Structure-activity studies of human tumour necrosis factors

The mechanism by which tumour necrosis factors (TNF and lymphotoxin,also called TNFß and TNFß respectively) exerttheir cytotoxic activity on many malignant cells, remains largelyunknown. Furthermore, the broad array of differentiation (geneinduction) and mitogenic activities towards many primary cellsis still a subject of intensive investigation. TNF is an importantmediator in inflammation, immune responses and infection-relatedphenomena and these activities contribute to the severe toxidtyseen when TNF is used as an anticancer agent. The first stepin the mechanism of action is the specific binding of the ligandto its receptors and dissection of the molecular mechanism involvedin this interaction is the subject of this review. The reasonsfor the interest in this aspect are obvious: first, the developmentof strong antagonistic TNF analogues can be useful in dampeningthe potentially lethal or debilitating effects of an overproductionof the cytokine (as in septic shock or rheumatoid arthritis).Secondly, since two distinct TNF receptors exist, constructionof TNF muteins that distinguish between both types may leadto derivatives of this plekrtropic agent with a more restrictedbiological activity pattern. Ideally, one would like to developa TNF mutant that has retained its cytotoxic action on tumourcells without inducing the deleterious systemic toxteity. Suchan optimized TNF molecule could become a potent anticancer agent     

Micro-electro-discharge machining as microsensor fabrication technology

This paper presents the design and fabrication of three miniaturized mechanical sensors to demonstrate the three-dimensional machining capabilities of micro-electro-discharge machining (EDM). The first sensor is an inertial bi-axial inclination sensor. The displacement of an inertial mass is measured optically by means of a two-dimensional position sensitive device (PSD). The machining freedom of micro-EDM makes it possible to produce both sensor and housing in one monolithic structure. The second sensor is an inertial uni-axial inclination sensor, which demonstrates the compatibility of the micro-EDM technology with the conventional photolithographic micromachining technologies. The mechanical structure of the sensor is machined by micro-EDM and the capacitive sensing part is produced by lithography. The aim of the integration is to set up a hybrid technology, which inherits the benefits of both micro-EDM and photolithography. The third miniaturized sensor is a three-component force sensor. The mechanical structure of the force sensor converts forces into displacements, which are measured optically. The mechanical structure of the force sensor is produced by wire-EDM and micro-EDM.     

Calcification of subcutaneously implanted collagens in relation to cytotoxicity,cellular interactions and crosslinking

In general, calcification of biomaterials occurs through an interaction of host and implanted material factors, but up to now the real origin of pathologic calcification is unknown. In this study we aimed to investigate incidence of calcification of (crosslinked) dermal sheep collagens (DSCs) with respect to their specific properties, during subcutaneous implantation in rats. Three types of DSCs were commercially obtained: non-crosslinked DSC (NDSC), and DSC crosslinked with glutaraldehyde (GDSC) and hexamethylenediisocyanate (HDSC). NDSC, HDSC and GDSC were (enzymatically) tissue culture pretreated to eliminate their cytotoxic products. Beside this, crosslinking methods were modified to optimize mechanical properties and to decrease cytotoxicity, which resulted in HDSC^* and GDSC^*. Furthermore, DSC was crosslinked by activation of the carboxylic groups, i.e. by means of acyl azide and carbodiimide, resulting in AaDSC and CDSC, respectively. After implantation of HDSCs and GDSCs a relation between cytotoxicity and calcification of crosslinked DSC could be made. No relation was found between cellular infiltration of DSCs and calcification. However, from the use of different types and modification of crosslinking methods it might be concluded that calcification is mainly related to stable crosslinks, i.e. to the chemical properties of the obtained material.     

A Genetic Dissociation of Learning and Recall in Caenorhabditis elegans.

A learning event can be dissociated into 3 components: acquisition, storage, and recall. When the laboratory wild-type strain of Caenorhabditis elegans (N2 strain) is exposed to benzaldehyde in the absence of food, the worms display a reduction of their attractive response to this volatile odorant. This results from the association between benzaldehyde and a nutrient-deficient environment. Another wild-type isolate, the CB4856 strain, fails to display this decreased response to benzaldehyde after exposure to benzaldehyde in the absence of food. However, like the N2 strain, when tested to isoamyl alcohol after benzaldehyde conditioning, the CB4856 strain displays a decreased isoamyl alcohol response. Therefore, the CB4856 strain does not have an acquisition deficit, but it suffers from a recall deficit specific to benzaldehyde. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Non-point sources and the waste discharge charge system.

The development of a waste discharge charge system (WDCS) in South Africa has been proposed to promote waste reduction and water conservation. The WDCS is based on the polluter pays principle and is designed such that the management of waste discharges achieves resource quality objectives (RQOs) at the minimum total cost to the catchment. Two charges are distinguished: first a charge for optimising use of the resource (incentive charge); and secondly, a charge for development and operation of mitigation measures in the resource (mitigation charge). The WDCS is applied to both point sources and non-point sources (NPS) of contamination. In the inclusion of NPS, the charge system distinguishes between registered and non-registered NPS, with the charge applied to the former group only, in the first instance. This paper introduces the WDCS by describing the principles and the theoretical basis of the WDCS, highlighting the link to RQOs as the benchmark of acceptable externalities. The paper explores the inclusion of NPS in the WDCS, describing: first, the principles of NPS inclusion in the WDCS; secondly, the types of NPS included in the present version of the WDCS; thirdly, the methodology for charge estimation; and finally, non-registered NPS and their potential inclusion in future editions of the WDCS. The paper concludes with remarks and challenges facing the first edition of the WDCS.