Enhancement of metastatic ability by ectopic expression of ST6GalNAcI on a gastric cancer cell line in a mouse model

ST6GalNAcI is a sialyltransferase responsible for the synthesis of sialyl Tn (sTn) antigen which is expressed in a variety of adenocarcinomas including gastric cancer especially in advanced cases, but the roles of ST6GalNAcI and sTn in cancer progression are largely unknown. We generated sTn-expressing human gastric cancer cells by ectopic expression of ST6GalNAcI to evaluate metastatic ability of these cells and prognostic effect of ST6GalNAcI and sTn in a mouse model, and identified sTn carrier proteins to gain insight into the function of ST6GalNAcI and sTn in gastric cancer progression. A green fluorescent protein-tagged human gastric cancer cell line was transfected with ST6GalNAcI to produce sTn-expressing cells, which were transplanted into nude mice. STn-positive gastric cancer cells showed higher intraperitoneal metastatic ability in comparison with sTn-negative control, resulting in shortened survival time of the mice, which was mitigated by anti-sTn antibody administration. Then, sTn-carrying proteins were immunoprecipitated from culture supernatants and lysates of these cells, and identified MUC1 and CD44 as major sTn carriers. It was confirmed that MUC1 carries sTn also in human advanced gastric cancer tissues. Identification of sTn carrier proteins will help understand mechanisms of metastatic phenotype acquisition of gastric cancer cells by ST6GalNAcI and sTn

Determination of the Failure Susceptibility of a Flat Die used in Biomass Pelletizing Machines by means of FEA based Design Exploration

This paper focuses on a design analysis of a flat die used in an agricultural biomass pelletizing machine by considering its high pressure loading failure susceptibility. The pellet die is one of the key elements in a pelletizing machine, and the strength of the die plate has an important role on the pellet’s quality and producibility. In fact, higher compression ratio (CR - the ratio of effective length and the internal (press channel) diameter of a die orifice/hole) will provide denser pellets which is a desired phenomenon, however, if the compression pressure is too high or CR is not determined to compensate high pressures, the raw material may block the die and the die may experience deformation failure due to overloading. If the desire is to make high quality pellets with no die failure, optimum flat die hole/orifice design parameters should be used which can provide the best CR for a specific compression pressure. This is the core motivation of this research. In this study, Finite Element Analysis (FEA) based design exploration has been utilised for a sample single hole flat die with various die geometry parameters against various compression pressure values. Following the FEA design exploration undertaken, a response surface analysis (RSA) was carried out and then estimation models (empirical equations), which could be used to calculate parameters of the die hole/orifice against applied compression pressure and failure susceptibility based on structural stress and deformation, was described. The results gained from the RSA has indicated that the estimation models have high R2 values (higher than 98 %) which could be used for adequately predicting failure susceptibility indicators. In addition to this, FEM-based simulation print-outs have provided useful stress distribution visuals on the die against different compression pressure values. Most especially, the study has highlighted that a detailed structural optimisation study may be scheduled in order to obtain die geometry design parameters with a focus on the failure susceptibility

Impaired bone and muscle development in young people treated with antiepileptic drugs

OBJECTIVE: Antiepileptic drugs (AEDs) are associated with reduced bone density, balance impairment, and increased fracture risk in adults. However, pediatric data are limited. Therefore, we aimed to examine bone, muscle, and balance outcomes in young patients taking AEDs. METHODS: We undertook a case-control study utilizing an AED exposure-discordant matched-pair approach. Subjects were aged 5-18 years with at least 12 months of AED exposure. Pairs were twins, nontwin siblings and first cousins, sex- and age-matched (to within 2 years), allowing for greater power than with unrelated control subjects. Dual energy x-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and muscle force/balance were tested, with questionnaires were administered for bone health and epilepsy details. RESULTS: Twenty-three pairs were recruited, (median age 12.9 years [subjects] and 13.5 years [controls])-7 twin, 14 sibling, and 2 cousin pairs. Those taking AEDs had an increased prevalence of fractures (15 fractures in 8 subjects, compared with 4 fractures in 3 controls, p < 0.01). Trabecular volumetric bone mineral density (vBMD) measured by pQCT at the 4% site (tibia) was reduced by 14% (p = 0.03) in subjects. Subjects exerted a decreased maximum force compared to body weight (Fmax total/g) at the tibia. There were no differences seen in either bone mineral parameters measured by DXA or balance measures. SIGNIFICANCE: Young people taking AEDs reported more fractures and had reductions in tibial vBMD and lower limb muscle force compared to their matched controls. These findings suggest that further exploration of bone health issues of young patients on AED therapy is required. Longitudinal studies are required to confirm these changes in the muscle-bone unit and to further explore the clinical outcomes