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1.
Topical photodynamic therapy is used for a variety of malignant and pre-malignant skin disorders, including Bowen's Disease and Superficial Basal Cell Carcinoma. A haem precursor, typically 5-aminolevulinic acid (ALA), acting as a prodrug, is absorbed and converted by the haem biosynthetic pathway to photoactive protoprophyrin IX (PpIX), which accumulates preferentially in rapidly dividing cells. Cell destruction occurs when PpIX is activated by an intense light source of appropriate wavelength. Topical delivery of ALA avoids the prolonged photosensitivity reactions associated with systemic administration of photosensitisers but its clinical utility is influenced by the tissue penetration characteristics of the drug, its ease of application and the stability of the active agent in the applied dose. This review, therefore, focuses on drug delivery applications for topical, ALA-based PDT. Issues considered in detail include physical and chemical enhancement strategies for tissue penetration of ALA and subsequent intracellular accumulation of PpIX, together with formulation strategies and drug delivery design solutions appropriate to various clinical applications. The fundamental aspects of drug diffusion in relation to the physicochemical properties of ALA are reviewed and specific consideration is given to the degradation pathways of ALA in formulated systems that, in turn, influence the design of stable topical formulations. 相似文献
2.
Palle E.T. Jorgensen Erin P.J. Pearse 《Journal of Mathematical Analysis and Applications》2019,469(2):765-807
Motivated by applications to machine learning, we construct a reversible and irreducible Markov chain whose state space is a certain collection of measurable sets of a chosen l.c.h. space . We study the resulting network (connected undirected graph), including transience, Royden and Riesz decompositions, and kernel factorization. We describe a construction for Hilbert spaces of signed measures which comes equipped with a new notion of reproducing kernels and there is a unique solution to a regularized optimization problem involving the approximation of functions by functions of finite energy. The latter has applications to machine learning (for Markov random fields, for example). 相似文献
3.
Two samples of mussels (Mytilus edulis) were collected from the southwest of Ireland. One sample contained domoic acid, the other sample contained okadaic acid,
dinophysistoxin-2 and azaspiracid-1, -2 and -3. Wet and freeze-dried reference materials were prepared from each of the two
samples to test for differences in homogeneity, stability and extractability of the analytes in either condition. Wet materials
were homogenised, aliquoted and hermetically sealed under argon and subsequently frozen at −80 °C. Dry materials were similarly
homogenised but frozen in flat cakes prior to freeze-drying. After grinding, sieving and further homogenisation, the resulting
powder was aliquoted and hermetically sealed. Domoic acid materials were characterised using HPLC–UV, while LC–MS was used
for the determination of lipophilic toxins. The extractabilities of all phycotoxins studied were comparable for wet and freeze-dried
materials once a sonication step had been carried out for reconstitution of the freeze-dried materials prior to extraction.
Homogeneity was assessed through replicate analysis of the phycotoxins (n = 10), and was found to be similar for wet and freeze-dried materials, for both hydrophilic and lipophilic toxins. Water
contents were determined for both wet and freeze-dried materials, and particle size was determined for the freeze-dried materials.
Stability was evaluated isochronously over eight months at four temperatures (−20, +4, +20 and +40 °C). The freeze-dried material
containing domoic acid was stable over the whole duration at all temperatures, while in the wet material domoic acid degraded
to some extent at all temperatures except −20 °C. In freeze-dried and wet materials containing lipophilic toxins, okadaic
acid, dinophysistoxin-2, azaspiracid-1 and azaspiracid-2 were stable over the whole duration at all conditions, while concentrations
of azaspiracid-3 changed significantly in both materials at some storage temperatures.
Figure Aliquots of freeze-dried and wet mussel tissue reference materials containing the various shellfish toxins examined in the
study 相似文献
4.
5.
McCarron P Emteborg H Giddings SD Wright E Quilliam MA 《Analytical and bioanalytical chemistry》2011,400(3):847-858
A candidate certified reference material (CRM) for multiple shellfish toxins (domoic acid, okadaic acid and dinophysistoxins,
pectenotoxins, yessotoxin, azaspiracids and spirolides) has been prepared as a freeze-dried powder from mussel tissues (Mytilus edulis). Along with the certified values, the most important characteristics for a reference material to be fit-for-purpose are
homogeneity and stability. Acceptable between-bottle homogeneity was found for this CRM. Within-bottle homogeneity was assessed
using domoic acid, and it was shown that repeated subsampling of the CRM can be performed precisely down to 0.35 g. Both short-
and long-term stability studies carried out under isochronous conditions demonstrated excellent stability of the various toxins
present in the material. While degradation of some analytes was observed at +60°C in short-term studies, it was determined
that shipping at ambient temperature is adequate. No instability was detected in long-term stability studies, and it was shown
that the material can be held at +18°C safely for up to 1 year. To guarantee stability of the CRM over its lifetime the stock
will be maintained at −20°C. The results of the homogeneity and stability testing show that CRM–FDMT1 is appropriate for its
intended use in quality assurance and quality control of shellfish toxin analysis methods. 相似文献
6.
On a finite network (connected weighted undirected graph), the relationship between the natural Dirichlet form E and the discrete Laplace operator Δ is given by $\varepsilon (u,v) = {\langle u,\Delta v\rangle _{{\ell ^2}}}$ , where the latter is the usual ? 2 inner product. This formula is not generally true for infinite networks; earlier authors have given various conditions under which this formula remains valid. Instead, we extend this formula to arbitrary infinite networks (including the case when Δ is unbounded) by including a new (boundary) term, in parallel with the classical Gauss-Green identity. This tool allows for detailed study of the boundary of the network. We construct a reproducing kernel for the space of functions of finite energy which allows us to specify a dense domain for Δ and give several criteria for the transience of the random walk on the network. The extended Gauss-Green identity and the reproducing kernel also yield a boundary integral representation for harmonic functions of finite energy. The boundary representation is developed further in [24]. 相似文献
7.
Total Synthesis of (6R,10R,13R,14R,16R,17R,19S,20R,21R,24S, 25S,28S,30S,32R,33R,34R,36S,37S,39R)‐Azaspiracid‐3 Reveals Non‐Identity with the Natural Product
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Nathaniel T. Kenton Dr. Daniel Adu‐Ampratwum Dr. Antony A. Okumu Dr. Zhigao Zhang Dr. Yong Chen Dr. Son Nguyen Dr. Jianyan Xu Dr. Yue Ding Dr. Pearse McCarron Dr. Jane Kilcoyne Prof. Dr. Frode Rise Prof. Dr. Alistair L. Wilkins Dr. Christopher O. Miles Prof. Dr. Craig J. Forsyth 《Angewandte Chemie (International ed. in English)》2018,57(3):805-809
A convergent and stereoselective total synthesis of the previously assigned structure of azaspiracid‐3 has been achieved by a late‐stage Nozaki–Hiyama–Kishi coupling to form the C21?C22 bond with the C20 configuration unambiguously established from l ‐(+)‐tartaric acid. Postcoupling steps involved oxidation to an ynone, modified Stryker reduction of the alkyne, global deprotection, and oxidation of the resulting C1 primary alcohol to the carboxylic acid. The synthetic product matched naturally occurring azaspiracid‐3 by mass spectrometry, but differed both chromatographically and spectroscopically. 相似文献
8.
Tao Gao Xiaogang Li Xiwen Wang Dr. Junkai Hu Fudong Han Dr. Xiulin Fan Dr. Liumin Suo Alex J Pearse Prof. Sang Bok Lee Prof. Gary W. Rubloff Dr. Karen J Gaskell Dr. Malachi Noked Prof. Chunsheng Wang 《Angewandte Chemie (International ed. in English)》2016,55(34):9898-9901
Aluminum metal is a promising anode material for next generation rechargeable batteries owing to its abundance, potentially dendrite‐free deposition, and high capacity. The rechargeable aluminum/sulfur (Al/S) battery is of great interest owing to its high energy density (1340 Wh kg?1) and low cost. However, Al/S chemistry suffers poor reversibility owing to the difficulty of oxidizing AlSx. Herein, we demonstrate the first reversible Al/S battery in ionic‐liquid electrolyte with an activated carbon cloth/sulfur composite cathode. Electrochemical, spectroscopic, and microscopic results suggest that sulfur undergoes a solid‐state conversion reaction in the electrolyte. Kinetics analysis identifies that the slow solid‐state sulfur conversion reaction causes large voltage hysteresis and limits the energy efficiency of the system. 相似文献
9.
Sabrina Kombrink Erin P. J. Pearse Steffen Winter 《Mathematische Zeitschrift》2016,283(3-4):1049-1070
A long-standing conjecture of Lapidus states that under certain conditions, self-similar fractal sets fail to be Minkowski measurable if and only if they are of lattice type. It was shown by Falconer and Lapidus (working independently but both using renewal theory) that nonlattice self-similar subsets of \({\mathbb {R}}\) are Minkowski measurable, and the converse was shown by Lapidus and v. Frankenhuijsen a few years later, using complex dimensions. Around that time, Gatzouras used renewal theory to show that nonlattice self-similar subsets of \({\mathbb {R}}^d\) that satisfy the open set condition are Minkowski measurable for \(d \ge 1\). Since then, much effort has been made to prove the converse. In this paper, we prove a partial converse by means of renewal theory. Our proof allows us to recover several previous results in this regard, but is much shorter and extends to a more general setting; several technical conditions appearing in previous work have been removed. 相似文献
10.
Fit-for-purpose shellfish reference materials for internal and external quality control in the analysis of phycotoxins 总被引:1,自引:0,他引:1
The need for reference materials for quality control of analysis of foodstuffs has been stressed frequently. This has been
particularly true in the phycotoxins field, where there is a great shortage of both pure calibration standards and reference
materials. Worldwide there are very few independent bodies that produce certified reference materials for phycotoxins, the
main producers currently being the National Research Council Canada and the Japanese Food Research Laboratory. Limited availability
of contaminated shellfish and algae, as well as the time and knowledge necessary for the production of adequate reference
materials, continuously lead to limited editions of certified reference materials and even more limited production of in-house
reference materials. The restricted availability of in-house quality control materials promotes the rapid use of the limited
certified reference materials, which in turn hampers the production of the suite of materials required globally for complete
protection of public health. This paper outlines the various options that analysts can pursue in the use of reference materials
for internal and external quality control, with a view to optimising the efforts of both reference materials users and reference
materials producers. For this purpose, the logical sequence is reviewed from the discovery of a new bioactive compound in
shellfish, through initial method development up to regulation for food safety purposes including accepted reference methods.
Subsequently, the requirements for and efforts typically spent in the production and characterisation of laboratory reference
materials, certified reference materials and other test materials used in inter-laboratory studies or proficiency testing,
in the area of marine biotoxins are evaluated. Particular emphasis is put on practical advice for the preparation of in-house
reference materials. The intricate link between reference material characterisation and method performance is outlined to
give guidance on the appropriate in-house method validation in the rapidly developing field of phycotoxins.
相似文献