Synthetic Studies in the Sesquiterpene Field

Part I: The synthesis of (+/-) cuparene and (+/-) cuparenic acid was achieved starting from 3-methylcyclohex-2-enone. A Friedel Crafts reaction with toluene gave 3-methyl-3-p-tolyleyclohexanone. The mono-furfurylidene derivative of this ketone was bis-alkylated to give 2-furfurylidene-5:6:6-trimethyl-5-p-tolylcyclohexanone which was subjected to ozonolysis, cyclization, and reduction to give (+/-) cuparene which was then oxidized to (+/-) cuparenic acid. Two unsuccessful synthetic approaches to cuparene are also described. Acid treatment of an alpha-ketol, 3:3 dimethyl-2-hydroxy-2-p-tolylcyclopentanone, brought about a novel 1:3-hydride shift leading to 4:4-dirnethyl-5-p-tolylcyclopentenone. The mechanism of enol-chloride formation of unsymmetrical cyclohexan-1:3-diones is also discussed. Part II: A novel approach to the spiro-[5:4]-decane system encountered in acorone was undertaken by 1:4 addition of acetylenic Grignard reagents to the cyclohexylidene malononitrile system. The ethynyl dinitrilea, so formed were found to undergo basic Internal hydration, Construction of the spiro system was effected by an internal Michael cyclization of ethyl 5-(4-methyl-3-oxo-cyclohexenyl)-3-oxo-hexanoate. The product of this cyclization was elaborated to the gross structure of acorone

Duelling Timber Floats of Japan's Fushiki Hikiyama Festival

Each spring the town of Fushiki in Japan's Toyama prefecture plays host to a unique cultural event - the Fushiki Hikiyama festival. Timber engineers will find interest in the culmination of the festival: a series of duels in which predominantly wooden festival floats armed with what can only be described as battering-rams, are brought together at speed in a series of spectacular collisions. The authors were brought together by the Civic Cultural Heritage Network Tottori, a Japanese cultural organisation, to carry out a preliminary investigation of the festival floats; both for engineering and cultural interest, and as a possible exemplar of the behaviour of traditionally carpentered structures subject to high dynamic loads. The second, third and fourth authors travelled to Fushiki to observe the May 2016 festival and to carry out an after-the-battle inspection of one of these unique duelling floats. High-speed and high-resolution video was used for digital image correlation measurement of the collisions, to quantify the magnitude of the impact

Stiffness and Slip in Multi-dowel Timber Connections with Slotted-in Steel Plates

Large multi-dowel connections can provide the strength and ductility required for large, highly-loaded timber structures, but their slip under load is not well understood. This is an important gap in knowledge, because accumulated local displacements at connections represent a large part of the deformation of a timber structure. The empirical relationships used in design codes commonly scale a single-dowel stiffness by the number of dowels, so do not capture the dowel interaction effects of the multi-dowel connections used in larger structures. We present the results of an experimental test series, elastic model and probabilistic numerical analysis investigating the development of stiffness in multi-dowel timber connections with slotted-in steel plates. Novel test methods record the development of stiffness due to each individual connector to show that the stiffness of the complete connection is not proportional to the number of dowels. An elastic stress-function model shows that this is partly due to interaction of the stress field around the dowels. For the first time, this work quantitatively considers the influence of misalignment of dowels due to manufacturing tolerances, and it is shown that this may greatly reduce the overall stiffness of a multi-dowel connection. The test series is used to validate a probabilistic model of this misalignment for the stiffness of such a connection. The model incorporates the nonlinear stiffness and hole opening observed in single-dowel connections to predict the behaviour of the group. The study shows that the random misalignment of dowels in multi-dowel connections reduces the range of displacements over which the connection displays zero stiffness slightly, but that this zone is not eliminated as a result of irreversible hole opening under load, even for a connection with 35 dowels and three steel plates. We conclude that two parameters are important for the design of these connections: the unload-reload stiffness and the zero-stiffness region measured between the zero load intercept of the unload-reload linear fit. With these, a reasonable estimate can be made of the displacement at any serviceability load level in either tension or compression

Designing, conducting, and reporting reproducible animal experiments

In biomedicine and many other fields, there are growing concerns around the reproducibility of research findings, with many researchers being unable to replicate their own or others' results. This raises important questions as to the validity and usefulness of much published research. In this review, we aim to engage researchers in the issue of research reproducibility and equip them with the necessary tools to increase the reproducibility of their research. We first highlight the causes and potential impact of non-reproducible research and emphasise the benefits of working reproducibly for the researcher and broader research community. We address specific targets for improvement and steps that individual researchers can take to increase the reproducibility of their work. We next provide recommendations for improving the design and conduct of experiments, focusing on in vivo animal experiments. We describe common sources of poor internal validity of experiments and offer practical guidance for limiting these potential sources of bias at different experimental stages, as well as discussing other important considerations during experimental design. We provide a list of key resources available to researchers to improve experimental design, conduct, and reporting. We then discuss the importance of open research practices such as study preregistration and the use of preprints and describe recommendations around data management and sharing. Our review emphasises the importance of reproducible work and aims to empower every individual researcher to contribute to the reproducibility of research in their field.</p

Size effect of large scale timber columns

The very large glued laminated timber columns that are needed for tall timber buildings are too large to be physically tested in most facilities. To safely design these columns, it is necessary to identify and extrapolate behaviour from the physical testing of smaller specimens. Compression testing of 27 glue-laminated timber columns showed a reduction in strength with increased member size. This phenomenon is known as a size effect. The laminated timber exhibited a compressive strength much higher than the characteristic strength that it was graded it. Comparisons between columns of different lengths and widths, suggests that the homogenisation of laminated timber may mitigate the size effect. An extrapolation of the size effect from the column sizes tested, to an ultra-large column for a timber skyscraper, indicated that the magnitude of the effect could be large enough to reduce the compressive strength of the glulam to below its characteristic strength

Essential role for proteinase-activated receptor-2 in arthritis

Using physiological, pharmacological, and gene disruption approaches, we demonstrate that proteinase-activated receptor-2 (PAR-2) plays a pivotal role in mediating chronic inflammation. Using an adjuvant monoarthritis model of chronic inflammation, joint swelling was substantially inhibited in PAR-2-deficient mice, being reduced by more than fourfold compared with wild-type mice, with virtually no histological evidence of joint damage. Mice heterozygous for PAR-2 gene disruption showed an intermediate phenotype. PAR-2 expression, normally limited to endothelial cells in small arterioles, was substantially upregulated 2 weeks after induction of inflammation, both in synovium and in other periarticular tissues. PAR-2 agonists showed potent proinflammatory effects as intra-articular injection of ASKH95, a novel synthetic PAR-2 agonist, induced prolonged joint swelling and synovial hyperemia. Given the absence of the chronic inflammatory response in the PAR-2-deficient mice, our findings demonstrate a key role for PAR-2 in mediating chronic inflammation, thereby identifying a novel and important therapeutic target for the management of chronic inflammatory diseases such as rheumatoid arthritis

Development of a High-Throughput Candida albicans Biofilm Chip

We have developed a high-density microarray platform consisting of nano-biofilms of Candida albicans. A robotic microarrayer was used to print yeast cells of C. albicans encapsulated in a collagen matrix at a volume as low as 50 nL onto surface-modified microscope slides. Upon incubation, the cells grow into fully formed “nano-biofilms”. The morphological and architectural complexity of these biofilms were evaluated by scanning electron and confocal scanning laser microscopy. The extent of biofilm formation was determined using a microarray scanner from changes in fluorescence intensities due to FUN 1 metabolic processing. This staining technique was also adapted for antifungal susceptibility testing, which demonstrated that, similar to regular biofilms, cells within the on-chip biofilms displayed elevated levels of resistance against antifungal agents (fluconazole and amphotericin B). Thus, results from structural analyses and antifungal susceptibility testing indicated that despite miniaturization, these biofilms display the typical phenotypic properties associated with the biofilm mode of growth. In its final format, the C. albicans biofilm chip (CaBChip) is composed of 768 equivalent and spatially distinct nano-biofilms on a single slide; multiple chips can be printed and processed simultaneously. Compared to current methods for the formation of microbial biofilms, namely the 96-well microtiter plate model, this fungal biofilm chip has advantages in terms of miniaturization and automation, which combine to cut reagent use and analysis time, minimize labor intensive steps, and dramatically reduce assay costs. Such a chip should accelerate the antifungal drug discovery process by enabling rapid, convenient and inexpensive screening of hundreds-to-thousands of compounds simultaneously

Proposal for defining a Tall, Timber Building

This is the author accepted manuscript. The final version is available from the American Society of Civil Engineers via http://dx.doi.org/10.1061/(ASCE)ST.1943-541X.0001615In order to talk about ‘tall’ buildings and more particularly ‘tall, timber’ buildings, it is useful to clarify what is meant by a ‘tall’ and a ‘tall, timber’ building. This clarification facilitates both productive discussion of the subject and secures the basis on which meaningful comparisons can be made between buildings using different structural systems and materials. The historic duopoly of steel and concrete as the structural materials of tall building construction is in the process of being broken by the introduction of engineered timber and it is appropriate that this change is reflected in the language of tall building design. The approach adopted in this paper has three parts. Existing definitions and terminology for ‘tall’ buildings are explored. A study is made of the structural systems and materials of existing buildings that use structural timber and have some claim to ‘tallness’. A proposal is made for the clarification and expansion of existing criteria for tall building terminology and definitions to accommodate the use of structural timber in tall building

Draft genome sequence of isolate Staphylococcus aureus LHSKBClinical, isolated from an infected hip

We report here the genome sequence of a clinical isolate of &lt;i&gt;Staphylococcus aureus&lt;/i&gt; from an orthopedic infection. Phenotypically diverse &lt;i&gt;Staphylococcus aureus&lt;/i&gt; strains are associated with orthopedic infections and subsequent implant failure, and some are highly resistant to antibiotics. This genome sequence will support further analyses of strains causing orthopedic infections