Sleep complaints and risk factors for excessive daytime sleepiness in adult males in Northern Ireland

The prevalence of sleep complaints in Northern Ireland is unknown. Sleep disruption can result in excessive daytime sleepiness (EDS), with significant socioeconomic consequences. The aim of this study was to assess the prevalence of sleep complaints and to determine risk factors for EDS in a Northern Irish community. From an urban and rural community of 499 111 people, a random sample of 3391 adult men were sent a questionnaire by mail. Questions were asked regarding sleep, EDS and medical history. There were 2364 completed questionnaires returned (response rate 70%). The mean age of respondents was 46.0 years (range 18-91 years). 26.7% of men were not satisfied with their usual night's sleep and 68% of men woke up at least once during the night. Based on pre-defined criteria, 24.6% of the population had insomnia and 19.8% had EDS. The strongest risk factor identified for EDS was a history of snoring loudly (odds ratio 2.62; 95% CI 1.82-3.77). Other risk factors included ankle swelling, feeling sad or depressed stopping sleep, experiencing vivid dreams while falling asleep, waking up feeling unrefreshed and age > 35 years. The prevalence rates of sleep complaints and EDS in this community-based study is high, although this does depend directly on the criteria used to define insomnia and EDS. Recognition of risk factors for EDS may help to identify and treat those affected.

JMJD6 is a driver of cellular proliferation and motility and a marker of poor prognosis in breast cancer

We developed an analytic strategy that correlates gene expression and clinical outcomes as a means to identify novel candidate oncogenes operative in breast cancer. This analysis, followed by functional characterization, resulted in the identification of Jumonji Domain Containing 6 (JMJD6) protein as a novel driver of oncogenic properties in breast cancer.

Impact of oncogenic driver mutations on feedback between the PI3K and MEK pathways in cancer cells

Inhibition of the PI3K (phosphoinositide 3-kinase)/Akt/mTORC1 (mammalian target of rapamycin complex 1) and Ras/MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase]/ERK pathways for cancer therapy has been pursued for over a decade with limited success. Emerging data have indicated that only discrete subsets of cancer patients have favourable responses to these inhibitors. This is due to genetic mutations that confer drug insensitivity and compensatory mechanisms. Therefore understanding of the feedback mechanisms that occur with respect to specific genetic mutations may aid identification of novel biomarkers that predict patient response. In the present paper, we show that feedback between the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways is cell-line-specific and highly dependent on the activating mutation of K-Ras or overexpression c-Met. We found that cell lines exhibited differential signalling and apoptotic responses to PD184352, a specific MEK inhibitor, and PI103, a second-generation class I PI3K inhibitor. We reveal that feedback from the PI3K/Akt/mTORC1 to the Ras/MEK/ERK pathway is present in cancer cells harbouring either K-Ras activating mutations or amplification of c-Met but not the wild-type counterparts. Moreover, we demonstrate that inhibition of protein phosphatase activity by OA (okadaic acid) restored PI103-mediated feedback in wild-type cells. Together, our results demonstrate a novel mechanism for feedback between the PI3K/Akt/mTORC1 and the Ras/MEK/ERK pathways that only occurs in K-Ras mutant and c-Met amplified cells but not the isogenic wild-type cells through a mechanism that may involve inhibition of a specific endogenous phosphatase(s) activity. We conclude that monitoring K-Ras and c-Met status are important biomarkers for determining the efficacy of PI103 and other PI3K/Akt inhibitors in cancer therapy.

Multi-Level Wordline Driver for Low Power SRAMs in Nano-Scale CMOS Technology

In this paper, a multi-level wordline driver scheme is presented to improve SRAM read and write stability while lowering power consumption during hold operation. The proposed circuit applies a shaped wordline voltage pulse during read mode and a boosted wordline pulse during write mode. During read, the applied shaped pulse is tuned at nominal voltage for short period of time, whereas for the remaining access time, the wordline voltage is reduced to a lower level. This pulse results in improved read noise margin without any degradation in access time which is explained by examining the dynamic and nonlinear behavior of the SRAM cell. Furthermore, during hold mode, the wordline voltage starts from a negative value and reaches zero voltage, resulting in a lower leakage current compared to conventional SRAM. Our simulations using TSMC 65nm process show that the proposed wordline driver results in 2X improvement in static read noise margin while the write margin is improved by 3X. In addition, the total leakage of the proposed SRAM is reduced by 10% while the total power is improved by 12% in the worst case scenario of a single SRAM cell. The total area penalty is 10% for a 128Kb standard SRAM array.

Multi-level wordline driver for robust SRAM design in nano-scale CMOS technology

In this paper, a multi-level wordline driver scheme is presented to improve 6T-SRAM read and write stability. The proposed wordline driver generates a shaped pulse during the read mode and a boosted wordline during the write mode. During read, the shaped pulse is tuned at nominal voltage for a short period of time, whereas for the remaining access time, the wordline voltage is reduced to save the power consumption of the cell. This shaped wordline pulse results in improved read noise margin without any degradation in access time for small wordline load. The improvement is explained by examining the dynamic and nonlinear behavior of the SRAM cell. Furthermore, during the hold mode, for a short time (depending on the size of boosting capacitance), wordline voltage becomes negative and charges up to zero after a specific time that results in a lower leakage current compared to conventional SRAM. The proposed technique results in at least 2× improvement in read noise margin while it improves write margin by 3× for lower supply voltages than 0.7 V. The leakage power for the proposed SRAM is reduced by 2% while the total power is improved by 3% in the worst case scenario for an SRAM array. The main advantage of the proposed wordline driver is the improvement of dynamic noise margin with less than 2.5% penalty in area. TSMC 65 nm technology models are used for simulations.