Stabilised p53 facilitates aneuploid clonal divergence in colorectal cancer

Mutations in the p53 tumour suppressor gene are amongst the most frequent genetic abnormalities acquired in tumours. Recent studies in vitro suggest that mutant p53 destabilises the genome and facilitates development of aneuploidy. Here, in a study of 83 colorectal carcinomas, we demonstrate that alterations in p53 (detected by immunocytochemical stabilisation) precede and apparently facilitate divergence of aneuploid sub-clones. Aneuploidy in these tumours (but not those with normal p53) is predominantly in the subtetraploid range, suggesting that endoreduplication is important in its origin. This association with a specific phase of carcinoma progression is not shared by other commonly acquired genetic abnormalities in these tumours. These observations highlight the critical role of p53 in the regulation of abnormal chromosome replication and afford an explanation for the association between p53 abnormalities, aneuploidy and biological aggression in cancer.     

Theory and application of charge pumping for the characterizationof Si-SiO2 interface and near-interface oxide traps

A generalized charge pumping model has been developed which extends the use of charge pumping from a study of traps at the Si-SiO ₂ interface to a study of traps in the oxide. The analytical model, based on tunneling theory, allows the spatial distribution of near-interface oxide traps to be determined from variable frequency charge pumping data. Profiling of near-interface oxide traps in irradiated MOSFET's as well as SONOS nonvolatile memory devices is presented     

Selective interactions among the multiple connexin proteins expressed in the vertebrate lens: the second extracellular domain is a determinant of compatibility between connexins

Gap junctions are collections of intercellular channels composed of structural proteins called connexins (Cx). We have examined the functional interactions of the three rodent connexins present in the lens, Cx43, Cx46, and Cx50, by expressing them in paired Xenopus oocytes. Homotypic channels containing Cx43, Cx46, or Cx50 all developed high conductance. heterotypic channels composed of Cx46 paired with either Cx43 or Cx50 were also well coupled, whereas Cx50 did not form functional channels with Cx43. We also examined the functional response of homotypic and heterotypic channels to transjunctional voltage and cytoplasmic acidification. We show that all lens connexins exhibited sensitivity to cytoplasmic acidification as well as to voltage, and that voltage-dependent closure of heterotypic channels for a given connexin was dramatically influenced by its partner connexins in the adjacent cell. Based on the observation that Cx43 can discriminate between Cx46 and Cx50, we investigated the molecular determinants that specify compatibility by constructing chimeric connexins from portions of Cx46 and Cx50 and testing them for their ability to form channels with Cx43. When the second extracellular (E2) domain in Cx46 was replaced with the E2 of Cx50, the resulting chimera could no longer form heterotypic channels with Cx43. A reciprocal chimera, where the E2 of Cx46 was inserted into Cx50, acquired the ability to functionally interact with Cx43. Together, these results demonstrate that formation of intercellular channels is a selective process dependent on the identity of the connexins expressed in adjacent cells, and that the second extracellular domain is a determinant of heterotypic compatibility between connexins.     

Emergent Properties of the BT SDH Network

When planning an SDH network, explicit structure, such as rings or a network hierarchy, is often imposed to allow for easier network protection and management. Decisions on node connectivity are also heavily dependent on available transmission capacity and network geography, as well as the demands placed on the SDH transport layer. The strictly imposed structure therefore makes it unlikely for unplanned properties to appear but here we describe how the BT SDH network exhibits emergent power-law properties in a range of metrics. These properties are similar to those previously found in the Internet, but the Internet in contrast is not globally planned, has adaptive elements such as dynamic routing and peering agreements, lacks explicit imposed structure, and is less coupled to transmission topologies.This paper shows that even with a wide range of restrictions and controls the BT SDH network topology follows power-laws and we offer possible sources for them, concentrating on the possible effect of adjacent network layers. The existence of these properties has wide implications in network modelling, as well as network scaling, growth, and robustness analysis.     

Advances in ALCHEMI analysis

The ALCHEMI method for locating the sites of foreign atoms within crystals is known to be sensitive to the delocalized emission of X-rays. This can result in large errors in some cases through differences in delocalization for different excitations or by error amplification in the ratio method of analysis. An alternative approach to the analysis of ALCHEMI data, using multivariate statistical analysis, is extended to the case of multiple impurities. Initial results from zone-axis channelling experiments for a Yb-doped zirconolite (CaZrTi₂O₇) are shown to confirm the improved accuracy of this method, especially for axial orientations. Data were collected using a 400-keV analytical electron microscope fitted with an intrinsic Ge X-ray detector. The potential advantages for ALCHEMI analysis of Ge detectors are considered.     

Precision winding of fiber optic filament. II. Winding control

For pt.I see ibid., vol.39, no.3, p.258-67 (1992). The winding of fiber optic filament in the hoop, or precision, pattern is considered. Various automatic control options that have been designed and tested are described. The controllers are designed to regulate the fiber lag angle, which is the angle at which the feed filament approaches the take-up spool. Successful, flawless winding is directly related to accurate lag regulation. The contributions are distinguished by the fact that the automatic winding rate is 10 to 30 times greater than that achieved before by operator-assisted winding     

The digi-neocognitron: a digital neocognitron neural network modelfor VLSI

One of the most complicated ANN models, the neocognitron (NC), is adapted to an efficient all-digital implementation for VLSI. The new model, the digi-neocognitron (DNC), has the same pattern recognition performance as the NC. The DNC model is derived from the NC model by a combination of preprocessing approximation and the definition of new model functions, e.g., multiplication and division are eliminated by conversion of factors to powers of 2, requiring only shift operations. The NC model is reviewed, the DNC model is presented, a methodology to convert NC models to DNC models is discussed, and the performances of the two models are compared on a character recognition example. The DNC model has substantial advantages over the NC model for VLSI implementation. The area-delay product is improved by two to three orders of magnitude, and I/O and memory requirements are reduced by representation of weights with 3 bits or less and neuron outputs with 4 bits or 7 bits.