Paget bone disease involving young adults in 3 generations of a Korean family

Pancreatic cancer is an aggressive disease with a dismal prognosis. It has long been regarded as one of the most difficult cancers to accurately diagnose and stage preoperatively. The purpose of this review is to provide an update of the state-of-the-art for early detection, diagnosis, and staging of pancreatic cancer. These methods include spiral CT scans, magnetic resonance imaging, positron emission tomography (PET) imaging, laparoscopy, endoscopic ultrasound, CA 19-9 serology, fine needle aspiration cytology, ERCP brush cytology, and screening for p53 and ras oncogenes. These advanced techniques should help us to detect pancreatic cancers in high-risk populations at a curative stage and to decrease pancreaticoduodenectomies for benign disease which could otherwise be treated with less morbid procedures. In addition, these tests will help reliably diagnose pancreatic cancer preoperatively.     

Cell cycle-dependent establishment of a late replication program

DNA replication origins in chromosomes of eukaryotes are activated according to a temporal program. In the yeast Saccharomyces cerevisiae, activation of origins in early S phase appears to be a default state. However, cis-acting elements such as telomeres can delay origin activation until late S phase. Site-specific recombination was used to separate origin from telomere in vivo, thereby demonstrating that the signal for late activation is established between mitosis and START in the subsequent G1 phase. Once set, the signal can persist through the next S phase in the absence of the telomere. Establishment of the temporal program and of initiation competence of origins may be coincident events.     

Mechanism of enolase: the crystal structure of asymmetric dimer enolase-2-phospho-D-glycerate/enolase-phosphoenolpyruvate at 2.0 A resolution

Enolase, a glycolytic enzyme that catalyzes the dehydration of 2-phospho-d-glycerate (PGA) to form phosphoenolpyruvate (PEP), is a homodimer in all eukaryotes and many prokaryotes. Here, we report the crystal structure of a complex between yeast enolase and an equilibrium mixture of PGA and PEP. The structure has been refined using 29 854 reflections with an F/sigma(F) of >/=3 to an R of 0.137 with average deviations of bond lengths and bond angles from ideal values of 0.013 A and 3.1 degrees , respectively. In this structure, the dimer constitutes the crystallographic asymmetric unit. The two subunits are similar, and their superposition gives a rms distance between Calpha atoms of 0.91 A. The exceptions to this are the catalytic loop Val153-Phe169 where the atomic positions in the two subunits differ by up to 4 A and the loop Ser250-Gln277, which follows the catalytic loop Val153-Phe169. In the first subunit, the imidazole side chain of His159 is in contact with the phosphate group of the substrate/product molecule; in the other it is separated by water molecules. A series of hydrogen bonds leading to a neighboring enolase dimer can be identified as being responsible for ordering and stabilization of the conformationally different subunits in the crystal lattice. The electron density present in the active site suggests that in the active site with the direct ligand-His159 hydrogen bond PGA is predominantly bound while in the active site where water molecules separate His159 from the ligand the binding of PEP dominates. The structure indicates that the water molecule hydrating carbon-3 of PEP in the PEP --> PGA reaction is activated by the carboxylates of Glu168 and Glu211. The crystals are unique because they have resolved two intermediates on the opposite sides of the transition state.     

Peptide-mass fingerprinting and the ideal covering set for protein characterisation

The rules that govern the dynamics of protein characterisation by peptide-mass fingerprinting (PMF) were investigated through multiple interrogations of a nonredundant protein database. This was achieved by analysing the efficiency of identifying each entry in the entire database via perfect in silico digestion with a series of 20 pseudo-endoproteinases cutting at the carboxy terminal of each amino acid residue, and the multiple cutters: trypsin, chymotrypsin and Glu-C. The distribution of peptide fragment masses generated by endoproteinase digestion was examined with a view to designing better approaches to protein characterisation by PMF. On average, and for both common and rare cutters, the combination of approximately two fragments was sufficient to identify most database entries. However, the rare cutters left more entries unidentified in the database. Total coverage of the entire database could not be achieved with one enzymatic cutter alone, nor when all 23 cutters were used together. Peptide fragments of > 5000 Da had little effect on the outcome of PMF to correctly characterise database entries, while those with low mass (near to 350 Da in the case of trypsin) were found to be of most utility. The most frequently occurring fragments were also found in this lower mass region. The maximum size of uncut database entries (those not containing a specific amino acid residue) ranged from 52,908 Da to 258,314 Da, while the failure rate for a single cutter in identifying database entries varied from 10,865 (8.4%) to 23,290 (18.1%). PMF is likely to be a mainstay of any high-throughput protein screening strategy for large-scale proteome analysis. A better understanding of the merits and limitations of this technique will allow researchers to optimise their protein characterisation procedures.     

Hydrogen usage in air transportation

Advanced versions of commercial transport aircraft which are designed to begin service in the 1990 decade may well be fueled with liquid hydrogen. Conventional petroleum-base jet fuel is predicted to become economically unattractive in that time period as the world's crude oil is consumed. Synthetic jet fuel, liquid methane and liquid hydrogen are the best alternative fuels to succeed the petroleum-base product. Studies have shown liquid hydrogen offers significant advantages over jet fuel in aircraft applications. LH_z-fueled aircraft are lighter, quieter, have smaller wing area, require shorter runways and minimize pollution. They also use less energy, not only in terms of the fuel required to fly the design mission, but also including the energy required to manufacture the alternate fuels from coal and water. The advantage for hydrogen increases as the aircraft fuel requirement for the design mission increases. Using hydrogen as fuel in supersonic transport aircraft is particularly advantageous. Liquid methane has not yet been evaluated on an equitable basis as a fuel for transport aircraft.     

Characterizing string-of-pearls colloidal silica by multidetector hydrodynamic chromatography and comparison to multidetector size-exclusion chromatography, off-line multiangle static light scattering, and transmission electron microscopy

The string-of-pearls-type morphology is ubiquitous, manifesting itself variously in proteins, vesicles, bacteria, synthetic polymers, and biopolymers. Characterizing the size and shape of analytes with such morphology, however, presents a challenge, due chiefly to the ease with which the "strings" can be broken during chromatographic analysis or to the paucity of information obtained from the benchmark microscopy and off-line light scattering methods. Here, we address this challenge with multidetector hydrodynamic chromatography (HDC), which has the ability to determine, simultaneously, the size, shape, and compactness and their distributions of string-of-pearls samples. We present the quadruple-detector HDC analysis of colloidal string-of-pearls silica, employing static multiangle and quasielastic light scattering, differential viscometry, and differential refractometry as detection methods. The multidetector approach shows a sample that is broadly polydisperse in both molar mass and size, with strings ranging from two to five particles, but which also contains a high concentration of single, unattached "pearls". Synergistic combination of the various size parameters obtained from the multiplicity of detectors employed shows that the strings with higher degrees of polymerization have a shape similar to the theory-predicted shape of a Gaussian random coil chain of nonoverlapping beads, while the strings with lower degrees of polymerization have a prolate ellipsoidal shape. The HDC technique is contrasted experimentally with multidetector size-exclusion chromatography, where, even under extremely gentle conditions, the strings still degraded during analysis. Such degradation is shown to be absent in HDC, as evidenced by the fact that the molar mass and radius of gyration obtained by HDC with multiangle static light scattering detection (HDC/MALS) compare quite favorably to those determined by off-line MALS analysis under otherwise identical conditions. The multidetector HDC results were also comparable to those obtained by transmission electron microscopy (TEM). Unlike off-line MALS or TEM, however, multidetector HDC is able to provide complete particle analysis based on the molar mass, size, shape, and compactness and their distributions for the entire sample population in less than 20 min.