401 research outputs found

    Paired and altruistic kidney donation in the UK: algorithms and experimentation

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    We study the computational problem of identifying optimal sets of kidney exchanges in the UK. We show how to expand an integer programming-based formulation [1, 19] in order to model the criteria that constitute the UK definition of optimality. The software arising from this work has been used by the National Health Service Blood and Transplant to find optimal sets of kidney exchanges for their National Living Donor Kidney Sharing Schemes since July 2008.We report on the characteristics of the solutions that have been obtained in matching runs of the scheme since this time. We then present empirical results arising from the real datasets that stem from these matching runs, with the aim of establishing the extent to which the particular optimality criteria that are present in the UK influence the structure of the solutions that are ultimately computed. A key observation is that allowing 4-way exchanges would be likely to lead to a significant number of additional transplants

    Changes in epidemiological patterns of sea lice infestation on farmed Atlantic salmon, Salmo salar L., in Scotland between 1996 and 2006

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    Analyses of a unique database containing sea lice records over an 11 year period provide evidence of changing infestation patterns in Scotland. The data, collected from more than 50 commercial Atlantic salmon farms, indicate that both species of sea lice commonly found in Scotland, Lepeophtheirus salmonis and Caligus elongatus, have declined on farms over the past decade. Reductions for both species have been particularly marked since 2001 when more effective veterinary medicines became available. Treatment data were also available in the database and these show a growing trend towards the use of the in feed medication emamectin benzoate (Slice), particularly in the first year of the salmon production cycle. However, this trend to wards single product use has not been sustained in 2006, the latest year for which data are available. There is some evidence of region to region variation within Scotland with the Western Isles experiencing higher levels of infestation. However, compared to the levels observed between 1996 and 2000, all regions have benefited from reduced lice infestation, with the overall pattern showing a particular reduction in the second and third quarters of the second year of production

    DNA Topoisomerase I Gene Copy Number and mRNA Expression Assessed as Predictive Biomarkers for Adjuvant Irinotecan in Stage II/III Colon Cancer.

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    PURPOSE: Prospective-retrospective assessment of theTOP1gene copy number andTOP1mRNA expression as predictive biomarkers for adjuvant irinotecan in stage II/III colon cancer. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded tissue microarrays were obtained from an adjuvant colon cancer trial (PETACC3) where patients were randomized to 5-fluorouracil/folinic acid with or without additional irinotecan.TOP1copy number status was analyzed by fluorescencein situhybridization (FISH) using aTOP1/CEN20 dual-probe combination.TOP1mRNA data were available from previous analyses. RESULTS: TOP1FISH and follow-up data were obtained from 534 patients.TOP1gain was identified in 27% using a single-probe enumeration strategy (≥4TOP1signals per cell) and in 31% when defined by aTOP1/CEN20 ratio ≥ 1.5. The effect of additional irinotecan was not dependent onTOP1FISH status.TOP1mRNA data were available from 580 patients with stage III disease. Benefit of irinotecan was restricted to patients characterized byTOP1mRNA expression ≥ third quartile (RFS: HRadjusted, 0.59;P= 0.09; OS: HRadjusted, 0.44;P= 0.03). The treatment byTOP1mRNA interaction was not statistically significant, but in exploratory multivariable fractional polynomial interaction analysis, increasingTOP1mRNA values appeared to be associated with increasing benefit of irinotecan. CONCLUSIONS: In contrast to theTOP1copy number, a trend was demonstrated for a predictive property ofTOP1mRNA expression. On the basis ofTOP1mRNA, it might be possible to identify a subgroup of patients where an irinotecan doublet is a clinically relevant option in the adjuvant setting of colon cancer.Clin Cancer Res; 22(7); 1621-31. ©2015 AACR

    Hydrodynamic excitations of trapped dipolar fermions

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    A single-component Fermi gas of polarized dipolar particles in a harmonic trap can undergo a mechanical collapse due to the attractive part of the dipole-dipole interaction. This phenomenon can be conveniently manipulated by the shape of the external trapping potential. We investigate the signatures of the instability by studying the spectrum of low-lying collective excitations of the system in the hydrodynamic regime. To this end, we employ a time-dependent variational method as well as exact numerical solutions of the hydrodynamic equations of the system.Comment: 4 pages, 2 eps figures, final versio

    Impact of chirality on the photoinduced charge transfer in linked systems containing naproxen enantiomers

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    [EN] The model reaction of photoinduced donor-acceptor interaction in linked systems (dyads) has been used to study the comparative reactivity of a well-known anti-inflammatory drug, (S)-naproxen (NPX) and its (R)-isomer. (R)- or (S)-NPX in these dyads is linked to (S)-N-methylpyrrolidine (Pyr) using a linear or cyclic amino acid bridge (AA or CyAA), to give (R)-/(S)-NPX-AA-(S)-Pyr flexible and (R)-/(S)-NPX-CyAA-(S)-Pyr rigid dyads. The donor-acceptor interaction is reminiscent of the binding (partial charge transfer, CT) and electron transfer (ET) processes involved in the extensively studied inhibition of the cyclooxygenase enzymes (COXs) by the NPX enantiomers. Besides that, both optical isomers undergo oxidative metabolism by enzymes from the P450 family, which also includes ET. The scheme proposed for the excitation quenching of the (R)- and (S)-NPX excited state in these dyads is based on the joint analysis of the chemically induced dynamic nuclear polarization (CIDNP) and fluorescence data. The H-1 CIDNP effects in this system appear in the back electron transfer in the biradical-zwitterion (BZ), which is formed via dyad photoirradiation. The rate constants of individual steps in the proposed scheme and the fluorescence quantum yields of the local excited (LE) states and exciplexes show stereoselectivity. It depends on the bridge's length, structure and solvent polarity. The CIDNP effects (experimental and calculated) also demonstrate stereodifferentiation. The exciplex quantum yields and the rates of formation are larger for the dyads containing (R)-NPX, which let us suggest a higher contribution from the CT processes with the (R)-optical isomer.The work was supported by the Russian Foundation for Fundamental Research (14-03-00192, 14-03-00692). All QS calculations were carried out on a cluster computer in the regional center for shared computer equipment at the Ufa Institute of Chemistry of RAS.Khramtsova, E.; Sosnovsky, D.; Ageeva, A.; Nuin Plá, NE.; Marín García, ML.; Purtov, P.; Borisevich, S.... (2016). Impact of chirality on the photoinduced charge transfer in linked systems containing naproxen enantiomers. Physical Chemistry Chemical Physics. 18(18):12733-12741. https://doi.org/10.1039/C5CP07305GS1273312741181

    Superconductivity in the two dimensional Hubbard Model.

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    Quasiparticle bands of the two-dimensional Hubbard model are calculated using the Roth two-pole approximation to the one particle Green's function. Excellent agreement is obtained with recent Monte Carlo calculations, including an anomalous volume of the Fermi surface near half-filling, which can possibly be explained in terms of a breakdown of Fermi liquid theory. The calculated bands are very flat around the (pi,0) points of the Brillouin zone in agreement with photoemission measurements of cuprate superconductors. With doping there is a shift in spectral weight from the upper band to the lower band. The Roth method is extended to deal with superconductivity within a four-pole approximation allowing electron-hole mixing. It is shown that triplet p-wave pairing never occurs. Singlet d_{x^2-y^2}-wave pairing is strongly favoured and optimal doping occurs when the van Hove singularity, corresponding to the flat band part, lies at the Fermi level. Nearest neighbour antiferromagnetic correlations play an important role in flattening the bands near the Fermi level and in favouring superconductivity. However the mechanism for superconductivity is a local one, in contrast to spin fluctuation exchange models. For reasonable values of the hopping parameter the transition temperature T_c is in the range 10-100K. The optimum doping delta_c lies between 0.14 and 0.25, depending on the ratio U/t. The gap equation has a BCS-like form and (2*Delta_{max})/(kT_c) ~ 4.Comment: REVTeX, 35 pages, including 19 PostScript figures numbered 1a to 11. Uses epsf.sty (included). Everything in uuencoded gz-compressed .tar file, (self-unpacking, see header). Submitted to Phys. Rev. B (24-2-95

    Cilengitide in newly diagnosed glioblastoma: biomarker expression and outcome.

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    Integrins αvβ3 and αvβ5 regulate angiogenesis and invasiveness in cancer, potentially by modulating activation of the transforming growth factor (TGF)-β pathway. The randomized phase III CENTRIC and phase II CORE trials explored the integrin inhibitor cilengitide in patients with newly diagnosed glioblastoma with versus without O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. These trials failed to meet their primary endpoints.Immunohistochemistry was used to assess the levels of the target integrins of cilengitide, αvβ3 and αvβ5 integrins, of αvβ8 and of their putative target, phosphorylation of SMAD2, in tumor tissues from CENTRIC (n=274) and CORE (n=224).αvβ3 and αvβ5 expression correlated well in tumor and endothelial cells, but showed little association with αvβ8 or pSMAD2 levels. In CENTRIC, there was no interaction between the biomarkers and treatment for prediction of outcome. In CORE, higher αvβ3 levels in tumor cells were associated with improved progression-free survival by central review and with improved overall survival in patients treated with cilengitide.Integrins αvβ3, αvβ5 and αvβ8 are differentially expressed in glioblastoma. Integrin levels do not correlate with the activation level of the canonical TGF-β pathway. αvβ3 integrin expression may predict benefit from integrin inhibition in patients with glioblastoma lacking MGMT promoter methylation

    Probing Sub-Micron Forces by Interferometry of Bose-Einstein Condensed Atoms

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    We propose a technique, using interferometry of Bose-Einstein condensed alkali atoms, for the detection of sub-micron-range forces. It may extend present searches at 1 micron by 6 to 9 orders of magnitude, deep into the theoretically interesting regime of 1000 times gravity. We give several examples of both four-dimensional particles (moduli), as well as higher-dimensional particles -- vectors and scalars in a large bulk-- that could mediate forces accessible by this technique.Comment: 32 pages, 5 figures, RevTeX4, expanded discussion of interactions, references added, to appear in PR
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