Theoretical underpinnings for maximal clique enumeration on perturbed graphs

The problem of enumerating the maximal cliques of a graph is a computationally expensive problem with applications in a number of different domains. Sometimes the benefit of knowing the maximal clique enumeration (MCE) of a single graph is worth investing the initial computation time. However, when graphs are abstractions of noisy or uncertain data, the MCE of several closely related graphs may need to be found, and the computational cost of doing so becomes prohibitively expensive.Here, we present a method by which the cost of enumerating the set of maximal cliques for related graphs can be reduced. By using the MCE for some baseline graph, the MCE for a modified, or perturbed, graph may be obtained by enumerating only the maximal cliques that are created or destroyed by the perturbation. When the baseline and perturbed graphs are relatively similar, the difference set between the two MCEs can be overshadowed by the maximal cliques common to both. Thus, by enumerating only the difference set between the baseline and perturbed graphs’ MCEs, the computational cost of enumerating the maximal cliques of the perturbed graph can be reduced.We present necessary and sufficient conditions for enumerating difference sets when the perturbed graph is formed by several different types of perturbations. We also present results of an algorithm based on these conditions that demonstrate a speedup over traditional calculations of the MCE of perturbed, real biological networks.     

Effect of nicotinic acid on cholera-induced fluid movement and unidirectional sodium fluxes in rabbit jejunum

Cholera toxin produces intestinal secretion and elevation of intestinal cyclic AMP. Nicotinic acid has been shown to prevent these responses. The effect of nicotinic acid on cholera toxin-induced secretion could be caused by decreased plasma-to-lumen flux, increased lumen-to-plasma flux, or a combination of both. The purpose of this study was to define the effects of nicotinic acid on net fluid movement and unidirectional sodium fluxes in rabbit jejunal loops exposed to cholera toxin. In the untreated animals receiving no nicotinic acid, the cholera toxin-exposed loops secreted 0.91 ml/cm/4h above the control loops receiving no cholera toxin (p < 0.01). On the other hand, pretreatment with 100 mg/kg nicotinic acid caused a striking decrease in secretion in the cholera toxin loop, so that the cholera toxin loop was not significantly different from the control loop. Unidirectional sodium fluxes in untreated animals showed that cholera toxin caused an increase in the plasma-to-lumen flux and a decrease in the lumen-to-plasma flux. Both effects were abolished by pretreating the animals with nicotinic acid. These studies indicate that nicotinic acid prevents cholera toxin-induced secretion by restoring the unidirectional fluxes to control levels.     

Effect analysis in higher-order languages

When programs are intended for parallel execution it becomes critical to determine whether the evaluations of two expressions can be carried out independently. We provide a scheme for making such determinations in a typed language with higher-order constructs and imperative features. The heart of our scheme is a mechanism for estimating thesupport of an expression, i.e., the set of global variables involved in its evaluation. This computation requires knowledge of all the aliases of an expression. The inference schemes are presented in a compositional fashion reminiscent of abstract interpretation. We prove the soundness of our estimates with respect to the standard semantics of the language.Supported by National Science Foundation Grant DCR-8602072.     

Flow field analysis in a spiral viscous micropump

The paper presents a stream function solution and a computational analysis for the flow field of a viscous spiral pump, which employs a rotating spiral channel to achieve pumping action. This pump is fabricated using surface micromachining technology. The stream function solution employs a simplified 2D model for the flow field in its spiral channel that neglects the curvature of the spiral, and replaces it with an equivalent straight channel. The effect of spiral wall height on flow rate is analyzed and discussed. 3D computational analyses are obtained and are compared with analytical predictions.     

Investigation of local mercury deposition from a coal-fired power plant using mercury isotopes

Coal combustion accounts for approximately two-thirds of global anthropogenic mercury (Hg) emissions. Enhanced deposition of Hg can occur close to coal-fired utility boilers (CFUBs), but it is difficult to link specific point sources with local deposition. Measurement of Hg stable isotope ratios in precipitation holds promise as a tool to assist in the identification of local Hg deposition related to anthropogenic emissions. We collected daily event precipitation samples in close proximity to a large CFUB in Crystal River, Florida. Precipitation samples collected in Crystal River were isotopically distinct and displayed large negative δ(202)Hg values (mean = -2.56‰, 1 SD = 1.10‰, n = 28). In contrast, precipitation samples collected at other sites in FL that were not greatly impacted by local coal combustion were characterized by δ(202)Hg values close to 0‰ (mean = 0.07‰, 1 SD = 0.17‰, n = 13). These results indicate that, depending on factors such as powdered coal isotopic composition and efficiency of Hg removal from flue gas, Hg deposited near CFUBs can be isotopically distinct. As this tool is further refined through future studies, Hg stable isotopes may eventually be used to quantify local deposition of Hg emitted by large CFUBs.     

New Anti-Nodal Monoclonal Antibodies Targeting the Nodal Pre-Helix Loop Involved in Cripto-1 Binding

Nodal is a potent embryonic morphogen belonging to the TGF-β superfamily. Typically, it also binds to the ALK4/ActRIIB receptor complex in the presence of the co-receptor Cripto-1. Nodal expression is physiologically restricted to embryonic tissues and human embryonic stem cells, is absent in normal cells but re-emerges in several human cancers, including melanoma, breast, and colon cancer. Our aim was to obtain mAbs able to recognize Nodal on a major CBR (Cripto-Binding-Region) site and to block the Cripto-1-mediated signalling. To achieve this, antibodies were raised against hNodal(44–67) and mAbs generated by the hybridoma technology. We have selected one mAb, named 3D1, which strongly associates with full-length rhNodal (K_D 1.4 nM) and recognizes the endogenous protein in a panel of human melanoma cell lines by western blot and FACS analyses. 3D1 inhibits the Nodal-Cripto-1 binding and blocks Smad2/3 phosphorylation. Data suggest that inhibition of the Nodal-Cripto-1 axis is a valid therapeutic approach against melanoma and 3D1 is a promising and interesting agent for blocking Nodal-Cripto mediated tumor development. These findings increase the interest for Nodal as both a diagnostic and prognostic marker and as a potential new target for therapeutic intervention.