Bcl-2-family proteins: the role of the BH3 domain in apoptosis

Bcl-2-related proteins have come to occupy a prominent position in the realm of programmed cell death. Members of this fast-growing family are highly related in one or more specific regions, commonly referred to as Bcl-2 homology (BH) domains. BH domains contribute at multiple levels to the function of these proteins in cell death and survival. Particularly intriguing is the emergence of the BH3 domain as a potent 'death domain' and of a growing subclass of pro-apoptotic proteins with no similarity to Bcl-2 beyond their BH3 homology. Here, the authors classify proteins of the Bcl-2 family on the basis of function and domain organization, discuss the importance of the BH3 domain in protein-protein interactions and in cell death and provide possible explanations for the perceived redundancy in the expression of this subclass of death promoters.     

Venezuelan equine encephalitis and Oropouche virus infections among Peruvian army troops in the Amazon region of Peru

An outbreak of a febrile illness characterized by headache, ocular pain, myalgia, and arthralgia occurred during June 1994 among Peruvian army troops in Northern Peru. On June 14-16, 1994, clinical data and blood samples were obtained from eight soldiers with a febrile illness, and from 26 others who had a history of febrile illness during the past three months. A follow-up blood sample was obtained 107 days later from four of the febrile and seven of the afebrile soldiers. Serum samples were tested for dengue (DEN), Oropouche (ORO), and Venezuelan equine encephalitis (VEE) IgM and IgG antibodies by an enzyme-linked immunosorbent assay (ELISA). Virus isolation was performed by inoculation of newborn mice and Vero cell cultures. Viral isolates were identified by immunofluorescence, ELISA, and nucleotide sequencing. A VEE virus infection was confirmed in three of the eight febrile soldiers, two by virus isolation, and one by serology. Antigenic analysis indicated that one of the virus isolates was similar to VEE subtype I, variety ID, viruses previously isolated in Colombia and Venezuela. Nucleotide sequence data showed that both viral isolates were identical to one another and closely related to VEE ID viruses previously isolated in Peru, Colombia, and Venezuela. Serologic results showed that two of 26 afebrile soldiers had IgM antibody to VEE and four had IgG antibody to VEE; two febrile soldiers had IgG antibody in their first serum samples. Oropouche-specific IgM antibody was detected in one of the eight febrile and five of the afebrile soldiers, and 18 of the 34 soldiers had low titers of ORO IgG antibody titers, which did not meet the diagnostic criteria for confirmed cases. All soldiers were negative for DEN IgM antibody, and 10 had flavivirus IgG antibody that reacted with DEN antigens. These data indicated that VEE ID virus was one of the causes of illness among Peruvians soldiers and that this was the first association of this VEE subtype with human disease in Peru.     

Intracellular pH in vascular smooth muscle: regulation by sodium-hydrogen exchange and multiple sodium dependent HCO3- mechanisms

OBJECTIVES: The aim was to determine the mechanisms, particularly bicarbonate dependent mechanisms, of intracellular pH (pHi) recovery from various acidoses in vascular smooth muscle and to explore the ATP dependency of the respective mechanisms. METHODS: Experiments were conducted in rat aortic smooth muscle cells grown in primary culture and synchronised in a non-growing state by serum deprivation. pHi was measured in cells loaded with the pH sensitive fluorescent dye, 2',7'-bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein (BCECF). Chloride efflux was studied by determination of the rate of efflux of 36Cl over 5 min. Cells were ATP depleted by substitution of glucose in the medium by 2-deoxyglucose. Acidoses were induced by CO2 influx and NH3 efflux techniques. RESULTS: In the absence of HCO3-, the 5-(N-ethyl-N-isopropyl) amiloride (EIPA) sensitive Na+/H+ exchange accounted for the recovery from intracellular acidosis. In the presence of HCO3- ions the response to respiratory acidosis (CO2 influx) was predominantly via activation of Na+/H+ exchange and an EIPA sensitive Na+ and HCO3- dependent mechanism. A 4-acetamido-4'-isothiocyanostilbene-2',2'-sulphonic acids (SITS) sensitive Na+ dependent Cl-/HCO3- mechanism which is also sensitive to EIPA makes a small contribution during severe intracellular acidosis. Under such conditions HCO3- dependent mechanisms contributed about 40% to the overall pHi regulating capacity of vascular smooth muscle cells. However, under conditions which deplete cellular ATP these pHi regulating mechanisms account for virtually all of theses cells' ability to regulate pHi. The inability of Na+/H+ exchange to participate in pHi recovery under these circumstances, reduces the ability of vascular smooth muscle cells to recover pHi by approximately 50-60%. Chloride efflux was approximately linear over 5 min and was increased by 36% in the presence of extracellular HCO3-. Efflux in the presence of HCO3- was inhibited similarly by both SITS and EIPA. CONCLUSIONS: At least three transporters contribute to recovery from acidosis in vascular smooth muscle: Na+/H+ exchange, an Na(+)-HCO3- cotransporter which is sensitive to EIPA, and an Na+ dependent HCO3-/Cl- exchange sensitive to both SITS and EIPA. The Na(+)-HCO3- cotransporter appears to be similar to that described in human vascular smooth muscle. When the Na+/H+ exchanger is attenuated by cellular ATP depletion, the alternative pathways, particularly the Na(+)-HCO3- cotransporter, ensure that substantial pHi regulatory capacity is maintained.     

The Design And Implementation of the MC68851 Paged Memory Management Unit

Pipelining, microsequencer start-up in parallel with bus arbitration, and a fully associative translation cache enhanced the performance of this 32-bit memory management device.     

A new label-based source routing for multi-ring networks

This paper presents a new source routing technique for ring and multi-ring networks, which uses short address labels. The main objectives for having this new method are that in case of one or more failures a frame will be guaranteed: (1) to be removed from the ring-termination property, and (2) to be copied at most once and only by its destinations-safety property. The scheme is based on dividing the label address space of each ring into subspaces, such that the address subspaces are physically disjoint. More specifically, each ring, in a multi-ring network, is divided into two or more parts such that adjacent address subspaces are disjoint. The route of each frame is described by a sequence of short address labels in the frame's header. The current route of a frame is determined by the first address label in its header, and it can be used for routing over at most one subspace of the ring     

Stereotactic ventrolateral thalamotomy: is ventriculography necessary?

In the computed tomography/magnetic resonance imaging (CT/MRI) era, the need for ventriculography to perform ventrolateral thalamotomy accurately has been debated. We retrospectively compared CT/MRI-derived coordinates for ventrolateral thalamotomy with the final lesion coordinates that were determined by ventriculography and microelectrode recording in 74 thalamotomies performed from 1984 to 1994. The median three-dimensional distance between the CT/MRI-derived loci and the ventriculography/microelectrode loci was 4.7 mm (range, 1.0-11.7 mm). The techniques correlated least along the Y axis (median, -0.3 mm; range, -8.2 to 8.0 mm). Correlation along the X axis was most consistent (median, 0.5 mm; range, -4.2 to 5.0 mm). Since 1990, the CT/MRI-derived coordinates have been generated by a multimodality correlative imaging technique (MCIT). A comparison of thalamotomies performed with and without the MCIT revealed a significant improvement in the correlation of CT/MRI- and ventriculography/microelectrode-derived coordinates when the MCIT was employed. The greatest improvement was noted along the Y axis where the median absolute difference was reduced from 4.0 to 1.8 mm (P = 0.0001). The result was a statistically significant reduction in the median three-dimensional distance from 5.6 to 3.7 mm (P = 0.0007). The authors conclude that thalamotomies can be safely and effectively performed without ventriculography when the MCIT is employed and supported by neurophysiological monitoring.     

Spacecraft Technology for Broadcasting Satellites--An Update

This paper surveys the special technologies for presently conceived direct broadcast satellite (DBS) projects using high RF power in the band 12.2-12.7 GHz, allocated to the broadcasting-satellite service in the western hemisphere. The technologies include launch vehicles, shapedbeam antennas, traveling wave tubes (TWT's), electronic power conditioners (EPC's) for TWT's, lightweight high-power solar arrays, heat-pipe radiators, and output multiplexers. It is concluded that the technology is available, and only detailed engineering development and testing is required for construction.     

Transient waves in inhomogeneous anisotropic elastic plates

Summary This paper considers the problem of transient wave propagation in elastic Cosserat plates that may be anisotropic, inhomogeneous, or of variable thickness. The methods of rays and of singular wave curves are combined to find and integrate the transport equations governing growth-decay behaviour of the extensional and bending wave modes to derive a common general formula involving the material parameters and wave geometry. For inhomogeneous isotropic plates of variable thickness, conditions for the uncoupling of the wave modes are obtained and some special cases are worked out in detail.