Rodent scrapie models have been exploited to define the molecular basis for the progression of neuropathological changes in TSE diseases. We aim to assess whether CNS gene expression changes ...consistently observed in mouse models are of generic relevance, for example to natural TSE diseases, or are TSE strain, host species or brain region specific. Six genes, representing distinct physiological pathways and showing consistent changes in expression levels with disease progression in murine scrapie models were analysed for expression (RT-qPCR) in defined regions of the sheep brain at various times after SSBP/1 scrapie infection. Gene expression was examined in relation to the development of neuropathological changes including PrPSc deposition and vacuolation. Peripheral infection of sheep with SSBP/1 showed consistent progression of neuropathology as assessed by the temporal course of PrPSc deposition and neuropil vacuolation. The first region affected was the medulla (obex), then the thalamus and finally the cerebellum and frontal cortex. In contrast to mouse scrapie, there were few significant changes in transcript expression for any of the six genes and no consistent changes in patterns of expression in relation to brain region, time after infection or neuropathology in sheep SSBP/1. Gene expression changes in mouse TSE models, even changes consistent with the neuropathology, cannot necessarily be extrapolated to species in which disease naturally occurs. This may represent differences in pathological processes of different scrapie strains or across species; and highlights the difficulties in identifying generic molecular pathways associated to the pathogenesis of TSE disease.
Diabetes impairs endothelial function and reparative neovascularization. The p75 receptor of neurotrophins (p75(NTR)), which is scarcely present in healthy endothelial cells (ECs), becomes strongly ...expressed by capillary ECs after induction of peripheral ischemia in type-1 diabetic mice. Here, we show that gene transfer-induced p75(NTR) expression impairs the survival, proliferation, migration, and adhesion capacities of cultured ECs and endothelial progenitor cells (EPCs) and inhibits angiogenesis in vitro. Moreover, intramuscular p75(NTR) gene delivery impairs neovascularization and blood flow recovery in a mouse model of limb ischemia. These disturbed functions are associated with suppression of signaling mechanisms implicated in EC survival and angiogenesis. In fact, p75(NTR) depresses the VEGF-A/Akt/eNOS/NO pathway and additionally reduces the mRNA levels of ITGB1 beta (1) integrin, BIRC5 (survivin), PTTG1 (securin) and VEZF1. Diabetic mice, which typically show impaired postischemic muscular neovascularization and blood perfusion recovery, have these defects corrected by intramuscular gene transfer of a dominant negative mutant form of p75(NTR). Collectively, our data newly demonstrate the antiangiogenic action of p75(NTR) and open new avenues for the therapeutic use of p75(NTR) inhibition to combat diabetes-induced microvascular liabilities.
By solving Helmholtz equations, relationships to describe propagating modes in an arbitrary graded-index planar waveguide are derived. We show that in the quadratic- and secant-index waveguides a ...minimal mode width is 0.4λ/n, where λ is the wavelength in free space and n is the refractive index on the fiber axis. By modeling in FullWAVE, we show that the high-resolution imaging can be achieved with half-pitch graded-index Mikaelian microlenses (ML) and Maxwell’s “fisheye” lenses. It is shown that using a 2D ML, the point source can be imaged near the lens surface as a light spot with the full width at half maximum (FWHM) of 0.12λ. This value is close to the diffraction limit for silicon (n=3.47) in 2D media FWHM=0.44λ/n=0.127λ. We also show that half-pitch ML is able to resolve at half-maximum two close point sources separated by a 0.3λ distance.
It is estimated that 3.2 million children ages 6 to 14 years participated in organized youth football in the United States in 2007. Approximately 240,000 children play football in the nation’s ...largest youth football organization, with tackle divisions starting at age 5 years. The number of children playing unsupervised football is much higher, and the overall number of children participating in American football is increasing. Sports are the leading cause of injury-related emergency room visits for teenagers, and football is a leading precipitating athletic activity for these visits. Football is also the most hazardous organized sports in the United States. Though most pediatric football-related injuries are minor, such as abrasions, sprains, and strains of the extremities, football accounts for more major and catastrophic injuries than any other sport. Given football’s popularity with children in the United States, combined with the high rate of injury associated with participation in this activity, radiologists should be familiar with the imaging features and injury patterns seen in this patient population.
The IceCube neutrino telescope at the South Pole has measured the atmospheric muon neutrino spectrum as a function of zenith angle and energy in the approximate 320 GeV to 20 TeV range, to search for ...the oscillation signatures of light sterile neutrinos. No evidence for anomalous ν_{μ} or νover ¯_{μ} disappearance is observed in either of two independently developed analyses, each using one year of atmospheric neutrino data. New exclusion limits are placed on the parameter space of the 3+1 model, in which muon antineutrinos experience a strong Mikheyev-Smirnov-Wolfenstein-resonant oscillation. The exclusion limits extend to sin^{2}2θ_{24}≤0.02 at Δm^{2}∼0.3 eV^{2} at the 90% confidence level. The allowed region from global analysis of appearance experiments, including LSND and MiniBooNE, is excluded at approximately the 99% confidence level for the global best-fit value of |U_{e4}|^{2}.
Since the recent detection of an astrophysical flux of high-energy neutrinos, the question of its origin has not yet fully been answered. Much of what is known about this flux comes from a small ...event sample of high neutrino purity, good energy resolution, but large angular uncertainties. In searches for point-like sources, on the other hand, the best performance is given by using large statistics and good angular reconstructions. Track-like muon events produced in neutrino interactions satisfy these requirements. We present here the results of searches for point-like sources with neutrinos using data acquired by the IceCube detector over 7 yr from 2008 to 2015. The discovery potential of the analysis in the northern sky is now significantly below = 10−12 TeV cm−2 s−1, on average 38% lower than the sensitivity of the previously published analysis of 4 yr exposure. No significant clustering of neutrinos above background expectation was observed, and implications for prominent neutrino source candidates are discussed.
Esomeprazole for asthma Wise, Matt P; Saayman, Anton G; Frost, Paul J
The New England journal of medicine,
2009-Jul-09, Letnik:
361, Številka:
2
Journal Article
Companies are facing a growing demand for small-scale production of ship components. This increases the relevance of production systems that optimize the production time of complex products. ...Automatic generation of individual blocks of CNC programs opens up great opportunities to accelerate and improve the preparation of production of complex and especially small-scale orders, such as the manufacture of Troost screws of various configurations. This study is devoted to the creation of blocks of CNC programs based on the parameters provided by product configuration systems. Various approaches to the pre-production process are described and characterized. It is shown that the direct transfer of parameters to the CNC program can be fully automated, but is limited by the geometry of the manufactured part, which can be obtained using parametric processing cycles. In order to determine the most appropriate procedure for generating a program for a specific case, a solution methodology was developed. An approximate implementation is presented, showing the possibilities of automated generation of CNC programs in the production of Troost screw parts. It is established that when choosing the optimal method of generating a program for a CNC machine in the manufacture of a Troost screw, the amount of ROM memory required can be reduced by 10.86 times. The processing time is reduced by 1.07 times, or 39 minutes
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