The thalamic reticular nucleus: a functional hub for thalamocortical network dysfunction in schizophrenia and a target for drug discovery

The thalamus (comprising many distinct nuclei) plays a key role in facilitating sensory discrimination and cognitive processes through connections with the cortex. Impaired thalamocortical processing has long been considered to be involved in schizophrenia. In this review we focus on the thalamic reticular nucleus (TRN) providing evidence for it being an important communication hub between the thalamus and cortex and how it may play a key role in the pathophysiology of schizophrenia. We first highlight the functional neuroanatomy, neurotransmitter localisation and physiology of the TRN. We then present evidence of the physiological roles of the TRN in relation to oscillatory activity, cognition and behaviour. Next we discuss the role of the TRN in rodent models of risk factors for schizophrenia (genetic and pharmacological) and provide evidence for TRN deficits in schizophrenia. Finally we discuss new drug targets for schizophrenia in relation to restoring TRN circuitry dysfunction

BDNF and JNK-signalling modulate cortical interneuron and perineuronal net development: implications for schizophrenia-linked 16p11.2 duplication syndrome

Schizophrenia is a neurodevelopmental disorder caused by the interaction of genetic and environmental risk factors. One of the strongest genetic risk variants is duplication of chr.16p11.2. Schizophrenia is characterised by cortical GABAergic interneuron dysfunction, and disruption to surrounding extracellular matrix structures, perineuronal nets (PNNs). Developmental maturation of GABAergic interneurons, and also the resulting closure of the critical period of cortical plasticity, is regulated by brain derived neurotrophic factor (BDNF), although the mechanisms involved are unknown. Here, we show that BDNF promotes GABAergic interneuron and PNN maturation through JNK signalling. In mice reproducing the 16p11.2 duplication, where the JNK upstream activator Taok2 is overexpressed, we find that JNK is overactive and there are developmental abnormalities in PNNs which persist into adulthood. Prefrontal cortex parvalbumin expression is reduced while PNN intensity is increased. Additionally, we report a unique role for TAOK2 signalling in the regulation of parvalbumin interneurons. Our work implicates TAOK2-JNK signalling in cortical interneuron and PNN development, and in the responses to BDNF. It also demonstrates that over-activation of this pathway in conditions associated with schizophrenia risk causes long-lasting disruption in cortical interneurons

Demonstration of Field Emission Cathode Operation in a Plasma Environment

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76844/1/AIAA-2005-3663-570.pd

Field Emission Cathodes used in the FEGI Get-Away-Special Shuttle Mission

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76377/1/AIAA-2004-3498-580.pd

Pre-determination of partial discharge inception voltage in power cables using electrode gaps in air under AC voltage

The breakdown of insulation in cables while in service can cause considerable damage to equipment and the accessories to which they are connected. PD in cables arises due to the overstressing of cable insulation resulting from electric field enhancement caused by imperfections in cable core and screen. The nature and magnitude of PD activity depends upon the type of defect, aging, environmental factors, applied voltage and cable loading. Reduction in system voltage can potentially reduce PD, which will correspondingly extend the service life of the cable. Currently, industry voltage statutory requirements permit ±6% tolerance setting on nominal voltage on distribution networks. This ±6% voltage reduction on may have little or an adverse effect on PD magnitude depending on the nature of defect present in the cable. Hence there is a clear requirement to pre-determine the PD inception voltage in cables through laboratory experiments to understand the significance of voltage reduction. This means to verify the effect of voltage reduction on extinguishing or minimizing PD activity in cables. In this paper, range of voltages at which PD incepts termed as partial discharge inception voltage(PDIV) is measured using a test cell containing different types of electrode configuration having different spacing. PDIV measured using the test cell is verified by conducting partial discharge testing in paper insulated lead covered (PILC) and cross-linked poly ethylene(XLPE) cables. It has been found that PDIV measured using the test cell and cable are in good agreement

Estimation of country-specific and global prevalence of male circumcision.

BACKGROUND: Male circumcision (MC) status and genital infection risk are interlinked and MC is now part of HIV prevention programs worldwide. Current MC prevalence is not known for all countries globally. Our aim was to provide estimates for country-specific and global MC prevalence. METHODS: MC prevalence data were obtained by searches in PubMed, Demographic and Health Surveys, AIDS Indicator Surveys, and Behavioural Surveillance Surveys. Male age was ≥15 years in most surveys. Where no data were available, the population proportion whose religious faith or culture requires MC was used. The total number of circumcised males in each country and territory was calculated using figures for total males from (i) 2015 US Central Intelligence Agency (CIA) data for sex ratio and total population in all 237 countries and territories globally and (ii) 2015 United Nations (UN) figures for males aged 15-64 years. RESULTS: The estimated percentage of circumcised males in each country and territory varies considerably. Based on (i) and (ii) above, global MC prevalence was 38.7 % (95 % confidence interval [CI]: 33.4, 43.9) and 36.7 % (95 % CI: 31.4, 42.0). Approximately half of circumcisions were for religious and cultural reasons. For countries lacking data we assumed 99.9 % of Muslims and Jews were circumcised. If actual prevalence in religious groups was lower, then MC prevalence in those countries would be lower. On the other hand, we assumed a minimum prevalence of 0.1 % related to MC for medical reasons. This may be too low, thereby underestimating MC prevalence in some countries. CONCLUSIONS: The present study provides the most accurate estimate to date of MC prevalence in each country and territory in the world. We estimate that 37-39 % of men globally are circumcised. Considering the health benefits of MC, these data may help guide efforts aimed at the use of voluntary, safe medical MC in disease prevention programs in various countries