The intrinsic shapes of starless cores in Ophiuchus

Using observations of cores to infer their intrinsic properties requires the solution of several poorly constrained inverse problems. Here we address one of these problems, namely to deduce from the projected aspect ratios of the cores in Ophiuchus their intrinsic three-dimensional shapes. Four models are proposed, all based on the standard assumption that cores are randomly orientated ellipsoids, and on the further assumption that a core's shape is not correlated with its absolute size. The first and simplest model, M1, has a single free parameter, and assumes that the relative axes of a core are drawn randomly from a log-normal distribution with zero mean and standard deviation \sigma o. The second model, M2a, has two free parameters, and assumes that the log-normal distribution (with standard deviation \sigma o) has a finite mean, \mu o, defined so that \mu o<0 means elongated (prolate) cores are favoured, whereas \mu o>0 means flattened (oblate) cores are favoured. Details of the third model (M2b, two free parameters) and the fourth model (M4, four free parameters) are given in the text. Markov chain Monte Carlo sampling and Bayesian analysis are used to map out the posterior probability density functions of the model parameters, and the relative merits of the models are compared using Bayes factors. We show that M1 provides an acceptable fit to the Ophiuchus data with \sigma o ~ 0.57+/-0.06; and that, although the other models sometimes provide an improved fit, there is no strong justification for the introduction of their additional parameters.Comment: 10 pages, 8 figures. Accepted by MNRA

The design and synthesis of duocarmycin-based conjugates for targeted delivery to tumours

The CC-1065 and duocarmycin family of compounds are ultrapotent antitumour antibiotics which demonstrate activity in the picomolar range. These agents exert their biological effect through a sequence selective alkylation at the N3 position of adenine resulting in apoptosis. Despite the potential of this family to exert themselves as successful chemotherapeutic agents, a lack of clinical success has been observed for these compounds. This has been attributed to a lack of selectivity resulting in off-target side effects and toxicity. For this reason, research now focuses on ways in which these alkylating agents could realise their potential using tumour specific, targeted delivery strategies. Herein, we investigate the use of a duocarmycin SA analogue, functionalised for solid phasesynthesis, in the design of conjugates for targeted delivery to cancerous tissue via the Thomsen-Friedenreich antigen (T-antigen). This antigen is overexpressed in 90% of primary human carcinomas, yet is cryptic in healthy cells, therefore presenting itself as an ideal moiety for the delivery of duocarmycin agents to cancerous tissue. The research presented in this thesis will begin with detailing the synthesis of the Fmoc-duocarmycin SA analogue along with attempted modifications to the synthetic route to try and achieve greater efficiency. Additionally, this chapter will detail investigations into alternative protecting group removal strategies to improve the effectiveness of this analogues use in solid phase synthesis. The chapters subsequent to this will detail the design, synthesis and biological evaluation of a series of duocarmycin-based conjugates for targeted delivery to the T-antigen. These conjugates involve the use of T-antigen specific lectins and peptides. Furthermore, the development of a gold nanoparticle delivery system involving duocarmycin and a T-antigen specific lectin will be detailed. The investigations presented herein provide scope for future investigations into the design of clinically successful duocarmycin-based conjugates

Third crime unlucky

This is a contemporary mystery novel set in the Eastern Cape. A town’s airstrip, situated between the golf club and the military base, acts as host to the local flying club and an active skydiving school. An amateur investigator uses unorthodox methods and the help of friends to find the cause of aeroplane fires and sabotage. His investigations lead him via geological research and insurance reports into contact with members of the aviation, property development and military fields

Cement nanotubes: on chemical gardens and cement

© 2016 Springer Science+Business Media New York“Do cement nanotubes exist?” is a question that has recently been asked. The answer is yes, they do exist. The evidence is in the literature, in tens of papers showing in detail chemical garden-type tubes in cement from the nanoscale upwards that were published in the 1970s and 1980s. Here, we present a nano-review of the literature

Monocytes/macrophages express chemokine receptor CCR9 in rheumatoid arthritis and CCL25 stimulates their differentiation

Available Gold OAAbstract Introduction Monocytes/macrophages accumulate in the rheumatoid (RA) synovium where they play a central role in inflammation and joint destruction. Identification of molecules involved in their accumulation and differentiation is important to inform therapeutic strategies. This study investigated the expression and function of chemokine receptor CCR9 in the peripheral blood (PB) and synovium of RA, non-RA patients and healthy volunteers. Methods CCR9 expression on PB monocytes/macrophages was analysed by flow cytometry and in synovium by immunofluorescence. Chemokine receptor CCR9 mRNA expression was examined in RA and non-RA synovium, monocytes/macrophages from PB and synovial fluid (SF) of RA patients and PB of healthy donors using the reverse transcription polymerase chain reaction (RT-PCR). Monocyte differentiation and chemotaxis to chemokine ligand 25 (CCL25)/TECK were used to study CCR9 function. Results CCR9 was expressed by PB monocytes/macrophages in RA and healthy donors, and increased in RA. In RA and non-RA synovia, CCR9 co-localised with cluster of differentiation 14+ (CD14+) and cluster of differentiation 68+ (CD68+) macrophages, and was more abundant in RA synovium. CCR9 mRNA was detected in the synovia of all RA patients and in some non-RA controls, and monocytes/macrophages from PB and SF of RA and healthy controls. CCL25 was detected in RA and non-RA synovia where it co-localised with CD14+ and CD68+ cells. Tumour necrosis factor alpha (TNFα) increased CCR9 expression on human acute monocytic leukemia cell line THP-1 monocytic cells. CCL25 induced a stronger monocyte differentiation in RA compared to healthy donors. CCL25 induced significant chemotaxis of PB monocytes but not consistently among individuals. Conclusions CCR9 expression by monocytes is increased in RA. CCL25 may be involved in the differentiation of monocytes to macrophages particularly in RA.Peer Reviewe

A peptide-duocarmycin conjugate targeting the Thomsen-Friedenreich antigen has potent and selective antitumour activity

Solid phase synthesis allowed the rapid generation of a peptide-drug conjugate. A peptide targeting the Thomsen-Friedenreich antigen (TFα) was conjugated to the alkylating subunit of the potent cytotoxin duocarmycin SA. The compound, containing a cathepsin B cleavable linker, was shown to be active and selective against TFα expressing tumour cell lines

Chemical and textural equilibration of garnet during amphibolite-facies metamorphism: The influence of coupled dissolution-reprecipitation

Metamorphic equilibration requires chemical communication between minerals and may be inhibited through sluggish volume diffusion and or slow rates of dissolution in a fluid phase. Relatively slow diffusion and the perceived robust nature of chemical growth zoning may preclude garnet porphyroblasts from readily participating in low temperature amphibolite-facies metamorphic reactions. Garnet is widely assumed to be a reactant in staurolite-isograd reactions, and the evidence for this has been assessed in the Late Proterozoic Dalradian pelitic schists of the Scottish Highlands. Three-D imaging of garnet porphyroblasts in staurolite-bearing schists reveal a good crystal shape and little evidence of marginal dissolution, however there is also lack of evidence for the involvement of either chlorite or chloritoid in the reaction. Staurolite forms directly adjacent to the garnet, and its nucleation is strongly associated with deformation of the muscovite-rich fabrics around the porphyroblasts. “Cloudy” fluid inclusion-rich garnet forms in both marginal and internal parts of the garnet porphyroblast and is linked both to the production of staurolite and to the introduction of abundant quartz inclusions within the garnet. Such cloudy garnet typically has a Mg-rich, Mn-poor composition and is interpreted to have formed during a coupled dissolution-reprecipitation process, triggered by a local influx of fluid. All garnet in the muscovite-bearing schists present in this area is potentially reactive, irrespective of the garnet composition, but very few of the schists contain staurolite. The staurolite-producing reaction appears to be substantially overstepped during the relatively high pressure Barrovian regional metamorphism reflecting the limited permeability of the schists in peak metamorphic conditions. Fluid influx and hence reaction progress appear to be strongly controlled by subtle differences in deformation history. The remaining garnet fails to achieve chemical equilibrium during the reaction creating distinctive patchy compositional zoning. Such zoning in metamorphic garnet created during coupled dissolution-reprecipitation reactions may be difficult to recognize in higher grade pelites due to subsequent diffusive re-equilibration. Fundamental assumptions about metamorphic processes are questioned by the lack of chemical equilibrium during this reaction and the restricted permeability of the regional metamorphic pelitic schists. In addition the partial loss of prograde chemical and textural information from the garnet porphyroblasts cautions against their routine use as a reliable monitor of metamorphic history. However the partial re-equilibration of the porphyroblasts during coupled dissolution-reprecipitation opens possibilities of mapping reaction progress in garnet as a means of assessing fluid access during peak metamorphic conditions