Influence of alpha-cyclodextrin and hydroxyalkylated beta-cyclodextrin derivatives on the in vitro corneal uptake and permeation of aqueous pilocarpine-HCl solutions

Interactions in aqueous solution between pilocarpine hydrochloride (P-HCl), a rather hydrophilic drug with good water solubility, and various cyclodextrins (CDs) were described recently. To assess the influence of CDs on the diffusion behavior of pilocarpine, in vitro studies were performed using porcine or bovine corneas as diffusion barriers. The affinity of P-HCl for porcine cornea in the presence of alpha-cyclodextrin (alpha-CD) and (hydroxyethyl)-beta-cyclodextrin (HE-beta-CD) was determined by drug uptake experiments. Additionally, in vitro permeation experiments through bovine corneas were conducted with a modified diffusion device optimized for corneal perfusion studies. The results obtained from the corneal uptake studies indicate that the addition of alpha-CD led to increased tissue drug levels. The increase in permeability of pilocarpine in the presence of alpha-CD was approximately 10-fold (log Papp = -4.87 +/- 0.03) in comparison with plain P-HCl solution (log Papp = -5.89 +/- 0.06). Permeation studies with corneas pretreated with alpha-CD solution revealed enhanced corneal permeability of pilocarpine due to alpha-CD induced membrane effects. The hydroxyalkylated beta-CD derivatives HE-beta-CD (log Papp = -6.27 +/- 0.09) and (hydroxypropyl)-beta-cyclodextrin (HP-beta-CD; log Papp = -6.40 +/- 0.03), however, seemed to cause slightly decreased permeation rates, supporting the concept of an interaction between pilocarpine and the hydroxyalkylated-beta-CD derivatives. Considering physiological compatibility, the addition of CDs seems to be an effective tool to modify and optimize the ocular availability of pilocarpine.     

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     

The held out wings (how) Drosophila gene encodes a putative RNA-binding protein involved in the control of muscular and cardiac activity

In an attempt to identify genes that are involved in Drosophila embryonic cardiac development, we have cloned and characterized a gene whose function is required late in embryogenesis to control heart rate and muscular activity. This gene has been named held out wings (how) because hypomorphic mutant alleles produce adult animals that have lost their ability to fly and that keep their wings horizontal at a 90 degree angle from the body axis. In contrast to the late phenotype observed in null mutants, the How protein is expressed early in the invaginating mesoderm and this expression is apparently under the control of twist. When the different mesodermal lineages segregate, the expression of How becomes restricted to the myogenic lineage, including the cardioblasts and probably all the myoblasts. Antibodies directed against the protein demonstrate that How is localized to the nucleus. how encodes a protein containing one KH-domain which has been implicated in binding RNA. how is highly related to the mouse quaking gene which plays a role at least in myelination and that could serve to link a signal transduction pathway to the control of mRNA metabolism. The properties of the how gene described herein suggest that this gene participates in the control of expression of as yet unidentified target mRNAs coding for proteins essential to cardiac and muscular activity.     

Reading in Arabic orthography: the effect of vowels and context on reading accuracy of poor and skilled native Arabic readers in reading paragraphs, sentences, and isolated words

This study investigated the effect of vowels and context on the reading accuracy of poor and skilled native Arabic readers in reading paragraphs, sentences, and words. Central to this study is the belief that reading theory today should consider additional variables, especially when explaining the reading process in Arabic orthography among poor and normal/skilled readers. This orthography has not been studied. Reading theory today is the sum of conclusions from studies conducted in Latin orthography. The subjects were 77 native Arabic speakers, 34 of them poor readers and 44 normal/skilled readers. The subjects had to read in Arabic 15 paragraphs, 60 sentences, and 210 words. There were three reading conditions: fully vowelized, partially vowelized, and unvowelized texts. The results showed that vowels and contexts were important variables to facilitate word recognition in poor and normal/skilled readers in Arabic orthography.     

Viscoelastic response of solid rocket motor components for service life assessment

A methodology for determining the response of rocket motor materials and bondlines to thermal loadings by measuring their dynamic mechanical properties is reported. The critical temperatures at which debonding and/or propellant cracking occur and the number of thermal cycles required to induce failure were evaluated. These results were compared with those from instrumented rocket motors subjected to similar thermal loadings. A model, developed for fibre reinforced composites, was applied to the propellant-inhibitor bimaterial obtained from a rocket motor. The internal energy dissipation due to a lack of perfect adhesion at the propellant–inhibitor interface, tan δ_adh, was used to give an indication of the failure mode of the bondline (i.e., adhesive failure at the interface or cohesive failure in the propellant) and the bond adhesion parameter, C, was related to the bond strength measured by rectangular bond-in-tension tests. This revised version was published online in November 2006 with corrections to the Cover Date.     

The residential gateway

Burgeoning competition in telecommunications is multiplying the number of communications paths into the home-but a standard multinetwork connection could sort them out. Services going into the residence may enter over copper wires, hybrid fiber coax, RF transmission, fiber to the curb, or, most importantly, by any combination of these sources and structures. To have a successful market, residential customers must be able to move smoothly from one combination of these offerings to another so that the customers consider the move worthwhile. For this multinetwork-to-multiservice interconnection to have value, it must be simple, and that simplicity is the basis for the residential gateway concept. In other words, the substantial complexity of the interconnection must be hidden from the consumer. The concept is essentially the development of a set of interface standards between the broadband residential access networks and the communication services (the internal networks) required for the consumer's home     

Mathematical foundations for error estimation in numericalsolutions of integral equations in electromagnetics

The problem of error estimation in the numerical solution of integral equations that arise in electromagnetics is addressed. The direct method (Green's theorem or field approach) and the indirect method (layer ansatz or source approach) lead to well-known integral equations both of the first kind [electric field integral equations (EFIE)] and the second kind [magnetic field integral equations (MFIE)]. These equations are analyzed systematically in terms of the mapping properties of the integral operators. It is shown how the assumption that field quantities have finite energy leads naturally to describing the mapping properties in appropriate Sobolev spaces. These function spaces are demystified through simple examples which also are used to demonstrate the importance of knowing in which space the given data lives and in which space the solution should be sought. It is further shown how the method of moments (or Galerkin method) is formulated in these function spaces and how residual error can be used to estimate actual error in these spaces. The condition number of all of the impedance matrices that result from discretizing the integral equations, including first kind equations, is shown to be bounded when the elements are computed appropriately. Finally, the consequences of carrying out all computations in the space of square integrable functions, a particularly friendly Sobolev space, are explained     

Designing better adaptive sampling algorithms for ECG Holtersystems

Let Ψ be any adaptive sampling algorithm that can run in real time on a tapeless multichannel electrocardiogram (ECG) Holter system. Simple methods which can significantly improve Ψ's fidelity are described and their results are compared in this paper. It is shown that by adding some simple tests to Ψ, the signals reconstructed by Ψ can be improved as much as 5.45 dB. It is also shown that under the same data rate, a good data compressor with slowly sampled input ECG is preferable to a bad data compressor with highly sampled input ECG