Stability of 5-aminolevulinic acid in novel non-aqueous gel and patch-type systems intended for topical application.

Aminolevulinic acid (ALA) stability within topical formulations intended for photodynamic therapy (PDT) is poor due to dimerisation to pyrazine-2,5-dipropionic acid (PY). Most strategies to improve stability use low pH vehicles, which can cause cutaneous irritancy. To overcome this problem, a novel approach is investigated that uses a non-aqueous vehicle to retard proton-induced charge separation across the 4-carbonyl group on ALA and lessen nucleophilic attack that leads to condensation dimerisation. Bioadhesive anhydrous vehicles based on methylvinylether-maleic anhydride copolymer patches and poly(ethyleneglycol) or glycerol thickened poly(acrylic acid) gels were formulated. ALA stability fell below pharmaceutically acceptable levels after 6 months, with bioadhesive patches stored at 5°C demonstrating the best stability by maintaining 86.2% of their original loading. Glycerol-based gels maintained 40.2% in similar conditions. However, ALA loss did not correspond to expected increases in PY, indicating the presence of another degradative process that prevented dimerisation. Nuclear magnetic resonance (NMR) analysis was inconclusive in respect of the mechanism observed in the patch system, but showed clearly that an esterification reaction involving ALA and both glycerol and poly(ethyleneglycol) was occurring. This was especially marked in the glycerol gels, where only 2.21% of the total expected PY was detected after 204 days at 5°C. Non-specific esterase hydrolysis demonstrated that ALA was recoverable from the gel systems, further supporting esterified binding within the gel matrices. It is conceivable that skin esterases could duplicate this finding upon topical application of the gel and convert these derivatives back to ALA in situ, provided skin penetration is not affected adversely.

Differential lifetime success and performance of native and non-native Atlantic salmon examined under communal natural conditions.

The lifetime success and performance characteristics of communally reared offspring of wild native Burrishoole (native), ranched native (ranched) and non-native (non-native) Atlantic salmon Salmo salar from the adjacent Owenmore River were compared. Non-native year parr showed a substantial downstream migration, which was not shown by native and ranched parr. This appears to have been an active migration rather than competitive displacement and may reflect an adaptation to environmental or physiographic conditions within the Owenmore River catchment where the main nursery habitat is downstream of the spawning area. There were no differences between native and ranched in smolt output or adult return. Both of these measures, however, were significantly lower for the non-native group. A greater proportion of the non-native Atlantic salmon was taken in the coastal drift nets compared to the return to the Burrishoole system, probably as a result of the greater size of the non-native fish. The overall lifetime success of the non-native group, from fertilized egg to returning adult, was some 35% of native and ranched. The ranched group showed a significantly greater male parr maturity, a greater proportion of 1+ year smolts, and differences in sex ratio and timing of freshwater entry of returning adults compared to native, which may have fitness implications under specific conditions.

Non-Markovian decoherence: complete positivity and decomposition

In this work, the non-Markovian decoherence is considered in two ways. Firstly, an effective Hamiltonian approach is demonstrated to investigate the decoherence of a quantum system in a non-Markovian environment, in which complete positivity of the reduced dynamics is achieved. This method uses the notion of an effective environment, that is a subsystem of the environment that causes the decoherence. Secondly, the evolution of the system and environment is decomposed, thus partially illuminating how they would interact given that memory effects are allowed. It should be noted that beam splitters and rotators are sufficient to explain this decomposition.

Completely positive non-Markovian decoherence

We propose an effective Hamiltonian approach to investigate decoherence of a quantum system in a non-Markovian reservoir, naturally imposing the complete positivity on the reduced dynamics of the system. The formalism is based on the notion of an effective reservoir, i.e., certain collective degrees of freedom in the reservoir that are responsible for the decoherence. As examples for completely positive decoherence, we present three typical decoherence processes for a qubit such as dephasing, depolarizing, and amplitude damping. The effects of the non-Markovian decoherence are compared to the Markovian decoherence.

Mapping the Education System in Northern Ireland

In this chapter we provide a broad overview of the education system discussing both the system of schooling and the network of both statutory and voluntary bodies that are responsible for the administration and management of the system. We begin with an examination of the administrative structures. This network of statutory and non-statutory bodies has increased in number over recent years, illustrating the diversity of vested interests in the system. This is followed by an examination of the system of schooling and the chapter concludes by exploring the significance of changes that have taken place in terms of its implications for a more pluralist society where each is accorded parity of esteem and equality of opportunity.

Self-consistent non-Markovian theory of a quantum-state evolution for quantum-information processing

We study non-Markovian decoherence phenomena by employing projection-operator formalism when a quantum system (a quantum bit or a register of quantum bits) is coupled to a reservoir. By projecting out the degree of freedom of the reservoir, we derive a non-Markovian master equation for the system, which is reduced to a Lindblad master equation in Markovian limit, and obtain the operator sum representation for the time evolution. It is found that the system is decohered slower in the non- Markovian reservoir than the Markovian because the quantum information of the system is memorized in the non-Markovian reservoir. We discuss the potential importance of non-Markovian reservoirs for quantum-information processing.

Non-local quantum gates: a cavity-quantum-electrodynamics implementation

The problems related to the management of large quantum registers could be handled in the context of distributed quantum computation: unitary non-local transformations among spatially separated local processors are realized performing local unitary transformations and exchanging classical communication. In this paper, a scheme is proposed for the implementation of universal non-local quantum gates such as a controlled NOT (CNOT) and a controlled quantum phase gate (CQPG). The system chosen for their physical implementation is a cavity-quantum-electrodynamics (CQED) system formed by two spatially separated microwave cavities and two trapped Rydberg atoms. The procedures to follow for the realization of each step necessary to perform a specific non-local operation are described.

Non-invasive in vivo imaging in small animal research

Non-invasive real time in vivo molecular imaging in small animal models has become the essential bridge between in vitro data and their translation into clinical applications. The tremendous development and technological progress, such as tumour modelling, monitoring of tumour growth and detection of metastasis, has facilitated translational drug development. This has added to our knowledge on carcinogenesis. The modalities that are commonly used include Magnetic Resonance Imaging (MRI), Computed Tomography (CT), Positron Emission Tomography (PET), bioluminescence imaging, fluorescence imaging and multi-modality imaging systems. The ability to obtain multiple images longitudinally provides reliable information whilst reducing animal numbers. As yet there is no one modality that is ideal for all experimental studies. This review outlines the instrumentation available together with corresponding applications reported in the literature with particular emphasis on cancer research. Advantages and limitations to current imaging technology are discussed and the issues concerning small animal care during imaging are highlighted.

Osteoclastogenesis induced by sRANKL and M-CSF from the non-adherent cell population of human bone marrow is inhibited by rhBMP-2 alone or together with rhVEGF

During bone development and repair, angiogenesis, osteogenesis and bone remodelling are closely associated processes that share some common mediators. In the present study non-adherent human bone marrow mononuclear cells under the induction of sRANKL and M-CSF, differentiated into osteoclasts with TRAP positive staining, VNR expression, and Ca-P resorptive activity. The effects of various combinations of rhBMP-2 (0, 3, 30, 300 ng/ml) and rhVEGF (0, 25 ng/ml) on osteoclastogenesis potentials were examined in this experimental system. The percentages of TRAP-positive multiple nucleated cells represent osteoclast differentiation potential and the percentages of resorptive areas in the Ca-P coated plates resemble osteoclast resorption capability. The presence of rhBMP-2 at 30 and 300 ng/ml showed inhibitory effects on osteoclast differentiation and their resorptive capability in the human osteoclast culture system. rhVEGF (25 ng/ml) enhanced the resorptive function of osteoclast whenever it was used alone or combined with 3 ng/ml rhBMP-2. However, rhVEGF induced resorptive function was inhibited by 30 ng/ml and 300 ng/ml rhBMP-2 at a dose-dependent manner. Statistical analysis demonstrated that an interactive effect exists between rhBMP-2 and rhVEGF on human osteoclastogenesis. These findings suggested that an interactive regulation may exist between BMPs and VEGF signaling pathways during osteoclastogenesis, exact mechanisms are yet to be elucidated.

Sequentially continuous non-linear fundamental systems of solutions of affine equations in locally convex spaces

According to the Mickael's selection theorem any surjective continuous linear operator from one Fr\'echet space onto another has a continuous (not necessarily linear) right inverse. Using this theorem Herzog and Lemmert proved that if $E$ is a Fr\'echet space and $T:E\to E$ is a continuous linear operator such that the Cauchy problem $\dot x=Tx$, $x(0)=x_0$ is solvable in $[0,1]$ for any $x_0\in E$, then for any $f\in C([0,1],E)$, there exists a continuos map $S:[0,1]\times E\to E$, $(t,x)\mapsto S_tx$ such that for any $x_0\in E$, the function $x(t)=S_tx_0$ is a solution of the Cauchy problem $\dot x(t)=Tx(t)+f(t)$, $x(0)=x_0$ (they call $S$ a fundamental system of solutions of the equation $\dot x=Tx+f$). We prove the same theorem, replacing "continuous" by "sequentially continuous" for locally convex spaces from a class which contains strict inductive limits of Fr\'echet spaces and strong duals of Fr\'echet--Schwarz spaces and is closed with respect to finite products and sequentially closed subspaces. The key-point of the proof is an extension of the theorem on existence of a sequentially continuous right inverse of any surjective sequentially continuous linear operator to some class of non-metrizable locally convex spaces.

Dilute acid hydrolysis of cellulose and cellulosic bio-waste using a microwave reactor system

The dilute acid hydrolysis of grass and cellulose with phosphoric acid was undertaken in a microwave reactor system. The experimental data and reaction kinetic analysis indicate that this is a potential process for cellulose and hemi-cellulose hydrolysis, due to a rapid hydrolysis reaction at moderate temperatures. The optimum conditions for grass hydrolysis were found to be 2.5% phosphoric acid at a temperature of 175 degrees C. It was found that sugar degradation occurred at acid concentrations greater than 2.5% (v/v) and temperatures greater than 175 degrees C. In a further series of experiments, the kinetics of dilute acid hydrolysis of cellulose was investigated varying phosphoric acid concentration and reaction temperatures. The experimental data indicate that the use of microwave technology can successfully facilitate dilute acid hydrolysis of cellulose allowing high yields of glucose in short reaction times. The optimum conditions gave a yield of 90% glucose. A pseudo-homogeneous consecutive first order reaction was assumed and the reaction rate constants were calculated as: k(1) = 0.0813 s(-1); k(2) = 0.0075 s(-1), which compare favourably with reaction rate constants found in conventional non-microwave reaction systems. The kinetic analysis would indicate that the primary advantages of employing microwave heating were to: achieve a high rate constant at moderate temperatures: and to prevent 'hot spot' formation within the reactor, which would have cause localised degradation of glucose.

A Survey of Search Methodologies and Automated System Development for Examination Timetabling

Exam timetabling is one of the most important administrative activities that takes place in academic institutions. In this paper we present a critical discussion of the research on exam timetabling in the last decade or so. This last ten years has seen an increased level of attention on this important topic. There has been a range of significant contributions to the scientific literature both in terms of theoretical andpractical aspects. The main aim of this survey is to highlight the new trends and key research achievements that have been carried out in the last decade.We also aim to outline a range of relevant important research issues and challenges that have been generated by this body of work.

We first define the problem and review previous survey papers. Algorithmic approaches are then classified and discussed. These include early techniques (e.g. graph heuristics) and state-of-the-art approaches including meta-heuristics, constraint based methods, multi-criteria techniques, hybridisations, and recent new trends concerning neighbourhood structures, which are motivated by raising the generality of the approaches. Summarising tables are presented to provide an overall view of these techniques. We discuss some issues on decomposition techniques, system tools and languages, models and complexity. We also present and discuss some important issues which have come to light concerning the public benchmark exam timetabling data. Different versions of problem datasetswith the same name have been circulating in the scientific community in the last ten years which has generated a significant amount of confusion. We clarify the situation and present a re-naming of the widely studied datasets to avoid future confusion. We also highlight which research papershave dealt with which dataset. Finally, we draw upon our discussion of the literature to present a (non-exhaustive) range of potential future research directions and open issues in exam timetabling research.

Clinical and immunohistochemical assessment of vulval intraepithelial neoplasia following photodynamic therapy using a novel bioadhesive patch-type system loaded with 5-aminolevulinic acid

Background: The work in this study appraised photodynamic treatment (PDT) as a treatment method for vulval intraepithelial neoplasia (VIN) using a novel bioadhesive patch to deliver aminolevulinic acid. An analysis of changes in expression of apoptotic and cell cycle proteins (p53, p21, Mdm2, Blc-2, Bax, Ki-67) in response to PDT was evaluated. Methods: PDT was performed using non-laser light, either as a one or two-cycle treatment, with clinical and pathological assessment following after 6 weeks. Twenty-three patients with 25 VIN lesions underwent 49 cycles of PDT Patches were designed to conform to uneven vulval skin and contained 38 mg cm(-2) aminolevulinic acid. Assessment was carried out at 6 weeks post-treatment. Patient-based treatment assessment, along with clinical and pathological changes, were monitored. Immunohistochemical staining was used to elucidate a possible biomolecular basis for induced cellular changes. Results: Most patients (52%) reported a symptomatic response, with normal pathology restored in 38% of lesions. The patch was easy to apply and remove, causing minimal discomfort. Fluorescence inspection confirmed protoporphyrin accumulation. Pain during implementation of PDT was problematic, necessitating some form of local analgesia. Changes in expression of cell cycle and apoptotic-related proteins suggested involvement of apoptotic pathways. Down regulation of p21 and inverse changes in Bcl-2 and Bax were key findings. Conclusion: Treatment of VIN lesions using a novel bioadhesive patch induced changes in cell cycle and apoptotic proteins in response to PDT with possible utilisation of apoptotic pathways. The efficacy of PDT in treating VIN could be improved by a better understanding of these apoptotic mechanisms, the influence of factors, such as HPV status, and of the need for effective pain management.

Towards variance-matrix characterization of complementarity relations in a continuous variable system

We discuss complementarity relations in a bipartite continuous variable system. Building up from the work done on discrete d-dimensional systems, we prove that for symmetric two-mode states, quantum complementarity relations can be put in a simple relation with the elements of the variance matrix. When this condition is not satisfied, such a connection becomes non-trivial. Our investigation is the first step towards an operative characterization of the complementarity in a scenario that has not been investigated so far.