The predominant contribution of oligopeptide transporter PepT1 to intestinal absorption of beta-lactam antibiotics in the rat small intestine

Although recent evidence suggests that certain beta-lactam antibiotics are absorbed via a specific transport mechanism, its nature is unclear. To confirm whether peptide transport in the rat can be largely ascribed to the intestinal oligopeptide transporter PepT1, the transporter has been functionally characterized and its significance in the intestinal absorption of beta-lactam antibiotics was evaluated. For evaluation of transport activity complementary RNA (cRNA) of rat PepT1 was synthesized in-vitro and expressed in Xenopus laevis oocytes. cRNA induced uptake of several beta-lactam antibiotics and the dipeptide [14C]glycylsarcosine; this was specifically inhibited by various dipeptides and tripeptides but not by their constituent amino acids or by tetra- or pentapeptides. The transport activity of PepT1 for beta-lactam antibiotics correlated well with their in-vivo intestinal transport and absorption. Furthermore, mutual inhibitory effects on uptake were observed between glyclsarcosine and beta-lactam antibiotics. Hybrid depletion of the functional expression of rat PepT1 in oocytes injected with rat intestinal epithelial total mRNA was studied using an antisense oligonucleotide corresponding to the 5'-coding region of PepT1. In oocytes injected with rat mRNA pre-hybridized with the antisense oligonucleotide against rat PepT1, the uptake of [14C]glycylsarcosine was almost completely abolished, whereas its uptake was not influenced by a sense oligonucleotide for the same region of PepT1. Similarly, the uptake of beta-lactam antibiotics was also reduced by the antisense oligonucleotide against rat PepT1. These results demonstrate that the intestinal proton-coupled oligopeptide transporter PepT1 plays a predominant role in the carrier-mediated intestinal absorption of beta-lactam antibiotics and native oligopeptides in the rat.     

Structuring communication software for quality-of-serviceguarantees

We propose architectural mechanisms for structuring host communication software to provide QoS guarantees. We present and evaluate a QoS sensitive communication subsystem architecture for end hosts that provides real time communication support for generic network hardware. This architecture provides services for managing communication resources for guaranteed QoS (real time) connections, such as admission control, traffic enforcement, buffer management, and CPU and link scheduling. The architecture design is based on three key goals: maintenance of QoS guarantees on a per connection basis, overload protection between established connections, and fairness in delivered performance to best effort traffic. Using this architecture we implement real time channels, a paradigm for real time communication services in packet switched networks. The proposed architecture features a process per channel model that associates a channel handler with each established channel. The model employed for handler execution is one of “cooperative” preemption, where an executing handler yields the CPU to a waiting higher priority handler at well defined preemption points. The architecture provides several configurable policies for protocol processing and overload protection. We present extensions to the admission control procedure for real time channels to account for cooperative preemption and overlap between protocol processing and link transmission at a sending host. We evaluate the implementation to demonstrate the efficacy with which the architecture maintains QoS guarantees on outgoing traffic while adhering to the stated design goals     

Selective employment of chemokine receptors as human immunodeficiency virus type 1 coreceptors determined by individual amino acids within the envelope V3 loop

The chemokine receptor CCR5 acts as an essential cofactor for cell entry by macrophage-tropic human immunodeficiency virus type 1 (HIV-1) strains, whereas CXCR4 acts as an essential cofactor for T-cell-line-adapted strains. We demonstrated that the specific amino acids in the V3 loop of the HIV-1 envelope protein that determine cellular tropism also regulate chemokine coreceptor preference for cell entry by the virus. Further, a strong correlation was found between HIV-1 strains classified as syncytium inducing in standard assays and those using CXCR4 as a coreceptor. These data support the hypothesis that progressive adaptation to additional coreceptors is a key molecular basis for HIV-1 phenotypic evolution in vivo.     

A process model for active brazing of ceramics: Part II Optimization of brazing conditions and joint properties

In the present investigation, the process model developed in Part I has been applied to evaluate the microstructure and strength evolution during active brazing of ceramics. As a starting point, reaction-layer growth is assumed to occur isothermally with no restrictions in the supply of reactive element. Different kinds of diagrams are then constructed to show how specific process variables (e.g. the heating and cooling period, the limiting layer thickness, and the diffusion mechanism) affect the growth kinetics. It is concluded that the key to improved joint properties lies in control of the reaction-layer thickness through optimization of the brazing conditions, and an illustration of this is given. This revised version was published online in November 2006 with corrections to the Cover Date.     

Effect of dynamic strain ageing on the tensile properties of a modified 9Cr–1Mo steel

Tensile testing of a modified 9Cr–1Mo steel in two microstructural conditions (710T– normalized at 1100°C, tempered at 710°C, and 550T – normalized at 1100°C tempered at 550°C) in the temperature range 25–450°C, under strain rates of 2.3×10-5–2.3×10-3s-1, exhibited serrated flow curves, with serrations appearing almost at the onset of deformation and disappearing before ultimate strengths were attained. The serrated flow curves (characteristics of dynamic strain ageing) were accompanied by increased ultimate strengths, loss of ductility and negative strain-rate sensitivity, relative to the ambient temperature properties. However, the increase in ultimate strength and the reduction in ductility were much larger for 710T specimens, as compared to 550T ones. In the dynamic strain ageing regime, the work-hardenability of 710T specimens increased rapidly while that of 550T specimens remained practically unaffected. Based on the microstructural consideration and the observed activation energy of 45 kJ mol-1, it is proposed that serrations are initiated by a nitrogen atmosphere formation on the waiting dislocations by a pipe diffusion mechanism, and they disappear by diffusion to the precipitate sinks during deformation. Because the fine alloy carbide precipitates in 550T specimens are more effective sinks than those of 710T ones, they can cause much faster depletion of the atmosphere, resulting in a much smaller effect of dynamic strain ageing on the tensile properties of 550T specimens.     

Chebyshev multilevel absorber design concept

Pyramidal- and wedge-absorber materials are used extensively in anechoic measurement chambers to attenuate stray signals. Typical absorber layouts result in large absorber walls in which the absorber tips and bases are roughly aligned in the same plane. Such a quasi-periodic configuration produces a strong coherent specular reflection which dominates the absorber scattered field. Based on the multisection impedance transformer concept, one can divide absorber elements into different levels (layers) so that this coherence can be destroyed to reduce the specular absorber scattering level. The synthesis of this desired behavior can be implemented by the Chebyshev transformer technique, which provides the largest bandwidth given a passband ripple threshold. The resulting reflected field is then the product of the original absorber response times the Chebyshev reduction factor, which is independent of polarization and absorber properties. Various measured results are used to show that more than a 10-dB improvement can be achieved at the critical low end of the frequency band using this approach. This improvement cannot be achieved using conventional design concepts unless the absorber size is doubled     

Genetic algorithms in engineering electromagnetics

This paper presents a tutorial and overview of genetic algorithms for electromagnetic optimization. Genetic-algorithm (GA) optimizers are robust, stochastic search methods modeled on the concepts of natural selection and evolution. The relationship between traditional optimization techniques and the GA is discussed. Step-by-step implementation aspects of the GA are detailed, through an example with the objective of providing useful guidelines for the potential user. Extensive use is made of sidebars and graphical presentation to facilitate understanding. The tutorial is followed by a discussion of several electromagnetic applications in which the GA has proven useful. The applications discussed include the design of lightweight, broadband microwave absorbers, the reduction of array sidelobes in thinned arrays, the design of shaped-beam antenna arrays, the extraction of natural resonance modes of radar targets from backscattered response data, and the design of broadband patch antennas. Genetic-algorithm optimization is shown to be suitable for optimizing a broad class of problems of interest to the electromagnetic community. A comprehensive list of key references, organized by application category, is also provided