Mechanisms of mono- and poly-ubiquitination : ubiquitination specificity depends on compatibility between the E2 catalytic core and amino acid residues proximal to the lysine

Ubiquitination involves the attachment of ubiquitin to lysine residues on substrate proteins or itself, which can result in protein monoubiquitination or polyubiquitination. Ubiquitin attachment to different lysine residues can generate diverse substrate-ubiquitin structures, targeting proteins to different fates. The mechanisms of lysine selection are not well understood. Ubiquitination by the largest group of E3 ligases, the RING-family E3 s, is catalyzed through co-operation between the non-catalytic ubiquitin-ligase (E3) and the ubiquitin-conjugating enzyme (E2), where the RING E3 binds the substrate and the E2 catalyzes ubiquitin transfer. Previous studies suggest that ubiquitination sites are selected by E3-mediated positioning of the lysine toward the E2 active site. Ultimately, at a catalytic level, ubiquitination of lysine residues within the substrate or ubiquitin occurs by nucleophilic attack of the lysine residue on the thioester bond linking the E2 catalytic cysteine to ubiquitin. One of the best studied RING E3/ E2 complexes is the Skp1/Cul1/F box protein complex, SCFCdc4, and its cognate E2, Cdc34, which target the CDK inhibitor Sic1 for K48-linked polyubiquitination, leading to its proteasomal degradation. Our recent studies of this model system demonstrated that residues surrounding Sic1 lysines or lysine 48 in ubiquitin are critical for ubiquitination. This sequence-dependence is linked to evolutionarily conserved key residues in the catalytic region of Cdc34 and can determine if Sic1 is mono- or poly-ubiquitinated. Our studies indicate that amino acid determinants in the Cdc34 catalytic region and their compatibility to those surrounding acceptor lysine residues play important roles in lysine selection. This may represent a general mechanism in directing the mode of ubiquitination in E2 s.

High mobility diketopyrrolopyrrole (DPP)-based organic semiconductor materials for organic thin film transistors and photovoltaics

In recent years, the electron-accepting diketopyrrolopyrrole (DPP) moiety has been receiving considerable attention for constructing donor-acceptor (D-A) type organic semiconductors for a variety of applications, particularly for organic thin film transistors (OTFTs) and organic photovoltaics (OPVs). Through association of the DPP unit with appropriate electron donating building blocks, the resulting D-A molecules interact strongly in the solid state through intermolecular D-A and π-π interactions, leading to highly ordered structures at the molecular and microscopic levels. The closely packed molecules and crystalline domains are beneficial for intermolecular and interdomain (or intergranular) charge transport. Furthermore, the energy levels can be readily adjusted, affording p-type, n-type, or ambipolar organic semiconductors with highly efficient charge transport properties in OTFTs. In the past few years, a number of DPP-based small molecular and polymeric semiconductors have been reported to show mobility close to or greater than 1 cm2 V -1 s-1. DPP-based polymer semiconductors have achieved record high mobility values for p-type (hole mobility: 10.5 cm2 V-1 s-1), n-type (electron mobility: 3 cm2 V-1 s-1), and ambipolar (hole/electron mobilities: 1.18/1.86 cm2 V-1 s-1) OTFTs among the known polymer semiconductors. Many DPP-based organic semiconductors have favourable energy levels and band gaps along with high hole mobility, which enable them as promising donor materials for OPVs. Power conversion efficiencies (PCE) of up to 6.05% were achieved for OPVs using DPP-based polymers, demonstrating their potential usefulness for the organic solar cell technology. This article provides an overview of the recent exciting progress made in DPP-containing polymers and small molecules that have shown high charge carrier mobility, around 0.1 cm2 V-1 s-1 or greater. It focuses on the structural design, optoelectronic properties, molecular organization, morphology, as well as performances in OTFTs and OPVs of these high mobility DPP-based materials.

Annealing-free high-mobility diketopyrrolopyrrole-quaterthiophene copolymer for solution-processed organic thin film transistors

A donor-acceptor polymer semiconductor, PDQT, comprising diketopyrrolopyrrole (DPP) and β-unsubstituted quaterthiophene (QT) for organic thin film transistors (OTFTs) is reported. This polymer forms ordered layer-by-layer lamellar packing with an edge-on orientation in thin films even without thermal annealing. The strong intermolecular interactions arising from the fused aromatic DPP moiety and the DPP-QT donor-acceptor interaction facilitate the spontaneous self-assembly of the polymer chains into close proximity and form a large π-π overlap, which are favorable for intermolecular charge hopping. The well-interconnected crystalline grains form efficient intergranular charge transport pathways. The desirable chemical, electronic, and morphological structures of PDQT bring about high hole mobility of up to 0.97 cm2/(V·s) in OTFTs with polymer thin films annealed at a mild temperature of 100 °C and similarly high mobility of 0.89 cm2/(V·s) for polymer thin films even without thermal annealing.

One-step macroscopic alignment of conjugated polymer systems by epitaxial crystallization during spin-coating

The one-step preparation of highly anisotropic polymer semiconductor thin films directly from solution is demonstrated. The conjugated polymer poly(3-hexylthiophene) (P3HT) as well as P3HT:fullerene bulk-heterojunction blends can be spin-coated from a mixture of the crystallizable solvent 1,3,5-trichlorobenzene (TCB) and a second carrier solvent such as chlorobenzene. Solidification is initiated by growth of macroscopic TCB spherulites followed by epitaxial crystallization of P3HT on TCB crystals. Subsequent sublimation of TCB leaves behind a replica of the original TCB spherulites. Thus, highly ordered thin films are obtained, which feature square-centimeter-sized domains that are composed of one spherulite-like structure each. A combination of optical microscopy and polarized photoluminescence spectroscopy reveals radial alignment of the polymer backbone in case of P3HT, whereas P3HT:fullerene blends display a tangential orientation with respect to the center of spherulite-like structures. Moreover, grazing-incidence wide-angle X-ray scattering reveals an increased relative degree of crystallinity and predominantly flat-on conformation of P3HT crystallites in the blend. The use of other processing methods such as dip-coating is also feasible and offers uniaxial orientation of the macromolecule. Finally, the applicability of this method to a variety of other semi-crystalline conjugated polymer systems is established. Those include other poly(3-alkylthiophene)s, two polyfluorenes, the low band-gap polymer PCPDTBT, a diketopyrrolopyrrole (DPP) small molecule as well as a number of polymer:fullerene and polymer:polymer blends. Macroscopic spherulite-like structures of the conjugated polymer poly(3-hexylthiophene) (P3HT) grow directly during spin-coating. This is achieved by processing P3HT or P3HT:fullerene bulk heterojunction blends from a mixture of the crystallizable solvent 1,3,5-trichlorobenzene and a second carrier solvent such as chlorobenzene. Epitaxial growth of the polymer on solidified solvent crystals gives rise to circular-symmetric, spherulite-like structures that feature a high degree of anisotropy.

Synthesis, characterization and comparative OFET behaviour of indenofluorene-bithiophene and terthiophene alternating copolymers

The synthesis of alternating copolymers of tetraalkylindenofluorene with bithiophene and terthiophene using Suzuki polycondensation route is reported. We report on the optical and electrochemical properties of these copolymers. AFM analysis of the microscopic morphology of thin deposits showed that the copolymer with terthiophene units produced the more ordered films, with well-defined fibrillar structures, resulting from highly-regular dense packing due to strong π-π interchain interactions, in contrast to the amorphous bithiophene copolymer. Upon testing these materials in FETs the terthienyl copolymers displayed the higher charge mobilities among the studied compounds, with values of over 10-4 cm2 V-1 s-1 being obtained.

Synthesis, characterization and comparative study of thiophene- benzothiadiazole based donor-acceptor-donor (D-A-D) materials

The synthesis and characterization of solution processable donor-acceptor-donor (D-A-D) based conjugated molecules with varying ratios of thiophene as donor (D) and benzothiadiazole as acceptor (A) are reported. Optical, electrochemical, thermal, morphological and organic thin film transistor (OTFT) device properties of these materials were investigated. The thermal and polarized optical microscope analysis indicates that the materials having higher D/A ratios exhibit both liquid crystalline (LC) and OTFT behavior. AFM analysis of the materials having D/A ratios of 3 and 4 (3T1B and 4T1B) show well ordered structures, resulting from strong π-π interchain interactions compared to the other molecules in this study. A XRD patterns for 3T1B and 4T1B thin films also shows high crystalline ordering. Solution processed OTFTs of 3T1B and 4T1B have shown un-optimized charge carrier mobilities of 2 × 10 -2 cm 2 V -1 s -1 and 4 × 10 -3 cm 2 V -1 s -1, respectively on bare Si/SiO 2 substrate.

Solid-state assemblies and optical properties of conjugated oligomers combining fluorene and thiophene units

Two conjugated oligomers, representing elementary segments of fluorene-thiophene copolymers, are compared in terms of the microscopic morphology and the optical properties of thin deposits. The atomic force microscopy morphological data and the solid-state absorption and emission spectra are interpreted in terms of the assembly of the conjugated molecules. The compound with a terthiophene central unit and fluorene end-groups shows well-defined monolayer-by-monolayer assembly into micrometer-long stripe-like structures, with a crystalline herringbone-type organization within the monolayers. Polarized confocal microscopy indicates a strong orientation of the crystalline domains within the stripes. In contrast, the compound with a terfluorene central unit and thiophene end groups forms no textured aggregates and the optical spectra in the solid-state are very similar to those recorded in solution, suggesting that the molecules interact only weakly in the solid. The difference in behaviour between the two compounds most probably originates from their different capability to form densely-packed assemblies of interacting π-systems.

CT Anatomy for Radiotherapy

Knowledge of CT anatomy is increasingly vital in daily radiotherapy practice, especially with more widespread use of cross-sectional image-guided radiotherapy (IGRT) techniques. Existing CT anatomy texts are predominantly written for the diagnostic practitioner and do not always address the radiotherapy issues while emphasising structures that are not common to radiotherapy practice. CT Anatomy for Radiotherapy is a new radiotherapy-specific text that is intended to prepare the reader for CT interpretation for both IGRT and treatment planning. It is suitable for undergraduate students, qualified therapy radiographers, dosimetrists and may be of interest to oncologists and registrars engaged in treatment planning. All essential structures relevant to radiotherapy are described and depicted on 3D images generated from radiotherapy planning systems. System-based labelled CT images taken in relevant imaging planes and patient positions build up understanding of relational anatomy and CT interpretation. Images are accompanied by comprehensive commentary to aid with interpretation. This simplified approach is used to empower the reader to rapidly gain image interpretation skills. The book pays special attention to lymph node identification as well as featuring a unique section on Head and Neck Deep Spaces to help understanding of common pathways of tumour spread. Fully labelled CT images using radiotherapy-specific views and positioning are complemented where relevant by MR and fusion images. A brief introduction to image interpretation using IGRT devices is also covered. The focus of the book is on radiotherapy and some images of common tumour pathologies are utilised to illustrate some relevant abnormal anatomy. Short self-test questions help to keep the reader engaged throughout.

On the operationalisation of conceptions of learning in higher education and their association with students’ knowledge and experiences of their learning

Conceptions of learning, as well as other associated aspects of prior knowledge, are theoretically important factors in influencing the manner in which the content and context of learning are engaged. The present study reports on: (a) the operationalisation of some of these factors aimed at isolating sources of explanatory variation that can be used for modelling purposes; and (b) a conservative exploration of the discriminatory power of, and exhibited patterns of association between, such sources of variation as have been isolated. Based on a conservative analytical approach, the results of the present study do not support a single clearly defined empirical model of conceptions of learning and associated constructs. Instead, there is consistent evidence that underlying empirical structures appear to be sensitive to the response context and other factors.

Promoting law student well-being through the curriculum

The Australian tertiary sector is becoming increasingly concerned about the psychological well-being of its students.Empirical research in Australia indicates that more than one-third of law students suffer from psychological distress, and the competitive, isolated, adversarial learning environment at law school has been suggested as partly responsible (Brain and Mind Research Institute, 2009). This fellowship program has mobilised strategic change to improve the psychological health of law students. It has lead and stimulated advancement in the legal curriculum, its pedagogy, and assessment practice to better engage, motivate and support student learning of law, focussing on the potential of non-adversarial legal practice. A new conceptual framework for legal education has been developed, demonstrating the pursuit of excellence in the teaching of law, and raising the profile of learning and teaching in Australian law schools. In addition the fellowship has created a national community of practice around this issue through the Wellness Network for Law, and made significant contributions to research and scholarship in the field.

Breathe easier online : evaluation of a randomized controlled pilot trial of an internet-based intervention to improve well-being in children and adolescents with a chronic respiratory condition

Background Chronic respiratory illnesses are the most common group of childhood chronic health conditions and are overrepresented in socially isolated groups. Objective To conduct a randomized controlled pilot trial to evaluate the efficacy of Breathe Easier Online (BEO), an Internet-based problem-solving program with minimal facilitator involvement to improve psychosocial well-being in children and adolescents with a chronic respiratory condition. Methods We randomly assigned 42 socially isolated children and adolescents (18 males), aged between 10 and 17 years to either a BEO (final n = 19) or a wait-list control (final n = 20) condition. In total, 3 participants (2 from BEO and 1 from control) did not complete the intervention. Psychosocial well-being was operationalized through self-reported scores on depression symptoms and social problem solving. Secondary outcome measures included self-reported attitudes toward their illness and spirometry results. Paper-and-pencil questionnaires were completed at the hospital when participants attended a briefing session at baseline (time 1) and in their homes after the intervention for the BEO group or a matched 9-week time period for the wait-list group (time 2). Results The two groups were comparable at baseline across all demographic measures (all F < 1). For the primary outcome measures, there were no significant group differences on depression (P = .17) or social problem solving (P = .61). However, following the online intervention, those in the BEO group reported significantly lower depression (P = .04), less impulsive/careless problem solving (P = .01), and an improvement in positive attitude toward their illness (P = .04) compared with baseline. The wait-list group did not show these differences. Children in the BEO group and their parents rated the online modules very favorably. Conclusions Although there were no significant group differences on primary outcome measures, our pilot data provide tentative support for the feasibility (acceptability and user satisfaction) and initial efficacy of an Internet-based intervention for improving well-being in children and adolescents with a chronic respiratory condition. Trial registration Australian New Zealand Clinical Trials Registry number: ACTRN12610000214033;

Bayesian hierarchical models for analysing spatial point-based data at a grid level: A comparison of approaches

Spatial data are now prevalent in a wide range of fields including environmental and health science. This has led to the development of a range of approaches for analysing patterns in these data. In this paper, we compare several Bayesian hierarchical models for analysing point-based data based on the discretization of the study region, resulting in grid-based spatial data. The approaches considered include two parametric models and a semiparametric model. We highlight the methodology and computation for each approach. Two simulation studies are undertaken to compare the performance of these models for various structures of simulated point-based data which resemble environmental data. A case study of a real dataset is also conducted to demonstrate a practical application of the modelling approaches. Goodness-of-fit statistics are computed to compare estimates of the intensity functions. The deviance information criterion is also considered as an alternative model evaluation criterion. The results suggest that the adaptive Gaussian Markov random field model performs well for highly sparse point-based data where there are large variations or clustering across the space; whereas the discretized log Gaussian Cox process produces good fit in dense and clustered point-based data. One should generally consider the nature and structure of the point-based data in order to choose the appropriate method in modelling a discretized spatial point-based data.

Engineering the mechanical properties of graphene nanotube hybrid structures through structural modulation

The excellent multi-functional properties of carbon nanotube (CNT) and graphene have enabled them as appealing building blocks to construct 3D carbon-based nanomaterials or nanostructures. The recently reported graphene nanotube hybrid structure (GNHS) is one of the representatives of such nanostructures. This work investigated the relationships between the mechanical properties of the GNHS and its structure basing on large-scale molecular dynamics simulations. It is found that increasing the length of the constituent CNTs, the GNHS will have a higher Young’s modulus and yield strength. Whereas, no strong correlation is found between the number of graphene layers and Young’s modulus and yield strength, though more graphene layers intends to lead to a higher yield strain. In the meanwhile, the presences of multi-wall CNTs are found to greatly strengthen the hybrid structure. Generally, the hybrid structures exhibit a brittle behavior and the failure initiates from the connecting regions between CNT and graphene. More interestingly, affluent formations of monoatomic chains and rings are found at the fracture region. This study provides an in-depth understanding of the mechanical performance of the GNHSs while varying their structures, which will shed lights on the design and also the applications of the carbon-based nanostructures.

The corporate governance effects of audit committees

Arguments associated with the promotion of audit committees in many countries are premised on their potential for alleviating weaknesses in corporate governance. This paper provides a synthesis and evaluation of empirical research on the governance effects associated with audit committees. Given recent policy recommendations in several countries aimed at strengthening these committees, it is important to establish what research evidence demonstrates about their existing governance contribution. A framework for analyzing the impact of audit committees is described, identifying potential perceived effects which may have led to their adoption and documented effects on aspects of the audit function, on financial reporting quality and on corporate performance. It is argued that there is only limited and mixed evidence of effects to support claims and perceptions about the value of audit committees for these elements of governance. It is also shown that most of the existing research has focused on factors associated with audit committee existence, characteristics and measures of activity and there is very little evidence on the processes associated with the operation of audit committees and the manner in which they influence organizational behaviour. It is clear that there is no automatic relationship between the adoption of audit committee structures or characteristics and the achievement of particular governance effects, and caution may be needed over expectations that greater codification around factors such as audit committee members’ independence and expertise as the means of ‘‘correcting’’ past weaknesses in the arrangements for audit committees. The most fundamental question concerning what difference audit committees make in practice continues to be an important area for research development. For future research we suggest: (i) greater consideration of the organizational and institutional contexts in which audit committees operate; (ii) explicit theorization of the processes associated with audit committee operation; (iii) complementing extant research methods with field studie, and; (iv) investigation of unintended (behavioural) as well as expected consequences of audit committees.