NADPH oxidase as a therapeutic target in Alzheimer\u27s disease

At present, available treatments for Alzheimer\u27s disease (AD) are largely unable to halt disease progression. Microglia, the resident macrophages in the brain, are strongly implicated in the pathology and progressively degenerative nature of AD. Specifically, microglia are activated in response to both β amyloid (Aβ) and neuronal damage, and can become a chronic source of neurotoxic cytokines and reactive oxygen species (ROS). NADPH oxidase is a multi-subunit enzyme complex responsible for the production of both extracellular and intracellular ROS by microglia. Importantly, NADPH oxidase expression is upregulated in AD and is an essential component of microglia-mediated Aβ neurotoxicity. Activation of microglial NADPH oxidase causes neurotoxicity through two mechanisms: 1) extracellular ROS produced by microglia are directly toxic to neurons; 2) intracellular ROS function as a signaling mechanism in microglia to amplify the production of several pro-inflammatory and neurotoxic cytokines (for example, tumor necrosis factor-α, prostaglandin E2, and interleukin-1β). The following review describes how targeting NADPH oxidase can reduce a broad spectrum of toxic factors (for example, cytokines, ROS, and reactive nitrogen species) to result in inhibition of neuronal damage from two triggers of deleterious microglial activation (Aβ and neuron damage), offering hope in halting the progression of AD

The Impact of External Audience on Second Graders\u27 Writing Quality

The overarching purpose of writing is to communicate; as such, the intended audience is a critical consideration for writers. However, elementary school writing instruction commonly neglects the role of the audience. Typically, children are asked to compose a piece of text without a specific audience that is usually evaluated by the classroom teacher. Previous studies have found a relationship between audience specification and higher quality writing among older children; this study examines the impact of audience specification on young children’s writing. Using a within-subjects design, the study compared writing quality when second-grade students wrote for internal versus external audiences and found that children are more likely to produce higher quality writing when writing for an external audience than when writing for their teacher

Bilateral police liaison officers: Practices and European policy

Police from the European Union (EU) Member States make significant use of bilateral liaison officers to cooperate with police in other countries. In the past decades, a number of TREVI and EU Council policy instruments have aimed to enhance the common use of liaison officers by the Member States. This research article discusses these policy instruments from the perspective of the practicalities of the work of liaison officers, examines the underlying rationalities of the instruments and assesses their effects. The findings show that national interests of Member States remain paramount in posting liaison officers. Practices of liaison officers are largely governed by national regulations and organisational particulars, but also depend on the high level of discretion that liaison officers can exercise. In contrast, the policy instruments are largely driven by a political rationality and little intended effect of these instruments can be detected

Evaluation of the Langley 4- by 7-meter tunnel for propeller noise measurements

An experimental and theoretical evaluation of the Langley 4- by 7- Meter Tunnel was conducted to determine its suitability for obtaining propeller noise data. The tunnel circuit and open test section are described. An experimental evaluation is performed using microphones placed in and on the tunnel floor. The reflection characteristics and background noise are determined. The predicted source (propeller) near-field/far-field boundary is given using a first-principles method. The effect of the tunnel-floor boundry layer on the noise from the propeller is also predicted. A propeller test stand used for part of his evaluation is also described. The measured propeller performance characteristics are compared with those obtained at a larger scale, and the effect of the test-section configuration on the propeller performance is examined. Finally, propeller noise measurements were obtained on an eight-bladed SR-2 propeller operating at angles of attack -8 deg, 0 deg, and 4.6 deg to give an indication of attainable signal-to-noise ratios

New physics, the cosmic ray spectrum knee, and pppp cross section measurements

We explore the possibility that a new physics interaction can provide an explanation for the knee just above $10^6$ GeV in the cosmic ray spectrum. We model the new physics modifications to the total proton-proton cross section with an incoherent term that allows for missing energy above the scale of new physics. We add the constraint that the new physics must also be consistent with published $pp$ cross section measurements, using cosmic ray observations, an order of magnitude and more above the knee. We find that the rise in cross section required at energies above the knee is radical. The increase in cross section suggests that it may be more appropriate to treat the scattering process in the black disc limit at such high energies. In this case there may be no clean separation between the standard model and new physics contributions to the total cross section. We model the missing energy in this limit and find a good fit to the Tibet III cosmic ray flux data. We comment on testing the new physics proposal for the cosmic ray knee at the Large Hadron Collider.Comment: 17 pages, 4 figure

Anxiety, Defense and Cognition: A Theoretical Basis for Practical Handling of the Surgical Patient

Both the anxiety-defense model and the cognitive model provide a scientific basis for practical handling of the surgical patient. Emerging from both models is a humanistic approach to the patient based on understanding and a nonjudgmental attitude as well as on a knowledge of where the patient is psychologically and a willingness to meet him on his ground. The rewards in terms of a reduction of anxiety, depression, and human suffering can be enormous