Covalent chemical modification of self- assembled fluorocarbon monolayers by low- energy CH<SUB>2</SUB>Br<SUB>2</SUB><SUP>+&#183;</SUP> ions: a combined ion/surface scattering and X-ray photoelectron spectroscopic investigation

Specific covalent chemical modification at the outermost atomic layers of fluorinated self-assembled monolayers (F-SAMs) on gold is achieved by bombardment with low-energy polyatomic ions (&lt;100 eV). The projectile ion CH2Br2+&#183; (m/z 172), mass and energy selected using a hybrid ion/surface scattering mass spectrometer and scattered from the F-SAM surface, CF3(CF2)7(CH2)2-S-Au, undergoes ion/surface reactions evident from the nature of the scattered ions, CH2F+ (m/z 33), CHBrF+ (m/z 111), and CF2Br+ (m/z 129). The chemical transformation of the reactive F-SAM surface was independently monitored by in situ chemical sputtering with the projectile Xe+&#183;. Representative species sputtered from the modified surface include CF2Br+, an indicator of terminal CF3 to CF2Br conversion. X-ray photoelectron spectroscopy (XPS) was used to confirm the presence of organic bromine at the surface; Br (3P3/2) and Br (3P&#189;) peaks were present at binding energies of 182 and 190 eV, respectively. XPS analysis also revealed increased surface modification at higher collision energies in these reactive ion bombardment experiments, as exemplified by the increased hydrocarbon/fluorocarbon peak ratio in the C(1s) region and incorporation of oxygen in the surface seen in the observation of an O(1s) peak

Evidence for a differential contribution of early perceptual and late cognitive processes during encoding to episodic memory impairment in schizophrenia

Objectives: Schizophrenia is characterised by significant episodic memory impairment that is thought to be related to problems with encoding, however the neuro-functional mechanisms underlying these deficits are not well understood. The present study used a subsequent recognition memory paradigm and event-related potentials (ERPs) to investigate temporal aspects of episodic memory encoding deficits in schizophrenia. Methods: Electroencephalographic data was recorded in 24 patients and 19 healthy controls whilst participants categorised single words as pleasant/unpleasant. ERPs were generated to subsequently recognised versus unrecognised words on the basis of a forced-choice recognition memory task. Subsequent memory effects were examined with the late positive component (LPP). Group differences in N1, P2, N400 and LPP were examined for words correctly recognised. Results: Patients performed more poorly than controls on the recognition task. During encoding patients had significantly reduced N400 and LPP amplitudes than controls. LPP amplitude correlated with task performance however amplitudes did not differ between patients and controls as a function of subsequent memory. No significant differences in N1 or P2 amplitude or latency were observed. Conclusions: The present results indicate that early sensory processes are intact and dysfunctional higher order cognitive processes during encoding are contributing to episodic memory impairments in schizophrenia

Assessment of cognitive safety in clinical drug development

Cognitive impairment is increasingly recognised as an important potential adverse effect of medication. However, many drug development programmes do not incorporate sensitive cognitive measurements. Here, we review the rationale for cognitive safety assessment, and explain several basic methodological principles for measuring cognition during clinical drug development, including study design and statistical analysis, from Phase I through to postmarketing. The crucial issue of how cognition should be assessed is emphasized, especially the sensitivity of measurement. We also consider how best to interpret the magnitude of any identified effects, including comparison with benchmarks. We conclude by discussing strategies for the effective communication of cognitive risks

Normalization of Sequential Top-Down Tree-to-Word Transducers

International audienceWe study normalization of deterministic sequential top-down tree-to-word transducers (STWs), that capture the class of deterministic top-down nested-word to word transducers. We identify the subclass of earliest STWs (eSTWs) that yield normal forms when minimized. The main result of this paper is an effective normalization procedure for STWs. It consists of two stages: we first convert a given STW to an equivalent eSTW, and then, we minimize the eSTW. Keywords: formal language theory, tree automata, transformations, XML databases, XSLTExtended Version: A long version is available here.</p

The novel mu-opioid antagonist, GSK1521498, reduces ethanol consumption in C57BL/6J mice.

RATIONALE Using the drinking-in-the-dark (DID) model, we compared the effects of a novel mu-opioid receptor antagonist, GSK1521498, with naltrexone, a licensed treatment of alcohol dependence, on ethanol consumption in mice. OBJECTIVE We test the ability of GSK1521498 to reduce alcohol consumption and compare its intrinsic efficacy to that of naltrexone by comparing the two drugs at doses matched for equivalent receptor occupancy. METHODS Thirty-six C57BL/6J mice were tested in a DID procedure. In 2-day cycles, animals experienced one baseline, injection-free session, and one test session when they received two injections, one of test drug and one placebo. All animals received GSK1521498 (0, 0.1, 1 and 3 mg/kg, i.p., 30 min pre-treatment) and naltrexone (0, 0.1, 1 and 3 mg/kg, s.c. 10 min pre-treatment) in a cross-over design. Receptor occupancies following the same doses were determined ex vivo in separate groups by autoradiography, using [3H]DAMGO. Binding in the region of interest was measured integrally by computer-assisted microdensitometry and corrected for non-specific binding. RESULTS Both GSK1521498 and naltrexone dose-dependently decreased ethanol consumption. When drug doses were matched for 70-75 % receptor occupancy, GSK1521498 3 mg/kg, i.p., caused a 2.5-fold greater reduction in alcohol consumption than naltrexone 0.1 mg/kg, s.c. Both GSK1521498 and naltrexone significantly reduced sucrose consumption at a dose of 1 mg/kg but not 0.1 mg/kg. In a test of conditioned taste aversion, GSK1521498 (3 mg/kg) reduced sucrose consumption 24 h following exposure to a conditioning injection. CONCLUSIONS Both opioid receptor antagonists reduced alcohol consumption but GK1521498 has higher intrinsic efficacy than naltrexone

Neurochemical enhancement of conscious error awareness

How the brain monitors ongoing behavior for performance errors is a central question of cognitive neuroscience. Diminished awareness of performance errors limits the extent to which humans engage in corrective behavior and has been linked to loss of insight in a number of psychiatric syndromes (e.g., attention deficit hyperactivity disorder, drug addiction). These conditions share alterations in monoamine signaling that may influence the neural mechanisms underlying error processing, but our understanding of the neurochemical drivers of these processes is limited.Weconducted a randomized, double-blind, placebo-controlled, cross-over design of the influence of methylphenidate, atomoxetine, and citalopram on error awareness in 27 healthy participants. The error awareness task, a go/no-go response inhibition paradigm, was administered to assess the influence of monoaminergic agents on performance errors during fMRI data acquisition. A single dose of methylphenidate, but not atomoxetine or citalopram, significantly improved the ability of healthy volunteers to consciously detect performance errors. Furthermore, this behavioral effect was associated with a strengthening of activation differences in the dorsal anterior cingulate cortex and inferior parietal lobe during the methylphenidate condition for errors made with versus without awareness. Our results have implications for the understanding of the neurochemical underpinnings of performance monitoring and for the pharmacological treatment of a range of disparate clinical conditions that are marked by poor awareness of errors