87 research outputs found
Gravitational Coupling and Dynamical Reduction of The Cosmological Constant
We introduce a dynamical model to reduce a large cosmological constant to a
sufficiently small value. The basic ingredient in this model is a distinction
which has been made between the two unit systems used in cosmology and particle
physics. We have used a conformal invariant gravitational model to define a
particular conformal frame in terms of large scale properties of the universe.
It is then argued that the contributions of mass scales in particle physics to
the vacuum energy density should be considered in a different conformal frame.
In this manner, a decaying mechanism is presented in which the conformal factor
appears as a dynamical field and plays a key role to relax a large effective
cosmological constant. Moreover, we argue that this model also provides a
possible explanation for the coincidence problem.Comment: To appear in GR
11β-HSD1 inhibition in men mitigates prednisolone-induced adverse effects in a proof-of-concept randomised double-blind placebo-controlled trial
Glucocorticoids prescribed to limit inflammation, have significant adverse effects. As 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoid, we investigated whether 11β-HSD1 inhibition with AZD4017 could mitigate adverse glucocorticoid effects without compromising their anti-inflammatory actions. We conducted a proof-of-concept, randomized, double-blind, placebo-controlled study at Research Unit, Churchill Hospital, Oxford, UK (NCT03111810). 32 healthy male volunteers were randomized to AZD4017 or placebo, alongside prednisolone treatment. Although the primary endpoint of the study (change in glucose disposal during a two-step hyperinsulinemic, normoglycemic clamp) wasn’t met, hepatic insulin sensitivity worsened in the placebo-treated but not in the AZD4017-treated group. Protective effects of AZD4017 on markers of lipid metabolism and bone turnover were observed. Night-time blood pressure was higher in the placebo-treated but not in the AZD4017-treated group. Urinary (5aTHF+THF)/THE ratio was lower in the AZD4017-treated but remained the same in the placebo-treated group. Most anti-inflammatory actions of prednisolone persisted with AZD4017 co-treatment. Four adverse events were reported with AZD4017 and no serious adverse events. Here we show that co-administration of AZD4017 with prednisolone in men is a potential strategy to limit adverse glucocorticoid effects
Movements of the bottlenose Dolphin (Tursiops truncatus) in the Rio de Janeiro State, Southeastern Brazil
Cultivares de trigo respondem diferentemente à qualidade da luz quanto à emissão de afilhos e acumulação de massa seca
The Sudbury Neutrino Observatory
The Sudbury Neutrino Observatory is a second generation water Cherenkov
detector designed to determine whether the currently observed solar neutrino
deficit is a result of neutrino oscillations. The detector is unique in its use
of D2O as a detection medium, permitting it to make a solar model-independent
test of the neutrino oscillation hypothesis by comparison of the charged- and
neutral-current interaction rates. In this paper the physical properties,
construction, and preliminary operation of the Sudbury Neutrino Observatory are
described. Data and predicted operating parameters are provided whenever
possible.Comment: 58 pages, 12 figures, submitted to Nucl. Inst. Meth. Uses elsart and
epsf style files. For additional information about SNO see
http://www.sno.phy.queensu.ca . This version has some new reference
Opposing authigenic controls on the isotopic signature of dissolved iron in hydrothermal plumes
Iron is a scarce but essential micronutrient in the oceans that limits primary productivity in many regions of the surface ocean. The mechanisms and rates of Fe supply to the ocean interior are still poorly understood and quantified. Iron isotope ratios of different Fe pools can potentially be used to trace sources and sinks of the global Fe biogeochemical cycle if these boundary fluxes have distinct signatures. Seafloor hydrothermal vents emit metal rich fluids from mid-ocean ridges into the deep ocean. Iron isotope ratios have the potential to be used to trace the input of hydrothermal dissolved iron to the oceans if the local controls on the fractionation of Fe isotopes during plume dispersal in the deep ocean are understood. In this study we assess the behaviour of Fe isotopes in a Southern Ocean hydrothermal plume using a sampling program of Total Dissolvable Fe (TDFe), and dissolved Fe (dFe). We demonstrate that δ56Fe values of dFe (δ56dFe) within the hydrothermal plume change dramatically during early plume dispersal, ranging from −2.39 ± 0.05‰ to −0.13 ± 0.06‰ (2 SD). The isotopic composition of TDFe (δ56TDFe) was consistently heavier than dFe values, ranging from −0.31 ± 0.03‰ to 0.78 ± 0.05‰, consistent with Fe oxyhydroxide precipitation as the plume samples age. The dFe present in the hydrothermal plume includes stabilised dFe species with potential to be transported to the deep ocean. We estimate that stable dFe exported from the plume will have a δ56Fe of −0.28 ± 0.17‰. Further, we show that the proportion of authigenic iron-sulfide and iron-oxyhydroxide minerals precipitating in the buoyant plume exert opposing controls on the resultant isotope composition of dissolved Fe passed into the neutrally buoyant plume. We show that such controls yield variable dissolved Fe isotope signatures under the authigenic conditions reported from modern vent sites elsewhere, and so ought to be considered during iron isotope reconstructions of past hydrothermalism from ocean sediment records
The effects of beta-amyloid peptide on microglial function
The role of microglia in Alzheimer’s Disease (AD) pathogenesis is widely
acknowledged, and the beta-amyloid (Aβ) peptide which accumulates in AD brain is
known to activate a range of microglial functions. In the present thesis, the acute
induction of some of these processes is examined using live cell imaging techniques.
Aβ causes activation of microglial NADPH oxidase, a membrane-localised enzyme
system which produces reactive oxygen species (ROS) thereby engendering oxidative
stress. The transfer of electrons across the membrane by this enzyme system to
produce ROS generates a potential difference, which will limit enzyme function unless
it is dissipated by a compensatory movement of charge. I show that chloride
intracellular channel 1 (CLIC1), a protein enriched in microglia and implicated in Aβ-
induced microglial-mediated neurotoxicity, mediates a chloride conductance which
sustains NADPH oxidase activity. Thus, blockade or knockdown of CLIC1 limits Aβ-
induced ROS production. Using a variety of imaging methods, I show that the
fascinating CLIC1 protein achieves its functions following an Aβ-induced redoxdependent
direct insertion into the plasma membrane from the cytosol.
Acute Aβ-induced microglial calcium signalling is also examined. Aβ is shown to elicit
rapid and complex changes in microglial cytosolic calcium concentration, although
these changes are less frequently observed in microglia than in astrocytes. The
changes are not linked to ROS damage nor to voltage-gated calcium channel (VGCC)
activity, but may be dependent on CD36 receptor function.
The effects of Aβ treatment on subsequent calcium signalling elicited by the neuronal
damage signalling molecule adenosine triphosphate (ATP) are investigated, and found
to be complex. Aβ causes disruption of microglial calcium homeostasis and a reduction
in the response to ATP, despite the calcium levels in the endoplasmic reticulum
required for the response being increased.
This work suggests that Aβ has diverse and consequential effects on microglial
function relevant to AD pathophysiology
Chloride intracellular channel 1 (CLIC1): Sensor and effector during oxidative stress
Oxidative stress, characterized by overproduction of reactive oxygen species (ROS), is a major feature of several pathological states. Indeed, many cancers and neurodegenerative diseases are accompanied by altered redox balance, which results from dysregulation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. In this review, we consider the role of the intracellular chloride channel 1 (CLIC1) in microglial cells during oxidative stress. Following microglial activation, CLIC1 translocates from the cytosol to the plasma membrane where it promotes a chloride conductance. The resultant anionic current balances the excess charge extruded by the active NADPH oxidase, supporting the generation of superoxide by the enzyme. In this scenario, CLIC1 could be considered to act as both a second messenger and an executor
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