Rhodium(I) catalyzed [2+2+2] cycloaddition reactions: experimental and theoretical studies

The [2+2+2] cycloaddition reaction involves the formation of three carbon-carbon bonds in one single step using alkynes, alkenes, nitriles, carbonyls and other unsaturated reagents as reactants. This is one of the most elegant methods for the construction of polycyclic aromatic compounds and heteroaromatic, which have important academic and industrial uses. The thesis is divided into ten chapters including six related publications. The first study based on the Wilkinson’s catalyst, RhCl(PPh3)3, compares the reaction mechanism of the [2+2+2] cycloaddition process of acetylene with the cycloaddition obtained for the model of the complex, RhCl(PH3)3. In an attempt to reduce computational costs in DFT studies, this research project aimed to substitute PPh3 ligands for PH3, despite the electronic and steric effects produced by PPh3 ligands being significantly different to those created by PH3 ones. In this first study, detailed theoretical calculations were performed to determine the reaction mechanism of the two complexes. Despite some differences being detected, it was found that modelling PPh3 by PH3 in the catalyst helps to reduce the computational cost significantly while at the same time providing qualitatively acceptable results. Taking into account the results obtained in this earlier study, the model of the Wilkinson’s catalyst, RhCl(PH3)3, was applied to study different [2+2+2] cycloaddition reactions with unsaturated systems conducted in the laboratory. Our research group found that in the case of totally closed systems, specifically 15- and 25-membered azamacrocycles can afford benzenic compounds, except in the case of 20-membered azamacrocycle (20-MAA) which was inactive with the Wilkinson’s catalyst. In this study, theoretical calculations allowed to determine the origin of the different reactivity of the 20-MAA, where it was found that the activation barrier of the oxidative addition of two alkynes is higher than those obtained for the 15- and 25-membered macrocycles. This barrier was attributed primarily to the interaction energy, which corresponds to the energy that is released when the two deformed reagents interact in the transition state. The main factor that helped to provide an explanation to the different reactivity observed was that the 20-MAA had a more stable and delocalized HOMO orbital in the oxidative addition step. Moreover, we observed that the formation of a strained ten-membered ring during the cycloaddition of 20-MAA presents significant steric hindrance. Furthermore, in Chapter 5, an electrochemical study is presented in collaboration with Prof. Anny Jutand from Paris. This work allowed studying the main steps of the catalytic cycle of the [2+2+2] cycloaddition reaction between diynes with a monoalkyne. First kinetic data were obtained of the [2+2+2] cycloaddition process catalyzed by the Wilkinson’s catalyst, where it was observed that the rate-determining step of the reaction can change depending on the structure of the starting reagents. In the case of the [2+2+2] cycloaddition reaction involving two alkynes and one alkene in the same molecule (enediynes), it is well known that the oxidative coupling may occur between two alkynes giving the corresponding metallacyclopentadiene, or between one alkyne and the alkene affording the metallacyclopentene complex. Wilkinson’s model was used in DFT calculations to analyze the different factors that may influence in the reaction mechanism. Here it was observed that the cyclic enediynes always prefer the oxidative coupling between two alkynes moieties, while the acyclic cases have different preferences depending on the linker and the substituents used in the alkynes. Moreover, the Wilkinson’s model was used to explain the experimental results achieved in Chapter 7 where the [2+2+2] cycloaddition reaction of enediynes is studied varying the position of the double bond in the starting reagent. It was observed that enediynes type yne-ene-yne preferred the standard [2+2+2] cycloaddition reaction, while enediynes type yne-yne-ene suffered β-hydride elimination followed a reductive elimination of Wilkinson’s catalyst giving cyclohexadiene compounds, which are isomers from those that would be obtained through standard [2+2+2] cycloaddition reactions. Finally, the last chapter of this thesis is based on the use of DFT calculations to determine the reaction mechanism when the macrocycles are treated with transition metals that are inactive to the [2+2+2] cycloaddition reaction, but which are thermally active leading to new polycyclic compounds. Thus, a domino process was described combining an ene reaction and a Diels-Alder cycloaddition.

À procura da identidade de Heinz : um modelo de compreensão da motivação moral

RESUMO: As teorias psicológicas da moralidade dividem-se na conceptualização da motivação moral, o tema desta dissertação. Os modelos construtivistas, apoiados na epistemologia genética, privilegiam a cognição como factor determinante mas, as teorias que enfatizam o funcionamento individual admitem que as emoções e a identidade interferem na tendência de cada pessoa agir moralmente. Particularmente apoiados na segunda perspectiva, testámos um modelo preditor da motivação moral com três variáveis, identidade, identidade moral e integridade, todas avaliadas por medidas psicométricas, em duas amostras. A primeira era composta por 320 estudantes do 12º ano de uma escola do concelho de Lisboa, com idades compreendidas entre 18 e 20 anos (M=18,22; Dp=0,49), 108 masculinos e 194 femininos e a segunda era composta por 174 sujeitos, estudantes finalistas de cursos profissionais de uma escola do concelho de Lisboa frequentada por alunos provenientes de ambientes sociais caracterizados pelo stresse sócio-económico e familiar, e até, em bastantes casos, que já tinham participado em actos ilegais relacionados com furto, vandalismo, tráfico de drogas, e agressões, com idades compreendidas entre 18 e 22 anos (M=18,98; Dp=1,075), 104 masculinos e 70 femininos. A primeira amostra foi considerada normativa e a segunda de risco psicossocial. Para avaliar a motivação moral foi construída uma medida que incluiu dois aspectos: a consciência moral, relativa à avaliação objectiva e subjectiva que os indivíduos fazem das situações morais que através de processos de análise de conteúdo foi distinguida em três categorias exclusivas: não transgressão, transgressão relativizada e transgressão; e a autoatribuição de emoções que indica a probabilidade objectiva dos indivíduos cometerem acções morais. Foi verificada a existência de diferenças individuais em ambas as medidas da motivação moral e, também, a existência de diferenças na atribuição de emoções em função da consciência moral: os sujeitos da categoria transgressão apresentaram atribuições mais negativas do que os sujeitos de transgressão relativizada e estes, por sua vez, apresentaram atribuições mais negativas que os sujeitos da categoria não transgressão. Estes resultados confirmam o papel da identidade na motivação moral. A análise da predição confirmou que a integridade, a identidade e a identidade moral, em ordem decrescente de capacidade explicativa, constituem factores preditores tanto da consciência moral como da auto-atribuição de emoções. ABSTRACT: Moral motivation, the subject of this thesis, is differently viewed by several psychological perspectives. Constructivist models supported by genetic epistemology define cognition as the determinant factor while theories that emphasize individual functioning admit that emotions and identity have a central role in the way that persons could morally act. Particularly supported in this second approach we tested a predictive model of moral motivation with three variables, identity, moral identity and integrity, all evaluated by psychometric scales, in two samples. The first sample had 320 graduate high school students with age between 18 and 20 (M=18,22; SD=0,49), 108 male and 194 female and the second sample had 174 graduate students of vocational courses in high school of a risk social and familiar environment, many of them had already done illegal acts such as stealing, vandalism, drug traffic and aggressions; they had ages between 18 and 22 (M=18,98; SD=1,08), 104 male and 70 female. The first sample was considered normative and the second one was classified as psychosocial risk. To evaluate moral motivation we developed a measure that assesses two aspects: moral conscience, who includes both objective and subjective evaluation of moral situations that was distinguished in three exclusive categories by procedures of content analysis: non-transgression, justifiable transgression and transgression; and self-attribution of emotion that indicates the likelihood of committing moral actions. We observed individual differences in both measurements of moral motivation and also verified differences in emotional attribution on the basis of moral conscience: the individuals of transgression category presented more negative attributions than those of justifiable transgression and in turn the latter presented more negative attributions than individuals of non-transgression category. These results confirm the role of identity in moral motivation. The predictor analysis confirmed integrity, identity and moral identity, in descending order of explanatory power, as predictive variables of moral consciousness and self-attribution of emotions.

Stress e estratégias de coping em Enfermeiros : estudo comparativo entre Portugal e Espanha

O presente estudo, tem como objetivo efetuar uma comparação entre os enfermeiros portugueses e espanhóis de modo a identificar os principais fatores que desencadeiam o stress bem como as estratégias de coping utilizadas. A amostra é constituída por 50 enfermeiros espanhóis e 50 enfermeiros portugueses. Dos resultados obtidos, verificam-se que em Portugal as situações indutoras de stress variam de acordo com o sexo, a idade, os anos de serviço, enquanto que em Espanha, apenas se verifica a influência do ambiente relacional nas situações que mais causam stress. Relativamente às estratégias de coping, em Portugal, o sexo, a idade, e o vínculo com a instituição influenciam na determinação das estratégias de coping, enquanto que na amostra espanhola, apenas se verifica a influência do sexo na determinação das mesmas.

A fisiologia da pele de rato é modificada pela idade

Os modelos animais têm sido úteis para estudar mecanismos específicos que afetam a pele humana. É o caso do envelhecimento e das alterações micromecânicas que determinam o enrugamento (a formação de rugas) nos ratinhos irradiados com UV. Estes modelos permitiram perceber que o envelhecimento envolve muitas respostas mecânicas peculiares que não podem ser explicadas pela deformação homogénea da pele. No entanto, a diferença entre o tempo de vida destas espécies afeta também os processos e este é um aspeto principal a ter em conta. Este projeto é direcionado à comparação das propriedades cutâneas de dois grupos de ratos Wistar com diferentes idades – ratos jovens-adultos (n=7, 20-24 semanas) e adultos-velhos (n=5, 48-72 semanas). Medições não-invasivas de perda transepidérmica de água (PTEA), hidratação superficial (MoistureMeter) e biomecânica (Reviscometer e Cutometer por MPA80) foram realizadas nas zonas dorsais (pescoço, dorso-posterior) do animal durante 5 dias, permitindo comparações estatísticas entre grupos. Os resultados não revelaram diferenças significativas para a PTEA, firmeza ou viscoelasticidade entre os dois grupos. Contudo, foi notada uma diminuição significativa, próxima de 40%, da hidratação da pele no grupo dos ratos adultos-velhos. Estes resultados, apesar de preliminares, se fizermos a translação para os seres humanos poderiam ser úteis para avaliar mudanças relacionadas à idade em processos como a recuperação cutânea, ou eficácia / segurança de pensos, onde a hidratação é um factor determinante. Asua potencial utilização para a predição da eficácia e/ou segurança dos produtos de aplicação tópica para idosos em comparação aos adultos merecem ser exploradas.

Formação em contexto, revitalizadora de aprendizagens pessoais, profissionais e organizacionais

Muito se tem teorizado sobre a formação contínua dos professores e a sua implicação no desenvolvimento pessoal e profissional dos docentes, tendo sempre presente as necessárias melhorias no sistema educativo. Entre a dimensão teórica que nos reconforta pela quantidade de saberes acumulados ao longo dos anos e a dimensão prática que se esvanece frequentemente na inércia e rotinas diárias dos professores fica a ausência de uma formação contínua adequada às verdadeiras necessidades dos seus profissionais. Falta proporcionar o encontro mais sistemático entre teoria e prática em contexto, ou vice-versa, numa simbiose perfeita de sentidos para que a formação se torne essencial e determinante na prática diária do professor. A reflexão e o profundo questionamento sobre esta temática colocaram-nos diante de uma questão extremamente pertinente: que formação contínua em contexto proporcionar aos docentes, promotora de aprendizagens (pessoais, profissionais, organizacionais) e da melhoria dos resultados escolares num Agrupamento de Escolas? As respostas estão implícitas na formulação do tema do presente trabalho: (i) a formação em contexto permite revitalizar aprendizagens pessoais, profissionais e organizacionais; (ii) (re)pensar e (re)dinamizar as dinâmicas de trabalho entre professores, bem como criar novas dinâmicas organizacionais, procurando desenvolver saberes e competências individuais que devidamente aproveitados farão da escola um espaço de trabalho agradável, onde a partilha, o trabalho colaborativo e reflexivo melhorarão naturalmente as práticas do quotidiano escolar. Efetuou-se um levantamento das ações realizadas pelos docentes do agrupamento e verificou-se que maioritariamente se faziam fora do âmbito disciplinar, constrangimento apontado pela falta de formações específicas nas áreas disciplinares. Esta e outras questões foram validadas a partir das entrevistas semiestruturadas realizadas a docentes do agrupamento que confirmaram existir no contexto escolar oportunidades de aprendizagem desaproveitadas. Partindo das fundamentações necessárias, quer a partir dos dados, quer a partir de um quadro concetual teórico, quer ainda da opinião muito favorável das professoras entrevistadas, propomos um projeto de formação pró-ativo concebido para um agrupamento de escolas que contribua para a melhoria das práticas letivas.

The triggers of competitiveness: the EFIGE cross-country report. Bruegel Blueprint 17, 17 July 2012

There is a pressing need for Europe to grow out of the crisis, meaning that Europe needs to become more competitive, enabling it to capture growth currently taking place mainly in emerging markets. But what are the triggers of competitiveness? The EFIGE project, led by Bruegel, takes a fresh look by inquiring into the determinants of firm-level international performance – focusing on external competitiveness. In the competitiveness debate, it is crucial to understand not only the macroeconomic challenge, but also to find the right micro-level triggers that will generate growth and exports. The authors identify firm-level total factor productivity as a major determinant of growth and exports. Human capital, research, equity finance and performance based incentives for employees also play their parts. Moreover, size matters and large firms typically are much better exporters than their smaller counterparts. This report builds on previous EFIGE research and studies in depth firm performance in seven countries (Austria, France, Germany, Hungary, Italy, Spain, United Kingdom) to identify the triggers of competitiveness.

Contributions of matric and osmotic potentials to the unfrozen water content of frozen soils

Recent reports show that biogeochemical processes continue when the soil is frozen, but are limited by water availability. However, there is little knowledge about the interactive effects of soil and environmental variables on amounts of unfrozen water in frozen soils. The aims of this study were to determine the contributions of matric and osmotic potentials to the unfrozen water content of frozen soil. We determined the effects of matric and osmotic potential on unfrozen water contents of frozen mineral soil fractions (ranging from coarse sand to fine silt) at -7 degrees C, and estimated the contributions of these potentials to liquid water contents in samples from organic surface layers of boreal soils frozen at -4 degrees C. In the mineral soil fractions the unfrozen water contents appeared to be governed solely by the osmotic potential, but in the humus layers of the sampled boreal soils both the osmotic and matric potentials control unfrozen water content, with osmotic potential contributing 20 to 69% of the total water potential. We also determined pore size equivalents, where unfrozen water resides at -4 degrees C, and found a strong correlation between these equivalents and microbial CO2 production. The larger the pores in which the unfrozen water is found the larger the microbial activity that can be sustained. The osmotic potential may therefore be a key determinant of unfrozen water and carbon dynamics in frozen soil. (C) 2008 Elsevier B.V. All rights reserved.

The water quality of the River Carnon, west Cornwall, November 1992 to March 1994: the impacts of Wheal Jane discharges

In January 1992, there was a major pollutant event for the River Canon and downstream with its confluence to the River Fal and the Fal estuary in the west Cornwall. This incident was associated with the discharge of several million gallons of highly polluted water from the abandoned Wheal Jane tin mine that also extracted Ag, Cu and Zn ore. Later that year, the Centre for Ecology and Hydrology (CBH; then Institute of Hydrology) Wallingford undertook daily monitoring of the River Canon for a range of major, minor and trace elements to assess the nature and the dynamics of the pollutant discharges. These data cover an 18-month period when there remained major water-quality problems after the initial phase of surface water contamination. Here, a summary is provided of the water quality found, as a backdrop to set against subsequent remediation. Two types of water-quality determinant grouping were observed. The first type comprises the determinants B, Cs, Ca, Li, K, Na, SO4, Rb and Sr, and their concentrations are positively correlated with each other but inversely correlated with flow. This type of water-quality determinant shows variations in concentration that broadly link to the normal hydrogeochemical processes within the catchment, with limited confounding issues associated with mine drainage. The second type of water-quality determinant comprises Al, Be, Cd, Ce, Co, Cu, Fe, La, Pb, Pr, Nd, Ni, Si, Sb, U, Y and Zn, and concentrations for all this group are positively correlated. The determinants in this second group all have concentrations that are negatively correlated with pH. This group links primarily to pollutant mine discharge. The water-quality variations in the River Camon are described in relation to these two distinct hydrogeochemical groupings. (C) 2004 Elsevier B.V All rights reserved.

Confronting social defence mechanisms: avoiding disorganization during crises

Crises cause social disturbances within their host organisation and the patterns of interpersonal ties that emerge are an important determinant of crisis management efficiency. In this article, social network analysis is used within a construction project context, to demonstrate that efficient crisis management depends upon the design and maintenance of an appropriate social fabric. However, crises have defence mechanisms that make management difficult by inducing forces that encourage people to pursue inappropriate social ties. Purposeful social intervention is therefore an essential part of the crisis management process to confront and avoid disorganisation.

Soils of the tropics

The conditions for soil development in the lowland tropics are described, in particular the soil-forming factors, climate, parent material, topography and organisms, and their interactions through time. Of particular importance is the climate of the lowland tropics, which has a major influence on the nature of soil development because of high temperatures and the duration of the periods when the soil is moist. The nature of the parent material is also a major determinant of the nature of the soil. Because soil development has taken place in much of the tropics over long time periods, the soils have distinctive characteristics. Soil-forming processes are described briefly, in particular the nature of the weathering of the inorganic fraction of the soil, and the removal of soluble materials in leaching and the translocation of materials in suspension. Typical soils developed in the humid and seasonally moist tropics are briefly described, and comparisons made between the two most widely used international soil classifications, Soil Taxonomy and World Reference Base for Soil Resources. Some of the other soils found within the tropics are briefly described.

Formation of dityrosine cross-links during breadmaking

To establish its significance during commercial breadmaking, dityrosine formation was quantified in flours and doughs of six commercial wheat types at various stages of the Chorleywood Bread Process. Dityrosine was formed mainly during mixing and baking, at the levels of nmol/g dry weight. Good breadmaking flours tended to exhibit higher dityrosine content in the final bread than low quality ones, but no relationship was found for dityrosine as a proportion of flour protein content, indicating that the latter was still a dominant factor in the analysis. There was no correlation between gluten yield of the six wheat types and their typical dityrosine concentrations, suggesting that dityrosine crosslinks were not a determinant factor for gluten formation. Ascorbic acid was found to inhibit dityrosine formation during mixing and proving, and have no significant effect on dityrosine in the final bread. Hydrogen peroxide promoted dityrosine formation, which suggests a radical mechanism involving endogenous peroxidases might be the responsible for dityrosine formation during breadmaking.

Incorporation of cis-9,trans-11 or trans-10,cis-12 conjugated linoleic acid into plasma and cellular lipids in healthy men

This study investigated the incorporation of cis-9,trans-11 conjugated linoleic acid (c9,t11 CLA) and trans-10,cis-12-CLA (t10,c12 CLA) into plasma and peripheral blood mononuclear cell (PBMC) lipids when consumed as supplements highly enriched in these isomers. Healthy men (n = 49, age 31 +/- 8 years) consumed one, two, and four capsules containing similar to600 mg of either c9,t11 CIA or t10,c12 CLA per capsule for sequential 8 week periods followed by a 6 week washout before consuming the alternative isomer. Both isomers were incorporated in a dosedependent manner into plasma phosphatidylcholine (PC) (c9,t11 CLA r = 0.779, t10,c12 CLA r = 0.738; P < 0.0001) and cholesteryl ester (CE) (c9,t11 CLA r = 0.706, t10,c12 CLA r = 0.788; P < 0.0001). Only t10,c12 CLA was enriched in plasma nonesterified fatty acids. Both c9,t11 CIA and t10,c12 CLA were incorporated linearly into PBMC total lipids (r = 0.285 and r = 0.273, respectively; P < 0.0005). The highest concentrations of c9,t11 CLA and t10,c12 CLA in PBMC lipids were 3- to 4-fold lower than those in plasma PC and CE. These data suggest that the level of intake is a major determinant of plasma and PBMC CLA content, although PBMCs appear to incorporate both CLA isomers less readily.

Toward a combined seasonal weather and crop productivity forecasting system: Determination of the working spatial scale

A methodology is presented for the development of a combined seasonal weather and crop productivity forecasting system. The first stage of the methodology is the determination of the spatial scale(s) on which the system could operate; this determination has been made for the case of groundnut production in India. Rainfall is a dominant climatic determinant of groundnut yield in India. The relationship between yield and rainfall has been explored using data from 1966 to 1995. On the all-India scale, seasonal rainfall explains 52% of the variance in yield. On the subdivisional scale, correlations vary between variance r(2) = 0.62 (significance level p < 10(-4)) and a negative correlation with r(2) = 0.1 (p = 0.13). The spatial structure of the relationship between rainfall and groundnut yield has been explored using empirical orthogonal function (EOF) analysis. A coherent, large-scale pattern emerges for both rainfall and yield. On the subdivisional scale (similar to 300 km), the first principal component (PC) of rainfall is correlated well with the first PC of yield (r(2) = 0.53, p < 10(-4)), demonstrating that the large-scale patterns picked out by the EOFs are related. The physical significance of this result is demonstrated. Use of larger averaging areas for the EOF analysis resulted in lower and (over time) less robust correlations. Because of this loss of detail when using larger spatial scales, the subdivisional scale is suggested as an upper limit on the spatial scale for the proposed forecasting system. Further, district-level EOFs of the yield data demonstrate the validity of upscaling these data to the subdivisional scale. Similar patterns have been produced using data on both of these scales, and the first PCs are very highly correlated (r(2) = 0.96). Hence, a working spatial scale has been identified, typical of that used in seasonal weather forecasting, that can form the basis of crop modeling work for the case of groundnut production in India. Last, the change in correlation between yield and seasonal rainfall during the study period has been examined using seasonal totals and monthly EOFs. A further link between yield and subseasonal variability is demonstrated via analysis of dynamical data.

Adaptation of crops to climate change through genotypic responses to mean and extreme temperatures

The importance of temperature in the determination of the yield of an annual crop (groundnut; Arachis hypogaea L. in India) was assessed. Simulations from a regional climate model (PRECIS) were used with a crop model (GLAM) to examine crop growth under simulated current (1961-1990) and future (2071-2100) climates. Two processes were examined: the response of crop duration to mean temperature and the response of seed-set to extremes of temperature. The relative importance of, and interaction between, these two processes was examined for a number of genotypic characteristics, which were represented by using different values of crop model parameters derived from experiments. The impact of mean and extreme temperatures varied geographically, and depended upon the simulated genotypic properties. High temperature stress was not a major determinant of simulated yields in the current climate, but affected the mean and variability of yield under climate change in two regions which had contrasting statistics of daily maximum temperature. Changes in mean temperature had a similar impact on mean yield to that of high temperature stress in some locations and its effects were more widespread. Where the optimal temperature for development was exceeded, the resulting increase in duration in some simulations fully mitigated the negative impacts of extreme temperatures when sufficient water was available for the extended growing period. For some simulations the reduction in mean yield between the current and future climates was as large as 70%, indicating the importance of genotypic adaptation to changes in both means and extremes of temperature under climate change. (c) 2006 Elsevier B.V. All rights reserved.

Climate change and the flowering time of annual crops

Crop production is inherently sensitive to variability in climate. Temperature is a major determinant of the rate of plant development and, under climate change, warmer temperatures that shorten development stages of determinate crops will most probably reduce the yield of a given variety. Earlier crop flowering and maturity have been observed and documented in recent decades, and these are often associated with warmer (spring) temperatures. However, farm management practices have also changed and the attribution of observed changes in phenology to climate change per se is difficult. Increases in atmospheric [CO2] often advance the time of flowering by a few days, but measurements in FACE (free air CO2 enrichment) field-based experiments suggest that elevated [CO2] has little or no effect on the rate of development other than small advances in development associated with a warmer canopy temperature. The rate of development (inverse of the duration from sowing to flowering) is largely determined by responses to temperature and photoperiod, and the effects of temperature and of photoperiod at optimum and suboptimum temperatures can be quantified and predicted. However, responses to temperature, and more particularly photoperiod, at supraoptimal temperature are not well understood. Analysis of a comprehensive data set of time to tassel initiation in maize (Zea mays) with a wide range of photoperiods above and below the optimum suggests that photoperiod modulates the negative effects of temperature above the optimum. A simulation analysis of the effects of prescribed increases in temperature (0-6 degrees C in + 1 degrees C steps) and temperature variability (0% and + 50%) on days to tassel initiation showed that tassel initiation occurs later, and variability was increased, as the temperature exceeds the optimum in models both with and without photoperiod sensitivity. However, the inclusion of photoperiod sensitivity above the optimum temperature resulted in a higher apparent optimum temperature and less variability in the time of tassel initiation. Given the importance of changes in plant development for crop yield under climate change, the effects of photoperiod and temperature on development rates above the optimum temperature clearly merit further research, and some of the knowledge gaps are identified herein.