Studies of Effectiveness of Commercial Home Treatment Systems

Eleven home water systems were tested representing six different types of filtering systems. Tests were made for Sulfates, Nitrates, Phosphate, Iron and Escherichia coli and Enterobacter aerogenes before and after passing through a home treatment system. All of the systems removed iron adequately but had little effect on the removal of nitrates, phosphates, sulfates or control of pH. Since none of the ground waters was contaminated by coli- forms, nothing was established regarding the effectiveness of bacterial removal by these systems

⁹⁹ᵐTc SPECT imaging agent based on cFLFLFK for the detection of FPR1 in inflammation

Non-invasive imaging of the inflammatory process can provide a great deal of insight into a wide variety of diseases states, aiding diagnosis, evaluation and effective targeted treatment. During inflammation, blood borne leukocytes are recruited, through a series of activation and adhesion steps, to the site of injury or infection where they migrate across the blood vessel wall into the tissue. Thus, tracking leukocyte recruitment and accumulation provides a dynamic and localised read out of inflammatory events. Current leukocyte imaging techniques require ex vivo labelling of patient blood, involving laborious processing and potential risks to both patient and laboratory staff. Utilising high affinity ligands for leukocyte specific receptors may allow for injectable tracers that label leukocytes in situ, omitting potentially hazardous ex vivo handling. Formyl peptide receptors (FPRs) are a group of G-protein coupled receptors involved in the chemotaxis and inflammatory functioning of leukocytes. Highly expressed on leukocytes, and up regulated during inflammation, these receptors provide a potential target for imaging inflammatory events. Herein we present the synthesis and initial in vitro testing of a potential Single Photon Emission Computed Tomography (SPECT) leukocyte tracer. The FPR1 antagonist cFLFLFK-NH₂, which displays high affinity with little physiological effect, has been linked via a PEG motif to a ⁹⁹ᵐTc chelate. This tracer shows in vitro binding to human embryonic kidney cells expressing the FPR1 receptor, and functional in vitro tests reveal cFLFLFK-NH₂ compounds to have no effect on inflammatory cell functioning. Overall, these data show that ⁹⁹ᵐTc.cFLFLFK-NH₂ may be a useful tool for non-invasive imaging of leukocyte accumulation in inflammatory disease states

Focusing and Calibration of Large Scale Network Sensors using GraphBLAS Anonymized Hypersparse Matrices

Defending community-owned cyber space requires community-based efforts. Large-scale network observations that uphold the highest regard for privacy are key to protecting our shared cyberspace. Deployment of the necessary network sensors requires careful sensor placement, focusing, and calibration with significant volumes of network observations. This paper demonstrates novel focusing and calibration procedures on a multi-billion packet dataset using high-performance GraphBLAS anonymized hypersparse matrices. The run-time performance on a real-world data set confirms previously observed real-time processing rates for high-bandwidth links while achieving significant data compression. The output of the analysis demonstrates the effectiveness of these procedures at focusing the traffic matrix and revealing the underlying stable heavy-tail statistical distributions that are necessary for anomaly detection. A simple model of the corresponding probability of detection ($p_{\rm d}$) and probability of false alarm ($p_{\rm fa}$) for these distributions highlights the criticality of network sensor focusing and calibration. Once a sensor is properly focused and calibrated it is then in a position to carry out two of the central tenets of good cybersecurity: (1) continuous observation of the network and (2) minimizing unbrokered network connections.Comment: Accepted to IEEE HPEC, 9 pages, 12 figures, 1 table, 63 references, 2 appendice

Flutriciclamide (18F-GE180) PET:first in human PET study of novel 3rd generation in vivo marker of human translator protein

Neuroinflammation is associated with neurodegenerative disease. PET radioligands targeting the 18-kDa translocator protein (TSPO) have been used as in vivo markers of neuroinflammation, but there is an urgent need for novel probes with improved signal-to-noise ratio. Flutriciclamide (18F-GE180) is a recently developed third-generation TSPO ligand. In this first study, we evaluated the optimum scan duration and kinetic modeling strategies for 18F-GE180 PET in (older) healthy controls

Positron Emission Tomography Imaging of Macrophages in Atherosclerosis with F-18-GE-180, a Radiotracer for Translocator Protein (TSPO)

Intraplaque inflammation plays an important role in the progression of atherosclerosis.) The 18 kDa translocator protein (TSPO) expression is upregulated in activated macrophages, representing a potential target to identify inflamed atherosclerotic plaques. We preclinically evaluated F-18-GE-180, a novel third-generation TSPO radioligand, in a mouse model of atherosclerosis. Methods. Nine hypercholesterolemic mice deficient in low density lipoprotein receptor and apolipoprotein B48 (LDLR(-/-)ApoB(100/100)) and six healthy C57BL/6N mice were injected with 10 MBq of F-18-GE-180. Specificity of binding was demonstrated in three LDLR(-/-)ApoB(100/100) mice by injection of nonradioactive reference compound of F-18-GE-180 before F-18-GE-180. Dynamic 30-minute PET was performed followed by contrast-enhanced CT, and the mice were sacrificed at 60 minutes after injection. Tissue samples were obtained for ex vivo biodistribution measurements, and aortas were cut into serial cryosections for digital autoradiography. The presence of macrophages and TSPO was studied by immunohistochemistry. The F-18-GE-180 retention in plaque areas with different macrophage densities and lesion-free vessel wall were compared. Results. The LDLR-/-ApoB(100/100) mice showed large, inflamed plaques in the aorta. Autoradiography revealed significantly higher 18F-GE-180 retention in macrophage-rich plaque areas than in noninflamed areas (count densities 150 +/- 45 PSL/mm(2) versus 51 +/- 12 PSL/mm2, p Conclusion. F-18-GE-180 shows specific uptake in macrophage-rich areas of atherosclerotic plaques in mice. However, retention in atherosclerotic lesions does not exceed that in lesion-free vessel wall. The third-generation TSPO radioligand F-18-GE-180 did not show improved characteristics for imaging atherosclerotic plaque inflammation compared to previously studied TSPO-targeting tracers.</div

Radiosynthesis of (R,S)-[18 F]GE387: A Potential PET Radiotracer for Imaging Translocator Protein 18 kDa (TSPO) with Low Binding Sensitivity to the Human Gene Polymorphism rs6971.

Translocator protein (TSPO) is a biomarker of neuroinflammation, which is a hallmark of many neurodegenerative diseases and has been exploited as a positron emission tomography (PET) target. Carbon-11-labelled PK11195 remains the most applied agent for imaging TSPO, despite its short-lived isotope and low brain permeability. Second-generation radiotracers show variance in affinity amongst subjects (low-, mixed-, and high-affinity binders) caused by the genetic polymorphism (rs6971) of the TSPO gene. To overcome these limitations, a new structural scaffold was explored based on the TSPO pharmacophore, and the analogue with a low-affinity binder/high-affinity binder (LAB/HAB) ratio similar (1.2 vs. 1.3) to that of (R)-[11 C]PK11195 was investigated. The synthesis of the reference compound was accomplished in six steps and 9 % overall yield, and the precursor was prepared in eight steps and 8 % overall yield. The chiral separation of the reference and precursor compounds was performed using supercritical fluid chromatography with >95 % ee. The absolute configuration was determined by circular dichroism. Optimisation of reaction conditions for manual radiolabelling revealed acetonitrile as a preferred solvent at 100 °C. Automation of this radiolabelling method provided R and S enantiomers in respective 21.3±16.7 and 25.6±7.1 % decay-corrected yields and molar activities of 55.8±35.6 and 63.5±39.5 GBq μmol-1 (n=3). Injection of the racemic analogue into a healthy rat confirmed passage through the blood-brain barrier.This work was supported by Medical Research Council (UK) grant awards RG46503 (LM, MH, XZ) and RG70550 (EF), National Institute of Health Research (UK), Cambridge Biomedical Research Unit in Dementia (EF, NKR) and the Herchel Smith Fellowship programme (LQ)

Distributive justice with and without culture

Academic treatments of distributive justice normally adopt a static approach centred on resource allocation among a set of individual agents. The resulting models, expressed in mathematical language, make no allowance for culture, as they never engage with the society’s way of life or the moulding of individuals within society. This paper compares the static approach to distributive justice with a cultural one, arguing that a case for redistribution should rest upon its cultural effects in assisting well-being and social cohesion. Unless we recognise culture, we can have little understanding of why inequalities matter, where they come from, and how they might be reduced. Redistribution may be motivated by universal value judgements taken from external sources, but it also entails internal cultural changes that refashion social relations through cumulative causation. In practical terms, it has to penetrate beyond reallocating resource endowments to bring revised attitudes in a society less tolerant of unequal outcomes. Egalitarian reforms will flourish only if they generate and reflect an egalitarian culture