High-resolution proton nuclear magnetic resonance: application to the study of leukaemic lymphocytes.

Proton Nuclear Magnetic Resonance spectroscopy (1H NMR) is able to monitor the changes that develop at a molecular level when leukaemic cells proliferate in the thymus of AKR mice. Furthermore, cultured human lymphocyte cell lines are shown to differ in their 1H-NMR spectra. These spectral differences are attributable to changes in membrane fluidity and composition, which in turn reflect the stage of differentiation and the type of transformation of the lymphocyte lines, i.e. Epstein-Barr virus (EBV) or leukaemic transformation..

1SXPS: A deep Swift X-ray Telescope point source catalog with light curves and spectra

We present the 1SXPS (Swift-XRT Point Source) catalog of 151,524 X-ray point-sources detected by the Swift-XRT in 8 years of operation. The catalog covers 1905 square degrees distributed approximately uniformly on the sky. We analyze the data in two ways. First we consider all observations individually, for which we have a typical sensitivity of ~3e-13 erg/cm2/s (0.3--10 keV). Then we co-add all data covering the same location on the sky: these images have a typical sensitivity of ~9e-14 erg/cm2/s (0.3--10 keV). Our sky coverage is nearly 2.5 times that of 3XMM-DR4, although the catalog is a factor of ~1.5 less sensitive. The median position error is 5.5" (90% confidence), including systematics. Our source detection method improves on that used in previous XRT catalogs and we report >68,000 new X-ray sources. The goals and observing strategy of the Swift satellite allow us to probe source variability on multiple timescales, and we find ~30,000 variable objects in our catalog. For every source we give positions, fluxes, time series (in four energy bands and two hardness ratios), estimates of the spectral properties, spectra and spectral fits for the brightest sources, and variability probabilities in multiple energy bands and timescales.Comment: 27 pages, 19 figures; accepted for publication in ApJS. The accompanying website, http://www.swift.ac.uk/1SXPS is live; the Vizier entry should be available shortl

Finite-size effects for anisotropic bootstrap percolation: logarithmic corrections

In this note we analyze an anisotropic, two-dimensional bootstrap percolation model introduced by Gravner and Griffeath. We present upper and lower bounds on the finite-size effects. We discuss the similarities with the semi-oriented model introduced by Duarte.Comment: Key words: Bootstrap percolation, anisotropy, finite-size effect

Is \gamma-ray emission from novae affected by interference effects in the 18F(p,\alpha)15O reaction?

The 18F(p,\alpha)15O reaction rate is crucial for constraining model predictions of the \gamma-ray observable radioisotope 18F produced in novae. The determination of this rate is challenging due to particular features of the level scheme of the compound nucleus, 19Ne, which result in interference effects potentially playing a significant role. The dominant uncertainty in this rate arises from interference between J\pi=3/2+ states near the proton threshold (Sp = 6.411 MeV) and a broad J\pi=3/2+ state at 665 keV above threshold. This unknown interference term results in up to a factor of 40 uncertainty in the astrophysical S-factor at nova temperatures. Here we report a new measurement of states in this energy region using the 19F(3He,t)19Ne reaction. In stark contrast with previous assumptions we find at least 3 resonances between the proton threshold and Ecm=50 keV, all with different angular distributions. None of these are consistent with J\pi= 3/2+ angular distributions. We find that the main uncertainty now arises from the unknown proton-width of the 48 keV resonance, not from possible interference effects. Hydrodynamic nova model calculations performed indicate that this unknown width affects 18F production by at least a factor of two in the model considered.Comment: 5 pages, 4 figures. Accepted for publication in Phys. Rev. Let

Signaling via interleukin-4, receptor alpha chain is required for successful vaccination against schistosomiasis in BALB/c mice

Radiation-attenuated (RA) schistosome larvae are potent stimulators of innate immune responses at the skin site of exposure (pinna) that are likely to be important factors in the development of Th1-mediated protective immunity. In addition to causing an influx of neutrophils, macrophages, and dendritic cells (DCs) into the dermis, RA larvae induced a cascade of chemokine and cytokine secretion following in vitro culture of pinna biopsy samples. While macrophage inflammatory protein 1 and interleukin-1 (IL-1) were produced transiently within the first few days, the Th1-promoting cytokines IL-12 and IL-18 were secreted at high levels until at least day 14. Assay of C3H/HeJ mice confirmed that IL-12 secretion was not due to lipopolysaccharide contaminants binding Toll-like receptor 4. Significantly, IL-12 p40 secretion was sustained in pinnae from vaccinated mice but not in those from nonprotected infected mice. In contrast, IL-10 was produced from both vaccinated and infected mice. This cytokine regulates IL-12-associated dermal inflammation, since in vaccinated IL-10/ mice, pinna thickness was greatly increased concurrent with elevated levels of IL-12 p40. A significant number of IL-12 p40 cells were detected as emigrants from in vitro-cultured pinnae, and most were within a population of rare large granular cells that were Ia, consistent with their being antigen-presenting cells. Labeling of IL-12 cells for CD11c, CD205, CD8, CD11b, and F4/80 indicated that the majority were myeloid DCs, although a proportion were CD11c F4/80, suggesting that macrophages were an additional source of IL-12 in the skin

Combined bezafibrate and medroxyprogesterone acetate: potential novel therapy for acute myeloid leukaemia

Background: The majority of acute myeloid leukaemia (AML) patients are over sixty years of age. With current treatment regimens, survival rates amongst these, and also those younger patients who relapse, remain dismal and novel therapies are urgently required. In particular, therapies that have anti-leukaemic activity but that, unlike conventional chemotherapy, do not impair normal haemopoiesis. Principal Findings: Here we demonstrate the potent anti-leukaemic activity of the combination of the lipid-regulating drug bezafibrate (BEZ) and the sex hormone medroxyprogesterone acetate (MPA) against AML cell lines and primary AML cells. The combined activity of BEZ and MPA (B/M) converged upon the increased synthesis and reduced metabolism of prostaglandin D2 (PGD2) resulting in elevated levels of the downstream highly bioactive, anti-neoplastic prostaglandin 15-deoxy Δ12,14 PGJ2 (15d-PGJ2). BEZ increased PGD2 synthesis via the generation of reactive oxygen species (ROS) and activation of the lipid peroxidation pathway. MPA directed prostaglandin synthesis towards 15d-PGJ2 by inhibiting the PGD2 11β -ketoreductase activity of the aldo-keto reductase AKR1C3, which metabolises PGD2 to 9α11β-PGF2α. B/M treatment resulted in growth arrest, apoptosis and cell differentiation in both AML cell lines and primary AML cells and these actions were recapitulated by treatment with 15d-PGJ2. Importantly, the actions of B/M had little effect on the survival of normal adult myeloid progenitors. Significance: Collectively our data demonstrate that B/M treatment of AML cells elevated ROS and delivered the anti-neoplastic actions of 15d-PGJ2. These observations provide the mechanistic rationale for the redeployment of B/M in elderly and relapsed AML

Discrete wetland groundwater discharges revealed with a three-dimensional temperature model and botanical indicators (Boxford, UK)

Wetlands provide unique goods and services, as habitats of high biodiversity. Hydrology is the principal control on wetland functioning; hence, understanding the water source is fundamental. However, groundwater inflows may be discrete and easily missed. Research techniques are required with low cost and minimal impact in sensitive settings. In this study, the effectiveness of using a three-dimensional (3D) temperature model and botanical indicators to characterise groundwater discharge is explored at the CEH (Centre for Ecology and Hydrology) River Lambourn Observatory, Boxford, UK. This comprises a 10 ha lowland riparian wetland, designated for its scientific interest and conservation value. Temperature data were collected in winter at multiple depths down to 0.9 m over approximately 3.6 ha and transformed into a 3D model via ordinary kriging. Anomalous warm zones indicated distinct areas of groundwater upwelling which were concurrent with relic channel structures. Lateral heat propagation from the channels was minimal and restricted to within 5–10 m. Vertical temperature sections within the channels suggest varying degrees of groundwater discharge along their length. Hydrochemical analysis showed that warmer peat waters were akin to deeper aquifer waters, confirming the temperature anomalies as areas of groundwater discharge. Subsequently, a targeted vegetation survey identified Carex paniculata as an indicator of groundwater discharge. The upwelling groundwater contains high concentrations of nitrate which is considered to support the spatially restricted growth of Carex paniculata against a background of poor fen communities located in reducing higher-phosphate waters

Optically pure, structural and fluorescent analogues of a dimeric Y4 receptor agonist derived by an olefin metathesis approach

The dimeric peptide 1 (BVD-74D, as a diastereomeric mixture) is a potent and selective Neuropeptide Y Y4 receptor agonist. It represents a valuable candidate in developing traceable ligands for pharmacological studies of Y4 receptors, and as a lead compound for anti-obesity drugs. Its optically pure stereoisomers along with analogues and fluorescently labelled variants were prepared by exploiting alkene metathesis reactions. The (2R,7R)- diaminosuberoyl containing peptide, (R,R)-1 had markedly higher affinity and agonist efficacy than its (S,S)-counterpart. Furthermore the sulfo-Cy5 labelled (R,R)-14 retained high agonist potency as a novel fluorescent ligand for imaging Y4 receptors