Distinction between artefactually shrunken and truly degenerated 'dark' neurons by in situ fixation with microwave irradiation

Dark, shrunken neurons frequently occur as artefacts in immersion fixed tissue. Perfusion fixation will prevent artefacts of this type. However, morphologically identical neurons have been described as truly degenerated cells in perfusion fixed brains in various pathological conditions. Since adequate perfusion is difficult to obtain in some pathological conditions, the question still remains whether the dark neurons found in some of these situations are true in vivo phenomena or artefacts caused by inadequate fixation. In the present study rat brains with cryogenic lesions were fixed in situ by microwave irradiation. With this method no artefactually changed dark neurons were observed in the normal parts of the brains. In the cryogenic lesions, however, a narrow rim of dark, shrunken neurons occurred adjacent to the normal cortex. This zone was identical to that observed in perfusion fixed tissue. Since inadequate fixation due to uneven perfusion of the damaged tissue is prevented with this method, we suggest that the neuronal changes represent true in vivo phenomena. Fixation with microwave irradiation can thus be used to differentiate between artefactually changed and truly degenerated dark neurons in various pathological conditions.     

Sterol and steryl ester regulation of phospholipase A2 from the mosquito parasiteLagenidium giganteum

Lagenidium giganteum, a facultative parasite of mosquito larvae, cannot synthesize sterols, and requires an exogenous source of these lipids in order to enter its reproductive cycle. This parasite grows vegetatively in the absence of sterols, but requires cholesterol or structurally related compounds to produce motile zoospores, which are the only stage capable of infecting mosquitoes. Sterols structurally related to cholesterol and some steryl esters inhibited the activity ofL. giganteum phospholipase A₂ (PLA₂), an enzyme that hydrolyzes fatty acids from thesn-2 position of glycerophospholipids. Sterols that induce reproduction inhibitedL. giganteum PLA₂ activity, while sterols and steroids that do not support sporulation had minimal effect. Most steryl esters had no effect on enzyme activity, but cholesteryl arachidonate (CA) was a potent inhibitor of parasite PLA₂. Not all enzymes partly purified using a DEAE-Sephacel column were affected by these lipids, demonstrating selective inhibition of specific enzymes. Potency was enhanced by up to several orders of magnitude if epoxy fatty acids were esterified to the cholesterol nucleus. The steryl ester pool was dynamic during morphogenesis, and the fatty acid composition of the steryl esters did not mimic total cell or membrane (glycerophospholipid) fatty acid composition asL. giganteum proceeded through its growth cycle. Synthesis of CA and monoepoxy CA by the parasite was confirmed using electrospray mass spectrometry and collision-induced dissociation. Steryl derivatives selectively inhibited PLA₂ enzymes from bovine pancreas, snake venom, and human cytoplasmic 85-kDa PLA₂.     

Influence of Glass Content on Damping Properties of Plasma-Sprayed Mixtures of Zirconia and Glass

The addition by vacuum infiltration of small quantities of a polymer has been found to increase significantly the ability of a plasma-sprayed coating to dissipate vibratory energy at temperatures in the glassy-rubbery transition range of the polymer. As vitreous enamels and glasses undergo a glassy transition, but at much higher temperatures, the addition of a small amount of glass to a ceramic has the potential of providing high damping at such temperatures. Mixtures of yttria-stabilized zirconia (YSZ) and a glass frit were plasma sprayed on specimens with bond coats. Measures of system response (resonant frequencies and loss factors) were extracted from frequency responses to excitations of cantilever beam specimens over a range of excitation amplitudes. Comparisons of values determined before and after coating were used to determine the damping properties of the coatings alone as functions of strain, at temperatures of special interest. Emphasis was given to identifying the lowest level of glass giving significantly more damping than that of the plasma-sprayed ceramic alone. Coatings with weight fractions of 5, 2, 1, ?, and 0% glass were tested. The inclusion of glass at all weight fractions considered was found to yield significant increases in both the stiffness and dissipation of the coatings.     

Early entry of plasma proteins into damaged neurons in brain infarcts. An immunohistochemical study on experimental animals

Entry of plasma proteins into damaged neurons has previously been demonstrated in various pathological conditions, but little is known about brain infarcts in this respect. In the present study, focal ischemic lesions were produced in rats by permanent occlusion of the middle cerebral artery (MCA). The animals were killed from 1 to 48 h postlesion. Leakage of plasma proteins across the blood-brain barrier into the infarcted area was visualized with immunostaining 2-3 h after the occlusion. This is earlier than in most previous reports. Entry of plasma proteins into ischemic neurons was seen 3 h after permanent occlusion of the MCA, while reliable changes were not seen until 12-24 h in sections stained with hematoxylin and eosin (H & E). Ischemic neurons stained for plasma proteins irrespective of their morphological appearance. Even cells that appeared normal with H & E staining were positively labeled. The technique may be used to diagnose very early ischemic lesions.     

The reliability issue of computer-aided breast cancer diagnosis.

This paper introduces a number of reliability criteria for computer-aided diagnostic systems for breast cancer. These criteria are then used to analyze some published neural network systems. It is also shown that the property of monotonicity for the data is rather natural in this medical domain, and it has the potential to significantly improve the reliability of breast cancer diagnosis while maintaining a general representation power. A central part of this paper is devoted to the representation/narrow vicinity hypothesis, upon which existing computer-aided diagnostic methods heavily rely. The paper also develops a framework for determining the validity of this hypothesis. The same framework can be used to construct a diagnostic procedure with improved reliability.     

Sterol and steryl ester regulation of phospholipase A2 from the mosquito parasite Lagenidium giganteum

Lagenidium giganteum, a facultative parasite of mosquito larvae, cannot synthesize sterols, and requires an exogenous source of these lipids in order to enter its reproductive cycle. This parasite grows vegetatively in the absence of sterols, but requires cholesterol or structurally related compounds to produce motile zoospores, which are the only stage capable of infecting mosquitoes. Sterols structurally related to cholesterol and some steryl esters inhibited the activity of L. giganteum phospholipase A2 (PLA2), an enzyme that hydrolyzes fatty acids from the sn-2 position of glycerophospholipids. Sterols that induce reproduction inhibited L. giganteum PLA2 activity, while sterols and steroids that do not support sporulation had minimal effect. Most steryl esters had no effect on enzyme activity, but cholesteryl arachidonate (CA) was a potent inhibitor of parasite PLA2. Not all enzymes partly purified using a DEAE-Sephacel column were affected by these lipids, demonstrating selective inhibition of specific enzymes. Potency was enhanced by up to several orders of magnitude if epoxy fatty acids were esterified to the cholesterol nucleus. The steryl ester pool was dynamic during morphogenesis, and the fatty acid composition of the steryl esters did not mimic total cell or membrane (glycerophospholipid) fatty acid composition as L. giganteum proceeded through its growth cycle. Synthesis of CA and monoepoxy CA by the parasite was confirmed using electrospray mass spectrometry and collision-induced dissociation. Steryl derivatives selectively inhibited PLA2 enzymes from bovine pancreas, snake venom, and human cytoplasmic 85-kDa PLA2.     

Comparison of GaN and 6H-SiC p-i-n photodetectors with excellentultraviolet sensitivity and selectivity

We fabricated GaN and 6H-SiC p-i-n photodetectors and compared their electrical and optical characteristics. The GaN diodes suffered from significant leakage current of 37 μA/mm² at -5 V, while the SiC diode leakage current was below the noise level at 10 pA/mm² at -20 V. The built-in potentials and the unintentional “i-layer” doping densities were obtained from capacitance-voltage (C-V) measurements. The SiC detectors exhibited a broad spectral response in contrast to the abrupt cutoff observed in the GaN detectors. The peak responsivities of the GaN and SiC photodetectors corresponded to internal quantum efficiencies of 57% at 3.42 eV and 82% at 4.49 eV, respectively. Furthermore, both detectors exhibited excellent visible rejection ratios which is needed for solar-blind applications. The response times at zero bias were 18 and 102 ns for the GaN and SiC detectors, respectively     

Interfacial effects during GaN growth on 6H-SiC

GaN growth on 6H-SiC was investigated for heterojunction device applications. Dopant diffusion and surface reactions were discovered at the GaN/SiC heterojunction. A systematic study was therefore conducted focusing on: 1) SiC substrate preparation, 2) SiC nitridation; the effect of flowing ammonia (NH₃) at 1050°C on the SiC, and 3) the conductivity type and carrier concentration of the SiC substrate. Atomic force microscopy measurements revealed that the SiC substrates became smoother after the nitridation process possibly due to nitrogen chemisorption and etching. Current-voltage and capacitance-voltage measurements on Cr-Schottky diodes made on SiC revealed evidence for an increased potential barrier in the nitrided samples that can be explained by an interfacial monolayer ofSiN_x. Furthermore, we compared GaN/SiC heterojunction n-n and n-p diodes made from direct and selective GaN growth. Capacitancevoltage measurements on GaN/SiC n-p heterojunctions indicate that the effective doping in the junction increases as the growth temperature increases. Secondary ion mass spectrometry measurements exposed a tail of Al in the GaN due to acceptor out-diffusion from the p-SiC.     

Effect of apolipoprotein E genotype on Alzheimer's disease neuropathology in a cohort of elderly Norwegians

A cohort of elderly Norwegians dying in nursing homes in the Oslo region have been genotyped for the Apolipoprotein E (ApoE) gene. Alzheimer's disease (AD) cortical neuropathology and clinical evidence of dementia were used to assign cases without evidence of other confounding neuropathology. Senile plaque (SP) and neurofibrillary tangle (NFT) densities in frontal, temporal and parietal cortex were then correlated with ApoE genotype to determine any relationship between ApoE genotype and AD pathology. Comparisons with ApoE epsilon 3, epsilon 4 and epsilon 2 allele dosage failed to show any significant effect on cortical SP densities in any cortical area. NFT densities were increased by epsilon 4 allele dosage in the frontal cortex but not in other cortical regions. A reduction was seen in cortical NFT densities with epsilon 2 allele, though again this was not consistently significant in any of the groups. The epsilon 3 allele failed to show any consistent effect on cortical NFT densities. Assessment by individual genotypes showed epsilon 2/3 < epsilon 2/4 < epsilon 3/3 < epsilon 3/4 < epsilon 4/4 which had highest cortical NFT densities in all areas. By genotype, SP densities were generally of the order epsilon 2/4 < epsilon 2/3 < epsilon 3/3 < epsilon 4/4 < epsilon 3/4 though in none of the groups was this significant. Duration of disease showed no consistent effect on neuropathological burden. ApoE genotype may have an effect on determining whether individuals suffer from AD and the age at onset of disease but may only have a minimal effect on pathology burden.     

Analysis of transit times and minority carrier mobility in n-p-n 4H-SiC bipolar junction transistors

An analysis of the transit times and minority carrier mobility in n-p-n 4H-SiC RF bipolar junction transistors is presented. These parameters were extracted from small signal RF measurements on 4H-SiC RF transistors with three different base thicknesses: 100, 140, and 200 nm. The study shows that the room temperature minority carrier electron mobility is 215 cm/sup 2//V/spl middot/s for a base Al doping of N/sub B/=4/spl times/10/sup 18/ cm/sup -3/. The analysis reveals that the collector charging time /spl tau//sub C/ and the parasitic charging time /spl tau//sub P/ from the capacitance between metal pads and the underlying collector region have a significant effect on the transistors RF performance. The calculated RF gain is in good agreement with the measured results.