Modeling of arylamide helix mimetics in the p53 peptide binding site of hDM2 suggests parallel and anti-parallel conformations are both stable.

The design of novel α-helix mimetic inhibitors of protein-protein interactions is of interest to pharmaceuticals and chemical genetics researchers as these inhibitors provide a chemical scaffold presenting side chains in the same geometry as an α-helix. This conformational arrangement allows the design of high affinity inhibitors mimicking known peptide sequences binding specific protein substrates. We show that GAFF and AutoDock potentials do not properly capture the conformational preferences of α-helix mimetics based on arylamide oligomers and identify alternate parameters matching solution NMR data and suitable for molecular dynamics simulation of arylamide compounds. Results from both docking and molecular dynamics simulations are consistent with the arylamides binding in the p53 peptide binding pocket. Simulations of arylamides in the p53 binding pocket of hDM2 are consistent with binding, exhibiting similar structural dynamics in the pocket as simulations of known hDM2 binders Nutlin-2 and a benzodiazepinedione compound. Arylamide conformations converge towards the same region of the binding pocket on the 20 ns time scale, and most, though not all dihedrals in the binding pocket are well sampled on this timescale. We show that there are two putative classes of binding modes for arylamide compounds supported equally by the modeling evidence. In the first, the arylamide compound lies parallel to the observed p53 helix. In the second class, not previously identified or proposed, the arylamide compound lies anti-parallel to the p53 helix

Construct-it: A board game to enhance built environment students’ understanding of the property life cycle

This article investigates the development of a board game entitled ‘Construct-it’ as an innovative pedagogical approach (as proof of concept) to augmenting the applied knowledge and understanding of built environment students studying property life cycle analysis. A largely qualitative and inductive methodological approach is conducted to identify and investigate the various pertinent theoretical frameworks that could be adopted; conduct a critical synthesis of extant literature; and develop Construct-it, a game intuitively grounded in practice-based knowledge. The study reveals that games provide a fun, engaging and challenging means of educating students at higher education institutions. It also notes a significant dearth of literature in terms of applying games to students enrolled on built environment programmes. Construct-it can enhance the student’s learning experience and knowledge of pertinent industry practice and standards and can complement traditional classroom teaching approaches. The study concludes with directions for the future work required to enhance the development of the novel pedagogical proof of concept presented. Such work will require robust testing and validation of the game to measure its impact on the student learning experience. </jats:p

Fluid therapy in critical illness

Major surgery and critical illnesses such as sepsis and trauma all disturb normal physiological fluid handling. Intravenous fluid therapy for resuscitation and fluid maintenance is a central part of medical care during these conditions, yet the evidence base supporting practice in this area lacks answers to a number of important questions. Recent research developments include a refinement of our knowledge of the endothelial barrier structure and function and a focus on the potential harm that may be associated with intravenous fluid therapy. Here, we briefly describe the contemporary view of fluid physiology and how this may be disrupted by pathological processes. The important themes in critical illness fluid research are discussed, with a particular focus on two emerging ideas: firstly, that individualising fluid treatment to the patient, their underlying disease state and the phase of that illness may be key to improving clinical outcomes using fluid interventions and, secondly, that fluids should be considered to be drugs, with specific indications and contraindications, dose ranges and potential toxicities

Approximately coloring graphs without long induced paths

It is an open problem whether the 3-coloring problem can be solved in polynomial time in the class of graphs that do not contain an induced path on $t$ vertices, for fixed $t$. We propose an algorithm that, given a 3-colorable graph without an induced path on $t$ vertices, computes a coloring with $\max\{5,2\lceil{\frac{t-1}{2}}\rceil-2\}$ many colors. If the input graph is triangle-free, we only need $\max\{4,\lceil{\frac{t-1}{2}}\rceil+1\}$ many colors. The running time of our algorithm is $O((3^{t-2}+t^2)m+n)$ if the input graph has $n$ vertices and $m$ edges

Public health implications of metals concentrations from prescribed burns: A study adjacent to the Perth metropolitan area.

Ash is not a homogenous product. It is the solid residue of combustion and contains a complex mixture of chemical products. The ash residue resulting from fires varies and is dependent on its source, and burn characteristics such as the temperature of the fire. Ash comprises particles of carbon, soot and trace elements. Ash presents public health risk to people and communities, through direct and indirect ingestion and inhalation. The health effects of ash exposure are not limited to symptoms affecting the eyes, throat and lungs. They can contribute to chronic disease and increase the risk of cancer. The purpose of this study was to evaluate the public health implications of controlled burns in the Darling Escarpment, adjacent to Perth’s metropolitan area in Western Australia. Concentrations of metals in unburnt vegetative litter and ash (post burn), stratified by size fraction, were determined to assess the potential mobilisation of metals caused by prescribed burns and the potential public health implications associated with burns. These data can also be used in predictive modelling to ascertain the amount of metals likely to be released per hectare when authorities plan future burns in the area.  Ash samples were collected immediately following the fire to capture fine material before it was blown away. The ash samples were separated into size fractions to investigate whether there are differences within each sub sample. Australia’s National Environmental Protection Measures were used to establish whether the metal concentrations were above designated thresholds for health and environmental investigation, these being the recognised levels above which metals are deemed to pose a risk to public (or environmental) health.  Vegetation and ash samples were collected from three sites immediately after the prescribed burn. Samples were analysed for thirteen (13) metals with nine (9) showing statistically significant increases in concentrations in vegetation as compared to ash. The percentages of metals are higher in ash than in vegetative ground litter. The metals identified are Manganese - Vegetation (158.3 ± 89.3 mg/kg), Ash (442.2 ± 462.6 mg/kg); Barium - Vegetation (19.4 ± 25.3 mg/kg); Ash (41.8 ± 62.7 mg/kg); Zinc - Vegetation (15.3 ± 9.7 mg/kg), Ash (25.6 ± 29.7 mg/kg); Vanadium - Vegetation (31.0 mg/kg ± 76.3 mg/kg), Ash (32.2 mg/kg ± 51.0 mg/kg); Copper - Vegetation (4.2 ± 1.5 mg/kg), Ash (10.9 ± 9.8 mg/kg); Chromium (Total) - Vegetation (8.3 ± 15.6 mg/kg), Ash (9.6 ± 12.4 mg/kg); Lead - Vegetation (6.1 ± 8.3 mg/kg), Ash (12.2 ± 8.5 mg/kg); Nickel - Vegetation (2.2 ± 2.2 mg/kg), Ash (4.7 ± 4.4mg/kg) and Cadmium - Vegetation (0.6 ± 0.9 mg/kg), Ash (0.6 ± 0.9 mg/kg). The ash samples were sieved through three aperture’s (2-4 mm, 1-2 mm, <1 mm) to stratify the samples by size fraction and concentrations in all but three of the metals increased as the ash size decreased.It was demonstrated that the level of metal present within the ash samples did not exceed health investigation levels and, with the exception of Manganese, and did not exceed environmental investigations levels. Metals were unlikely to pose a risk if left insitu. However, modelling estimated the volume of metal released and it was determined that metals can pose a subsequent risk if mobilised by wind or water. The likelihood of such mobilisation is high and this finding therefore has public health implications for surrounding communities that are subjected to increases in their exposure to metals, associated with bushfires.The findings from this study contribute to the management of prescribed burns by providing a better understanding of the composition of ash and the effects of potential distribution via aerial deposition or runoff. Data from this study can be used to do predictive modelling of heavy metal mobilisation that may result from burns of similar vegetation environments. This becomes particularly significant where burns are conducted in water catchment areas 

Gamification for health promotion: systematic review of behaviour change techniques in smartphone apps

Funding from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical, Research Council and the National Institute for Health Research, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged