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Imidazo[1,2-a]pyridyl N-arylpyridazinones were hybridized from the classic pyridinylimidazoles and the more recent dual hydrogen bond acceptors, resulting in a new structural class of selective p38 MAP kinase inhibitors.

A 10 kDa collagenous peptide, derived from a 30 kDa disulfide bonded fragment, was purified from bovine periodontal ligament. Amino acid sequence analysis of tryptic peptides demonstrated a 92.8% homology with the chicken α 1(XII) cDNA derived sequence, demonstrating for the first time the presence of type XII collagen in a mammalian species and in an adult tissue.

This paper examines three themes of modelling. Its primary concern is with the problem of representing uncertainty in models, while the issues of interactive computer modelling and the use of models as decision aids also receive some attention. These issues are addressed by way of a comparative analysis of three models of the acid-deposition problem which have been developed in recent years in the UK and USA. The design of these models and the methods employed to represent uncertainty are described. The strengths and weaknesses of these techniques, and the various unresolved issues which these models have highlighted, are discussed.

Improved upper and lower bounds are found for the number of hamiltonian circuits in the -cube.

The deposition of the beta amyloid peptide in neuritic plaques and cerebral blood vessels is a hallmark of Alzheimer's disease (AD) pathology. The major component of the amyloid deposit is a 4.2-kDa polypeptide termed amyloid beta-protein of 39-43 residues, which is derived from processing of a larger amyloid precursor protein (APP). It is hypothesized that a chymotrypsin-like enzyme is involved in the processing of APP. We have discovered a new serine protease from the AD brain by polymerase chain reaction amplification of DNA sequences representing active site homologous regions of chymotrypsin-like enzymes. A cDNA clone was identified as one out of one million that encodes Zyme, a serine protease. Messenger RNA encoding Zyme can be detected in some mammalian species but not in mice, rats, or hamster. Zyme is expressed predominantly in brain, kidney, and salivary gland. Zyme mRNA cannot be detected in fetal brain but is seen in adult brain. The Zyme gene maps to chromosome 19q13.3, a region which shows genetic linkage with late onset familial Alzheimer's disease. When Zyme cDNA is co-expressed with the APP cDNA in 293 (human embryonic kidney) cells, amyloidogenic fragments are detected using C-terminal antibody to APP. These co-transfected cells release an abundance of truncated amyloid beta-protein peptide and shows a reduction of residues 17-42 of Abeta (P3) peptide. Zyme is immunolocalized to perivascular cells in monkey cortex and the AD brain. In addition, Zyme is localized to microglial cells in our AD brain sample. The amyloidogenic potential and localization in brain may indicate a role for this protease in amyloid precursor processing and AD.

Measurements of the spectral distribution of Australian daylight falling on a horizontal plane over the wavelength range 280–2800 nm have been made at two locations in southeastern Australia, one set of measurements in an urban environment and the other in the country. Each set has been subjected to characteristic vector analysis. The major differences between the results and those of northern hemisphere workers are a higher ultraviolet-to-visible ratio and a chromaticity locus slightly to the purple side of the full radiator locus.

The type 1 human immunodeficiency virus (HIV-1) encodes a 27-kDa protein termed Nef (negative factor). Nef has been reported to down-regulate viral gene transcription directed by the HIV-1 long terminal repeat. To assess the possible role of Nef in the initiation or maintenance of viral latency, we prepared two different nef expression vectors (pNEF from the HXB-3 proviral clone; pNEF-2/3 from HXB-2 and HXB-3) and a control vector containing a frameshift mutation in the HXB-3 nef coding sequence (pNEF-fs). Consistent with prior studies, the Nef proteins produced by pNEF and pNEF-2/3 were approximately 27 kDa in size, posttranslationally modified by myristoylation, and primarily associated with cytoplasmic membrane structures. However, in contrast to previous reports, these Nef proteins failed to inhibit transcriptional activity of the HIV-1 long terminal repeat in any of a variety of cell types, including primary human T lymphocytes, Jurkat or YT-1 leukemic T cells, U-937 promonocytic cells, and nonlymphoid COS cells. Furthermore, HXB-3 proviral clones of HIV-1 containing either a wild-type or mutated version of the nef gene replicated in an indistinguishable manner when transfected into COS cells. Our findings suggest that Nef is neither a transcriptional inhibitor nor a negative viral factor under these assay conditions. Rather, we suggest that the primary biological function of this conserved HIV-1 protein has yet to be defined, perhaps reflecting an intrinsic shortcoming in the in vitro experimental systems presently available for the study of HIV-1.

A 10 kDa collagenous peptide, derived from a 30 kDa disulfide bonded fragment, was purified from bovine periodontal ligament. Amino acid sequence analysis of tryptic peptides demonstrated a 92.8% homology with the chicken α1(XII) cDNA derived sequence, demonstrating for the first time the presence of type XII collagen in a mammalian species and in an adult tissue.

In the Geological Magazine for February the limestone-boulders in the Bowland Shales of School Share near Settle were redescribed by Dr. R. G. S. Hudson and the writer, and the conclusion reached that they represented a landslip from a fault-scarp raised along part of the Craven Fault-system during the mid-Carboniferous earth-movement. Whilst that article was in the press the writer became aware that great limestone-boulders occur in the Caney Shale of Oklahoma and that they have occasioned much discussion or even, owing to their size and varied fossils, uncertainty as to the age of the associated beds. His interest was piqued, for he recalled that a close comparison had been drawn by Bisat between the contrast of Bowland Shale (Culm) and Yoredale facies of sedimentation, displayed in the Craven Lowlands and in the Craven Uplands and the Yorkshire Dales, and a contrast in Oklahoma between the sedimentation in the Ouachita Mountains and that in the nearby Arbuckle Mountains.

Dr. Robb, in his rejoinder to my criticism of his paper, asks me a direct question; and as, to me at least, the matter under discussion is of far greater importance than any mere difference of opinion between us, I hope I may be permitted to reply.

I Propose in these papers to demonstrate, or rather to indicate the nature of the demonstration of, the proposition that—All Geometry, whether projective or metrical, may logically be regarded as merely a particular concrete application of the general theory of Order, as defined by Boundaries.It is true that Geometry, as ordinarily understood, is something more than this; it is concerned with the actual subjective conceptions we -entertain of Space, and so far provides matter of discussion to the Psychologist; and it is concerned with the actual objective measurements we make upon physical bodies in Space, and so far concerns the Physicist; while in both these respects it extends beyond the region of pure Logic into those of Epistemology and Philosophy generally. But so far as the pure Mathematician is concerned, every geometrical theorem is embraced in the Theory about to be discussed.

In this simulator the amplitude and phase of a light wave are represented by the amplitude and phase of an ac voltage. Each layer in the film is simulated by a four-terminal network containing adjustable attenuators and an adjustable phase shifter. The network obeys the same difference equation [See: Lord Rayleigh , Proc. Roy. Soc. (London)93, 565 ( 1917); P. Rouard , Ann. Phys., Ser. 11, 7, 291 ( 1937); W. Pfister O. H. Roth , Hochfrequenztechnik und Elektroakustik51, 156 ( 1938); S. M. MacNeille , U. S. Patent No. 2 403 731; A. Vasicek , J. Opt. Soc. Am.37, 623 ( 1947); D. Caballero , J. Opt. Soc. Am.37, 176 ( 1947)] as that which relates the reflectance of n+1 interference layers to the separate reflectances of the first n layers taken together and of the n+1th layer. With these networks connected in sequence and the circuit parameters adjusted to correspond to the optical constants of the various layers of the film, either the reflectance or transmittance of the multilayer can be read directly on a meter. Since the circuit parameters correspond to (1) reflectance at the interface between layers, (2) phase retardation, and (3) attenuation with passage through the layer, the instrument can treat problems involving oblique as well as normal incidence, polarization, and absorption.

Heretofore unrecognized effects of high impact pressures developed by forging steel in closed dies have been studied. Mechanical properties are compared for conditions of varying restraint to metal flow. Forging tests have been devised to permit analysis of impact pressure with and without accompanying plastic flow as separate effects. High impact pressures developed in drop forging contribute substantially to the improvement in ductility and notched-bar toughness. This is demonstrated under conditions of negligible plastic flow.