Model For Use In Studies Research Articles

A Human Immortalized Cell-Based Blood-Brain Barrier Triculture Model: Development and Characterization as a Promising Tool for Drug-Brain Permeability Studies.

Brain microvascular endothelial cells (BMEC), together with astrocytes and pericytes, form the blood-brain barrier (BBB) that strictly restricts drug penetration into the brain. Therefore, in central nervous system drug development, the establishment of an in vitro human BBB model for use in studies estimating the in vivo human BBB permeability of drug candidates has long been awaited. The current study developed and characterized a human immortalized cell-based BBB triculture model, termed the "hiBBB" model. To set up the hiBBB model, human immortalized BMEC (HBMEC/ci18) were cocultured with human immortalized astrocytes (HASTR/ci35) and brain pericytes (HBPC/ci37) in a transwell system. The trans-endothelial electrical resistance of the hiBBB model was 134.4 ± 5.5 (Ω × cm2), and the efflux ratios of rhodamine123 and dantrolene were 1.72 ± 0.11 and 1.72 ± 0.45, respectively, suggesting that the hiBBB model possesses essential cellular junction and efflux transporter functions. In BBB permeability assays, the mean value of the permeability coefficients (Pe) of BBB permeable compounds (propranolol, pyrilamine, memantine, and diphenhydramine) was 960 × 10-6 cm/s, which was clearly distinguishable from that of BBB nonpermeable compounds (sodium fluorescein and Lucifer yellow, 18 × 10-6 cm/s). Collectively, this study successfully developed the hiBBB model, which exhibits essential BBB functionality. Taking into consideration the high availability of the immortalized cells used in the hiBBB model, our results are expected to become an initial step toward the establishment of a useful human BBB model to investigate drug penetration into the human brain.

Quantifying Dispositional Fear as Threat Sensitivity: Development and Initial Validation of a Model-Based Scale Measure.

The Research Domain Criteria initiative aims to reorient the focus of psychopathology research toward biobehavioral constructs that cut across different modalities of measurement, including self-report and neurophysiology. Constructs within the Research Domain Criteria framework are intentionally transdiagnostic, with the construct of "acute threat," for example, broadly relevant to clinical problems and associated traits involving fearfulness and stress reactivity. A potentially valuable referent for research on the construct of acute threat is a structural model of fear/fearlessness questionnaires known to predict variations in physiological threat reactivity as indexed by startle potentiation. The aim of the current work was to develop an efficient, item-based scale measure of the general factor of this structural model for use in studies of dispositional threat sensitivity and its relationship to psychopathology. A self-report scale consisting of 44 items from a conceptually relevant, nonproprietary questionnaire was first developed in a sample of 1,307 student participants, using the general factor of the fear/fearlessness model as a direct referent. This new Trait Fear scale was then evaluated for convergent and discriminant validity with measures of personality and psychopathology in a separate sample (n = 213) consisting of community adults and undergraduate students. The strong performance of the scale in this criterion-validation sample suggests that it can provide an effective means for indexing variations along a dispositional continuum of fearfulness reflecting variations in sensitivity to acute threat.

PERFORMANCE ANALYSIS OF DIGITAL ELEVATION MODELS - A CASE STUDY OF BASIN LOW MIDDLE SÃO FRANCISCO RIVER

Corresponding author: madson_tavares@hotmail.comThe performance assessment of digital elevation models, from the handling of the mission SRTM elevation data , ASTER imager instrument , and project TOPODATA compared to elevation data obtained in the field from GPS was the aim of this work, in view the adequacy of the best model for use in studies of morphometric analysis of watersheds , as well as applications in hydrological models . To conduct this study we used the ArcGIS 9.3 software. The results demonstrate that the elevation data extracted from SRTM , ASTER and TOPODATA are extremely satisfactory for presenting high correlation with the data collected by GPS (r = 0.97 , 0.96 and 0.97 , respectively) , was also observed that the smallest errors associated were obtained for the SRTM DEM , being observed PBIAS equal to 2.71 % and MAE of 11.45 m . Finally from the index c Camargo & Sentelhas be excellent in the criterion of model performance. In conclusion it was observed that the DEM SRTM showed the best results, possibly due to the lower number of cells to compose your image, thus generating more homogeneous areas than other models.

A Dehydration Avoidance Mechanism: Leaf Rolling

Plants have several defense mechanisms against unfavorable environmental conditions. One of these mechanisms is leaf rolling. In this review, leaf rolling as a response to water deficit stress and biochemical changes during leaf rolling in higher plants are reported. For instance, the activities of some enzymes and osmotic substances change during leaf rolling. Leaf rolling increases drought resistance in numerous species in theGramineae as well as inCtenanthe setosa, a perennial herbaceous plant that is a suitable model for use in studies of leaf rolling.

Platelet aggregation and dense granule secretion in a colony of dogs with spontaneous hypertension.

Since canine hereditary essential hypertension has been previously reported in a colony of Siberian husky dogs, we tested the suitability of this model for use in studies on the platelet defect identified in humans with essential hypertension. Platelet aggregation and dense granule ATP secretion were measured in dogs with essential hypertension and normotensive control dogs. The platelets from the hypertensive group showed significantly increased aggregation and secretion in response to stimulation with ADP. There was no significant increase in aggregation or secretion when platelets from hypertensive dogs were stimulated by platelet-activating factor, thrombin, calcium ionophore A23187 or phorbol myristate acetate. The increased aggregation and secretion responses in platelets from the hypertensive dogs suggest that a defect similar to that reported in humans with essential hypertension exists and that further investigation is warranted.

Epidemiology and prevention of blood pressure-related renal disease

To examine the relationship between blood pressure and end-stage renal disease. Review of recent reports on blood pressure in relation to renal function. The incidence and prevalence of treated end-stage renal disease are increasing progressively in economically developed countries. To combat this problem, the treatment of established end-stage renal disease must be complemented by strategies to treat and prevent risk factors for the development of renal failure. Severe hypertension and malignant hypertension are well accepted as risk factors for renal insufficiency. Recent reports suggest a strong relationship between blood pressure and renal function, throughout the entire range of blood pressure. Most blood pressure-related renal disease can probably be attributed to mild hypertension or a high normal blood pressure. Additional clinical trials are needed to assess the value of different antihypertensive drugs and different levels of blood pressure control in preserving renal function in subjects at risk of blood pressure-related renal disease. Primary prevention of hypertension may be an important complement to the treatment of established hypertension in reducing the burden of renal disease in the community.

Anticardiolipin antibodies in NZW x BXSB F1 mice. A model of antiphospholipid syndrome.

NZW x BXSB F1 (W/B F1) male mice develop systemic lupus-like disease, and several autoantibodies, circulating immune complexes, and lupus nephritis become apparent. The abnormally high incidence of degenerative coronary vascular disease with myocardial infarction and thrombocytopenia due to the presence of both platelet-associated antibodies and circulating antiplatelet antibodies in this animal has been reported. We found that W/B F1 male mice produced autoantibodies against cardiolipin (aCL) and that the titer of aCL increases with age. aCL from W/B F1 male mice were mainly IgG and binding activity to cardiolipin was aCL-cofactor (beta 2-glycoprotein I (beta 2-GPI)) dependent. We developed monoclonal aCL from these animals and examined specificity of the autoantibodies. All the mAb used reacted with the negatively charged phospholipids, cardiolipin, phosphatidylserine, and phosphatidylinositol, and some reacted with platelets and DNA. The addition of human or mouse beta 2-GPI enhanced the titer for monoclonal aCL from the W/B F1 mice. From the results of competitive inhibition enzyme immunoassay with monoclonal aCL and purified beta 2-GPI, aCL from the W/B F1 mice recognized the complex of CL and beta 2-GPI. The W/B F1 male mouse may be an appropriate model for use in studies on the pathologic significance of aCL in patients with antiphospholipid syndrome.

Effects of anti-motion sickness drugs on motion sickness in rats.

Pica, the eating of nonnutritive substances such as kaolin, can be induced by rotation in rats. We used this rotation-induced pica as a behavioral index of motion sickness in rats and examined whether diphenhydramine, methamphetamine and scopolamine, which are anti-motion sickness drugs for humans, are effective for reducing motion sickness in rats. Intraperitoneal injection of diphenhydramine or methamphetamine suppressed the rotation-induced kaolin intake of rats. Intraperitoneal injection of scopolamine had no effect on the rotation-induced kaolin intake, but its transdermal administration reduced this kaolin intake. These findings show that human anti-motion sickness drugs also prevent motion sickness in rats. Since the pharmacological mechanisms for preventing motion sickness in rats and humans are similar, we conclude that rats are a suitable animal model for use in studies on putative anti-motion sickness drugs.

Synthetic analogues (indolactams) of (-)-indolactam-V are new congeners of the teleocidin class of tumor promoters.

(-)-Indolactam-V, which has the partial structure of teleocidins A and B, and has tumor-promoting activity, is a good model for use in studies on the relation between structure and tumor-promoting activity, whereas (+)-indolactam-V has no tumor-promoting activity. In this work, five racemic indolactams differing only in their alkyl group at C-12 of (-)-indolactam-V were synthesized and tested for biological and biochemical activities related to tumor promotion. The activities tested were inductions of ornithine decarboxylase in mouse skin and human promyelocytic leukemia (HL-60) cell adhesion, inhibition of specific [3H]12-O-tetradecanoyl-phorbol-13-acetate binding to a mouse particulate fraction and activation of protein kinase C in vitro. The results showed that (+/-)-indolactam-L and (+/-)-indolactam-F had almost the same activities as (+/-)-indolactam-V, suggesting that (-)-indolactam-L and (-)-indolactam-F are new tumor promoters with as high potency as (-)-indolactam-V. (+/-)-Indolactam-t-L, which has a highly lipophilic group at C-12 of (-)-indolactam-V, showed the highest activities in the above tests. (-)-Indolactam-t-L might have stronger tumor-promoting activity than (-)-indolactam-V. Furthermore, the results with (-)-indolactam-t-L indicated the possibility of designing new tumor promoters with stronger activity than teleocidin.

Mesoscale sea floor roughness

Data relating to ocean floor roughness on scales from hundreds of meters to hundreds of kilometers are analyzed and applied to the synthesis of a statistical rooghness model for use in studies of mesoscale ocean dynamics. Essential features of the roughness model are a mean suqar elevation that increases linearly with scale, a 5:1 anisotropy at scales in excess of several hundred meters, and a component of inhomogeneity that correlates with regional variations in geological setting.

General-purpose model of power-system loads

The paper is concerned with the derivation of a load model for use in studies of power-system dynamics and with he parameters to be used in such a model. It describes some system tests in which small voltage disturbances were imposed on a power-station auxiliary system and on consumer loads. The objectives of the tests were to determine the important factors in the power/voltage response of loads and to explore the possibility of determining the load composition and characteristics from such tests. The parameters obtained from the analysis of the small-disturbance tests on the power-station auxiliary system are used in an attempt to simulate a large disturbance to that system.

Counting error in petrographic point-count analysis: A theoretical and experimental study

The binomial model, commonly used to estimate counting error in point-count analysis, misestimates this error when the observation points on a grid are positively or negatively correlated. A model, called the “cell model,” is proposed as an alternative to the binomial model for use in studies, especially with coarse-grained rocks, in which such correlation is known or thought to exist. In the new model the thin section is conceptually partitioned into a number of cells (six is recommended), and the assumption is made that the proportions in the individual cells are statistically independent and that their variance does not differ from cell to cell. Empirical relations obtained from a suite of 200 thin sections of limestones are in reasonable support of the prediction that large particle size adversely affects counting error estimates based on the binomial model.