Small‐Molecule Proteomimetic Inhibitors of the HIF‐1α–p300 Protein–Protein Interaction

The therapeutically relevant hypoxia inducible factor HIF‐1α–p300 protein–protein interaction can be orthosterically inhibited with α‐helix mimetics based on an oligoamide scaffold that recapitulates essential features of the C‐terminal helix of the HIF‐1α C‐TAD (C‐terminal transactivation domain). Preliminary SAR studies demonstrated the important role of side‐chain size and hydrophobicity/hydrophilicity in determining potency. These small molecules represent the first biophysically characterised HIF‐1α–p300 PPI inhibitors and the first examples of small‐molecule aromatic oligoamide helix mimetics to be shown to have a selective binding profile. Although the compounds were less potent than HIF‐1α, the result is still remarkable in that the mimetic reproduces only three residues from the 42‐residue HIF‐1α C‐TAD from which it is derived.     

Fast,automatic character animation pipelines

Humanoid three‐dimensional (3D) models can be easily acquired through various sources, including through online marketplaces. The use of such models within a game or simulation environment requires human input and intervention in order to associate such a model with a relevant set of motions and control mechanisms. In this paper, we demonstrate a pipeline where humanoid 3D models can be incorporated within seconds into an animation system and infused with a wide range of capabilities, such as locomotion, object manipulation, gazing, speech synthesis and lip syncing. We offer a set of heuristics that can associate arbitrary joint names with canonical ones and describe a fast retargeting algorithm that enables us to instill a set of behaviors onto an arbitrary humanoid skeleton on‐the‐fly. We believe that such a system will vastly increase the use of 3D interactive characters due to the ease that new models can be animated.Copyright © 2013 John Wiley & Sons, Ltd.     

An investigation into the relationship between processing,structure and properties for high-modulus PBO fibres: part 3: analysis of fibre microstructure using transmission electron microscopy

A detailed morphological study of the microstructure of poly(p-phenylene benzobisoxazole) (PBO) fibres (HM and HM+) and a polypyridobisimidazole (PIPD) (HT) fibre has been undertaken using transmission electron microscopy. Both PBO and PIPD fibres are composed of rigid-rod polymers having p-phenylene rings in the molecular backbone and show high modulus (280–360 GPa) and high strength (4–6 GPa). It is found that the PBO HM+ fibre has the highest degree of molecular orientation of the three fibres and the longest crystal length along the fibre axis, while the PIPD fibre shows a lower degree of orientation and a shorter crystal length than the PBO fibres. To understand the effect of crystalline size and fine structure of the fibres upon mechanical properties, dark-field and high-resolution lattice images were obtained and analysed in detail.     

Digital image correlation techniques to investigate strain fields and cracking phenomena in asphalt materials

This paper is the outcome of a specific task group of the RILEM Technical Committee 241-MCD “Mechanisms of Cracking and Debonding in Asphalt and Composite Pavements”. The group on “Advanced Measurement Techniques” was established in 2011 to investigate DIC applications for non-destructive and non-contact measurements of strain fields during laboratory testing. The paper illustrates different DIC/optical flow applications in measuring strain distribution during laboratory testing. Specific applications of DIC for evaluating crack initiation and crack propagation in asphalt materials are presented.     

A situated approach to the acquisition of shared SA in team contexts

Theories of team situation awareness (SA) differ in the information they require operators to have for effective coordination. Endsley stresses shared SA, whereas distributed SA argues that coordination involves transactive and compatible SA. We distinguish between weak and strong shared SA, and argue the latter enhances communication and increases team cohesion. Although we agree with Endsley on the importance of shared SA, we argue her account of how it is acquired exceeds the working memory capacity of individual team members. We offer an account consistent with our situated SA perspective that claims individuals off-load information to their environment whenever possible to minimise effortful internal processing. We argue that our approach, in conjunction with Pickering and Garrod's (2004, Towards a mechanistic psychology of dialogue. Behavioral and Brain Sciences, 27, pp. 169–226) interactive-alignment model, can explain how shared SA is acquired, relying on automatic processes enacted when individuals interact in conversations. This approach can be used to study team SA in many complex and distributed systems.     

Gadolinium‐Conjugated Gold Nanoshells for Multimodal Diagnostic Imaging and Photothermal Cancer Therapy

Multimodal imaging offers the potential to improve diagnosis and enhance the specificity of photothermal cancer therapy. Toward this goal, gadolinium‐conjugated gold nanoshells are engineered and it is demonstrated that they enhance contrast for magnetic resonance imaging, X‐ray, optical coherence tomography, reflectance confocal microscopy, and two‐photon luminescence. Additionally, these particles effectively convert near‐infrared light to heat, which can be used to ablate cancer cells. Ultimately, these studies demonstrate the potential of gadolinium‐nanoshells for image‐guided photothermal ablation.     

Active Targeting Using HER‐2‐Affibody‐Conjugated Nanoparticles Enabled Sensitive and Specific Imaging of Orthotopic HER‐2 Positive Ovarian Tumors

Despite advances in cancer diagnosis and treatment, ovarian cancer remains one of the most fatal cancer types. The development of targeted nanoparticle imaging probes and therapeutics offers promising approaches for early detection and effective treatment of ovarian cancer. In this study, HER‐2 targeted magnetic iron oxide nanoparticles (IONPs) are developed by conjugating a high affinity and small size HER‐2 affibody that is labeled with a unique near infrared dye (NIR‐830) to the nanoparticles. Using a clinically relevant orthotopic human ovarian tumor xenograft model, it is shown that HER‐2 targeted IONPs are selectively delivered into both primary and disseminated ovarian tumors, enabling non‐invasive optical and MR imaging of the tumors as small as 1 mm in the peritoneal cavity. It is determined that HER‐2 targeted delivery of the IONPs is essential for specific and sensitive imaging of the HER‐2 positive tumor since we are unable to detect the imaging signal in the tumors following systemic delivery of non‐targeted IONPs into the mice bearing HER‐2 positive SKOV3 tumors. Furthermore, imaging signals and the IONPs are not detected in HER‐2 low expressing OVCAR3 tumors after systemic delivery of HER‐2 targeted‐IONPs. Since HER‐2 is expressed in a high percentage of ovarian cancers, the HER‐2 targeted dual imaging modality IONPs have potential for the development of novel targeted imaging and therapeutic nanoparticles for ovarian cancer detection, targeted drug delivery, and image‐guided therapy and surgery.