373 research outputs found

    Sensitivity of the Exporting Economy on the External Shocks: Evidence from Slovene Firms

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    In this paper we investigate the export participation of Slovene firms. We first show that sunk costs are an important factor for explaining the export behavior of Slovene firms. Next we show that when the absorption power of the exporting market declines, firms still trade with their established buyers (hysteresis) despite the fact that due to lower prices their exporting revenues decline. We show that this can be explained with high exit costs, which consist of switching costs (costs of replacing stable buyers with new ones) and cost of reducing the production (compensation money for excess workers) and high re-entry costs.http://deepblue.lib.umich.edu/bitstream/2027.42/40020/3/wp634.pd

    Assessing Alkali-Metal Effects in the Structures and Reactivity of Mixed-Ligand Alkyl/Alkoxide Alkali-Metal Magnesiates

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    Advancing the understanding of using alkali‐metal alkoxides as additives to organomagnesium reagents in Mg−Br exchange reactions, a homologous series of mixed‐ligand alkyl/alkoxide alkali‐metal magnesiates [MMg(CH(2)SiMe(3))(2)(dmem)](2) [dmem=2‐{[2‐(dimethylamino)ethyl]methylamino} ethoxide; M=Li, 1; Na, 2; (THF)K, 3] has been prepared. Structural and spectroscopic studies have established the constitutions of these heteroleptic/heterometallic species, which are retained in arene solution. Evaluation of their reactivity towards 2‐bromoanisole has uncovered a marked alkali‐metal effect with potassium magnesiate 3 being the most efficient of the three ate reagents. Studies probing the constitution of the exchange product from this reaction suggest that the putative [KMgAr(2)(dmem)](2) (Ar=o‐OMe−C(6)H(4)) intermediate undergoes redistribution into its single metal components [KAr](n) and [MgAr(dmem)](2) (5). This process can be circumvented by using a different potassium alkoxide containing an aliphatic chain such as KOR’ (R’=2‐ethylhexyl) which undergoes co‐complexation with Mg(CH(2)SiMe(3)) to give [KMg(CH(2)SiMe(3))(2)(OR’)](2) (7). This ate, in turn, reacts quantitatively with 2‐bromoanisole furnishing [KMgAr(2)(OR’)](2) (9) which is stable in solution as a bimetallic compound. Collectively this work highlights the complexity of these alkali‐metal mediated Mg−Br exchange reactions, where each reaction component can have a profound effect not only on the success of the reaction; but also the stability of the final metalated intermediates prior to their electrophilic interception

    Dietary nitrate-induced increases in human muscle power: High versus low responders

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    Maximal neuromuscular power is an important determinant of athletic performance and also quality of life, independence, and perhaps even mortality in patient populations. We have shown that dietary nitrate (NO3- ), a source of nitric oxide (NO), improves muscle power in some, but not all, subjects. The present investigation was designed to identify factors contributing to this interindividual variability. Healthy men (n = 13) and women (n = 7) 22-79 year of age and weighing 52.1-114.9 kg were studied using a randomized, double-blind, placebo-controlled, crossover design. Subjects were tested 2 h after ingesting beetroot juice (BRJ) either containing or devoid of 12.3 ± 0.8 mmol of NO3- . Plasma NO3- and nitrite (NO2- ) were measured as indicators of NO bioavailability and maximal knee extensor speed (Vmax ), power (Pmax ), and fatigability were determined via isokinetic dynamometry. On average, dietary NO3- increased (P < 0.05) Pmax by 4.4 ± 8.1%. Individual changes, however, ranged from -9.6 to +26.8%. This interindividual variability was not significantly correlated with age, body mass (inverse of NO3- dose per kg), body mass index (surrogate for body composition) or placebo trial Vmax or fatigue index (in vivo indicators of muscle fiber type distribution). In contrast, the relative increase in Pmax was significantly correlated (r = 0.60; P < 0.01) with the relative increase in plasma NO2- concentration. In multivariable analysis female sex also tended (P = 0.08) to be associated with a greater increase in Pmax. We conclude that the magnitude of the dietary NO3- -induced increase in muscle power is dependent upon the magnitude of the resulting increase in plasma NO2- and possibly female sex

    Synthesis and biological evaluation of novel pyrazole derivatives as urease inhibitors

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    Studies on enzyme inhibition remain an important area of pharmaceutical research since these studies have led to the discoveries of drugs useful in a variety of physiological conditions. The enzyme inhibitors can interact with enzymes and block their activity towards natural substrates. Urease inhibitors have recently attracted much attention as potential new anti-ulcer drugs. A series of novel substituted pyrazoles 8(a-j) has been synthesized by diazotization of fluoro chloro aniline (1) and the reaction of the corresponding diazonium salt solution (2) with ethyl cyanoacetate (3) to give the intermediate, ethyl 2-((3-chloro-4-fluorophenyl) diazenyl-2- cyanoacetate (4). The intermediate is then cyclised with chloroacetonitrile (5) using triethyl amine as the base to give the final compound, ethyl 4-amino-1-(3-chloro-4-flurophenyl)-5- cyano-1H-pyrazole-3-carboxylate (6). Nucleophilic substitution group is removed from the final compound and 8(a-j) derivatives have been synthesized. All the synthesized compounds were characterized by physical data (M.P. & TLC) and spectral Data (IR & 1H NMR). The synthesized compounds were evaluated for urease-inhibition activity. Molecular docking studies were carried out for these compounds with the enzyme urease. From the observations it has been noticed that some of the compounds possesses remarkable urease-inhibitory effect

    Magnesium-mediated arylation of amines via C-F bond activation of fluoroarenes

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    A series of new Mg(II) amides featuring a bulky β-diketiminate backstop ligand, has been synthesised. These complexes are demonstrated to be excellent sources of nucleophilic amides that can participate in rapid C–F activation of several fluoroarenes at room temperature or using microwave assistance, leading to the installment of synthetically important C–N bonds via nucleophilic substitution

    Preparation of polyfunctional arylzinc organometallics in toluene by halogen/zinc exchange reactions

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    A wide range of polyfunctional diaryl-and diheteroarylzinc species were prepared in toluene within 10 min to 5 h through an I/Zn or Br/Zn exchange reaction using bimetallic reagents of the general formula R’2Zn·2LiOR (R’=sBu, tBu, pTol). Highly sensitive functional groups, such as a triazine, a ketone, an aldehyde, or a nitro group, were tolerated in these exchange reactions, enabling the synthesis of a plethora of functionalized (hetero)arenes after quenching with various electrophiles. Insight into the constitution and reactivity of these bimetallic mixtures revealed the formation of highly active lithium diorganodialkoxyzincates of type[R’2Zn-(OR)2Li2]

    Exploiting Coordination Effects for the Regioselective Zincation of Diazines Using TMPZnX⋅LiX (X=Cl, Br)

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    A new method for regioselective zincations of challenging N-heterocyclic substrates such as pyrimidines and pyridazine was reported using bimetallic bases TMPZnX⋅LiX (TMP=2,2,6,6-tetramethylpiperidyl; X=Cl, Br). Reactions occurred under mild conditions (25-70 °C, using 1.75 equivalents of base without additives), furnishing 2-zincated pyrimidines and 3-zincated pyridazine, which were then trapped with a variety of electrophiles. Contrasting with other s-block metalating systems, which lack selectivity in their reactions even when operating at low temperatures, these mixed Li/Zn bases enabled unprecedented regioselectivities that cannot be replicated by either LiTMP nor Zn(TMP)2 on their own. Spectroscopic and structural interrogations of organometallic intermediates involved in these reactions have shed light on the complex constitution of reaction mixtures and the origins of their special reactivities

    Pharmacokinetics of ibuprofen in man. I. Free and total area/dose relationships

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110022/1/cptclpt1983136.pd

    Dietary Nitrate Increases VO2peak and Performance but Does Not Alter Ventilation or Efficiency in Patients With Heart Failure With Reduced Ejection Fraction

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    Background Patients with heart failure with reduced ejection fraction (HFrEF) exhibit lower efficiency, dyspnea, and diminished peak oxygen uptake (VO2peak) during exercise. Dietary nitrate (NO3−), a source of nitric oxide (NO), has improved these measures in some studies of other populations. We determined the effects of acute NO3− ingestion on exercise responses in 8 patients with HFrEF using a randomized, double-blind, placebo-controlled, crossover design. Methods and Results Plasma NO3−, nitrite (NO2−), and breath NO were measured at multiple time points and respiratory gas exchange was determined during exercise after ingestion of beetroot juice containing or devoid of 11.2 mmol of NO3−. NO3− intake increased (P < .05–0.001) plasma NO3− and NO2− and breath NO by 1469 ± 245%, 105 ± 34%, and 60 ± 18%, respectively. Efficiency and ventilation during exercise were unchanged. However, NO3− ingestion increased (P < .05) VO2peak by 8 ± 2% (ie, from 21.4 ± 2.1 to 23.0 ± 2.3 mL.min−1.kg−1). Time to fatigue improved (P < .05) by 7 ± 3 % (ie, from 582 ± 84 to 612 ± 81 seconds). Conclusions Acute dietary NO3− intake increases VO2peak and performance in patients with HFrEF. These data, in conjunction with our recent data demonstrating that dietary NO3− also improves muscle contractile function, suggest that dietary NO3− supplementation may be a valuable means of enhancing exercise capacity in this population

    Cell Elasticity Determines Macrophage Function

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    Macrophages serve to maintain organ homeostasis in response to challenges from injury, inflammation, malignancy, particulate exposure, or infection. Until now, receptor ligation has been understood as being the central mechanism that regulates macrophage function. Using macrophages of different origins and species, we report that macrophage elasticity is a major determinant of innate macrophage function. Macrophage elasticity is modulated not only by classical biologic activators such as LPS and IFN-γ, but to an equal extent by substrate rigidity and substrate stretch. Macrophage elasticity is dependent upon actin polymerization and small rhoGTPase activation, but functional effects of elasticity are not predicted by examination of gene expression profiles alone. Taken together, these data demonstrate an unanticipated role for cell elasticity as a common pathway by which mechanical and biologic factors determine macrophage function
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