Src can regulate carboxy terminal interactions with AFAP-110, which influence self-association, cell localization and actin filament integrity

The SH2 and SH3 binding partner AFAP-110 is a tyrosine phosphorylated substrate of Src. AFAP-110 has been hypothesized to link Src to actin filaments, which may contribute to the effects of Src upon actin filament integrity. However, it has been unclear what effect activated Src (Src527F) has upon AFAP-110 structure or function and whether AFAP-110 plays a role in actin filament integrity. We report here that the carboxy terminal 127 amino acids of AFAP-110 are comprised of an alpha-helical region that contains a leucine zipper motif. This indicated the potential of AFAP-110 to self-associate. Expression of the carboxy terminus as a fusion protein (GST-cterm) will permit affinity absorption of cellular AFAP-110. The integrity of the alpha-helical leucine zipper motif in GST-cterm is required for affinity absorption, but binding is not due to a classical leucine zipper interaction. Co-expression of Src527F, unlike cSrc, will abrogate affinity absorption of AFAP-110 with GST-cterm. These data indicate that Src527F has affected a change in the carboxy terminal structure that renders AFAP-110 unavailable for affinity absorption. Superose chromatography demonstrate that AFAP-110 will fractionate as a monomer or multimer, indicating AFAP-110 can be detected in a self-associated form in cell lysates. Co-expression of Src527F resulted in AFAP-110 fractionating with a molecular weight that predicts only a multimeric population. Deletional mutagenesis also indicate a biological role for the carboxy terminus in cellular localization and actin filament integrity. Deletion of the entire carboxy terminal alpha-helix (84 amino acids) will not permit AFAP-110 to efficiently colocalize with actin filaments or the cell membrane. Deletion of only the leucine zipper region of the carboxy terminal alpha-helix (44 amino acids) from AFAP-110 (AFAPAdeltazip) demonstrate that both AFAPdeltalzip and actin filaments are repositioned into rosette-like structures, similar to the effects of Src527F, while co-expression of AFAP-110 with cSrc will not affect actin filaments. These data indicate that AFAP-110 can play an important role in modulating actin filament integrity through carboxy terminal interactions that can be affected by Src527F.     

Posthyperventilation apnea associated with severe hypoxemia

We studied a 14-year-old girl who suffered fractures of her mandible and tegmen following a fall from a balance beam. Thirteen days after hospitalization, she developed severe, protracted, recurrent episodes of hyperventilation; subsequently, she suffered posthyperventilation apnea, which at times was prolonged and association with severe hypoxemia with an arterial oxygen pressure as low as 25 mm Hg. The patient was treated with added dead space and chlorpromazine hydrochloride (Thorazine). Postulated mechanisms for her disorder are discussed. The importance of close clinical and laboratory observation in similar cases is stressed.     

An indexed atlas of digital mammograms for computer-aided diagnosis of breast cancer

Computer-aided diagnosis (cad) systems are being developed to assist radiologists in the interpretation of ambiguous mammographic features corresponding to possible signs of early breast cancer. Databases of digital mammograms are needed for testing such systems; we present an overview of a few such databases. Most databases are limited to single-exam sets of two or four mammograms on which the diagnosis was made, some ground-truth information related to the position of diagnostically significant mammographic features, and the diagnosis. We propose the design of a comprehensive, indexed atlas of digital mammograms. The design of an appropriate indexing scheme facilitates the implementation of content-based retrieval techniques needed for efficient access to and retrieval of relevant cases from the atlas. We also propose the use of mobile software agents for facilitating remote consultation of the atlas. Mobile agents can move between data sources such as the atlas and hospital repositories, perform computational tasks at each site, and return only relevant data to the user. These features reduce the computational requirements of the local computer system, bandwidth requirements, and overall network traffic. Proposed applications of the atlas include research, remote consultation, teaching, evaluation ofcad systems, and self-evaluation by radiologists.     

Estimation of Electric Transformer Service Life from Oil Degradation Kinetics

Petroleum-based transformer oil performs the dual roles of insulator and electrolyte depending on charges in the oil. The availability of charges for conduction influences the level of voltage breakdown in the mineral oil and depends on the intensity of physicochemical processes such as redox action, hydrolysis, photodegradation, sludge/particle development, and gas formation arising from thermal, mechanical, chemical, and electrical stresses in the oil. Previous investigators have focused mostly on single oil aging indicators to build models for estimation of the aging rates of transformer oils, within a time frame that is too short relative to the operational service life of transformers. In this research, the interdependence of oil voltage breakdown and changes in oil physicochemical characteristics was investigated experimentally using T24 and T14 oils. Tests were performed with a DTS-100D oil tester for voltage breakdown and a HKV 4000 series high kinematic viscosity bath. The calculated activation energies are 26.2?KJm?3 for T24 and 25.4?KJm?3 for T24 transformer oils, respectively. Neglecting catastrophic failure from environmental hazards, the estimated service lives of T14 and T24 transformers that are herein analyzed are 40 and 43 years, respectively. Their degradation constants were experimentally determined to be 7.38×10?12 and 6.98×10?12?L?1?S?1, respectively.     

Descent via isogeny on elliptic curves with large rational torsion subgroups

We outline PARI programs which assist with various algorithms related to descent via isogeny on elliptic curves. We describe, in this context, variations of standard inequalities which aid the computation of members of the Tate–Shafarevich group. We apply these techniques to several examples: in one case we use descent via 9-isogeny to determine the rank of an elliptic curve; in another case we find nontrivial members of the 9-part of the Tate–Shafarevich group, and in a further case, nontrivial members of the 13-part of the Tate–Shafarevich group.     

The utility of rapid application development in large-scale, complex projects

This paper describes an investigation into the utility of an agile development approach known as rapid application development (RAD) within a large-scale development project conducted within the public sector in the UK. Features of RAD as an 'agile' information systems development method (ISDM) are discussed and previous research identifying properties of development environments most conducive to its application are described. A case study is then presented based upon a long-term qualitative investigation of the 'unbundling' of a commercial RAD-like ISDM. The evidence from this case leads us to question established wisdom in relation to appropriate adoption and application of agile development within large-scale and complex development environments.