Phase behaviour of block copolymer melts with arbitrary architecture

The Leibler theory [L. Leibler, Macromolecules, v.13, 1602 (1980)] for microphase separation in AB block copolymer melts is generalized for systems with arbitrary topology of molecules. A diagrammatic technique for calculation of the monomeric correlation functions is developed. The free energies of various mesophases are calculated within the second-harmonic approximation. Model highly-branched tree-like structures are considered as an example and their phase diagrams are obtained. The topology of molecules is found to influence the spinodal temperature and asymmetry of the phase diagrams, but not the types of phases and their order. We suggest that all model AB block-copolymer systems will exhibit the typical phase behaviour.Comment: Submitted to J. Chem. Phys., see also http://rugmd4.chem.rug.nl/~morozov/research.htm

Magical Verse from Early Medieval England: The Metrical Charms in Context

This thesis contextualises the Old English Metrical Charms, a selection of twelve alliterative texts from early medieval England. These compositions approach poetic language in a different way from most other literary genres. When performed, they should produce changes in the physical world. Their desired results reflect early medieval concerns. Some are occupied with bodily wellbeing and hope to cure sick patients or prevent undesirable conditions. Others focus on restoring material wellbeing, redressing theft or requesting agricultural benefits. Scholars conventionally find the Metrical Charms challenging. There are several reasons for this circumstance. The Old English texts sometimes presuppose an awareness to obscure stories and events, and they employ a poetic register characterised by rare words and neologisms. Similarly, the Metrical Charms blur modern distinctions between science, magic, and religion, maintaining a complicated relationship with Christianity. They also demonstrate intricate transmission patterns: some show influences of written and oral media; most preserve overt and covert connections to texts in other languages. The thesis employs a comparative methodology and examines the Metrical Charms against a broader background of (often medieval but sometimes modern) European charm traditions. Old English charms are rare. Middle English, Latin, German, Dutch, and Scandinavian charms survive in greater numbers and sometimes resemble the Old English texts. The precise relationships between these compositions have remained underexplored. A comparative methodology affords the unique possibility of linking notoriously complex passages in the Metrical Charms to similar sections from analogous texts. The thesis finds this approach is effective in retrieving the meaning of obscure words and phrases. It offers new solutions for some of the field’s most longstanding interpretative problems

Design of artificial alcohol oxidases:alcohol dehydrogenase - NADPH oxidase fusions for continuous oxidations

With the aim of expanding the arsenal of industrially-applicable oxidative enzymes, fusions of alcohol dehydrogenases with an NADPH-oxidase were designed. In total three different alcohol dehydrogenases (LbADH, TbADH, ADHA) were expressed with a thermostable NADPH-oxidase fusion partner (PAMO C65D), and purified. The resulting bifunctional biocatalysts retained the catalytic properties of the individual enzymes, and act essentially like alcohol oxidases: transforming alcohols to ketones using dioxygen as mild oxidant, while merely requiring a catalytic amount of NADP+. In small-scale reactions the purified fusion enzymes show good performances, with 69-99% conversions, 99% ee with a racemic substrate, and high cofactor and enzyme total turnover numbers. As the fusion enzymes essentially act as oxidases, we found that commonly used high-throughput oxidase-activity screening methods can be used. Therefore, if needed, the fusion enzymes can be easily engineered to tune their properties

Effect of azole fungicide mixtures, alternations and dose on azole sensitivity in the wheat pathogen Zymoseptoria tritici

The evolution of fungicide resistance in the cereal pathogen Zymoseptoria tritici, is a serious threat to the sustainability and profitability of wheat production in Europe. Application of azole fungicides has been shown to affect fitness of Z. tritici variants differentially, so it has been hypothesised that combinations of azoles could slow the evolution of resistance. This work was initiated to assess the effects of dose, mixtures and alternations of two azoles on selection for isolates with reduced sensitivity and on disease control. Naturally infected field trials were carried out at six sites across Ireland and the sensitivity of Z. tritici isolates monitored pre- and post-treatment. The azoles epoxiconazole and metconazole were applied as solo products, in alternation with each other and as a pre-formulated mixture. Full and half label doses were tested. The two azoles were partially cross-resistant, with a common azole resistance principal component accounting for 75% of the variation between isolates. Selection for isolates with reduced azole sensitivity was correlated with disease control. Decreased doses were related to decreases in sensitivity but the effect was barely significant (P = 0.1) and control was reduced. Single applications of an active ingredient (a.i.) caused smaller decreases in sensitivity than double applications. Shifts in sensitivity to the a.i. applied to a plot were greater than to the a.i. not applied, and the decrease in sensitivity was greater to the a.i. applied at the second timing. These results confirm the need to mix a.i.s with different modes of action

Natural Flavins:Occurrence, Role, and Noncanonical Chemistry

Flavoproteins are of key importance to all life on earth for both primary and secondary metabolism. Most flavin-dependent enzymes utilize flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD) as redox cofactor for single-electron and hydride transfer as well as oxidation and oxygenation chemistry at the C4a-locus. Over the last decades, several naturally occurring modified flavins, like 8-formylFAD, F420, and prenylFMN, and covalently bound flavins have been discovered, and were found to further expand the toolbox of flavin chemistry, showcasing extraordinary redox potentials and unprecedented chemistry. Recently, also several examples of “exotic” flavin chemistry, such as N5-oxygenation, have been identified in enzymes that utilize the standard flavins FMN and FAD. It shows that nature has been extremely inventive in exploiting flavins and flavin derivatives as cofactors for an exceptionally wide variety of reactions. Future research will reveal whether other, so far hidden, flavoenzyme-catalyzed chemistries exit.</p

A novel substitution 1381V in the sterol 14alpha-demethylase (CYP51) of Mycosphaerella graminicola is differentially selected by azole fungicides

The recent reduction in the efficacy of azole fungicides in controlling Septoria leaf blotch of wheat, caused by Mycosphaerella graminicola, has prompted concerns over possible development of resistance, particularly in light of the recent emergence of widespread resistance to quinone outside inhibitors (QoIs). We have recently implicated alterations in the target-encoding sterol 14 alpha-demethylase protein (CYP51), and over-expression of genes encoding efflux pumps, in reducing sensitivity to the azole class of sterol demethylation inhibitors (DMIs) in M. graminicola. Here we report on the prevalence and selection of two CYP51 alterations, substitution I381V and deletion of codons 459 and 460 (Delta Y459/G460), in populations of M. graminicola. Neither alteration has previously been identified in human or plant pathogenic fungi resistant to azoles. The presence of Delta Y459/G460 showed a continuous distribution of EC50 values across isolates with either I381 or V381, and had no measurable effect on azole sensitivity. Data linking fungicide sensitivity with the presence of I381V in M. graminicola show for the first time that a particular CYP51 alteration is differentially selected by different azoles in field populations of a plant pathogen. Substitution I381V although not an absolute requirement for reduced azole sensitivity, is selected by tebuconazole and difenoconazole treatment, suggesting an adaptive advantage in the presence of these two compounds. Prochloraz treatments appeared to select negatively for I381V, whereas other azole treatments did not or only weakly impacted on the prevalence of this substitution. These findings suggest treatments with different members of the azole class of fungicides could offer a resistance management strategy

Modes of Flavin-Based Catalysis

Flavin derivatives participate in various chemical transformations in natural and artificial systems. The unique flavin versatility resulted in the development of many different bio-, organo-, and photocatalytic processes. This chapter draws attention to the ways in which members of the flavin family are involved in catalysis, regardless of whether the reactions take place in enzymes or in artificial catalytic systems. Both light-dependent transformations as well as processes occurring in the absence of light are involved.</p

Flavin-Based Catalysis - Preface

Participationincatalyticprocessesisoneofthemainrolesofflavins.Naturehasbeenusing this concept for millions of years. The discovery, description of the structureand function of flavins in the late nineteenth and first half of the twentieth cen-tury has triggered exploitation of the catalytic capabilities of flavins in man-madesynthetic transformations, either using enzymatic or artificial systems. Nowadays,flavins and flavoproteins are enjoying an increased interest from a broad audience,which includes researchers active in synthetic chemistry, enzymology, biocatalysis,and spectroscopy. With new natural flavins still being discovered in recent years,newflavoenzymestructuresandmechanismselucidated,newflavinderivativessyn-thesized, and new photocatalytic and biomimetic approaches developed, it is a verydynamicfieldofresearch.Evenifthemostcommonflavincofactorswerediscoveredabout one century ago, the field is alive and kicking. There are more than 1000 newscientific literature contributions on flavin-related research per year. Many of themare relevant to catalysis. Considering the increasing frequency of new discoveries, one may ask: Are there any limits to flavin catalysis

Flavin-Based Catalysis - Preface

Participationincatalyticprocessesisoneofthemainrolesofflavins.Naturehasbeenusing this concept for millions of years. The discovery, description of the structureand function of flavins in the late nineteenth and first half of the twentieth cen-tury has triggered exploitation of the catalytic capabilities of flavins in man-madesynthetic transformations, either using enzymatic or artificial systems. Nowadays,flavins and flavoproteins are enjoying an increased interest from a broad audience,which includes researchers active in synthetic chemistry, enzymology, biocatalysis,and spectroscopy. With new natural flavins still being discovered in recent years,newflavoenzymestructuresandmechanismselucidated,newflavinderivativessyn-thesized, and new photocatalytic and biomimetic approaches developed, it is a verydynamicfieldofresearch.Evenifthemostcommonflavincofactorswerediscoveredabout one century ago, the field is alive and kicking. There are more than 1000 newscientific literature contributions on flavin-related research per year. Many of themare relevant to catalysis. Considering the increasing frequency of new discoveries, one may ask: Are there any limits to flavin catalysis

Flavin-Based Catalysis - Preface

Participationincatalyticprocessesisoneofthemainrolesofflavins.Naturehasbeenusing this concept for millions of years. The discovery, description of the structureand function of flavins in the late nineteenth and first half of the twentieth cen-tury has triggered exploitation of the catalytic capabilities of flavins in man-madesynthetic transformations, either using enzymatic or artificial systems. Nowadays,flavins and flavoproteins are enjoying an increased interest from a broad audience,which includes researchers active in synthetic chemistry, enzymology, biocatalysis,and spectroscopy. With new natural flavins still being discovered in recent years,newflavoenzymestructuresandmechanismselucidated,newflavinderivativessyn-thesized, and new photocatalytic and biomimetic approaches developed, it is a verydynamicfieldofresearch.Evenifthemostcommonflavincofactorswerediscoveredabout one century ago, the field is alive and kicking. There are more than 1000 newscientific literature contributions on flavin-related research per year. Many of themare relevant to catalysis. Considering the increasing frequency of new discoveries, one may ask: Are there any limits to flavin catalysis