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.     

Interaction of protein percent with caloric density and protein source for lactating cows

Experiment 1 was to test effect of three ratios of energy to protein in complete mixed diets for 36 lactating cows in three, 28-d periods. Energy was varied with cottonseed hulls, pelleted ground corrugated boxes, and a mixture of the two. Crude protein was varied with soybean meal to give energy:crude protein of 5.7, 5.0, and 4.6 for each energy amount. Cottonseed meal was compared with soybean meal in corrugated box diets. Feed intake was much higher with cottonseed hulls, and appreciable feedlot bloat resulted from pelleted ground corrugated box diets. Data adjusted to equal feed intake showed significant effect of energy to crude protein ratio on milk yield and improved digestion of organic matter with soybean meal vs. cottonseed meal. Experiment 2 tested the hypothesis that lactating cows consuming high-protein alfalfa may benefit from supplemental protein. Diets were 50% forage. Six diets were 14 or 18% crude protein in three ratios of alfalfa hay to corn silage (0:100, 50:50, 100:0). Additional corn silage diets were to compare: 14 versus 18% protein from distiller's dried grains with solubles only and with .5 or .9% urea (four diets); two 14% protein diets compared .6% added potassium chloride with or without .5% urea. Thirty-six Holstein cows in early lactation received one of the 12 diets in each of three 28-d periods. Distiller's grains with solubles markedly depressed milk yield (2.2 kg/d) and milk protein (.22%); heat damage of distiller's grains was evident. Protein interacted with alfalfa so gain in milk from 18 versus 14% increased from .55 to 1.36 to 2.66 kg/d as alfalfa changed from 0 to 50 to 100%. Thus, crude protein of alfalfa was not as effective as that from soybean meal in supporting milk yield.     

The forward muon detector of the DELPHI experiment at LEP

The layout and construction of the muon drift chambers equipping the end caps of the DELPHI detector are described. The performance of this forward muon detection system, determined from cosmic ray tests and data collected during the first year of LEP operation, is presented.     

Influence of Storage Time and Temperature on Absorption of Flavor Compounds from Solutions by Plastic Packaging Materials

ABSTRACT: Linear low-density polyethylene (LLDPE), oriented polypropylene (OPP), polycarbonate (PC), polyethylene terephthalate (PET film and PET bottle), and polyethylene naphthalate (PEN) were stored in a model solution containing 10 flavor compounds at 4, 20, and 40 °C and flavor absorption by the plastic materials was followed in time. The absorption rate and/or total amount absorbed increased considerably with temperature from 4 to 40 °C. Depending on storage temperature, total flavor absorption by the polyolefins (LLDPE and OPP) was 3 to 2400 times higher than by the polyesters (PC, PET, and PEN). Therefore, in the factor of flavor absorption, polyesters are preferred over polyolefins as packaging material.     

Cyclic variations in the permeability of the cell wall of Saccharomyces cerevisiae.

To study cell-cycle-related variations in wall permeability of Saccharomyces cerevisiae, two approaches were used. First, an asynchronous culture was fractionated by centrifugal elutriation into subpopulations containing cells of increasing size. The subpopulations represented different stages of the cell cycle as judged by light microscopy. Cell wall porosity increased when these subpopulations became enriched with budded cells. Secondly, synchronous cultures were obtained by releasing MATa cells from alpha-factor induced G1-arrest. These cultures grew synchronously for at least two generations. The cell wall porosity increased sharply in these cultures, shortly before buds became visible and was maximal during the initial stages of bud growth. It decreased in cells which had completed nuclear migration and before abscission of the bud had occurred. The porosity reached its lowest value during abscission and in unbudded cells. We examined the incorporation of mannoproteins into the wall during the cell cycle. SDS-extractable mannoproteins were incorporated continuously. However, the incorporation of glucanase-extractable mannoproteins, which are known to affect cell wall porosity, showed cyclic oscillations and reached its maximum after nuclear migration. This coincided with a rapid decrease in cell wall porosity, indicating that glucanase-extractable mannoproteins might contribute to this decrease.     

Longitudinal analysis of semiconductor lasers with low reflectivity facets

An analysis is made of longitudinal effects in semiconductor lasers with low facet reflectivities. For this purpose, a self-consistent model is used based on the beam propagation method, which takes into account both the lateral and longitudinal dimension. The calculations show that longitudinal effects have a significant influence on the output fields in the laser.     

Development of Online Ultrasound Instructional Module and Comparison to Traditional Teaching Methods

A Web‐based teaching device was constructed to deliver information on fundamentals of ultrasound imaging to approximately one‐half the students in an undergraduate medical imaging course, while the remaining students were taught the same material via traditional lectures and typed notes. The students participating in this study were separated randomly but in such a manner that prior achievement was statistically equivalent for the two groups. After approximately two weeks of instruction, an ultrasound imaging exam was administered. Results indicated no statistically significant difference in scores on homework assigned during the instructional period between the traditional and online groups. Similarly, there was no statistically significant difference in the average exam scores of students in the two groups. The traditional group required significantly more time on learning activities than did the online group. These results indicated that level of understanding was not affected by use of the online device, while efficiency of learning improved dramatically. Reasons reported by the students for the improved efficiency of the online method included flexibility in time usage and ability to cater to the individual, which came with the added responsibility of self‐discipline. The traditional teaching method, meanwhile, allowed interaction with and instant feedback from a professor and other students. In this study we have demonstrated that the nature of an online device yields a higher level of efficiency than traditional lectures, despite the inherent drawbacks of the approach. The effectiveness of this device could potentially be improved by implementing enhancements to increase the level of interaction for the user and to help with discipline and time management.