The mechanical properties of anisotropic polymers: progress report no. 5

A report of work carried out during the period 1st October, 1967, to 31st March, 1963

The mechanical properties of anisotropic polymers: Progress report no. 6

Part 1 General Developments The basic development work on the tensile creep apparatus was completed by March, 1968. A description of the latest 'heavy-duty' creep rig and two types of contraction extensometer, together with the relevant creep trials, was given in Progress Report No. 5. Since then two further 'heavy-duty' creep rigs have been assembled and tested and are now ready for use with rigid plastics. In addition, further trials of the double transducer contraction extensometer described in Report No. 5 have been carried out. These trials are described in part 2 of this report The trials were considered reasonably satisfactory and each of the three heavy-duty creep rigs has now been fitted with a device of this type in addition to the normal tensile extensometer. The polythene creep rig described in Progress Report No. 3 has been working satisfactorily for over a year and no further modifications have been made in the period under review. At the conclusion of the above-mentioned trials it was considered that the creep apparatus was unlikely to require any further major changes. A detailed report of all the apparatus has therefore been prepared with the intention of submitting it for publication to the Journal of Scientific Instruments. It is at present being examined at the Ministry of Technology. (CoA Memo. No. 158)

The mechanical properties of anisotropic polymers: progress report no. 7

Part I General Developments The major part of the period under review was devoted to a study of the tensile creep properties of isotropic and uniaxially oriented Perspex sheets (standard grade) using the three heavy-duty creep rigs mentioned in the previous Progress Report (No. 6. September, 1968). Measurements of lateral contraction were made simultaneously with the tensile strain measurements during most of the creep tests. The creep rupture behaviour and optical anisotropy of the oriented sheets were also studied in an attempt to present a more complete picture of the behaviour of the material. Some of the early results of this work have already been published and copies sent to the Ministry. (Darlington and Saunders; 1969). Details of the complete work will be found in part II of this report. The two types of contraction extensometer described in Progress Report No. 5 were used during the Perspex studies and reasonable agreement was obtained between the results. The techniques required with the contraction devices were considerably improved during the period under review and the absolute validity of the contraction measurements is now more certain. Some comments on the general performance of the apparatus are given in section 2.8.4

Creep studies on oriented thermoplastics

The enhancement of many of the mechanical properties of thermoplastics which may be achieved by orienting the molecules has been known for some time. It has been exploited in the production of textile fibres end oriented films. Molecular orientation also occurs during processes such as extrusion, moulding or forming. Here, unless carefully controlled, it may well cause a deterioration in the properties of the finished article. In view of this a systematic study on the anisotropy of the mechanical properties of thermoplastics, resulting from molecular orientation, is being carried out at present in these laboratories … [cont.]

An apparatus for the measurement of tensile creep and contraction ratios in small non-rigid specimens

An apparatus is described for precise measurement of creep properties in specimens with gauge lengths down to 1.2 cm. An extensometer has been developed which is supported independently of the specimen and exerts a load on the specimen of less than 5 grams. It can thus be used with small non-rigid specimens. The extensometer will detect strains down to 2 x 10-6. The stability is excellent. An adaptation of the system which allows simultaneous measurement of tensile strain and lateral strain during creep is also described. The apparatus was designed for the measurement of anisotropy of creep properties in oriented thermoplastics and reference to such measurements is given. It is however entirely suitable for general application to small specimens

Microbial carcinogenic toxins and dietary anti-cancer protectants

Several toxins are known which account for the ability of some bacteria to initiate or promote carcinogenesis. These ideas are summarised and evidence is discussed for more specific mechanisms involving chymotrypsin and the bacterial chymotryptic enzyme subtilisin. Subtilisin and Bacillus subtilis are present in the gut and environment and both are used commercially in agriculture, livestock rearing and meat processing. The enzymes deplete cells of tumour suppressors such as deleted in colorectal cancer (DCC) and neogenin, so their potential presence in the food chain might represent an important link between diet and cancer. Over-eating increases secretion of chymotrypsin which is absorbed from the gut and could contribute to several forms of cancer linked to obesity. Inhibition of these serine proteases by Bowman–Birk inhibitors in fruit and vegetables could account for some of the protective effects of a plant-rich diet. These interactions represent previously unknown non-genetic mechanisms for the modification of tumour suppressor proteins and provide a plausible explanation contributing to both the pro-oncogenic effects of meat products and the protective activity of a plant-rich diet. The data suggest that changes to farming husbandry and food processing methods to remove these sources of extrinsic proteases might significantly reduce the incidence of several cancers

An expanding range of targets for kynurenine metabolites of tryptophan

The kynurenine pathway of tryptophan metabolism accounts for most of the tryptophan that is not committed to protein synthesis and includes compounds active in the nervous and immune systems. Kynurenine acts on the aryl hydrocarbon receptor, affecting the metabolism of xenobiotics and promoting carcinogenesis. Quinolinic acid is an agonist at N-methyl-D-aspartate receptors (NMDARs), but is also pro-oxidant, has immunomodulatory actions, and promotes the formation of hyperphosphorylated tau proteins. Kynurenic acid blocks NMDARs and α7-homomeric nicotinic cholinoceptors and is also an agonist at the orphan G-protein-coupled receptor GPR35. 3-Hydroxykynurenine and 3-hydroxyanthranilic acid have pronounced redox activity and regulate T cell function. Cinnabarinic acid can activate metabotropic glutamate receptors. This review highlights the increasing range of molecular targets for components of the kynurenine pathway in both the nervous and immune systems in relation to their relevance to disease and drug development

Obesity and cancer: existing and new hypotheses for a causal connection

Existing explanations of obesity-associated cancer emphasise direct mutagenic effects of dietary components or hormonal imbalance. Some of these hypotheses are reviewed briefly, but recent evidence suggests a major role for chronic inflammation in cancer risk, possibly involving dietary content. These ideas include the inflammation-induced activation of the kynurenine pathway and its role in feeding and metabolism by activation of the aryl hydrocarbon receptor (AHR) and by modulating synaptic transmission in the brain. Evidence for a role of the kynurenine pathway in carcinogenesis then provides a potentially major link between obesity and cancer. A second new hypothesis is based on evidence that serine proteases can deplete cells of the tumour suppressors Deleted in Colorectal Cancer (DCC) and neogenin. These enzymes include mammalian chymotryptic proteases released by pro-inflammatory neutrophils and macrophages. Blood levels of chymotrypsin itself increase in parallel with food intake. The mechanistically similar bacterial enzyme subtilisin is widespread in the environment, animal probiotics, meat processing and cleaning products. Simple public health schemes in these areas, with selective serine protease inhibitors and AHR antagonists and could prevent a range of intestinal and other cancers

Dependence receptor involvement in subtilisin-induced long-term depression and in long-term potentiation

The serine protease subtilisin induces a form of long-term depression (LTD) which is accompanied by a reduced expression of the axo-dendritic guidance molecule Unco-ordinated-5C (Unc-5C). One objective of the present work was to determine whether a loss of Unc-5C function contributed to subtilisin-induced LTD by using Unc-5C antibodies in combination with the pore-forming agents Triton X-100 (0.005%) or streptolysin O in rat hippocampal slices. In addition we have assessed the effect of subtilisin on the related dependence receptor Deleted in Colorectal Cancer (DCC) and used antibodies to this protein for functional studies. Field excitatory postsynaptic potentials (fEPSPs) were analysed in rat hippocampal slices and protein extracts were used for Western blotting. Subtilisin produced a greater loss of DCC than of Unc-5C, but the antibodies had no effect on resting excitability or fEPSPs and did not modify subtilisin-induced LTD. However, antibodies to DCC but not Unc-5C did reduce the amplitude of theta-burst long-term potentiation (LTP). In addition, two inhibitors of endocytosis – dynasore and tat-gluR2(3Y) – were tested and, although the former compound had no effect on neurophysiological responses, tat-gluR2(3Y) did reduce the amplitude of subtilisin-induced LTD without affecting the expression of DCC or Unc-5C but with some loss of PostSynaptic Density Protein-95. The results support the view that the dependence receptor DCC may be involved in LTP and suggest that the endocytotic removal of a membrane protein or proteins may contribute to subtilisin-induced LTD, although it appears that neither Unc-5C nor DCC are involved in this process. (220)