The role of the lateral prefrontal cortex and anterior cingulate in stimulus–response association reversals

Many complex tasks require us to flexibly switch between behavioral rules, associations, and strategies. The prefrontal cerebral cortex is thought to be critical to the performance of such behaviors, although the relative contribution of different components of this structure and associated subcortical regions are not fully understood. We used functional magnetic resonance imaging to measure brain activity during a simple task which required repeated reversals of a rule linking a colored cue and a left/right motor response. Each trial comprised three discrete events separated by variable delay periods. A colored cue instructed which response was to be executed, followed by a go signal which told the subject to execute the response and a feedback instruction which indicated whether to ‘‘hold’’ or ‘‘f lip’’ the rule linking the colored cue and response. The design allowed us to determine which brain regions were recruited by the specific demands of preparing a rule contingent motor response, executing such a response, evaluating the significance of the feedback, and reconfiguring stimulus–response (SR) associations. The results indicate that an increase in neural activity occurs within the anterior cingulate gyrus under conditions in which SR associations are labile. In contrast, lateral frontal regions are activated by unlikely/unexpected perceptual events regardless of their significance for behavior. A network of subcortical structures, including the mediodorsal nucleus of the thalamus and striatum were the only regions showing activity that was exclusively correlated with the neurocognitive demands of reversing SR associations. We conclude that lateral frontal regions act to evaluate the behavioral significance of perceptual events, whereas medial frontal–thalamic circuits are involved in monitoring and reconfiguring SR associations when necessary

Changes in subcellular localization reveal interactions between human cytomegalovirus terminase subunits

BACKGROUND: During herpesvirus replication, terminase packages viral DNA into capsids. The subunits of herpes simplex virus terminase, UL15, UL28, and UL33, assemble in the cytoplasm prior to nuclear import of the complex. METHODS: To detect similar interactions between human cytomegalovirus terminase subunits, the orthologous proteins UL89, UL56, and UL51 were expressed in HEK-293 T cells (via transfection) or insect cells (via baculovirus infection) and subcellular localizations were detected by cellular fractionation and confocal microscopy. RESULTS: In both cell types, UL56 and UL89 expressed alone were exclusively cytoplasmic, whereas UL51 was ~50% nuclear. Both UL89 and UL56 became ~50% nuclear when expressed together, as did UL56 when expressed with UL51. Nuclear localization of each protein was greatest when all three proteins were co-expressed. CONCLUSIONS: These results support inclusion of UL51 as an HCMV terminase subunit and suggest that nuclear import of human cytomegalovirus terminase may involve nuclear import signals that form cooperatively upon subunit associations

Adiabatic-Nonadiabatic Transition in the Diffusive Hamiltonian Dynamics of a Classical Holstein Polaron

We study the Hamiltonian dynamics of a free particle injected onto a chain containing a periodic array of harmonic oscillators in thermal equilibrium. The particle interacts locally with each oscillator, with an interaction that is linear in the oscillator coordinate and independent of the particle's position when it is within a finite interaction range. At long times the particle exhibits diffusive motion, with an ensemble averaged mean-squared displacement that is linear in time. The diffusion constant at high temperatures follows a power law D ~ T^{5/2} for all parameter values studied. At low temperatures particle motion changes to a hopping process in which the particle is bound for considerable periods of time to a single oscillator before it is able to escape and explore the rest of the chain. A different power law, D ~ T^{3/4}, emerges in this limit. A thermal distribution of particles exhibits thermally activated diffusion at low temperatures as a result of classically self-trapped polaronic states.Comment: 15 pages, 4 figures Submitted to Physical Review

Constraining uncertainty in aerosol direct forcing

The uncertainty in present-day anthropogenic forcing is dominated by uncertainty in the strength of the contribution from aerosol. Much of the uncertainty in the direct aerosol forcing can be attributed to uncertainty in the anthropogenic fraction of aerosol in the present-day atmosphere, due to a lack of historical observations. Here we present a robust relationship between total present-day aerosol optical depth and the anthropogenic contribution across three multi-model ensembles and a large single-model perturbed parameter ensemble. Using observations of aerosol optical depth, we determine a reduced likely range of the anthropogenic component and hence a reduced uncertainty in the direct forcing of aerosol

Improving precision and reducing bias in biological surveys: estimating false-negative error rates

The use of presence/absence data in wildlife management and biological surveys is widespread. There is a growing interest in quantifying the sources of error associated with these data. We show that false-negative errors (failure to record a species when in fact it is present) can have a significant impact on statistical estimation of habitat models using simulated data. Then we introduce an extension of logistic modeling, the zero-inflated binomial (ZIB) model that permits the estimation of the rate of false-negative errors and the correction of estimates of the probability of occurrence for false-negative errors by using repeated. visits to the same site. Our simulations show that even relatively low rates of false negatives bias statistical estimates of habitat effects. The method with three repeated visits eliminates the bias, but estimates are relatively imprecise. Six repeated visits improve precision of estimates to levels comparable to that achieved with conventional statistics in the absence of false-negative errors In general, when error rates are less than or equal to50% greater efficiency is gained by adding more sites, whereas when error rates are >50% it is better to increase the number of repeated visits. We highlight the flexibility of the method with three case studies, clearly demonstrating the effect of false-negative errors for a range of commonly used survey methods

Anisotropic thermally activated diffusion in percolation systems

We present a study of static and frequency-dependent diffusion with anisotropic thermally activated transition rates in a two-dimensional bond percolation system. The approach accounts for temperature effects on diffusion coefficients in disordered anisotropic systems. Static diffusion shows an Arrhenius behavior for low temperatures with an activation energy given by the highest energy barrier of the system. From the frequency-dependent diffusion coefficients we calculate a characteristic frequency $\omega_{c}\sim 1/t_{c}$, related to the time $t_c$ needed to overcome a characteristic barrier. We find that $\omega_c$ follows an Arrhenius behavior with different activation energies in each direction.Comment: 5 pages, 4 figure

Response Modality and the Stroop Task: Are there phonological Stroop effects with manual responses?

A long-standing debate in the Stroop literature concerns whether the way we respond to the color dimension determines how we process the irrelevant dimension, or whether word processing is purely stimulus driven. Models and findings in the Stroop literature differ in their predictions about how response modes (e.g., responding manually vs. vocally) affect how the irrelevant word is processed (i.e., phonologically, semantically) and the interference and facilitation that results, with some predicting qualitatively different Stroop effects. Here, we investigated whether response mode modifies phonological facilitation produced by the irrelevant word. In a fully within-subject design, we sought evidence for the use of a serial print-to-speech prelexical phonological processing route when using manual and vocal responses by testing for facilitating effects of phonological overlap between the irrelevant word and the color name at the initial and final phoneme positions. The results showed phoneme overlap leads to facilitation with both response modes, a result that is inconsistent with qualitative differences between the two response modes

The effect of high-frequency rTMS over left DLPFC and fluid abilities on goal neglect

Goal neglect refers to when an aspect of task instructions is not utilised due to increased competition between goal representations, an attentional limit theoretically linked to working memory. In an attempt to alleviate goal neglect and to investigate the association between dorsolateral prefrontal cortex (DLPFC)-supported working memory and goal neglect, we used high-frequency repetitive transcranial magnetic stimulation to the left DLPFC whilst participants completed the letter-monitoring task, a measure of goal neglect, and an N3-back task, a working memory task known to be affected by rTMS of the left DLPFC, following 20 min of active and sham stimulation (run on separate days). We found increased accuracy on the N3-back task in addition to decreased goal neglect in the active compared to sham condition when controlling for age and fluid abilities (as assessed by matrix reasoning performance). Furthermore, analysis showed that active stimulation improvements on both the N3-back and letter-monitoring tasks were greater for those with higher fluid abilities. These findings provide support for the link between the DLPFC-support working memory and goal neglect. Increased performance on the N3-back task also supports the literature reporting a link between left DLPFC and verbal working memory. Results are evaluated in the context of potential use to alleviate symptoms of disorders related to goal neglect

Investigating TriHaloMethanes with respect to humidity

The disinfection of potable water has dramatically reduced the instances of Cholera and similar ailments within a population drawing upon that water source. There is however the possibility that Natural Organic Matter (NOM) can interact with the disinfection compounds to form Disinfection By-Products (DBP). One group of DBPs are Trihalomethanes (THMs) with several compounds of the group being suspected carcinogens. Within the UK the total concentration of all THMs within drinking water must not exceed 100µg/l. At present water authorities take samples of the water supply and return them to a central laboratory for analysis. This provides an accurate test but one which can involve a long lead time in discovering a potential hazard to public health. A Field Asymmetric Ion Mobility Spectrometer (FAIMS) sensor may be ideally placed to perform in situ continuous monitoring at particular sites. As part of a PhD co-sponsored by The Open University and Owlstone Nanotech Plc an investigation is ongoing to discover how sensitive a FAIMS device is with respect to THMs and humidity when sampling. Initial results and the method of data processing, which involves peak fitting to evolving spectra are presented