Fitting an extended INDSCAL model to three-way proximity data

The INDSCAL individual differences scaling model is extended by assuming dimensions specific to each stimulus or other object, as well as dimensions common to all stimuli or objects. An alternating maximum likelihood procedure is used to seek maximum likelihood estimates of all parameters of this EXSCAL (Extended INDSCAL) model, including parameters of monotone splines assumed in a quasi-nonmetric approach. The rationale for and numerical details of this approach are described and discussed, and the resulting EXSCAL method is illustrated on some data on perception of musical timbres.     

A History of the Action Learning,Action Research,and Process Management Association (ALARPM): From Brisbane (Australia) to the World Through Inclusion and Networks

Action Learning, Action Research, and Process Management Association (ALARPM) is an organization of volunteers dedicated to the international expansion of action learning, action research, and process management, through world congresses. It has existed for over a dozen years now, despite significant stresses and strains, and has successfully conducted five world congresses with a sixth one in 2003. This history of ALARPM shows that a small group can set out to be international and inclusive from the beginning, so long as it also develops processes to sustain itself internally.     

Vesicular restriction of synaptobrevin suggests a role for calcium in membrane fusion

Release of neurotransmitter occurs when synaptic vesicles fuse with the plasma membrane. This neuronal exocytosis is triggered by calcium and requires three SNARE (soluble-N-ethylmaleimide-sensitive factor attachment protein receptors) proteins: synaptobrevin (also known as VAMP) on the synaptic vesicle, and syntaxin and SNAP-25 on the plasma membrane. Neuronal SNARE proteins form a parallel four-helix bundle that is thought to drive the fusion of opposing membranes. As formation of this SNARE complex in solution does not require calcium, it is not clear what function calcium has in triggering SNARE-mediated membrane fusion. We now demonstrate that whereas syntaxin and SNAP-25 in target membranes are freely available for SNARE complex formation, availability of synaptobrevin on synaptic vesicles is very limited. Calcium at micromolar concentrations triggers SNARE complex formation and fusion between synaptic vesicles and reconstituted target membranes. Although calcium does promote interaction of SNARE proteins between opposing membranes, it does not act by releasing synaptobrevin from synaptic vesicle restriction. Rather, our data suggest a mechanism in which calcium-triggered membrane apposition enables syntaxin and SNAP-25 to engage synaptobrevin, leading to membrane fusion.     

Specific inhibition of human leukocyte elastase by substituted alpha-pyrones

Several a-pyrones have been synthesized and investigated for their in vitro inhibitory activity using a-chymotrypsin (a-CT), porcine pancreatic elastase (PPE) and human leukocyte elastase (HLE). 4-Hydroxy-6-undecyl-2H-pyran-2-one 4, 4-Hydroxy-6-[(1-butyl)heptyl]-2H-pyran-2-one 5 and 4-Methoxy-6-[(1-butyl) heptyl]-2H-pyran-2-one 6 were found to be specific inhibitors of HLE. These compounds constitute a promising new class of HLE inhibitors.     

Apoptosis induced by vitamin A signaling is crucial for connecting the ureters to the bladder

Removal of toxic substances from the blood depends on patent connections between the kidney, ureters and bladder that are established when the ureter is transposed from its original insertion site in the male genital tract to the bladder. This transposition is thought to occur as the trigone forms from the common nephric duct and incorporates into the bladder. Here we re-examine this model in the context of normal and abnormal development. We show that the common nephric duct does not differentiate into the trigone but instead undergoes apoptosis, a crucial step for ureter transposition controlled by vitamin A-induced signals from the primitive bladder. Ureter abnormalities occur in 1-2% of the human population and can cause obstruction and end-stage renal disease. These studies provide an explanation for ureter defects underlying some forms of obstruction in humans and redefine the current model of ureter maturation.     

WNT7b mediates macrophage-induced programmed cell death in patterning of the vasculature

Macrophages have a critical role in inflammatory and immune responses through their ability to recognize and engulf apoptotic cells. Here we show that macrophages initiate a cell-death programme in target cells by activating the canonical WNT pathway. We show in mice that macrophage WNT7b is a short-range paracrine signal required for WNT-pathway responses and programmed cell death in the vascular endothelial cells of the temporary hyaloid vessels of the developing eye. These findings indicate that macrophages can use WNT ligands to influence cell-fate decisions--including cell death--in adjacent cells, and raise the possibility that they do so in many different cellular contexts.