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 .     

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.     

Automated conceptual model clustering: a relator-centric approach

Software and Systems Modeling - In recent years, there has been a growing interest in the use of reference conceptual models to capture information about complex and sensitive business domains...     

Using an eye tracker for accurate eye movement artifact correction

We present a new method to correct eye movement artifacts in electroencephalogram (EEG) data. By using an eye tracker, whose data cannot be corrupted by any electrophysiological signals, an accurate method for correction is developed. The eye-tracker data is used in a Kalman filter to estimate which part of the EEG is of ocular origin. The main assumptions for optimal correction are summed and their validity is proven. The eye-tracker-based correction method is objectively evaluated on simulated data of four different types of eye movements and visually evaluated on experimental data. Results are compared to three established correction methods: Regression, Principal Component Analysis, and Second-Order Blind Identification. A comparison of signal to noise ratio after correction by these methods is given in Table II and shows that our method is consistently superior to the other three methods, often by a large margin. The use of a reference signal without electrophysiological influences, as provided by an eye tracker, is essential to achieve optimal eye movement artifact removal.     

A Design-Based Structural Test Method for a Switched-Resistor DAC

In this paper, a design-based structural testing method is presented to enable a fast, low cost test for a switched-resistor digital-to-analogue converter (DAC). A 24-bit stereo DAC is used to demonstrate this. After schematic-level simulations and experimental verification, it is found that the dynamic parameter THD can be predicted by the static test. Practical production wafer test and final test results evaluate this structural test method by comparing it with the traditional THD test method. In this paper the simulation results, the relevant measurement results, and the testing results are discussed. Finally, the application recommendations are given.

The Role of the Immune System in IBD-Associated Colorectal Cancer: From Pro to Anti-Tumorigenic Mechanisms

Patients with inflammatory bowel disease (IBD) have increased incidence of colorectal cancer (CRC). IBD-associated cancer follows a well-characterized sequence of intestinal epithelial changes, in which genetic mutations and molecular aberrations play a key role. IBD-associated cancer develops against a background of chronic inflammation and pro-inflammatory immune cells, and their products contribute to cancer development and progression. In recent years, the effect of the immunosuppressive microenvironment in cancer development and progression has gained more attention, mainly because of the unprecedented anti-tumor effects of immune checkpoint inhibitors in selected groups of patients. Even though IBD-associated cancer develops in the background of chronic inflammation which is associated with activation of endogenous anti-inflammatory or suppressive mechanisms, the potential role of an immunosuppressive microenvironment in these cancers is largely unknown. In this review, we outline the role of the immune system in promoting cancer development in chronic inflammatory diseases such as IBD, with a specific focus on the anti-inflammatory mechanisms and suppressive immune cells that may play a role in IBD-associated tumorigenesis.     

Incorporating fuzziness in the classical decision table formalism

In this article different aspects of the decision table formalism are discussed. First, crisp decision tables are defined and their construction is described. Next, fuzzy extensions are made to crisp decision tables in order to deal with imprecision and uncertainty. As a result, with crisp decision tables as special cases, a form of fuzzy decision tables is defined which include fuzziness in the conditions as well as in the actions. Consequently, the concept of completeness is introduced in the context of fuzzy decision tables. Furthermore, fuzzy consultation of decision tables is discussed, which allows decision making with fuzziness based on the matching between fuzzy conditions and the concept of fuzzy logical implication. © 1996 John Wiley & Sons, Inc.