Anthrapyrazolone analogues intercept inflammatory JNK signals to moderate endotoxin induced septic shock

Severe sepsis or septic shock is one of the rising causes for mortality worldwide representing nearly 10% of intensive care unit admissions. Susceptibility to sepsis is identified to be mediated by innate pattern recognition receptors and responsive signaling pathways of the host. The c-Jun N-terminal Kinase (JNK)-mediated signaling events play critical role in bacterial infection triggered multi-organ failure, cardiac dysfunction and mortality. In the context of kinase specificities, an extensive library of anthrapyrazolone analogues has been investigated for the selective inhibition of c-JNK and thereby to gain control over the inflammation associated risks. In our comprehensive biochemical characterization, it is observed that alkyl and halogen substitution on the periphery of anthrapyrazolone increases the binding potency of the inhibitors specifically towards JNK. Further, it is demonstrated that hydrophobic and hydrophilic interactions generated by these small molecules effectively block endotoxin-induced inflammatory genes expression in in vitro and septic shock in vivo, in a mouse model, with remarkable efficacies. Altogether, the obtained results rationalize the significance of the diversity oriented synthesis of small molecules for selective inhibition of JNK and their potential in the treatment of severe sepsis.

Modification of the biological intercept model to account for ontogenetic effects in laboratory-reared delta smelt (Hypomesus transpacificus)*

We investigated age, growth, and ontogenetic effects on the proportionality of otolith size to fish size in laboratory-reared delta smelt (Hypomesus transpacificus) from the San Francisco Bay estuary. Delta smelt larvae were reared from hatching in laboratory mesocosms for 100 days. Otolith increments from known-age fish were enumerated to validate that growth increments were deposited daily and to validate the age of fish at first ring formation. Delta smelt were found to lay down daily ring increments; however, the first increment did not form until six days after hatching. The relationship between otolith size and fish size was not biased by age or growth-rate effects but did exhibit an interruption in linear growth owing to an ontogenetic shift at the postflexon stage. To back-calculate the size-at-age of individual fish, we modified the biological intercept (BI) model to account for ontogenetic changes in the otolith-size−fish-size relationship and compared the results to the time-varying growth model, as well as the modified Fry model. We found the modified BI model estimated more accurately the size-at-age from hatching to 100 days after hatching. Before back-calculating size-at-age with existing models, we recommend a critical evaluation of the effects that age, growth, and ontogeny can have on the otolith-size−fish-size relations

Movement and Perceptual Strategies to Intercept Virtual Sound Sources

To intercept a moving object, one needs to be in the right place at the right time. In order to do this, it is necessary to pick up and use perceptual information that specifies the time to arrival of an object at an interception point. In the present study, we examined the ability to intercept a laterally moving virtual sound object by controlling the displacement of a sliding handle and tested whether and how the interaural time difference (ITD) could be the main source of perceptual information for successfully intercepting the virtual object. The results revealed that in order to accomplish the task, one might need to vary the duration of the movement, control the hand velocity and time to reach the peak velocity (speed coupling), while the adjustment of movement initiation did not facilitate performance. Furthermore, the overall performance was more successful when subjects employed a time-to-contact (tau) coupling strategy. This result shows that prospective information is available in sound for guiding goal-directed actions.

Survey of coral lagoons of Laksbadweep Atolls using line intercept transect (LIT) technique

The present study aims at surveying the coral lagoons of four islands viz. Kavarathi, Kalpeni, Kadmat and Agathi, which include quantitative survey of the major benthic forms using Line Intercept Transect (LIT) technique and hydrographical study of these lagoon waters The distribution of PHC in the lagoons has also been followed to understand, the effects of introduction of flat bottomed ferry boats to the islands.From a biological monitoring stand point for the assessment of manmade disturbance of the coral reefs, it IS highly essential to identify faunal assemblages which will contain 'flag-stones' specIes as indicators of such disturbances. Among the known faunal assemblages In coral reefs the most diverse groups of sensitive species belongs to bryozoan assemblage. Therefore, the most common species of bryozoans distributed along the atolls and reef flats were collected and described in this work Along with this, bryozoans associated with coral from other parts of Indian ocean have also been added so as to provide a comprehensive picture of the distribution of bryozoans in the coral reefs.

Bayesian analysis of skew-t multivariate null intercept measurement error model

The multivariate skew-t distribution (J Multivar Anal 79:93-113, 2001; J R Stat Soc, Ser B 65:367-389, 2003; Statistics 37:359-363, 2003) includes the Student t, skew-Cauchy and Cauchy distributions as special cases and the normal and skew-normal ones as limiting cases. In this paper, we explore the use of Markov Chain Monte Carlo (MCMC) methods to develop a Bayesian analysis of repeated measures, pretest/post-test data, under multivariate null intercept measurement error model (J Biopharm Stat 13(4):763-771, 2003) where the random errors and the unobserved value of the covariate (latent variable) follows a Student t and skew-t distribution, respectively. The results and methods are numerically illustrated with an example in the field of dentistry.

Hypotheses Testing on a Multivariate Null Intercept Errors-in-Variables Model

Considering the Wald, score, and likelihood ratio asymptotic test statistics, we analyze a multivariate null intercept errors-in-variables regression model, where the explanatory and the response variables are subject to measurement errors, and a possible structure of dependency between the measurements taken within the same individual are incorporated, representing a longitudinal structure. This model was proposed by Aoki et al. (2003b) and analyzed under the bayesian approach. In this article, considering the classical approach, we analyze asymptotic test statistics and present a simulation study to compare the behavior of the three test statistics for different sample sizes, parameter values and nominal levels of the test. Also, closed form expressions for the score function and the Fisher information matrix are presented. We consider two real numerical illustrations, the odontological data set from Hadgu and Koch (1999), and a quality control data set.

Bayesian analysis for a skew extension of the multivariate null intercept measurement error model

Skew-normal distribution is a class of distributions that includes the normal distributions as a special case. In this paper, we explore the use of Markov Chain Monte Carlo (MCMC) methods to develop a Bayesian analysis in a multivariate, null intercept, measurement error model [R. Aoki, H. Bolfarine, J.A. Achcar, and D. Leao Pinto Jr, Bayesian analysis of a multivariate null intercept error-in -variables regression model, J. Biopharm. Stat. 13(4) (2003b), pp. 763-771] where the unobserved value of the covariate (latent variable) follows a skew-normal distribution. The results and methods are applied to a real dental clinical trial presented in [A. Hadgu and G. Koch, Application of generalized estimating equations to a dental randomized clinical trial, J. Biopharm. Stat. 9 (1999), pp. 161-178].

Two- and three-dimensional shape fabric analysis by the intercept method in grey levels

The count intercept is a robust method for the numerical analysis of fabrics Launeau and Robin (1996). It counts the number of intersections between a set of parallel scan lines and a mineral phase, which must be identified on a digital image. However, the method is only sensitive to boundaries and therefore supposes the user has some knowledge about their significance. The aim of this paper is to show that a proper grey level detection of boundaries along scan lines is sufficient to calculate the two-dimensional anisotropy of grain or crystal distributions without any particular image processing. Populations of grains and crystals usually display elliptical anisotropies in rocks. When confirmed by the intercept analysis, a combination of a minimum of 3 mean length intercept roses, taken on 3 more or less perpendicular sections, allows the calculation of 3-dimensional ellipsoids and the determination of their standard deviation with direction and intensity in 3 dimensions as well. The feasibility of this quick method is attested by numerous examples on theoretical objects deformed by active and passive deformation, on BSE images of synthetic magma flow, on drawing or direct analysis of thin section pictures of sandstones and on digital images of granites directly taken and measured in the field. (C) 2010 Elsevier B.V. All rights reserved.

Inference and local influence assessment in skew-normal null intercept measurement error model

In this article, we discuss inferential aspects of the measurement error regression models with null intercepts when the unknown quantity x (latent variable) follows a skew normal distribution. We examine first the maximum-likelihood approach to estimation via the EM algorithm by exploring statistical properties of the model considered. Then, the marginal likelihood, the score function and the observed information matrix of the observed quantities are presented allowing direct inference implementation. In order to discuss some diagnostics techniques in this type of models, we derive the appropriate matrices to assessing the local influence on the parameter estimates under different perturbation schemes. The results and methods developed in this paper are illustrated considering part of a real data set used by Hadgu and Koch [1999, Application of generalized estimating equations to a dental randomized clinical trial. Journal of Biopharmaceutical Statistics, 9, 161-178].

A robust Bayesian approach to null intercept measurement error model with application to dental data

Measurement error models often arise in epidemiological and clinical research. Usually, in this set up it is assumed that the latent variable has a normal distribution. However, the normality assumption may not be always correct. Skew-normal/independent distribution is a class of asymmetric thick-tailed distributions which includes the Skew-normal distribution as a special case. In this paper, we explore the use of skew-normal/independent distribution as a robust alternative to null intercept measurement error model under a Bayesian paradigm. We assume that the random errors and the unobserved value of the covariate (latent variable) follows jointly a skew-normal/independent distribution, providing an appealing robust alternative to the routine use of symmetric normal distribution in this type of model. Specific distributions examined include univariate and multivariate versions of the skew-normal distribution, the skew-t distributions, the skew-slash distributions and the skew contaminated normal distributions. The methods developed is illustrated using a real data set from a dental clinical trial. (C) 2008 Elsevier B.V. All rights reserved.

Type of Intercept Trap Not Important for Capturing Female Sirex noctilio and S-nigricornis (Hymenoptera: Siricidae) in North America

Current detection tools for Sirex noctilio F. (Hymenoptera: Siricidae) in North America are poor. To determine the importance of intercept trap type for capturing females of S. noctilio and its native congener, Sirex nigricornis F., in eastern North America, we report on seven trap comparison studies from different years and geographic locations. Among studies, total numbers of S. noctilio captured were low (mean of <= 1waspper trap). Total numbers of S. nigricornis caught were generally greater, andranged from ameanof 1-13 wasps per trap. Nearly all studies found no significant differencesamongintercept trap types in the number of woodwasps caught. For future studies, we recommend that either panel or 12-unit Lindgren funnel traps be used to catch S. noctilio or S. nigricornis in eastern North America.

Effects of Perspective on the Amplification of Object Sizes that Intercept the Horizon Line

We investigated the effects of texture gradient and the position of test stimulus in relation to the horizon on the perception of relative sizes. By using the staircase method, 50 participants adjusted the size of a bar presented above, below or on the horizon as it could be perceived in the same size of a bar presented in the lower visual field. Stimuli were presented during 100ms on five background conditions. Perspective gradient contributed more to the overestimation of relative sizes than compression gradient. The sizes of the objects which intercepted the horizon line were overestimated. Visual system was very effective in extracting information from perspective depth cues, making it even during very brief exposure.

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Includes index.

Operator, organizational, direct and general support maintenance manual : intercept-aerial guided missile MIM-23B, MTM-23B, and M18E2 (improved HAWK air-defense guided missile system).

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"16 September 1985."