Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / O &#946;-citronelol à um Ãlcool monoterpÃnico de ocorrÃncia natural em vÃrios Ãleos essenciais como o Ãleo de citronela (obtido de Cymbopogon winterianus), de ampla utilizaÃÃo popular por suas propriedades repelentes de insetos. Recentemente, a esta molÃcula tem sido atribuÃdas outras propriedades que envolvem atividade antibacteriana, antifÃngica, antiespasmÃdica, hipotensora e vasorrelaxante. Sendo assim, objetivamos estudar suas possÃveis aÃÃes no comportamento motor do mÃsculo liso do sistema respiratÃrio de ratos Wistar. Os animais considerados nesse estudo foram divididos em 04 grupos: controle, sensibilizado, desafiado e tratado, em seguida, registros isomÃtricos, in vitro, foram obtidos a partir de anÃis isolados de traqueia. A inalaÃÃo de &#946;-citronelol (300 ÂM) preveniu a hiperreatividade traqueal mediante a adiÃÃo de K+ ou ACh em animais submetidos a um modelo de asma, no entanto, a adiÃÃo cumulativa de &#946;-citronelol (10 a 1000 ÂM), na cuba para ÃrgÃos isolados, nÃo produziu alteraÃÃo significativa das preparaÃÃes mantidas sob tÃnus basal. Em preparaÃÃes de traqueia mantidas contraÃdas, a adiÃÃo de &#946;-citronelol relaxou total e significativamente (p < 0,001; Two-Way ANOVA, seguido do teste Holm-Sidak) os anÃis de traqueia, com CI50 de 120,44 [73,29 - 197,91] ÂM para o K+ e 211,10 [114,13 â 390,46] ÂM para a ACh, e esse efeito nÃo foi alterado (p > 0,05; Teste de Mann-Whitney) apÃs o tratamento com Propranolol, L-NAME, TEA, Azul de Metileno, Ortovanadato de SÃdio, Capsazepina, Indometacina e A-967079. Em experimentos realizados com a remoÃÃo do Ca2+ e contendo EGTA, o &#946;-citronelol inibiu a contraÃÃo mediante a entrada de Ca2+ preferencialmente em canais VOC, mas em altas concentraÃÃes, pÃde atuar tambÃm nos canais ROC e SOC, esse efeito foi mais pronunciado (p < 0,001; Two-Way ANOVA, seguido do teste Holm-Sidak) na contraÃÃo promovida pela adiÃÃo de Ba2+, demonstrando uma maior especificidade em atuar nos canais de Ca2+ operados por voltagem do tipo L. O &#946;-citronelol tambÃm foi capaz de diminuir a contraÃÃo induzida pela estimulaÃÃo elÃtrica. Esses resultados demonstram que o &#946;-citronelol caracteriza-se como uma substÃncia antiespasmÃdica e miorrelaxante do mÃsculo liso respiratÃrio, e esse efeito està parcialmente relacionado à sua capacidade de reduzir principalmente o acoplamento eletromecÃnico. / The &#946;-citronellol is an alcoholic monoterpene of natural occurrence that is found in several essential oils, including the citronella oil (obtained from Cymbopogon winterianus). In general, it is widely used as insect repellent. Recently this molecule has been studied as antibacterial, antifungal, antispasmodic, hypotensive and vasorelaxant agent. We aimed to study the effects of &#946;-citronellol on smooth muscle contractility of rat airways. The animals were divided in four groups namely Control, Sensitized, Challenged and Treated. Isometric recordings were obtained from isolated preparations from tracheal tissues cut as rings. Inhalation of &#946;-citronellol (300 ÂM) before antigen (ovalbumin, OVA) challenge prevented development of tracheal hyperreactivity in response to K+ or ACh in tissues of OVA-sensitized animals. In vitro, the cumulative addition of &#946;-citronellol (10 to 1000 ÂM) did not change basal tone in tracheal smooth muscle preparations. In tracheal rings pre-contracted with K+ or acetylcholine (ACh), the addition of &#946;-citronellol fully relaxed (p < 0.001, Two-Way ANOVA, Holm-Sidak) tracheal rings with IC50 values of 120.44 [73.29 â 197.91] ÂM for K+ and 211.10 [114.13 - 390.46] ÂM for ACh. The relaxing effect of &#946;-citronellol was not altered (p > 0.05, Mann-Whitney test) after treatment with propranolol, N (G)-nitro-L- arginine methyl ester (L-NAME), tetraethylammonium (TEA), methylene blue, sodium orthovanadate, capsazepine, indomethacin and A-967079. Experiments performed in Ca2+ depleted medium containing EGTA revealed that low concentrations of &#946;-citronellol preferentially inhibited contractions induced by recruiting Ca2+ influx via voltage-operated channels (VOC), although at higher concentrations it could also inhibit either on contractions evocked with receptor-operated (ROC) or store-operated (SOC) pathways. Such effect was supported by the more pronounced inhibitory effects of &#946;-citronellol (p < 0.001, Two-Way ANOVA, Holm-Sidak) against contractions promoted in tracheal tissues maintained in Ba2+-containing medium. &#946;-Citronellol also decreased the contractions induced by electrical field stimulation. These results suggest that &#946;-citronellol has antispasmodic and myorelaxant properties on airway smooth muscle, which could be partly related to its ability in inhibiting the electromechanical coupling.

No description available.

Recent advances in Wireless Mesh Networks (WMNs) have overcome the drawbacks of traditional wired networks and wireless ad hoc networks. WMNs will play a leading role in the next generation of networks, and the question of how to provide smooth mobility for WMNs is the driving force behind the research. The inherent characteristics of WMNs, such as relatively static backbones and highly mobile clients, require new handoff management solutions to be designed and implemented. This thesis first presents our research work on handoff management schemes in traditional WMNs. In general, a handoff process includes two parts, the MAC layer handoff and the network layer handoff. For the MAC layer handoff, a self-configured handoff scheme with dynamic adaptation is presented. Before the mobile node starts the probe process, it configures parameters for each channel to optimize the scan process. Moreover, a fast authentication scheme to reduce authentication latency for WiFi-based mesh networks is introduced. A tunnel is introduced to forward data packets between the new access router and the original reliable access router to recover data communication before the complete authentication process is finished. To minimize the network layer handoff latency, a hybrid routing protocol for forwarding packets is proposed: this involves both the link layer routing and the network layer routing. Based on the hybrid routing protocol, both intra-domain and inter-domain handoff management have been designed to support smooth roaming in WMNs. In addition, we extend our work to Vehicular Mesh Networks (VMNs). Considering the characteristics of VMNs, a fast handoff scheme is introduced to reduce handoff latency by using a multi-hop clustering algorithm. Using this scheme, vehicle nodes are divided into different multi-hop clusters according to the relative mobility. Some vehicle nodes are selected as assistant nodes; and these assistant nodes will help the cluster head node to determine the next access router for minimizing handoff latency. Extensive simulation results demonstrate that the proposed scheme can reduce handoff latency significantly.

Different drugs which can affect various aspects of sodium transport were tested on contractile activity of a variety of vascular smooth muscles. In the rabbit anterior mesenteric-portal vein, diphenylhydantoin sodium (DPH) attenuated the contractile responses to noradrenaline (NA) and the inhibition was reversible by washing. The p-hydroxy derivative, 5-p-hydroxyphenyl)-5-phenylhydantoin (DPHOH), which was reported to lack the anticonvulsant activity and the inhibitory effect of DPH on insulin secretion was without any effect on the rabbit anterior mesenteric vein. The inhibitory effect of DPH on contractile responses to NA was almost abolished by prior treatment with ouabain and in K-free solutions. Evidence of a Na-Ca interaction is provided by the finding that both low Na and high Ca Krebs attenuates the inhibitory effect of DPH while low Ca Krebs accentuates it. Electrolyte studies using rat tail arteries showed that DPH could counteract the K loss and Na gain produced by either ouabain containing or K-deficient solutions. Prior cooling of the tissue for one hour at 1° C. and then testing the effect of DPH in K-deficient solutions at 1° C., abolished the ability of DPH to counteract the electrolyte changes in K-deficient solutions. DPH in normal Krebs solution did not significantly affect the Na content of rat tail arteries. Under this condition, there was a slight diminution in the K content. The results suggest that DPH can stimulate the Na pump in rat tail arteries under conditions In which Na and Rare going along their electrochemical gradient, and/or under conditions simulating the depolarized state. In normal Krebs, DPH does not seem to stimulate the Na pump of rat tail arteries. Under such experimental conditions, our data are more suggestive of an inhibition of the Na-K ATPase. Evidence is also provided that the attenuation of contractile responses to NA in the rabbit anterior mesenteric vein, might be related to stimulation of the Na pump. Further studies were done to outline the effect of alteration of other parameters of Na transport in vascular smooth muscles. Ouabain and ethacrynic acid, both inhibitors of the Na-K ATPase, produced a characteristic pattern of response in the rabbit anterior mesenteric vein. There was at first a contraction, followed by relaxation, which was followed by more persistent contractures at higher doses. The diuretic agent, amiloride, which is reported to inhibit the passive Na influx in a variety of tissues, was found to attenuate contractile responses to NA in rabbit aortic strips, A.M.V., and rat tail arteries. In aortic strips its effect was specific on the rapid phase of NA contraction. Since the rapid phase is believed to be the result f the release of a more tightly bound Ca⁺⁺ pool, the latter effect suggests that amiloride affects mainly the availability of a bound Ca pool to the contractile protein. Our results so far suggest that alteration of different parameters of the Na transport might be involved in altering the amount of ionized Ca⁺⁺ available to the contractile protein. More studies on this subject are needed and might open the way for a better understanding of the Na-Ca interaction in vascular smooth muscles and their possible relation to the hypertensive state. Further experiments were done to study the relaxation of the rabbit anterior mesenteric vein following contractile responses. It seems that extracellular Na is involved in the relaxation of the rabbit anterior mesenteric vein following contractile responses, since this tissue, when contracted in low Na solutions, would not relax unless some of the Na is returned to the Krebs solution. Li could not substitute for Na in this function since the contracture occurred in low Na solutions irrespective of whether the substitute was Tris-HCl or Li. the latter was even more effective than Tris-HCl in inducing contractures in low Na Krebs. Moreover, relaxation of the rabbit anterior mesenteric vein, following contractile responses to NA was delayed in low Na Krebs irrespective of whether the substitute was Li or Tris-HCl. Preliminary electron microscopic studies were carried on rabbit anterior mesenteric veins to evaluate the effect of the inhibitors of the ATPase, ethacrynic acid and ouabain, on ultrastructure. Both drugs induced disruption of the myofibrillar structures in doses of 1 mM and 10⁻⁵ M, respectively, when the tissue was exposed to the drug for 2 hours. An impressive finding was the dramatic diminution in the number of plasma-lemmal vesicles in the ethacrynic acid treated tissue. This finding raises the possibility that the formation of these vesicles might be an energy dependent process and opens the way for further studies to evaluate their possible importance in active ionic transport processes. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

There are two opposing schools of thought concerning the source of calcium ions for the initiation and maintenance of contractions of smooth muscle. Bohr (1964) and Woodward et al. (1970) believe that the calcium for the initiation of contraction is released from bound intracellular stores, whereas Somlyo et al. (1969) believe that most of the activator calcium comes from the extracellular fluid. It was felt that the determination of the source(s) and sink(s) of calcium ions in arteriolar smooth muscle would be required for an understanding of the control of peripheral blood pressure, and so experiments to obtain this information were carried out using the rabbit anterior mesenteric portal vein as a model of arteriolar smooth muscle. Spontaneous contractions of the vein stop within one minute after the addition of EGTA to the bath and can be returned by simply raising the extracellular calcium concentration. The addition of 1 mM MnC1₂, or raising the MgC1₂ concentration above 5 mM, or raising the CaC1₂ concentration above 10 mM all inhibit spontaneous activity; this inhibition can be rapidly reversed by the addition of appropriate amounts of EGTA. The removal of free extracellular calcium either by adding EGTA or placing the vein in calcium-free solution inhibits the responses to all agonists within five minutes. If the calcium concentration is reduced from 2.5 mM to 0.1 mM, the responses to agonists are greatly decreased. If one sets the response in normal Kreb's solution to each concentration of agonist equal to 100 per cent, then the relative reduction of responses in low calcium solution is inversely proportional to both the potency and concentration of the agonist used. If, however, one produces contractions by adding calcium to tissues bathed in calcium-free solution containing noradrenaline, then the curves of the relative response versus calcium concentrations are independent of the concentration of noradrenaline. The addition of either EGTA or manganese to a tissue already contracted in response to any agonist produces a rapid relaxation to a decreased, but sustained tension. The degree of relaxation is proportional to the concentration of manganese or EGTA added. The addition of manganese is also able to inhibit the initiation of responses to noradrenaline, KC1, serotonin, histamine and procaine. The inhibition by manganese of the responses to noradrenaline, KC1, and serotonin but not histamine and procaine can be reversed by increasing the extracellular calcium concentration. The addition of MnC1₂ or LaCl₃ does not selectively inhibit a slow phase of the contraction to noradrenaline in the mesenteric portal vein as it does in aorta (Van Breeman, 1969). The effect of adding MnCl₂ is similar to the effect of decreasing extracellular calcium, in that the relative inhibition of response is inversely proportional to the potency and concentration of agonist used. The effect of altering pH is the same on contractions produced by each agonist tested; lowering the pH below 7.4 inhibits the responses, raising it above pH 7.4 potentiates the responses. If the vein is placed in calcium-free solution containing EGTA for 10 minutes, the addition of CaC1₂ produces a contraction. The response to calcium is transient unless the final concentration of the added calcium is 5 mM or greater; at these higher calcium concentrations the response is biphasic; an initial transient response is followed by a slow tonic response. The addition of stock solutions to produce final concentrations of 5 mM Mg⁺⁺ or 0.5 mM Mn⁺⁺ or 0.1 mM Ca⁺⁺ in the bath after the EGTA treatment abolishes the transient responses to calcium but has little effect on the tonic portion of a contraction produced by 10 mM Ca⁺⁺. When these EGTA experiments are carried out in low sodium solution (17% of normal or less) the response to 2.5 mM Ca⁺⁺ which is normally transient, becomes instead a sustained contraction. It is concluded then that: 1. Calcium ions themselves are able to control the permeability of the membrane to calcium. 2. The initiation of responses to all agonists probably involves the release of membrane-bound calcium and the influx of extracellular calcium. Differences in efficacy are probably due to differences in ability to release the membrane-bound calcium. 3. A continued influx of calcium is required to maintain a contraction produced by any agonist. 4. Manganese competes with calcium at a membrane site to inhibit the initiation of contraction, and to relax a tissue which is already contracted. 5. Responses to all agonists are potentiated at a pH greater than 7.4, and decreased below pH 7.4. 6. The relaxation process in the mesenteric-portal vein seems to depend in some manner upon extracellular sodium ions. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

Large populations of controlled hybrids are essential to the most rapid progress in many phases of plant breeding programs. Plant species vary in the ease with which they may be hybridized. Hand hybridization of forage grasses is usually slow and laborious, and the minuteness of the floral parts of most of the species which have perfect flowers renders their hybridization by hand especially difficult and tedious. This difficulty limits the use that forage grass breeders are making of the significant principles of hybridization and thereby retards progress in this phase of plant breeding. Any dependable, rapid technique of hybridization which would eliminate many of the present hand operations, that is "bulk" hybridization, would make possible more rapid progress in the breeding of forage grasses. The study herein reported was designed to estimate the feasibility of applying various methods of bulk emasculation and bulk pollination to forage grasses. In limiting the scope of the study, smooth bromegrass (Bromus inermis) was selected to receive the greatest attention because of its importance among forage grasses and the wide range of self-fertility among individual plants of the species, a characteristic which proved very helpful in the study.

In U.S. America and much of the Western world, natural is a venerated symbolic placeholder for any number of assumed virtues and ideals. Present conflicts have brought forward questions about what natural (which I argue functions as an ideograph) should mean in contexts that seem to call for a formal, enforceable definition. In this study, I use the vocabulary of Deleuze and Guattari (1987) and the context of bodybuilding to work towards a theory of how ambiguous ideographs become "striated" or “crystallized.” Within this discussion I present instances where natural has been employed as a vehicle to cause harm, and I offer an advisement to rhetorical scholars on how we might approach striated ideographs in the future.

Obesity is a major risk factor for insulin resistance, type 2 diabetes, cardiovascular disease (CVD), and vascular calcification. Vascular calcification is correlated with advanced CVD and a significant predictor of cardiovascular events. Obese individuals tend to have increased levels of circulating leptin, an adipocytokine that is a significant independent predictor of cardiovascular disease. We have shown that daily intraperitoneal injections of exogenous leptin (125 μg/mouse/d) can promote vascular calcification in an ApoE-/- mouse model of atherosclerosis. This increase in calcification is associated with an increase in the expression of several osteoblast-specific markers and is independent of any affect on atherosclerotic lesion size. Our studies suggest that leptin mediates the osteogenic differentiation of vascular smooth muscle cells (VSMCs) to promote vascular calcification via a pathway involving the inhibition of glycogen synthase kinase (GSK)-3 activity. Other studies have suggested that endoplasmic reticulum (ER) stress-induced GSK-3 activity promotes the development of atherosclerosis. Therefore, we hypothesized that during the progression of vascular disease, GSK-3 functions as a checkpoint for VSMCs at which cells can commit to: i) de-differentiation, thereby contributing to atherosclerosis, or ii) osteogenic differentiation, thereby contributing to vascular calcification. We investigated the effects of modulating GSK-3 activity on the differentiation of VSMCs in vitro. We found that many of the molecular tools that are typically used to modulate ER stress can promote the expression of osteoblast-specific markers and the osteogenic differentiation of MOVAS cells. However, because many of these interventions affect multiple pathways in MOVAS cells, the specific role of the ER stress – GSK-3 pathway is difficult to discern. Future studies are required to determine the effects of direct modulation of GSK-3 on vascular calcification and to delineate the mechanisms/effects of various ER stressors in the osteogenic differentiation of VSMCs. / Thesis / Doctor of Philosophy (Medical Science)

Mobility models serve as the foundation for evaluating and designing airborne networks. Due to the significant impact of mobility models on the network performance, mobility models for airborne networks (ANs) must realistically capture the attributes of ANs. In this paper, I develop a comprehensive modeling framework for ANs. The work I have done is concluded as the following three parts. First, I perform a comprehensive and comparative analysis of AN mobility models and evaluate the models based on several metrics: 1) networking performance, 2) ability to capture the mobility attributes of ANs, 3) randomness levels and 4) associated applications. Second, I develop two 3D mobility models and realistic boundary models. The mobility models follow physical laws behind aircraft maneuvering and therefore capture the characteristics of aircraft trajectories. Third, I suggest an estimation procedure to extract parameters in one of the models that I developed from real flight test data. The good match between the estimated trajectories and real flight trajectories also validate the suitability of the model. The mobility models and the estimation procedure lead to the creation of “realistic” simulation and evaluation environment for airborne networks.

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