Nd/Ca ratios in plankton-towed and core top foraminifera

Planktic foraminifera have been used as recorders of the neodymium (Nd) isotopic composition of seawater, although there is still controversy over the precise provenance of the Nd signal. We present an extensive, multispecific plankton tow Nd/Ca data set from several geographic locations (SE Atlantic, NE Atlantic, Norwegian Sea, and western Mediterranean), together with core top samples from the Mediterranean region. The range of Nd/Ca ratios in plankton-towed foraminifera, cleaned only of organic material, from all regions (0.01-0.7 µmol/mol), is similar to previously published analyses of sedimentary foraminifera cleaned using both oxidative and reductive steps, with distribution coefficients (Kd) ranging between 4 and 302. For the Mediterranean, where core top and plankton tow data are both available, the range for plankton tows (0.05-0.7 µmol/mol) is essentially identical to that for the core tops (0.1-0.5 µmol/mol). Readsorption of Nd during cleaning is ruled out by the fact that the plankton tow samples underwent only an oxidative cleaning process. We find a relationship between manganese (Mn) and Nd in plankton tow samples that is mirrored by a similar correlation in core top samples. This relationship suggests that Fe-Mn coatings are of negligible importance to the Nd budgets of foraminifera as the Nd/Mn ratio it implies is over an order of magnitude greater than that seen in other Fe-Mn oxide phases. Rather, since both plankton tows and core tops present a similar behavior, the Nd/Mn relationship must originate in the upper water column. The data are consistent with the acquisition of Nd and Mn from the water column by binding to organic material and the fact that intratest organic material is shielded from both aggressive cleaning and diagenetic processes. Collectively, the results help to explain two abiding puzzles about Nd in sedimentary planktic foraminifera: their high REE contents and the fact that they record a surface water Nd isotopic signal, regardless of the cleaning procedure used.

Boron isotope and B/Ca ratios of planktonic foraminifera

Here a new analytical methodology is described for measuring the isotopic composition of boron in foraminifera using multicollector inductively coupled plasma mass spectrometry (MC-ICPMS). This new approach is fast (~10 samples analysed in duplicate per analytical session) and accurate (to better than 0.25 per mil at 95% confidence) with acceptable sample size requirements (1-3 mg of carbonate). A core top calibration of several common planktic and two benthic species from geographically widespread localities shows a very close agreement between the isotopic composition measured by MC-ICPMS and the isotopic composition of B(OH)-4 in seawater (as predicted using the recently measured isotopic equilibrium factor of 1.0272) at the depth of habitat. A down core and core top investigation of boron concentration (B/Ca ratio) shows that the partition coefficient is influenced by [CO2-3] complicating the application of this proxy. Nevertheless, it is demonstrated that these two proxies can be used to fully constrain the carbonate system of surface water in the Caribbean Sea (ODP Site 999A) over the last 130 kyr. This reconstruction shows that during much of the Holocene and the last interglacial period surface water at Site 999A was in equilibrium with the atmosphere with respect to CO2. During the intervening colder periods although the surface water pCO2 was lower than the Holocene, it was a minor to significant source of CO2 to the atmosphere possibly due to either an expansion of the eastern equatorial Atlantic upwelling zone, or a more local expansion of coastal upwelling in the southern Caribbean. Such reorganisation of the oceanic carbonate system in favour of a larger source of CO2 to the atmosphere from the equatorial ocean may require mechanisms responsible for lowering atmospheric CO2 during glacial periods to be more efficient than previously supposed.

Acceptance of relapse fears in breast cancer patients: effects of an act-based abridged intervention

Objective: Relapse fear is a common psychological scar in cancer survivors. The aim of this study is to assess the effects of an abridged version of Acceptance and Commitment Therapy (ACT) in breast cancer patients.Method: An open trial was developed with 12 non-metastatic breast cancer patients assigned to 2 conditions, ACT and waiting list. Interventions were applied in just one session and focused on the acceptance of relapse fears through a ‘defusion’ exercise. Interference and intensity of fear measured through subjective scales were collected after each intervention and again 3 months later. Distress, hypochondria and ‘anxious preocupation’ were also evaluated through standardized questionnaires.Results: The analysis revealed that ‘defusion’ contributed to decrease the interference of the fear of recurrence, and these changes were maintained three months after intervention in most subjects. 87% of participants showed clinically significant decreases in interference at follow-up sessions whereas no patient in the waiting list showed such changes. Statistical analysis revealed that the changes in interference were significant when comparing pre, post and follow-up treatment, and also when comparing ACT and waiting list groups. Changes in intensity of fear, distress, anxious preoccupation and hypochondria were also observed.Conclusions: Exposure through ‘defusion’ techniques might be considered a useful option for treatment of persistent fears in cancer patients. This study provides evidence for therapies focusing on psychological acceptance in cancer patients through short, simple and feasible therapeutic methods.

Differential susceptibility of mitochondrial complex II to inhibition by oxaloacetate in brain and heart

Mitochondrial Complex II is a key mitochondrial enzyme connecting the tricarboxylic acid (TCA) cycle and the electron transport chain. Studies of complex II are clinically important since new roles for this enzyme have recently emerged in cell signalling, cancer biology, immune response and neurodegeneration. Oxaloacetate (OAA) is an intermediate of the TCA cycle and at the same time is an inhibitor of complex II with high affinity (Kd ~ 10− 8 M). Whether or not OAA inhibition of complex II is a physiologically relevant process is a significant, but still controversial topic. We found that complex II from mouse heart and brain tissue has similar affinity to OAA and that only a fraction of the enzyme in isolated mitochondrial membranes (30.2 ± 6.0% and 56.4 ± 5.6% in the heart and brain, respectively) is in the free, active form. Since OAA could bind to complex II during isolation, we established a novel approach to deplete OAA in the homogenates at the early stages of isolation. In heart, this treatment significantly increased the fraction of free enzyme, indicating that OAA binds to complex II during isolation. In brain the OAA-depleting system did not significantly change the amount of free enzyme, indicating that a large fraction of complex II is already in the OAA-bound inactive form. Furthermore, short-term ischemia resulted in a dramatic decline of OAA in tissues, but it did not change the amount of free complex II. Our data show that in brain OAA is an endogenous effector of complex II, potentially capable of modulating the activity of the enzyme.

Role of Vascular Smooth Muscle Cell PiT-2 in Basal Ganglia Calcification

Thesis (Master's)--University of Washington, 2016-08

There exists circularity between WACC and value? Another solution.

Although we know there exists a simple approach to solve the circularity between value and the discount rate, known as the Adjusted Present Value proposed by Myers, 1974, it seems that practitioners still rely on the traditional Weighted Average Cost of Capital, WACC approach of weighting the cost of debt, Kd and the cost of equity, Ke and discounting the Free Cash Flow, FCF. We show how to solve circularity when calculating value with the free cash flow, FCF and the WACC. As a result of the solution we arrive at a known solution when we assume the discount rate of the tax equity: the capital cash flow, CCF discounted at Ku. When assuming Kd as the discount rate for the tax savings, we find an expression for calculating value that does not implies circularity. We do this for a single period and for N periods.

Kaivinkonekuoppa-aineistot osana ydinjätteen loppusijoituksen pitkäaikaisturvallisuutta, OL-KK25 ja 26 koekuoppien maaperän geokemialliset ja fysikaaliset ominaisuudet

Käytetyn ydinpolttoaineen loppusijoitus Olkiluodon kallioperään edellyttää kattavaa turvallisuusarviointia. Turvallisuusarviointi koostuu monista osista, joista yksi on biosfääriarviointi. Sen tavoitteena on selvittää mahdollisten säteilyannosten määriä ihmisille ja muulle luonnolle. Annosarvioinnin edellytyksenä on tuntea Olkiluodon paikalliset olosuhteet ja mahdolliset kehityskulut. Yksi keskeinen osa biosfääriarviointia on mallintaa radionuklidien kulkeutumista kallioperästä maanpinnalle. Kulkeutumisen kannalta on olennaista tuntea maaperän ominaisuudet, koska maaperä toimii rajapintana kallioperän ja elävän luonnon välillä. Tässä tutkimuksessa selvitettiin Olkiluodon saarelle tehtyjen koekuoppien OL-KK25-26 maaperän geokemiallisia ja fysikaalisia ominaisuuksia sekä alkuaineiden in situ jakaantumiskertoimia (Kd). Jakaantumiskertoimilla selvitetään alkuaineiden ja radionuklidien liikkuvuutta erilaisissa ympäristöissä. Tässä tutkimuksessa keskityttiin käytetystä ydinpolttoaineesta löytyviin analogisiin alkuaineisiin (Ag, Cl, Cs, I, Mo, Nb, Ni, Pb, Se, Sn ja Sr), jotka ovat turvallisuusarvioinnin kannalta kaikkein tärkeimpiä. Kd – arvot laskettiin alkuaineiden konsentraatioista, jotka mitattiin maanäytteistä kahdella erilaisella uuttomenetelmällä. Heikkoliukoisten ja kasvien saatavilla olevien alkuaineiden konsentraatiot määritettiin NH4Ac (pH 4,5) uutolla ja kokonaispitoisuudet HNO3-HF uutolla sekä LiBO2- fuusiolla. Lisäksi näytteistä maaritettiin maalajit ja niiden raekokojakaumat, orgaaninen aines (LOI), pH, liuennut orgaaninen ja epäorgaanin hiili, pääanionit, mineraalikoostumus, kationinvaihtokapasiteetti (CEC) sekä emäskylläisyys (BS). Koekuopista määritetyile Kd – arvoille ja muille muuttujille tehtiin lopuksi korrelaatioanalyysit, joilla pyrittiin löytämään alkuaineiden liikkuvuuteen eniten vaikuttavia tekijöitä. Maaperää Olkiluodossa voidaan pitää hyvin heterogeenisenä, koska hyvin lähellä toisiian sijainneissa koekuopissa niin maalajit kuin muut ominaisuudet vaihtelivat runsaasti. Myös ominaisuudet eri maakerroksissa vaihtelivat merkittävästi. Alkuaineiden konsentraatioiden sekä Kd - arvojen muutokset olivat voimakkaasti yhteydessä maalajityyppeihin. Merkittävimmin Kd - arvoihin vaikuttivat mineraalikoostumus, savipitoisuus ja raekoko. Muita konsentraatioihin ja jakaantumiskertoimiin vaikuttavia muuttujia olivat orgaanisen aineksen määrä sekä pH. Lisäksi tietyillä, luonnossa pääasiassa anionisilla, alkuaineilla korrelaatiot olivat heikompia tai päinvastaisia kuin muilla aineilla. Tutkimuksen tulokset lisäävät ymmärrystä maaperän ominaisuuksien ja alkuaineiden liikkuvuuden riippuvuuksista. Tuntemalla maaperän ominaisuudet ja alkuaineiden Kd - arvot sekä niiden väliset riippuvuudet, voidaan radionuklidien kulkeutumista kallioperästä maanpinnalle arvioida entistä luotettavammin. Tutkimuksessa tuotettuja tuloksia ja aineistoja hyödynnetään myös pintaympäristön ekosysteemien ja maaperän mallinnuksissa.

Proyecto de inversión para la instalación de una planta procesadora de frutas en el distrito de Motupe

Tesis de pregrado

Purificação, modelagem e simulação da adsorção de bioprodutos por troca iônica em coluna de leito expandido

A produção de proteínas através de microrganismos tornou-se uma técnica muito importante na obtenção de compostos de interesse da indústria farmacêutica e alimentícia. Extratos brutos nos quais as proteínas são obtidas são geralmente complexos, contendo sólidos e células em suspensão. Usualmente, para uso industrial destes compostos, é necessário obtê-los puros, para garantir a sua atuação sem interferência. Um método que vem recebendo destaque especialmente nos últimos 10 anos é o uso da cromatografia de troca iônica em leito expandido, que combina em uma única etapa os passos de clarificação, concentração e purificação da molécula alvo, reduzindo assim o tempo de operação e também os custos com equipamentos para realização de cada etapa em separado. Combinado a este fato, a última década também é marcada por trabalhos que tratam da modelagem matemática do processo de adsorção de proteínas em resinas. Está técnica, além de fornecer informações importantes sobre o processo de adsorção, também é de grande valia na otimização da etapa de adsorção, uma vez que permite que simulações sejam feitas, sem a necessidade de gasto de tempo e material com experimentos em bancada, especialmente se é desejado uma ampliação de escala. Dessa forma, o objetivo desta tese foi realizar a modelagem e simulação do processo de adsorção de bioprodutos em um caldo bruto na presença de células, usando inulinase e C-ficocianina como objeto de estudo e purificar C-ficocianina utilizando resina de troca iônica em leito expandido. A presente tese foi então dividida em quatro artigos. O primeiro artigo teve como objeto de estudo a enzima inulinase, e a otimização da etapa de adsorção desta enzima em resina de troca iônica Streamline SP, em leito expandido, foi feita através da modelagem matemática e simulação das curvas de ruptura em três diferentes graus de expansão (GE). As máximas eficiências foram observadas quando utilizadas maiores concentrações de inulinase (120 a 170 U/mL), e altura de leito entre 20 e 30 cm. O grau de expansão de 3,0 vezes foi considerado o melhor, uma vez que a produtividade foi consideravelmente superior. O segundo artigo apresenta o estudo das condições de adsorção de C-ficocianina em resina de troca iônica, onde foi verificado o efeito do pH e temperatura na adsorção e após construída a isoterma de adsorção. A isoterma de adsorção da C-ficocianina em resina Streamline Q XL feita em pH 7,5 e a 25°C (ambiente), apresentou um bom ajuste ao modelo de Langmuir (R=0,98) e os valores qm (capacidade máxima de adsorção) e Kd (constante de equilíbrio) estimados pela equação linearizada da isoterma, foram de 26,7 mg/mL e 0,067mg/mL. O terceiro artigo aborda a modelagem do processo de adsorção de extrato não clarificado de C-ficocianina em resina de troca iônica Streamline Q XL em coluna de leito expandido. Três curvas de ruptura foram feitas em diferentes graus de expansão (2,0, 2,5 e 3,0). A condição de adsorção de extrato bruto não clarificado de C-ficocianina que se mostrou mais vantajosa, por apresentar maior capacidade de adsorção, é quando se alimenta o extrato até atingir 10% de saturação da resina, em grau de expansão 2,0, com uma altura inicial de leito de 30 cm. O último artigo originado nesta tese foi sobre a purificação de C-ficocianina através da cromatografia de troca iônica em leito expandido. Uma vez que a adsorção já havia sido estudada no artigo 2, o artigo 4 enfoca na otimização das condições de eluição, visando obter um produto com máxima pureza e recuperação. A pureza é dada pela razão entre a absorbância a 620 nm pela absorbância a 280 nm, e dizse que quando C-ficocianina apresenta pureza superior a 0,7 ela pode ser usada em como corante em alimentos. A avaliação das curvas de contorno indicou que a faixa de trabalho deve ser em pH ao redor de 6,5 e volumes de eluição próximos a 150 mL. Tais condições combinadas a uma etapa de pré-eluição com 0,1M de NaCl, permitiu obter C-ficocianina com pureza de 2,9, concentração 3 mg/mL, e recuperação ao redor de 70%.

Case-Based Reasoning as a Heuristic Selector in a Hyper-Heuristic for Course Timetabling Problems

This paper studies Knowledge Discovery (KD) using Tabu Search and Hill Climbing within Case-Based Reasoning (CBR) as a hyper-heuristic method for course timetabling problems. The aim of the hyper-heuristic is to choose the best heuristic(s) for given timetabling problems according to the knowledge stored in the case base. KD in CBR is a 2-stage iterative process on both case representation and the case base. Experimental results are analysed and related research issues for future work are discussed.

English syllable confusion and imitation in Korean bilingual and monolingual children and adults

In the present study, Korean-English bilingual (KEB) and Korean monolingual (KM) children, between the ages of 8 and 13 years, and KEB adults, ages 18 and older, were examined with one speech perception task, called the Nonsense Syllable Confusion Matrix (NSCM) task (Allen, 2005), and two production tasks, called the Nonsense Syllable Imitation Task (NSIT) and the Nonword Repetition Task (NRT; Dollaghan & Campbell, 1998). The present study examined (a) which English sounds on the NSCM task were identified less well, presumably due to interference from Korean phonology, in bilinguals learning English as a second language (L2) and in monolinguals learning English as a foreign language (FL); (b) which English phonemes on the NSIT were more challenging for bilinguals and monolinguals to produce; (c) whether perception on the NSCM task is related to production on the NSIT, or phonological awareness, as measured by the NRT; and (d) whether perception and production differ in three age-language status groups (i.e., KEB children, KEB adults, and KM children) and in three proficiency subgroups of KEB children (i.e., English-dominant, ED; balanced, BAL; and Korean-dominant, KD). In order to determine English proficiency in each group, language samples were extensively and rigorously analyzed, using software, called Systematic Analysis of Language Transcripts (SALT). Length of samples in complete and intelligible utterances, number of different and total words (NDW and NTW, respectively), speech rate in words per minute (WPM), and number of grammatical errors, mazes, and abandoned utterances were measured and compared among the three initial groups and the three proficiency subgroups. Results of the language sample analysis (LSA) showed significant group differences only between the KEBs and the KM children, but not between the KEB children and adults. Nonetheless, compared to normative means (from a sample length- and age-matched database provided by SALT), the KEB adult group and the KD subgroup produced English at significantly slower speech rates than expected for monolingual, English-speaking counterparts. Two existing models of bilingual speech perception and production—the Speech Learning Model or SLM (Flege, 1987, 1992) and the Perceptual Assimilation Model or PAM (Best, McRoberts, & Sithole, 1988; Best, McRoberts, & Goodell, 2001)—were considered to see if they could account for the perceptual and production patterns evident in the present study. The selected English sounds for stimuli in the NSCM task and the NSIT were 10 consonants, /p, b, k, g, f, θ, s, z, ʧ, ʤ/, and 3 vowels /I, ɛ, æ/, which were used to create 30 nonsense syllables in a consonant-vowel structure. Based on phonetic or phonemic differences between the two languages, English sounds were categorized either as familiar sounds—namely, English sounds that are similar, but not identical, to L1 Korean, including /p, k, s, ʧ, ɛ/—or unfamiliar sounds—namely, English sounds that are new to L1, including /b, g, f, θ, z, ʤ, I, æ/. The results of the NSCM task showed that (a) consonants were perceived correctly more often than vowels, (b) familiar sounds were perceived correctly more often than unfamiliar ones, and (c) familiar consonants were perceived correctly more often than unfamiliar ones across the three age-language status groups and across the three proficiency subgroups; and (d) the KEB children perceived correctly more often than the KEB adults, the KEB children and adults perceived correctly more often than the KM children, and the ED and BAL subgroups perceived correctly more often than the KD subgroup. The results of the NSIT showed (a) consonants were produced more accurately than vowels, and (b) familiar sounds were produced more accurately than unfamiliar ones, across the three age-language status groups. Also, (c) familiar consonants were produced more accurately than unfamiliar ones in the KEB and KM child groups, and (d) unfamiliar vowels were produced more accurately than a familiar one in the KEB child group, but the reverse was true in the KEB adult and KM child groups. The KEB children produced sounds correctly significantly more often than the KM children and the KEB adults, though the percent correct differences were smaller than for perception. Production differences were not found among the three proficiency subgroups. Perception on the NSCM task was compared to production on the NSIT and NRT. Weak positive correlations were found between perception and production (NSIT) for unfamiliar consonants and sounds, whereas a weak negative correlation was found for unfamiliar vowels. Several correlations were significant for perceptual performance on the NSCM task and overall production performance on the NRT: for unfamiliar consonants, unfamiliar vowels, unfamiliar sounds, consonants, vowels, and overall performance on the NSCM task. Nonetheless, no significant correlation was found between production on the NSIT and NRT. Evidently these are two very different production tasks, where immediate imitation of single syllables on the NSIT results in high performance for all groups. Findings of the present study suggest that (a) perception and production of L2 consonants differ from those of vowels; (b) perception and production of L2 sounds involve an interaction of sound type and familiarity; (c) a weak relation exists between perception and production performance for unfamiliar sounds; and (d) L2 experience generally predicts perceptual and production performance. The present study yields several conclusions. The first is that familiarity of sounds is an important influence on L2 learning, as claimed by both SLM and PAM. In the present study, familiar sounds were perceived and produced correctly more often than unfamiliar ones in most cases, in keeping with PAM, though experienced L2 learners (i.e., the KEB children) produced unfamiliar vowels better than familiar ones, in keeping with SLM. Nonetheless, the second conclusion is that neither SLM nor PAM consistently and thoroughly explains the results of the present study. This is because both theories assume that the influence of L1 on the perception of L2 consonants and vowels works in the same way as for production of them. The third and fourth conclusions are two proposed arguments: that perception and production of consonants are different than for vowels, and that sound type interacts with familiarity and L2 experience. These two arguments can best explain the current findings. These findings may help us to develop educational curricula for bilingual individuals listening to and articulating English. Further, the extensive analysis of spontaneous speech in the present study should contribute to the specification of parameters for normal language development and function in Korean-English bilingual children and adults.

Purificação de C-ficocianina e sua incorporação em nanofibras

C-ficocianina (C-FC) é uma ficobiliproteína, de cor natural azul, com diversas aplicações na indústria alimentícia, farmacêutica e biomédica, dependendo do seu grau específico de pureza, que pode variar de 0,7 a 4,0, com respectivo aumento de seu valor comercial. Essa pureza é alcançada através de diversas técnicas de purificação, que podem ser aplicadas em diferentes sequências. Um destes processos de purificação de proteínas baseia-se na cromatografia de troca iônica, que utiliza trocadores que adsorvem as proteínas como resultado de interações iônicas entre a superfície da proteína e o trocador. Resinas e colunas de leito expandido podem ser utilizadas para aumentar a produtividade dessa técnica. É fundamental conhecer o perfil do processo de adsorção, para melhor aplicá-lo como ferramenta para o design e otimização de parâmetros operacionais. Outra tecnologia para o tratamento de biomoléculas é a ultrafiltração. Esta técnica é aplicável em larga escala, apresenta baixa complexidade de aplicação e pode ser realizada em condições brandas, minimizando o dano para o produto. Para aumentar a estabilidade da C-FC, e facilitar a sua aplicação, podem ser avaliadas técnicas recentes, não exploradas para este fim, como as nanofibras obtidas através do processo de electrospinning. Estas fibras possuem uma área superficial específica extremamente elevada devido a seu pequeno diâmetro. O objetivo deste trabalho foi avaliar parâmetros de adsorção e diferentes técnicas para purificação de C-ficocianina de Spirulina platensis e obter nanofibras poliméricas incorporadas de C-ficocianina. O trabalho foi dividido em quatro artigos. No primeiro artigo, foram avaliados os parâmetros e as isotermas de adsorção de C-ficocianina em resina de troca iônica para leito expandido Streamline® DEAE. Verificou-se que o maior coeficiente de partição foi obtido em pH 7,5, nas temperaturas de 15 e 25 °C. As isotermas de adsorção da Cficocianina foram bem representadas pelos modelos de Langmuir, de Freundlich e de Langmuir-Freundlich, sendo os valores estimados para Qm e Kd obtidos pela isoterma de Langmuir foram, respectivamente, 33,92 mg.mL-1 e 0,123 mg.mL-1, respectivamente. No segundo artigo foi avaliada a purificação de C-FC até grau alimentar, utilizando ultrafiltração (UF). Com a membrana de 50 kDa, identificou-se que somente a temperatura e a aplicação de diferentes ciclos de diafiltração (DF) causaram influência significativa sobre a purificação e recuperação da C-ficocianina. Foram então aplicados o aumento gradativo da quantidade de ciclos, e a diafiltração previamente à ultrafiltração (DF/UF), onde obteve-se um extrato de Cficocianina com pureza de 0,95. No terceiro artigo foram propostos processos de purificação, envolvendo a utilização das diferentes técnicas para obtenção de C-FC com diferentes purezas. Determinou-se que a partir de cromatografia de troca iônica em leito fixo seguido de DF/UF, obtém-se C-FC para uso em cosméticos e a partir de precipitação com sulfato de amônio, e DF/UF obtém-se C-FC para uso em biomarcadores. Com uma sequência de precipitação com sulfato de amônio, DF/UF e cromatografia de troca iônica em leito fixo chega-se a C-FC de grau analítico. No último artigo, C-FC foi incorporada a nanofibras de óxido de polietileno (PEO) através de processo de electrospinning. Foram determinadas a condutividade da solução de C-FC/PEO, a estrutura e comportamento termogravimétrico das nanofibras formadas. Soluções de polímeros com concentração de 6 e 8% proporcionaram a formação de nanofibras com diâmetro médio inferior a 800 nm, homogêneas, sem a presença de gotas. A análise termogravimétrica identificou aumento na resistência térmica da C-FC incorporada nas fibras.

Betalain rich functional extract with reduced salts and nitrate content from red beetroot (Beta vulgaris L.) using membrane separation technology

An initial laboratory-scale evaluation of separation characteristics of membranes with nominal molecular weight cut-offs (NMWCO) ranging from 30 kD down to 0.5 kD indicated effective separation of betalains in the 0.5 kD region. Subsequent pilot-level trials using 1 kD, loose reverse osmosis (LRO) and reverse osmosis (RO) spiral-wound membranes showed LRO membrane to be very efficient with up to 96% salt and 47% other dissolved solids removed while retaining majority of the pigment (∼98%) in the betalain rich extract (BRE). The total betalain content in the BRE increased up to 46%, the highest recovery reported so far at pilot scale level. Interestingly, more than 95% of the nitrates were removed from the BRE after the three diafiltrations. These studies indicate that membrane technology is the most efficient technique to produce BRE with highly reduced amounts of salts and nitrate content.

Is the legal protection for the foetus adequate in clinical trials?

In 2009 and 2010, the major drug regulatory bodies, the European Medicines Agency and the Food and Drug Administration in the USA, issued requests for the generation of information relating to the absorption, distribution, metabolism, excretion, efficacy and safety of investigational drugs in pregnant women prior to approval. In the wake of thalidomide, research involving pregnant women other than for obstetric or gynaecologic purposes became rare, and studies of investigational drugs practically unknown. Consequently, none of the legislation applicable in the UK and few of the guidelines introduced in the last 40 years properly addresses the conduct of clinical trials of investigational drugs in this population. This thesis questions whether the legal protection for the foetus is adequate in clinical trials. The answer appears to be a qualified “no”. Arguments persist regarding the moral standing of the foetus, particularly regarding abortion. That will not be the intent of such trials, and a moral case is made for the conduct of clinical trials in this population by analogy with the neonate, and the pregnant woman’s autonomy. Legally, we already recognise the foetus has ‘interests’ which crystallise upon live birth, and that compensation is recoverable for harm inflicted in utero manifesting as congenital injury. The essence of research is quite different from medical practice, and the extent to which this is understood by trial participants is unclear. The approvals processes contain a number of inadequacies which have the potential to expose the foetus to harm and affect the consent of the pregnant woman. The recovery of compensation in the event of children born injured following clinical trials during pregnancy in many ways may be more complex than other personal injury cases.. The conclusions of this thesis are that the existence of a foetus does merit recognition by the law in this setting and that morally such studies are justifiable. However, the present legislation and approval processes potentially expose the foetus to avoidable risk and may not be appropriate to enable the recovery of compensation, thereby creating potential to deter future trial participants. A proposal is made regarding an approach to simplify the process for recovery of compensation, and thereby strengthen the approval and consent processes.