Investigation of the absorption pathways of some poorly absorbed drugs using human intestinal (CAC0-2) cell monolayers

Absorption across the gastro-intestinal epithelium is via two pathways; the transcellular and paracellular pathway. Caco-2 cells, when cultured on polycarbonate filters, formed a confluent monolayer with many properties of differentiated intestinal epithelial cells, As a model of human gastro-intestinaJ tract epithelia they were used to elucidate and characterise the transepithelial transport of two protein kinase C inhibitors, N-(3-chlorophenyl)-4-[2-(3-hydroxypropylamino)-4-pyridyl]-2-pyrimidinamin (CHPP) and N-benzoyl-staurosporine (NBS), and the polypeptide, human calcitonin. Lanthanum ions are proposed as a paracellular pathway inhibitor and tested with D-mannitol permeability and transepithelial electrical resistance measurements. The effect La3+ has on the carrier-mediated transport of D-glucose and Sodium taurocholate as well as the vesicularly transcytosed horseradish peroxidase was also investigated. As expected, 2 mM apical La3+ increases transepithelial electrical resistance 1.S-fold and decreases mannitol permeability by 63.0 % ± 1.37 %. This inhibition was not repeated by other cations. Apical 2 mM La3+ was found to decrease carrier-mediated D-glucose and taurocholate permeability by only 8.7 % ± 1.6 %, 26.3 % ± 5.0 %. There was no inhibitory effect on testosterone or PEG 4000 permeability observed with La3+. However, for horseradish peroxidase and human calcitonin permeability was decreased by 98.7 % ± 11.7%, and 96.2 % ± 0.8 % respectively by 2 mM La3+. Indicating that human calcitonin could also be transported by vesicular transcytosis. The addition of 2 mM La3+ to the apical surface of Caco-2 monolayers produces a paracellular pathway inhibition. Therefore, La3+ could be a useful additional tool in delineating the transepithelial pathway of passive drug absorption.

Modelling and simulation strategies for the electric systems of large passenger aircraft

The simulation of a power system such as the More Electric Aircraft is a complex problem. There are conflicting requirements of the simulation, for example in order to reduce simulation run-times, power ratings that need to be established over long periods of the flight can be calculated using a fairly coarse model, whereas power quality is established over relatively short periods with a detailed model. An important issue is to establish the requirements of the simulation work at an early stage. This paper describes the modelling and simulation strategy adopted for the UK TIMES project, which is looking into the optimisation of the More Electric Aircraft from a system level. Essentially four main requirements of the simulation work have been identified, resulting in four different types of simulation. Each of the simulations is described along with preliminary models and results.

On the hydrothermal stability of MCM-41. Evidence of capillary tension-induced effects

MCM-41's limited hydrothermal stability has been often related to the hydrolysis of Si-O-Si bonds due to the low degree of condensation, its thin walls or a combination of them. In this work, evidence for an additional factor is provided; a physical effect that occurs during the drying of the hydrothermally treated calcined material due to the intense capillary stress exerted in water. Depending on both physical (i.e. mechanical) and chemical (i.e. hydrolysis) resistances, the structure undergoes differently. Three MCM-41 samples with different degree of condensation were investigated. The most remarkable results are found with un-aged TEOS based material, which gets fully disordered and shrunk for all applied hydrothermal temperatures in water. Comparison between water and a low-surface-tension-solvent drying revealed that capillarity is responsible for the loss of ordering (and shrinkage) at moderate hydrothermal temperatures. The material's structure is hexagonal and shrinkage-free under the low-surface-tension-solvent route. At a high hydrothermal temperature, hydrolysis is extensive and responsible for the loss of ordering. The other remarkable finding regards the aged MCM-41 mesostructure that maintains the hexagonal features at all applied temperatures in water, and it is more stable against capillarity at high temperature. The Na-metasilicate based material is mechanically very stable and gets disordered at high temperature due to hydrolysis.

Free surface and mesh control for the FV simulation of semi-levitation melting

Abstract not available

Recent observations on the exploitation of the fish stocks of Lake Victoria, Uganda

The data from the able sources has been used in this paper to make observations on the exploitation of the fish stocks in Lake Victoria since 1981. The paper focuses on species composition of the catch, catch rates, average size of the individual fish landed and fish production. On the basis of these parameters and developments in the fishery, the paper also presents some observations and comments on the future prospects of the fish stocks in the lake.

The socio-economic aspects of the fishing communities of Lake Victoria, Uganda

A baseline survey of the fishing communities was conducted in 2005/06 as one of the main studies under the Socio-economic Research and Monitoring Working Group on Lake Victoria. The overall objective of the survey was to provide a deeper understanding of the broad socio-economic characteristics and well being of the different stakeholder groups immediately dependent on the Lake Victoria fisheries. An understanding of socioeconomic status of the fishery primary stakeholders, who include fishers, artisanal processors and traders, is essential for any subsequent periodic evaluation of development. During the survey, a total of 1,235 respondents were interviewed, at 34 landing sites in all the Ugandan districts on Lake Victoria. The purpose of this fact sheet is to provide information on the fish landing beaches, people involved in fisheries, their livelihood activities and facilities available to them.

The changing fisheries of Lake Victoria, Uganda

Lake Victoria had a complex multi-species fishery dominated until the late 1970s by the tilapiine and haplochromine cichlids but with important subsidiary fisheries of more than 20 genera of non-cichlid fishes. Since the 1980s, however, the fishery has been dominated by the Nile perch (Lates niloticus), Nile tilapia (Oreochromis niloticus eduardianus) both introduced into the lake during the late 1950s and early 1960s and Rastrineobola argentea, a pelagic cyprinid. Although the actual landed commercial catch figures from the Uganda sector of the lake point to the increased landings since 1984, the catch rates in the experimental trawl fishery and mean weight of fish in both experimental trawl and commercial fishery have been on the decline.

The healing power of grandparents who parent

This paper explores the changing role of contemporary grandparents with many demonstrating a willingness and ability to take on parental responsibilities for their grandchildren, where they may face challenges and opportunities in difficult times. Three main forms of grand parenting are identified in the literature, those who hâve primary responsibility and are raising their grand children as their main carers perhaps in response to crisis situations, those who live in extended families and participate in care, and those who provide day care while the child's parents work. The rôle of Grandparents encompasses ail three areas in the United Kingdom. This has occurred as a resuit of the increased récognition of children living in abusive families, of the increasing frequency of divorce, single parenting, children and families living in poverty, socio-economic deprivation and the lack of available or subsidised child care in the United Kingdom when parents hâve to work to support the family. Ail of this against the backdrop the Every Child Matters change for children Agenda. When grandparents step into a troubled situation and attempt to offer stability and security for their grandchildren they may hâve to manage the combined responsibilities of family caregivers and parental figures. Grandparenthood is atenuous rôle, lacking clear agreement on behaviour norms. In the current culture of advice and parenting support, while care must be taken not to undermine parenting skills or make judgements about the ability to cope with the demands of childcare, an exploration of the impact on grandparents, and children in the context of families must be undertaken. Due to the complex web of interrelated factors the process and outcomes of care giving by grandparents is not well known in the literature. It is proposed therefore that it is timely to explore the impact of this on the health of children and their families in the current climate of change when there has been dissolution of the nuclear family and grandparents are playing increasingly significant rôles in healing and supporting their families.

Synergistic effect of ethanol and mitomycin C on corneal stroma

PURPOSE: To investigate the combined effects of ethanol and mitomycin C (MMC) application on the corneal stroma of rabbits that underwent photorefractive keratectomy (PRK). METHODS: Twenty-four rabbits (24 eyes) underwent PRK to correct -9.00 diopters of myopia. Twelve eyes had ethanol application before removing the epithelium and 12 eyes had the epithelium manually removed without ethanol, Eyes in both groups had topical MMC 0.02% application for 12 seconds immediately after excimer laser ablation. Twelve rabbits were sacrificed at two time points-4 hours and 4 weeks after surgery-and immunohistochemistry was performed with TUNEL assay, alpha-smooth muscle actin (alpha-SMA), and DAPI. RESULTS: More TUNEL-positive cells were observed in the ethanol-treated group compared to the mechanical debridement group at 4 hours after surgery (P<.01). No significant difference in alpha-SMA-positive cells was detected, between the two groups at 4 weeks after sugery. However, decreased keratocyte density in the anterior stroma was more pronounced in the ethanol-treated group compared to the mechanical debridement (P<.02). CONCLUSIONS: Ethanol application for epithelial removal during PRK seems to produce a synergistic effect with MMC, resulting in fewer keratocytes in the anterior stroma of rabbit corneas treated with MMC and ethanol than in corneas treated with MMC alone after PRK.

The Cuntz semigroup, the Elliott conjecture, and dimension functions on C*-Algebras

We prove that the Cuntz semigroup is recovered functorially from the Elliott invariant for a large class of C¤-algebras. In particular, our results apply to the largest class of simple C¤-algebras for which K-theoretic classification can be hoped for. This work has three significant consequences. First, it provides new conceptual insight into Elliott's classification program, proving that the usual form of the Elliott conjecture is equivalent, among Z-stable algebras, to a conjecture which is in general substantially weaker and for which there are no known counterexamples. Second and third, it resolves, for the class of algebras above, two conjectures of Blackadar and Handelman concerning the basic structure of dimension functions on C¤-algebras. We also prove in passing that the Kuntz-Pedersen semigroup is recovered functorially from the Elliott invariant for all simple unital C¤-algebras of interest.

STABILITY AND FOLDING OF MUTANT FORMS OF ISO-1 CYTOCHROME-C FROM SACCHAROMYCES CEREVISIAE

Partially functional forms of iso-1-cytochrome c from Saccharomyces cerevisiae were obtained by replacements of the evolutionarily conserved proline 71 with valine, isoleucine and threonine (Ernst et.al.,1985). Pro-71 lies at the juncture of two short helical regions and is believed to be important for proper local polypeptide chain folding within the iso-1-cytochrome c structure.^ To study folding in the absence of intermolecular disulfide dimer formation the free sulfhydryl group of Cys-102 was modified in both wild type and mutant proteins with an alkylating reagent, methyl methanethiosulfonate. Spectral analysis of the wild type and mutant proteins shows that the native-like functional (or partially functional) folded structure of cytochrome c is retained in the chemically modified derivatives. The replacement of Pro-71 with valine, isoleucine or threonine reduces the intensity of the 696 nm absorbance band which is an indicator of the Met-80 ligation to the heme. Thermal stability and guanidine hydrochloride unfolding studies of the mutant proteins shows a destabilization of the protein as a result of mutation. The degree of destabilization depends on the chemical nature of the substituent amino acid in the mutant protiens.^ Kinetics of folding/unfolding reactions of the proteins were monitored by fluorescence changes using stopped flow mixing to obtain guanidine hydrochloride concentration jumps ending below, within, and above the transition zone. The replacement of Pro-71 alters the rate on one of the fastest phases, $\tau\sb3$, while the two other phases, $\tau\sb1$ & $\tau\sb2$, remain the same.^ Slow refolding kinetic studies indicate that replacement of Pro-71 does not completely eliminate the absorbance or fluorescence detected slow phases leading to the conclusion that Pro-71 is not involved in the generation of the slow phases in the folding kinetics of iso-1-cytochrome c.^ The alkaline conformational change involving the disappearance of the 696 nm absorbance band occurs with increasing pH in the alkaline pH region (Davis et al., 1974). The apparent pK of this conformational change in mutant proteins is shifted as much as two pH units compared to wild type. The equilibrium and kinetic data of alkaline transition for the wild type follows a simple mechanism proposed by Davis et al., (1974) for horse heart cytochrome c. A more complex mechanism is proposed for the behavior of the mutant proteins. ^

An exact and curious suruey of all the East Indies, euen to Canton, the chiefe cittie of China : all duly performed by land, by Monsieur de Monfart, the like whereof was neuer hetherto, brought to an end : Wherein also are described the huge dominions of the great Mogor, to whom that honorable knight, Sir Thomas Roe, was lately sent ambassador from the King : newly translated out of the trauailers manuscript.

Es la traducción de la obra: "Voyage faict par terre depuis Paris jusques à la Chine, par le sieur de Feynes,... avec son retour par mer"