Application and use of isothermal calorimetry in pharmaceutical development

There are many steps involved in developing a drug candidate into a formulated medicine and many involve analysis of chemical interaction or physical change. Calorimetry is particularly suited to such analyses as it offers the capacity to observe and quantify both chemical and physical changes in virtually any sample. Differential scanning calorimetry (DSC) is ubiquitous in pharmaceutical development, but the related technique of isothermal calorimetry (IC) is complementary and can be used to investigate a range of processes not amenable to analysis by DSC. Typically, IC is used for longer-term stability indicating or excipient compatibility assays because both the temperature and relative humidity (RH) in the sample ampoule can be controlled. However, instrument design and configuration, such as titration, gas perfusion or ampoule-breaking (solution) calorimetry, allow quantification of more specific values, such as binding enthalpies, heats of solution and quantification of amorphous content. As ever, instrument selection, experiment design and sample preparation are critical to ensuring the relevance of any data recorded. This article reviews the use of isothermal, titration, gas-perfusion and solution calorimetry in the context of pharmaceutical development, with a focus on instrument and experimental design factors, highlighted with examples from the recent literature. © 2011 Elsevier B.V.

An investigation of environmental conditions experienced during the life of high-value wood components and products

Australian forest industries have a long history of export trade of a wide range of products from woodchips (for paper manufacturing), sandalwood (essential oils, carving and incense) to high value musical instruments, flooring and outdoor furniture. For the high value group, fluctuating environmental conditions brought on by changes in temperature and relative humidity, can lead to performance problems due to consequential swelling, shrinkage and/or distortion of the wood elements. A survey determined the types of value-added products exported, including species and dimensions packaging used and export markets. Data loggers were installed with shipments to monitor temperature and relative humidity conditions. These data were converted to timber equilibrium moisture content values to provide an indication of the environment that the wood elements would be acclimatising to. The results of the initial survey indicated that primary high value wood export products included guitars, flooring, decking and outdoor furniture. The destination markets were mainly located in the northern hemisphere, particularly the United States of America, China, Hong Kong, Europe (including the United Kingdom), Japan, Korea and the Middle East. Other regions importing Australian-made wooden articles were south-east Asia, New Zealand and South Africa. Different timber species have differing rates of swelling and shrinkage, so the types of timber were also recorded during the survey. Results from this work determined that the major species were ash-type eucalypts from south-eastern Australia (commonly referred to in the market as Tasmanian oak), jarrah from Western Australia, spotted gum, hoop pine, white cypress, black butt, brush box and Sydney blue gum from Queensland and New South Wales. The environmental conditions data indicated that microclimates in shipping containers can fluctuate extensively during shipping. Conditions at the time of manufacturing were usually between 10 and 12% equilibrium moisture content, however conditions during shipping could range from 5 (very dry) to 20% (very humid). The packaging systems incorporated were reported to be efficient at protecting the wooden articles from damage during transit. The research highlighted the potential risk for wood components to ‘move’ in response to periods of drier or more humid conditions than those at the time of manufacturing, and the importance of engineering a packaging system that can account for the environmental conditions experienced in shipping containers. Examples of potential dimensional changes in wooden components were calculated based on published unit shrinkage data for key species and the climatic data returned from the logging equipment. The information highlighted the importance of good design to account for possible timber movement during shipping. A timber movement calculator was developed to allow designers to input component species, dimensions, site of manufacture and destination, to see validate their product design.

Examining the impact of climate change on dengue transmission in the Asia-Pacific region

Dengue fever (DF) is a serious public health concern in many parts of the world. An increase in DF incidence has been observed globally over the past decades. Multiple factors including urbanisation, increased international travels and global climate change are thought to be responsible for increased DF. However, little research has been conducted in the Asia-Pacific region about the impact of these changes on dengue transmission. The overarching aim of this thesis is to explore the spatiotemporal pattern of DF transmission in the Asia-Pacific region and project the future risk of DF attributable to climate change. Annual data of DF outbreaks for sixteen countries in the Asia-Pacific region over the last fifty years were used in this study. The results show that the geographic range of DF in this region increased significantly over the study period. Thailand, Vietnam and Laos were identified as the highest risk areas and there was a southward expansion observed in the transmission pattern of DF which might have originated from Philippines or Thailand. Additionally, the detailed DF data were obtained and the space-time clustering of DF transmission was examined in Bangladesh. Monthly DF data were used for the entire country at the district level during 2000-2009. Dhaka district was identified as the most likely DF cluster in Bangladesh and several districts of the southern part of Bangladesh were identified as secondary clusters in the years 2000-2002. In order to examine the association between meteorological factors and DF transmission and to project the future risk of DF using different climate change scenarios, the climate-DF relationship was examined in Dhaka, Bangladesh. The results show that climate variability (particularly maximum temperature and relative humidity) was positively associated with DF transmission in Dhaka. The effects of climate variability were observed at a lag of four months which might help to potentially control and prevent DF outbreaks through effective vector management and community education. Based on the quantitative assessment of the climate-DF relationship, projected climate change will likely increase mosquito abundance and activity and DF in this area. Assuming a temperature increase of 3.3oC without any adaptation measures and significant changes in socio-economic conditions, the consequence will be devastating, with a projected annual increase of 16,030 cases in Dhaka, Bangladesh by the end of this century. Therefore, public health authorities need to be prepared for likely increase of DF transmission in this region. This study adds to the literature on the recent trends of DF and impacts of climate change on DF transmission. These findings may have significant public health implications for the control and prevention of DF, particularly in the Asia- Pacific region.

Pen studies on the control of cattle tick (Rhipicephalus (Boophilus) microplus) with Metarhizium anisopliae (Sorokin)

Three field trials were conducted over 12 months to assess the pathogenicity of Metarhizium anisopliae to parasitic stages of Rhipicephalus (Boophilus) microplus on dairy heifers under different environmental conditions. Two isolates were selected based on their high optimal growth temperature (30 °C), good spore production characteristics and ability to quickly kill adult engorged ticks in the laboratory. Spores were formulated in an oil emulsion and applied using a motor driven spray unit. Surface temperatures of selected animals were monitored, as were the ambient temperature and relative humidity. Unengorged ticks sampled from each animal immediately after treatment were incubated in the laboratory to assess the efficacy of the formulation and application. Egg production by engorged ticks collected in the first 3 days after treatment was monitored. Side counts of standard adult female ticks were conducted daily, before and after treatment to assess the performance of the fungus against all tick stages on the animals. In each trial the formulation rapidly caused 100% mortality in unengorged ticks that were removed from cattle and cultured in the laboratory. A significant reduction in egg production was recorded for engorged ticks collected in the 3 days post-treatment. However, there was little effect of the formulation on the survival of ticks on cattle, indicating that there is an interaction between the environment of the ticks on the cattle and the biopesticide, which reduces its efficacy against ticks.

Estudo do impacto do descarte dos comprimidos de captopril no meio ambiente

O Captopril é um dos medicamentos anti-hipertensivos mais consumidos no Brasil. Constitui-se em um pó cristalino, branco ou levemente amarelado, com leve odor característico de sulfeto, facilmente solúvel em água, etanol, clorofórmio e metanol. Em soluções aquosas, o captopril sofre reação de oxidação, formando em quantidade crescente como produto de degradação o dímero dissulfeto de captopril. Além disso, no período de 24 horas, mais de 95% da dose absorvida é eliminada pela urina, sendo 40 a 50% na forma inalterada, e o restante na forma do dímero dissulfeto de captopril e de outros metabólitos, os quais são encaminhados para o esgoto, podendo assim atingir os corpos dágua. O presente trabalho foi planejado de maneira a estudar o impacto e o comportamento do medicamento e do seu produto de degradação em águas ambientais. Para isso, foi feita a validação do método analítico escolhido, cromatografia líquida de alta eficiência, que foi a ferramenta adequada para garantir a confiabilidade dos dados analíticos do método. Foi monitorada também a estabilidade do fármaco na forma de comprimidos e em solução aquosa, ao longo de 144 dias. Os resultados mostraram que quando os comprimidos de captopril são armazenados em sua embalagem original, nesse caso blister, a uma temperatura controlada igual a 40o C e umidade controlada igual a 75 %, eles permaneceram estáveis. A concentração de captopril apresentou uma média igual a 97,4 %. Por outro lado, quando diluído e armazenado nas mesmas condições de temperatura e umidade citadas anteriormente para a obtenção de uma solução aquosa na concentração igual a 1 mg/mL, a substância captopril chegou a variar de 95,7% a 68,5%. Já o seu produto de degradação, dissulfeto de captopril, atingiu um aumento na concentração de 1,7 para 31,1%, ambos em 144 dias

Energy retrofits in social housing. Analysis of its thermal behaviour.

468 p.

Toxigenic molds on fish feeds-1: impact of climatic change

The present communication is a survey report carried out to assess the incidence of toxic mycoflora on seven types of agriculture products/by products incorporated during fish culture as supplementary dietary items. Samples were obtained from various sources at Darbhanga, Madhubani and Samashtipur districts during summer, winter and monsoon months. Out of the total 1774 samples, only 894 appeared to be fresh visually reflecting average incidence of contamination around 46.6%. However, the apparently fresh samples, when subjected to culture, 26.9% of them were found to be contaminated. Thus, degree of fungal spoilage in feed ingredients in parts of north Bihar appears to be significantly high (73.5%). The present study illustrates the facts with special reference to Aspergillus flavus, A. parasiticus (elaborating aflatoxins) A. ochraceous, Penicilium viradicatuin (elaborating ochratoxins) and A. versicolor (elaborating sterigmatocystin). The other strains already known for their toxigenic potentials that appeared on the present substrates included A. niger, A. fumigatus, A. candidus, P. islandicum, Rhizopus spp. and Mucur spp. Studies indicate that the prevalent climatic factors like temperature and relative humidity facilitate a congenial condition almost all through the year and in particular during summer and monsoon months. But water content of the substrates is a vital factor that further accelerates the pace of mycobial spoilage. A thorough sun-drying of the agricultural commodities before prolonged storage to bring water content below the "low risk limit" may significantly reduce the incidence of molds.

Production of quality dried small indigenous fish species products using low cost solar tunnel drier

A low cost solar drier was constructed using locally available materials. The size of the drier was 20x3.6x3 having drying capacity of 80 kg of SIS (w/w). Optimization of moisture content was observed for mola, dhela, chapila, chanda and puti at temperature ranges between 40-45°C and 50-55°C in solar tunnel drier. There was little or no change in moisture content at temperature below 40°C during the first 3 hours. Then the moisture content declined gradually with the increase of drying period. On the other hand, at temperature between 50-55°C, moisture content started to decline after 2 hours of drying. The moisture content of the sample reached at about 16% after 26 hours of sun drying at 40-45°C and 20 hours at 50-55°C. The optimum temperature for producing high quality dried products was 45-50°C in solar tunnel drier. The temperature and relative humidity outside and inside the dryers (with fish) at various locations were recorded from 8.00am to 4.00pm. The normal atmospheric ambient temperature was recorded in the range of 25-37°C from at 8:00am to 4:00pm. During the same period the atmospheric relative humidity recorded was in the range of 30-58%. On the other hand, the maximum temperature inside the dryers was recorded in the range of 28-65°C. The lowest temperature recorded was 28°C in the morning and at 13.00pm the highest temperature 65°C was recorded. The maximum relative humidity 58% found in the afternoon and minimum of 28% at noon. There was inverse relationship between temperature intensity of sunshine and humidity which decreased as sunshine increased. In total, it took around 26 hours of drying to reduce the moisture level to about 16%.

Severidade de mancha de alternaria em genótipos de girassol no Cerrado do Distrito Federal.

RESUMO: Este trabalho teve como objetivo comparar a severidade da mancha de Alternaria de genótipos de girassol em ambientes do Cerrado do Distrito Federal. Três experimentos foram avaliados, dois na Embrapa Cerrados (Planaltina, DF) e um localizado na Embrapa Produtos e Mercado (Recanto das Emas, DF). Foram feitas análises ao longo do ciclo da cultura com um intervalo de 15 dias, sendo a primeira aos 35 dias após emergência. Cada planta foi analisada em três partes: terço inferior, terço médio e terço superior. Ao final de cada experimento, a área abaixo da curva de progresso da doença (AACPD) foi calculada para cada genótipo. De acordo com os resultados observados, o ambiente de sequeiro na Embrapa Cerrados, que deteve a maior média da severidade da doença, entre os ambientes avaliados. Dentre os genótipos avaliados, MG 360 mostrou menor severidade da doença no sequeiro e AGUARA 06 no irrigado da Embrapa Cerrados. O genótipo BSG 42 na Embrapa Produtos e Mercado, se destacou pela menor severidade do fungo. Houve influência significativa do ambiente nos resultados de severidade da doença, que está estreitamente relacionada com os fatores climáticos como temperatura e umidade relativa do ar. A compreensão dessas condições favoráveis ao desenvolvimento do fungo é essencial quando se avalia a resistência em genótipos de girassol. ABSTRACT: This study had the purpose of comparing the severity of Alternaria leaf spot on genotypes of sunflower in the Brazilian Cerrado. Three field trials were established, two at Embrapa Cerrados (Planaltina, DF) and one at Embrapa Produtos e Mercados (Recanto das Emas, DF). Evaluations were made during the crop cycle every 15 days, the first one happening 35 days after crop emergency. Each plant was analyzed in three parts: lower, middle and upper thirds. At the end of each trial the average area under the disease progress curve (AUDPC), for each third, was calculated for all genotypes. According to the observed results, the dryland environment at Embrapa Cerrados had the highest mean disease severity, among the studied environments. Between the evaluated genotypes, MG360 showed less severity in dryland and AGUARA 06 in the irrigated environment at Embrapa Cerrados. At Embrapa Produtos e Mercado the genotype that presented the best performance was BRS G42. Environmental conditions deeply affected the trials, mainly temperature and relative humidity. Their influence on Alternaria leaf spot epidemics in the Cerrado region must be studied in more detail, to avoid misinterpreting data when evaluating sunflower genotypes for resistance to this important fungal disease.

Effectiveness of in situ moisture preconditioning methods for concrete

With greater emphasis now being placed on the durability of concrete and the need for on-site characterization of concrete for durability, there is an increasing dependence on the measurement of the permeation properties of concrete. Such properties can be measured in the laboratory under controlled ambient conditions, namely, temperature and relative humidity, and comparisons made between samples not affected by testing conditions. An important factor that influences permeation measurements is the moisture state of the concrete prior to testing. Moisture gradients are known to exist in exposed concretes; therefore, all laboratory tests are generally carried out after preconditioning to a reference moisture state. This is reasonably easy to achieve in the laboratory, but more difficult to carry out on-site. Different methods of surface preconditioning in situ concrete are available; however, there is no general agreement on the suitability of any one method. Therefore, a comprehensive set of experiments was carried out with four different preconditioning methods. Results from these investigations indicated that only superficial drying could be achieved by using any of the preconditioning methods investigated and that significant moisture movement below a depth of 15 mm was not evident.

Revestimentos compatíveis para alvenarias antigas sujeitas a ação severa da água

Uma das maiores causas de degradação dos revestimentos é a presença de sais solúveis, tanto nas zonas costeiras como nas zonas continentais. Estes sais podem ter origens distintas, tais como: humidade ascensional, nevoeiro salino, inundações ou ainda estarem presentes nos próprios materiais, como é o caso da utilização de areias mal lavadas. O local onde os sais cristalizam é dependente do tipo de transporte entre a alvenaria e o revestimento, assim como da severidade da envolvente ambiental (temperatura e humidade relativa). Com esta tese pretende-se desenvolver revestimentos de substituição compatíveis, eficazes e duráveis para alvenarias antigas sujeitas à ação severa da água (humidade ascensional através das fundações com elevada concentração de NaCl); desenvolver ensaios de envelhecimento acelerado baseados em ciclos de dissolução e cristalização que permitam simular a ação severa da água; perceber a influência de revestimentos com caraterísticas extremas de permeabilidade ao vapor de água aplicados nas duas faces do mesmo suporte (argamassas de cimento e resina versus argamassas de cal), e sujeitos à ação severa da água; perceber a influência de vários fatores, tais como : rasgos verticais contínuos executados no emboço e a utilização de hidrófugo no reboco no desempenho dos vários sistemas de revestimento desenvolvidos, quando sujeitos à ação severa da água;; utilizar a remoção eletrocinética de sais, em provetes simulando a influência da alvenaria e dos revestimentos, com o objetivo de reduzir a sua concentração de NaCl, para que no futuro possa ser aplicado de forma eficaz em paredes de edifícios antigos, enquanto ação de manutenção, e desta forma aumentar a durabilidade dos revestimentos. Para atingir os objetivos descritos, foram considerados: i) o desenvolvimento de provetes que permitam considerar os sistemas de revestimento desenvolvidos nesta tese e o suporte, e que simulem uma alvenaria revestida em ambas as faces, e com os quais seja possível a simulação da ação severa da água em laboratório e, ii) o desenvolvimento ciclos de dissolução e cristalização numa parede de grandes dimensões existente em laboratório, que permitam simular a ação severa da água em condições tão reais quanto possível. O objetivo final deste estudo é o desenvolvimento de um revestimento de substituição denominado “emboço ventilado” para paredes de edifícios antigos com revestimentos degradados devido à presença de humidade ascensional e sais solúveis. Pretende-se que este sistema de revestimento, composto por duas camadas de revestimento (camada base e reboco), seja compatível, durável e eficaz, e que funcione como um sistema de acumulação no qual os sais cristalizem na camada base do sistema de revestimento (executada com rasgos verticais) e não na alvenaria ou na camada exterior.

In vitro spore germination of Polystichum drepanum, a threatened fern from Madeira Island

Polystichum drepanum (Sw) C. Presl is a threatened fern endemic to a few forest areas in the north-west of Madeira Island. The aims of this work were to establish suitable culture conditions for in vitro germination of spores, and to evaluate short-term storage conditions for P drepanum spores. The highest frequency of germination was obtained in Murishage and Skoog (MS) liquid medium, without agitation. However, gametophytes maintained in MS liquid medium did not grow and, after 4 weeks, became anoxic and died. Thus, after germination in liquid medium, gametophytes were transferred to an MS double-phase culture system for further growth. The effects of storage period, temperature, and relative humidity during storage on in vitro spore germination were studied. Spore viability was assessed after 2, 4 and 6 months, and high viability (> 94%) was observed in all the assays. However, germination capability decreased with increased storage periods. The number of sporophytes obtained also decreased with prolonged storage periods. The results indicate that spores of R drepanum stored for 4 months at 21 degrees C maintain high viability and high germination frequency. ne sporophytes obtained were acclimatised in a mixture of peat and vermiculite [2:1 (v/v)] under high relative humidity (90-95%). Seventy-five sporophytes were successfully acclimatised to ex vitro conditions and showed active growth in the glasshouse.

Estudo da redução de consumos energéticos de uma Piscina Municipal

As cada vez mais importantes questões ambientais levam à imprescindibilidade da eficiência energética, sendo que esta tem cada vez mais importância a nível mundial. Deste modo, a eficiência energética, quer por uma obrigação legal (devido aos níveis de consumo) quer por questões de estatuto no mercado (imagem de uma empresa amiga do ambiente), está bem presente no mundo industrial. Portugal apresenta, no que diz respeito à situação energética, uma forte dependência externa, acima dos 70 %. Em 2012, informação disponível pela Direção Geral de Energia e Geologia (DGEG), o consumo total de energia primária era de 21.482 ktep e mais de 55 % desse consumo era proveniente de origem fóssil. Os setores que apresentam maiores consumos de eletricidade por setor de atividade são a Indústria e o setor de Serviços, onde estão presentes os edifícios com consumos perto dos 33 %. De forma a promover a eficiência energética e implementar a utilização racional de energia foram criados programas, estratégias e legislação que permitiram incentivar a diminuição dos consumos de energia nos edifícios de serviço. Uma das metodologias implementadas passa pela gestão de energia, ou seja, para atuar é necessário conhecer os fluxos de energia de um edifício. As auditorias energéticas permitem realizar um levantamento e análise desses mesmos fluxos, com o desígnio de identificar oportunidades de racionalização de consumo de energia. Nesta dissertação foi realizado um estudo da redução de consumos energéticos de uma piscina municipal baseado em dados de uma auditoria energética. Através da auditoria foi possível obter um resultado do exame energético, caracterizar o perfil real de utilização da energia elétrica e caracterizar os equipamentos dos consumidores energéticos instalados. Também permitiu realizar um levantamento térmico, de forma conhecer as temperaturas e a humidade relativa do edifício. Por fim, são apresentadas cinco medidas e algumas recomendações de eficiência energética, que permitem uma redução do consumo anual à instalação de cerca de 20%. Procedeu-se, também, a uma análise dos dados obtidos na auditoria, de forma a identificar algumas oportunidades de racionalização de energia.

X-ray diffraction of a gram-negative bacterial membrane mimetic

This thesis applies x-ray diffraction to measure he membrane structure of lipopolysaccharides and to develop a better model of a LPS bacterial melilbrane that can be used for biophysical research on antibiotics that attack cell membranes. \iVe ha'e Inodified the Physics department x-ray machine for use 3.'3 a thin film diffractometer, and have lesigned a new temperature and relative humidity controlled sample cell.\Ve tested the sample eel: by measuring the one-dimensional electron density profiles of bilayers of pope with 0%, 1%, 1G :VcJ, and 100% by weight lipo-polysaccharide from Pse'udo'lTwna aeTuginosa. Background VVe now know that traditional p,ntibiotics ,I,re losing their effectiveness against ever-evolving bacteria. This is because traditional antibiotic: work against specific targets within the bacterial cell, and with genetic mutations over time, themtibiotic no longer works. One possible solution are antimicrobial peptides. These are short proteins that are part of the immune systems of many animals, and some of them attack bacteria directly at the membrane of the cell, causing the bacterium to rupture and die. Since the membranes of most bacteria share common structural features, and these featuret, are unlikely to evolve very much, these peptides should effectively kill many types of bacteria wi Lhout much evolved resistance. But why do these peptides kill bacterial cel: '3 , but not the cells of the host animal? For gramnegative bacteria, the most likely reason is that t Ileir outer membrane is made of lipopolysaccharides (LPS), which is very different from an animal :;ell membrane. Up to now, what we knovv about how these peptides work was likely done with r !10spholipid models of animal cell membranes, and not with the more complex lipopolysa,echaricies, If we want to make better pepticies, ones that we can use to fight all types of infection, we need a more accurate molecular picture of how they \vork. This will hopefully be one step forward to the ( esign of better treatments for bacterial infections.

Representation of model error in a convective-scale ensemble prediction system

In this paper ensembles of forecasts (of up to six hours) are studied from a convection-permitting model with a representation of model error due to unresolved processes. The ensemble prediction system (EPS) used is an experimental convection-permitting version of the UK Met Office’s 24- member Global and Regional Ensemble Prediction System (MOGREPS). The method of representing model error variability, which perturbs parameters within the model’s parameterisation schemes, has been modified and we investigate the impact of applying this scheme in different ways. These are: a control ensemble where all ensemble members have the same parameter values; an ensemble where the parameters are different between members, but fixed in time; and ensembles where the parameters are updated randomly every 30 or 60 min. The choice of parameters and their ranges of variability have been determined from expert opinion and parameter sensitivity tests. A case of frontal rain over the southern UK has been chosen, which has a multi-banded rainfall structure. The consequences of including model error variability in the case studied are mixed and are summarised as follows. The multiple banding, evident in the radar, is not captured for any single member. However, the single band is positioned in some members where a secondary band is present in the radar. This is found for all ensembles studied. Adding model error variability with fixed parameters in time does increase the ensemble spread for near-surface variables like wind and temperature, but can actually decrease the spread of the rainfall. Perturbing the parameters periodically throughout the forecast does not further increase the spread and exhibits “jumpiness” in the spread at times when the parameters are perturbed. Adding model error variability gives an improvement in forecast skill after the first 2–3 h of the forecast for near-surface temperature and relative humidity. For precipitation skill scores, adding model error variability has the effect of improving the skill in the first 1–2 h of the forecast, but then of reducing the skill after that. Complementary experiments were performed where the only difference between members was the set of parameter values (i.e. no initial condition variability). The resulting spread was found to be significantly less than the spread from initial condition variability alone.