Radiation-induced insulator discharge pulses in the CRRES internal discharge monitor satellite experiment

The Internal Discharge Monitor (IDM) was designed to observe electrical pulses from common electrical insulators in space service. The sixteen insulator samples included twelve planar printed circuit boards and four cables. The samples were fully enclosed, mutually isolated, and space radiation penetrated 0.02 cm of aluminum before striking the samples. Pulsing began on the seventh orbit, the maximum pulse rate occurred on the seventeenth orbit when 13 pulses occurred, and the pulses slowly diminished to about one per 3 orbits six months later. After 8 months, the radiation belts abruptly increased and the pulse rates attained a new high. These pulse rates were in agreement with laboratory experience on shorter time scales. Several of the samples never pulsed. If the pulses were not confined within IDM, the physical processes could spread to become a full spacecraft anomaly. The IDM results indicate the rate at which small insulator pulses occur. Small pulses are the seeds of larger satellite electrical anomalies. The pulse rates are compared with space radiation intensities, L shell location, and spectral distributions from the radiation spectrometers on the Combined Release and Radiation Effects Satellite

A survey of aspects of pathology detection in optometric practice

A survey of aspects of pathology detection in optometric practic

Low altitude flux and dose measurements during two solar flare events

The dosimeter on board the low altitude polar orbiting DMSP/F7 satellite makes dose and flux measurements for electrons with energies greater than 1.0, 2.5, 5.0 and 10.0 MeV; and for protons with energies greater than 20, 35, 51, and 75 MeV. The characteristics and performance of the dosimeter are illustrated by presenting dose and flux data taken during the solar flare proton events of February 16 and April 26, 1984

Nonstorm time dynamics of electron radiation belts observed by the Van Allen Probes

Abstract Storm time electron radiation belt dynamics have been widely investigated for many years. Here we present a rarely reported nonstorm time event of electron radiation belt evolution observed by the Van Allen Probes during 21-24 February 2013. Within 2 days, a new belt centering around L=5.8 formed and gradually merged with the original outer belt, with the enhancement of relativistic electron fluxes by a factor of up to 50. Strong chorus waves (with power spectral density up to 10-4nT2/Hz) occurred in the region L\u3e5. Taking into account the local acceleration driven by these chorus waves, the two-dimensional STEERB can approximately reproduce the observed energy spectrums at the center of the new belt. These results clearly illustrate the complexity of electron radiation belt behaviors and the importance of chorus-driven local acceleration even during the nonstorm times

How ready is China for a China-style world order? China's state media discourse under construction

What exactly is the China-style world order that Chinese officials and intellectual elites have recently been talking about, and how ready is China for it? An examination and analysis of discourses on ‘Africa Live’ on CCTV Africa, the first overseas news center of China Central Television (CCTV), yields some highly noticeable features and significant themes, confirming that although China has shifted from a low-profile approach to a more assertive one, in an attempt to change the global order, its verbal challenge and sometimes harsh criticism of the American-led international system is accompanied by an obvious absence of a clear vision of what the new world order should be like. This lack of a clear vision may be due to the fact that the Chinese discourse on world order is still a work in progress, constrained by internal practices, and Africa is its testing ground for the construction of a discourse that China envisages as an alternative

Intrinsic Thermodynamics of Protein-Ligand Binding by Isothermal Titration Calorimetry as Aid to Drug Design

Isothermal titration calorimetry (ITC) is one of the main techniques to determine specific interactions between molecules dissolved in aqueous solution. This technique is commonly used in drug development programs when low-molecular-weight molecules are sought that bind tightly and specifically to a protein (disease target) molecule. The method allows a complete thermodynamic characterization of an interaction, i.e., ITC enables direct determination of the model-independent observed interaction change in enthalpy (ΔH) and a model-dependent observed interaction affinity (change in Gibbs free energy, ΔG) in a single experiment. The product of temperature and change in entropy (TΔS) can be obtained by the subtraction of ΔG from ΔH, and the change in heat capacity (ΔC p ) can be determined as a slope of the temperature dependence of the binding ΔH. Despite the apparent value of ITC in characterization of interactions, it is often forgotten that many protein-ligand binding reactions are linked to protonation-deprotonation reactions or various conformational changes. In such cases, it is important to determine the linked-reaction contributions and obtain the intrinsic values of the changes in Gibbs energy (affinity), enthalpy, and entropy. These energy values can then be used in various SAR-type structure-thermodynamics and combined with structure-kinetics correlations in drug design, when searching for small molecules that would bind the protein target molecule. This manuscript provides a detailed protocol on how to determine the intrinsic values of protein-ligand binding thermodynamics by ITC

Dietary composition modulates brain mass and solubilizable Aβ levels in a mouse model of aggressive Alzheimer's amyloid pathology

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.Abstract Objective Alzheimer's disease (AD) is a progressive neurodegenerative disease of the central nervous system (CNS). Recently, an increased interest in the role diet plays in the pathology of AD has resulted in a focus on the detrimental effects of diets high in cholesterol and fat and the beneficial effects of caloric restriction. The current study examines how dietary composition modulates cerebral amyloidosis and neuronal integrity in the TgCRND8 mouse model of AD. Methods From 4 wks until 18 wks of age, male and female TgCRND8 mice were maintained on one of four diets: (1) reference (regular) commercial chow; (2) high fat/low carbohydrate custom chow (60 kcal% fat/30 kcal% protein/10 kcal% carbohydrate); (3) high protein/low carbohydrate custom chow (60 kcal% protein/30 kcal% fat/10 kcal% carbohydrate); or (4) high carbohydrate/low fat custom chow (60 kcal% carbohydrate/30 kcal% protein/10 kcal% fat). At age 18 wks, mice were sacrificed, and brains studied for (a) wet weight; (b) solubilizable Aβ content by ELISA; (c) amyloid plaque burden; (d) stereologic analysis of selected hippocampal subregions. Results Animals receiving a high fat diet showed increased brain levels of solubilizable Aβ, although we detected no effect on plaque burden. Unexpectedly, brains of mice fed a high protein/low carbohydrate diet were 5% lower in weight than brains from all other mice. In an effort to identify regions that might link loss of brain mass to cognitive function, we studied neuronal density and volume in hippocampal subregions. Neuronal density and volume in the hippocampal CA3 region of TgCRND8 mice tended to be lower in TgCRND8 mice receiving the high protein/low carbohydrate diet than in those receiving the regular chow. Neuronal density and volume were preserved in CA1 and in the dentate gyrus. Interpretation Dissociation of Aβ changes from brain mass changes raises the possibility that diet plays a role not only in modulating amyloidosis but also in modulating neuronal vulnerability. However, in the absence of a study of the effects of a high protein/low carbohydrate diet on nontransgenic mice, one cannot be certain how much, if any, of the loss of brain mass exhibited by high protein/low carbohydrate diet-fed TgCRND8 mice was due to an interaction between cerebral amyloidosis and diet. Given the recent evidence that certain factors favor the maintenance of cognitive function in the face of substantial structural neuropathology, we propose that there might also exist factors that sensitize brain neurons to some forms of neurotoxicity, including, perhaps, amyloid neurotoxicity. Identification of these factors could help reconcile the poor clinicopathological correlation between cognitive status and structural neuropathology, including amyloid pathology.Published versio

Human topoisomerase IIα uses a two-metal-ion mechanism for DNA cleavage

The DNA cleavage reaction of human topoisomerase IIα is critical to all of the physiological and pharmacological functions of the protein. While it has long been known that the type II enzyme requires a divalent metal ion in order to cleave DNA, the role of the cation in this process is not known. To resolve this fundamental issue, the present study utilized a series of divalent metal ions with varying thiophilicities in conjunction with DNA cleavage substrates that replaced the 3′-bridging oxygen of the scissile bond with a sulfur atom (i.e. 3′-bridging phosphorothiolates). Rates and levels of DNA scission were greatly enhanced when thiophilic metal ions were included in reactions that utilized sulfur-containing substrates. Based on these results and those of reactions that employed divalent cation mixtures, we propose that topoisomerase IIα mediates DNA cleavage via a two-metal-ion mechanism. In this model, one of the metal ions makes a critical interaction with the 3′-bridging atom of the scissile phosphate. This interaction greatly accelerates rates of enzyme-mediated DNA cleavage, and most likely is needed to stabilize the leaving 3′-oxygen

Below the Belt? Territory and Development in China’s International Rise

China’s internationalization has been heralded by some as a new era of South–South cooperation. Yet such framings of development are pitched at an abstract space of the ‘global South’ which conceals more than it reveals. With some theory moving towards ontologies of ‘global development’, we need to capture both the connectedness and the local specificity of increasingly diffuse processes. This article sets out a more fine-grained understanding of how political territories and processes are imagined and produced by and through China’s internationalization, focusing on infrastructure as a ‘technology’ of territorialization. Much of the focus on China’s internationalization has been on state-to-state relations, but this obscures the ‘omni-channel politics’ that China practises. Using a critical literature review and illustrative case study, this article develops the idea of omni-channel politics to posit a view of ‘twisted’ territories in which political processes and development outcomes are more complex and contingent

Neurochemical Changes in the Mouse Hippocampus Underlying the Antidepressant Effect of Genetic Deletion of P2X7 Receptors.

Recent investigations have revealed that the genetic deletion of P2X7 receptors (P2rx7) results in an antidepressant phenotype in mice. However, the link between the deficiency of P2rx7 and changes in behavior has not yet been explored. In the present study, we studied the effect of genetic deletion of P2rx7 on neurochemical changes in the hippocampus that might underlie the antidepressant phenotype. P2X7 receptor deficient mice (P2rx7-/-) displayed decreased immobility in the tail suspension test (TST) and an attenuated anhedonia response in the sucrose preference test (SPT) following bacterial endotoxin (LPS) challenge. The attenuated anhedonia was reproduced through systemic treatments with P2rx7 antagonists. The activation of P2rx7 resulted in the concentration-dependent release of [3H]glutamate in P2rx7+/+ but not P2rx7-/- mice, and the NR2B subunit mRNA and protein was upregulated in the hippocampus of P2rx7-/- mice. The brain-derived neurotrophic factor (BDNF) expression was higher in saline but not LPS-treated P2rx7-/- mice; the P2rx7 antagonist Brilliant blue G elevated and the P2rx7 agonist benzoylbenzoyl ATP (BzATP) reduced BDNF level. This effect was dependent on the activation of NMDA and non-NMDA receptors but not on Group I metabotropic glutamate receptors (mGluR1,5). An increased 5-bromo-2-deoxyuridine (BrdU) incorporation was also observed in the dentate gyrus derived from P2rx7-/- mice. Basal level of 5-HT was increased, whereas the 5HIAA/5-HT ratio was lower in the hippocampus of P2rx7-/- mice, which accompanied the increased uptake of [3H]5-HT and an elevated number of [3H]citalopram binding sites. The LPS-induced elevation of 5-HT level was absent in P2rx7-/- mice. In conclusion there are several potential mechanisms for the antidepressant phenotype of P2rx7-/- mice, such as the absence of P2rx7-mediated glutamate release, elevated basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability in the hippocampus