KBS Development

The Knowledge Based System (KBS) has two main objectives, the provision of easy access to all the industrial and scientific codes through an executive program, and the provision of an easy to use user interface for the analysis codes. The user interface is designed to minimize the effort expended in dealing with the mechanics of using a computer, allowing the user to concentrate on seal design and analysis

KBS Demonstration

The Knowledge Based System (KBS) demonstration included five different items: the executive program, three of the industrial codes, and graphical display capability using current MYI MS-DOS programs. The graphics capability included two and three dimensional plots viewed from different angles. This capability will be ported to OS/2 and made an integral part of the KBS executive program. The three codes demonstrated included Spiral Groove Gas Seals (SPIRAL), Gas Cylindrical Seals (GCYL), and Incompressible Seals (ICYL). The SPIRAL and GCYL interface has the standard PM interface, while the ICYL interface was designed using ToolBook

Urologic manifestations of inflammatory pseudotumor: Report of 2 cases and review of the literature.

We report two adult patients with varied urologic symptoms who were found to have inflammatory pseudotumor on histopathology. The first patient had a large, solid, enhancing retroperitoneal mass lesion and presented with increased frequency of urination and recurrent urinary tract infections. The second patient had an obstructing left distal ureteric stricture and presented with painless hematuria. Though preoperative radiological diagnosis of this entity is not feasible, the present article illustrates the imaging findings in this unusual disease entity with review of the relevant literature

Numerical, analytical, experimental study of fluid dynamic forces in seals

NASA/Lewis Research Center is sponsoring a program for providing computer codes for analyzing and designing turbomachinery seals for future aerospace and engine systems. The program is made up of three principal components: (1) the development of advanced three dimensional (3-D) computational fluid dynamics codes, (2) the production of simpler two dimensional (2-D) industrial codes, and (3) the development of a knowledge based system (KBS) that contains an expert system to assist in seal selection and design. The first task has been to concentrate on cylindrical geometries with straight, tapered, and stepped bores. Improvements have been made by adoption of a colocated grid formulation, incorporation of higher order, time accurate schemes for transient analysis and high order discretization schemes for spatial derivatives. This report describes the mathematical formulations and presents a variety of 2-D results, including labyrinth and brush seal flows. Extensions of 3-D are presently in progress

Γ-Tocotrienol Inhibits Nuclear Factor-κB Signaling Pathway Through Inhibition of Receptor-Interacting Protein and TAK1 Leading to Suppression of Antiapoptotic Gene Products and Potentiation of Apoptosis

Unlike the tocopherols, the tocotrienols, also members of the vitamin E family, have an unsaturated isoprenoid side chain. In contrast to extensive studies on tocopherol, very little is known about tocotrienol. Because the nuclear factor-κB (NF-κB) pathway has a central role in tumorigenesis, we investigated the effect of γ-tocotrienol on the NF-κB pathway. Although γ-tocotrienol completely abolished tumor necrosis factor α (TNF)-induced NF-κB activation, a similar dose of γ-tocopherol had no effect. Besides TNF, γ-tocotrienol also abolished NF-κB activation induced by phorbol myristate acetate, okadaic acid, lipopolysaccharide, cigarette smoke, interleukin-1β, and epidermal growth factor. Constitutive NF-κB activation expressed by certain tumor cells was also abrogated by γ-tocotrienol. Reducing agent had no effect on the γ-tocotrienol-induced down-regulation of NF-κB. Mevalonate reversed the NF-κB inhibitory effect of γ-tocotrienol, indicating the role of hydroxymethylglutaryl-CoA reductase. γ-Tocotrienol blocked TNF-induced phosphorylation and degradation of IκBα through the inhibition of IκBα kinase activation, thus leading to the suppression of the phosphorylation and nuclear translocation of p65. γ-Tocotrienol also suppressed NF-κB-dependent reporter gene transcription induced by TNF, TNFR1, TRADD, TRAF2, TAK1, receptor-interacting protein, NIK, and IκBαkinase but not that activated by p65. Additionally, the expressions of NF-κB-regulated gene products associated with antiapoptosis (IAP1, IAP2, Bcl-xL, Bcl-2, cFLIP, XIAP, Bfl-1/A1, TRAF1, and Survivin), proliferation (cyclin D1, COX2, and c-Myc), invasion (MMP-9 and ICAM-1), and angiogenesis (vascular endothelial growth factor) were down-regulated by γ-tocotrienol. This correlated with potentiation of apoptosis induced by TNF, paclitaxel, and doxorubicin. Overall, our results demonstrate that γ-tocotrienol inhibited the NF-κB activation pathway, leading to down-regulation of various gene products and potentiation of apoptosis

Boswellic Acid Suppresses Growth and Metastasis of Human Pancreatic Tumors in an Orthotopic Nude Mouse Model through Modulation of Multiple Targets

Pancreatic cancer (PaCa) is one of the most lethal cancers, with an estimated 5-year survival of <5% even when patients are given the best treatment available. In addition, these treatments are often toxic and expensive, thus new agents which are safe, affordable and effective are urgently needed. We describe here the results of our study with acetyl-11-keto-β-boswellic acid (AKBA), an agent obtained from an Ayurvedic medicine, gum resin of Boswellia serrata. Whether AKBA has an activity against human PaCa, was examined in in vitro models and in an orthotopic nude mouse model of PaCa. We found that AKBA inhibited the proliferation of four different PaCa cell lines (AsPC-1, PANC-28, and MIA PaCa-2 with K-Ras and p53 mutations, and BxPC-3 with wild-type K-Ras and p53 mutation). These effects correlated with an inhibition of constitutively active NF-κB and suppression of NF-κB regulating gene expression. AKBA also induced apoptosis, and sensitized the cells to apoptotic effects of gemcitabine. In the orthotopic nude mouse model of PaCa, p.o. administration of AKBA alone (100 mg/kg) significantly inhibited the tumor growth; this activity was enhanced by gemcitabine. In addition, AKBA inhibited the metastasis of the PaCa to spleen, liver, and lungs. This correlated with decreases in Ki-67, a biomarker of proliferation, and CD31, a biomarker of microvessel density, in the tumor tissue. AKBA produced significant decreases in the expression of NF-κB regulating genes in the tissues. Immunohistochemical analysis also showed AKBA downregulated the expression of COX-2, MMP-9, CXCR4, and VEGF in the tissues. Overall these results demonstrate that AKBA can suppress the growth and metastasis of human pancreatic tumors in an orthotopic nude mouse model that correlates with modulation of multiple targets