Identification of an unknown b-agonist in feed by liquid chromatography/bioassay/quadrupole time-of-flight tandem mass spectrometry with accurate mass measurement.

A new approach to the search for residues of unknown growth promoting agents such as anabolic steroids and -agonists in feed is presented. Following primary extraction and clean-up, samples are separated using gradient liquid chromatography (LC). The effluent is split towards two identical 96-well fraction collectors and an optional electrospray quadrupole time-of-flight mass spectrometry (QTOFMS) system for accurate mass measurement. One 96-well plate is used for a bioassay (enzyme-immuno assay, receptor assay) and will detect the bioactivity and position of the relevant peak in the chromatogram. The positive well in the second 96-well plate is used for identification by LC/QTOFMS/MS. The value of this LC/bioassay/QTOFMS/MS methodology is highlighted by the finding and structure elucidation of a new -agonist in a feed extract.

On the reasons for stepwise changes in the tunnelling current across nanogaps

The role of the crystalline orientation of the STM tip in the generation of metal clusters is studied by atom dynamics simulations. When a (111) facet is facing the surface, the process is accompanied by a perturbation of the surface stronger than that observed for more open tip structures. This implies a technological application: the possibility of orienting a nanocrystallite deposited on a tip according to the changes observed in the force on the tip.

Synthesis of highly substituted pyrrolidines via palladium-catalyzed cyclization of 5-vinyloxazolidinones and activated alkenes

N-Tosyl-5,5-divinyloxazolidin-2-one undergoes a palladium-catalyzed decarboxylative cyclization across a range of electrophilic alkenes to give the corresponding pyrrolidine derivatives bearing two contiguous quaternary centres. Alkenes bearing two electron-withdrawing groups are required; pyrrolidines were not formed from mono-activated alkenes. Bulky, electron-rich phosphines promote pyrrolidine formation with less highly electrophilic, doubly activated alkenes, and a dramatic improvement is observed in the presence of iodide.

NPY and cardiac diseases

Hypertension-induced left ventricular hypertrophy (LVH), along with ischemic heart disease, result in LV remodeling as part of a continuum that often leads to congestive heart failure. The neurohormonal model has been used to underpin many treatment strategies, but optimal outcomes have not been achieved. Neuropeptide Y (NPY) has emerged as an additional therapeutic target, ever since it was recognised as an important mediator released from sympathetic nerves in the heart, affecting coronary artery constriction and myocardial contraction. More recent interest has focused on the mitogenic and hypertrophic effects that are observed in endothelial and vascular smooth muscle cells, and cardiac myocytes. Of the six identified NPY receptor subtypes, Y-1, Y-2, and Y-5 appear to mediate the main functional responses in the heart. Plasma levels of NPY become elevated due to the increased sympathetic activation present in stress-related cardiac conditions. Also, NPY and Y receptor polymorphisms have been identified that may predispose individuals to increased risk of hypertension and cardiac complications. This review examines what understanding exists regarding the likely contribution of NPY to cardiac pathology. It appears that NPY may play a part in compensatory or detrimental remodeling of myocardial tissue subsequent to hemodynamic overload or myocardial infarction, and in angiogenic processes to regenerate myocardium after ischemic injury. However, greater mechanistic information is required in order to truly assess the potential for treatment of cardiac diseases using NPY-based drugs.

Enhanced proton flux in the MeV range by defocused laser irradiation

Thin Al foils (50 nm and 6 mu m) were irradiated at intensities of up to 2x10(19) W cm(-2) using high contrast (10(8)) laser pulses. Ion emission from the rear of the targets was measured using a scintillator-based Thomson parabola and beam sampling 'footprint' monitor. The variation of the ion spectra and beam profile with focal spot size was systematically studied. The results show that while the maximum proton energy is achieved around tight focus for both target thicknesses, as the spot size increases the ion flux at lower energies is seen to peak at significantly increased spot sizes. Measurements of the proton footprint, however, show that the off-axis proton flux is highest at tight focus, indicating that a previously identified proton deflection mechanism may alter the on-axis spectrum. One-dimensional particle-in-cell modelling of the experiment supports our hypothesis that the observed change in spectra with focal spot size is due to the competition of two effects: decrease in laser intensity and an increase in proton emission area.

Immunophenotypic shift in a case of mycosis fungoides with vitreous invasion

The case of an 82-year-old man who developed intraocular extension from mycosis fungoides, a cutaneous T-cell lymphoma, is presented. The patient died soon after intra-ocular involvement occurred. Immunohistochemistry of a skin biopsy, taken early in the course of the disease, disclosed a predominance of T cells with a helper/inducer phenotype (CD4). However, an intraocular infiltrate obtained 7 years later contained mostly T cells with a suppressor/cytotoxic phenotype (CD8). The occurrence of ocular invasion, the change in immunophenotype, and the predominant proliferation of CD8 lymphocytes may have been related to the poor outcome in this patient.

Anatomy and Neurophysiology of Coughing: CHEST Guideline and Expert Panel Report

Bronchopulmonary C-fibers and a subset of mechanically sensitive, acid-sensitive myelinated sensory nerves play essential roles in regulating cough. These vagal sensory nerves terminate primarily in the larynx, trachea, carina and large intrapulmonary bronchi. Other bronchopulmonary sensory nerves, sensory nerves innervating other viscera as well as somatosensory nerves innervating the chest wall, diaphragm and abdominal musculature regulate cough patterning and cough sensitivity. The responsiveness and morphology of the airway vagal sensory nerve subtypes and the extrapulmonary sensory nerves that regulate coughing are described. The brainstem and higher brain control systems that process this sensory information are complex, but our current understanding of them is considerable and increasing. The relevance of these neural systems to clinical phenomena, such as urge to cough and psychological methods for treatment of dystussia, is high and modern imaging methods have revealed potential neural substrates for some features of cough in the human.