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     

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 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.