986 research outputs found
Probit models: Regression parameter estimation using the ML principle despite misspecification of the correlation structure
In this paper it is shown that using the maximum likelihood (ML) principle for the estimation of multivariate probit models leads to consistent and normally distributed pseudo maximum likelihood regression parameter estimators (PML estimators) even if the `true' correlation structure of the responses is misspecified. As a consequence, e.g. the PML estimator of the random effects probit model may be used to estimate the regression parameters of a model with any `true' correlation structure. This result is independent of the kind of covariates included in the model. The results of a Monte Carlo experiment show that the PML estimator of the independent binary probit model is inefficient relative to the PML estimator of the random effects binary panel probit model and two alternative estimators using the `generalized estimating equations' approach proposed by Liang and Zeger (1986), if the `true' correlations are high. If the `true' correlations are low, the differences between the estimators are small in finite samples and for the models used. Generally, the PML estimator of the random effects probit panel model is very efficient relative to the GEE estimators. Therefore, if correlations between binary responses cannot be ruled out and the `true' structure of association is unknown or infeasible to estimate, the PML estimator of the random effects probit model is recommended
Tolerability of inhaled N-chlorotaurine in an acute pig streptococcal lower airway inflammation model
<p>Abstract</p> <p>Background</p> <p>Inhalation of N-chlorotaurine (NCT), an endogenous new broad spectrum non-antibiotic anti-infective, has been shown to be very well tolerated in the pig model recently. In the present study, inhaled NCT was tested for tolerability and efficacy in the infected bronchopulmonary system using the same model.</p> <p>Methods</p> <p>Anesthetized pigs were inoculated with 20 ml of a solution containing approximately 10<sup>8 </sup>CFU/ml <it>Streptococcus pyogenes </it>strain d68 via a duodenal tube placed through the tracheal tube down to the carina. Two hours later, 5 ml of 1% NCT aqueous solution (test group, n = 15) or 5 ml of 0.9% NaCl (control group, n = 16) was inhaled via the tracheal tube connected to a nebulizer. Inhalation was repeated every hour, four times in total. Lung function and haemodynamics were monitored. Bronchoalveolar lavage samples were removed for determination of colony forming units (CFU), and lung samples for histology.</p> <p>Results</p> <p>Arterial pressure of oxygen (PaO<sub>2</sub>) decreased rapidly after instillation of the bacteria in all animals and showed only a slight further decrease at the end of the experiment without a difference between both groups. Pulmonary artery pressure increased to a peak 1-1.5 h after application of the bacteria, decreased in the following hour and remained constant during treatment, again similarly in both groups. Histology demonstrated granulocytic infiltration in the central parts of the lung, while this was absent in the periphery. Expression of TNF-alpha, IL-8, and haemoxygenase-1 in lung biopsies was similar in both groups. CFU counts in bronchoalveolar lavage came to 170 (10; 1388) CFU/ml (median and 25 and 75 percentiles) for the NCT treated pigs, and to 250 (10; 5.5 × 10<sup>5</sup>) CFU/ml for NaCl treated pigs (p = 0.4159).</p> <p>Conclusions</p> <p>Inhaled NCT at a concentration of 1% proved to be very well tolerated also in the infected bronchopulmonary system. This study confirms the tolerability in this delicate body region, which has been proven in healthy pigs previously. Regarding efficacy, no conclusions can be drawn, mainly because of the limited test period of the model.</p
Genetic variation and relationships among spring camelina (Camelina sativa, Brassicaceae) accessions of different origin
Camelina sativa L. is one of the oldest crops of the Brassicaceae family, first domesticated in the region of south-eastern Europe. It has regained interest as a very promising alternative oilseed crop with broad adaptability, a wide range of tolerances to pests and diseases, and low-input requirements. The genetic diversity in spring camelina proved to be limited, so the identification and characterization of genetic variations is considered very useful for development of efficient breeding programmes. The aim of the study was to use SSR markers in order to investigate genetic variation of twenty spring camelina accessions and their relatedness. Forty-five individual samples were taken from each accession and used for amplification of SSR markers P4C11, P6E4 and LIB19. The accessions expressed different levels of genetic variation, AMOVA (analysis of molecular variance) showed that 64% of the total genetic variation was attributed to variance within accessions. Genetic distance analysis indicated that there was overlapping in certain breeding programs and exchange of breeding germplasm
Tumor necrosis factor is a necroptosis-associated alarmin
Necroptosis is a form of regulated cell death that can occur downstream of several immune pathways. While previous studies have shown that dysregulated necroptosis can lead to strong inflammatory responses, little is known about the identity of the endogenous molecules that trigger these responses. Using a reductionist in vitro model, we found that soluble TNF is strongly released in the context of necroptosis. On the one hand, necroptosis promotes TNF translation by inhibiting negative regulatory mechanisms acting at the post-transcriptional level. On the other hand, necroptosis markedly enhances TNF release by activating ADAM proteases. In studying TNF release at single-cell resolution, we found that TNF release triggered by necroptosis is activated in a switch-like manner that exceeds steady-state TNF processing in magnitude and speed. Although this shedding response precedes massive membrane damage, it is closely associated with lytic cell death. Further, we found that lytic cell death induction using a pore-forming toxin also triggers TNF shedding, indicating that the activation of ADAM proteases is not strictly related to the necroptotic pathway but likely associated with biophysical changes of the cell membrane upon lytic cell death. These results demonstrate that lytic cell death, particularly necroptosis, is a critical trigger for TNF release and thus qualify TNF as a necroptosis-associated alarmin
Army Professionalism, the Military Ethic, and Officership in the 21st Century
The authors address what they—and many others—perceived to be a decline in military professionalism in the Army officer corps. The authors first describe the ethical, technical, and political components of military professionalism and then address the causes for the decline. They conclude by proposing a set of principles which, if adhered to, will reinvigorate the vision of the officer corps and motivate the corps to selfless service.https://press.armywarcollege.edu/monographs/1145/thumbnail.jp
Tolerability of inhaled N-chlorotaurine in the pig model
<p>Abstract</p> <p>Background</p> <p>N-chlorotaurine, a long-lived oxidant produced by human leukocytes, can be applied in human medicine as an endogenous antiseptic. Its antimicrobial activity can be enhanced by ammonium chloride. This study was designed to evaluate the tolerability of inhaled N-chlorotaurine (NCT) in the pig model.</p> <p>Methods</p> <p>Anesthetized pigs inhaled test solutions of 1% (55 mM) NCT (n = 7), 5% NCT (n = 6), or 1% NCT plus 1% ammonium chloride (NH<sub>4</sub>Cl) (n = 6), and 0.9% saline solution as a control (n = 7), respectively. Applications with 5 ml each were performed hourly within four hours. Lung function, haemodynamics, and pharmacokinetics were monitored. Bronchial lavage samples for captive bubble surfactometry and lung samples for histology and electron microscopy were removed.</p> <p>Results</p> <p>Arterial pressure of oxygen (PaO<sub>2</sub>) decreased significantly over the observation period of 4 hours in all animals. Compared to saline, 1% NCT + 1% NH<sub>4</sub>Cl led to significantly lower PaO<sub>2 </sub>values at the endpoint after 4 hours (62 ± 9.6 mmHg vs. 76 ± 9.2 mmHg, p = 0.014) with a corresponding increase in alveolo-arterial difference of oxygen partial pressure (AaDO<sub>2</sub>) (p = 0.004). Interestingly, AaDO<sub>2 </sub>was lowest with 1% NCT, even lower than with saline (p = 0.016). The increase of pulmonary artery pressure (PAP) over the observation period was smallest with 1% NCT without difference to controls (p = 0.91), and higher with 5% NCT (p = 0.02), and NCT + NH<sub>4</sub>Cl (p = 0.05).</p> <p>Histological and ultrastructural investigations revealed no differences between the test and control groups. The surfactant function remained intact. There was no systemic resorption of NCT detectable, and its local inactivation took place within 30 min. The concentration of NCT tolerated by A549 lung epithelial cells <it>in vitro </it>was similar to that known from other body cells (0.25–0.5 mM).</p> <p>Conclusion</p> <p>The endogenous antiseptic NCT was well tolerated at a concentration of 1% upon inhalation in the pig model. Addition of ammonium chloride in high concentration provokes a statistically significant impact on blood oxygenation.</p
Mechanistic investigation of the effect of endoglucanases related to pulp refining
Endoglucanases are increasingly being touted as the ultimate solution for reducing energy consumption during the refining process in the pulp and paper industry. However, due to the high variety of endoglucanases in different enzyme formulations, these perform heterogeneously when applied to different pulps. In this study, the effect of four endoglucanases on softwood and hardwood pulp was studied using confocal laser scanning microscopy (CLSM) after addition of fluorescently labelled carbohydrate binding modules (CBMs). Nuclear magnetic resonance (NMR) analysis and high-performance liquid chromatography quantification of released oligo- and monosaccharides was performed for in-depth mechanistical investigation. Changes in the crystallinity levels caused by enzymatic degradation of amorphous regions were monitored by incubation with two different CBMs from Caldicellulosiruptor bescii and from Thermobifida fusca with high preference to either amorphous or crystalline regions of cellulose, respectively. When dosed at identical activity on the endoglucanase specific CellG5 substrate, CLSM analysis indicated the highest decrease of amorphous regions for those endoglucanases which were also most active in laboratory refining trials and which released highest amounts of cellooligomers from pulp. Using 13C-NMR analysis, an increase in para-crystalline cellulose caused by enzyme application was observed. Release of reducing sugars was determined at identical CellG5 dosage, indicating a high variance between the enzymes, especially when complex enzyme formulations were used. Scanning electron microscopy images were obtained for visualization of the endoglucanase activity. The results of mechanistical studies indicate that reduction of amorphous moieties of pulp by endoglucanases is especially beneficial for the refining proces
Regiospecific Synthesis and X-ray Structural Study of Trifluoromethyl Substituted Dibenzosemibullvalene
Preparation of the novel regiospecifically trifluoromethyl substituted dibenzobarrelene 5 and dibenzosemibullvalene 6 is described. Unequivocal proof for the stereostructure of 6 was obtained by its X-ray crystallographic analysis. Geometrical data from X-ray structural analysis showed that the ester carbonyl groups adopt unfavorable conformations for conjugative interactions with respect to the cyclopropane ring involved in the skeleton of 6
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