Interrelated Responses Research Articles

Polystyrene microsphere and 5-fluorouracil release from custom-designed wound dressing films.

Custom-designed wound dressing films of chitosan and alginate have been prepared by a casting/solvent evaporation method for hydrophobic therapeutic agent encapsulation. In this parametric study, the propylene glycol (PG) and calcium chloride (CaCl2) concentrations were varied for chitosan and alginate films, respectively. Mechanical and chemical inter-related responses under observations included thickness (th), elasticity (E), tensile strength (TS), sorption ability (S%) and kinetics of in-vitro drug release, specifically in terms of membrane time to burst (tB) and duration of release (tR). As shown by results of a one tailed t-test significance testing at the 95% confidence interval (α = 0.05), alginate films were significantly more elastic (p = 0.003), thinner (p = 0.004) and more susceptible to osmotic burst (p = 0.011) and characterized by a longer duration of release (p = 0.03). Meanwhile chitosan films exhibited superior moisture permeability (p = 0.006) and sorption characteristics (p = 0.001), indicative of higher hydrophilicity. There were no significant differences in tensile strength (p = 0.324) for alginate and chitosan-based formulations. Preliminary testing was conducted using 0.71 μm in diameter microspheres for modeling film dissolution into Lactated Ringer’s solution. Experimental release profiles were modeled for each film from which the average release from alginate films (MAGCa = 81%) was estimated to be twice the percentage associated with chitosan films (MCD = 42%). The film comprised of 2.5% (w/v) medium MW chitosan/dextran 70 kDa (5:1) was selected for studying the release of 5-Fluorouracil (5-FU) as a model hydrophobic drug. Diffusion coupled with film disintegration is immediate (tB = 0) in case of encapsulated 5-FU as compared to the control film encapsulating microspheres characterized by tB = 70 min ± 7 min. This shift in release profile and the ability to modulate the timing of membrane burst can be attributed to the approximate ratio (1: 505) in molecular size between drug and microsphere. This hypothesis has been validated by the film pore size measured to be 430 nm ± 88 nm using atomic force microscopy.Electronic supplementary materialThe online version of this article (doi:10.1186/2194-0517-2-1) contains supplementary material, which is available to authorized users.

Tissue factor–positive neutrophils bind to injured endothelial wall and initiate thrombus formation

AbstractFor a long time, blood coagulation and innate immunity have been viewed as interrelated responses. Recently, the presence of leukocytes at the sites of vessel injury has been described. Here we analyzed interaction of neutrophils, monocytes, and platelets in thrombus formation after a laser-induced injury in vivo. Neutrophils immediately adhered to injured vessels, preceding platelets, by binding to the activated endothelium via leukocyte function antigen-1–ICAM-1 interactions. Monocytes rolled on a thrombus 3 to 5 minutes postinjury. The kinetics of thrombus formation and fibrin generation were drastically reduced in low tissue factor (TF) mice whereas the absence of factor XII had no effect. In vitro, TF was detected in neutrophils. In vivo, the inhibition of neutrophil binding to the vessel wall reduced the presence of TF and diminished the generation of fibrin and platelet accumulation. Injection of wild-type neutrophils into low TF mice partially restored the activation of the blood coagulation cascade and accumulation of platelets. Our results show that the interaction of neutrophils with endothelial cells is a critical step preceding platelet accumulation for initiating arterial thrombosis in injured vessels. Targeting neutrophils interacting with endothelial cells may constitute an efficient strategy to reduce thrombosis.

A new probabilistic distribution matching PATC formulation using polynomial chaos expansion

In the existing probabilistic hierarchical optimization approaches, such as probabilistic analytical target cascading (PATC), all the stochastic interrelated responses are characterized only by the first two statistical moments. However, due to the high nonlinear relation between the inputs and outputs, the interrelated responses are not necessarily normally distributed. The existing approaches, therefore, may not accurately quantify the probabilistic characteristics of the interrelated responses, and would further prevent achieving the real optimal solution. To overcome this deficiency, a novel PATC approach, named PATC-PCE is developed. By employing the polynomial chaos expansion (PCE) technique, the entire distribution of interrelated response can be characterized by a PCE coefficients vector, and then matched and propagated in the hierarchy. Comparative studies show that PATC-PCE outperforms PATC in terms of yielding more accurate optimal solutions and fewer design cycles when the interrelated response are random non-normal quantities, while at a sacrifice of extra function evaluations.

Plotlessness, Ethnography, Ethology

The authors of this article hail from perhaps disparate fields of biology and cultural studies. The authors use ethnography and ethology, which have offered parallel modernist responses to the challenge posed by Otherness, as touchstones for exploring modernist responses to the theories/methods of the research texts that are produced and performed in their respective disciplines; for example, ethnography typically promises a supreme moment of insight, an intellectual epiphany, when the trained ethnographer’s patient and painstaking field work finally cracks the code of the alien culture to reveal the philosophical and metaphysical essence that constitutes that culture’s previously baffling Otherness. Similarly, field studies of animal behavior promise a royal road to the Umwelten (encompassing worlds, milieux) of natures and cultures far more alien and “Other” than even the most exotic forms of the human condition. The article highlights that scholars in 20th-century ethnography—and, to a lesser extent, ethology—began to question these philosophical and methodological bases and that by the beginning of the 21st century, their criticisms and answers to such dilemmas sparked a range of interrelated responses, which the article briefly overviews: epistemological decentering and recontextualizing of inquiry; illumination of the tensions between, and experimentation with traditional and avant-garde rhetorical, statistical, evidence-based, performance and literary forms necessary for presentation of research; and return to and/or finer articulation of the goals of ethology and ethnography. Within these responses the authors are particularly interested in understanding “plotlessness,” a concept that emerges from recent ethnographic and ethological investigations of “Other-ology” but that is rarely dissected in ethnography. The authors further explore and refine the idea of plotlessness, especially in regard to possible commonalities that this idea might reveal in thinking about play, broadly and loosely conceived, and the “openings” that play may afford present, and future work and thought in ethnography and ethology. Reminding readers of thought on the imperatives of play, on the ordinary/extraordinary nature of play, the authors push play as an all-encompassing paradigm for scholarship across the disciplines and much more (play as core of the ontological-epistemological human condition?).

Application of Probabilistic Distribution Matching PATC on Robust Multi-Scale Design

Multiscale design dealing with a 2-scale material and product system is implemented by employing the probabilistic distribution matching probabilistic analytical target cascading method (PATC-PCE) in this paper. PATC-PCE allows design autonomy at each scale subsystem by formulating the multiscale design system as a multilevel design structure. The probabilistic distribution matching strategy in PATC-PCE can quantify the stochastic interrelated responses accurately enough. Comparative study on a multiscale bracket design problem shows that the results obtained by our method are very close to the benchmark values. PATC-PCE is demonstrated to be highly effective and applicable on multi-scale design.

Epitope Mapping of Tobacco Mosaic Virus Capsid Protein: Prediction and Experimental Data from Spot Synthesis

The immune system is a network of thousands of molecules, cells and regulatory factors that produce many interrelated responses. In this study, we used spot synthesis to map tobacco mosaic virus (TMV) epitopes in a mice animal model (Balb/c) and compared the results with those obtained using immunoinformatic prediction tools. Mice were inoculated with TMV and after immunization the sera were incubated with an array of overlapping pentadecapeptides that corresponded to the full sequence of the TMV capside protein (TMVcp) that had been synthesized on a cellulose membrane for spot synthesis analysis. Six linear epitopes were identified experimentally, as shown by the IgG-elicited immune responses in mice. The data for epitope prediction based on epitope databases agreed with the results obtained by spot synthesis results. Comparison of the findings for spot intensities and those obtained with the prediction software allowed the identification of different responses according to the MHC class I alleles. The results of this work provide a detailed antigenic profile for TMV.

Enhanced probabilistic analytical target cascading with application to multi-scale design

Probabilistic analytical target cascading (PATC) is an approach for multi-level multi-disciplinary design optimization under uncertainty. In the original PATC approach, only the mean and variance of each interrelated response and linking variable are matched in a multi-level hierarchy. The ignorance of response correlation introduces difficulties in finding optimal solutions especially when the covariance of interrelated responses has a significant impact. In this article, an enhanced PATC (EPATC) approach is proposed. In addition to matching the first two statistical moments, the covariance between the interrelated responses is also considered by applying a modified updating strategy for estimating the statistical performance of an upper-level subsystem. A mathematical example and a multi-scale design problem are used to demonstrate the effectiveness and efficiency of the proposed EPATC approach. This study shows that the EPATC approach outperforms the original PATC by providing more accurate optimal solutions.

Application of desirability-based multi(bi)-objective optimization in the design of selective arylpiperazine derivates for the 5-HT 1A serotonin receptor

The multiobjective optimization technique based on the desirability estimation of several interrelated responses (MOOP-DESIRE) has been recently applied to quantitative structure–activity relationship (QSAR) studies. However, the advantage of applying this new methodology to the study of selectivity and affinity to competitive targets has been little explored. We used the MOOP-DESIRE methodology and a variation of this, to study the arylpiperazine derivates that could interact with 5-HT 1A and 5-HT 2A, serotonin receptor subtypes with the objective of designing more selective molecules for the 5-HT 1A receptor. We did show that the model results are in agreement with the available pharmacophore descriptions, guaranteeing an appropriate structural correlation and proving the methodology, as a useful tool for the important problem of selective drug design.

The anabolic and catabolic responses in bone repair

The literature on fracture repair has been reviewed. The traditional concepts of delayed and nonunion have been examined in terms of the phased and balanced anabolic and catabolic responses in bone repair. The role of medical manipulation of these inter-related responses in the fracture healing have been considered.

Pattern recognition receptors: an update

The vertebrate immune system consists of two inter-related components, the innate and adaptive responses, which are required for the resolution of infection. The innate immune response is critical for the immediate protection from infection and for marshalling the B- and T-cell responses of the adaptive response. A key component of the innate immune response is germline-encoded pattern recognition receptors that detect pathogens. Several families of these pattern recognition receptors have now been described. Microbial recognition by these receptors triggers appropriate immune responses, including the direct uptake and killing of pathogens and/or initiation of intracellular signaling pathways that culminate in the activation of immune responsive transcriptional programs. Pattern recognition receptors include soluble receptors in serum (collectins), transmembrane receptors on cell surfaces or vacuolar membranes (C-type lectins and Toll-like receptors) or cytoplasmic sensors (NACHT-LRR proteins and RNA helicases). Roles for these pattern recognition receptor families are emerging in the susceptibility to bacterial and viral infections and in acute and chronic conditions, such as sepsis, autoimmune disease and atherosclerosis. These findings suggest that the selective targeting of pattern recognition receptors and the pathways they trigger may be useful clinically. Progress towards therapeutics designed to target Toll-like receptor signaling is already well underway. This review will describe our current understanding of innate immune sensors and the mechanisms regulating their activity.

Probabilistic Analytical Target Cascading: A Moment Matching Formulation for Multilevel Optimization Under Uncertainty

Abstract Analytical target cascading (ATC) is a methodology for hierarchical multilevel system design optimization. In previous work, the deterministic ATC formulation was extended to account for random variables represented by expected values to be matched among subproblems and thus ensure design consistency. In this work, the probabilistic formulation is augmented to allow the introduction and matching of additional probabilistic characteristics. A particular probabilistic analytical target cascading (PATC) formulation is proposed that matches the first two moments of interrelated responses and linking variables. Several implementation issues are addressed, including representation of probabilistic design targets, matching responses and linking variables under uncertainty, and coordination strategies. Analytical and simulation-based optimal design examples are used to illustrate the new formulation. The accuracy of the proposed PATC formulation is demonstrated by comparing PATC results to those obtained using a probabilistic all-in-one formulation.

Ethylene Production and Activation of Hydrolytic Enzymes during Acclimation of Maize Seedlings to Partial Flooding

The effects of partial flooding on the partial pressure of oxygen and carbon dioxide in water around the roots, ethylene production by intact maize (Zea mays L.) seedlings, the activities of hydrolytic enzymes (pectinase, xylanase, and cellulase) in adventitious roots, and the growth of adventitious and main roots were studied. Aggravated hypoxia resulted in the accelerated ethylene production and the activation of enzymes destroying cell walls in the adventitious roots; as a result, the latter changed their growth pattern. The conclusion is that the interrelated responses are adaptive ones, and the adventitious roots play a key role in plant adaptation.

Reduced-Rank Models for Nutrition Knowledge Assessment

The dependence of multiple interrelated responses on a set of covariates can be efficiently and parsimoniously modeled using reduced-rank methods. Two forms of reduced-rank models are possible depending on assumptions about response error correlations. When the response outcomes are binary, a minimum distance estimator based on first-stage marginal probit regressions can be used to estimate the reduced-rank models. The alternative models and the estimation procedure are illustrated using a data set on the dietary fats and cholesterol knowledge of a sample of U.S. household meal planners.

Foraging in a variable environment: weather patterns and the behavioral ecology of baboons

We investigated the long-standing premise in behavioral ecology that the environment affects behavior and demography. We did this by evaluating the extent to which year-to-year variability in the behavioral ecology of a nonhuman primate population could be modeled from meteorological patterns. Data on activity profiles and home range use for baboons (Papio cynocephalus) in Amboseli, Kenya, were obtained over a 10-year period for three social groups: two completely wild-foraging ones, and a third that supplemented its diet with refuse from a nearby tourist lodge. The relationships across years among activity budgeting, travel distance, group size, and measures of temperature and rainfall patterns differed among the social groups. Although meteorological variation generally correlated with behavioral variation in the completely wild-foraging groups, different weather variables and direction of relationships resulted for each group. In addition, different relationships among variables were found before and after home-range shifts. The food-enhanced group spent half as much time foraging as did the other groups and therefore could be used to evaluate the relative extent to which foraging time was a limiting factor for resting and social time. Under their relaxed ecological conditions, the food-enhanced animals increased resting time much more than social time. These findings, combined with supplementary information on the population, lead us to suggest that baboons use a suite of interrelated responses to ecological variability that includes not only changes in activity budgets, but also home-range shifts, changes in the length of the active period, and changes in group size through fissions. Moreover, our results imply that group differences as well as interpopulational and interspecific differences in behavioral ecology provide significant sources of variability. Therefore, social groups rather than populations may be the appropriate unit of analysis for understanding the behavioral ecology of baboons and other highly social primates. The different patterns we observed among groups may have fitness consequences for the individuals in those groups and thereby affect population structure over time.

Impact of maternal supine position on some parameters of fetal function in rabbits

Fixation of a pregnant rabbit in the supine position is shown to result in hemodynamic disturbances in the maternal-placental-fetal system, apparently due to a hypotensive syndrome developing in the mother. The heart rate, body temperature, and motor activity in the fetuses of such mothers were similar to those recorded for fetuses with retarded development. It is concluded that maternal position needs to be taken into consideration in experiments designed to examine interrelated responses of mother and fetus to external stimuli.

Carbachol‐induced increase in inositol trisphosphate (IP3) content is attenuated by adrenergic stimulation in the isolated working rat heart

The interrelated responses of concomitant adrenergic and muscarinic receptor stimulation on second messengers and mechanical activity in the isolated perfused working rat heart were studied. The hearts were perfused with Krebs-Henseleit buffer in a modified Langendorff apparatus. The hearts were perfused with noradrenaline (10(-6) mol L-1, n = 20), with carbachol (3 x 10(-7) mol L-1, n = 11) or with noradrenaline plus carbachol (n = 20) in the above-mentioned concentrations. The hearts were frozen at 20 s, 30 s and 40 min after addition of noradrenaline and noradrenaline plus carbachol and at 20 s and 40 min after addition of carbachol. Five hearts were freeze-clamped directly after preperfusion and another five hearts after 40 min of perfusion and used as controls. Myocardial cAMP increased at 20 s and 40 min after noradrenaline perfusion. In contrast to this cAMP was unchanged at 20 s and decreased at 40 min after perfusion with noradrenaline plus carbachol. IP3 content increased after 20 s of carbachol- and after 40 min of noradrenaline perfusion (P < 0.05). However, noradrenaline plus carbachol did not induced any significant increase in IP3 content after 20 s and 30 s, but after 40 min a decrease below basal level was found (P < 0.05). Noradrenaline stimulation attenuated muscarinic agonist induced IP3 formation. A reciprocity existed in that noradrenaline induced IP3 formation was attenuated by carbachol. No direct relationship was observed between the IP3 response and contractility, also valid for cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of Cadmium on Life-History Characteristics of Folsomia candida (Willem) in an Artificial Soil Substrate

To understand the consequences of soil pollution on higher levels of biological organization, the chain of effects of cadmium on several interrelated responses was studied in a chronic toxicity experiment using the collembolan species Folsomia candida (Willem) in an artificial soil. The individual parameters survival, growth, and number of offspring were determined after different time intervals up to 9 weeks. The accumulation of cadmium in springtails and the population increase during the experimental period were also determined. By combining all the mentioned parameters and their development in time, a detailed picture of the action of cadmium on F. candida was obtained. In order of decreasing sensitivity the EC 50 values for Von Bertalanffy growth, number of offspring, population increase, and survival were 256, >326, 475, and 850 μg Cd/g dry soil. respectively. The ultimate LC 50 value and also the equilibrium body burden were reached after about 20 days. Reproduction started later because of retarded growth, but was not affected directly and eventually reached the control level. The results are discussed in light of the seemingly contradictory ideas of Halbach (1984, Hydrobiologia 109, 79-96) and Meyer et al. (1987, Environ. Toxicol. Chem. 6, 115-126) about the sensitivity of individual and population parameters. It appears to be very important to know how individual parameters develop in time so that the most sensitive parameter and the consequences for higher levels of biological organization can be determined.

Effects of dietary interventions on glomerular pathophysiology

Numerous dietary interventions have been utilized to modify the course of and further elucidate the pathophysiological processes involved in experimental progressive glomerulopathy. Alterations in dietary constituents can affect the glomerular capillary hemodynamic parameters, the permselectivity features of the filtration apparatus, as well as the morphology and function of resident glomerular cells and influxing bone marrow-derived monocytes. The three dietary modifications examined in this review are protein restriction, dietary cholesterol supplementation, and essential fatty acid deficiency. These maneuvers have been chosen from the myriad dietary interventions in the experimental and clinical literature and are not meant to be all inclusive. The implementation of these three dietary modifications, in experimental models of glomerular disease, amply demonstrate the concept of a stratified alteration in glomerular structure and function. Since perturbed glomerular pathobiology, involving the above-mentioned structures and cell types, is believed to contribute to progressive glomerulopathy, a review of these seemingly diverse, yet perhaps, interrelated responses to dietary modifications will only aid us in understanding this process.

Pulmonary Host Defense Mechanisms

T he major function of the respiratory system is to procure oxygen from the external environment and to eliminate carbon dioxide from the body at rates required by tissue metabolism. Unfortunately, ambient inspired air contains not only oxygen which is vital to survival, but also noxious gases and a multitude of particulates, including viable microorganisms, which the lungs must exclude to maintain good health. Toxic substances in air are derived from many sources. For example, naturally occurring processes can give rise to large amounts of aerosolized particles. The latter includes resuspension ofsoil and emissions from volcanic activity, forest fires, photochemical reactions, and even sea spray. Airborne particles also include biologically derived viruses, bacteria, fungi, algae, spores, and pollens. In addition, industrial and occupational sources add sulfur dioxide, carbon monoxide, nitrogen dioxide, ammonia, hydrocarbons, ozone, and inorganic and organic particles to our inspired air. This article will briefly overview the various pulmonary defense mechanisms which usually prevent the development of lung disease by resisting invasion by pathogenic organisms and by absorbing, detoxifying, and/or removing toxic gases and inanimate particulates. Although the respiratory tract defenses encompass many interrelated responses, for simplicity of presentation, we have arbitrarily divided them into two major parts (Table 1). One is referred to as physical defense mechanisms which primarily comprise structural and physiochemical adaptations in the proximal upper and lower airways and their lining layers. The second is cellular defense mechanisms which operate mostly in the distal alveolar parts ofthe lung. The latter largely depends on alveolar macrophages (AM) and their ability to mediate phagocytic and immunologic responses. Finally, although the aforementioned prox-

Components of Variance in Measurements of Nestling European Starlings (Sturnus vulgaris) in Southeastern Pennsylvania

Abstract I report the results of experiments designed to distinguish factors affecting within-population variability in measurements of nestling European Starlings (Sturnus vulgaris). Individuals were switched among pairs of nests at the beginning of the incubation period and at the beginning of the nestling period. Variables were analyzed in a replicated (nested), three-way factorial analysis of variance to distinguish the contributions of factors associated with (1) the genotype of the embryo or composition of the egg, (2) the incubation period, and (3) the nestling period. In addition, I analyzed the correlations among growth variables within the sample as a whole and among main effects in the experimental design to search for patterns of genotypic and phenotypic interrelationship. I also related growth variables of nestlings to the size and composition of sibling eggs and to the length of the incubation period. The present experiment did not reveal any genetic or egg-quality component to within-population variation in rate of mass increase and mass asymptote achieved, length of the tarsus of fully grown nestlings, or rates of growth of the wing and outer primary feather. Similarly, the nest in which the individual was incubated had no effect on postnatal growth. The nest in which the individual was reared significantly contributed between 19 and 29% of the sums of squares in rate of mass increase, length of the tarsus, rate of increase in length of the wing, and the maximum length of the sheathed portion of the outer primary feather. Rearing nest did not have a significant effect on the mass plateau of the chick. These results, particularly the absence of some effects, are difficult to interpret, because a large proportion of the variation in several variables occurred between pairs of switched nests. These differences undoubtedly included some of the variation that might have been attributable to effects within experiments. Growth variables were weakly correlated over the entire sample, revealing little pattern of variation in postnatal growth. Over certain of the effects in the experimental design, however, particular groups of variables were strongly correlated, indicating interrelated responses of some of the growth parameters to environmental and, perhaps, genetic factors. The size of the egg had a small effect only on the mass plateau and the length of the tarsus of the chick. The composition of a sibling egg influenced only the maximum length of the sheath of the outer primary feather. The present study was somewhat weakened by small sample size and an inexplicable between-experiment effect that reduced its power to distinguish among effects of interest. The experimental design has the potential, however, to disentangle many classes of factors associated with genotype and parental care that contribute to within-population variation in phenotypic measurements.