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In human subjects, chronic beta2-agonist dosing reduces mononuclear leukocyte (MNL) beta-adrenoceptor numbers. The aim of this study was to investigate whether this downregulation also occurs in the lung. Seven healthy male subjects were treated for 2 wk with oral (up to 16 mg/d) and inhaled (up to 1.6 mg/d) albuterol (salbutamol in Europe). Pulmonary maximal beta-adrenoceptor binding capacity (Bmax) was determined in vivo using positron emission tomography (PET) and the beta-receptor antagonist ligand, 11C-labeled CGP-12177, before and after the 2-wk chronic dosing. MNL Bmax was also measured, using a radioligand binding assay and 3H-labeled CGP-12177. Bronchodilator responses to the beta2-agonist were determined after each PET scan by measuring the change in specific airway conductance (SGaw) after increasing doses of inhaled albuterol. Pulmonary and MNL Bmax fell by 22% +/- 14% (p < 0.05) and 42% +/- 19% (p < 0.05) respectively. The changes in pulmonary and MNL Bmax were correlated (r = 0.9, p < 0.05). There was also a reduction in the bronchodilator response to inhaled albuterol. In a further six subjects, pulmonary and MNL Bmax did not change during an acute infusion of albuterol (2 to 4 microg/kg/h). The reduction in pulmonary beta-adrenoceptor numbers after chronic albuterol dosing may be predictable from the changes observed in circulating MNL cells.

Ionesco’s surrealism, or, more precisely, Theatre of the Absurd, is a homeopathic remedy for twentieth-century madness. It works by giving us controlled doses of the insanities that we have engendered to stimulate our own defence systems and so bring us to heal ourselves. The experiencing of Ionesco engages us in madness to bring us to sanity.

Chemical stress relaxation methods are employed to study chemical and mechanical factors influencing the degradation of uncoated polyglycolic (PG) sutures. Specially constructed instrumentation is used to study the kinetics of the load bearing capability of PG (Dexon¿) 3-0 sutures in hydrolytic solution. The effects of pH, temperature, strain rate, and initial load on the rate of chemical stress relaxation are presented. Data show how mechanical factors such as the rate of loading (related to the speed of knot tying), as well as the final tension, are related to the rate of structural degradation. Maximum stability is observed at approximately 40 degrees C, with slower degradation both above and below this point. Results show that the slower and tighter the suture is pulled, the greater its ability to sustain tensile loads during hydrolysis.

The emergence of functional genomics and proteomics has added to the growing need for improved analysis methods that can detect and distinguish between protein variants resulting from allelic variation, mutation, or post-translational modification. Aptamers, single-stranded DNA or RNA molecules that fold into three-dimensional structures conducive to binding targets, have become an attractive alternative to antibodies for this type of analysis. Although aptamers have been developed for a wide range of target species, very few sequences have been identified that bind selectively to proteins with specific post-translational modifications. Using capillary electrophoresis-based selection, we have developed DNA aptamer sequences that selectively bind an N-glycosylated peptide fragment of vascular endothelial growth factor (VEGF). The selection method incorporates alternating positive- and counter-selection steps in free solution in order to obtain aptamers with both high affinity toward the glycosylated target and high selectivity versus a non-glycosylated variant. Affinity capillary electrophoresis and surface plasmon resonance binding assays indicate these sequences have low-µM dissociation constants and preferentially bind the glycosylated peptide with as much as 50-fold specificity. Such aptamers could serve as tools for rapid and simple monitoring of disease-linked functional changes in proteins, with potential applications in drug screening and disease diagnosis.

‘Your name is David Cornwell?’‘Yes … and no’. ‘Yes and no? What does that mean?’ ‘My name is David Conrwell, but you as critic are interested only in John le Carre, my other name’. ‘You dont’t like critics’. ‘Even the word makes my whippets growl’.1. ‘Aren’t you being unfair? After all a critic might be an ideal reader, or even Eliot’s mild mannered man exercising a certain braggadocio from behind the refuge of his typewriter’. ‘Which are you?’ ‘I’m neither, I’m an interrogator. You might say my role is that of one of Bakhtin’s hoods. Something intrigues me, I start digging. At the moment my tradecraft bears the marks of my spymaster, Bakhtin. ‘How conspicuously fashionable!’ ‘Somewhat like yourself Mr le Carre conspicuously fashionable, lso like yourself disguised. Not so much a hoodlum as a hooded figure bearing an allegiance, as I have said, to Bakhtin.

Rogue Male opens with the hero stalking the leader of a foreign power at his country retreat near the Polish border.1 The assumption is usually made that the figure in question is Hitler. Perhaps it is, but Household never states that it is, and one asks, did Hitler wear waistcoats? The figure in the sights of the hunting rifle certainly does (p. 18). One might dismiss the point as fairly trivial, fictionists’ licence, and given the date of publication, just before the war in 1939, courtesy might demand circumspection.

We spend our lives interpreting, or as Barthes would say ‘reading’, not only the language but also the objects, actions and activities that constitute our environment. If somebody says they are going to have an aperitif we know they are going to have a certain kind of drink as a prelude to a meal. The use of the word ‘aperitif’ and the actual drink they choose, be it whisky, sherry or white wine and cassis, further reveals something of their lifestyle. If, moreover, they should give a self-consciously exaggerated pronunciation to the word ‘aperitif’ itself, we would suggest they are aping their own pretensions to the lifestyle announced by using the word, or even parodying that lifestyle in order to distance themselves from its social implications. They might be saying something such as ‘we like the drink but don’t want to be associated with the social conventions it implies’.

Condensation of 3,4-diethylpyrrole with 1,3-diformylindane in the presence of catalytic HBr afforded, following oxidation with FeCl3, the first example of a dicarbaporphyrin in moderate yield; this novel bridged annulene system retains a strong diamagnetic ring current in 1H NMR spectroscopy as well as a porphyrin-like UV–VIS spectrum.

The search for evidence of decadal climatic variability (DCV) has a very long history. In the past decade, a research community has coalesced around a series of roughly biennial workshops that have emphasized description of past DCV events; their causes and their “teleconnections” responsible for droughts, floods, and warm and cold spells around the world; and recently, the predictability of DCV events. Researchers studying climate change put great emphasis on prospective impacts, but the DCV community has yet to do so. To begin rectifying this deficiency, a short but ambitious workshop was convened in Waikoloa, near Kona, Hawaii, from 26–28 April 2007. This workshop, sponsored by the Center for Research on the Changing Earth System (CRCES), NOAA, the U.S. Geological Survey, and the U.S. Army Corps of Engineers, brought together climatologists and sectoral specialists representing agriculture, water resources, economics, the insurance industry, and developing country interests.

Treatment of benzocarbaporphyrin 2 with refluxing FeCl3 in CHCl3–alcohol mixtures leads to a remarkably selective oxidation at the interior carbon atom to produce dialkoxy products 5; these species show potentially valuable long wavelength absorptions in their UV–VIS spectra.

Objective To present a case of a rare pulmonary reaction to carbamazepine. Clinical features One month after starting carbamazepine therapy, a previously well 38-year-old man developed pulmonary interstitial pneumonitis associated with debilitating systemic symptoms, the cause of which was not diagnosed for a further three months. Transbronchial lung biopsy showed granulomatous inflammation consistent with an allergic drug reaction. Intervention and outcome The patient's clinical status, chest x-ray appearance and arterial blood gas tensions all normalised after withdrawal of the drug without any specific therapy. Conclusion Pneumonitis is a rare adverse reaction to carbamazepine therapy. However, awareness may reduce delays in both diagnosis and withdrawal of the drug.

In the Rocky Mountain region between central Montana and central New Mexico, sedimentologically isolated nonmarine basins were produced by basement deformation during the Laramide orogeny within the area formerly occupied by a broad Late Cretaceous foreland basin in which laterally continuous marine facies had accumulated previously. Laramide structures of varying trend and scale reflect heterogeneity of crustal strain caused by shear between the continental lithosphere and an underlying subhorizontal slab of subducted oceanic lithosphere. Laramide basins include perimeter basins along the cratonic periphery of the arcuate Laramide province, axial basins along a north-south intramontane trend, and ponded basins located farther west closer to the overthrust belt. Twelve specific stratigraphic and sedimentologic criteria for the onset, duration, and termination of Laramide deformation allow the chronology of basin development to be inferred independently for each basin. Maastrichtian initiation of Laramide deformation was approximately synchronous throughout the Laramide province, but termination of Laramide deformation was systematically diachronous from north to south between early and late Eocene time. Widespread Eocene erosion surfaces truncate syntectonic Laramide sequences and are overlain by largely volcanic and volcaniclastic post-Laramide strata of Eocene age in the north and Oligocene age in the south. Fluvial depositional systems draining toward the Great Plains were dominant in perimeter and axial basins, but ponded basins were occupied at times by large lakes that served as regional sediment traps. Paleocene drainages from ponded basins also led eastward toward the continental interior, but partly interconnected lakes that developed within several ponded basins by mid-Eocene time were either closed hydrologically, or else they drained westward into the "Tyee" paleoriver of the Pacific Northwest.

I observed and measured the orientations of common physical sedimentary structures on the beach and spit, estero, tidal channel, and inner and outer tidal flats of Bahia la Choya. The spit is characterized by wind ripples and the beach typically displays swash marks. Mudcracks typify the high marsh portions of the estero while the meandering estero channel contains ripples and megaripples. The inner and outer tidal flats are dominated by small, ebb-oriented, straight-crested to undulatory current ripples. The current ripples are often superimposed on flood-oriented ridges and runnels of the outer flat. Rill marks, tool marks, and current crescents occur sporadically. Ebb-oriented megaripples, small current ripples, and primary current lineations occur in the tidal channel.Ripple crests trend from N15E - N40E on the southern tidal flats to N10W - N20W on the northern flats. The crests roughly parallel the shoreline and are normal to tidal currents.

With just the minimum of phonological fuss we can turn GBH into GVH: Grievous Bodily Harm becomes George V. Higgins. The transformation is so easily achieved by merely turning the plosive bi-labial b into a lip-biting labio-dental v. To continue the image, the blustering explosion of physical violence, which has Bernie Morgan ‘Beatin’ the shit out of’ the kid who scratches his car is succeeded by the shrewd pragmatism of the likes of Lyle Putter, who will ‘bite [his] lower lips if necessary clean through [to] cut a fucking deal with Bernie Morgan’.1