First crystallographic signature of an acyclic peptide nanorod: molecular mechanism of nanorod formation by a self-assembled tetrapeptide

A terminally protected acyclic tetrapeptide Boc-Aib-Val-Aib-beta-Ala-OMe 1 (Aib: alpha-aminoisobutyric acid, beta-Ala: beta-Alanine) self-assembles into a continuous hydrogen-bonded supramolecular helix with an average diameter of 10Angstrom (1nm) starting from a double bend molecular conformation in crystals and further self-assembly of this supramolecular architecture leads to the formation of polydisperse nanorods of diameters 10-40 nm.

Low-molecular-weight gelators: Elucidating the principles of gelation based on gelator solubility and a cooperative self-assembly model

This paper highlights the key role played by solubility in influencing gelation and demonstrates that many facets of the gelation process depend on this vital parameter. In particular, we relate thermal stability (T-gel) and minimum gelation concentration (MGC) values of small-molecule gelation in terms of the solubility and cooperative self-assembly of gelator building blocks. By employing a van't Hoff analysis of solubility data, determined from simple NMR measurements, we are able to generate T-calc values that reflect the calculated temperature for complete solubilization of the networked gelator. The concentration dependence of T-calc allows the previously difficult to rationalize "plateau-region" thermal stability values to be elucidated in terms of gelator molecular design. This is demonstrated for a family of four gelators with lysine units attached to each end of an aliphatic diamine, with different peripheral groups (Z or Bee) in different locations on the periphery of the molecule. By tuning the peripheral protecting groups of the gelators, the solubility of the system is modified, which in turn controls the saturation point of the system and hence controls the concentration at which network formation takes place. We report that the critical concentration (C-crit) of gelator incorporated into the solid-phase sample-spanning network within the gel is invariant of gelator structural design. However, because some systems have higher solubilities, they are less effective gelators and require the application of higher total concentrations to achieve gelation, hence shedding light on the role of the MGC parameter in gelation. Furthermore, gelator structural design also modulates the level of cooperative self-assembly through solubility effects, as determined by applying a cooperative binding model to NMR data. Finally, the effect of gelator chemical design on the spatial organization of the networked gelator was probed by small-angle neutron and X-ray scattering (SANS/SAXS) on the native gel, and a tentative self-assembly model was proposed.

Self-organisation in the assembly of gels from mixtures of different dendritic peptide building blocks

This paper investigates dendritic peptides capable of assembling into nanostructured gels, and explores the effect on self-assembly of mixing different molecular building blocks. Thermal measurements, small angle Xray scattering (SAXS) and circular dichroism (CD) spectroscopy are used to probe these materials on macroscopic, nanoscopic and molecular length scales. The results from these investigations demonstrate that in this case, systems with different "size" and "chirality" factors can self-organise, whilst systems with different "shape" factors cannot. The "size" and "chirality" factors are directly connected with the molecular information programmed into the dendritic peptides, whilst the shape factor depends on the group linking these peptides together-this is consistent with molecular recognition hydrogen bond pathways between the peptidic building blocks controlling the ability of these systems to self-recognise. These results demonstrate that mixtures of relatively complex peptides, with only subtle differences on the molecular scale, can self-organise into nanoscale structures, an important step in the spontaneous assembly of ordered systems from complex mixtures.

A direct comparison of one- and two-component dendritic self-assembled materials: elucidating molecular recognition pathways

This paper compares and contrasts, for the first time, one- and two-component gelation systems that are direct structural analogues and draws conclusions about the molecular recognition pathways that underpin fibrillar self-assembly. The new one-component systems comprise L-lysine-based dendritic headgroups covalently connected to an aliphatic diamine spacer chain via an amide bond, One-component gelators with different generations of headgroup (from first to third generation) and different length spacer chains are reported. The self-assembly of these dendrimers in toluene was elucidated using thermal measurements, circular dichroism (CD) and NMR spectroscopies, scanning electron microscopy (SEM), and small-angle X-ray scattering (SAXS). The observations are compared with previous results for the analogous two-component gelation system in which the dendritic headgroups are bound to the aliphatic spacer chain noncovalently via acid-amine interactions. The one-component system is inherently a more effective gelator, partly as a consequence of the additional covalent amide groups that provide a new hydrogen bonding molecular recognition pathway, whereas the two-component analogue relies solely on intermolecular hydrogen bond interactions between the chiral dendritic headgroups. Furthermore, because these amide groups are important in the assembly process for the one-component system, the chiral information preset in the dendritic headgroups is not always transcribed into the nanoscale assembly, whereas for the two-component system, fiber formation is always accompanied by chiral ordering because the molecular recognition pathway is completely dependent on hydrogen bond interactions between well-organized chiral dendritic headgroups.

Correlation-type structure activity relationships for the kinetics of gas-phase RO2 self-reactions and reaction with HO2

Structure activity relationships (SARs) are presented for the gas-phase reactions of RO2 with HO2, and the self- and cross-reactions of RO2. For RO2+HO2 the SAR is based upon a correlation between the logarithm of the measured rate coefficient and a calculated ionisation potential for the molecule R-CH=CH2, R being the same group in both the radical and molecular analogue. The correlation observed is strong and only for one RO2 species does the measured rate coefficient deviate by more than a factor of two from the linear least-squares regression line. For the self- and cross-reactions of RO2 radicals, the SAR is based upon a correlation between the logarithm of the measured rate coefficient and the calculated electrostatic potential (ESP) at the equivalent carbon atom in the RH molecule to which oxygen is attached in RO2, again R being the same group in the molecule and the radical. For cases where R is a simple alkyl-group, a strong linear correlation observed. For RO2 radicals which contain lone pair-bearing substituents and for which the calculated ESP<-0.05 self-reaction rate coefficients appear to be insensitive to the value of the ESP. For RO2 of this type with ESP>-0.05 a linear relationship between log k and the ESP is again observed. Using the relationships, 84 out of the 85 rate coefficients used to develop the SARs are predicted to within a factor of three of their measured values. A relationship is also presented that allows the prediction of the Arrhenius parameters for the self-reactions of simple alkyl RO2 radicals. On the basis of the correlations, predictions of room-temperature rate coefficients are made for a number of atmospherically important peroxyl-peroxyl radical reactions. (C) 2003 Elsevier Ltd. All rights reserved.

Design of supramolecular beta-sheet forming beta-turns containing aromatic rings and non-coded alpha-aminoisobutyric acid and the formation of flat fibrillar structures through self-assembly

Single crystal X-ray diffraction studies show that the three designed tripeptides Boc-Leu-Aib-m-NA-NO2 (I), Boc-Phe-Aib-m-NA-NO2 (II) and Boc-Pro-Aib-m-ABA-OMe (III) (Aib, -aminoisobutyric acid; m-NA, m-nitroaniline; m-ABA, m-aminobenzoic acid; Boc, t-butyloxycarbonyl) containing aromatic rings in the backbones adopt -turn structures that are self-assembled through intermolecular hydrogen bonds and van der Waals interactions to create layers of -sheets. Solvent-dependent NMR titration and CD studies show that the -turn structures of the peptides also exist in the solution phase. The field emission scanning electron microscopic and transmission electron microscopic images of the peptides in the solid state reveal fibrillar structures of flat morphology that are formed through -sheet mediated self-assembly of the preorganised -turn building blocks.

Self-assembly and hydrogelation of an amyloid peptide fragment

The self-assembly of a fragment of the amyloid beta peptide that has been shown to be critical in amyloid fibrillization has been studied in aqueous solution. There are conflicting reports in the literature on the fibrillization of A beta (16-20), i.e., KLVFF, and our results shed light on this. In dilute solution, self-assembly of NH2-KLVFF-COOH is strongly influenced by aromatic interactions between phenylalanine units, as revealed by UV spectroscopy and circular dichroism. Fourier transform infrared (FTIR) spectroscopy reveals beta-sheet features in spectra taken for more concentrated solutions and also dried films. X-ray diffraction and cryo-transmission electron microscopy (cryo-TEM) provide further support for beta-sheet amyloid fibril formation. A comparison of cryo-TEM images with those from conventional dried and negatively stained TEM specimens highlights the pronounced effects of sample preparation on the morphology. A comparison of FTIR data for samples in solution and dried samples also highlights the strong effect of drying on the self-assembled structure. In more concentrated phosphate-buffered saline (PBS) solution, gelation of NH2-KLVFF-COOH is observed. This is believed to be caused by screening of the electrostatic charge on the peptide, which enables beta sheets to aggregate into a fibrillar gel network. The rheology of the hydrogel is probed, and the structure is investigated by light scattering and small-angle X-ray scattering.

Hydrogelation of self-assembling RGD-based peptides

The self-assembly of tripeptides based on the RGD cell adhesion motif is investigated. Two tripeptides containing the Fmoc [N-(fluorenyl)-9-methoxycarbonyl] aromatic unit were synthesized, Fmoc-RGD and a control peptide containing a scrambled sequence, Fmoc-GRD. The Fmoc is used to control selfassembly via aromatic stacking interactions. The self-assembly and hydrogelation properties of the two Fmoc-tripeptides are compared. Both form well defined amyloid fibrils (as shown by cryo-TEM and SAXS) with b-sheet features in their circular dichroism and FTIR spectra. Both peptides form selfsupporting hydrogels, the dynamic shear modulus of which was measured. Preliminary cell culture experiments reveal that Fmoc-RGD can be used as a support for bovine fibroblasts, but not Fmoc- GRD, consistent with the incorporation of the cell adhesion motif in the former peptide.

Health-related quality of life in Huntington’s Disease patients: a comparison of proxy assessment and patient self-rating using the disease-specific Huntington’s Disease health-related quality of life questionnaire (HDQoL)

Huntington’s disease (HD) is a fatal, neurodegenerative disease for which there is no known cure. Proxy evaluation is relevant for HD as its manifestation might limit the ability of persons to report their health-related quality of life (HrQoL). This study explored patient–proxy ratings of HrQoL of persons at different stages of HD, and examined factors that may affect proxy ratings. A total of 105 patient–proxy pairs completed the Huntington’s disease health-related quality of life questionnaire (HDQoL) and other established HrQoL measures (EQ-5D and SF-12v2). Proxy–patient agreement was assessed in terms of absolute level (mean ratings) and intraclass correlation. Proxies’ ratings were at a similar level to patients’ self-ratings on an overall Summary Score and on most of the six Specific Scales of the HDQoL. On the Specific Hopes and Worries Scale, proxies on average rated HrQoL as better than patients’ self-ratings, while on both the Specific Cognitive Scale and Specific Physical and Functional Scale proxies tended to rate HrQoL more poorly than patients themselves. The patient’s disease stage and mental wellbeing (SF-12 Mental Component scale) were the two factors that primarily affected proxy assessment. Proxy scores were strongly correlated with patients’ self-ratings of HrQoL, on the Summary Scale and all Specific Scales. The patient–proxy correlation was lower for patients at moderate stages of HD compared to patients at early and advanced stages. The proxy report version of the HDQoL is a useful complementary tool to self-assessment, and a promising alternative when individual patients with advanced HD are unable to self-report.

Self-ratings and observer-ratings of social skill: a manipulation of state social anxiety in anxious and non-anxious children

The role of state and trait anxiety on observer ratings of social skill and negatively biased self-perception of social skill was examined. Participants were aged between 7 and 13 years (mean=9.65; sd=1.77; N=102), 47 had a current anxiety diagnosis and 55 were non-anxious controls. Participants were randomly allocated to a high or low anxiety condition and asked to complete social tasks. Task instructions were adjusted across conditions to manipulate participants’ state anxiety. Observers rated anxious participants as having poorer social skills than non-anxious controls but there was no evidence that anxious participants exhibited a negative self-perception bias, relative to controls. However, as participants’ ratings of state anxiety increased, their perception of their performance became more negatively biased. The results suggest that anxious children may exhibit real impairments in social skill and that high levels of state anxiety can lead to biased judgements of social skills in anxious and non-anxious children.

Tuning self-assembled nanostructures through enzymatic degradation of a peptide amphiphile

The enzymatic cleavage of a peptide amphiphile (PA) is investigated. The self-assembly of the cleaved products is distinct from that of the PA substrate. The PA C16-KKFFVLK is cleaved by α-chymotrypsin at two sites leading to products C16-KKF with FVLK and C16-KKFF with VLK. The PA C16-KKFFVLK forms nanotubes and helical ribbons at room temperature. Both PAs C16-KKF and C16-KKFF corresponding to cleavage products instead self-assemble into 5-6 nm diameter spherical micelles, while peptides FVLK and VLK do not adopt well-defined aggregate structures. The secondary structures of the PAs and peptides are examined by FTIR and circular dichroism spectroscopy and X-ray diffraction. Only C16-KKFFVLK shows substantial β-sheet secondary structure, consistent with its self-assembly into extended aggregates, based on PA layers containing hydrogen-bonded peptide headgroups. This PA also exhibits a thermoreversible transition to twisted tapes on heating.

Unpacking the mechanism by which psychological ownership manifests at the level of the individual: a dynamic model of identity and self

Increasing prominence of the psychological ownership (PO) construct in management studies raises questions about how PO manifests at the level of the individual. In this article, we unpack the mechanism by which individuals use PO to express aspects of their identity and explore how PO manifestations can display congruence as well as incongruence between layers of self. As a conceptual foundation, we develop a dynamic model of individual identity that differentiates between four layers of self, namely, the “core self,” “learned self,” “lived self,” and “perceived self.” We then bring identity and PO literatures together to suggest a framework of PO manifestation and expression viewed through the lens of the four presented layers of self. In exploring our framework, we develop a number of propositions that lay the foundation for future empirical and conceptual work and discuss implications for theory and practice.

Construction management research: a field of application

Research in construction management is diverse in content and in quality. There is much to be learned from more fundamental disciplines. Construction is a sub-set of human experience rather than a completely separate phenomenon. Therefore, it is likely that there are few problems in construction requiring the invention of a completely new theory. If construction researchers base their work only on that of other construction researchers, our academic community will become less relevant to the world at large. The theories that we develop or test must be of wider applicability to be of any real interest. In undertaking research, researchers learn a lot about themselves. Perhaps the only difference between research and education is that if we are learning about something which no-one else knows, then it is research, otherwise it is education. Self-awareness of this will help to reduce the chances of publishing work which only reveals a researcher’s own learning curve. Scientific method is not as simplistic as non-scientists claim and is the only real way of overcoming methodological weaknesses in our work. The reporting of research may convey the false impression that it is undertaken in the sequence in which it is written. Construction is not so unique and special as to require a completely different set of methods from other fields of enquiry. Until our research is reported in mainstream journals and conferences, there is little chance that we will influence the wider academic community and a concomitant danger that it will become irrelevant. The most useful insights will come from research which challenges the current orthodoxy rather than research which merely reports it.

Construction research: a field of application

Research in construction management is diverse in content and in quality. There is much to be learned from more fundamental disciplines. Construction is a sub-set of human experience rather than a completely separate phenomenon. Therefore, it is likely that there are few problems in construction requiring the invention of a completely new theory. If construction researchers base their work only on that of other construction researchers, our academic community will become less relevant to the world at large. The theories that we develop or test must be of wider applicability to be of any real interest. In undertaking research, researchers learn a lot about themselves. Perhaps the only difference between research and education is that if we are learning about something which no-one else knows, then it is research, otherwise it is education. Self-awareness of this will help to reduce the chances of publishing work which only reveals a researcher’s own learning curve. Scientific method is not as simplistic as non-scientists claim and is the only real way of overcoming methodological weaknesses in our work. The reporting of research may convey the false impression that it is undertaken in the sequence in which it is written. Construction is not so unique and special as to require a completely different set of methods from other fields of enquiry. Until our research is reported in mainstream journals and conferences, there is little chance that we will influence the wider academic community and a concomitant danger that it will become irrelevant. The most useful insights will come from research which challenges the current orthodoxy rather than research which merely reports it.

How is the language of medicines use review leaflets symbolising the service?

Introduction The medicines use review (MUR), a new community pharmacy ‘service’, was launched in England and Wales to improve patients’ knowledge and use of medicines through a private, patient–pharmacist appointment. After 18 months, only 30% of pharmacies are providing MURs; at an average of 120 per annum (maximum 400 allowed).1 One reason linked to low delivery is patient recruitment.2 Our aim was to examine how the MUR is symbolised and given meaning via printed patient information, and potential implications. Method The language of 10 MUR patient leaflets, including the NHS booklet,3 and leaflets from multiples and wholesalers was evaluated by discourse analysis. Results and Discussion Before experiencing MURs, patients conceivably ‘categorise’ relationships with pharmacists based on traditional interactions.4 Yet none of the leaflets explicitly describe the MUR as ‘new’ and presuppose patients would become involved in activities outside of their pre-existing relationship with pharmacists such as appointments, self-completion of charts, and pharmacy action plans. The MUR process is described inconsistently, with interchangeable use of formal (‘review meeting‘) and informal (‘friendly’) terminology, the latter presumably to portray an intended ‘negotiation model’ of interaction.5 Assumptions exist about attitudes (‘not understanding’; ‘problems’) that might lead patients to an appointment. However, research has identified a multitude of reasons why patients choose (or not) to consult practitioners,6 and marketing of MURs should also consider other barriers. For example, it may be prudent to remove time limits to avoid implying patients might not be listened to fully, during what is for them an additional practitioner consultation.