Heme Oxygenase-1 Expression Affects Murine Abdominal Aortic Aneurysm Progression.

Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is a cytoprotective enzyme upregulated in the vasculature by increased flow and inflammatory stimuli. Human genetic data suggest that a diminished HO-1 expression may predispose one to abdominal aortic aneurysm (AAA) development. In addition, heme is known to strongly induce HO-1 expression. Utilizing the porcine pancreatic elastase (PPE) model of AAA induction in HO-1 heterozygous (HO-1+/-, HO-1 Het) mice, we found that a deficiency in HO-1 leads to augmented AAA development. Peritoneal macrophages from HO-1+/- mice showed increased gene expression of pro-inflammatory cytokines, including MCP-1, TNF-alpha, IL-1-beta, and IL-6, but decreased expression of anti-inflammatory cytokines IL-10 and TGF-beta. Furthermore, treatment with heme returned AAA progression in HO-1 Het mice to a wild-type profile. Using a second murine AAA model (Ang II-ApoE-/-), we showed that low doses of the HMG-CoA reductase inhibitor rosuvastatin can induce HO-1 expression in aortic tissue and suppress AAA progression in the absence of lipid lowering. Our results support those studies that suggest that pleiotropic statin effects might be beneficial in AAA, possibly through the upregulation of HO-1. Specific targeted therapies designed to induce HO-1 could become an adjunctive therapeutic strategy for the prevention of AAA disease

Low-temperature tapered-fiber probing of diamond NV ensembles coupled to GaP microcavities

In this work we present a platform for testing the device performance of a cavity-emitter system, using an ensemble of emitters and a tapered optical fiber. This method provides high-contrast spectra of the cavity modes, selective detection of emitters coupled to the cavity, and an estimate of the device performance in the single- emitter case. Using nitrogen-vacancy (NV) centers in diamond and a GaP optical microcavity, we are able to tune the cavity onto the NV resonance at 10 K, couple the cavity-coupled emission to a tapered fiber, and measure the fiber-coupled NV spontaneous emission decay. Theoretically we show that the fiber-coupled average Purcell factor is 2-3 times greater than that of free-space collection; although due to ensemble averaging it is still a factor of 3 less than the Purcell factor of a single, ideally placed center.Comment: 15 pages, 6 figure

Fano Effect in a Few-Electron Quantum Dot

We have studied the Fano effect in a few-electron quantum dot side-coupled to a quantum wire. The conductance of the wire, which shows an ordinal staircase-like quantization without the dot, is modified through the interference (the Fano effect) and the charging effects. These effects are utilized to verify the exhaustion of electrons in the dot. The "addition energy spectrum" of the dot shows a shell structure, indicating that the electron confinement potential is fairly circular. A rapid sign inversion of the Fano parameter on the first conductance plateau with the change of the wire gate voltage has been observed, and explained by introducing a finite width of dot-wire coupling.Comment: 11 pages, 7 figure

A robust, scanning quantum system for nanoscale sensing and imaging

Controllable atomic-scale quantum systems hold great potential as sensitive tools for nanoscale imaging and metrology. Possible applications range from nanoscale electric and magnetic field sensing to single photon microscopy, quantum information processing, and bioimaging. At the heart of such schemes is the ability to scan and accurately position a robust sensor within a few nanometers of a sample of interest, while preserving the sensor's quantum coherence and readout fidelity. These combined requirements remain a challenge for all existing approaches that rely on direct grafting of individual solid state quantum systems or single molecules onto scanning-probe tips. Here, we demonstrate the fabrication and room temperature operation of a robust and isolated atomic-scale quantum sensor for scanning probe microscopy. Specifically, we employ a high-purity, single-crystalline diamond nanopillar probe containing a single Nitrogen-Vacancy (NV) color center. We illustrate the versatility and performance of our scanning NV sensor by conducting quantitative nanoscale magnetic field imaging and near-field single-photon fluorescence quenching microscopy. In both cases, we obtain imaging resolution in the range of 20 nm and sensitivity unprecedented in scanning quantum probe microscopy

Raising argument strength using negative evidence: A constraint on models of induction

Both intuitively, and according to similarity-based theories of induction, relevant evidence raises argument strength when it is positive and lowers it when it is negative. In three experiments, we tested the hypothesis that argument strength can actually increase when negative evidence is introduced. Two kinds of argument were compared through forced choice or sequential evaluation: single positive arguments (e.g., “Shostakovich’s music causes alpha waves in the brain; therefore, Bach’s music causes alpha waves in the brain”) and double mixed arguments (e.g., “Shostakovich’s music causes alpha waves in the brain, X’s music DOES NOT; therefore, Bach’s music causes alpha waves in the brain”). Negative evidence in the second premise lowered credence when it applied to an item X from the same subcategory (e.g., Haydn) and raised it when it applied to a different subcategory (e.g., AC/DC). The results constitute a new constraint on models of induction

Feature integration in natural language concepts

Two experiments measured the joint influence of three key sets of semantic features on the frequency with which artifacts (Experiment 1) or plants and creatures (Experiment 2) were categorized in familiar categories. For artifacts, current function outweighed both originally intended function and current appearance. For biological kinds, appearance and behavior, an inner biological function, and appearance and behavior of offspring all had similarly strong effects on categorization. The data were analyzed to determine whether an independent cue model or an interactive model best accounted for how the effects of the three feature sets combined. Feature integration was found to be additive for artifacts but interactive for biological kinds. In keeping with this, membership in contrasting artifact categories tended to be superadditive, indicating overlapping categories, whereas for biological kinds, it was subadditive, indicating conceptual gaps between categories. It is argued that the results underline a key domain difference between artifact and biological concepts

Immunoblot analysis of the seroreactivity to recombinant Borrelia burgdorferi sensu lato antigens, including VlsE, in the long-term course of treated patients with Erythema migrans

Objective: We evaluated whether immunoblotting is capable of substantiating the posttreatment clinical assessment of patients with erythema migrans ( EM), the hallmark of early Lyme borreliosis. Methods: In 50 patients, seroreactivity to different antigens of Borrelia burgdorferi sensu lato was analyzed by a recombinant immunoblot test (IB) in consecutive serum samples from a minimum follow-up period of 1 year. Antigens in the IgG test were decorin- binding protein A, internal fragment of p41 (p41i), outer surface protein C (OspC), p39, variable major protein-like sequence expressed (VlsE), p58 and p100; those in the IgM test were p41i, OspC and p39. Immune responses were correlated with clinical and treatment-related parameters. Results: Positive IB results were found in 50% before, in 57% directly after therapy and in 44% by the end of the follow-up for the IgG class, and in 36, 43 and 12% for the IgM class. In acute and convalescence phase sera, VlsE was most immunogenic on IgG testing 60 and 70%), and p41i (46 and 57%) and OspC (40 and 57%) for the IgM class. By the end of the follow-up, only the anti-p41i lgM response was significantly decreased to 24%. Conclusions: No correlation was found between IB results and treatment-related parameters. Thus, immunoblotting does not add to the clinical assessment of EM patients after treatment. Copyright (c) 2008 S. Karger AG, Basel

Optimal management of an insurer's exposure in a competitive general insurance market

The qualitative behavior of the optimal premium strategy is determined for an insurer in a finite and an infinite market using a deterministic general insurance model. The optimization problem leads to a system of forward-backward differential equations obtained from Pontryagin’s Maximum Principle. The focus of the modelling is on how this optimization problem can be simplified by the choice of demand function and the insurer’s objective. Phase diagrams are used to characterize the optimal control. When the demand is linear in the relative premium, the structure of the phase diagram can be determined analytically. Two types of premium strategy are identified for an insurer in an infinite market, and which is optimal depends on the existence of equilibrium points in the phase diagram. In a finite market there are four more types of premium strategy, and optimality depends on the initial exposure of the insurer and the position of a saddle point in the phase diagram. The effect of a nonlinear demand function is examined by perturbing the linear price function. An analytical optimal premium strategy is also found using inverse methods when the price function is nonlinear

Sources of Nonnative Centrarchids in the Upper Colorado River Revealed by Stable Isotope and Microchemical Analyses of Otoliths

Nonnative fishes represent a significant impediment to the recovery of imperiled fishes, including those endemic to the Colorado River in the southwestern United States. Efforts to control nonindigenous fish abundance in the upper Colorado River basin have been unsuccessful owing in part to lack of knowledge regarding nonnative fish recruitment sources. We determined the source habitat (floodplain pond versus riverine habitats) for nonnative centrarchid fishes (largemouth bass Micropterus salmoides, green sunfish Lepomis cyanellus, bluegill L. macrochirus, and black crappie Pomoxis nigromaculatus) in the upper Colorado River using stable hydrogen isotopic composition (δD) and strontium:calcium (Sr:Ca) ratios in fish otoliths as natural markers of environmental history. Stable hydrogen isotope analysis revealed that 59% of centrarchids exhibited the otolith core signatures expected for riverine-origin fish, while 22% had emigrated from floodplain ponds and 19% were of uncertain origin. Strontium:calcium ratio data were consistent with the δD assays and indicated that relatively few fish immigrated to the river from high-salinity habitats. Black crappie was the only species that originated primarily from floodplain ponds. Efforts to control the abundance of most of the fishes included in this study should be concentrated in riverine habitats given the hydrologic conditions (below-average river discharge) present during our study. However, the proportion of pond-origin fish increased with fish age, which, coupled with historical river discharge data, suggested that floodplain pond contributions to riverine nonnative fish populations fluctuate with the interannual variations in flow regime and river–pond connectivity. Our results are the first to demonstrate the utility of δD as a natural marker of fish environmental history that will probably provide valuable insights into the management of fish in other environments

Direct medical costs of adverse events in Dutch hospitals

Background: Various international studies have shown that a substantial number of patients suffer from injuries or even die as a result of care delivered in hospitals. The occurrence of injuries among patients caused by health care management in Dutch hospitals has never been studied systematically. Therefore, an epidemiological study was initiated to determine the incidence, type and impact of adverse events among discharged and deceased patients in Dutch hospitals. Methods/Design: Three stage retrospective patient record review study in 21 hospitals of 8400 patient records of discharged or deceased patients in 2004. The records were reviewed by trained nurses and physicians between August 2005 and October 2006. In addition to the determination of presence, the degree of preventability, and causes of adverse events, also location, timing, classification, and most responsible specialty of the adverse events were measured. Moreover, patient and admission characteristics and the quality of the patient records were recorded. Discussion: In this paper we report on the design of the retrospective patient record study on the occurrence of adverse events in Dutch hospitals. Attention is paid to the strengths and limitations of the study design. Furthermore, alterations made in the original research protocol in comparison with former international studies are described in detail.