Design, synthesis and in vitro degradation of a novel co-drug for the treatment of psoriasis

Psoriasis is a common, chronic and relapsing inflammatory skin disease. It affects approximately 2% of the western population and has no cure. Combination therapy for psoriasis often proves more efficacious and better tolerated than monotherapy with a single drug. Combination therapy could be administered in the form of a co-drug, where two or more therapeutic compounds active against the same condition are linked by a cleavable covalent bond. Similar to the pro-drug approach, the liberation of parent moieties post-administration, by enzymatic and/or chemical mechanisms, is a pre-requisite for effective treatment. In this study, a series of co-drugs incorporating dithranol in combination with one of several non-steroidal anti-inflammatory drugs, both useful for the treatment of psoriasis, were designed, synthesized and evaluated. An ester co-drug comprising dithranol and naproxen in a 1:1 stoichiometric ratio was determined to possess the optimal physicochemical properties for topical delivery. The co-drug was fully hydrolyzed in vitro by porcine liver esterase within four hours. When incubated with homogenized porcine skin, 9.5% of the parent compounds were liberated after 24 h, suggesting in situ esterase-mediated cleavage of the co-drug would occur within the skin. The kinetics of the reaction revealed first order kinetics, Vmax = 10.3 μM/min and Km = 65.1 μM. The co-drug contains a modified dithranol chromophore that was just 37% of the absorbance of dithranol at 375 nm and suggests reduced skin/clothes staining. Overall, these findings suggest that the dithranol-naproxen co-drug offers an attractive, novel approach for the treatment of psoriasis.

On the stability and convergence of the finite section method for integral equation formulations of rough surface scattering

We consider the Dirichlet and Robin boundary value problems for the Helmholtz equation in a non-locally perturbed half-plane, modelling time harmonic acoustic scattering of an incident field by, respectively, sound-soft and impedance infinite rough surfaces.Recently proposed novel boundary integral equation formulations of these problems are discussed. It is usual in practical computations to truncate the infinite rough surface, solving a boundary integral equation on a finite section of the boundary, of length 2A, say. In the case of surfaces of small amplitude and slope we prove the stability and convergence as A→∞ of this approximation procedure. For surfaces of arbitrarily large amplitude and/or surface slope we prove stability and convergence of a modified finite section procedure in which the truncated boundary is ‘flattened’ in finite neighbourhoods of its two endpoints. Copyright © 2001 John Wiley & Sons, Ltd.

Grouping of 24 apple cultivars on the basis of starch degradation rate and their fruit pattern

The ripening processes of 24 apple cultivars were examined in the United Kingdom National Fruit Collection in 2010. Basically the starch content, and additionally ground colour, water-soluble solids content and flesh firmness were studied during ripening. The degradation of the starch content was evaluated using a 0–10 scale. A starch degradation value of 50% was taken to be the optimum harvest date, with harvest beginning at a value of 40% and finishing at 60%. Depending on the cultivar, this represented a harvest window of 9 to 21 days. Later ripening cultivars matured more slowly, leading to a longer harvesting period, with the exception of cv. Feuillemorte. Pronounced differences were observed among the cultivars on the basis of the starch degradation pattern, allowing them to be divided into four groups. Separate charts were elaborated for each group that are recommended for use in practice.

Success and failure of grassroots innovations for addressing climate change: the case of the Transition Movement

Grassroots innovations emerge as networks generating innovative solutions for climate change adaptation and mitigation. However, it is unclear if grassroots innovations can be successful in responding to climate change. Little evidence exists on replication, international comparisons are rare, and research tends to overlook discontinued responses in favour of successful ones. We take the Transition Movement as a case study of a rapidly spreading transnational grassroots network, and include both active and non-active local transition initiatives. We investigate the replication of grassroots innovations in different contexts with the aim to uncover general patterns of success and failure, and identify questions for future research. An online survey was carried out in 23 countries (N=276). The data analysis entailed testing the effect of internal and contextual factors of success as drawn from the existing literature, and the identification of clusters of transition initiatives with similar internal and contextual factor configurations. Most transition initiatives consider themselves successful. Success is defined along the lines of social connectivity and empowerment, and external environmental impact. We find that less successful transition initiatives might underestimate the importance of contextual factors and material resources in influencing success. We also find that their diffusion is linked to the combination of local-global learning processes, and that there is an incubation period during which a transition initiative is consolidated. Transition initiatives seem capable of generalising organisational principles derived from unique local experiences that seem to be effective in other local contexts. However, the geographical locations matter with regard to where transition initiatives take root and the extent of their success, and ‘place attachment’ may have a role in the diffusion of successful initatives. We suggest that longitudinal comparative studies can advance our understanding in this regard, as well as inform the changing nature of the definition of success at different stages of grassroots innovation development, and the dynamic nature of local and global linkages.

Variability of the interplanetary medium at 1 A.U. over 24 years: 1963–1986

A survey is presented of hourly averages of observations of the interplanetary medium, made by satellites close to the Earth (i.e. at l a.u.) in the years 1963-1986. This survey therefore covers two complete solar cycles (numbers 20 and 21). The distributions and solar-cycle variations of IMF field strength, B, and its northward component (in GSM coordinates), B(z), and of the solar-wind density, n, speed, v, and dynamic pressure, P, are discussed. Because of their importance to the terrestrial magnetosphere/ionosphere, particular attention is given to B(z) and P. The solar-cycle variation in the magnitude and variability of B(z) previously reported for cycle 20, is also found for cycle 21. However, the solar-wind data show a number of differences between cycles 20 and 21. The average dynamic pressure is found to show a solar-cycle variation and a systematic increase over the period of the survey. The minimum of dynamic pressure at sunspot maximum is mainly due to reduced solar-wind densities in cycle 20, but lower solar-wind speed in cycle 21 is a more significant factor. The distribution of the duration of periods of stable polarity of the IMF B(z) component shows that the magnetosphere could achieve steady state for only a small fraction of the time and there is some evidence for a solar-cycle variation in this fraction. It is also found that the polarity changes in the IMF B(z) fall into two classes: one with an associated change in solar-wind dynamic pressure, the other without such a change. However, in only 20% of cases does the dynamic pressure change exceed 50%.

Life before ‘The New Biography’: Modernist biographical methods in the Hogarth Press ‘Books on Tolstoi’ 1920-24

In the early 1920s, before Virginia Woolf wrote her now well-known essays “The New Biography” and “The Art of Biography,” the Hogarth Press published four biographies of Tolstoy. Each of these English translations of Russian works takes a different approach to biographical composition, and as a group they offer multiple and contradictory perspectives on Tolstoy’s character and on the genre of biography in the early twentieth century. These works show that Leonard and Virginia Woolf’s Hogarth Press took a multi-perspectival, modernist approach to publishing literary lives.

Evaluation of the Plant–Craig stochastic convection scheme (v2.0) in the ensemble forecasting system MOGREPS-R (24 km) based on the Unified Model (v7.3)

The Plant–Craig stochastic convection parameterization (version 2.0) is implemented in the Met Office Regional Ensemble Prediction System (MOGREPS-R) and is assessed in comparison with the standard convection scheme with a simple stochastic scheme only, from random parameter variation. A set of 34 ensemble forecasts, each with 24 members, is considered, over the month of July 2009. Deterministic and probabilistic measures of the precipitation forecasts are assessed. The Plant–Craig parameterization is found to improve probabilistic forecast measures, particularly the results for lower precipitation thresholds. The impact on deterministic forecasts at the grid scale is neutral, although the Plant–Craig scheme does deliver improvements when forecasts are made over larger areas. The improvements found are greater in conditions of relatively weak synoptic forcing, for which convective precipitation is likely to be less predictable.

Dietary practices and nutritional status of 0-24-month-old children from Brazilian Amazonia

Objective: To assess the nutritional status and dietary practices of 0-24-month-old children living in Brazilian Amazonia. Design: Cross-sectional study. Information oil children`s dietary intakes was obtained from diet history data. Weight and length Were measured for anthropometric evaluation. Fe status Was assessed Using fasting venous blood samples; Hb, serum ferritin and soluble tranferrin receptor concentrations were measured. Setting: The towns of Assis Brasil and Acrelandia in the state of Acre, north-west Brazil. Subjects: A total of sixty-nine randomly selected 0-24-month-old children. Results: Of these children, 40.3 % were anaemic, 63.1% were Fe-deficient, 28.1% had Fe-deficiency anaemia and 11.6% were stunted. Breast-feeding was initiated by 97.1% of mother followed by early feeding with complementary foods. The dietary pattern reflected a high intake of carbohydrate-rich foods and cow`s milk, with irregular intakes Of fruit, Vegetables and meat. All infants and 92.3% of toddlers were at risk Of inadequate Fe intakes. Fe from animal foods contributed Oil average 0.5% and 14.3% to total dietary Fe intake among infants and toddlers, respectively. Conclusions: Poor nutritional status and inadequate feeding practices in this study population reinforce the importance of exclusive breast-feeding during the first 6 months of life. Greater emphasis is required to improve the bioavailability of dietary Fe during complementary feeding practices.

The electronic and optical properties of sodalite (Na(8)Al(6)Si(6)O(24)Cl(2)) from first principles

This study reports the results of ab initio electronic and optical calculations for pure socialite crystal using the linear augmented plane wave (LAPW) method within density functional theory (DFT). The calculated electronic structure revealed predominantly orbital characters of the valence band and the conduction band, and enabled us to determine the type and the value of the fundamental gap of the compound. The imaginary part of the dielectric tensor, extinction coefficient and refraction index were calculated as functions of the incident radiation wavelength. It is shown that the O 2p states and Na 3s states play the major role in optical transitions as initial and final states, respectively. The absorption spectrum is localized in the ultraviolet range between 40 and 250 nm. Furthermore, we concluded that the material does not absorb radiation in the visible range. (C) 2009 Elsevier Ltd. All rights reserved.

Culture and exopolysaccharide production from sugarcane molasses by Gordonia polyisoprenivorans CCT 7137, isolated from contaminated groundwater in Brazil

Gordonia polyisoprenivorans CCT 7137 was isolated from groundwater contaminated with leachate in an old controlled landfill (Sauo Paulo, Brazil), and cultured in GYM medium at different concentrations of sugarcane molasses (2%, 6%, and 10%). The strain growth was analyzed by monitoring the viable cell counts (c.f.u. mL(-1)) and optical density and EPS production was evaluated at the end of the exponential phase and 24 h after it. The analysis of the viable cell counts showed that the medium that most favored bacterial growth was not the one that favored EPS production. The control medium (GYM) was the one that most favored the strain growth, at the maximum specific growth rate of 0.232 h(-1). Differences in bacterial growth when cultured at three different concentrations of molasses were not observed. Production of EPS, in all culture media used, began during the exponential phase and continued during the growth stationary phase. The highest total EPS production, after 24 h of stationary phase, was observed in 6% molasses medium (172.86 g L(-1)) and 10% (139.47 g L(-1)) and the specific total EPS production was higher in 10% molasses medium (39.03 x10(-11)g c.f.u.(-1)). After the exponential phase, in 2%, 6%, and 10% molasses media, a higher percentage of free exopolysaccharides (EPS) was observed, representing 88.4%, 62.4%, and 64.2% of the total, respectively. A different result was observed in pattern medium, which presented EPS made up of higher percentage of capsular EPS (66.4% of the total). This work is the first study on EPS production by G. polyisoprenivorans strain in GYM medium and in medium utilizing sugarcane molasses as the sole nutrient source and suggests its potential use for EPS production by G. polyisoprenivorans CCT 7137 aiming at application in biotechnological processes.

24-timmars myndigheten, säkerhet, design och definition

Via Internet kan vi sköta många av våra dagliga rutiner. Vi kan handla, betala räkningar, beställa biljetter till diverse evenemang, resor med mera. Även den offentliga sektorn erbjuder alltfler av sina tjänster elektroniskt. Det största hindret för utvecklingen av elektroniska tjänster är den höga säkerhet som måste ställas på exempelvis identifiering och signering. För denna säkerhet kan med fördel PKI, Public Key Infrastructure, användas. Det är en säkerhetsmetod som innebär att man använder privata och publika nycklar. PKI-tekniken skyddar bra mot avlyssning eftersom identifieringen bygger på att ett slumptal krypteras, och att resultatet därför ser olika ut från gång till gång.Socialtjänsten på Borlänge Kommun har påbörjat utvecklingen av en elektronisk tjänst som kommer att innebära att personer som beviljats ekonomiskt bistånd, ska kunna förnya sin ansökan via Internet. Personen i fråga ska även kunna se de uppgifter som Socialtjänsten har ifrån övriga inblandade myndigheter, samt vika utbetalningar som Socialtjänsten gjort och ska göra till personen. I och med detta exjobb kan Borlänge Kommun visa upp en prototyp som fungerar i stort sett som de vill att den skarpa tjänsten ska göraSverige är en av pionjärerna i världen att öppna förvaltningen på Internet, och Borlänge kommun har som en av de första kommunerna i Sverige startat utvecklingen av en tjänst i enlighet med "24-timmars myndigheten".

Perspective: LaGuardia Community College Newsletter (24 January 1977)

A newsletter published periodically to keep the faculty, students, staff, and community informed about the activities taking place on the campus of LaGuardia Community College. Information for PERSPECTIVE should be sent to Bob McVeigh In Room 341, Main Bldg., ext. 248, 249.