Magnesium global development: Outcomes from the TMS 2007 annual meeting

The magnesium industry is experiencing dramatic growth, due in part to the demands of the automotive industry to improve fuel economy and emissions. As a result, the TMS annual magnesium symposium is one of the fastest-growing subject areas at TMS. In addition, TMS is recognized as the global light metals community’s preeminent forum for the presentation of magnesium science and technological issues. As a focal point of the 2007 TMS Annual Meeting in Orlando, Florida, the TMS Magnesium Committee held its first plenary session with expert representatives from around the world. In order to address the surge in magnesium technology in recent years, the TMS Magnesium Globalization plenary session included a variety of subjects that ranged from economic to technical.     

So who was Gerdy... and how did he get his own tubercle?

To elucidate the role of apoptosis in the pathological lesion of hepatitis B virus (HBV) infection, biopsied liver tissue specimens of 38 patients with chronic hepatitis B of varying severity were investigated with in situ immunohistochemistry and TUNEL test. Apoptotic hepatocytes were found to be rare, while the nuclei of many cells were positively stained with TUNEL, suggesting 3'-OH ends generated as the DNA was impaired. Of the 17 cases with mild lesion or without piecemeal necrosis, 14 were negative or weakly positive with both Fas and TUNEL test. Of the 7 cases with piecemeal and bridging necrosis, none was strongly positive. In the 14 cases with active hepatitis and early cirrhosis, strongly positive results with Fas were found in 9 and with TUNEL in 3 respectively. It is suggested that the cytotoxic T lymphocyte (CTL)-Fas-apoptosis mechanism was involved in the hepatocyte death of hepatitis B as well. The Fas expression, DNA damage and apoptotic cells distributed mostly in the piecemeal necrosis region, and the ballooning and the necrotic hepatocytes were also clustering in this region. As both the apoptosis and necrosis are mediated by CTL, they are closely related: while transducted by different ways, they occurred independently.     

Fatigue behaviour of porous polysulphone surface coatings for orthopaedic applications

Porous polysulphone (PPSF) has recently been selected as a candidate material for use as a prosthetic surface coating in orthopaedic applications to acommodate ‘bone ingrowth’ for fixation to the skeletal system. The tension-loaded fatigue behaviour of PPSF was characterized based on the interpretation of stress/life (S/N) data. Results of this investigation indicate that the fatigue life of PPSF is governed by crack propagation across the sintered necks of the porous structure. In addition, experimental data revealed that the fatigue strength-reduction factor, K_f, remains equivalent to the tensile notch strength-reduction factor for a wide range of fatigue lives. However, analytical results indicate that the material has a low notch sensitivity and that a single application of a theoretical elastic stress-concentration factor in a fatigue analysis would be inappropriate.     

A novel cell ablation strategy blocks tobacco anther dehiscence

We utilized a new cell ablation strategy to ablate specific anther cell types involved in the dehiscence process. The tobacco TA56 gene promoter is active within the circular cell cluster, stomium, and connective regions of the anther at different developmental stages. We introduced a cytotoxic TA56/barnase gene into tobacco plants together with three different anticytotoxic barstar genes. The anticytotoxic barstar genes were used to protect subsets of anther cell types from the cytotoxic effects of the TA56/barnase gene. The chimeric barstar genes were fused with (1) the tobacco TP12 gene promoter that is active at high levels in most anther cell types; (2) the soybean lectin gene promoter that is active earlier in the connective, and at lower levels in the circular cell cluster and stomium, than is the TA56 promoter; and (3) the tobacco TA20 gene promoter that is active at high levels in most anther cell types but has a different developmental profile than does the TP12 promoter. Normal anther development and dehiscence occurred in plants containing the TA56/barnase and TP12/barstar genes, indicating that barstar protects diverse anther cell types from the cytotoxic effects of barnase. Anthers containing the TA56/barnase and lectin/barstar genes also developed normally but failed to dehisce because of extensive ablation of the circular cell cluster, stomium, and contiguous connective regions. Anthers containing the TA56/barnase and TA20/barstar genes failed to dehisce as well. However, only the stomium region was ablated in these anthers. The connective, circular cell cluster, and adjacent wall regions were protected from ablation by the formation of barnase/barstar complexes. We conclude that anther dehiscence at flower opening depends on the presence of a functional stomium region and that chimeric barnase and barstar genes containing promoters that are active in several overlapping cell types can be used for targeted cell ablation experiments.     

Potential pitfalls in the work-up and diagnosis of choanal atresia

To increase an awareness of the developmental anatomy of the nasal cavity as it applies to the radiologic work-up of choanal atresia and frontoethmoidal cephaloceles, we report two cases that demonstrate potentially serious imaging pitfalls. Two neonates with nasopharyngeal obstruction were imaged with CT and MR. Both patients had surgically proved bilateral bony choanal atresia. In addition to choanal atresia, CT showed a radiolucent, or nonossified cribriform plate and mucoid secretions within the nasal fossa, adjacent to the cribriform plate, which approximated the attenuation of brain parenchyma. In one of the patients, a preoperative diagnosis of nasopharyngeal encephalocele resulted in surgical exploration. At surgery, however, the cartilaginous cribriform plate was found to be intact.     

Fatigue performance of ultra-high-molecular-weight polyethylene: effect of gamma radiation sterilization

Ultra-high-molecular-weight polyethylene (UHMWPE) failure presents a significant materials concern in the orthopaedic community. Clinical failure following joint arthroplasty can result from the biological response to wear debris as well as structural failure owing to UHMWPE fatigue. In this study, cantilever rotating beam fatigue testing was conducted on GUR 415 UHMWPE in both the unsterilized and gamma radiation sterilized conditions. Calculations of flexural fatigue stresses were based on extreme fibre stresses and assumed negligible plastic deformation. Both material conditions exhibited similar fatigue strengths at 250,000 cycles (approximately 41 MPa) and at one million cycles (approximately 36 MPa), but a large difference developed after two million cycles. At ten million cycles, the unsterilized condition exhibited a fatigue strength of approximately 31 MPa, while the gamma-sterilized condition exhibited a reduced fatigue strength of approximately 18 MPa, an approximate decrease of 42%. High-cycle fatigue testing was necessary to fully characterize this behaviour owing to the pronounced difference in fatigue behaviour beyond two million cycles. These results suggest that gamma radiation sterilization of UHMWPE medical implants reduces their resistance to cyclic loading and, subsequently, may contribute to the associated fatigue-related failures which have been reported clinically.     

Data extrapolation for high resolution radar imaging

In radar imaging, AR modeling is sometimes used to extrapolate the scattered field data to obtain a high resolution image. In general, the Burg method is used to estimate the prediction parameters. The Burg method leads to a stable prediction filter but can also cause bias in the estimated spectra. One can also use the modified covariance method (MCM) to estimate the prediction parameters. These parameters lead to unbiased spectra. However, the MCM does not guarantee a stable prediction filter. One may have to modify the prediction parameters to ensure a stable prediction filter. One way to ensure stability is to reflect the unstable poles inside the unit circle. It is shown that the modified parameters can be used effectively for data extrapolation. The radar images obtained using this extrapolated data are more accurate than those obtained using the extrapolated data from the Burg prediction parameters     

In vivo deamidation characterization of monoclonal antibody by LC/MS/MS

The spontaneous nonenzymatic deamidation of glutaminyl and asparaginyl residues of peptides and proteins has been observed both in vitro and in vivo. Deamidation may change the structure and function of a peptide or protein, potentially resulting in decreased bioactivity, as well as alterations in pharmacokinetics and antigenicity of the protein pharmaceutical. Therefore, it is necessary to monitor the effect of storage and formulation conditions on deamidation of a protein drug candidate. Of particular interest is the investigation of in vivo deamidation mechanisms of protein drug candidates. Several methods are available to characterize the deamidation of peptides and proteins. We present here a LC/MS/MS method used to evaluate the deamidation of an antibody after in vivo administration. A humanized monoclonal IgG1 antibody (MAb) has several "hot spots" for spontaneous deamidation. One site, amino acid residue Asn55 located in the CDR2 region of the heavy chain, is of particular interest since deamidation at this site greatly decreases the binding activity. MAb was administered to cynomolgus monkeys by intravenous and subcutaneous routes. At various times after dosing, monkey serum was prepared and MAb captured by the immobilized antigen or a goat anti-human IgG Fcgamma antibody. The captured MAb was treated with trypsin followed by endoproteinase Glu-C. The digests were separated on RP-HPLC and analyzed by MS/MS on Q-Tof Global mass spectrometer. Using this method, we were able to determine the deamidation half-life of amino acid residue Asn55 in vivo and the ratio of the deamidated derivatives, i.e., isoAsp55 and Asp55. The method is rapid and sensitive with low-nanogram quantities of protein detected in the biological matrix.