Fair‐Weather Friends: Evidence of Lipoxin Dysregulation in Neurodegeneration

Lipoxins (LXs) are autacoids, specialized proresolving lipid mediators (SPMs) acting locally in a paracrine or autocrine fashion. They belong to a complex superfamily of dietary small polyunsaturated fatty acid (PUFA)–metabolites, which direct potent cellular responses to resolve inflammation and restore tissue homeostasis. Together, these SPM activities have been intensely studied in systemic inflammation and acute injury or infection, but less is known about LX signaling and activities in the central nervous system. LXs are derived from arachidonic acid, an omega‐6 PUFA. In addition to well‐established roles in systemic inflammation resolution, they have increasingly become implicated in regulating neuroinflammatory and neurodegenerative processes. In particular, chronic inflammation plays a central role in Alzheimer's disease (AD) etiology, and dysregulated LX production and activities have been reported in a variety of AD rodent models and clinical tissue samples, yet with complex and sometimes conflicting results. In addition, reduced LX production following retinal injury has been reported recently by the authors, and an intriguing direct neuronal activity promoting survival and homeostasis in retinal and cortical neurons is demonstrated. Here, the authors review and clarify this growing literature and suggest new research directions to further elaborate the role of lipoxins in neurodegeneration.     

Measuring hospital performance: are we asking the right questions?

The aim of this randomized cross-over trial was to evaluate the dose effect and systemic absorption of epinephrine nebulized at 2 and 5 mg in comparison with salbutamol (5 mg). Thirteen asthmatic patients (29 +/- 15 years, 4 men and 9 women) were randomly assigned to receive one nebulization of each of the three treatment regimens at 24 h interval. The evaluation concerned forced expiratory volume in 1 second (FEV1), heart rate, respiratory rate and arterial pressure. All measurements were done at baseline, every 15 minutes during the first hour, and hourly thereafter until return to baseline FEV1. Serum potassium was measured at baseline (T0) and sixty minutes after (T60). Plasma levels of epinephrine were measured at T0, T20, T60. Fifteen minutes after the beginning of nebulization FEV1 improved significantly over baseline in the three groups. These changes were similar in the three groups until T45, while FEV1 improvement was significantly greater in A5 and S groups than A2 group (+640 +/- 470 ml, +721 +/- 349 ml, +406 +/- 306 ml in A5, S and A2 groups respectively, p < 0.01). Bronchodilation lasted significantly longer with salbutamol than with epinephrine (p < 0.05). No side effects were recorded in spite of substantial and dose-dependent systemic absorption of epinephrine. CONCLUSION: Increasing epinephrine doses produces greater bronchodilation without additional side effects. However this bronchodilation lasts shorter than with salbutamol.     

Inductive learning from preclassified training examples: anempirical study

Many real-world decision-making problems fall into the general category of classification. Algorithms for constructing knowledge by inductive inference from example have been widely used for some decades. Although these learning algorithms frequently address the same problem of learning from preclassified examples and much previous work in inductive learning has focused on the algorithms' predictive accuracy, little attention has been paid to the effect of data factors on the performance of a learning system. An experiment was conducted using five learning algorithms on two data sets to investigate how the change in labeling the class attribute can alter the behavior of learning algorithms. The results show that different preclassification rules applied on the training examples can affect either the classification accuracy or classification structure     

Abnormalities in plasma and red blood cell fatty acid profiles of patients with colorectal cancer

Intravenous injection of stearoyl vanillylamide (C18-VA), a nonpungent capsaicin (CAP) analog, enhances adrenaline secretion significantly and as effectively as CAP in rats. Because swimming capacity was enhanced by CAP in mice due to CAP-induced adrenal catecholamine secretion, we investigated the effects of oral administration of C18-VA on swimming capacity using an adjustable-current water pool. Male Std ddY 6-wk-old mice were fed a commercial diet for this study and one group was orally administered C18-VA via a stomach tube. Treated mice were able to swim longer before exhaustion than the control mice (62.9 +/- 5.6 vs. 49.6 +/- 7. 0 min, P < 0.05). The swimming capacity of two groups administered C18-VA (0.02 and 0.033 mmol/kg) was significantly greater than that of those administered vehicle alone, (P < 0.05). Substance P concentration in cerebrospinal fluid, which is involved in pain transmission and is the first direct measure of pungency, was not affected by C18-VA administration. In an experiment examining the effects of C18-VA on serum adrenaline concentration, adrenaline was significantly greater in C18-VA treated mice than in controls at 2-h post-dose (C18-VA group, 26.09 +/- 2.82; control group 13.29 +/- 0. 96 microg/L, P < 0.01). In a separate study free fatty acids in serum were elevated in treated mice at 2-h post-dose (P < 0.01). While serum glucose concentration was not affected. These results suggest that C18-VA increased swimming capacity of mice via adrenaline release, independent of pungency. In addition, the present study suggests the usefulness of its application to humans.     

Reversibility of scrapie inactivation is enhanced by copper

The only known difference between the cellular (PrPC) and scrapie-specific (PrPSc) isoforms of the prion protein is conformational. Because disruption of PrPSc structure decreases scrapie infectivity, restoration of the disease-specific conformation should restore infectivity. In this study, disruption of PrPSc (as monitored by the loss of proteinase K resistance) by guanidine hydrochloride (GdnHCl) resulted in decreased infectivity. Upon dilution of the GdnHCl, protease resistance of PrP was restored and infectivity was regained. The addition of copper facilitated restoration of both infectivity and protease resistance of PrP in a subset of samples that did not renature by the simple dilution of the GdnHCl. These data demonstrate that loss of scrapie infectivity can be a reversible process and that copper can enhance this restoration of proteinase K resistance and infectivity.     

Uncertainty modeling and robust minimax LQR control of multivariable nonlinear systems with application to hypersonic flight

For a class of multi‐input and multi‐output nonlinear uncertainty systems, a novel approach to design a nonlinear controller using minimax linear quadratic regulator (LQR) control is proposed. The proposed method combines a feedback linearization method with the robust minimax LQR approach in the presence of time‐varying uncertain parameters. The uncertainties, which are assumed to satisfy a certain integral quadratic constraint condition, do not necessarily satisfy a generalized matching condition. The procedure consists of feedback linearization of the nominal model and linearization of the remaining nonlinear uncertain terms with respect to each individual uncertainty at a local operating point. This two‐stage linearization process, followed by a robust minimax LQR control design, provides a robustly stable closed loop system. To demonstrate the effectiveness of the proposed approach, an application study is provided for a flight control problem of an air‐breathing hypersonic flight vehicle (AHFV), where the outputs to be controlled are the longitudinal velocity and altitude, and the control variables are the throttle setting and elevator deflection. The proposed method is used to derive a linearized uncertainty model for the longitudinal motion dynamics of the AHFV first, and then a robust minimax LQR controller is designed, which is based on this uncertainty model. The controller is synthesized considering seven uncertain aerodynamic and inertial parameters. The stability and performance of the synthesized controller is evaluated numerically via single scenario simulations for particular cruise conditions as well as a Monte‐Carlo type simulation based on numerous cases. It is observed that the control scheme proposed in this paper performs better, especially from the aspect of robustness to large ranges of uncertainties, than some controller design schemes previously published in the literature. Copyright © 2011 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society     

Ultrastructural neurobiology of the olfactory mucosa of the brown trout, Salmo trutta.

This paper describes four investigations of the olfactory mucosa of the brown trout: 1) the ultrastructure of the olfactory mucosa as revealed by scanning (SEM), conventional transmission (TEM), and high voltage (HVEM) electron microscopy; 2) light and electron-microscopic investigations of retrograde transport of the tracer macromolecule horseradish peroxidase (HRP) when applied to the cut olfactory nerve; 3) SEM and TEM investigations of the effects of olfactory nerve transection on cell populations within the olfactory epithelium; and 4) ultrastructural investigations of reversible degeneration of olfactory receptors caused by elevated copper concentrations. The trout olfactory epithelium contains five cell types: ciliated epithelial cells, ciliated olfactory receptor cells, microvillar olfactory receptor cells, supporting cells, and basal cells. The ciliated and microvillar olfactory receptor cells and a small number of basal cells are backfilled by HRP when the tracer is applied to the cut olfactory nerve. When the olfactory nerve is cut, both ciliated and microvillar olfactory receptor cells degenerate within 2 days and are morphologically intact again within 8 days. When wild trout are taken from their native stream and placed in tanks with elevated copper concentrations, ciliated and microvillar cells degenerate. Replacement of these trout into their stream of origin is followed by morphologic restoration of both types of olfactory receptor cells. Ciliated and microvillar receptor cells are primary sensory bipolar neurons whose dendrites make contact with the environment; their axons travel directly to the brain. Consequently, substances can be transported directly from the environment into the brain via these "naked neurons." Since fish cannot escape from the water in which they swim, and since that water may occasionally contain brain-toxic substances, the ability to close off--and later reopen--this anatomic gateway to the brain would confer a tremendous selective advantage upon animals that evolved the "brain-sparing" capacity to do so. Consequently, the unique regenerative powers of vertebrate olfactory receptor neurons may have their evolutionary origin in fishes.     

Thermoluminescence Dating and the Problem of Geochemical Evolution of Sediments — A Case Study: The Mousterian Levels at Hayonim

The thermoluminescence dating of burnt flints has become a major tool in the elaboration of the chronology of human settlements of the last half a million years. The reliability of an age estimate depends to a great extent on the accuracy with which the internal and external radiation dose rates prevailing during the duration of burial can be determined. While determining the internal dose rate is relatively straightforward, the same cannot be said of the external, particularly if the sediment surrounding the flints is mineralogically heterogeneous or has undergone diagenetic changes during prolonged burial. In this article we show some examples of the problems confronted when one attempts to determine the external dose rates experienced by flints buried in a relatively heterogeneous environment of sediments, such as those sampled at the Middle Paleolithic occupation levels at Hayonim (Israel) which show evidence of past mineralogical evolution. The impact of changes produced by leaching and chemical reactions between the components of hearth ashes on the radioisotopic composition of the sediment and consequently the environmental dose rates were examined by subjecting several distinct sediment layers to thorough mineralogical, radiochemical, and dosimetric analyses. The problems of external dose-rate determinations in mineralogically heterogeneous sediments are examined, particularly in those consisting of variable amounts of siliceous aggregates, apatite, and other phosphorus-rich minerals produced by diagenetic reactions with bone residues.     

Recent progress in road and lane detection: a survey

The problem of road or lane perception is a crucial enabler for advanced driver assistance systems. As such, it has been an active field of research for the past two decades with considerable progress made in the past few years. The problem was confronted under various scenarios, with different task definitions, leading to usage of diverse sensing modalities and approaches. In this paper we survey the approaches and the algorithmic techniques devised for the various modalities over the last 5 years. We present a generic break down of the problem into its functional building blocks and elaborate the wide range of proposed methods within this scheme. For each functional block, we describe the possible implementations suggested and analyze their underlying assumptions. While impressive advancements were demonstrated at limited scenarios, inspection into the needs of next generation systems reveals significant gaps. We identify these gaps and suggest research directions that may bridge them.