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Methylphenidate (MPH) is used clinically to treat attention-deficit/hyperactivity disorder (ADHD) and off-label as a performance-enhancing agent in healthy individuals. MPH enhances catecholamine transmission via blockade of norepinephrine (NE) and dopamine (DA) reuptake transporters. However, it is not clear how this action affects neural circuits performing cognitive and sensorimotor functions driving performance enhancement. The dorsal lateral geniculate nucleus (dLGN) is the primary thalamic relay for visual information from the retina to the cortex and is densely innervated by NE-containing fibers from the locus coeruleus (LC), a pathway known to modulate state-dependent sensory processing. Here, MPH was evaluated for its potential to alter stimulus-driven sensory responses and behavioral outcomes during performance of a visual signal detection task. MPH enhanced activity within individual neurons, ensembles of neurons, and visually-evoked potentials (VEPs) in response to task light cues, while increasing coherence within theta and beta oscillatory frequency bands. MPH also improved reaction times to make correct responses, indicating more efficient behavioral performance. Improvements in reaction speed were highly correlated with faster VEP latencies. Finally, immunostaining revealed that catecholamine innervation of the dLGN is solely noradrenergic. This work suggests that MPH, acting via noradrenergic mechanisms, can substantially affect early-stage sensory signal processing and subsequent behavioral outcomes.

The gene encoding the dipeptidyl-like protein DPP6 (also known as DPPX) has been associated with human neural disease. However, until recently no function had been found for this protein. It has been proposed that DPP6 is an auxiliary subunit of neuronal Kv4 K+ channels, the ion channels responsible for the somato-dendritic A-type K+ current, an ionic current with crucial roles in the regulation of firing frequency, dendritic integration and synaptic plasticity. This view has been supported mainly by studies showing that DPP6 is necessary to generate channels with biophysical properties resembling the native channels in some neurons. However, independent evidence that DPP6 is a component of neuronal Kv4 channels in the brain, and whether this protein has other functions in the CNS is still lacking. We generated antibodies to DPP6 proteins to compare their distribution in brain with that of the Kv4 pore-forming subunits. DPP6 proteins were prominently expressed in neuronal populations expressing Kv4.2 proteins and both types of protein were enriched in the dendrites of these cells, strongly supporting the hypothesis that DPP6 is an associated protein of Kv4 channels in brain neurons. The observed similarity in the cellular and subcellular patterns of expression of both proteins suggests that this is the main function of DPP6 in brain. However, we also found that DPP6 antibodies intensely labeled the hippocampal mossy fiber axons, which lack Kv4 proteins, suggesting that DPP6 proteins may have additional, Kv4-unrelated functions.

We used hot-film anemometry to quantify fine-scale spatial and temporal flow variations near the surfaces of stones inhabited by suspension-feeding larval blackflies (Simulium vittatum). We focused especially on within-stone patterns of covariation between patchy microdistributions of larvae and local spatial variations in current speed. Current speeds were sampled at 256 Hz for heights between 1 and 10 mm above the bed. Profiles of current speed exhibited complex shapes, and boundary-layer thicknesses ranged from <1 to >5 mm. Average current speeds measured 2 mm above the bed (the approximate height of larval feeding appendages) ranged between 7 and 59 cm s-1. Current speeds measured 10 mm above the bed were very poor predictors of speeds measured at the 2-mm height. Larval abundance exhibited a significant positive relationship to current speed at 2-mm height, and within-stone variation in speed explained$\\ticksim 59%$of the variation in abundance. Times series of current speed exhibited marked fine-scale temporal heterogeneity, fluctuating by as much as$80 cm s^-1 in <0.1 s$. Maximum accelerations sometimes exceeded 1 × 104cm s-2, which suggests that the forces tending to dislodge benthic organisms from the bed may be greater than previous estimates based on assumptions of steady flow. Observed levels of turbulence were greater than predicted from traditional boundary-layer theory. We suggest that much of the turbulence evident on individual stones is not produced by local shear but is inherited from upstream roughness elements that cause flow separation.

Anatomical and physiological changes were evaluated in the median nerves of rats trained to perform repetitive reaching. Motor degradation was evident after 4 weeks. ED1-immunoreactive macrophages were seen in the transcarpal region of the median nerve of both forelimbs by 5–6 weeks. Fibrosis, characterized by increased immunoexpression of collagen type I by 8 weeks and connective tissue growth factor by 12 weeks, was evident. The conduction velocity (NCV) within the carpal tunnel showed a modest but significant decline after 9–12 weeks. The lowest NCV values were found in animals that refused to participate in the task for the full time available. Thus, both anatomical and physiological signs of progressive tissue damage were present in this model. These results, together with other recent findings indicate that work-related carpal tunnel syndrome develops through mechanisms that include injury, inflammation, fibrosis and subsequent nerve compression.

The objective of this study is to reevaluate the statistically significant elevated risk of lung cancer among men with ≥20 years of employment at Dow Corning Corporation, a manufacturer of silicon-based materiah. The cohort included 712 deaths among 8266 employees who were hired from 1943 to 1992 with follow-up through 1994. Standardized mortality ratios (SMRs) were calculated for 63 causes of death. Analysis confirmed a statistically significant increased mortality from cancer of the bronchus, trachea, and lung among men, prior to 1985, who jointly classified with ≥30 years of work duration and ≥30 years since first employed. SMRs for lung cancer after 1985, however, were not statistically significant and were inconsistent across work duration and years since first employed intervals. The study provides no evidence for elevated mortality among Dow Corning workers since the 1991 cohort mortality study. This study describes the updated mortality experience of a large employee cohort from a major silicon-based manufacturer. It illustrates that a well-designed mortality study can be a key component of employee health surveillance efforts in an industrial setting with potential hazardous workplace exposures.

What should be the aims, scope and objectives of public participation in EIA? And how has public participation been treated by the EC Member States, the UK in particular, the World Bank in its enabling role in developing countries, and the European Bank for Reconstruction and Development in its activities in central and eastern Europe?

Ion channels are critical regulators of neuronal excitability in the central nervous system and mutations in these proteins produce human disease such as epilepsy and ataxia. Potassium channels are by far the most diverse group of ion channels and influence many aspects of neuronal communication from subthreshold synaptic integration to action potential generation and neurotransmitter release. In this thesis, I investigate the functional roles of Kv1 potassium channels in a specialized subtype of neocortical GABAergic interneuron known as the fast-spiking (FS) cell. Fast and reliable operation of these neurons is thought to be essential for normal cortical function. Using immunohistochemical methods, we show that Kv1.1 protein subunits are highly enriched at the axon initial segment of FS cells--the site of action potential generation. By recording FS cell activity in response to naturalistic fluctuating inputs combined with Kv1 specific pharmacology and recordings in Kv1.1 null mice, we show that Kv1 channels with specific biophysical properties are important determinants of input selectivity and precise spike generation in FS cells. These studies may have implications for the mechanisms regulating FS cell action potential generation in vivo and for the cellular basis of seizures in animal models of epilepsy.

The number of audits for state and local sales tax compliance are steadily increasing because of the tough economy, anti-tax climate, better tracking equipment and budget crunches. However, compliance is difficult because many companies are unaware of their liability and what amount of business constitutes a nexus. Accountants need to inform their clients of the audit increases and become more knowledgeable about state and local tax laws.

Theories concerning the structure of cities in the developing world have only recently been formulated, and many of these theories are broad generalizations which may not necessarily be applicable in individual countries. The evolution of social patterns in Iranian cities is briefly examined and the dimensions of Iran's city system are analysed using multivariate techniques. It is postulated that the cities may be affected by social, economic and demographic changes operating at all levels in the urban hierarchy and that their varied internal response to change may be related to the major dimensions of social difference between them. The various processes influencing the contemporary social patterns in cities are analysed. The evidence suggests that social polarization in cities is now very marked, the dual centres in several of the largest being an extreme form of this continuing trend. Three cities, Aran/Bidgol, Kashan and Kermanshah ranging in size from 23 265 to 187 930 and having different scores in the factor analysis, are evaluated in the light of these processes to show the similarities and contrasts in their social patterns. Many of the generalizations postulated by several authors concerning density gradients and residential areas of different income groups are not applicable to Iran.