Immune Aging and Immunotherapy in Cancer

Immune functions decline as we age, while the incidence of cancer rises. The advent of immune checkpoint blockade (ICB) has not only revolutionized cancer therapy, but also spawned great interest in identifying predictive biomarkers, since only one third of patients show treatment response. The aging process extensively affects the adaptive immune system and thus T cells, which are the main target of ICB. In this review, we address age-related changes regarding the adaptive immune system with a focus on T cells and their implication on carcinogenesis and ICB. Differences between senescence, exhaustion, and anergy are defined and current knowledge, treatment strategies, and studies exploring T cell aging as a biomarker for ICB are discussed. Finally, novel approaches to improve immunotherapies and to identify biomarkers of response to ICB are presented and their potential is assessed in a comparative analysis.     

Management and enterprise architecture click: The FAD(E)E framework

Enterprises are living things. They constantly need to be (re-)architected in order to achieve the necessary agility, alignment and integration. This paper gives a high-level overview of how companies can go about doing ‘enterprise architecture’ in the context of both the classic (isolated) enterprise and the Extended Enterprise. By discussing the goals that are pursued in an enterprise architecture effort we reveal some basic requirements that can be put on the process of architecting the enterprise. The relationship between managing and architecting the enterprise is discussed and clarified in the FAD(E)E, the Framework for the Architectural Development of the (Extended) Enterprise. Frank G. Goethals completed his Master studies in economics (option informatics), at the Katholieke Universiteit Leuven, Belgium, in 2000. He is presently researching for a Ph.D. under the theme of `Managing data in the Extended Enterprise'. This research is conducted at the K.U.Leuven under the guidance of professor J. Vandenbulcke, and is financed by SAP Belgium. Frank has a strong interest in coordination and dependency theory and Enterprise Architecture. Monique Snoeck obtained her Ph.D. in May 1995 from The Department of Computer Science of the Katholieke Universiteit Leuven with a thesis that lays the formal foundations of the object-oriented business modelling method MERODE. Since then she has done further research in the area of formal methods for object-oriented conceptual modelling. She now is Full Professor with the Management Information Systems Group of the Faculty of Economics and Applied Economics at the Katholieke Universiteit Leuven in Belgium. She has been involved in several industrial conceptual modelling projects. Her research interests are object oriented conceptual modelling, software architecture and software quality. Wilfried Lemahieu holds a Ph.D. from the Department of Applied Economic Sciences of the Katholieke Universiteit Leuven, Belgium (1999). At present, he is associate professor at the Management Informatics research group of the Faculty of Economics and Applied Economics. His teaching includes Database Management, Data Storage Architectures and Management Informatics. His research interests comprise distributed object architectures and web services, object-relational and object-oriented database systems and hypermedia systems. Jacques A. Vandenbulcke is professor at the Faculty of Economics and Applied Economics of the Katholieke Universiteit Leuven, Belgium. His main research interests are in Database management, Data modelling, and Business Information Systems. He is co-ordinator of the Leuven Institute for Research on Information Systems (LIRIS) and holder of the SAP-chair on ‘Extended enterprise infrastructures’. He is president of ‘Studiecentrum voor Automatische Informatieverwerking (SAI)’, the largest society for computer professionals in Belgium, and co-founder of the ‘Production and Inventory Control Society (PICS)’ in Belgium.     

Energy transfer in hydrogen/air and methane/air mixtures

This article presents gas kinetic calculation methods for the energy transport in hydrogen/ air and methane/ air mixture. The total molecular heat conductivity as well as its various shares are calculated and discussed for a temperature range of 400 to 3500 K and for a pressure of 10⁵ Pa. The variation of the air/ fuel ratio under the conditions of chemical equilibrium is also investigated. As opposed to our previous article, an extension of the Chapman-Knskog method which goes beyond the classical 1st approximation for elastic collisions is applied for the evaluation of suitable calculation methods. This is carried out following the method for strong relaxing thermal nonequilibrium according to Brun. The equations applied in this work are simplified formulations for the proximity to equilibrium. The method for the evaluation of the parameters of the inelastic collision and some chosen results are presented. A discussion of the various shares of the molecular heat conductivity emphasizes the considerable influence of the diffusion and the thermal diffusion processes in fuel/ air mixtures compared to the Fourier heat conductivity.     

FAMOCUTN and CUTQN: programs for fast analysis of large fault treeswith replicated and negated gates

The paper describes the principal difficulties arising with cutset evaluation for large fault trees containing many replicated gates and events. The usual bottom-up algorithms based on the usual modularization technique with truncation of low-probability cutsets can lead to great computer-tine expenditures with a large upper bound for the probability of the system failure due to the truncated cutsets (truncation error). This paper presents a new method for multi-level representation of fault trees with replicated gates. This method finds and simplifies cutsets on the level of gates, and then descending from the higher to the lower level of fault-tree representation. This method essentially reduces both the computer time and memory needed for cutset evaluation and delivers a more exact upper bound for the truncation error. The computer codes FAMOCUTN using this method for fast evaluation of minimal cutsets (MCS) for large fault trees with negated and/or replicated gates and CUTQN for system reliability calculation on the basis of the determined MCS are described. These computer codes are illustrated by examples of real systems from the German Risk Study for Nuclear Power Stations, Phase B and tested with two fault trees from a fault-tree computer-code benchmark exercise. These codes are now used in Germany, by: (1) Gesellschaft fur Reaktorsicherheit (GRS) mbH, 85748 Garching, and (2) KFA-Forschungszentrum Julich GmbH, Institute for Safety Research and Reactor Technology (ISR-1), 52425 Julich     

Transient behaviour of shell and tube heat exchangers

Based on the dispersion model rather than on the conventional pluf-flow model, a method of predicting the transient behaviour of parallel and counterflow heat exchangers is developed, whereby the effects of shell-side flow maldistribution and the finite heat capacities of both fluids, tube bundle and shell are considered. The final solution has been obtained by numerical inversion of the Laplace transform, to determine the transient responses to arbitrary inlet temperature variations. The experiment was carried out in a one pass tube heat exchanger. The comparison between therotical and experimental results is presented and the feasibility of this method is discussed.     

Amino acid composition and nutritional value of italian ryegrass,red clover and lucerne as influenced by application and content of nitrogen

In experiments with increasing applications of nitrogen to ryegrass, red clover and lucerne grown in pots, freeze-dried plant material with widely varying N-content was obtained. Increasing N-concentrations were associated with increasing nitrate contents which proportionally decreased the concentrations (g/16 g total-N) of all amino acids. Expressed as g amino acid/16 g total-N minus NO₃-N, concentrations of all amino acids were closely similar at different N-levels. Differences between the three species ' amino acid composition were negligible except for a lower concentration of lysine in the crude protein of ryegrass and of methionine + cystine in the crude protein of clover and lucerne. In feeding experiments with rats increasing total-N concentrations were generally associated with higher true digestibilities of the crude protein of ryegrass, red clover and lucerne, but slightly lower biological values, especially in red clover. Net crude protein utilisation was increased by increasing total-N concentration in ryegrass, decreased in red clover and unchanged in lucerne. When ranked according to the nutritional value of the crude protein, ryegrass comes first, lucerne second and red clover last. Addition of synthetic methionine to ryegrass and lucerne improved their biological values by 30 and 47% respectively.     

Nutritive value of oat and rye grain protein as influenced by nitrogen and amino acid composition

In experiments with increasing applications of nitrogen to oats and rye grown in pots, grain with widely varying N-content was obtained. In rye increasing N-concentrations were associated with decreases in the protein of lysine and several other amino acids including threonine, tryptophan, methionine and cystine, whereas glutamic acid, proline and phenylalanine increased. In oat protein the amino acid composition was less affected by increasing N-content in grain. Concentrations of most essential amino acids were higher in oat than in rye protein, especially at high N-levels. The ratio lysine + arginine/proline was higher in oat than in rye protein and did not, as in rye, decrease with increasing N-concentration. Lysine as a percentage of dry matter increased up to the highest N-level in both cereals. In rat feeding experiments true digestibility of the protein of oats and rye increased to the same extent with increasing N-concentration in grain, whereas the biological value of the protein decreased considerably in rye but only slightly in oats. Net protein utilisation decreased with increasing N-content in rye but increased in oats.