Pharmacological analysis of cyclooxygenase-1 in inflammation

The enzymes cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) catalyze the conversion of arachidonic acid to prostaglandin (PG) H2, the precursor of PGs and thromboxane. These lipid mediators play important roles in inflammation and pain and in normal physiological functions. While there are abundant data indicating that the inducible isoform, COX-2, is important in inflammation and pain, the constitutively expressed isoform, COX-1, has also been suggested to play a role in inflammatory processes. To address the latter question pharmacologically, we used a highly selective COX-1 inhibitor, SC-560 (COX-1 IC50 = 0.009 microM; COX-2 IC50 = 6.3 microM). SC-560 inhibited COX-1-derived platelet thromboxane B2, gastric PGE2, and dermal PGE2 production, indicating that it was orally active, but did not inhibit COX-2-derived PGs in the lipopolysaccharide-induced rat air pouch. Therapeutic or prophylactic administration of SC-560 in the rat carrageenan footpad model did not affect acute inflammation or hyperalgesia at doses that markedly inhibited in vivo COX-1 activity. By contrast, celecoxib, a selective COX-2 inhibitor, was anti-inflammatory and analgesic in this model. Paradoxically, both SC-560 and celecoxib reduced paw PGs to equivalent levels. Increased levels of PGs were found in the cerebrospinal fluid after carrageenan injection and were markedly reduced by celecoxib, but were not affected by SC-560. These results suggest that, in addition to the role of peripherally produced PGs, there is a critical, centrally mediated neurological component to inflammatory pain that is mediated at least in part by COX-2.     

The Mediating Role of Self-Efficacy in the Development of Entrepreneurial Intentions.

The purpose of this study was to investigate the mediating role of self-efficacy in the development of students' intentions to become entrepreneurs. The authors used structural equation modeling with a sample of 265 master of business administration students across 5 universities to test their hypotheses. The results showed that the effects of perceived learning from entrepreneurship-related courses, previous entrepreneurial experience, and risk propensity on entrepreneurial intentions were fully mediated by entrepreneurial self-efficacy. Contrary to expectations, gender was not mediated by self-efficacy but had a direct effect such that women reported lower entrepreneurial career intentions. The authors discuss practical implications and directions for future research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Towards the integration of dark and photo fermentative waste treatment. 1. Hydrogen photoproduction by purple bacterium Rhodobacter capsulatus using potential products of starch fermentation

In this study, the H₂-photoproduction capacity of Rhodobacter capsulatus B10 was measured as a function of variations in the nature and concentration of volatile fatty acids (VFAs) and other products of dark fermentation. When an equimolar mixture of VFAs was provided, C4 substrates (butyrate and isobutyrate) were not consumed until the C2–C3 substrates (acetate, propionate, and lactate) became unavailable, but in order for the cells to produce H₂ at high rates they could not be exposed to severe growth substrate depletion. Among other possible fermentation products, the highest inhibition was observed by the addition of butanol (50% inhibition at 50 mM). The influence of high concentrations of VFAs, phosphate (used to stabilize the pH during dark fermentation) and some heavy metals (known inhibitors of methanogenesis) was also shown. Based on the results, the conditions of fermentation can be manipulated to avoid the inhibition of subsequent H₂ photoproduction by photosynthetic bacteria.     

Simulation of the forming of mash seam welded sheets

The paper presents results on the optimization of the process of mash seam welding for improving the formability of the joined sheet metal semi-products. An integrated concept including the welding, smoothing and heat treatment of mash welded sheets has been developed. As an example, fatigue tests and the simulation of the forming behaviour of a mash seam welded tensile specimen simulated by the finite element method (FEM) is discussed. The determination of the material properties of the seam which, so far, have been determined experimentally is thus considerably simplified.     

Determination of kinetic and retention properties of cartridge and disk devices for solid-phase extraction

The kinetic properties of cartridge and disk solid-phase extraction devices are determined by forced-flow liquid chromatography. Typical cartridges provide about 5-15 theoretical plates per cm of bed height and particle-loaded membranes provide about 4-9 theoretical plates for a 0.5-mm-thick membrane. It is shown that cartridge devices fail to provide their maximum trapping performance because of inadequate packing density and that the required packing density could be easily achieved in practice with particles of a standard size. The retention properties of common sorbents for extraction from water and air are characterized with the solvation parameter model. For predominantly aqueous solutions a favorable cavity term results in increased retention while polar interactions tend to reduce retention. Retention on porous polymer sorbents is more complicated because of their capacity to absorb significant amounts of the sample processing solvent resulting in solvent-dependent changes in retention properties. For trapping organic volatiles from air cavity formation and dispersion interactions are important, and in the case of Tenax its capacity for induction interactions is also significant.     

Synthesis and in Vitro Evaluation of Novel 5-Nitroindole Derivatives as c-Myc G-Quadruplex Binders with Anticancer Activity

Lead-optimization strategies for compounds targeting c-Myc G-quadruplex (G4) DNA are being pursued to develop anticancer drugs. Here, we investigate the structure-activity- relationship (SAR) of a newly synthesized series of molecules based on the pyrrolidine-substituted 5-nitro indole scaffold to target G4 DNA. Our synthesized series allows modulation of flexible elements with a structurally preserved scaffold. Biological and biophysical analyses illustrate that substituted 5-nitroindole scaffolds bind to the c-Myc promoter G-quadruplex. These compounds downregulate c-Myc expression and induce cell-cycle arrest in the sub-G1/G1 phase in cancer cells. They further increase the concentration of intracellular reactive oxygen species. NMR spectra show that three of the newly synthesized compounds interact with the terminal G-quartets (5′- and 3′-ends) in a 2 : 1 stoichiometry.     

Use of power Doppler in pediatric neurosonography: a pictorial essay

In pediatric neurosonography, conventional color Doppler imaging has been the primary adjunct to routine gray-scale imaging. Power Doppler sonography is a relatively recent development that does not have the limitations of conventional color Doppler ultrasound. The power Doppler technique measures the energy of moving red blood cells instead of the velocity and direction of flow. Advantages of this technique include increased sensitivity for identifying flow in slow-flow states, more complete evaluation of a vessel, and more accurate evaluation of the course of the vessel. Power Doppler sonography is helpful in evaluation of the neonatal brain in a variety of clinical situations: identifying the exact locations of extraaxial fluid collections, differentiating intraventricular clot from normal choroid plexus, detecting intraventricular hemorrhage, and demonstrating asymmetries in cerebral perfusion. However, in certain difficult cases, use of both conventional color Doppler sonography and power Doppler sonography produces increased diagnostic accuracy because these techniques furnish complementary information.     

Adaptive 3-D object recognition from multiple views

The authors address the problem of generating representations of 3-D objects automatically from exploratory view sequences of unoccluded objects. In building the models, processed frames of a video sequence are clustered into view categories called aspects, which represent characteristic views of an object invariant to its apparent position, size, 2-D orientation, and limited foreshortening deformation. The aspects as well as the aspect transitions of a view sequence are used to build (and refine) the 3-D object representations online in the form of aspect-transition matrices. Recognition emerges as the hypothesis that has accumulated the maximum evidence at each moment. The `winning' object continues to refine its representation until either the camera is redirected or another hypothesis accumulates greater evidence. This work concentrates on 3-D appearance modeling and succeeds under favorable viewing conditions by using simplified processes to segment objects from the scene and derive the spatial agreement of object features     

Proactive personality and career success.

This study examined the relationship between proactive personality and career success by surveying a sample of 496 employees (320 men and 176 women) from a diverse set of occupations and organizations. Proactive personality was positively associated with both self-reported objective (salary and promotions) and subjective (career satisfaction) indicators of career success. Hierarchical regression analyses showed that proactive personality explained additional variance in both objective and subjective career success even after controlling for several relevant variables (demographic, human capital, motivational, organizational, and industry) that have previously been found to be predictive of career outcomes. These findings were consistent using both self-report and significant-other ratings of proactive personality. (PsycINFO Database Record (c) 2010 APA, all rights reserved)