Proadrenomedullin N-terminal 20 peptide: minimal active region to regulate nicotinic receptors

Proadrenomedullin N-terminal 20 peptide (PAMP-[1-20]; ARLDVASEFRKKWNKWALSR-amide) is a potent hypotensive and catecholamine release-inhibitory peptide released from chromaffin cells. We studied the mechanism of PAMP action and how its function is linked to structure. We tested human PAMP-[1-20] on catecholamine secretion in PC12 pheochromocytoma cells and found it to be a potent, dose-dependent (IC50 approximately 350 nmol/L) secretory inhibitor. Inhibition was specific for nicotinic cholinergic stimulation since PAMP-[1-20] failed to inhibit release by agents that bypass the nicotinic receptor. Nicotinic cationic (22Na+,45Ca2+) signal transduction was disrupted by this peptide, and potencies for inhibition of 22Na+ uptake and catecholamine secretion were comparable. Even high-dose nicotine failed to overcome the inhibition, suggesting noncompetitive nicotinic antagonism. N- and C-terminal PAMP truncation peptides indicated a role for the C-terminal amide and refined the minimal active region to the C-terminal 8 amino acids (WNKWALSR-amide), a region likely to be alpha-helical. PAMP also blocked (EC50 approximately 270 nmol/L) nicotinic cholinergic agonist desensitization of catecholamine release, as well as desensitization of nicotinic signal transduction (22Na+ uptake). Thus, PAMP may exert both inhibitory and facilitatory effects on nicotinic signaling, depending on the prior state of nicotinic stimulation. PAMP may therefore contribute to a novel, autocrine, homeostatic (negative-feedback) mechanism controlling catecholamine release.     

Carbon fibre composites based on polyimide/silica ceramers: aspects of structure-properties relationship

Polyimide/silica ceramers, based on the products of the hydrolysis of tetraethoxysilane (TEOS) and a commercial poly(amic acid) solution, were used to fabricate unidirectional carbon fibre composites, which were subsequently evaluated with respect to thermal and mechanical properties. There is evidence to suggest that the silica component of these ceramers is present as dispersed discrete particles at low silica concentration (i.e. 7 wt%) and as fine interconnected domains trapped within the polyimide matrix at higher silica content (i.e. 14 wt%). The dimensions of the silica domains were in the region of 7–20 nm. Carbon fibre composites produced from ceramer solutions (CF/ceramers) were found to exhibit lower thermal expansion and a greater retention of flexural and interlaminar shear properties at elevated temperature than the corresponding polyimide-matrix composites (CF/polyimide). The properties of CF/ceramers were generally better for systems containing the higher amount of silica and were improved further by lowering the pH value of the precursor ceramer solution. This is believed to have resulted from the enhanced fluidity of the ceramer gel within the pre-impregnated fibres, giving rise to a higher packing density of the fibres and a more homogeneous distribution of fibres. CF/ceramers were also found to exhibit a better thermal oxidative stability at 350°C than the corresponding CF/polyimide, although a substantial amount of porosity developed in the case of ceramers with the higher silica content.     

Comparison of EEG and ECoG for detecting cerebrocortical activity during slaughter of calves

Parallel electrocorticograms (ECoG) and electroencephalograms (EEG) were recorded during stun-recovery and stun-slaughter of eight calves 4-6 weeks old. Epochs of 8·2 s duration, derived from the ECoG and EEG signals pre-stun, during recovery and during exsanguination, were compared for differences in power content and frequency distribution using Fast Fourier Transform analysis. ECoG signals recorded during the quiescent phase post-stun had a markedly lower power content compared with pre-stun, whereas the EEG signal showed no such reduction in power content. During exsanguination, the mean rate of decline in the ECoG power content was 0·025 log units/s, three times faster than the mean rate of decline of the EEG at 0·008 log units/s. The duration of the electroplectic fit post-stun was detected equally well by the two techniques. The differences between EEG and ECoG traces in this study are thought to arise from differences in the signal-noise ratio of the two techniques and by artefacts in the EEG signal, caused by microscopic movement between EEG electrodes and the surrounding tissue. The slower rate of decline in the power content of the EEG during slaughter means that the time to onset of isoelectric cortical electrical activity will be longer if determined by EEG measurements than by ECoG recording.     

Favorable influence of ssDNA-functionalized SWCNT on the navigation pattern of C. elegans

Microsystem Technologies - Single-Walled Carbon Nanotubes (SWCNTs) are widely used as potential carriers in drug delivery systems. The objective of this work was to observe the effects of pristine,...     

Stress intensification in a viscoelastic plate on a Winkler foundation and under a large thermal gradient

Summary A thin viscoelastic plate on a Winkler foundation is subjected to vertical loads. Its response is strongly affected by the presence of a vertical temperature gradient which causes a very pronounced change in the viscosity coefficient through the plate thickness. While eventually the entire load will be transferred to the underlying foundation, during the time dependent deformation process it is possible that some bending stresses will actually increase rather than decrease as would normally be expected with this relaxation process. The rationale for this behavior lies in the competition between the two physical processes of a) the load transfer to the foundation causing an overall relief of the bending moment and thus the bending stress and b) the rapid relaxation of bending stress in the hot lower portion of the plate causing the colder upper portion to carry a larger share of that portion of the bending moment still carried by the plate. The simple case of a clamped circular plate of a metallic material and subjected to a uniform load is used to illustrate this behavior. Certain simplifications are made to allow an analytic solution; these simplifications do not alter the basic behavior. In the present case, these simplifications are the neglect of Poisson's ratio effects and the assumption of a linear equivalent viscoelastic material behavior. This latter point is discussed in an appendix. Numerical solutions containing more general behavior indicate that the basic behavior is still well modeled even with these assumptions.With 4 Figures     

Active memory chips: A brief survey and case study

Conventional random access memories are capable only of writing data into and reading data from the storage location corresponding to a given address. The availability of VLSI circuits containing hundreds of thousands of switching devices, however, has recently made practical the implementation of active memory chips capable of performing a range of complex operations on their stored data. Such designs are characterized by the extensive intermingling of processing and memory resources within a single chip to achieve the rapid and cost-effective parallel execution of operations relevant to such tasks as image processing, computer graphics, artificial intelligence, and database management.This paper presents a brief survey of a number of active memory chips that have been implemented or proposed, along with a more detailed examination of a particular active memory circuit, the NON-VON 3 primary processing subsystem chip.This research was supported in part by the Defense Advanced Research Projects Agency, under contract N00039-84-C-0165, in part by the New York Center for Advanced Technology in Computers and Information Systems at Columbia University, and in part by an IBM Faculty Development Award.     

Evaluation of tempering induced changes in the hardness profile of case-carburised EN36 steel using magnetic Barkhausen noise analysis

The effect of tempering on the magnetic Barkhausen noise (MBN) signal profile was studied in case-carburised EN36 steel using a range of magnetic excitation frequencies and a number of frequency ranges for analysis of the MBN signal. The MBN level generally increases with tempering due to coarsening of the microstructure. With higher values of excitation frequency, f_EX, the MBN profile exhibits a single peak, but with low values of f_EX, double peaks are observed. The MBN peak obtained with higher f_EX was found to correlate well with hardness changes in a region, down to 100 μm below the surface. The analysis of the MBN signal produced with low f_EX, in narrow frequency ranges selected by software frequency filtering, showed variations in the extent of changes in the relative height of the two MBN peaks in the profile. After taking into account the skin depth-frequency relation for the MBN signal, variations in the values of the two MBN peaks in different analysing frequency ranges were found to correlate well with hardness variations at different depths down to 425 μm below the surface. An empirical relationship has been established between the hardness-depth profile and the MBN measurements.     

Enhanced oil recovery using carboxylate surfactant systems

Oil displacement tests in water wet Berea sandstone cores containing residual crude oil flooded with water have shown that high tertiary oil recoveries can be obtained using the sodium salts of readily available carboxylic acids. Using a 10% pore volume surfactant slug containing 3.0% sodium isostearate and 3.0% isopentyl alcohol followed by a polyacrylamide mobility buffer resulted in a 92% tertiary oil recovery, which compares well with recoveries using petroleum solfonates. Oil recoveries were highly dependent on pH and added base. Aliphatic C18 carboxylates gave higher recoveries at lower pH using sodium bicarbonate as the added base (pH 8.5) rather than sodium hydroxide, sodium carbonate or sodium orthosilicate (pH 11–13). In contrast, aromatic carboxylates e.g., sodium p-(1-pentylnonyl)benzoate, gave higher recoveries at higher pH using sodium carbonate rather than sodium bicarbonate. Carboxylates with branched alkyl groups, e.g., isostearate, gave higher tertiary oil recoveries than unbranched carboxylates, e.g., oleate or stearate. Low cost tall oils and tall-oil fatty acids, when neutralized with base, gave oil recoveries of 60–80%. Carboxylates were found to give good oil recoveries even when significant amounts of calcium ion were present.     

Property-composition relationships for diesel and kerosene fuels

A range of 18 diesel fuels and 21 kerosene fuels from mainly Australian petroleum and synthetic fuel sources, including coal, shale and peat, was investigated. Compositional details were defined as the weight per cent abundances of n-alkanes, branched plus cyclic saturates, single-ring aromatics, doublering aromatics and polynuclear aromatics, using both h.p.l.c. and ¹³C n.m.r. techniques. Relationships between fuel composition and a range of fuel properties were sought. Simple linear relationships between property values and compositional data were used. Explicit correlative expressions were derived using multiple linear regression analysis, with the coefficient of multiple determination, R², indicating the quality of the fit between observed and calculated property values. In most cases good correlations were achieved. For diesels the properties investigated, with R² values in parentheses, were: inverse specific gravity (0.99); ¹³C n.m.r. aromaticity (0.99); ¹H n.m.r. aromaticity (0.88); cetane index (0.97); aniline point (0.96); diesel index (0.98); and FIA-measured aromatics content (0.77). For kerosenes the properties, with R² values in parentheses, were: ¹³C n.m.r. aromaticity (0.98); ¹H n.m.r. aromaticity (0.97); smoke point (0.88); and FIA-measured aromatics content (0.94). The results are shown to be of value in assessing the potential and limitations of hydrotreating as a process for upgrading synfuels.