Alloantigen gene therapy for squamous cell carcinoma of the head and neck: results of a phase-1 trial

OBJECTIVE: To determine the safety and efficacy of an immunogenic gene therapy using a drug designed to produce expression of a foreign class I major histocompatibility complex protein in patients with head and neck cancer. DESIGN: Phase 1 prospective clinical trial. SETTING: Academic medical setting. PATIENTS: Nine patients with advanced head and neck squamous cell carcinoma who had failed conventional therapy and did not express HLA-B7, a class I major histocompatibility complex protein. INTERVENTION: Patients were treated with Allovectin-7 (Vical Inc, San Diego, Calif) by direct intratumoral injection. Allovectin-7 contains a plasmid complementary DNA complexed with a cationic lipid, which results in expression of HLA-B7. MAIN OUTCOME MEASURES: Patients were assessed for any toxic effects and for any change in tumor volume. Biopsy specimens obtained before and after therapy were evaluated by immunohistochemistry to detect HLA-B7 expression and with the terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay to detect any induction of apoptosis. RESULTS: There were no toxic effects of the gene therapy. In 4 of these 9 patients there was a partial response to treatment, evidenced by a gradual reduction in tumor size. One patient has remained alive for more than 17 months since commencing treatment, with no clinical evidence of disease but with persistent histological evidence of cancer. Analysis of the biopsy specimens from 2 of the patients who responded to therapy demonstrated HLA-B7 expression. The TUNEL assay demonstrated extensive apoptosis in both of these patients, suggesting that this may be the mechanism of tumor reduction. CONCLUSIONS: These data demonstrate the potential efficacy and lack of toxicity of this form of alloantigen gene therapy. A multi-institutional study has been initiated to expand on these findings.     

Stochastic Petri nets for the reliability analysis of communication network applications with alternate-routing

In this paper, we present a comparative reliability analysis of an application on a corporate B-ISDN network under various alternate-routing protocols. For simple cases, the reliability problem can be cast into fault-tree models and solved rapidly by means of known methods. For more complex scenarios, state space (Markov) models are required. However, generation of large state space models can get very labor intensive and error prone. We advocate the use of stochastic reward nets (a variant of stochastic Petri nets) for the concise specification, automated generation and solution of alternate-routing protocols in networks. This paper is written in a tutorial style so as to make it accessible to a large audience.     

Transient analysis of heat pump assisted distillation systems. 1 The heat pump

A simple algorithm to simulate the transient behaviour of a vapour compression heat pump is described. Individual models are developed for various components of the heat pump such as compressor, evaporator, condenser and expansion valve. The components are simulated separately and are combined to form the total system. The compressor is a hermetically sealed, reciprocating piston type with adiabatic compression, the evaporator and condenser are coiled copper tubes, and the expansion valve is assumed to be adiabatic. The transport and thermodynamic properties of the refrigerant used are obtained from empirical equations. The total system is viewed in a simplified manner in order to apply the results of this transient analysis to the behaviour of a chemical process operation, namely, distillation.     

Inhibition effect of sodium boro-gluconate on mild steel with and without nitrite ions in low chloride containing water

As an alternative for the replacement of chromate containing corrosion inhibitors for mild steel in cooling water systems, sodium borogluconate (SBG) has been evaluated by gravimetric and electrochemical methods in water containing 100 p.p.m. Cl^– in an open system at ambient temperature. An inhibitor efficiency of 90% has been obtained in the presence of optimum concentration (50 p.p.m.) of SBG alone. However, the inhibition efficiency tends to decrease after 48 h of immersion due to the formation of soluble iron gluconate complexes. The formation of the complex is evident from the shift of the u.v. absorption peaks of Fe(II) and Fe(III) in the presence of gluconate ions. To stabilize the inhibitive action of SBG, NO ₂ ^– ions were added in an equal mass ratio and their combined effect was found to be very effective in maintaining inhibition efficiency up to 100 h of immersion.     

Robust likelihood inference for regression parameters in partially linear models

A robust likelihood approach is proposed for inference about regression parameters in partially-linear models. More specifically, normality is adopted as the working model and is properly corrected to accomplish the objective. Knowledge about the true underlying random mechanism is not required for the proposed method. Simulations and illustrative examples demonstrate the usefulness of the proposed robust likelihood method, even in irregular situations caused by the components of the nonparametric smooth function in partially-linear models.     

Dependence of dc and ac conduction on the pre-sintering temperature in sol–gel derived Ba0.5Sr0.5TiO3 thin films

The effect of pre-sintering temperature on the activation energies of dc and ac conduction in sol–gel spin-coated Ba_0.5Sr_0.5TiO₃ (BST) thin films is reported in this paper. Layer by layer coating of BST sol on Pt/TiN/SiO₂/Si substrates was done with varying pre-sintering temperatures (drying temperature for individual layers). Dominant mechanism of dc conduction was identified as Schottky process whereas ac conduction was governed by trap controlled hopping process. The activation energy for dc conduction decreased from 0.45 to 0.38 eV with increase in the pre-sintering temperature from 400 to 600 °C; whereas, that for ac conduction increased from 0.17 to 0.21 eV. The results have been correlated with grain growth phenomena and reduction of oxygen vacancies in the films with increase in the pre-sintering temperature.     

Room-temperature optically-pumped GaSb quantum well based VCSEL monolithically grown on Si (100) substrate

Monolithic vertical cavity surface emitting lasers (VCSELs) on Si are demonstrated. The GaSb multi-quantum well active region embedded in an Al(Ga)Sb half-wave cavity spacer layer enables lasing under room-temperature optically-pumped conditions. The 13% lattice mismatch is accommodated by a spontaneously formed 2-D array of 90/spl deg/ misfit dislocations at the AlSb/Si interface. This growth mode produces very low defect density (/spl sim/8/spl times/10/sup 5//cm/sup 2/) and relaxed materials growth (98%) without the use of a buffer layer. Presented are VCSEL lasing spectra, light-in against light-out curves along with defect density measurements performed by microscopy and etch-pit density. A threshold excitation density of I/sub th/=0.1 mJ/cm/sup 2/ and a multimode lasing spectrum peaked at 1.62 /spl mu/m, results from a 3 mm pump-spot size.     

Development of hybrid genetic algorithms for product line designs.

In this paper, we investigate the efficacy of artificial intelligence (AI) based meta-heuristic techniques namely genetic algorithms (GAs), for the product line design problem. This work extends previously developed methods for the single product design problem. We conduct a large scale simulation study to determine the effectiveness of such an AI based technique for providing good solutions and bench mark the performance of this against the current dominant approach of beam search (BS). We investigate the potential advantages of pursuing the avenue of developing hybrid models and then implement and study such hybrid models using two very distinct approaches: namely, seeding the initial GA population with the BS solution, and employing the BS solution as part of the GA operator's process. We go on to examine the impact of two alternate string representation formats on the quality of the solutions obtained by the above proposed techniques. We also explicitly investigate a critical managerial factor of attribute importance in terms of its impact on the solutions obtained by the alternate modeling procedures. The alternate techniques are then evaluated, using statistical analysis of variance, on a fairy large number of data sets, as to the quality of the solutions obtained with respect to the state-of-the-art benchmark and in terms of their ability to provide multiple, unique product line options.