Muscular dystrophy: from gene to patient

4. Conclusions Altered expression of dystrophin led to a reduction in the myocardial PCr to ATP ratio in MD carriers and BMD patients. Decreased myocardial PCr was also observed in the mouse model of MD, themdx mouse, which had decreased myocardial glucose uptake in response to insulin and during ischaemia, with increased susceptibility to ischaemic damage. However, utrophin transgene expression corrected the functional and metabolic abnormalities in the dystrophin-deficient mouse heart. To our knowledge, this is the first report of beneficial effects resulting from the expression of a dystrophin-related transgene in heart, making the findings important for the use of gene therapy in the treatment of cardiomyopathy in dystrophic patients.     

Report of the FEAC Inertial Fusion Energy Review Panel: July 1996

This report presents the results and recommendations of the U. S. Department of Energy Fusion Energy Advisory Committee (FEAC) review of its Inertial Fusion Energy (IFE) program. The subpanel charged with the review was chaired by John Sheffield of Oak Ridge National Laboratory. The FEAC, to which the subpanel reported, was chaired by Robert Conn of the University of California at San Diego.     

Lexical ambiguity resolution in good and poor comprehenders: An eye fixation and self-paced reading study in primary school children.

To investigate the use of context and monitoring of comprehension in lexical ambiguity resolution in children, the authors asked 10- to 12-year-old good and poor comprehenders to read sentences consisting of 2 clauses, 1 containing the ambiguous word and the other the disambiguating information. The order of the clauses was reversed so that disambiguating information either preceded or followed the ambiguous word. Context use and comprehension monitoring were examined by measuring eye fixations (Experiment 1) and self-paced reading times (Experiment 2) on the ambiguous word and disambiguating region. The results of Experiment 1 and 2 showed that poor comprehenders made use of prior context to facilitate lexical ambiguity resolution as effectively as good comprehenders but that they monitored their comprehension less effectively than good comprehenders. Good comprehenders corrected an initial interpretation error on an ambiguous word and restored comprehension once they encountered the disambiguating region. Poor comprehenders failed to deal with this type of comprehension failure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Semantic priming in fully recurrent network models of lexical knowledge.

The claim that A E. Masson's (1995) model of lexical knowledge provides an account of semantic priming is evaluated in a series of simulations. It was found that although a semantically unrelated prime produces slower simulated naming of the target word than a related prime, the difference reflects interference by the unrelated prime and not facilitation by the related prime, which has little absolute effect. The facilitation reported by Masson was produced by the simulated "neutral" stimulus that intervened between prime and target, not by the semantically related prime. Simulations of a stochastic variant of Masson's model and a "brain-state-in-a-box" model of word naming also failed to produce semantic facilitation, raising the possibility that in fully connected recurrent networks, facilitation does not occur via indirect collateral pathways. Methodological implications for evaluating priming in simulated networks are raised. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tunnel emission into an insulating film with traps

The effect of space charge and traps on the current density of electrons tunnelling from a metal into the conduction band of an insulating film is calculated for the case of very low free carrier mobility in the insulator. It is shown that free carrier space charge is ineffective in lowering the tunnelling current even for extremely low free carrier mobility but that a high trap density can severely limit the tunnel current density.     

Dismantling motivational interviewing and feedback for college drinkers: A randomized clinical trial.

Motivational interviewing (MI) is a counseling style that has been shown to reduce heavy drinking among college students. To date, all studies of MI among college students have used a format that includes a feedback profile delivered in an MI style. This study was a dismantling trial of MI and feedback among heavy-drinking college students. After an initial screen, 279 heavy-drinking students were randomized to (a) Web feedback only, (b) a single MI session without feedback, (c) a single MI session with feedback, or (d) assessment only. At 6 months, MI with feedback significantly reduced drinking, as compared with assessment only (effect size = .54), MI without feedback (effect size = .63), and feedback alone (effect size = .48). Neither MI alone nor feedback alone differed from assessment only. Neither sex, race or ethnicity, nor baseline severity of drinking moderated the effect of the intervention. Norm perceptions mediated the effect of the intervention on drinking. MI with feedback appears to be a robust intervention for reducing drinking and may be mediated by changes in normative perceptions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Protein Chemical Synthesis Combined with Mirror-Image Phage Display Yields d-Peptide EGF Ligands that Block the EGF–EGFR Interaction

The epidermal growth factor (EGF) pathway, being overactive in a number of cancers, is a good target for clinical therapy. Although several drugs targeting the EGF receptor (EGFR) are on the market, tumours acquire resistance very rapidly. As an alternative, small molecules and peptides targeting EGF have been developed, although with moderate success. Herein, we report the use of mirror-image phage display technology to discover protease-resistant peptides with the capacity to inhibit the EGF–EGFR interaction. After the chemical synthesis of the enantiomeric protein d -EGF, two phage-display peptide libraries were used to select binding sequences. The d versions of these peptides bound to natural EGF, as confirmed by surface acoustic waves (SAWs). High-field NMR spectroscopy showed that the best EGF binder, d -PI_4, interacts preferentially with an EGF region that partially overlaps with the receptor binding interface. Importantly, we also show that d -PI_4 efficiently disrupts the EGF–EGFR interaction. This methodology represents a straightforward approach to find new protease-resistant peptides with potential applications in cancer therapy.     

Reducing conduct problems among children exposed to intimate partner violence: A randomized clinical trial examining effects of Project Support.

This study was a randomized clinical trial of Project Support, an intervention designed to reduce conduct problems among children exposed to intimate partner violence. Participants were 66 families (mothers and children) with at least 1 child exhibiting clinical levels of conduct problems. Families were recruited from domestic violence shelters. The Project Support intervention involves (a) teaching mothers child management skills and (b) providing instrumental and emotional support to mothers. Families were randomly assigned to the Project Support intervention condition or to an existing services comparison condition. They were assessed on 6 occasions over 20 months, following their departure from the shelter. Children in families in the Project Support condition, compared with those in the comparison condition, exhibited greater reductions in conduct problems. Mothers in the Project Support condition, compared with those in the comparison condition, displayed greater reductions in inconsistent and harsh parenting behaviors and psychiatric symptoms. Changes in mothers’ parenting and psychiatric symptoms accounted for a sizable proportion of Project Support’s effects on child conduct problems at the end of treatment. Clinical and policy implications are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)