Immune and Anticancer Responses Elicited by Fully Synthetic Aberrantly Glycosylated MUC1 Tripartite Vaccines Modified by a TLR2 or TLR9 Agonist

The mucin MUC1 is overexpressed and aberrantly glycosylated by many epithelial cancer cells manifested by truncated O‐linked saccharides. Although tumor‐associated MUC1 has generated considerable attention because of its potential for the development of a therapeutic cancer vaccine, it has been difficult to design constructs that consistently induce cytotoxic T‐lymphocytes (CTLs) and ADCC‐mediating antibodies specific for the tumor form of MUC1. We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous T_helper peptide, and a TLR2 (Pam₃CysSK₄) or TLR9 (CpG‐ODN 1826) agonist. It was found that the Pam₃CysSK₄‐containing compound elicits more potent antigenic and cellular immune responses, resulting in a therapeutic effect in a mouse model of mammary cancer. It is thus shown, for the first time, that the nature of an inbuilt adjuvant of a tripartite vaccine can significantly impact the quality of immune responses elicited against a tumor‐associated glycopeptide. The unique adjuvant properties of Pam₃CysSK₄, which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor‐specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1 .     

On information and communication technology and production cost in construction industry: evidence from the Netherlands

The interplay between information and communication technology (ICT) and the competitiveness of construction firms is considered. More specifically, the question is whether firms that invest in information and communication technology have a production cost advantage. The economics literature hypothesizes that ICT brings about a production cost advantage, as ICT brings flexibility and improves the planning, organization and control of work. To test this proposition for the construction industry, a production cost function allowing for the inclusion of ICT is formulated. Using statistical nearest-neighbour matching methods it is possible to identify the effect of ICT on production costs thereby controlling for economic moderators. Data from a sample of Dutch construction firms reveal that those firms that installed ICT capital do have a production cost advantage. The results indicate further that firms need a minimum level of ICT capital to fully benefit from its production cost advantage.     

Evaluating the effectiveness of a post-license education program for young novice drivers in Belgium

The disproportionately large number of traffic accidents of young novice drivers highlights the need for an effective driver education program. The Goals for Driving Education (GDE) matrix shows that driver education must target both lower and higher levels of driver competences. Research has indicated that current education programs do not emphasize enough the higher levels, for example awareness and insight. This has raised the importance of insight programs. On the Road (OtR), a Flemish post-license driver education program, is such an insight program that aims to target these higher levels. The program focus is on risky driving behavior like speeding and drink driving. In addition, the program addresses risk detection and risk-related knowledge. The goal of the study was to do an effect evaluation of this insight program at immediate post-test and 2 months follow-up. In addition, the study aimed to generalize the results of this program to comparable programs in order to make usable policy recommendations. A questionnaire based on the Theory of Planned Behavior (TPB) was used in order to measure participants’ safety consciousness of speeding and drink driving. Moreover, we focused on risk detection and risk-related knowledge. Participants (N = 366) were randomly assigned to a baseline—follow-up group or a post-test—follow-up group.     

Evaluation of DNA extraction methods for Bacillus anthracis spores spiked to food and feed matrices at biosafety level 3 conditions

The DNA extraction efficiency from milk, whey, soy, corn gluten meal, wheat powders and heat-treated corn grain that were spiked with Bacillus anthracis and Bacillus thuringiensis spores was determined. Two steps were critical: lysis of the spores and binding of the free DNA to the DNA binding magnetic beads in the presence of the interfering powders. For the guanidine-thiocyanate based Nuclisens lysis buffer from Biomerieux we found that between 15 and 30% of the spores survived the lysis step. As most lysis buffers in DNA/RNA extraction kits are guanidine based it is likely that other lysis buffers will show a similar partial lysis of the Bacillus spores. Our results show that soybean flour and wheat flour inhibited the DNA extraction process strongest, leading to unreliable DNA extractions when using too much of the matrix. For corn gluten meal, heat-treated corn grain and milk powders, DNA extraction efficiencies in the presence of 100mg and 10mg of powder resulted in 70%-95% reduced DNA recoveries. The inhibition was, however, reliable and intermediate compared to the inhibition by soy and wheat. Whey powder had the lowest inhibitory effect on DNA-extraction efficiency and recoveries of 70-100% could be reached when using 10mg of powder. The results show that reducing the amount of matrix leads to better DNA-extraction efficiencies, particularly for strongly inhibiting powders such as soy and wheat. Based on these results, a standard protocol to directly isolate DNA from micro-organisms present in complex matrixes such as food and feed powders was designed.     

On-line monitoring of fatigue cracks using ultrasonic surface waves

During the last decade many techniques were developed to detect fatigue cracks, and estimate their location and size. Unfortunately, most of the currently available nondestructive testing methods are off-line: the operational (or fatigue) loading and the inspection are considered as two distinct stages. Mostly, the loading should be released before inspection can take place, and sometimes the device under test even has to be disassembled. In this article, an experimental methodology based on ultrasonic surface waves will be developed to continuously inspect a structure during its operation. The proposed method uses spectral information of transmitted surface waves at several working points of the operational load. Simple statistical indicators of the transmitted wave energy during loading are introduced in order to be able to monitor the structural health on-line. As a validation experiment, a propagating fatigue crack in a sinusoidally loaded beam will be considered. In addition, a comparison with an off-line method is made, showing that the on-line method is also much more sensitive.     

From decision tables to expert system shells

Building and maintaining high quality knowledge based systems is not a trivial task. Decision tables have sometimes been recommended in this process, mainly in verification and validation. In this paper, however, it is shown how decision tables can also be used to generate, and not just to validate, knowledge bases and how the transformation process from decision tables to knowledge bases can be organized. Several options to generate rules or other knowledge representation from decision tables are described and evauluated.

The proposed generation strategy enables the knowledge engineer to concentrate on the acquisition and modelling issues and allows him to isolate the knowledge body from its implementation. The generation process has been implemented for two commercial tools, AionDS and KBMS and has been applied to real world applications.     

An initial comparison of a fuzzy neural classifier and a decision tree based classifier

At the present time a large number of AI methods have been developed in the field of pattern classification. In this paper, we will compare the performance of a well-known algorithm in machine learning (C4.5) with a recently proposed algorithm in the fuzzy set community (NEFCLASS). We will compare the algorithms both on the accuracy attained and on the size of the induced rule base. Additionally, we will investigate how the selected algorithms perform after they have been pre-processed by discretization and feature selection.     

Team-optimal closed-loop Stackelberg strategies in hierarchical control problems

This paper is concerned with the derivation of closed-loop Stackelberg (CLS) solutions of a class of continuous-time two-player nonzero-sum differential games characterized by linear state dynamics and quadratic cost functionals. Explicit conditions are obtained for both the finite and infinite horizon problems under which the CLS solution is a representation of the optimal feedback solution of a related team problem which is defined as the joint minimization of the leader's cost function. First, a specific class of representations is considered which depend linearly on the current and initial values of the state, and then the results are extended to encompass a more general class of linear strategies that also incorporate the whole past trajectory. The conditions obtained all involve solutions of linear matrix equations and are amenable to computational analysis for explicit determination of CLS strategies.     

Removal of some elements from washed and cooked rice studied by inductively coupled plasma mass spectrometry and synchrotron based confocal micro-X-ray fluorescence

Extraction of As, Cd, Cu, Mn, Ni and Ti from two white as well as from one brown rice samples was studied by inductively coupled plasma sector field mass spectrometry (ICP-SF-MS). Samples were subjected to cold and hot water extraction (rice mass to deionised water volume ratio = 1:6, and 1:3, respectively). The discarded liquids were freeze-dried and digested by microwave-assisted digestion. About 50% of the content of the investigated elements could be extracted from the white rice. In case of the brown rice, the boiling water contained As, Cd, Ni and Ti in significant percentages. Elemental distributions in the rice grains determined by synchrotron radiation confocal micro-X-ray fluorescence analysis revealed that a surface layer having a thickness of about 80 μm is the richest region in elements. Ti was detectable only in this so-called skin region. Good correlation was observed for the extraction of As, Mn, Ni and Ti by the above-mentioned two techniques. Thus, in regions affected by heavy metal and other toxic element contamination, those rice dishes would be preferred whose preparation should need abundant amounts of water for washing and cooking, which later should be discarded.     

The oxidation of Fe(II) with Cu(II) in acidic sulfate solutions with air at elevated pressures

The oxidation of ferrous ions in acidic sulfate solutions in the presence of cupric ions at elevated air pressures was investigated in a high-intensity gas–liquid contactor. The study was required for the design of the regeneration steps of the novel Vitrisol^® desulphurization process. The effects of the Fe²⁺ concentration, Cu²⁺ concentration, Fe³⁺ concentration, initial H₂SO₄ concentration, and partial oxygen pressure on the reaction rate were determined at three different temperatures, i.e., T?=?50?°C, 70?°C, and 90?°C. Most of the experiments were determined to be affected by the mass transfer of oxygen, and therefore true intrinsic kinetics could not be fully determined. An increase in Fe²⁺ and Cu²⁺ concentrations, as well as the partial pressure of oxygen and temperature, increased the Fe²⁺ oxidation rate. H₂SO₄ did not influence the Fe²⁺ oxidation rate. An increase in Fe³⁺ concentration decreased the Fe²⁺ oxidation rate. Although determined from experiments partially affected by mass transfer, a first order of reaction in Fe²⁺ was observed, fractional orders in both Cu²⁺ and O₂ were measured, a zero order in H₂SO₄ was determined, and a negative, fractional order in Fe³⁺ was obtained. The activation energy was estimated to be 31.3?kJ/mol.