Three distinct D-amino acid substitutions confer potent antiangiogenic activity on an inactive peptide derived from a thrombospondin-1 type 1 repeat

Mal II, a 19-residue peptide derived from the second type 1 properdin-like repeat of the antiangiogenic protein thrombospondin-1 (TSP-1), was inactive in angiogenesis assays. Yet the substitution of any one of three L-amino acids by their D-enantiomers conferred on this peptide a potent antiangiogenic activity approaching that of the intact 450-kDa TSP-1. Substituted peptides inhibited the migration of capillary endothelial cells with an ED50 of 8.5 nM for the D-Ile-15 substitution, 10 nM for the D-Ser-4 substitution, and 0.75 nM for the D-Ser-5 substitution. A peptide with D-Ile at position 15 could be shortened to its last seven amino acids with little loss in activity. Like whole TSP-1, the Mal II D-Ile derivative inhibited a broad range of angiogenic inducers, was selective for endothelial cells, and required CD36 receptor binding for activity. A variety of end modifications further improved peptide potency. An ethylamide-capped heptapeptide was also active systemically in that when injected i.p. it rendered mice unable to mount a corneal angiogenic response, suggesting the potential usefulness of such peptides as antiangiogenic therapeutics.     

Long-term inhalable particles and other air pollutants related to mortality in nonsmokers

Long-term ambient concentrations of inhalable particles less than 10 microm in diameter (PM10) (1973- 1992) and other air pollutants-total suspended sulfates, sulfur dioxide, ozone (O3), and nitrogen dioxide-were related to 1977-1992 mortality in a cohort of 6,338 nonsmoking California Seventh-day Adventists. In both sexes, PM10 showed a strong association with mortality for any mention of nonmalignant respiratory disease on the death certificate, adjusting for a wide range of potentially confounding factors, including occupational and indoor sources of air pollutants. The adjusted relative risk (RR) for this cause of death as associated with an interquartile range (IQR) difference of 43 d/yr when PM10 exceeded 100 microg/m3 was 1.18 (95% confidence interval [CI]: 1.02, 1.36). In males, PM10 showed a strong association with lung cancer deaths-RR for an IQR was 2.38 (95% CI: 1.42, 3.97). Ozone showed an even stronger association with lung cancer mortality for males with an RR of 4.19 (95% CI: 1.81, 9.69) for the IQR difference of 551 h/yr when O3 exceeded 100 parts per billion. Sulfur dioxide showed strong associations with lung cancer mortality for both sexes. Other pollutants showed weak or no association with mortality.     

Axonal damage revealed by accumulation of beta-APP in HIV-positive individuals without AIDS

The presence of neuropsychological disturbances in HIV-positive, pre-symptomatic individuals is a controversial issue. Neuroimaging studies have not shown brain atrophy or hyperintensity in the white matter, whereas proton magnetic resonance spectroscopy has revealed some abnormality of cerebral biochemistry. Using an antibody to beta-amyloid precursor protein (beta-APP), we previously demonstrated frequent and widespread axonal changes in the brains of AIDS patients. In this study, we extended the use of beta-APP to asymptomatic patients in order to establish a possible morphological correlation with neuropsychological disorders. Brain samples from 29 patients were examined. Results showed bundles of beta-APP-positive axons in 8/29 cases (27%). The changes, seen in both superficial and deep white matter, were either focal or diffuse, could not be visualized by silver or ubiquitin stains, and did not coexist with any change in distribution or morphology of astrocytes and microglial cells. We conclude that in HIV-positive asymptomatic individuals, axonal changes: (a) may be related to the state of immune activation with consequent presence of toxic substances, including cytokines, observed in these patients; (b) may represent mild changes that could undergo repair, unless other pathological events, such as the supervening of the AIDS stage and the specific encephalitis, make them permanent.     

Ethological data mining: an automata-based approach to extract behavioral units and rules

We propose an efficient automata-based approach to extract behavioral units and rules from continuous sequential data of animal behavior. By introducing novel extensions, we integrate two elemental methods—the N-gram model and Angluin’s machine learning algorithm into an ethological data mining framework. This allows us to obtain the minimized automaton-representation of behavioral rules that accept (or generate) the smallest set of possible behavioral patterns from sequential data of animal behavior. With this method, we demonstrate how the ethological data mining works using real birdsong data; we use the Bengalese finch song and perform experimental evaluations of this method using artificial birdsong data generated by a computer program. These results suggest that our ethological data mining works effectively even for noisy behavioral data by appropriately setting the parameters that we introduce. In addition, we demonstrate a case study using the Bengalese finch song, showing that our method successfully grasps the core structure of the singing behavior such as loops and branches. Yasuki Kakishita and Kazutoshi Sasahara have contributed equally to this work.     

Characterization of interface stress at InGaPAs/GaAs by cr-related luminescence line in GaAs

The interface stress at InGaPAs/GaAs heterostructure has been investigated using the energy shift and splitting of the Cr-related zero-phonon photoluminescence line at 0.839 eV observed in GaAs. It has been found that the GaAs substrate suffers both compressive uniaxial stress and tensile hydrostatic pressure at the InGaPAs/GaAs heterointerface. These shifts and splittings of the 0.839 eV line have been systematically examined as a function of the lattice mismatch between InGaPAs and GaAs, and the thicknesses of the epitaxial-layer and substrate. The amount of the interface stress existing at InGaPAs/GaAs heterostructure has been estimated, based on uniaxial stress data for GaAs: Cr wafers.     

Impurity Effects on the Slippage of Nonsuperfluid Helium Films

We measured the mechanical response of ⁴ He films adsorbed on an oscillating substrate with a small amount of N₂ molecules using an ultrasonic technique. Compared with the substrate with no N₂ molecules, it was found that nonsuperfluid ⁴ He films undergo slipping at lower temperature. This means that the frictional force acting on these films is increased by N₂ molecules adsorbed on the substrate.