Investigating the intrinsic noise limit of Dayem bridge NanoSQUIDs

NanoSQUIDs made from Nb thin films have been produced with nanometre loop sizes down to 200 nm, using weak-link junctions with dimensions less than 60 nm. These composite (W/Nb) single layer thin film devices, patterned by FIB milling, show extremely good low-noise performance ∼170 nΦ0 at temperatures between 5 and 8.5 K and can operate in rather high magnetic fields (at least up to 1 T). The devices produced so far have a limited operating temperature range, typically only 1–2 K. We have the goal of achieving operation at 4.2 K, to be compatible with the best SQUID series array (SSA) preamplifier available. Using the SSA to readout the nanoSQUIDs provides us with a means of investigating the intrinsic noise of the former. In this paper we report improved white noise levels of these nanoSQUIDs, enabling potential detection of a single electronic spin flip in a 1-Hz bandwidth. At low frequencies the noise performance is already limited by SSA preamplifier noise

Evaluation of poly (ADP-ribose) polymerase inhibitor ABT-888 combined with radiotherapy and temozolomide in glioblastoma.

BACKGROUND: The cytotoxicity of radiotherapy and chemotherapy can be enhanced by modulating DNA repair. PARP is a family of enzymes required for an efficient base-excision repair of DNA single-strand breaks and inhibition of PARP can prevent the repair of these lesions. The current study investigates the trimodal combination of ABT-888, a potent inhibitor of PARP1-2, ionizing radiation and temozolomide(TMZ)-based chemotherapy in glioblastoma (GBM) cells. METHODS: Four human GBM cell lines were treated for 5 h with 5 μM ABT-888 before being exposed to X-rays concurrently with TMZ at doses of 5 or 10 μM for 2 h. ABT-888's PARP inhibition was measured using immunodetection of poly(ADP-ribose) (pADPr). Cell survival and the different cell death pathways were examined via clonogenic assay and morphological characterization of the cell and cell nucleus. RESULTS: Combining ABT-888 with radiation yielded enhanced cell killing in all four cell lines, as demonstrated by a sensitizer enhancement ratio at 50% survival (SER50) ranging between 1.12 and 1.37. Radio- and chemo-sensitization was further enhanced when ABT-888 was combined with both X-rays and TMZ in the O6-methylguanine-DNA-methyltransferase (MGMT)-methylated cell lines with a SER50 up to 1.44. This effect was also measured in one of the MGMT-unmethylated cell lines with a SER50 value of 1.30. Apoptosis induction by ABT-888, TMZ and X-rays was also considered and the effect of ABT-888 on the number of apoptotic cells was noticeable at later time points. In addition, this work showed that ABT-888 mediated sensitization is replication dependent, thus demonstrating that this effect might be more pronounced in tumour cells in which endogenous replication lesions are present in a larger proportion than in normal cells. CONCLUSIONS: This study suggests that ABT-888 has the clinical potential to enhance the current standard treatment for GBM, in combination with conventional chemo-radiotherapy. Interestingly, our results suggest that the use of PARP inhibitors might be clinically significant in those patients whose tumour is MGMT-unmethylated and currently derive less benefit from TMZ.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Pharmacological assessment of ibuprofen arginate on platelet aggregation and colon cancer cell killing

This work was funded in part by grants from the Wellcome Trust (0852551Z108/Z, to J.A.M.) and British Heart Foundation (FS/16/1/31699, to NSK). SM is a recipient of a PhD award from the King of Saud University, AT is a recipient of a MRC PhD studentship

Comparison of optical model results from a microscopic Schr\"odinger approach to nucleon-nucleus elastic scattering with those from a global Dirac phenomenology

Comparisons are made between results of calculations for intermediate energy nucleon-nucleus scattering for 12C, 16O, 40Ca, 90Zr, and 208Pb, using optical potentials obtained from global Dirac phenomenology and from a microscopic Schr\"odinger model. Differential cross sections and spin observables for scattering from the set of five nuclei at 65 MeV and 200 MeV have been studied to assess the relative merits of each approach. Total reaction cross sections from proton-nucleus and total cross sections from neutron-nucleus scattering have been evaluated and compared with data for those five targets in the energy range 20 MeV to 800 MeV. The methods of analyses give results that compare well with experimental data in those energy regimes for which the procedures are suited.Comment: 22 pages, 12 figure

Systematic study of constitutive cyclo-oxygenase-2 expression: role of NFκB and NFAT transcriptional pathways

Cyclooxygenase-2 (COX-2) is an inducible enzyme that drives inflammation and is the therapeutic target for widely used nonsteroidal antiinflammatory drugs (NSAIDs). However, COX-2 is also constitutively expressed, in the absence of overt inflammation, with a specific tissue distribution that includes the kidney, gastrointestinal tract, brain, and thymus. Constitutive COX-2 expression is therapeutically important because NSAIDs cause cardiovascular and renal side effects in otherwise healthy individuals. These side effects are now of major concern globally. However, the pathways driving constitutive COX-2 expression remain poorly understood. Here we show that in the kidney and other sites, constitutive COX-2 expression is a sterile response, independent of commensal microorganisms and not associated with activity of the inflammatory transcription factor NF-κB. Instead, COX-2 expression in the kidney but not other regions colocalized with nuclear factor of activated T cells (NFAT) transcription factor activity and was sensitive to inhibition of calcineurin-dependent NFAT activation. However, calcineurin/NFAT regulation did not contribute to constitutive expression elsewhere or to inflammatory COX-2 induction at any site. These data address the mechanisms driving constitutive COX-2 and suggest that by targeting transcription it may be possible to develop antiinflammatory therapies that spare the constitutive expression necessary for normal homeostatic functions, including those important to the cardiovascular-renal system

A bioassay system of autologous human endothelial, smooth muscle cells and leucocytes for use in drug discovery, phenotyping and tissue engineering

Purpose: Blood vessels are comprised of endothelial and smooth muscle cells. Obtaining both types of cells from vessels of living donors is not possible without invasive surgery. To address this we have devised a strategy whereby human endothelial and smooth muscle cells derived from blood progenitors from the same donor could be cultured with autologous leucocytes to generate a same donor ‘vessel in a dish’ bioassay. Basic procedures: Autologous sets of blood outgrowth endothelial cells (BOECs), smooth muscle cells (BO-SMCs) and leucocytes were obtained from 4 donors. Cells were treated in mono and cumulative co-culture conditions. The endothelial specific mediator endothelin-1 along with interleukin (IL)-6, IL-8, tumour necrosis factor α, and interferon gamma-induced protein 10 were measured under control culture conditions and after stimulation with cytokines. Main findings: Co-cultures remained viable throughout. The profile of individual mediators released from cells was consistent with what we know of endothelial and smooth muscle cells cultured from blood vessels. Principle conclusions: For the first time, we report a proof of concept study where autologous blood outgrowth ‘vascular’ cells and leucocytes were studied alone and in co-culture. This novel bioassay has utility in vascular biology research, patient phenotyping, drug testing and tissue engineering

The LSST DESC data challenge 1: Generation and analysis of synthetic images for next-generation surveys

Data Challenge 1 (DC1) is the first synthetic data set produced by the Rubin Observatory Legacy Survey of Space and Time (LSST) Dark Energy Science Collaboration (DESC). DC1 is designed to develop and validate data reduction and analysis and to study the impact of systematic effects that will affect the LSST data set. DC1 is comprised of r-band observations of 40 deg2 to 10 yr LSST depth. We present each stage of the simulation and analysis process: (a) generation, by synthesizing sources from cosmological N-body simulations in individual sensor-visit images with different observing conditions; (b) reduction using a development version of the LSST Science Pipelines; and (c) matching to the input cosmological catalogue for validation and testing. We verify that testable LSST requirements pass within the fidelity of DC1. We establish a selection procedure that produces a sufficiently clean extragalactic sample for clustering analyses and we discuss residual sample contamination, including contributions from inefficiency in star-galaxy separation and imperfect deblending. We compute the galaxy power spectrum on the simulated field and conclude that: (i) survey properties have an impact of 50 per cent of the statistical uncertainty for the scales and models used in DC1; (ii) a selection to eliminate artefacts in the catalogues is necessary to avoid biases in the measured clustering; and (iii) the presence of bright objects has a significant impact (2-6) in the estimated power spectra at small scales (> 1200), highlighting the impact of blending in studies at small angular scales in LSST