DNA recognition by the EcoK methyltransferase. The influence of DNA methylation and the cofactor S-adenosyl-L-methionine

The methyltransferase of the EcoK type I restriction/modification system is trimeric, M2S1, where the S subunit determines the sequence specificity of the enzyme. The methyltransferase has a strong preference for hemimethylated substrate DNA and, therefore, we have investigated the effect of the methylation state of DNA on binding by the enzyme, together with the effects on binding of the cofactor S-adenosyl-L-methionine. Our results indicate that the methyltransferase has two non-interacting S-adenosyl-L-methionine binding sites, each with a dissociation constant of 3.60 (+/- 0.42) microM determined by equilibrium dialysis, or 2.21 (+/- 0.29) microM determined by the displacement of a fluorescent probe. Ultraviolet light-induced crosslinking showed that S-adenosyl-L-methionine binds strongly only to the modification (M) subunits. Changes in the sedimentation velocity of the methyltransferase imply a protein conformational change due to S-adenosyl-L-methionine binding. Gel retardation results show that the binding of S-adenosyl-L-methionine to the methyltransferase enhances binding to both specific and non-specific DNAs, but the enhancement is greater for the specific DNA. Differences in binding affinities contribute to the recognition of the specific nucleotide sequence AAC(N)6GTGC by the methyltransferase in preference to a non-specific sequence. In contrast, although the complexes of unmodified and hemimethylated DNAs with the methyltransferase have different mobilities in non-denaturing gels, there appears to be no contribution of binding affinity to the distinction between these two substrates. Therefore, the preference for a hemimethylated substrate must be due to a difference in catalysis.     

Survey of minor surgery in general practice in the west of Scotland

BACKGROUND: Noncutaneous psammomatous melanotic schwannoma has recently been reported as an unusual component of Carney's complex (myxomas, spotty pigmentation, and endocrinopathy). The most common locations for this lesion include peripheral nerve roots and the gastrointestinal tract. OBSERVATIONS: A cutaneous psammomatous melanotic schwannoma is reported in a patient with known Carney's complex. This neoplasm was pseudoencapsulated, with epithelioid to spindle-shaped cells and no nuclear atypia. Immunostaining was positive for S100 protein and vimentin, as well for HMB-45 antibody. Electron microscopy showed melanosomes in cytoplasmic processes of cells that were ensheathed by layers of reduplicated basal lamina. CONCLUSIONS: Location in the superficial soft tissues is extremely unusual for psammomatous melanotic schwannomas. Recognition of this new cutaneous marker as a part of this complex may aid in identification of individuals at risk for cardiac myxomas. It is also important that this lesion is not mistaken for melanoma, given the strong HMB-45 positivity.     

National and regional corporate spatial structure

Much is known about the macro-impacts of business activities on national and regional economies; however, comparatively little is known at the micro level about the impact spatial agglomeration of corporate wealth and performance has on urban systems. This paper reports on a collaborative research project between the Australian Housing and Urban Research Institute and Dun and Bradstreet, an international financial credit agency, to analyse the spatial implications of corporate structure in metropolitan regions. This paper analyses spatial patterns of medium to large businesses in three Australian State capital cities at the postcode level in order to assess the agglomeration of corporate capital, sales, and performance. The research indicates that ratio analysis can provide a useful insight into the competitiveness of metropolitan regions and the control corporate headquarters have over decision making and investment processes. The findings of this research are of special interest to capital markets, business and urban researchers in the Asia Pacific Region. Received: September 1997/Accepted: September 2001     

Frontolimbic Response to Negative Feedback in Clinical Depression.

Functional neuroimaging suggests that limbic regions of the medial frontal cortex may be abnormally active in individuals with depression. These regions, including the anterior cingulate cortex, are engaged in both action regulation, such as monitoring errors and conflict, and affect regulation, such as responding to pain. The authors examined whether clinically depressed subjects would show abnormal sensitivity of frontolimbic networks as they evaluated negative feedback. Depressed subjects and matched control subjects performed a video game in the laboratory as a 256-channel EEG was recorded. Speed of performance on each trial was graded with a feedback signal of A, C, or F. By 350 ms after the feedback signal, depressed subjects showed a larger medial frontal negativity for all feedback compared with control subjects with a particularly striking response to the F grade. This response was strongest for moderately depressed subjects and was attenuated for subjects who were more severely depressed. Localization analyses suggested that negative feedback engaged sources in the anterior cingulate and insular cortices. These results suggest that moderate depression may sensitize limbic networks to respond strongly to aversive events. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Egg Thiamine Status of Lake Ontario Salmonines 1995–2004 with Emphasis on Lake Trout

Alewives (Alosa pseudoharengus), the major prey fish for Lake Ontario, contain thiaminase. They are associated with development of a thiamine deficiency in salmonines which greatly increases the potential for developing an early mortality syndrome (EMS). To assess the possible effects of thiamine deficiency on salmonine reproduction we measured egg thiamine concentrations for five species of Lake Ontario salmonines. From this we estimated the proportion of families susceptible to EMS based on whether they were below the ED20, the egg thiamine concentration associated with 20% mortality due to EMS. The ED20s were 1.52, 2.63, and 2.99 nmol/g egg for Chinook salmon (Oncorhynchus tshawytscha), lake trout (Salvelinus namaycush), and coho salmon (Oncorhynchus kisutch), respectively. Based on the proportion of fish having egg thiamine concentrations falling below the ED20, the risk of developing EMS in Lake Ontario was highest for lake trout, followed by coho (O. kisutch), and Chinook salmon, with the least risk for rainbow trout (O. mykiss). For lake trout from western Lake Ontario, mean egg thiamine concentration showed significant annual variability during 1994 to 2003, when the proportion of lake trout at risk of developing EMS based on ED20 ranged between 77 and 100%. Variation in the annual mean egg thiamine concentration for western Lake Ontario lake trout was positively related (p < 0.001, r² = 0.94) with indices of annual adult alewife biomass. While suggesting the possible involvement of density-dependent changes in alewives, the changes are small relative to egg thiamine concentrations when alewife are not part of the diet and are of insufficient magnitude to allow for natural reproduction by lake trout.     

Superplasticity in a high strength powder aluminum

The superplastic properties of a rapidly solidified, high strength P/M Al alloy and the same alloy reinforced with SiC particulates (SiC _p ) have been studied. To prepare superplastic test materials, a matrix alloy powder of composition 7.2Zn-2.4Mg-2Cu-0.2Zr-0.12Cr-0.2Co (Kaiser PM-64) and the powder mixed with 10 to 20 vol pct SiC _p (~5 μm diameter) were thermomechanically processed to very fine equiaxed grain structures of ~6 μm and ~8 μm, respectively. Superplasticity in these materials was evaluated by characterizing (1) high temperature stability, (2) dynamic grain growth, (3) strain rate sensitivity, (4) flow stress behavior, (5) cavitation and cavitation control, and (6) total superplastic strain. It was observed that the PM-64 alloy could achieve a total elongation of over 800 pct, while the SiC_p reinforced alloy could attain an elongation greater than 500 pct before failure. Also, it was shown that with the use of hydrostatic pressure during superplastic flow, cavitation could be controlled. Observations were made of the effect SiC _p reinforcement particles had on the superplastic flow stress behavior. Interpretations are proposed to explain the role of particulates during superplastic straining.     

Pulse arithmetic in VLSI neural networks

This review explores the use of biological signaling methods to build silicon networks. Recent designs using a technique called `pulse stream', which employs fully analog, dynamic weight storage, are described. The pulse-stream concept is explained, and a comparison is made with conventional analog neural networks. An analog synapse based on the pulse-stream approach is presented. Chip details and simulation results are given     

Memory scanning: Are fixed and varied sets scanned concurrently or successively?

Subjects were timed as they decided whether individually presented probe letters were or were not contained in pairs of memorized sets of one, two, or four letters. One set was fixed in advance of a block of trials, while the other varied from trial to trial. In Experiments 1 and 2, subjects responded positively if the probe was in either set and negatively otherwise; in Experiment 3 they made different responses to fixed-set, varied-set, and negative probes. In all three experiments, reaction time (RT) to varied-set probes depended more on the size of the varied set than of the fixed set, whereas RT to fixed-set and negative probes depended more on the size of the fixed set. These results were generally consistent with the hypothesis that scanning of the two sets was at least to some extent concurrent rather than successive, with the fixed set scanned more slowly than the varied set. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

THE QUEST FOR WORLD CLASS IT CAPABILITY IT Is Key to Achieving Quality Goals

In today's competitive world, many organizations are pursuing total quality improvement programs, and as a result of these initiatives, are seeking to define world class capabilities. The organizations with these aspirations are trying to improve product and service quality, business process quality, or delivered quality, and are becoming aware that information technology is playing a more substantial role in realizing these quality goals.     

Call admission control schemes under generalized processor sharing scheduling

Provision of Quality‐of‐Service (QoS) guarantees is an important and challenging issue in the design of integrated‐services packet networks. Call admission control is an integral part of the challenge and is closely related to other aspects of networks such as service models, scheduling disciplines, traffic characterization and QoS specification. In this paper we provide a theoretical framework within which call admission control schemes with multiple statistical QoS guarantees can be constructed for the Generalized Processor Sharing (GPS) scheduling discipline. Using this framework, we present several admission control schemes for both session‐based and class‐based service models. The theoretical framework is based on recent results in the statistical analysis of the GPS scheduling discipline and the theory of effective bandwidths. Both optimal schemes and suboptimal schemes requiring less computational effort are studied under these service models. The QoS metric considered is loss probability. This revised version was published online in June 2006 with corrections to the Cover Date.