Oxetanes: Recent Advances in Synthesis, Reactivity and Medicinal Chemistry

The 4-membered oxetane ring has been increasingly exploited for its behaviors, i.e. influence on physicochemical properties as a stable motif in medicinal chemistry, and propensity to undergo ring opening reactions as a synthetic intermediate. These applications have driven numerous studies into the synthesis of new oxetane derivatives. This review takes an overview of the literature for the synthesis of oxetane derivatives, concentrating on advances in the last 5 years up to the end of 2015. These methods are clustered by strategy for preparation of the ring (Sections 3 and 4), and further derivatisation of preformed oxetane-containing building blocks (Sections 5-7). Examples of the use of oxetanes in medicinal chemistry are reported, including a collation of oxetane derivatives appearing in recent patents for medicinal chemistry applications. Finally examples of oxetane derivatives in ring opening and ring expansion reactions are described

Staying Close to Home: The Significance of Relationships for Immigrant-Origin Local College Students.

For local college students from immigrant backgrounds, entering college involves navigating both existing and new obligations to family, community, and school. This qualitative study describes the relational experiences of 14 immigrant-origin students, alumni of a college preparation program who attended college while living at or near home in New York City. In-depth, semi-structured interviews suggested that supportive relationships with family, peers, and mentors were key to helping students transition to college while maintaining existing ties, while some students also felt torn between their own needs and those of their families. Implications for culturally competent social work practice are discussed

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

A high-precision age estimate of the Holocene Plinian eruption of Mount Mazama, Oregon, USA

© The Author(s) 2015 The climactic eruption of Mount Mazama in Oregon, North America, resulted in the deposition of the most widespread Holocene tephra deposit in the conterminous United States and south-western Canada. The tephra forms an isochronous marker horizon for palaeoenvironmental, sedimentary and archaeological reconstructions, despite the current lack of a precise age estimate for the source eruption. Previous radiocarbon age estimates for the eruption have varied, and Greenland ice-core ages are in disagreement. For the Mazama tephra to be fully utilised in tephrochronology and palaeoenvironmental research, a refined (precise and accurate) age for the eruption is required. Here, we apply a meta-analysis of all previously published radiocarbon age estimations (n = 81), and perform Bayesian statistical modelling to this data set, to provide a refined age of 7682–7584 cal. yr BP (95.4% probability range). Although the depositional histories of the published ages vary, this estimate is consistent with that estimated from the GISP2 ice-core of 7627 ± 150 yr BP (Zdanowicz et al., 1999)

Cosmic strings from pseudo-anomalous Fayet-Iliopoulos U(1) in D3/D7 brane inflation

We examine the consequences of recent developments on Fayet-Iliopoulos (FI) terms for D-term inflationary models. There is currently no known way to couple constant FI terms to supergravity consistently; only field-dependent FI terms are allowed. These are natural in string theory and we argue that the FI term in D3/D7 inflation turns out to be of this type, corresponding to a pseudo-anomalous U(1). T he anomaly is canceled by the Green-Schwarz mechanism in 4 dimensions. Inflation proceeds as usual, except that the scale is set by the GS parameter. Cosmic strings resulting from a pseudo-anomalous U(1) have potentially interesting characteristics. Originally expected to be global, they turn out to be local in the string theory context and can support currents. We outline the nature of these strings, discuss bounds on their formation, and summarize resulting cosmological consequences.Comment: 10 pages; minor changes to match published versio

On the Hardness of SAT with Community Structure

Recent attempts to explain the effectiveness of Boolean satisfiability (SAT) solvers based on conflict-driven clause learning (CDCL) on large industrial benchmarks have focused on the concept of community structure. Specifically, industrial benchmarks have been empirically found to have good community structure, and experiments seem to show a correlation between such structure and the efficiency of CDCL. However, in this paper we establish hardness results suggesting that community structure is not sufficient to explain the success of CDCL in practice. First, we formally characterize a property shared by a wide class of metrics capturing community structure, including "modularity". Next, we show that the SAT instances with good community structure according to any metric with this property are still NP-hard. Finally, we study a class of random instances generated from the "pseudo-industrial" community attachment model of Gir\'aldez-Cru and Levy. We prove that, with high probability, instances from this model that have relatively few communities but are still highly modular require exponentially long resolution proofs and so are hard for CDCL. We also present experimental evidence that our result continues to hold for instances with many more communities. This indicates that actual industrial instances easily solved by CDCL may have some other relevant structure not captured by the community attachment model.Comment: 23 pages. Full version of a SAT 2016 pape