Process Modelling for Control of Product Wall Thickness in Thermoforming

The present paper describes the results of an investigation into the modelling of plug assisted thermoforming. The objective of this work was to improve the finite element modelling of thermoforming through an enhanced understanding of the physical elements underlying the process. Experiments were carried out to measure the effects on output of changes in major parameters and simultaneously simple finite element models were constructed. The experimental results show that the process creates conflicting and interrelated contact friction and heat transfer effects that largely dictate the final wall thickness distribution. From the simulation work it was demonstrated that a high coefficient of friction and no heat transfer can give a good approximation of the actual wall thickness distribution. However, when conduction was added to the model the results for lower friction values were greatly improved. It was concluded that further work is necessary to provide realistic measurements and models for contact effects in thermoforming.

Translational control of SEPT9 isoforms is perturbed in disease

A common feature of the mammalian septin gene family is complex genomic architecture with multiple alternate splice variants. Septin 9 has 18 distinct transcripts encoding 15 polypeptides, with two transcripts (SEPT9_v4 and v4*) encoding the same polypeptide. We have previously reported that the ratio of these distinct transcripts is altered in neoplasia, with the v4 transcript being the usual form in normal cells but v4* becoming predominant in tumours. This led us to ask what the functional differences between these two transcripts might be. The 5'-UTRs of v4 and v4* have distinct 5' ends encoded by exons 1 beta (v4) and 1 zeta and 2 (v4*) and a common 3' region and initiating ATG encoded within exon 3. Here we show that the two mRNAs are translated with different efficiencies and that cellular stress can alter this. A putative internal ribosome entry site can be identified in the common region of the v4 and v4* 5'-UTRs and translation is modulated by an upstream open-reading frame in the unique region of the v4 5'-UTR. Germline mutations in hereditary neuralgic amyotrophy (HNA) map to the region which is common to the two UTRs. These mutations dramatically enhance the translational efficiency of the v4 5'-UTR, leading to elevated SEPT9_v4 protein under hypoxic conditions. Our data provide a mechanistic insight into how the HNA mutations can alter the fine control of SEPT9_v4 protein and its regulation under physiologically relevant conditions and are consistent with the episodic and stress-induced nature of the clinical features of HNA.