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.     

Linear output feedback compensation of rank-one systems

A new method is presented for arbitrarily assigning the closed-loop poles of a linear multi-input/multi-output system using linear output feedback. The method employs a new notion of rank-one system representations and involves the use of state transformation matrices which preserve such representations while reducing the degree of the feedforward matrix     

Polynomial-complexity deadlock avoidance policies for sequentialresource allocation systems

The development of efficient deadlock avoidance policies (DAPs) for sequential resource allocation systems (RASs) is a problem of increasing interest in the scientific community, largely because of its relevance to the design of large-scale flexibly automated manufacturing systems. Much of the work on this problem existing in the literature is focused on the so-called single-unit RAS model, which is the simplest model in the considered class of RASs. Furthermore, due to a well-established result stating that, even for single-unit RASs, the computation of the maximally permissive DAP is intractable (NP-hard), many researchers (including our group) have focused on obtaining good suboptimal policies which are computationally tractable (scalable) and provably correct. In the first part of the paper, it is shown, however, that for a large subset (in fact, a majority) of single-unit RASs, the optimal DAP can be obtained in real-time with a computational cost which is a polynomial function of the system size (i.e., the number of resource types and the distinct route stages of the processes running through the system). The implications of this result for the entire class of single-unit RASs are also explored. With a result on the design of optimal DAPs for single-unit RASs, the second part of the paper concentrates on the development of scalable and provably correct DAPs for the more general case of conjunctive RASs     

Infinite-dimensional convex optimization in optimal and robustcontrol theory

Many engineering problems can be shown to be equivalent to solving semidefinite programs (SPs), i.e., convex optimization problems involving linear matrix inequalities (LMIs). Powerful computation tools are available for such problems in the finite-dimensional case. However, the problems arising in optimal and robust control theory are often infinite dimensional, and so adequate computation tools are not available. The key to tackling such problems with finite computation tools is to have a primal-dual formulation of the problem without duality gap. In this paper we study infinite-dimensional SPs and present a lifting technique to recast SPs as parameterized linear programs (LPs). This enables the wealth of theoretical tools available for infinite-dimensional LPs to be extended to infinite-dimensional SPs. In particular, we develop some new sufficient conditions for the lack of a duality gap for infinite-dimensional SPs and give an exact characterization of the primal and dual problems for these cases. Both primal and dual problems are formed as infinite-dimensional SP problems, with finite truncations to each giving upper and lower bounds, respectively, on the exact solution to the infinite-dimensional problem. Thus, these results can form the basis of practical computation schemes for infinite-dimensional problems, which require only finite-dimensional computation tools. To illustrate the power of these tools we apply the results to two previously unsolved optimization problems, namely minimizing the l₁ norm of a closed-loop system subject to bounds on the frequency response magnitude at a finite number of points and/or bounds on the H₂ norm     

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     

The effect of microreflections on decision feedback equalization

In coaxial cable modems and terrestrial broadcasting, the appearance and disappearance of microreflections cause a temporary drop in SNR at the equalizer output. We describe mathematically the effect of the appearance/disappearance of a microreflection on the performance of a previously trained fractionally spaced equalizer