Computer Systems Based on Silicon Photonic Interconnects

We present a computing microsystem that uniquely leverages the bandwidth, density, and latency advantages of silicon photonic interconnect to enable highly compact supercomputer-scale systems. We describe and justify single-node and multinode systems interconnected with wavelength-routed optical links, quantify their benefits vis-a-vis electrically connected systems, analyze the constituent optical component and system requirements, and provide an overview of the critical technologies needed to fulfill this system vision. This vision calls for more than a hundredfold reduction in energy to communicate an optical bit of information. We explore the power dissipation of a photonic link, suggest a roadmap to lower the energy-per-bit of silicon photonic interconnects, and identify the challenges that will be faced by device and circuit designers towards this goal.     

Uncertainty and planning for water pollution control

This paper addresses the problem of planning the construction and expansion of a sewage treatment facility operating on a river. It is argued that any model for solution of the problem must take explicit account of the many uncertainties with which the problem is fraught. An expository model of this kind is constructed and its solution discussed.     

Subsidence in impaction grafting: the effect of adding a ceramic bone graft extender to bone

The incidence of revision total hip arthroplasty is increasing dramatically and the associated demand for allograft bone is likely to exceed the available supply. In addition, allograft presents potential problems with regard to infection, antigenicity, availability, reproducibility and cost. It is therefore desirable to develop an alternative to allograft. This study investigated BoneSave, a porous tricalcium phosphate-hydroxyapatite ceramic for use in impaction grafting of the femur at revision total hip arthroplasty. The findings of an in vitro mechanical study comparing the initial stability of pure allograft, a volume mixture of 50 per cent allograft and 50 per cent BoneSave, and a volume mixture of 10 per cent allograft and 90 per cent BoneSave are reported. The BoneSave-allograft mixtures exhibit both much greater mechanical stability and reproducibility than the pure allograft (p < 0.05) at all tested loads (200-800 N). At high peak loads the high volume (90%, v/v) BoneSave mix also provided higher mechanical stability than the medium volume (50 per cent BoneSave-50 per cent allograft) mix (p < 0.05). These results demonstrate thatfrom a mechanical standpoint the tested ceramic provides adequate initial stability to be used as a bone graft extender with allograft in impaction grafting of the femur.     

Application of simulated annealing to the biclustering of gene expression data.

In a gene expression data matrix, a bicluster is a submatrix of genes and conditions that exhibits a high correlation of expression activity across both rows and columns. The problem of locating the most significant bicluster has been shown to be NP-complete. Heuristic approaches such as Cheng and Church's greedy node deletion algorithm have been previously employed. It is to be expected that stochastic search techniques such as evolutionary algorithms or simulated annealing might improve upon such greedy techniques. In this paper we show that an approach based on simulated annealing is well suited to this problem, and we present a comparative evaluation of simulated annealing and node deletion on a variety of datasets. We show that simulated annealing discovers more significant biclusters in many cases. Furthermore, we also test the ability of our technique to locate biologically verifiable biclusters within an annotated set of genes.     

Acquiring Customers' Requirementsin Electronic Commerce

A key role for Artificial Intelligencetechnology in electronic commerce is in findingproducts and services that meet a user'srequirements. This may be implemented as athree-stage process of requirementselicitation, product search, and finallyproduct presentation. Alternatively the searchof the product space may happen in tandem withthe requirements elicitation process. It isalso possible to use product presentation as amechanism to focus and give context torequirements elicitation. A variety ofdifferent approaches to this issue of matchingproducts to requirements have been explored inAI research. Thus, while the focus in thispaper is on different approaches torequirements elicitation, these related issuesof product search and product presentation arealso discussed in detail. The paper concludesby placing the other papers in this specialissue in the context of this structuredoverview.     

Expression of human aldehyde dehydrogenase-3 associated with hepatocellular carcinoma: promoter regions and nuclear protein factors related to the expression

Studies in our laboratory have shown that as early as day 8.5 of development, mouse yolk sac cells can generate T cells when placed in a thymic microenvironment. At this stage, yolk sac cells can also differentiate into myeloid cells in vitro. B cell differentiation in vitro was achieved with day 9 yolk sac by providing a bone marrow stromal feeder layer. We have now established endothelial cell lines and clones from yolk sacs of day 8-12 mouse embryos. These vary in their ability to support stem cell maintenance and differentiation. Our principal work has been carried out with day 12 cloned endothelial cell lines. One clone supported the > 100 fold expansion of yolk sac hematopoietic stem cells that subsequently could generate B cells, T cells and myeloid cells both in vitro and in vivo. Preliminary experiments with endothelial cells from younger embryos are also described.     

Molecular analysis of the third component of canine complement (C3) and identification of the mutation responsible for hereditary canine C3 deficiency

Genetically determined deficiency of the third component of complement (C3) in the dog is characterized by a predisposition to recurrent bacterial infections and to type 1 membranoproliferative glomerulonephritis. The current studies were undertaken to characterize the cDNA for wild-type canine C3 and identify the molecular basis for hereditary canine C3 deficiency. Amplification, cloning, and sequence analysis indicated that canine C3 is highly conserved in comparison with human, mouse, and guinea pig C3. Southern blot analysis failed to show any gross deletions or rearrangements of DNA from C3-deficient animals. Northern blot analysis indicated that the livers of these animals contain markedly reduced quantities of a normal length C3 mRNA. The full-length 5.1-kb canine C3 cDNA was amplified in overlapping PCR fragments. Sequence analysis of these fragments has shown a deletion of a cytosine at position 2136 (codon 712), leading to a frameshift that generates a stop codon 11 amino acids downstream. The deletion has been confirmed in genomic DNA, and its inheritance has been demonstrated by allele-specific oligonucleotide hybridization.     

Hydatid cyst of the interventricular septum in a 3.5-year-old child

An asymptomatic cardiac cyst located in the interventricular septum was diagnosed in a 3.5-year-old child by echocardiographic findings. Surgical ablation was done and histopathologic analysis confirmed a hydatid cyst. The patient was discharged without symptoms.     

Sickle cell adhesion to laminin: potential role for the alpha5 chain

Sickle red blood cell (RBC) adhesion to the endothelium and to exposed, underlying subendothelial proteins is believed to contribute to vascular occlusion in sickle cell disease. Laminin, a major component of the subendothelium, supports significant adhesion of sickle, but not normal RBCs. The purpose of this study was to define the adhesive region for sickle RBCs within a human laminin preparation using a flow adhesion assay designed to mimic physiologic flow through postcapillary venules. Because sickle RBCs did not adhere to the common laminin contaminants entactin or collagen type IV, neither of these proteins are likely to contribute to the observed adhesion to laminin. Known adhesive regions of laminin neither supported nor inhibited sickle RBC adhesion to laminin, suggesting a mechanism of adhesion previously uncharacterized in other laminin adhesion studies. Moreover, sickle RBCs did not adhere to mouse EHS laminin or to human laminin-2 (merosin), eliminating the alpha1, alpha2, beta1, and gamma1 chains as mediators of sickle cell adhesion. The monoclonal antibody 4C7, which binds at or near the G-domain of the laminin alpha5 chain, significantly inhibited sickle RBC adhesion. These results suggest that an adhesive region for sickle RBCs is contained within the laminin alpha5 chain.     

Molecular mapping with functional antibodies localizes critical sites on the human IL receptor common gamma (gamma c) chain

The IL receptor common gamma (gamma c) chain is required for the formation of high affinity cytokine receptor complexes for IL-2, IL-4, IL-7, IL-9, and IL-15, and for signals regulating cell survival, growth, and differentiation. Our current understanding of how gamma c chain associates with multiple ligands and receptor subunits is drawn largely from its structural homology to the human growth hormone (hGH) receptor and known structure of the hGH/hGH receptor complex. These receptors share distinct features in their extracellular portions and are believed to function by a mechanism of ligand-induced association of receptor subunits. Here, we report the first directed mutational analysis of the human gamma c chain by alanine scanning conducted across seven regions likely to contain residues required for intermolecular contact. Functionally distinct, neutralizing anti-gamma c mAbs were employed to define critical residues. One particular mAb, CP.B8, unique in its ability to inhibit IL-2-, IL-4-, IL-7-, and IL-15-induced proliferation and high affinity cytokine binding of normal T cells as an intact mAb and as a Fab fragment, localized critical residues to four noncontinuous stretches, namely residues in loops AB and EF of domain 1, in the interdomain segment, and in loop FG of domain 2. Notably, these residues form a contiguous patch on the gamma c chain surface in a three-dimensional structural model. These results provide functional evidence for the location of contact points on gamma c chain required for its association with multiple ligands.