5,912 research outputs found

    The utility of the nitric oxide electrochemical sensor in biomedical research

    Get PDF
    In recent years World Precision Instruments Inc. (WPI) produced for commercial use a selective and sensitive electrochemical sensor for the detection of the important biological free radical nitric oxide (NO). Though many kinds of NO sensors are now commercially available WPI offers a range of sensors of variable size and applicability for the detection of NO in vivo and in in vitro biomedical samples. This article overviews the working characteristics of the sensors and their utility for biomedical research

    How willing are you to accept sexual requests from slightly unattractive to exceptionally attractive imagined requestors?

    Get PDF
    This is the post print version of the article. The official published version can be accessed from the link below.In their classic study of differences in mating strategies (Clark & Hatfield, 1989), men and women demonstrated a striking difference in interest in casual sex. The current study examined the role of requestor physical attractiveness (slightly unattractive, moderately attractive and exceptionally attractive) on men's and women's willingness to accept three different requests (go out, come to apartment, go to bed) in a questionnaire study. We tested two hypotheses, using a sample of 427 men and 443 women from three countries. Hypothesis 1 states that men, relative to women, will demonstrate a greater willingness to accept the “come to apartment” and “go to bed” requests but not the “go out” request for all three levels of requestor attractiveness. This hypothesis reflects Clark and Hatfield's (1989) main findings. Hypothesis 2 states that the physical attractiveness of a potential partner will have a greater effect on women's than on men's willingness to accept all three requests, and particularly for the explicit request for casual sex. The results partially supported Hypothesis 1 and fully supported Hypothesis 2. The discussion highlights limitations of the current research and presents directions for future research

    DPRESS: Localizing estimates of predictive uncertainty

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>The need to have a quantitative estimate of the uncertainty of prediction for QSAR models is steadily increasing, in part because such predictions are being widely distributed as tabulated values disconnected from the models used to generate them. Classical statistical theory assumes that the error in the population being modeled is independent and identically distributed (IID), but this is often not actually the case. Such inhomogeneous error (heteroskedasticity) can be addressed by providing an individualized estimate of predictive uncertainty for each particular new object <it>u</it>: the standard error of prediction <it>s</it><sub>u </sub>can be estimated as the non-cross-validated error <it>s</it><sub>t* </sub>for the closest object <it>t</it>* in the training set adjusted for its separation <it>d </it>from <it>u </it>in the descriptor space relative to the size of the training set.</p> <p><display-formula><graphic file="1758-2946-1-11-i1.gif"/></display-formula></p> <p>The predictive uncertainty factor <it>γ</it><sub>t* </sub>is obtained by distributing the internal predictive error sum of squares across objects in the training set based on the distances between them, hence the acronym: <it>D</it>istributed <it>PR</it>edictive <it>E</it>rror <it>S</it>um of <it>S</it>quares (DPRESS). Note that <it>s</it><sub>t* </sub>and <it>γ</it><sub>t*</sub>are characteristic of each training set compound contributing to the model of interest.</p> <p>Results</p> <p>The method was applied to partial least-squares models built using 2D (molecular hologram) or 3D (molecular field) descriptors applied to mid-sized training sets (<it>N </it>= 75) drawn from a large (<it>N </it>= 304), well-characterized pool of cyclooxygenase inhibitors. The observed variation in predictive error for the external 229 compound test sets was compared with the uncertainty estimates from DPRESS. Good qualitative and quantitative agreement was seen between the distributions of predictive error observed and those predicted using DPRESS. Inclusion of the distance-dependent term was essential to getting good agreement between the estimated uncertainties and the observed distributions of predictive error. The uncertainty estimates derived by DPRESS were conservative even when the training set was biased, but not excessively so.</p> <p>Conclusion</p> <p>DPRESS is a straightforward and powerful way to reliably estimate individual predictive uncertainties for compounds outside the training set based on their distance to the training set and the internal predictive uncertainty associated with its nearest neighbor in that set. It represents a sample-based, <it>a posteriori </it>approach to defining applicability domains in terms of localized uncertainty.</p

    The inevitable QSAR renaissance

    Get PDF
    QSAR approaches, including recent advances in 3D-QSAR, are advantageous during the lead optimization phase of drug discovery and complementary with bioinformatics and growing data accessibility. Hints for future QSAR practitioners are also offered

    Identification and characterization of the intracellular poly-3-hydroxybutyrate depolymerase enzyme PhaZ of Sinorhizobium meliloti

    Get PDF
    <p>Abstract</p> <p>Background</p> <p><it>S. meliloti </it>forms indeterminate nodules on the roots of its host plant alfalfa (<it>Medicago sativa</it>). Bacteroids of indeterminate nodules are terminally differentiated and, unlike their non-terminally differentiated counterparts in determinate nodules, do not accumulate large quantities of Poly-3-hydroxybutyrate (PHB) during symbiosis. PhaZ is in intracellular PHB depolymerase; it represents the first enzyme in the degradative arm of the PHB cycle in <it>S. meliloti </it>and is the only enzyme in this half of the PHB cycle that remains uncharacterized.</p> <p>Results</p> <p>The <it>S. meliloti phaZ </it>gene was identified by <it>in silico </it>analysis, the ORF was cloned, and a <it>S. meliloti phaZ </it>mutant was constructed. This mutant exhibited increased PHB accumulation during free-living growth, even when grown under non-PHB-inducing conditions. The <it>phaZ </it>mutant demonstrated no reduction in symbiotic capacity; interestingly, analysis of the bacteroids showed that this mutant also accumulated PHB during symbiosis. This mutant also exhibited a decreased capacity to tolerate long-term carbon starvation, comparable to that of other PHB cycle mutants. In contrast to other PHB cycle mutants, the <it>S. meliloti phaZ </it>mutant did not exhibit any decrease in rhizosphere competitiveness; however, this mutant did exhibit a significant increase in succinoglycan biosynthesis.</p> <p>Conclusions</p> <p><it>S. meliloti </it>bacteroids retain the capacity to synthesize PHB during symbiosis; interestingly, accumulation does not occur at the expense of symbiotic performance. <it>phaZ </it>mutants are not compromised in their capacity to compete for nodulation in the rhizosphere, perhaps due to increased succinoglycan production resulting from upregulation of the succinoglycan biosynthetic pathway. The reduced survival capacity of free-living cells unable to access their accumulated stores of PHB suggests that PHB is a crucial metabolite under adverse conditions.</p

    Evidence of Dopaminergic Processing of Executive Inhibition

    Get PDF
    Inhibition of unwanted response is an important function of the executive system. Since the inhibitory system is impaired in patients with dysregulated dopamine system, we examined dopamine neurotransmission in the human brain during processing of a task of executive inhibition. The experiment used a recently developed dynamic molecular imaging technique to detect and map dopamine released during performance of a modified Eriksen's flanker task. In this study, young healthy volunteers received an intravenous injection of a dopamine receptor ligand (11C-raclopride) after they were positioned in the PET camera. After the injection, volunteers performed the flanker task under Congruent and Incongruent conditions in a single scan session. They were required to inhibit competing options to select an appropriate response in the Incongruent but not in the Congruent condition. The PET data were dynamically acquired during the experiment and analyzed using two variants of the simplified reference region model. The analysis included estimation of a number of receptor kinetic parameters before and after initiation of the Incongruent condition. We found increase in the rate of ligand displacement (from receptor sites) and decrease in the ligand binding potential in the Incongruent condition, suggesting dopamine release during task performance. These changes were observed in small areas of the putamen and caudate bilaterally but were most significant on the dorsal aspect of the body of left caudate. The results provide evidence of dopaminergic processing of executive inhibition and demonstrate that neurochemical changes associated with cognitive processing can be detected and mapped in a single scan session using dynamic molecular imaging

    Dietary exposure to copper sulphate compared to a copper oxide nanomaterial in rainbow trout: Bioaccumulation with minimal physiological effects.

    Get PDF
    The dietary bioaccumulation potential of engineered nanomaterials (ENMs) remains poorly understood. The aim of the current study was to assess the dietary bioaccumulation of copper from copper oxide (CuO) ENMs...</p
    corecore