Interactions of natural products with β-lactoglobulins, members of the lipocalin family

Natural products constitute an important source of new drugs. The bioavailability of the drugs depends on their absorption, distribution, metabolism and elimination. To achieve good bioavailability, the drug must be soluble in water, stable in the gastrointestinal tract and palatable. Binding proteins may improve the solubility of drug compounds, masking unwanted properties, such as bad taste, bitterness or toxicity, transporting or protecting these compounds during processing and storage. The focus of this thesis was to study the interactions, including ligand binding and the effect of pH and temperature, of bovine and reindeer β-lactoglobulin (βLG) with such compounds as retinoids, phenolic compounds as well as with compounds from plant extracts, and to investigate the transport properties of the βLG-ligand complex. To examine the binding interactions of different ligands to βLG, new methods were developed. The fluorescence binding method for the evaluation of ligand binding to βLG was miniaturized from a quartz cell to a 96-well plate. A method of ultrafiltration sampling combined with high-performance liquid chromatography was developed to assess the binding of compounds from extracts. The interactions of phenolic compounds or retinoids and βLG were investigated using the 96-well plate method. The majority of flavones, flavonols, flavanones and isoflavones and all of the retinoids included were shown to bind to bovine and reindeer βLG. Phenolic compounds, contrary to retinol, were not released at acidic pH. Those results suggest that βLG may have more binding sites, probably also on the surface of βLG. An extract from Camellia sinensis (L.) O. Kunze (black tea), Urtica dioica L. (nettle) and Piper nigrum (black pepper) were used to evaluate whether βLG could bind compounds from plant extracts. Piperine from P. nigrum was found to bind tightly and rutin from U. dioica weakly to βLG. No components from C. sinensis bound to βLG in our experiment. The uptake and membrane permeation of bovine and reindeer βLG, free and bound with retinol, palmitic acid and cholesterol, were investigated using Caco-2 cell monolayers. Both bovine and reindeer βLG were able to cross the Caco-2 cell membrane. Free and βLG-bound retinol and palmitic acid were transported equally, whereas cholesterol could not cross the Caco-2 cell monolayer free or bound to βLG. Our results showed that βLG can bind different natural product compounds, but cannot enhance transport of retinol, palmitic acid or cholesterol through Caco-2 cells. Despite this, βLG, as a water-soluble binding protein, may improve the solubility of natural compounds, possibly protecting them from early degradation and transporting some of them through the stomach. Furthermore, it may decrease their bad or bitter taste during oral administration of drugs or in food preparations. βLG can also enhance or decrease the health benefits of herbal teas and food preparations by binding compounds from extracts.

Brain-specific epigenetic markers of schizophrenia

Epigenetics plays a crucial role in schizophrenia susceptibility. In a previous study, we identified over 4500 differentially methylated sites in prefrontal cortex (PFC) samples from schizophrenia patients. We believe this was the first genome-wide methylation study performed on human brain tissue using the Illumina Infinium HumanMethylation450 Bead Chip. To understand the biological significance of these results, we sought to identify a smaller number of differentially methylated regions (DMRs) of more functional relevance compared with individual differentially methylated sites. Since our schizophrenia whole genome methylation study was performed, another study analysing two separate data sets of post-mortem tissue in the PFC from schizophrenia patients has been published. We analysed all three data sets using the bumphunter function found in the Bioconductor package minfi to identify regions that are consistently differentially methylated across distinct cohorts. We identified seven regions that are consistently differentially methylated in schizophrenia, despite considerable heterogeneity in the methylation profiles of patients with schizophrenia. The regions were near CERS3, DPPA5, PRDM9, DDX43, REC8, LY6G5C and a region on chromosome 10. Of particular interest is PRDM9 which encodes a histone methyltransferase that is essential for meiotic recombination and is known to tag genes for epigenetic transcriptional activation. These seven DMRs are likely to be key epigenetic factors in the aetiology of schizophrenia and normal brain neurodevelopment.

At the Limits of Presentation : Coming-into-Presence and its Aesthetic Relevance in Jean-Luc Nancy's Philosophy

This study investigates the significance of art in Jean-Luc Nancy s philosophy. I argue that the notion of art contributes to some of Nancy s central ontological ideas. Therefore, I consider art s importance in its own right whether art does have ontological significance, and if so, how one should describe this with respect to the theme of presentation. According to my central argument, with his thinking on art Nancy attempts to give one viewpoint to what is called the metaphysics of presence and to its deconstruction. On which grounds, as I propose, may one say that art is not reducible to philosophy? The thesis is divided into two main parts. The first part, Presentation as a Philosophical Theme, is a historical genesis of the central concepts associated with the birth of presentation in Nancy s philosophy. I examine this from the viewpoint of the differentiation between the ontological notions of presentation and representation by concentrating on the influence of Martin Heidegger and Jacques Derrida, as well as of Hegel and Kant. I give an overview of the way in which being or sense for Nancy is to be described as a coming-into-presence or presentation . Therefore, being takes place in its singular plurality. I argue that Nancy redevelops Heidegger s account of being in two principal ways: first, in rethinking the ontico-ontological difference, and secondly, by striving to radicalize the Heideggerian concept of Mitsein, being-with . I equally wish to show the importance of Derrida s notion of différance and its inherence in Nancy s questioning of being that rests on the unfoundedness of existence. The second part, From Ontology to Art, draws on the importance of art and the aesthetic. If, in Nancy, the question of art touches upon its own limit as the limit of nothingness, how is art able to open its own strangeness and our exposure to this strangeness? My aim is to investigate how Nancy s thinking on art finds its place within the conceptual realm of its inherent difference and interval. My central concern is the thought of originary ungroundedness and the plurality of art and of the arts. As for the question of the difference between art and philosophy, I wish to show that what differentiates art from thought is the fact that art exposes what is obvious but not apparent, if apparent is understood in the sense of givenness. As for art s ability to deconstruct Nancy s ontological notions, I suggest that in question in art is its original heterogeneity and diversity. Art is a matter of differing art occurs singularly, as a local difference. With this in mind, I point out that in reflecting on art in terms of spacing and interval, as a thinker of difference Nancy comes closer to Derrida and his idea of différance than to the structure of Heidegger s ontological difference.

Reducing Browning of Fresh-cut ‘Maha’ Carambola with Chemical Additives and Low-oxygen Atmospheres

The greatest attraction to using carambola (Averrhoa carambola L.) in the fresh-cut market is the star shape that the fruit presents after a transverse cut. Carambola is well-suited for minimal processing, but cut surface browning is a main cause of deterioration. This problem is exacerbated as a result of mechanical injuries occurring during processing and is mainly induced by the leakage of phenolic compounds from the vacuole and subsequent oxidation by polyphenol oxidase (PPO) (Augustin et al., 1985). The use of browning inhibitors in processed fruits is restricted to compounds that are non-toxic, ‘wholesome’, and that do not adversely affect taste and flavour (Gil et al., 1998). In the past, browning was mainly controlled by the action of sulphites, but the use of this compound has declined due to allergic reactions in asthmatics (Weller et al., 1995). The shelf life of fresh-cut products may be extended by a combination of oxygen exclusion and the use of enzymatic browning inhibitors. The objectives of this work were to determine the effects of: (1) post-cutting chemical treatments of ascorbic, citric, oxalic acids, and EDTA-Ca; (2) atmospheric modification; and (3) combinations of the above, on the shelf life of carambola slices based on appearance, colour and polyphenol oxidase activity

Getting value out of your sensory testing - the difference from control test

Non-parametric difference tests such as triangle and duo-trio tests traditionally are used to establish differences or similarities between products. However they only supply the researcher with partial answers and often further testing is required to establish the nature, size and direction of differences. This paper looks at the advantages of the difference from control (DFC) test (also known as degree of difference test) and discusses appropriate applications of the test. The scope and principle of the test, panel composition and analysis of results are presented with the aid of suitable examples. Two of the major uses of the DFC test are in quality control and shelf-life testing. The role DFC takes in these areas and the use of other tests to complement the testing is discussed. Controls or standards are important in both these areas and the use of standard products, mental and written standards and blind controls are highlighted. The DFC test has applications in products where the duo-trio and triangle tests cannot be used because of the normal heterogeneity of the product. While the DFC test is a simple difference test it can be structured to give the researcher more valuable data and scope to make informed decisions about their product.

Heparin versus 0.9% sodium chloride intermittent flushing for the prevention of occlusion in long term central venous catheters in infants and children

Background Guidelines and clinical practice for the prevention of complications associated with central venous catheters (CVC) around the world vary greatly. Most institutions recommend the use of heparin to prevent occlusion, however there is debate regarding the need for heparin and evidence to suggest 0.9% sodium chloride (normal saline) may be as effective. The use of heparin is not without risk, may be unnecessary and is also associated with increased cost. Objectives To assess the clinical effects (benefits and harms) of intermittent flushing of heparin versus normal saline to prevent occlusion in long term central venous catheters in infants and children. Search Methods The Cochrane Vascular Trials Search Co-ordinator searched the Specialised Register (last searched April 2015) and the Cochrane Register of Studies (Issue 3, 2015). We also searched the reference lists of retrieved trials. Selection criteria Randomised controlled trials that compared the efficacy of normal saline with heparin to prevent occlusion of long term CVCs in infants and children aged up to 18 years of age were included. We excluded temporary CVCs and peripherally inserted central catheters (PICC). Data Collection and Analysis Two review authors independently assessed trial inclusion criteria, trial quality and extracted data. Rate ratios were calculated for two outcome measures - occlusion of the CVC and central line-associated blood stream infection. Other outcome measures included duration of catheter placement, inability to withdraw blood from the catheter, use of urokinase or recombinant tissue plasminogen, incidence of removal or re-insertion of the catheter, or both, and other CVC-related complications such as dislocation of CVCs, other CVC site infections and thrombosis. Main Results Three trials with a total of 245 participants were included in this review. The three trials directly compared the use of normal saline and heparin, however, between studies, all used different protocols for the standard and experimental arms with different concentrations of heparin and different frequency of flushes reported. In addition, not all studies reported on all outcomes. The quality of the evidence ranged from low to very low because there was no blinding, heterogeneity and inconsistency between studies was high and the confidence intervals were wide. CVC occlusion was assessed in all three trials (243 participants). We were able to pool the results of two trials for the outcomes of CVC occlusion and CVC-associated blood stream infection. The estimated rate ratio for CVC occlusion per 1000 catheter days between the normal saline and heparin group was 0.75 (95% CI 0.10 to 5.51, two studies, 229 participants, very low quality evidence). The estimated rate ratio for CVC-associated blood stream infection was 1.48 (95% CI 0.24 to 9.37, two studies, 231 participants; low quality evidence). The duration of catheter placement was reported to be similar between the two study arms, in one study (203 participants). Authors' Conclusions The review found that there was not enough evidence to determine the effects of intermittent flushing of heparin versus normal saline to prevent occlusion in long term central venous catheters in infants and children. Ultimately, if this evidence were available, the development of evidenced-based clinical practice guidelines and consistency of practice would be facilitated.

Nucleocapsid gene variability reveals two subgroups of Lettuce necrotic yellows virus

The complete nucleocapsid (N) genes of eight Australian isolates of Lettuce necrotic yellows virus (LNYV) were amplified by reverse transcription PCR, cloned and sequenced. Phylogenetic analyses of these sequences revealed two distinct subgroups of LNYV isolates. Nucleotide sequences within each subgroup were more than 96% identical but heterogeneity between groups was about 20% at the nucleotide sequence level. However, less than 4% heterogeneity was noted at the amino acid level, indicating mostly third nucleotide position changes and a strong conservation for N protein function. There was no obvious geographical or temporal separation of the subgroups in Australia.

Behagets betydelser : Döttrarnas edukation i det sena 1700-talets adelskultur

By the end of the 18th century the daughters of the nobility in the northern parts of Europe received a quite different kind of education from their brothers. Although the cultural aims of the upbringing of girls were similar to that of boys, the practice of the raising of girls was less influenced by tradition. The education of boys was one of classical humanistic and military training, but the girls were more freely educated. The unity and exclusiveness of the culture of nobility were of great importance to the continued influence of this elite. The importance of education became even greater, partly because of the unstable political situation, and partly because of the changes the Enlightenment had caused in the perception of the human essence. The delicate and ambitious hônnete homme was expected to constantly strive to a greater perfection as a Christian. On the other hand, the great weight given to aesthetics - etiquette and taste - made individual variation of the contents of education possible. Education consisted mainly in aesthetic studies; girls studied music, dancing, fine arts, epistolary skills and also the art of polite conversation. On the other hand, there was a demand for enlightenment, and one often finds personal political and social ambitions, which made competition in all skills necessary for the daughters as well. Literary sources for the education of girls are Madame LePrince de Beaumont, Madame d'Epinay, Madame de Genlis and Charles Rollin. Other, perhaps even more important sources are the letters between parents and children and papers originating from studies. Diaries and memoirs also tell us about the practice of education in day to day life. The approach of this study is semiotic. It can be stated that the code of the culture was well hidden from the outsider. This was achieved, for instance, by the adaptation of the foreign French language and culture. The core of the culture consisted of texts which only thorough examples stated the norms which were expressed as good taste. Another important feature of the culture was its tendency towards theatricalisation. The way of life was dictated by taste, and moral values were included in the aesthetic norms through the constant striving for modesty. Pleasant manners were also correct in an ethical perspective. Morality could thus also be taught through etiquette.

The Relationship Between University Culture and Climate and Research Scientists’ Spin-off Intentions

Over the past decades, universities have increasingly become involved in entrepreneurial activities. Despite efforts to embrace their 'third mission', universities still demonstrate great heterogeneity in terms of their involvement in academic entrepreneurship. This chapter adopts an institutional perspective to understand how organizational characteristics affect research scientists' entrepreneurial intentions. We study the impact of university culture and climate on entrepreneurial intentions, thereby specifically focusing on intentions to spin off a company. Using a sample of 437 research scientists from Swedish and German universities, our results reveal that the extent to which universities articulate entrepreneurship as a fundamental element of their mission fosters research scientists' spin-off intentions. Furthermore, the presence of university role models positively affects research scientists' propensity to engage in entrepreneurial activities, both directly and indirectly through entrepreneurial self-efficacy. Finally, research scientists working at universities which explicitly reward people for 'third mission' related output show higher levels of spin-off intentions. This study has implications for both academics and practitioners, including university managers and policy makers.

Makt, konst, elit - konstfältets positioner, relationer och resurser i 1940- och 1950-talens Helsingfors

The dissertation examines the power mechanisms and institutional power hierarchies of the 1940s-1950s era arts elite in Helsinki and their influence on issues of taste in the visual arts. For the purposes of this study, the elite is understood to consist mainly of the board members of the principal elected bodies in the field of the arts. The theoretical framework employed is based on Pierre Bourdieu s field theory and the network perspective. The author has examined what the key, pervasive valuations were that governed the exercising of power by the arts elite in issues of taste, involving determination of who was an acknowledged artist and what was good art. The dissertation demonstrates that this exercising of power was governed by certain collective practices which maintained the illusion that the exercising of power was democratic and based on artistic quality. These practices were the corporate system, using artistic arguments in issues of taste, and using networks in the exercising of power. The struggle in the field of the arts was about who ultimately was entitled to define the value of contemporary art; the issue did not arise regarding historical art. Artists managed to gain a leading position as gatekeepers in issues regarding contemporary art. The author discusses a number of conflicts in the field of the arts that highlight the institutional hierarchies and the capital held by the various players. The structural changes that occurred in administration in the field of cultural production in the 1950s led to the separation of bureaucratic competence on the one hand and aesthetic competence on the other. There was a hierarchy in the field of the arts between institutions, between instruments of legitimisation, and between the symbolic and social capital of players in the field. The hierarchy in the arts ultimately depended on how well the elite could influence tastes through the instruments at their disposal. The various instruments of legitimisation grants, purchases, etc. were ranked differently in the evaluation of acknowledged artists and good art. The dissertation discusses what values, in the form of types of symbolic capital, the arts elite embraced and what role these played in the elite s exercising of power, with particular focus on gender, language, region and economic capital. The aesthetic capital of an artist was of only minor importance in the exercising of power by the arts elite. The dissertation further discusses the points of contact between the arts elite and players in other fields, such as the economic, media and consumer fields. When the arts elite, through the Academy of Fine Arts, became an active player in the art market, this led to a hierarchy where the division between acknowledged and not-acknowledged galleries became sharper.

The freezing of mango slices (Mangifera indica var. Kensington)

'Kensington' mango slices were frozen with sucrose syrup, with dry sucrose and without sugar addition, using blast freezing at -30°C, and still air freezing at -18°C. According to taste panel assessment, slices frozen in syrup were best. A syrup strength of 200 g/L was sufficient to produce a high quality product. the blast-frozen slices had a higher texture score than the still air-frozen slices.

Limitations of soil microbial biomass carbon as an indicator of soil pollution in the field

The size of the soil microbial biomass carbon (SMBC) has been proposed as a sensitive indicator for measuring the adverse effects of contaminants on the soil microbial community. In this study of Australian agricultural systems, we demonstrated that field variability of SMBC measured using the fumigation-extraction procedure limited its use as a robust ecotoxicological endpoint. The SMBC varied up to 4-fold across control samples collected from a single field site, due to small-scale spatial heterogeneity in the soil physicochemical environment. Power analysis revealed that large numbers of replicates (3-93) were required to identify 20% or 50% decreases in the size of the SMBC of contaminated soil samples relative to their uncontaminated control samples at the 0.05% level of statistical significance. We question the value of the routine measurement of SMBC as an ecotoxicological endpoint at the field scale, and suggest more robust and predictive microbiological indicators.

Governance and regional variation of homicide rates: Evidence from cross-national data

Criminological theories of cross-national studies of homicide have underestimated the effects of quality governance of liberal democracy and region. Data sets from several sources are combined and a comprehensive model of homicide is proposed. Results of the spatial regression model, which controls for the effect of spatial autocorrelation, show that quality governance, human development, economic inequality, and ethnic heterogeneity are statistically significant in predicting homicide. In addition, regions of Latin America and non-Muslim Sub-Saharan Africa have significantly higher rates of homicides ceteris paribus while the effects of East Asian countries and Islamic societies are not statistically significant. These findings are consistent with the expectation of the new modernization and regional theories.

Verkkoradio, musiikki ja radio - katsaus verkkoradioihin osana suomalaisten musiikin kuuntelua

This thesis examines Internet-radios and other web-based music services, and different ways these services are used in music listening in Finland. The research material was gathered in eight interviews that took place between spring 2005 and spring 2006 in southern Finland. The analysis distinguishes between five main types of Internet-radios: a) simulcasting, b) webcasting, c) podcasting, d) web-based sound archives, e) interactive music services. As a medium for music listening these combine aspects of computers and traditional radio. The role of Internet-radios in everyday life as well as different types of listening motivation are examined in the light of earlier research on taste, music listening and radio listening.

Modelling the impact of traffic incidents on travel time reliability

Traffic incidents are recognised as one of the key sources of non-recurrent congestion that often leads to reduction in travel time reliability (TTR), a key metric of roadway performance. A method is proposed here to quantify the impacts of traffic incidents on TTR on freeways. The method uses historical data to establish recurrent speed profiles and identifies non-recurrent congestion based on their negative impacts on speeds. The locations and times of incidents are used to identify incidents among non-recurrent congestion events. Buffer time is employed to measure TTR. Extra buffer time is defined as the extra delay caused by traffic incidents. This reliability measure indicates how much extra travel time is required by travellers to arrive at their destination on time with 95% certainty in the case of an incident, over and above the travel time that would have been required under recurrent conditions. An extra buffer time index (EBTI) is defined as the ratio of extra buffer time to recurrent travel time, with zero being the best case (no delay). A Tobit model is used to identify and quantify factors that affect EBTI using a selected freeway segment in the Southeast Queensland, Australia network. Both fixed and random parameter Tobit specifications are tested. The estimation results reveal that models with random parameters offer a superior statistical fit for all types of incidents, suggesting the presence of unobserved heterogeneity across segments. What factors influence EBTI depends on the type of incident. In addition, changes in TTR as a result of traffic incidents are related to the characteristics of the incidents (multiple vehicles involved, incident duration, major incidents, etc.) and traffic characteristics.