Vascular network density determines the amount of oxygen and nutrients delivered to host tissues, but how the vast diversity of densities is generated is unknown. Reiterations of endothelial-tip-cell selection, sprout extension and anastomosis are the basis for vascular network generation, a process governed by the VEGF/Notch feedback loop. Here, we find that temporal regulation of this feedbac...

Current in vitro systems mimicking bone tissues fail to fully integrate the three-dimensional (3D) microvasculature and bone tissue microenvironments, decreasing their similarity to in vivo conditions. Here, we propose 3D microvascular networks in a hydroxyapatite (HA)-incorporated extracellular matrix (ECM) for designing and manipulating a vascularized bone tissue model in a microfluidic devic...

Regulation of neurite outgrowth and structural plasticity may involve the expression of intrinsic determinants controlling growth competence. We have tested this concept by targeting constitutive expression of the growth-associated protein GAP-43 to the neurons of adult transgenic mice. Such mice showed striking spontaneous nerve sprouting at the neuromuscular junction and in the terminal field...

β-Secretase (BACE1), the enzyme responsible for the first and rate-limiting step in the production of amyloid-β peptides, is an attractive target for the treatment of Alzheimer's disease. In this study, we report the application of the de novo fragment-based molecular design program SPROUT to the discovery of a series of nonpeptide BACE1 inhibitors based upon a biphenylacetamide scaffold. The b...

We propose a deterministic two-scale tissue-cellular approach for modeling growth factor-induced angiogenesis. The bioreaction and diffusion of capillary growth factors (CGF) are modeled at a tissue scale, whereas capillary extension, branching and anastomosis are modeled at a cellular scale. The capillary indicator function is used to bridge these two scales. To solve the equation system numer...

A statistical quantity suitable for distinguishing simply-connected RobertsonWalker (RW) universes is introduced, and its explicit expressions for the three possible classes of simply-connected RW universes with an uniform distribution of matter are determined. Graphs of the distinguishing mark for each class of RW universes are presented and analyzed. There sprout from our results an improveme...

We have read the contribution of Proctor et al. (10) with great interest. It illustrates most explicitly that food products of vegetable origin may be associated with outbreaks of salmonellosis with an attack rate of the order of 10, until recently considered to be due mainly to products of animal origin. The finding that decontamination of seeds (1) does not preclude the possibility that sprou...

SPROUT is an interactive computer system for structure based molecular design. The system consists of several modules that address the different subproblems of structure based drug design. This paper describes the visualisation techniques applied in the program: the display of the novel (geometric region) representation of the interaction sites and the molecular surface display based on a 3D gr...