414 research outputs found
Brownian transport in corrugated channels with inertia
The transport of suspended Brownian particles dc-driven along corrugated
narrow channels is numerically investigated in the regime of finite damping. We
show that inertial corrections cannot be neglected as long as the width of the
channel bottlenecks is smaller than an appropriate particle diffusion length,
which depends on the the channel corrugation and the drive intensity. Being
such a diffusion length inversely proportional to the damping constant,
transport through sufficiently narrow obstructions turns out to be always
sensitive to the viscosity of the suspension fluid. The inertia corrections to
the transport quantifiers, mobility and diffusivity, markedly differ for
smoothly and sharply corrugated channels.Comment: 9 pages including figures. arXiv admin note: substantial text overlap
with arXiv:1202.436
BLAST: the Redshift Survey
The Balloon-borne Large Aperture Submillimeter Telescope (BLAST) has recently
surveyed ~8.7 deg^2 centered on GOODS-South at 250, 350, and 500 microns. In
Dye et al. (2009) we presented the catalogue of sources detected at 5-sigma in
at least one band in this field and the probable counterparts to these sources
in other wavebands. In this paper, we present the results of a redshift survey
in which we succeeded in measuring redshifts for 82 of these counterparts. The
spectra show that the BLAST counterparts are mostly star-forming galaxies but
not extreme ones when compared to those found in the Sloan Digital Sky Survey.
Roughly one quarter of the BLAST counterparts contain an active nucleus. We
have used the spectroscopic redshifts to carry out a test of the ability of
photometric redshift methods to estimate the redshifts of dusty galaxies,
showing that the standard methods work well even when a galaxy contains a large
amount of dust. We have also investigated the cases where there are two
possible counterparts to the BLAST source, finding that in at least half of
these there is evidence that the two galaxies are physically associated, either
because they are interacting or because they are in the same large-scale
structure. Finally, we have made the first direct measurements of the
luminosity function in the three BLAST bands. We find strong evolution out to
z=1, in the sense that there is a large increase in the space-density of the
most luminous galaxies. We have also investigated the evolution of the
dust-mass function, finding similar strong evolution in the space-density of
the galaxies with the largest dust masses, showing that the luminosity
evolution seen in many wavebands is associated with an increase in the
reservoir of interstellar matter in galaxies.Comment: Accepted for publication in the Astrophysical Journal. Maps and
associated results are available at http://blastexperiment.info
Mapping spot blotch resistance genes in four barley populations
Bipolaris sorokiniana (teleomorph: Cochliobolus sativus) is the fungal pathogen responsible for spot blotch in barley (Hordeum vulgare L.) and occurs worldwide in warmer, humid growing conditions. Current Australian barley varieties are largely susceptible to this disease and attempts are being made to introduce sources of resistance from North America. In this study we have compared chromosomal locations of spot blotch resistance reactions in four North American two-rowed barley lines; the North Dakota lines ND11231-12 and ND11231-11 and the Canadian lines TR251 and WPG8412-9-2-1. Diversity Arrays Technology (DArT)-based PCR, expressed sequence tag (EST) and SSR markers have been mapped across four populations derived from crosses between susceptible parental lines and these four resistant parents to determine the location of resistance loci. Quantitative trait loci (QTL) conferring resistance to spot blotch in adult plants (APR) were detected on chromosomes 3HS and 7HS. In contrast, seedling resistance (SLR) was controlled solely by a locus on chromosome 7HS. The phenotypic variance explained by the APR QTL on 3HS was between 16 and 25% and the phenotypic variance explained by the 7HS APR QTL was between 8 and 42% across the four populations. The SLR QTL on 7HS explained between 52 to 64% of the phenotypic variance. An examination of the pedigrees of these resistance sources supports the common identity of resistance in these lines and indicates that only a limited number of major resistance loci are available in current two-rowed germplasm
Ladder operator for the one-dimensional Hubbard model
The one-dimensional Hubbard model is integrable in the sense that it has an
infinite family of conserved currents. We explicitly construct a ladder
operator which can be used to iteratively generate all of the conserved current
operators. This construction is different from that used for Lorentz invariant
systems such as the Heisenberg model. The Hubbard model is not Lorentz
invariant, due to the separation of spin and charge excitations. The ladder
operator is obtained by a very general formalism which is applicable to any
model that can be derived from a solution of the Yang-Baxter equation.Comment: 4 pages, no figures, revtex; final version to appear in Phys. Rev.
Let
Pharmacological Inhibition of polysialyltransferase ST8SiaII Modulates Tumour Cell Migration
YesPolysialic acid (polySia), an α-2,8-glycosidically linked polymer of sialic acid, is a developmentally regulated posttranslational
modification predominantly found on NCAM (neuronal cell adhesion molecule). Whilst high levels are expressed during development, peripheral adult organs do not express polySia-NCAM. However, tumours of neural crest-origin re-express polySia-NCAM: its occurrence correlates with aggressive and invasive disease and poor clinical prognosis in different cancer types, notably including small cell lung cancer (SCLC), pancreatic cancer and neuroblastoma. In neuronal development, polySia-NCAM biosynthesis is catalysed by two polysialyltransferases, ST8SiaII and ST8SiaIV, but it is ST8SiaII that is the prominent enzyme in tumours. The aim of this study was to determine the effect of ST8SiaII inhibition by a small molecule on tumour cell migration, utilising cytidine monophosphate (CMP) as a tool compound. Using immunoblotting we showed that CMP reduced ST8iaII-mediated polysialylation of NCAM. Utilizing a novel HPLC-based assay to quantify polysialylation of a fluorescent acceptor (DMB-DP3), we demonstrated that CMP is a competitive inhibitor of ST8SiaII (Ki = 10 μM). Importantly, we have shown that CMP causes a concentration-dependent reduction in tumour cell-surface polySia expression, with an absence of toxicity. When ST8SiaII-expressing tumour cells (SH-SY5Y and C6-STX) were evaluated in 2D cell migration assays, ST8SiaII inhibition led to significant reductions in migration, while CMP had no effect on cells not expressing ST8SiaII (DLD-1 and C6-WT). The study demonstrates for the first time that a polysialyltransferase inhibitor can modulate migration in ST8SiaII-expressing tumour cells. We conclude that ST8SiaII can be considered a druggable target with the potential for interfering with a critical mechanism in tumour cell dissemination in metastatic cancers.Yorkshire Cancer Research; EPSRC; Association for International Cancer Research; Jordanian Government PhD scholarshi
Exploring and Exploiting Acceptor Preferences of the Human Polysialyltransferases as a Basis for an Inhibitor Screen
Yesα2,8-Linked polysialic acid (polySia) is an oncofoetal antigen with high abundance during embryonic development. It reappears in malignant tumours of neuroendocrine origin. Two polysialyltransferases (polySTs) ST8SiaII and IV are responsible for polySia biosynthesis. During development, both enzymes are essential to control polySia expression. However, in tumours ST8SiaII is the prevalent enzyme. Consequently, ST8SiaII is an attractive target for novel cancer therapeutics. A major challenge is the high structural and functional conservation of ST8SiaII and -IV. An assay system that enables differential testing of ST8SiaII and -IV would be of high value to search for specific inhibitors. Here we exploited the different modes of acceptor recognition and elongation for this purpose. With DMB-DP3 and DMB-DP12 (fluorescently labelled sialic acid oligomers with a degree of polymerisation of 3 and 12, respectively) we identified stark differences between the two enzymes. The new acceptors enabled the simple comparative testing of the polyST initial transfer rate for a series of CMP-activated and N-substituted sialic acid derivatives. Of these derivatives, the non-transferable CMP-Neu5Cyclo was found to be a new, competitive ST8SiaII inhibitor
Switching the stereochemical outcome of 6-endo-trig cyclizations; Synthesis of 2,6-Cis-6-substituted 4-oxopipecolic acids
A base-mediated 6-endo-trig cyclization of
readily accessible enone-derived α-amino acids has been
developed for the direct synthesis of novel 2,6-cis-6-
substituted-4-oxo-L-pipecolic acids. A range of aliphatic and
aryl side chains were tolerated by this mild procedure to give
the target compounds in good overall yields. Molecular
modeling of the 6-endo-trig cyclization allowed some insight as
to how these compounds were formed, with the enolate
intermediate generated via an equilibrium process, followed by irreversible tautomerization/neutralization providing the driving force for product formation. Stereoselective reduction and deprotection of the resulting 2,6-cis-6-substituted 4-oxo-L-pipecolic acids to the corresponding 4-hydroxy-L-pipecolic acids was also performed
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Synthesis and biological evaluation of cyclobutane-based β3 integrin antagonists: A novel approach to targeting integrins for cancer therapy
YesThe Arg-Gly-Asp (RGD)-binding family of integrin receptors, and notably the β3 subfamily, are key to multiple physiological processes involved in tissue development, cancer proliferation, and metastatic dissemination. While there is compelling preclinical evidence that both αvβ3 and αIIbβ3 are important anticancer targets, most integrin antagonists developed to target the β3 integrins are highly selective for αvβ3 or αIIbβ3. We report the design, synthesis, and biological evaluation of a new structural class of ligand-mimetic β3 integrin antagonist. These new antagonists combine a high activity against αvβ3 with a moderate affinity for αIIbβ3, providing the first evidence for a new approach to integrin targeting in cancer.This work was supported by the EPSRC (RCUK Academic Fellowship and Grant EP/H002626/1 to H.M.S.) and Prostate Cancer UK (Pilot Grant PA10-01). F.O.F.O.A-S.. was funded by the Public Authority for Applied Education and Training, Kuwait (PhD studentship)
Algebraic Bethe ansatz method for the exact calculation of energy spectra and form factors: applications to models of Bose-Einstein condensates and metallic nanograins
In this review we demonstrate how the algebraic Bethe ansatz is used for the
calculation of the energy spectra and form factors (operator matrix elements in
the basis of Hamiltonian eigenstates) in exactly solvable quantum systems. As
examples we apply the theory to several models of current interest in the study
of Bose-Einstein condensates, which have been successfully created using
ultracold dilute atomic gases. The first model we introduce describes Josephson
tunneling between two coupled Bose-Einstein condensates. It can be used not
only for the study of tunneling between condensates of atomic gases, but for
solid state Josephson junctions and coupled Cooper pair boxes. The theory is
also applicable to models of atomic-molecular Bose-Einstein condensates, with
two examples given and analysed. Additionally, these same two models are
relevant to studies in quantum optics. Finally, we discuss the model of
Bardeen, Cooper and Schrieffer in this framework, which is appropriate for
systems of ultracold fermionic atomic gases, as well as being applicable for
the description of superconducting correlations in metallic grains with
nanoscale dimensions. In applying all of the above models to physical
situations, the need for an exact analysis of small scale systems is
established due to large quantum fluctuations which render mean-field
approaches inaccurate.Comment: 49 pages, 1 figure, invited review for J. Phys. A., published version
available at http://stacks.iop.org/JPhysA/36/R6
A horizon scan of global conservation issues for 2014
This paper presents the output of our fifth annual horizon-scanning exercise, which aims to identify topics that increasingly may affect conservation of biological diversity, but have yet to be widely considered. A team of professional horizon scanners, researchers, practitioners, and a journalist identified 15 topics which were identified via an iterative, Delphi-like process. The 15 topics include a carbon market induced financial crash, rapid geographic expansion of macroalgal cultivation, genetic control of invasive species, probiotic therapy for amphibians, and an emerging snake fungal disease. © 2013 Elsevier Ltd
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