Characterization of EspC, a 110-kilodalton protein secreted by enteropathogenic Escherichia coli which is homologous to members of the immunoglobulin A protease-like family of secreted proteins

Enteropathogenic Escherichia coli (EPEC) secretes at least five proteins. Two of these proteins, EspA and EspB (previously called EaeB), activate signal transduction pathways in host epithelial cells. While the role of the other three proteins (39, 40, and 110 kDa) remains undetermined, secretion of all five proteins is under the control of perA, a known positive regulator of several EPEC virulence factors. On the basis of amino-terminal protein sequence data, we cloned and sequenced the gene which encodes the 110-kDa secreted protein and examined its possible role in EPEC signaling and interaction with epithelial cells. In accordance with the terminology used for espA and espB, we called this gene espC, for EPEC-secreted protein C. We found significant homology between the predicted EspC protein sequence and a family of immunoglobulin A (IgA) protease-like proteins which are widespread among pathogenic bacteria. Members of this protein family are found in avian pathogenic Escherichia coli (Tsh), Haemophilus influenzae (Hap), and Shigella flexneri (SepA). Although these proteins and EspC do not encode IgA protease activity, they have considerable homology with IgA protease from Neisseria gonorrhoeae and H. influenzae and appear to use a export system for secretion. We found that genes homologous to espC also exist in other pathogenic bacteria which cause attaching and effacing lesions, including Hafnia alvei biotype 19982, Citrobacter freundii biotype 4280, and rabbit diarrheagenic E. coli (RDEC-1). Although these strains secrete various proteins similar in molecular size to the proteins secreted by EPEC, we did not detect secretion of a 110-kDa protein by these strains. To examine the possible role of EspC in EPEC interactions with epithelial cells, we constructed a deletion mutant in espC by allelic exchange and characterized the mutant by standard tissue culture assays. We found that EspC is not necessary for mediating EPEC-induced signal transduction in HeLa epithelial cells and does not play a role in adherence or invasion of tissue culture cells.     

Protein translocation: delivering virulence into the host cell

A wide variety of plant and human bacterial pathogens use a specialized 'type III' protein secretion system to deliver virulence factors into host cells. Appendage-like surface structures have recently been identified on several bacterial pathogens and there are indications that these may be conduits for virulence factor delivery.     

Are we modelling the right thing? The impact of incorrect problem specification in credit scoring

Classification and regression models are widely used by mainstream credit granting institutions to assess the risk of customer default. In practice, the objectives used to derive model parameters and the business objectives used to assess models differ. Models parameters are determined by minimising some function or error or by maximising likelihood, but performance is assessed using global measures such as the GINI coefficient, or the misclassification rate at a specific point in the score distribution. This paper seeks to determine the impact on performance that results from having different objectives for model construction and model assessment. To do this a genetic algorithm (GA) is utilized to generate linear scoring models that directly optimise business measures of interest. The performance of the GA models is then compared to those constructed using logistic and linear regression. Empirical results show that all models perform similarly well, suggesting that modelling and business objectives are well aligned.     

Machine learning: A tool to support usability?

One problem facing designers of interactive systems is catering to the wide range of users who will use a particular application. Understanding the user is critical to designing a usable interface. There are a number of ways of addressing this problem, including improved design methodologies using ''intuitive'' interface styles, adaptive interfaces, and better training and user support materials. In this article, we argue that each of these solutions involves pattern recognition in one form or another and that machine learning can therefore aid designers of interactive systems in these areas. We report on experiments that demonstrate the potential of machine learning to user modeling that has application to two of these areas in particular: adaptive systems and design methodologies.     

The fibrous components of bovine ligamentum nuchae observed in the scanning electron microscope

A combination of enzymes have been employed to remove certain components of the adult bovine ligament sequentially. The course of this sequential enzymic dissection has been followed by scanning electron microscopy. We have been able to define the organization of elastic fibres embedded in matrix of collagen fibrils. The elastic fibres themselves appear to be made up from an amorphous core of elastin surrounded by a knitted sheath; the latter probably contains a mixture of collagen together with an unidentified protein component.     

Surface Mechanical Properties of the Spore Adhesive of the Green Alga Ulva

The mechanical properties of the adhesive produced by spores of the green, marine, fouling alga Ulva linza are reported. Atomic force microscopy studies were performed and nanoindentation data were analyzed using a model for an asymmetric indenter. Freshly secreted adhesive is characterized by multiple layers. We found that the modulus of the outer ∼600-nm thick layer was about 0.2 ± 0.1 MPa, whereas the modulus of the inner layer was about 3 ± 1 MPa. Older adhesive showed the formation of a “crust” of harder material with a yield strength of ∼20 MPa at a loading rate of 2.5 × 10^-6 N · s^-1. Mechanical properties under tension are also described, and extension profiles that showed either constant or nonlinear force changes with tip-sample separation were observed. Models for both kinds of behavior are described. The work of adhesion between poly-dimethylsiloxane (PDMS)-coated AFM tips and the adhesive was determined to be less than 1.5 mJ · m^-2.     

Influence of carl Jung and William james on the origin of Alcoholic Anonymous.

Alcoholics Anonymous is probably the most influential self-help organization in the world, with a current worldwide membership approaching 2 million. The origin of the organization has ties to Carl Gustav Jung and William James, 2 very prominent figures in the history of psychology. A brief history of the events that led to the formation of Alcoholics Anonymous is presented, with particular emphasis on the influence of Jung and James. An account of relevant life events of both Jung and James is provided, in addition to a summary of their views on alcoholism and its treatment. Speculation is offered on how the 2 men might view their unsolicited association with the organization. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Applying tribological principles to improve the performance of the Hoffmann external fixator's universal joint

As part of a continuing investigation of sources of slippage in the universal joints of external fixation devices, a study was conducted to determine if selected interfaces of the Hoffmann external fixator (rod/clip torsional, cheek/bowl and clip/cheek) could be improved by moving the point of contact between the wing-nut clamp and cheek closer to the centre of the wing-nut clamp. It was felt that the movement of the point of contact would reduce the magnitude of the frictional torque resisting the tightening of the wing-nut clamp. The point of contact was changed by the addition of a Belleville washer between the interface of the wing-nut clamp and the cheek. Increased slippage torques of approximately 100 per cent were noted in all interfaces at low values of tightening torque (6 and 8 N m) of the wing-nut clamp and improvements of not less than 50 per cent were obtained at higher tightening torques (10 and 12 N m) on the wing-nut clamp.     

Deposition of Inhaled Ultrafine Aerosols in Replicas of Nasal Airways of Infants

Experimentally measured deposition of ultrafine particles, ranging from 13–100 nm in diameter, in nasal airway replicas of ten infants aged 3–18 months is presented. The replicas included the face, nostrils, and nasal airways including the upper trachea. A differential mobility analyzer (DMA) and a condensation particle counter (CPC) were used to quantify the nasal deposition by comparing the number of polydisperse sodium chloride particles, generated by evaporation from a Collison atomizer, at the inlet and outlet of the replicas. Particles were individually classified in size by DMA and subsequently were counted one size bin at a time by CPC upstream and downstream of each replica. Since in vivo data is not available for infants to compare to, we validated our experimental procedure instead by comparing deposition in nasal airway replicas of six adults with in vivo measurements reported in literature. In the infant replicas, tidal inhalation was simulated at two physiologically compatible flow rates and the effect of flow rate on deposition was found to be small. Deposition obtained at constant flow rates is lower than with tidal breathing, indicating the importance of unsteadiness, in contrast to similar data in adults where unsteadiness is known to be unimportant. An empirical equation, containing geometrical features of the nasal airways in the form of related non-dimensional dynamical parameters (Reynolds, Schmidt, and Womersley numbers), was best fitted to the infant data. This equation may be useful for a priori prediction of nasal deposition and intersubject variability during exposure of infants to ultrafine aerosols.