Influence of a non-ionic amphiphilic copolymer on the self-assembly of a peptide amphiphile that forms nanotapes

The influence of a non-ionic polymeric surfactant on the self-assembly of a peptide amphiphile (PA) that forms nanotapes is investigated using a combination of microscopic, scattering and spectroscopic techniques. Mixtures of Pluronic copolymer P123 with the PA C16-KTTKS in aqueous solution were studied at a fixed concentration of the PA at which it is known to self-assemble into extended nanotapes, but varying P123 concentration. We find that P123 can disrupt the formation of C16- KTTKS nanotapes, leading instead to cylindrical nanofibril structures. The spherical micelles formed by P123 at room temperature are disrupted in the presence of the PA. There is a loss of cloudiness in the solutions as the large nanotape aggregates formed by C16-KTTKS are broken up, by P123 solubilization. At least locally, b-sheet structure is retained, as confirmed by XRD and FTIR spectroscopy, even for solutions containing 20 wt% P123. This indicates, unexpectedly, that peptide secondary structure can be retained in solutions with high concentration of non-ionic surfactant. Selfassembly in this system exhibits slow kinetics towards equilibrium, the initial self-assembly being dependent on the order of mixing. Heating above the lipid chain melting temperature assists in disrupting trapped non-equilibrium states.

Conductance of amyloid β based peptide filaments: structure–function relations.

Controlling the morphology of self-assembled peptide nanostructures, particularly those based on amyloid peptides, has been the focus of intense research. In order to exploit these structures in electronic applications, further understanding of their electronic behavior is required. In this work, the role of peptide morphology in determining electronic conduction along self-assembled peptide nanofilament networks is demonstrated. The peptides used in this work were based on the sequence AAKLVFF, which is an extension of a core sequence from the amyloid b peptide. We show that the incorporation of a non-natural amino acid, 2-thienylalanine, instead of phenylalanine improves the obtained conductance with respect to that obtained for a similar structure based on the native sequence, which was not the case for the incorporation of 3-thienylalanine. Furthermore, we demonstrate that the morphology of the self-assembled structures, which can be controlled by the solvent used in the assembly process, strongly affects the conductance, with larger conduction obtained for a morphology of long, straight filaments. Our results demonstrate that, similar to natural systems, the assembly and folding of peptides could be of great importance for optimizing their function as components of electronic devices. Hence, sequence design and assembly conditions can be used to control the performance of peptide based structures in such electronic applications.

Structural and morphological studies of the dipeptide based L-Pro-L-Val organocatalytic gels and their rheological behaviour

Organocatalytic gels based on the dipeptide sequence L-Pro-L-Val have been studied by two different FTIR techniques. This suggests a different arrangement of the gelator molecules in the self-assembled fibers depending on the organic solvent employed. In acetonitrile and nitromethane the structure of the supramolecular aggregates is similar and provides similar catalytic properties (supramolecularenhancement of basicity). In contrast, the self-assembled fibers obtained in toluene clearly presented a different molecular arrangement consistent with its different catalytic behaviour (enamine-based catalysis). In addition these gels have been studied by microscopy and rheology.

Skilloscopy: Bayesian modeling of decision makers' skill

This paper proposes and demonstrates an approach, Skilloscopy, to the assessment of decision makers. In an increasingly sophisticated, connected and information-rich world, decision making is becoming both more important and more difficult. At the same time, modelling decision-making on computers is becoming more feasible and of interest, partly because the information-input to those decisions is increasingly on record. The aims of Skilloscopy are to rate and rank decision makers in a domain relative to each other: the aims do not include an analysis of why a decision is wrong or suboptimal, nor the modelling of the underlying cognitive process of making the decisions. In the proposed method a decision-maker is characterised by a probability distribution of their competence in choosing among quantifiable alternatives. This probability distribution is derived by classic Bayesian inference from a combination of prior belief and the evidence of the decisions. Thus, decision-makers’ skills may be better compared, rated and ranked. The proposed method is applied and evaluated in the gamedomain of Chess. A large set of games by players across a broad range of the World Chess Federation (FIDE) Elo ratings has been used to infer the distribution of players’ rating directly from the moves they play rather than from game outcomes. Demonstration applications address questions frequently asked by the Chess community regarding the stability of the Elo rating scale, the comparison of players of different eras and/or leagues, and controversial incidents possibly involving fraud. The method of Skilloscopy may be applied in any decision domain where the value of the decision-options can be quantified.

Complexation of lanthanides, actinides and transition metal cations with a 6-(1,2,4-triazin-3-yl)-2,2′:6′,2′′-terpyridine ligand: implications for actinide(III)/lanthanide(III) partitioning

The quadridentate N-heterocyclic ligand 6-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzotriazin- 3-yl)-2,2′ : 6′,2′′-terpyridine (CyMe4-hemi-BTBP) has been synthesized and its interactions with Am(III),U(VI), Ln(III) and some transition metal cations have been evaluated by X-ray crystallographic analysis, Am(III)/Eu(III) solvent extraction experiments, UVabsorption spectrophotometry, NMR studies and ESI-MS. Structures of 1 : 1 complexes with Eu(III), Ce(III) and the linear uranyl (UO2 2+) ion were obtained by X-ray crystallographic analysis, and they showed similar coordination behavior to related BTBP complexes. In methanol, the stability constants of the Ln(III) complexes are slightly lower than those of the analogous quadridentate bis-triazine BTBP ligands, while the stability constant for the Yb(III)complex is higher. 1H NMR titrations and ESI-MS with lanthanide nitrates showed that the ligand forms only 1 : 1 complexes with Eu(III), Ce(III) and Yb(III), while both 1 : 1 and 1 : 2 complexes were formed with La(III) and Y(III) in acetonitrile. A mixture of isomeric chiral 2 : 2 helical complexes was formed with Cu(I), with a slight preference (1.4 : 1) for a single directional isomer. In contrast, a 1 : 1 complex was observed with the larger Ag(I) ion. The ligand was unable to extract Am(III) or Eu(III) from nitric acid solutions into 1-octanol, except in the presence of a synergist at low acidity. The results show that the presence of two outer 1,2,4-triazine rings is required for the efficient extraction and separation of An(III)from Ln(III) by quadridentate N-donor ligands.

Normative, systemic and procedural aspects: a review of indicator-based sustainability assessments in agriculture

Methods for assessing the sustainability of agricultural systems do often not fully (i) take into account the multifunctionality of agriculture, (ii) include multidimensionality, (iii) utilize and implement the assessment knowledge and (iv) identify conflicting goals and trade-offs. This chapter reviews seven recently developed multidisciplinary indicator-based assessment methods with respect to their contribution to these shortcomings. All approaches include (1) normative aspects such as goal setting, (2) systemic aspects such as a specification of scale of analysis and (3) a reproducible structure of the approach. The approaches can be categorized into three typologies: first, top-down farm assessments, which focus on field or farm assessment; second, top-down regional assessments, which assess the on-farm and the regional effects; and third, bottom-up, integrated participatory or transdisciplinary approaches, which focus on a regional scale. Our analysis shows that the bottom-up, integrated participatory or transdisciplinary approaches seem to better overcome the four shortcomings mentioned above.

Role for flagella but not intimin in the persistent infection of the gastrointestinal tissues of specific-pathogen-free chicks by Shiga toxin-negative Escherichia coli O157:H7

Shiga toxin (Stx)-positive Escherichia coli O157:117 readily colonize and persist in specific-pathogen-free (SPF) chicks, and we have shown that an Stx-negative E. coli O157:117 isolate (NCTC12900) readily colonizes SPF chicks for up to 169 days after oral inoculation at 1 day of age. However, the role of intimin in the persistent colonization of poultry remains unclear. Thus, to investigate the role of intimin and flagella, which is a known factor in the persistence of non-O157 E. coli in poultry, isogenic single- and double-intimin and aflagellar mutants were constructed in E. coli O157:117 isolate NCTC12900. These mutants were used to inoculate (10(5) CFU) 1-day-old SPF chicks. In general, significant attenuation of the aflagellate and intiminaflagellate mutants, but not the intimin mutant, was noted at similar time points between 22 and 92 days after inoculation. The intimin-deficient mutant was still being shed at the end of the experiment, which was 211 days after inoculation, 84 days more than the wild type. Shedding of the aflagellar and intimin-aflagellar mutants ceased 99 and 113 days after inoculation, respectively. Histological analysis of gastrointestinal tissues from inoculated birds gave no evidence for true microcolony formation by NCTC12900 or intimin and aflagellar mutants to epithelial cells. However, NCTC12900 mutant derivatives associated with the mucosa were observed as individual cells and/or as large aggregates. Association with luminal contents was also noted. These data suggest that O157 organisms do not require intimin for the persistent colonization of chickens, whereas flagella do play a role in this process.

Tobit estiamtion with unknown point of censoring with an application to milk market participation in the Ethiopian highlands

Data augmentation is a powerful technique for estimating models with latent or missing data, but applications in agricultural economics have thus far been few. This paper showcases the technique in an application to data on milk market participation in the Ethiopian highlands. There, a key impediment to economic development is an apparently low rate of market participation. Consequently, economic interest centers on the “locations” of nonparticipants in relation to the market and their “reservation values” across covariates. These quantities are of policy interest because they provide measures of the additional inputs necessary in order for nonparticipants to enter the market. One quantity of primary interest is the minimum amount of surplus milk (the “minimum efficient scale of operations”) that the household must acquire before market participation becomes feasible. We estimate this quantity through routine application of data augmentation and Gibbs sampling applied to a random-censored Tobit regression. Incorporating random censoring affects markedly the marketable-surplus requirements of the household, but only slightly the covariates requirements estimates and, generally, leads to more plausible policy estimates than the estimates obtained from the zero-censored formulation

Expression, purification and crystallization of the ectodomain of the envelope glycoprotein E2 from Bovine viral diarrhoea virus

Bovine viral diarrhoea virus (BVDV) is an economically important animal pathogen which is closely related to Hepatitis C virus. Of the structural proteins, the envelope glycoprotein E2 of BVDV is the major antigen which induces neutralizing antibodies; thus, BVDV E2 is considered as an ideal target for use in subunit vaccines. Here, the expression, purification of wild-type and mutant forms of the ectodomain of BVDV E2 and subsequent crystallization and data collection of two crystal forms grown at low and neutral pH are reported. Native and multiple-wavelength anomalous dispersion (MAD) data sets have been collected and structure determination is in progress.

A complex system perspective on the emergence and spread of infectious diseases: integrating economic and ecological aspects

The emergence and spread of infectious diseases reflects the interaction of ecological and economic factors within an adaptive complex system. We review studies that address the role of economic factors in the emergence and spread of infectious diseases and identify three broad themes. First, the process of macro-economic growth leads to environmental encroaching, which is related to the emergence of infectious diseases. Second, there are a number of mutually reinforcing processes associated with the emergence/spread of infectious diseases. For example, the emergence and spread of infectious diseases can cause significant economic damages, which in turn may create the conditions for further disease spread. Also, the existence of a mutually reinforcing relationship between global trade and macroeconomic growth amplifies the emergence/spread of infectious diseases. Third, microeconomic approaches to infectious disease point to the adaptivity of human behavior, which simultaneously shapes the course of epidemics and responds to it. Most of the applied research has been focused on the first two aspects, and to a lesser extent on the third aspect. With respect to the latter, there is a lack of empirical research aimed at characterizing the behavioral component following a disease outbreak. Future research should seek to fill this gap and develop hierarchical econometric models capable of integrating both macro and micro-economic processes into disease ecology.

Response of the EAA FRSC to the EFRAG/ANC/FRC discussion paper: 'Towards a Disclosure Framework for the Notes'

We summarise the response of the EAA’s FRSC to Towards a Disclosure Framework for the Notes, a Discussion Paper (DP) issued jointly by EFRAG, ANC and FRC. While supportive of much of the DP, and in particular of the underlying aim to place disclosures on a sounder conceptual foundation, we identify two broad themes for further development. The first concerns the DP’s diagnosis of the problem, which is that the existing financial reporting is characterised by, on the one hand, disclosure overload and, on the other hand, an absence of a conceptual framework for organising and communicating disclosures. Our review of the literature suggests much greater support for the second of these two factors than for the first. The second broad theme is the purpose of the proposed DF, and the principles that are derived from this purpose. Here, we stress the need for the framework to better accommodate the context within which financial statement disclosures are used. In practice, this context is characterised by variation in information, incentives and enforcement, each of which has a considerable effect on the appropriate disclosure policy and practice in any given situation.

Self-assembly of a peptide amphiphile: transition from nanotape fibrils to micelles

A thermal transition is observed in the peptide amphiphile C16-KTTKS (TFA salt) from nanotapes at 20 degrees C to micelles at higher temperature (the transition temperature depending on concentration). The formation of extended nanotapes by the acetate salt of this peptide amphiphile, which incorporates a pentapeptide from type I procollagen, has been studied previously [V. Castelletto et al., Chem. Commun., 2010, 46, 9185]. Here, proton NMR and SAXS provide evidence for the TFA salt spherical micelles at high temperature. The phase behavior, with a Krafft temperature separating insoluble aggregates (extended nanotapes) at low temperature from the high temperature micellar phase resembles that for conventional surfactants, however this has not previously been reported for peptide amphiphiles.

Self-assembly of a model amphiphilic oligopeptide incorporating an arginine headgroup

The self-assembly in aqueous solution of the alanine-rich peptide A12R2 containing twelve alanine residues and two arginine residues has been investigated. This oligomeric peptide was synthesized via NCA-polymerization methods. The surfactant-like peptide is found via FTIR to form antiparallel dimers which aggregate into twisted fibrils, as revealed by cryogenic-transmission electron microscopy. The fibril substructure is probed via detailed X-ray scattering experiments, and are uniquely comprised of twisted tapes only 5 nm wide, set by the width of the antiparallel A12R2 dimers. The packing of the alanine residues leads to distinct “b-sheet” spacings compared to those for amyloid-forming peptides. For this peptide, b-sheet structure coexists with some a-helical content. These ultrafine amyloid fibrils present arginine at high density on their surfaces, and this may lead to applications in nanobiotechnology.

Stephen Martin Leake: a Victorian's view of the Common Law

This article considers the life and work of Stephen Martin Leake and seeks to locate his work within the wider context of the procedural and substantive transformation of the mid-to-late Victorian legal world. In particular, the article attempts to rescue Leake from obscurity and emphasise his importance in this process. It is argued that Leake’s work began the process whereby common lawyers conceived of their law as organised in a principled rather than procedural manner. Later common law jurists built upon this work. Consideration is also given to the philosophical and jurisprudential sources upon which Leake drew in constructing his treatises.