298 resultados para Therapeutics, Experimental
Resumo:
Identifying crash “hotspots”, “blackspots”, “sites with promise”, or “high risk” locations is standard practice in departments of transportation throughout the US. The literature is replete with the development and discussion of statistical methods for hotspot identification (HSID). Theoretical derivations and empirical studies have been used to weigh the benefits of various HSID methods; however, a small number of studies have used controlled experiments to systematically assess various methods. Using experimentally derived simulated data—which are argued to be superior to empirical data, three hot spot identification methods observed in practice are evaluated: simple ranking, confidence interval, and Empirical Bayes. Using simulated data, sites with promise are known a priori, in contrast to empirical data where high risk sites are not known for certain. To conduct the evaluation, properties of observed crash data are used to generate simulated crash frequency distributions at hypothetical sites. A variety of factors is manipulated to simulate a host of ‘real world’ conditions. Various levels of confidence are explored, and false positives (identifying a safe site as high risk) and false negatives (identifying a high risk site as safe) are compared across methods. Finally, the effects of crash history duration in the three HSID approaches are assessed. The results illustrate that the Empirical Bayes technique significantly outperforms ranking and confidence interval techniques (with certain caveats). As found by others, false positives and negatives are inversely related. Three years of crash history appears, in general, to provide an appropriate crash history duration.
Resumo:
Modelling of water flow and associated deformation in unsaturated reactive soils (shrinking/swelling soils) is important in many applications. The current paper presents a method to capture soil swelling deformation during water infiltration using Particle Image Velocimetry (PIV). The model soil material used is a commercially available bentonite. A swelling chamber was setup to determine the water content profile and extent of soil swelling. The test was run for 61 days, and during this time period, the soil underwent on average across its width swelling of about 26% of the height of the soil column. PIV analysis was able to determine the amount of swelling that occurred within the entire face of the soil box that was used for observations. The swelling was most apparent in the top layers with strains in most cases over 100%.
Resumo:
Shaft-mounted gearboxes are widely used in industry. The torque arm that holds the reactive torque on the housing of the gearbox, if properly positioned creates the reactive force that lifts the gearbox and unloads the bearings of the output shaft. The shortcoming of these torque arms is that if the gearbox is reversed the direction of the reactive force on the torque arm changes to opposite and added to the weight of the gearbox overloads the bearings shortening their operating life. In this paper, a new patented design of torque arms that develop a controlled lifting force and counteract the weight of the gearbox regardless of the direction of the output shaft rotation is described. Several mathematical models of the conventional and new torque arms were developed and verified experimentally on a specially built test rig that enables modelling of the radial compliance of the gearbox bearings and elastic elements of the torque arms. Comparison showed a good agreement between theoretical and experimental results.
Resumo:
β-Adrenoceptor blocking agents (β-blockers) that at low concentrations antagonize cardiostimulant effects of catecholamines, but at high concentrations also cause cardiostimulation, have been appearing since the late 1960s. These cardiostimulant β-blockers, coined non-conventional partial agonists, antagonize the effects of catecholamines through a high-affinity site (β1HAR), but cause cardiostimulation mainly through a low-affinity site (β1LAR) of the myocardial β1-adrenoceptor. The experimental non-conventional partial agonist (−)-CGP12177 increases cardiac L-type Ca2+ current density and Ca2+ transients, shortens action potential duration but augments action potential plateau, increases heart rate and force, as well as causes arrhythmic Ca2+ transients and arrhythmic cardiocyte contractions. Other β-blockers, which do not cause cardiostimulation, consistently have lower affinity for β1LAR than β1HAR. These sites were verified and the cardiac pharmacology of non-conventional partial agonists confirmed on recombinant β1-adrenoceptors and on β1-adrenoceptors overexpressed into the heart. A targeted mutation of Asp138 to Glu138 virtually abolished the pharmacology of β1HAR but left intact the pharmacology of β1LAR. Non-conventional partial agonists may be beneficial for the treatment of peripheral autonomic neuropathy but probably due to their arrhythmic propensities, may be harmful for the treatment of chronic heart failure.
Resumo:
Two-stroke outboard boat engines using total loss lubrication deposit a significant proportion of their lubricant and fuel directly into the water. The purpose of this work is to document the velocity and concentration field characteristics of a submerged swirling water jet emanating from a propeller in order to provide information on its fundamental characteristics. The properties of the jet were examined far enough downstream to be relevant to the eventual modelling of the mixing problem. Measurements of the velocity and concentration field were performed in a turbulent jet generated by a model boat propeller (0.02 m diameter) operating at 1500 rpm and 3000 rpm in a weak co-flow of 0.04 m/s. The measurements were carried out in the Zone of Established Flow up to 50 propeller diameters downstream of the propeller, which was placed in a glass-walled flume 0.4 m wide with a free surface depth of 0.15 m. The jet and scalar plume development were compared to that of a classical free round jet. Further, results pertaining to radial distribution, self similarity, standard deviation growth, maximum value decay and integral fluxes of velocity and concentration were presented and fitted with empirical correlations. Furthermore, propeller induced mixing and pollutant source concentration from a two-stroke engine were estimated.
Resumo:
In silico experimental modeling of cancer involves combining findings from biological literature with computer-based models of biological systems in order to conduct investigations of hypotheses entirely in the computer laboratory. In this paper, we discuss the use of in silico modeling as a precursor to traditional clinical and laboratory research, allowing researchers to refine their experimental programs with an aim to reducing costs and increasing research efficiency. We explain the methodology of in silico experimental trials before providing an example of in silico modeling from the biomathematical literature with a view to promoting more widespread use and understanding of this research strategy.
Resumo:
Experiments were undertaken to study effect of initial conditions on the expansion ratio of two grains in a laboratory scale, single speed, single screw extruder at Naresuan University, Thailand. Jasmine rice and Mung bean were used as the material. Three different initial moisture contents were adjusted for the grains and classified them into three groups according to particle sizes. Mesh sizes used are 12 and 14. Expansion ratio was measured at a constant barrel temperature of 190oC. Response surface methodology was used to obtain optimum conditions between moisture content and particle size of the materials concerned.
Resumo:
There is an urgent need to develop safe, effective, dual-purpose contraceptive agents that combine the prevention of pregnancy with protection against sexually transmitted diseases. Here we report the identification of a group of compounds that on contact with human spermatozoa induce a state of “spermostasis,” characterized by the extremely rapid inhibition of sperm movement without compromising cell viability. These spermostatic agents were more active and significantly less toxic than the reagent in current clinical use, nonoxynol 9, giving therapeutic indices (ratio of spermostatic to cytotoxic activity) that were orders of magnitude greater than this traditional spermicide. Although certain compounds could trigger reactive oxygen species generation by spermatozoa, this activity was not correlated with spermostasis. Rather, the latter was associated with alkylation of two major sperm tail proteins that were identified as A Kinase-Anchoring Proteins (AKAP3 and AKAP4) by mass spectrometry. As a consequence of disrupted AKAP function, the abilities of cAMP to drive protein kinase A-dependent activities in the sperm tail, such as the activation of SRC and the consequent stimulation of tyrosine phosphorylation, were suppressed. Furthermore, analysis of microbicidal activity using Chlamydia muridarum revealed powerful inhibitory effects at the same low micromolar doses that suppressed sperm movement. In this case, the microbicidal action was associated with alkylation of Major Outer Membrane Protein (MOMP), a major chlamydial membrane protein. Taken together, these results have identified for the first time a novel set of cellular targets and chemical principles capable of providing simultaneous defense against both fertility and the spread of sexually transmitted disease.
Resumo:
Purpose: The aim of this study was to investigate the extent and pattern of use of grading scales for contact lens complications (‘grading scales’) in optometric practice. Methods: An anonymous postal survey was sent to all 756 members of the Queensland Division of Optometrists Association Australia. Information was elicited relating to level of experience, practice type and location, and mode of usage of grading scales. Results: Survey forms were returned by 237 optometrists, representing a 31 per cent response rate. The majority of respondents (61 per cent) reported using grading scales frequently in practice, while 65 per cent of these preferred to use the Efron Grading Scales for Contact Lens Complications. Seventy-six per cent of optometrists use a method of incremental grading rather than simply grading with whole numbers. Grading scales are more likely to be used by optometrists who have recently graduated (p < 0.001), have a postgraduate certificate in ocular therapeutics (p = 0.018), see more contact lens patients (p = 0.027) and use other forms of grading scales (p < 0.001). The most frequently graded ocular conditions were corneal staining, papillary conjunctivitis and conjunctival redness. The main reasons for not using grading scales included a preference for sketches, photographs or descriptions (87 per cent) and unavailability of scales (29 per cent). Conclusion: Grading scales for contact lens complications are used extensively in optometric practice for a variety of purposes. This tool can now be considered as an expected norm in contact lens practice. We advocate the incorporation of such grading scales into professional guidelines and standards for good optometric clinical practice.