Amyloid peptides incorporating a core sequence from the amyloid beta peptide and gamma amino acids: relating bioactivity to self-assembly

A series of heptapeptides comprising the core sequence Ab(16–20), KLVFF, of the amyloid b peptide coupled with paired N-terminal c-amino acids are investigated in terms of cytotoxicity reduction and binding to the full Ab peptide, both pointing to inhibition of fibrillisation for selected compounds. This is related to the self-assembly capacity of the heptapeptides.

Formation of vesicles through solvent assisted self-assembly of hydrophobic pentapeptides: encapsulation and pH responsive release of dyes by the vesicles

In the biomimetic design two hydrophobic pentapetides Boc-Ile-Aib-Leu-Phe-Ala-OMe ( I) and Boc-Gly-Ile-Aib-Leu-Phe-OMe (II) (Aib: alpha-aminoisobutyric acid) containing one Aib each are found to undergo solvent assisted self-assembly in methanol/water to form vesicular structures, which can be disrupted by simple addition of acid. The nanovesicles are found to encapsulate dye molecules that can be released by the addition of acid as confirmed by fluorescence microscopy and UV studies. The influence of solvent polarity on the morphology of the materials generated from the peptides has been examined systematically, and shows that fibrillar structures are formed in less polar chloroform/petroleum ether mixture and vesicular structures are formed in more polar methanol/water. Single crystal X-ray diffraction studies reveal that while beta-sheet mediated self-assembly leads to the formation of fibrillar structures, the solvated beta-sheet structure leads to the formation of vesicular structures. The results demonstrate that even hydrophobic peptides can generate vesicular structures from polar solvent which may be employed in model studies of complex biological phenomena.

Making sense of survival: refining the treatment of state preferences in neorealist theory

The assumption that ‘states' primary goal is survival’ lies at the heart of the neorealist paradigm. A careful examination of the assumption, however, reveals that neorealists draw upon a number of distinct interpretations of the ‘survival assumption’ that are then treated as if they are the same, pointing towards conceptual problems that surround the treatment of state preferences. This article offers a specification that focuses on two questions that highlight the role and function of the survival assumption in the neorealist logic: (i) what do states have to lose if they fail to adopt self-help strategies?; and (ii) how does concern for relevant losses motivate state behaviour and affect international outcomes? Answering these questions through the exploration of governing elites' sensitivity towards regime stability and territorial integrity of the state, in turn, addresses the aforementioned conceptual problems. This specification has further implications for the debates among defensive and offensive realists, potential extensions of the neorealist logic beyond the Westphalian states, and the relationship between neorealist theory and policy analysis.

Training pharmacists to deliver a complex information technology intervention (PINCER) using the principles of educational outreach and root cause analysis

Objective: To describe the training undertaken by pharmacists employed in a pharmacist-led information technology-based intervention study to reduce medication errors in primary care (PINCER Trial), evaluate pharmacists’ assessment of the training, and the time implications of undertaking the training. Methods: Six pharmacists received training, which included training on root cause analysis and educational outreach, to enable them to deliver the PINCER Trial intervention. This was evaluated using self-report questionnaires at the end of each training session. The time taken to complete each session was recorded. Data from the evaluation forms were entered onto a Microsoft Excel spreadsheet, independently checked and the summary of results further verified. Frequencies were calculated for responses to the three-point Likert scale questions. Free-text comments from the evaluation forms and pharmacists’ diaries were analysed thematically. Key findings: All six pharmacists received 22 hours of training over five sessions. In four out of the five sessions, the pharmacists who completed an evaluation form (27 out of 30 were completed) stated they were satisfied or very satisfied with the various elements of the training package. Analysis of free-text comments and the pharmacists’ diaries showed that the principles of root cause analysis and educational outreach were viewed as useful tools to help pharmacists conduct pharmaceutical interventions in both the study and other pharmacy roles that they undertook. The opportunity to undertake role play was a valuable part of the training received. Conclusions: Findings presented in this paper suggest that providing the PINCER pharmacists with training in root cause analysis and educational outreach contributed to the successful delivery of PINCER interventions and could potentially be utilised by other pharmacists based in general practice to deliver pharmaceutical interventions to improve patient safety.

The treatment of child anxiety disorders via guided parent-delivered cognitive-behavioural therapy: a randomised controlled trial

Background Promising evidence has emerged of clinical gains using guided self-help cognitive-behavioural therapy (CBT) for child anxiety and by involving parents in treatment; however, the efficacy of guided parent-delivered CBT has not been systematically evaluated in UK primary and secondary settings. Aims To evaluate the efficacy of low-intensity guided parent-delivered CBT treatments for children with anxiety disorders. Method A total of 194 children presenting with a current anxiety disorder, whose primary carer did not meet criteria for a current anxiety disorder, were randomly allocated to full guided parent-delivered CBT (four face-to-face and four telephone sessions) or brief guided parent-delivered CBT (two face-to-face and two telephone sessions), or a wait-list control group (trial registration: ISRCTN92977593). Presence and severity of child primary anxiety disorder (Anxiety Disorders Interview Schedule for DSM-IV, child/parent versions), improvement in child presentation of anxiety (Clinical Global Impression-Improvement scale), and change in child anxiety symptoms (Spence Children’s Anxiety Scale, child/parent version and Child Anxiety Impact scale, parent version) were assessed at post-treatment and for those in the two active treatment groups, 6 months post-treatment. Results Full guided parent-delivered CBT produced superior diagnostic outcomes compared with wait-list at post-treatment, whereas brief guided parent-delivered CBT did not: at post-treatment, 25 (50%) of those in the full guided CBT group had recovered from their primary diagnosis, compared with 16 (25%) of those on the wait-list (relative risk (RR) 1.85, 95% CI 1.14-2.99); and in the brief guided CBT group, 18 participants (39%) had recovered from their primary diagnosis post-treatment (RR = 1.56, 95% CI 0.89-2.74). Level of therapist training and experience was unrelated to child outcome. Conclusions Full guided parent-delivered CBT is an effective and inexpensive first-line

The Article 51 reporting requirement for self-defense actions

This article examines one legal criterion for the exercise of the right of self-defense that has been significantly overlooked by commentators: the so-called “reporting requirement.” Article 51 of the United Nations (UN) Charter provides, inter alia, that “[m]easures taken by members in the exercise of this right of self-defense shall be immediately reported to the Security Council.” Although the requirement to report all self-defense actions to the Council is clearly set out in Article 51, the Charter offers no further guidance with regard to this obligation. Reference to the practice of states since the UN’s inception in 1945 is therefore essential to understanding the scope and nature of the reporting requirement. As such, this article is underpinned by an extensive original dataset of reporting practice covering the period from January 1, 1998 to December 31, 2013. We know from Article 51 that states “shall” report, but do they, and—if so—in what manner? What are the various implications of reporting, of failing to report, and of the way in which states report? How are reports used, and by whom? Most importantly, this article questions the ultimate value of states reporting their self-defense actions to the Security Council in modern interstate relations.

The 'ratione temporis' elements of self-defence

This article focuses on one particular factor that is of crucial importance to all self-defence actions. It is a factor that is almost always present in the application and appraisal of the right, but one that is not always explicitly engaged with: time. There are various ratione temporis elements underpinning the lawful exercise of the right of self-defence, and questions related to the timing of both an attack being responded to in self-defence and the response itself are notably controversial. The self-defence timeline is therefore charted, and the key legal debates encountered along its trajectory are identified. In particular, there is a focus on three temporal ‘stages’ of the right of self-defence: (i) the much-debated question of preventative forms of self-defence (the ‘before’); (ii) the timeliness of a state's defensive action, or what is sometimes called the need for the response to be ‘immediate’ (the ‘during’); and (iii) the duration of self-defence actions, including the crucial issue of when they must end (the ‘after’). The aim of this article is not to break new substantive ground with regard to these ‘stages’ as such, but is, rather, to draw together the temporal strands of self-defence in a more focused manner than is often the case in the literature.

New self-assembling multifunctional templates for the biofabrication and controlled self-release of cultured tissue

The need to source live human tissues for research and clinical applications has been a major driving force for the development of new biomaterials. Ideally, these should elicit the formation of scaffold-free tissues with native-like structure and composition. In this study, we describe a biologically interactive coating that combines the fabrication and subsequent self-release of live purposeful tissues using template–cell–environment feedback. This smart coating was formed from a self-assembling peptide amphiphile comprising a proteasecleavable sequence contiguous with a cell attachment and signaling motif. This multifunctional material was subsequently used not only to instruct human corneal or skin fibroblasts to adhere and deposit discreet multiple layers of native extracellular matrix but also to govern their own self-directed release from the template solely through the action of endogenous metalloproteases. Tissues recovered through this physiologically relevant process were carrier-free and structurally and phenotypically equivalent to their natural counterparts. This technology contributes to a new paradigm in regenerative medicine, whereby materials are able to actively direct and respond to cell behavior. The novel application of such materials as a coating capable of directing the formation and detachment of complex tissues solely under physiological conditions can have broad use for fundamental research and in future cell and tissue therapies.

The metaphysics of self in Praśastapāda's differential naturalism

In A Compendium of the Characteristics of Categories (Padārthadharmasaṃgraha) the classical Vaiśeṣika philosopher Praśastapāda (6th c. CE) presents an innovative metaphysics of the self. This article examines the defining metaphysical and axiological features of this conception of self and the dualist categorial schema in which it is located. It shows how this idea of the self, as a reflexive and ethical being, grounds a multinaturalist view of natural order and offers a conception of agency that claims to account for all the reflexive features of human mental and bodily life. Finally, it discusses the ends of self’s reflexivity and of human life as a return to the true self. It argues that at the heart of Praśastapāda’s metaphysics of self is the idea that ethics is metaphysics, and that epistemic practice is ethical practice.

Self-reported conflict management competence among nursing students on the point of graduating and registered nurses with professional experience

Objective: It has been shown that specific competence is necessary for preventing and managing conflicts in healthcare settings. The aim of this descriptive and correlation study was to investigate and compare the self-reported conflict management competence (CMC) of nursing students who were on the point of graduating (NSPGs), and the CMC of registered nurses (RNs) with professional experience. Methods: The data collection, which consisted of soliciting answers to items measuring CMC in the Nurse Professional Competence (NPC) Scale, was performed as a purposive selection of 11 higher education institutions (HEIs) in Sweden. Three CMC items from the NPC Scale were answered by a total of 569 nursing students who were on the point of graduating and 227 RN registered nurses with professional experience. Results: No significant differences between NSPGs and RNs were found, and both groups showed a similar score pattern, with the lowest score for the item: “How do you perceive your ability to develop the group and strengthen competence in conflict management and problem-solving, based on knowledge of group dynamics?”. RNs with long professional experience (>24 months) rated their overall CMC as significantly better than RNs with short (<24 months) professional experience did (p = .05). NSPGs who had experience of international studies during their nursing education reported higher CMC, compared with those who did not have this experience (p = .03). RNs who reported a high degree of utilisation of CMC during the previous month scored higher regarding self-reported overall CMC (p < .0001). Conclusions: Experience of international studies during nursing education, or long professional experience, resulted in higher self-reported CMC. Hence, the CMC items in the NPC Scale can be suitable for identifying self-reported conflict management competence among NSPGs and RNs

The self-polarization effect in Pb(Zr0.50Ti0.50)O-3 thin films with no preferential orientation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The growing importance of materials that prevent microbial adhesion: antimicrobial effect of medical devices containing silver

Research has clarified the properties required for polymers that resist bacterial colonisation for use in medical devices. The increase in antibiotic-resistant microorganisms has prompted interest in the use of silver as an antimicrobial agent. Silver-based polymers can protect the inner and outer surfaces of devices against the attachment of microorganisms. Thus, this review focuses on the mechanisms of various silver forms as antimicrobial agents against different microorganisms and biofilms as well as the dissociation of silver ions and the resulting reduction in antimicrobial efficacy for medical devices. This work suggests that the characteristics of released silver ions depend on the nature of the silver antimicrobial used and the polymer matrix. In addition, the elementary silver, silver zeolite and silver nanoparticles, used in polymers or as coatings could be used as antimicrobial biomaterials for a variety of promising applications. (C) 2009 Elsevier B. V. and the International Society of Chemotherapy. All rights reserved.

Quality of life (QoL) in relation to disease severity in Brazilian Parkinson's patients as measured using the WHOQOL-BREF

This study aimed at evaluating and describing the QoL and its association with the severity of disease among Brazilian Parkinson's disease (PD) patients. In this cross-sectional study 68 PD patients were interviewed using the World Health Organization Quality of Life instrument Short Form (WHOQOL-BREF) and the Hoehn-Yahr (HY) scale. Analysis of variance, chi(2), Kruskal-Wallis and Mann-Whitney U-tests, Spearman and Cronbach reliability coefficients were used to analyze the data. The results indicate: (1) physical capacity was the domain that showed the most deterioration; (2) severity of PD is associated with QoL measured by WHOQOL-BREF; (3) overall QoL, working capacity, activities of daily living (ADL) and self-esteem are affected in both transitional periods in the progression of PD (mild to moderate and moderate to advanced). Satisfaction with general health, pain, energy, positive feelings, personal relationship and satisfaction with home are affected in the first period of transition while mobility, body image, sexual activity and access to information are affected in the second. This study mainly shows specific facets that are affected depending on the specific periods of PD progression, which can help to understand the impact of the disease, the effectiveness of care, and the demand for health care resources. (C) 2007 Elsevier B.V. All rights reserved.

Biochemical characterization of Neurospora crassa glycogenin (GNN), the self-glucosylating initiator of glycogen synthesis

Glycogenin acts in the initiation step of glycogen biosynthesis by catalyzing a self-glucosylation reaction. In a previous work [de Paula et al., Arch. Biochem. Biophys. 435 (2005) 112-124], we described the isolation of the cDNA gnn, which encodes the protein glycogenin (GNN) in Neurospora crassa. This work presents a set of biochemical and functional studies confirming the GNN role in glycogen biosynthesis. Kinetic experiments showed a very low GNN K-m (4.41 mu M) for the substrate UDP-glucose. Recombinant GNN was produced in Escherichia coli and analysis by mass spectroscopy identified a peptide containing an oligosaccharide chain attached to Tyr196 residue. Site-directed mutagenesis and functional complementation of a Saccharomyces cerevisiae mutant strain confirmed the participation of this residue in the GNN self-glucosylation and indicated the Tyr198 residue as an additional, although less active, glucosylation site. The physical interaction between GNN and glycogen synthase (GSN) was analyzed by the two-hybrid assay. While the entire GSN was required for full interaction, the C-terminus in GNN was more important. Furthermore, mutation in the GNN glucosylation sites did not impair the interaction with GSN. (c) 2005 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

On the coupling of the self-dual field to dynamical U(1) matter and its dual theory

We consider arbitrary U (1) charged matter non-minimally coupled to the self-dual field in d = 2 + 1. The coupling includes a linear and a rather general quadratic term in the self-dual field. By using both Lagragian gauge embedding and master action approaches we derive the dual Maxwell Chern-Simons-type model and show the classical equivalence between the two theories. At the quantum level the master action approach in general requires the addition of an awkward extra term to the Maxwell Chern-Simons-type theory. Only in the case of a linear coupling in the self-dual field can the extra term be dropped and we are able to establish the quantum equivalence of gauge invariant correlation functions in both theories.