regeneration derives from proliferative mesenchymal cells (blastema) that subsequently differentiate into soft and skeletal tissues. Clinically, conservative treatment of the amputated fingertip under occlusive dressing can shift the response to tissue loss from a wound repair process towards regeneration. When analyzing by Immunoassay the wound exudate from occlusive dressings, the concentrations of brain-derived neurotrophic factor (BDNF) and leukemia inhibitory factor (LIF) were higher in fingertip exudates than in burn wounds (used as controls for wound repair versus regeneration). Vascular endothelial growth factor A (VEGF-A) and platelet-derived growth factor (PDGF) were highly expressed in both samples in comparable levels. In our study, pro-inflammatory cytokines were relatively higher expressed in regenerative fingertips than in the burn wound exudates while chemokines were present in lower levels. Functional, vascular and mechanical properties of the regenerated fingertips were analyzed three months after trauma and the data were compared to the corresponding fingertip on the collateral uninjured side. While sensory recovery and morphology (pulp thickness and texture) were similar to uninjured sides, mechanical parameters (elasticity, vascularization) were increased in the regenerated fingertips. Further studies should be done to clarify the importance of inflammatory cells, immunity and growth factors in determining the outcome of the regenerative process and its influence on the clinical outcome

East Bay Coalition for the Homeless: Branding Study and Marketing Strategy

There are a number of potential positioning strategies. The two which make the most sense for the EBCH are to “position the EBCH away from others in the category” and to “position the EBCH as unique.” These strategies have the advantage of setting the EBCH apart from the other organizations that address homelessness. Occupying its own “position” in the minds of potential and current donors is not only an effective communications/marketing strategy but also a less costly one because it avoids head-to-head competition and comparisons

Submicron Structures Technology and Research

Contains reports on ten research projects.Joint Services Electronics Program (Contract DAAG29-83-K-0003)Joint Services Electronics Program (Contract DAAL03-86-K-0002)National Science Foundation (Grant ECS82-05701)National Science Foundation (Grant ECS85-06565)Lawrence Livermore Laboratory (Subcontract 2069209)National Science Foundation (Grant ECS85-03443)U.S. Air Force - Office of Scientific Research (Grant AFOSR-85-0154)National Aeronautics and Space Administration (Grant NGL22-009-638)National Science Foundation (through KMS Fusion, Inc.)U.S. Navy - Office of Naval Research (Contract N00014-79-C-0908

900 Km Nile City - 5th IABR International Architecture Biennale Rotterdam 2012

The Nile City has an astonishingly simple layout that is clearly defined by its geographical limits. In the middle, there is the Nile, an approximately half-kilometre-wide body of water that is strongly controlled by the Aswan Dams, several Nile barriers and man-made riverbanks. On both sides of the Nile there is a small strip of land irrigated with Nile water via an ingenious network of water chan- nels, which create an artificial and very fertile oasis. On av- erage, the valley is no wider than 12 kilometres, and it ends abruptly when it reaches the two mountain chains that soar as high as 300 metres and form the edges of the Sahara. The infrastructure of the Nile City is closely linked to these morphological conditions. A single railway line, which was already built by the British in the 19th century, runs over 900 kilometres along the middle of the valley up to Aswan, forming a kind of “subway” for the Nile City with stops every 50 kilometres or so. Along both desert edges run two very functional highways connecting the Nile City to Cairo and the Red Sea. Every 200 kilometres there is a little district capital with its own bridge over the river and a small airport, each of them serving as an urban satellite in the desert. In light of these conditions, the Nile City can be read on a larger scale as a very logical and beautiful diagram of in- frastructure and landscape, and it can be understood as a natural linear city, one that is placed not in a lush Arca- dian landscape but in the harsh and beautiful emptiness of the Sahara. The Nile City is a linear city in the middle of nowhere – the only place where man can survive in an otherwise endless ocean of sand and stones

A naphthyridine carboxamide provides evidence for discordant resistance between mechanistically identical inhibitors of HIV-1 integrase

The increasing incidence of resistance to current HIV-1 therapy underscores the need to develop antiretroviral agents with new mechanisms of action. Integrase, one of three viral enzymes essential for HIV-1 replication, presents an important yet unexploited opportunity for drug development. We describe here the identification and characterization of L-870,810, a small-molecule inhibitor of HIV-1 integrase with potent antiviral activity in cell culture and good pharmacokinetic properties. L-870,810 is an inhibitor with an 8-hydroxy-(1,6)-naphthyridine-7-carboxamide pharmacophore. The compound inhibits HIV-1 integrase-mediated strand transfer, and its antiviral activity in vitro is a direct consequence of this ascribed effect on integration. L-870,810 is mechanistically identical to previously described inhibitors from the diketo acid series; however, viruses selected for resistance to L-870,810 contain mutations (integrase residues 72, 121, and 125) that uniquely confer resistance to the naphthyridine. Conversely, mutations associated with resistance to the diketo acid do not engender naphthyridine resistance. Importantly, the mutations associated with resistance to each of these inhibitors map to distinct regions within the integrase active site. Therefore, we propose a model of the two inhibitors that is consistent with this observation and suggests specific interactions with discrete binding sites for each ligand. These studies provide a structural basis and rationale for developing integrase inhibitors with the potential for unique and nonoverlapping resistance profiles

The regulations and role of circadian clock and melatonin in uterine receptivity and pregnancy – An immunological perspective

During normal pregnancy, the mechanism by which the fetus escapes immunological rejection by the maternal womb remains elusive. Given the biological complexities, the immunological mechanism is unlikely to be simply an allograft response in acceptance or rejection of the early pregnancy. Circadian clock responsible for the mammalian circadian rhythm is an endogenously generated rhythm associated with almost all physiological processes including reproduction. There is now growing evidence to suggest that the circadian clocks are intricately linked to the immune system and pregnancy. When perturbed, the role of immune cells can be affected on maintaining the enriched vascular system needed for placentation. This alteration can be triggered by the irregular production of maternal and placental melatonin. Hence, the role of circadian rhythm modulators such as melatonin offers intriguing opportunities for therapy. In this review, we evaluate the complex interaction between the circadian clock and melatonin within the immune system and their roles in the circadian regulation and maintenance of normal pregnancy.</p