The Electronic Spectrum of Gaseous CoO in the Visible Region

Laser excitation spectra of gaseous CoO have been recorded using Doppler-limited intracavity spectroscopy and supersonic jet-cooled molecular beam methods. As seen in the molecular beam spectra there are nearly 100 bands arising from the X4Delta7/2 spin component of the ground state in the wavelength region 430-720 nm. All of them are very strongly red-degraded and most of them are perturbed. 59Co hyperfine broadenings or splittings have been observed in many. The bands can be arranged into five electronic transitions, together with a considerable number of "extra" bands induced by perturbations; two of the excited electronic states are 4Phi, while the other three, which lie within 1700 cm-1, are 4Delta. Semi-empirical calculations have been carried out for the 4Delta excited states, using exchange integrals transferred from the TiO and VO spectra; the predicted energies, spin-orbit structures, and relative intensities in absorption are consistent with the assignment of all three 4Delta states to the same electron configuration, (4ssigma)1(3ddelta)3(3dpi)2(3dsigma)1. It seems that there are extensive interactions between the excited 4Delta states, because only one of them gives rise to a recognizable, though irregular, long vibrational progression in absorption. The other two progressions die out abruptly and unexpectedly after three or four members, presumably as a result of interference effects; however, wavelength-resolved fluorescence studies, together with calculations of the Franck-Condon overlap integrals to the various vibrational levels of the ground state, show that the upper state progressions reappear following a region of confused absorption. All of the excited states show highly irregular variations of their vibrational intervals and rotational constants with the vibrational quantum number, v. The wavelength-resolved fluorescence spectra give evidence for new low-lying electronic states of CoO at 3038, 5989, and 9105 cm-1; based on its vibrational frequency the 3038 cm-1 state is possibly the sigmadelta4pi2 B4Sigma- state. Copyright 1997 Academic Press. Copyright 1997Academic Press     

Origin of genes

We discuss two tests of the hypothesis that the first genes were assembled from exons. The hypothesis of exon shuffling in the progenote predicts that intron phases will be correlated so that exons will be an integer number of codons and predicts that the exons will be correlated with compact regions of polypeptide chain. These predictions have been tested on ancient conserved proteins (proteins without introns in prokaryotes but with introns in eukaryotes) and hold with high statistical significance. We conclude that introns are correlated with compact features of proteins 15-, 22-, or 30-amino acid residues long, as was predicted by "The Exon Theory of Genes."     

Recent advances in the treatment of Hodgkin's disease

Most patients who present with Hodgkin's disease today can be cured of their disease. Current treatments strive to maintain a high level of efficacy while reducing side effects that limit the quality and length of survival. Sophisticated molecular techniques continue to aid our understanding of the etiology and pathogenesis of this disease. However, the heterogeneity and paucity of "malignant" cells in Hodgkin's disease continue to limit our ability to articulate a coherent and encompassing model.     

Structural and functional analysis of the Pig-a protein that is mutated in paroxysmal nocturnal hemoglobinuria

There is now convincing evidence that the Pig-a gene is mutated in patients with paroxysmal nocturnal hemoglobinuria (PNH), a disease in which one or more clones of hematopoietic cells have incomplete assembly of glycosylphosphatidylinositol (GPI) anchors and absence of GPI-linked protein expression on the cell surface. Little is known, however, about the Pig-a protein product that is necessary for GPI anchor bioassembly. Relatively few substitution (missense) Pig-a gene mutations have been identified, but we noted two apparent clusters at codons 128-129 and 151-156 and hypothesized that these might represent critical regions of the Pig-a protein. We therefore used site-directed mutagenesis to create conservative mutations in the Pig-a protein, then performed structural and functional analysis. Each Pig-a mutation generated a Pig-a protein of normal size and stability, but certain mutations had substantial deleterious effects on protein function. Conservative mutation of codons histidine 128 (H128), serine 129 (S129), and serine 155 (S155) had greatly diminished function, while mutations of flanking residues had no effect on function. Our results represent the first structure/function analysis of the Pig-a protein, and suggest that codons H128, S129, and S155 represent critical regions of the Pig-a protein. Our results also suggest a means by which transgenic mice with a "partial knock-out" of Pig-a function could be generated, which would allow investigation of PNH in an animal model.     

Cross-linking of the CAMPATH-1 antigen (CD52) mediates growth inhibition in human B- and T-lymphoma cell lines, and subsequent emergence of CD52-deficient cells

Emotional hyperthermia, circadian variations and the rise of body temperature related to exercise, have all been attributed to setpoint temperature shifts. The accepted theory holds that core temperature is regulated by corrective thermoregulatory responses opposing the core temperature deviations from the setpoint level. However, in fever and anapyrexia the thermoregulatory responses appear to be not corrective but helping, that is in the same direction as the core temperature deviation. A supplementary ad hoc hypothesis that setpoint level shifts explains why the thermoregulatory responses still could be considered "corrective" in spite of being in the same direction as the core temperature deviation. But supplementary ad hoc hypotheses immunize a theory to experimental challenges and therefore can no longer be considered a scientific theory. The present work shows that most of the arguments adduced to explain almost every biothermal phenomenon as being due to setpoint shifts cannot withstand a critical analysis.     

A naturally occurring hPMS2 mutation can confer a dominant negative mutator phenotype

Defects in mismatch repair (MMR) genes result in a mutator phenotype by inducing microsatellite instability (MI), a characteristic of hereditary nonpolyposis colorectal cancers (HNPCC) and a subset of sporadic colon tumors. Present models describing the mechanism by which germ line mutations in MMR genes predispose kindreds to HNPCC suggest a "two-hit" inactivation of both alleles of a particular MMR gene. Here we present experimental evidence that a nonsense mutation at codon 134 of the hPMS2 gene is sufficient to reduce MMR and induce MI in cells containing a wild-type hPMS2 allele. These results have significant implications for understanding the relationship between mutagenesis and carcinogenesis and the ability to generate mammalian cells with mutator phenotypes.     

Simultaneous multislice acquisition using rosette trajectories (SMART): a new imaging method for functional MRI

OBJECTIVES: Despite the recent introduction of new peroral drugs as well as neurosurgical methods for Parkinson's disease, treatment of late stage parkinsonian patients remains difficult and many patients become severely handicapped because of fluctuations in their motor status. Injections and infusions of apomorphine has been suggested as an alternative in the treatment of these patients, but the number of studies describing the effects of such a treatment over longer time periods is still limited. The objective was to investigate the therapeutic response and range of side effects during long term treatment with apomorphine in advanced Parkinson's disease. METHODS: Forty nine patients (30 men, 19 women; age range 42-80 years) with Parkinson's disease were treated for 3 to 66 months with intermittent subcutaneous injections or continuous infusions of apomorphine. RESULTS: Most of the patients experienced a long term symptomatic improvement. The time spent in "off" was significantly reduced from 50 to 29.5% with injections and from 50 to 25% with infusions of apomorphine. The quality of the remaining "off" periods was improved with infusion treatment, but was relatively unaffected by apomorphine injections. The overall frequency and intensity of dyskinesias did not change. The therapeutic effects of apomorphine were stable over time. The most common side effect was local inflammation at the subcutaneous infusion site, whereas the most severe were psychiatric side effects occurring in 44% of the infusion and 12% of the injection treated patients. CONCLUSION: Subcutaneous apomorphine is a highly effective treatment which can substantially improve the symptomatology in patients with advanced stage Parkinson's disease over a prolonged period of time.     

Spectrophotometric measurement of swelling of polymer films by very poor solvents

Solvent swelling of polymers is important for many applications, but can be difficult to measure when thin films or very poor solvents are involved. A novel spectrophotometric method is presented that is well suited for measuring swelling of thick or thin polymer films by very poor solvents. In this method, the solvent is stained with iodine, and solvent uptake is measured by observing the change in visible light absorption of the polymer using a spectrophotometer. Using this method, swelling can be accurately measured in thin (< 2 μm) polymer films and with poor solvents that cause little swelling, even water. Results are presented for PMMA films of varying molecular weights swelled by water, by water–alcohol mixtures, and by undiluted alcohols. Swelling of these films is more rapid and more Fickian than has been reported for bulk samples, probably due to differences in PMMA molecular weight and processing. The properties of the iodine–PMMA complex are also explored. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 97: 1082–1089, 2005     

Effects of non-conservative changes to tyrosine 76, a key DNA binding residue of DNase I, on phosphodiester bond cleavage and DNA hydrolysis selectivity

Non-conservative changes, consisting of Y76E, Y76L, Y76Q and Y76W, have been made to tyrosine 76, one of the key DNA binding residues in DNase I. Normally Y76 inserts into the minor groove of DNA and makes an unusual, hydrophobic, stacking interaction with one of the sugars. All four mutants bind to DNA more tightly than the wild type, but cut it more slowly as assessed by Kunitz assays. This gives a rather small decrease in the specificity constants (Vmax/K(m)) for the hydrolysis of DNA, which is roughly paralleled by the loss of activity towards the non-DNA small chromophoric substrate, thymidine-3',5'-di(p- nitrophenyl)phosphate. These non-conservative mutants, therefore, show different behaviour to Y76A and Y76G, studied previously [Doherty A.J., Worrall A.F. and Connolly B.A. (1995) J: Mol. Biol., 251, 366-377]. These two mutants both bind to and cut DNA poorly, resulting in large decreases in Vmax/K(m) values. However, they showed little reduction in rates with the chromophoric substrate. It is likely that the altered side chains in the non-conservative mutants are still able to interact productively with the DNA and contribute to the observed DNA distortion that is essential for efficient catalysis. However, these mutations disrupt the active site, most probably by interference with the hydrogen bonded Y76-E78-H134 triad. H134 is a critical hydrolytic residue of DNase I that is essential for catalysis. The DNA cleavage selectivity of the Y76E, Y76L, Y76Q and Y76W mutants were little altered as compared with the wild-type enzyme as measured using the cutting patterns of a 160 base-pair Escherichia coli Tyr T promoter DNA fragment. This confirms earlier observations, with Y76F, Y76A and Y76G, that showed that this tyrosine has little role in DNA cleavage specificity.