meta-Selective C−H Borylation of Benzylamine-, Phenethylamine-, and Phenylpropylamine-Derived Amides Enabled by a Single Anionic Ligand

Selective functionalization at the meta position of arenes remains a significant challenge. In this work, we demonstrate that a single anionic bipyridine ligand bearing a remote sulfonate group enables selective iridium-catalyzed borylation of a range of common amine-containing aromatic molecules at the arene meta position. We propose that this selectivity is the result of a key hydrogen bonding interaction between the substrate and catalyst. The scope of this meta-selective borylation is demonstrated on amides derived from benzylamines, phenethylamines and phenylpropylamines; amine-containing building blocks of great utility in many applications.We are grateful to the EPSRC and Pfizer for a CASE studentship (H.J.D.), the EPSRC (EP/N005422/1, G.R.G.) and the Royal Society for a University Research Fellowship (R.J.P.)

Abundance and exploitation rate of the blue crab (Callinectes sapidus) in Chesapeake Bay

We estimated absolute abundance of the blue crab stock in Chesapeake Bay during winter from stratified random surveys conducted baywide from 1990 to 1999, using the swept-area method. We estimated catching efficiency of the survey gear from multiple depletion experiments to correct for temporal and vessel/area differences in catchability. The survey was conducted during the winter, when crabs are dormant and buried in the bottom. Analysis of crab carapace width (CW) frequency distributions revealed two size modes: CW less or equal 60 mm and CW greater than 60 mm, corresponding to age-0 (recruits) and age-1+ (one year and older), respectively. Absolute density of blue crab recruits varied from 10 to 55 crabs per 1,000 m(2) across years (95 million to 540 million baywide), with no significant trends over time. Abundance of age-1 + crabs declined significantly from 35 to 38 crabs per I 000 m(2) in 1990-1991 (342 million to 371 million crabs baywide) to 8.3 in 1999 (92 million crabs baywide). A stronger decline in the number of males indicates that males were exploited more intensively than females. A three-year moving average of spawning stock abundance (age- 1+ females) declined twofold from the early to the late 1990s. The absolute abundance of the blue crab population in Chesapeake Bay varied from 241 million to 867 million. Over-wintering mortality was usually less than 2%, but substantially higher mortality occurred in 1994 (7.3%) and 1996 (11.9%). High correlation between January water temperature and the percentage of dead crabs provides strong evidence of the adverse effect of cold winter on survival of crabs. Large crabs were affected most by cold winter temperatures. We estimated exploitation rates for the commercial fishery by comparing abundance with total landings. The estimated exploitation rates varied from 40% to 52% from 1990 to 1998 and increased to a record high of 70% in 1999. Fishing mortality rates varied from 0.6 to 0.9 year(-1) ill most years and were above the level providing maximum yield per recruit (F-max = 0.64 year(-1)) in nearly all years. The record fishing mortality in 1999 (F-1999, = 1.6 year(-1)) exceeded the overfishing threshold (F-10% = 1.0 year(-1)). Despite evidence of growth overfishing, the blue crab population supported large harvests throughout the 1990s. Increase of fishing mortality above the F-10% in 1999, indicates that the population was overfished and is at risk of recruitment overfishing if fishing mortality remains at this level

Ion Pair-Directed C-H Activation on Flexible Ammonium Salts: Meta-Selective Borylation of Quaternized Phenethylamines and Phenylpropylamines

Ion pairing has unexplored potential as a key catalyst-substrate interaction for controlling regioselectivity and site-selectivity in transition metal catalysis, particularly in the area of C-H activation. However, there is a significant perceived challenge that has meant that few have investigated this approach to date – that of the low directionality, which could present an insurmountable challenge if seeking positional selectivity on flexible substrates. Herein, we demonstrate that even flexible substrates with several freely rotatable bonds undergo ion pair-directed CH borylation with good to excellent levels of regiocontrol for the arene meta position. Furthermore, we demonstrate that in specially designed competition substrates, ion pair direction prevails over competing hydrogen bond direction. We anticipate that these findings will inspire the greater incorporation of ion-pairing into site-selective catalytic strategies

Fragmenting densely mineralised acellular protrusions from articular calcified cartilage: a role in osteoarthritis?

Fragmenting densely mineralised acellular protrusions from articular calcified cartilage: a role in osteoarthritis? A. Boyde a, G.R. Davis a, D. Mills a, T. Zikmund a, V.L. Adams b, L.R. Ranganath b, N. Jeffery b, J.A. Gallagher b a Dental Physical Sciences, Oral Growth and Development, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK b Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK Objectives High density mineralised protrusions (HDMP) from the tidemark mineralising front into hyaline articular cartilage (HAC) were first discovered in Thoroughbred racehorse fetlock joints and later in Icelandic horse hock joints. If these fragment, they could make a significant contribution to joint destruction in osteoarthritis. We looked for them in human material. Methods Whole femoral heads removed at operation for joint replacement or from dissection room cadavers were studied by MRI DESS at 0.23mm resolution and 26 micron resolution high contrast x-ray microtomography (XMT), then sectioned and embedded in PMMA, and block faces polished and the blocks re-imaged with 6 micron resolution XMT. Tissue mineralisation density was imaged qualitatively by backscattered electron SEM (BSE SEM) at 20kV using uncoated samples at 50Pa chamber pressure to achieve charge neutralisation. HAC histology was studied by BSE SEM after staining block faces with ammonium triiodide solution. Block surfaces were sequentially repolished and restained. Results Figure: 3D rendering of 6 micron voxel resolution XMT data set showing HDMP complex projecting above subchondral bone plate. Human femoral head removed at arthroplasty. We found examples of HDMP in HAC in human hips. Their 3D shapes are complex and may show cutting blade forms. Their mineral content (a) exceeds that of articular calcified cartilage (ACC), otherwise the densest tissue in the joint and (b) is not uniform. The mineral phase morphology frequently shows the agglomeration of many fine particles into larger concretions. Cracks within them are frequent. Dense fragments may be found within damaged HAC. Conclusions HDMP arise via the extrusion of an uncharacterised matrix into clefts in HAC. Little evidence of their existence remains after tissue has been decalcified with usual histological protocols. Their formation may be an extension of a normal but poorly recognised crack self-healing mechanism found in bone and ACC. They are surrounded by HAC, are dense and brittle and show innumerable fault lines within them. We provide evidence that they break in vivo by being able to find matching fragments in HAC. We conclude that these hard and sharp particles contribute to the shredding destruction of HAC. The osteoarthritis research community should be aware of their existence so that the frequency and possible clinical significance can be assessed in the future. Larger HDMP can be detected with the best MRI imaging

Comparison of efficacy of dental varnish containing fluoride either with CPP-ACP or bioglass on root caries: Ex vivo study.

OBJECTIVES: To compare the efficacy of fluoride varnishes either casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) or bioglass particles on the severity index of root caries. METHODS: Visual-tactile assessments including lesion hardness was carried out to categorise the severity index of 80 extracted teeth with primary root caries. These teeth were randomly divided into four groups; CPP-ACP and fluoride, bioglass and fluoride, fluoride only, and no treatment. Standardised toothbrushing using a dentifrice containing 1450 ppm fluoride was carried out twice a day for all groups. All samples were stored in remineralising solution at 37°C for 45 days. Visual-tactile assessments were carried out at baseline, and after 45 days. Surface roughness measurements (Ra) were performed at baseline and after 7, 14, 30 and 45 days. X-ray Microtomography was performed at the baseline and after 45 days for three samples from each group to quantify the change in mineral contents in the lesion area. RESULTS: The Visual-tactile assessment results showed a reduction in the severity index of root caries, being 20% in CPP-ACP and fluoride, 100% in bioglass and fluoride, 80% in fluoride only, and 60% in non-varnish (toothbrushing only). Non-significant change in surface roughness was observed in all groups. X-ray Microtomography assessment showed a highly significant increase in the mineral deposition in all cases (p > .001). CONCLUSION: The combination of bioglass with fluoride has a potentially superior effect than either CPP-ACP with fluoride or fluoride only to reverse and arrest the root caries in a laboratory setting. CLINICAL SIGNIFICANCE: The combination of bioglass particles and fluoride formulation is likely to have a significant impact in reversing and arresting root caries in a minimally invasive approach. However, randomised controlled double-blinded clinical trials are required to translate these results into clinical practice.This work was financially supported by the Ministry of Higher Education in Iraqi as a part of a PhD project. The authors declare no potential conflicts of interest with respect to publication of this article

Composite 3D printing of biomimetic human teeth

Human teeth are mechanically robust through a complex structural composite organisation of materials and morphology. Efforts to replicate mechanical function in artificial teeth (typodont teeth), such as in dental training applications, attempt to replicate the structure and morphology of real teeth but lack tactile similarities during mechanical cutting of the teeth. In this study, biomimetic typodont teeth, with morphology derived from X-ray microtomography scans of extracted teeth, were 3D printed using an approach to develop novel composites. These composites with a range of glass, hydroxyapatite and porcelain reinforcements within a methacrylate-based photopolymer resin were compared to six commercial artificial typodont teeth. Mechanical performance of the extracted human teeth and 3D printed typodont teeth were evaluated using a haptic approach of measuring applied cutting forces. Results indicate 3D printed typodont teeth replicating enamel and dentine can be mechanically comparable to extracted human teeth despite the material compositions differing from the materials found in human teeth. A multiple parameter variable of material elastic modulus and hardness is shown to describe the haptic response when cutting through both human and biomimetic, highlighting a critical dependence between the ratio of material mechanical properties and not absolute material properties in determining tooth mechanical performance under the action of cutting forces

Real-time observations of tooth demineralization in 3 dimensions using X-ray microtomography.

OBJECTIVES: The immediate aim of this study was to develop and test a method to record, visualize and quantify real-time demineralization (or remineralization) of teeth in vitro using X-ray microtomography (XMT or micro-CT). The longer term objective is to improve understanding of demineralization processes, allowing the creation of better artificial models of dental caries and better quantification of the efficacy of caries treatment and prevention regimes. METHODS: For demineralization studies, the tooth is mounted in a plastic container through which the demineralizing solution is circulated during simultaneous repeated scanning. Key features of the method are safe circulation of the demineralizing solution, periodic interruption to adjust X-ray filament current and re-focus, accurate beam-hardening correction and calibration, alignment of reconstructed scans, and normalization of grey-levels to compensate for changes in the X-ray spectrum. The method was tested by scanning an extracted third molar during 8days of demineralization. RESULTS: From the reconstructed 3D images, the progression of an artificial carious lesion could be visualized and quantified. The lesion progressed at approximately 0.1mm per day and appeared to be more erosive in nature. CONCLUSIONS: A successful method has been developed to monitor real-time demineralization in 3 dimensions. Further work is now needed to create better models of true carious lesions. CLINICAL SIGNIFICANCE: Observation of the dynamics of demineralization and remineralization will aid in the development of therapies to treat and prevent dental caries

Imaging a microfocus X-ray focal spot with a thin coded aperture

Imaging of the focal spot size in X-ray generators can be achieved by means of a pinhole in a highly attenuating material, such as gold. For microfocus generators with spot sizes of only around 10 microns or less, the material must be very thin to avoid an impractical aspect ratio. With a 90 kV source, only 11% attenuation is attained with 5 µm gold. For a pinhole that is smaller than the focal spot, the signal-to-noise ratio (SNR) may be less than 1. To image the focal spot of a medical X-ray generator, a coded aperture has been used previously to reduce the exposure time required, however the same technique does not appear to have been used to increase the SNR when the attenuation is very low. Such a method is used here, using a no-two-holes-touching variation of a modified uniformly redundant array (MURA). In a prototype sample, with only 5 µm gold having 2.75 µm holes, the focal spot of a microfocus X-ray generator used in a micro-CT system could be clearly visualised and quantified. Directionality of the aberrations made focussing of the X-ray spot more intuitive and reduced the time required to obtain an optimal, quantifiable focus

Enabling three-dimensional densitometric measurements using laboratory source X-ray micro-computed tomography

We present new software allowing significantly improved quantitative mapping of the three-dimensional density distribution of objects using laboratory source polychromatic X-rays via a beam characterisation approach (c.f. filtering or comparison to phantoms). One key advantage is that a precise representation of the specimen material is not required. The method exploits well-established, widely available, non-destructive and increasingly accessible laboratory-source X-ray tomography. Beam characterisation is performed in two stages: (1) projection data are collected through a range of known materials utilising a novel hardware design integrated into the rotation stage; and (2) a Python code optimises a spectral response model of the system. We provide hardware designs for use with a rotation stage able to be tilted, yet the concept is easily adaptable to virtually any laboratory system and sample, and implicitly corrects the image artefact known as beam hardening