An engineered Tetrahymena tRNA(Gln) for in vivo incorporation of unnatural amino acids into proteins by nonsense suppression

A new tRNA, THG73, has been designed and evaluated as a vehicle for incorporating unnatural amino acids site-specifically into proteins expressed in vivo using the stop codon suppression technique. The construct is a modification of tRNAGln(CUA) from Tetrahymena thermophila, which naturally recognizes the stop codon UAG. Using electrophysiological studies of mutations at several sites of the nicotinic acetylcholine receptor, it is established that THG73 represents a major improvement over previous nonsense suppressors both in terms of efficiency and fidelity of unnatural amino acid incorporation. Compared with a previous tRNA used for in vivo suppression, THG73 is as much as 100-fold less likely to be acylated by endogenous synthetases of the Xenopus oocyte. This effectively eliminates a major concern of the in vivo suppression methodology, the undesirable incorporation of natural amino acids at the suppression site. In addition, THG73 is 4-10-fold more efficient at incorporating unnatural amino acids in the oocyte system. Taken together, these two advances should greatly expand the range of applicability of the in vivo nonsense suppression methodology

Gold substrate-induced single-mode lasing of GaN nanowires

We demonstrate a method for mode-selection by coupling a GaN nanowire laser to an underlying gold substrate. Multimode lasing of GaN nanowires is converted to single-mode behavior following placement onto a gold film. A mode-dependent loss is generated by the absorbing substrate to suppress multiple transverse-mode operation with a concomitant increase in lasing threshold of only ∼13%. This method provides greater flexibility in realizing practical single-mode nanowire lasers and offers insight into the design of metal-contacted nanoscale optoelectronics

Literacy Assessment New Zealand Style

It\u27s mostly performance based. It assesses students in teams as well as individually. What\u27s more, students like it

D₂ Dopamine Receptors Colocalize Regulator of G-Protein Signaling 9-2 (RGS9-2) via the RGS9 DEP Domain, and RGS9 Knock-Out Mice Develop Dyskinesias Associated with Dopamine Pathways

Regulator of G-protein signaling 9-2 (RGS9-2), a member of the RGS family of Gα GTPase accelerating proteins, is expressed specifically in the striatum, which participates in antipsychotic-induced tardive dyskinesia and in levodopa-induced dyskinesia. We report that RGS9 knock-out mice develop abnormal involuntary movements when inhibition of dopaminergic transmission is followed by activation of D₂-like dopamine receptors (DRs). These abnormal movements resemble drug-induced dyskinesia more closely than other rodent models. Recordings from striatal neurons of these mice establish that activation of D₂-like DRs abnormally inhibits glutamate-elicited currents. We show that RGS9-2, via its DEP domain (for Disheveled, EGL-10, Pleckstrin homology), colocalizes with D₂DRs when coexpressed in mammalian cells. Recordings from oocytes coexpressing D₂DR or the m2 muscarinic receptor and G-protein-gated inward rectifier potassium channels show that RGS9-2, via its DEP domain, preferentially accelerates the termination of D₂DR signals. Thus, alterations in RGS9-2 may be a key factor in the pathway leading from D₂DRs to the side effects associated with the treatment both of psychoses and Parkinson's disease

Effectiveness of a Heads-Up Adaptive Lane Deviation Warning System for Middle-Aged and Older Adults

46 participants (24 younger and 22 older) completed at least one out of four simulated drives designed to test the effectiveness of an Adaptive Lane Deviation Warning (LDW) system, and they drove through both a warnings-on and warnings-off version of each drive. Findings showed that LDW was effective in reducing reaction time for lane deviation corrections for both older (by 1.2 seconds) and younger drivers (by 1.6 seconds). The older and younger drivers did not differ in correction RTs when the warnings were turned off. But older drivers showed slower correction RTs than younger drivers in the warning-on drives. The data indicate that these benefits were specific to LDW rather than general improvement in driving performance. Cognitive processing speed emerged as a particularly robust predictor of benefits from the LDW compared to other domains of cognitive function

Pilot Results on Forward Collision Warning System Effectiveness in Older Drivers

Advanced Driver Assistance Systems (ADAS) have largely been developed with a “one-size-fits-all” approach. This approach neglects the large inter-individual variability in perceptual and cognitive abilities that affect aging ADAS users. We investigated the effectiveness of a forward collision warning (FCW) with fixed response parameters in young and older drivers with differing levels of cognitive functioning. Drivers responded to a pedestrian stepping into the driver’s path on a simulated urban road. Behavioral metrics included response times (RT) for pedal controls and two indices of risk penetration (e.g., maximum deceleration and minimum time-to-collision (TTC)). Older drivers showed significantly slower responses at several time points compared to younger drivers. The FCW facilitated response times (RTs) for older and younger drivers. However, older drivers still showed smaller safety gains compared to younger drivers at accelerator pedal release and initial brake application when the FCW was active. No significant differences in risk metrics were observed within the condition studied. The results demonstrate older drivers likely differ from younger drivers using a FCW with a fixed parameter set. Finally, we briefly discuss how future research should examine predictive relationships between domains of cognitive functioning and ADAS responses to develop parameter sets to fit the individual

Causes of death in Vanuatu

Background The population of the Pacific Melanesian country of Vanuatu was 234,000 at the 2009 census. Apart from subsistence activities, economic activity includes tourism and agriculture. Current completeness of vital registration is considered too low to be usable for national statistics; mortality and life expectancy (LE) are derived from indirect demographic estimates from censuses/surveys. Some cause of death (CoD) data are available to provide information on major causes of premature death. Methods Deaths 2001–2007 were coded for cause (ICDv10) for ages 0–59 years from: hospital separations (HS) (n = 636), hospital medical certificates (MC) of death (n = 1,169), and monthly reports from community health facilities (CHF) (n = 1,212). Ill-defined causes were 3 % for hospital deaths and 20 % from CHF. Proportional mortality was calculated by cause (excluding ill-defined) and age group (0–4, 5–14 years), and also by sex for 15–59 years. From total deaths by broad age group and sex from 1999 and 2009 census analyses, community deaths were estimated by deduction of hospital deaths MC. National proportional mortality by cause was estimated by a weighted average of MC and CHF deaths. Results National estimates indicate main causes of deaths <5 years were: perinatal disorders (45 %) and malaria, diarrhea, and pneumonia (27 %). For 15–59 years, main causes of male deaths were: circulatory disease 27 %, neoplasms 13 %, injury 13 %, liver disease 10 %, infection 10 %, diabetes 7 %, and chronic respiratory disease 7 %; and for females: neoplasms 29 %, circulatory disease 15 %, diabetes 10 %, infection 9 %, and maternal deaths 8 %. Infection included tuberculosis, malaria, and viral hepatitis. Liver disease (including hepatitis and cancer) accounted for 18 % of deaths in adult males and 9 % in females. Non-communicable disease (NCD), including circulatory disease, diabetes, neoplasm, and chronic respiratory disease, accounted for 52 % of premature deaths in adult males and 60 % in females. Injuries accounted for 13 % in adult males and 6 % in females. Maternal deaths translate into an annual maternal mortality ratio of 130/100,000 for the period. Conclusion Vanuatu manifests a double burden of disease with significant proportional mortality from perinatal disorders and infection/pneumonia <5 years and maternal mortality, coupled with significant proportional mortality in adults (15–59 years) from cardiovascular disease (CVD), neoplasms, and diabetes

Natural History of the Porcine Bioprosthetic Heart Valve

The porcine bioprosthesis has been the prosthetic valve of choice at Henry Ford Hospital since October 1971. By 1979, 23 cases of degeneration had been seen, and the rate seven years after implantation was 16%. Now, with a ten-year follow-up, there are 41 degenerated valves. After seven years, the percent free of degeneration is 88%, (SE of 2% [standard error]); at eight years, 82% (SE of 2.9%,); at nine years, 80% (SE of 3.4%); and at ten years, the percent free of degeneration is 69% (SE of 6.5%,). There was no difference in degeneration between men and women, between aortic or mitral position, or between the valves which were or were not rinsed in antibiotics. The incidence of degeneration was significantly greater in patients under 35 years of age. Contrary to our expectations, the number of valves removed for degeneration has not increased linearly, although the number at risk has continued to rise. In 1977, we removed four valves for degeneration; in 1978, eight valves; in 1979, 77 valves; in 1980, five valves; and in 1981, ten valves. The duration of implantation for degenerated valves has increased from 56 months (SD [standard deviation] of 11 months) in 1977-78 to 77 months (SD of 19 months) in 1981. Analysis of cohorts from 1972,1973, 1974, all now followed for seven years, reveals that at seven years the percent free of degeneration for 1972 is 88% (SE of 4.4%,); for 1973, 83% (SE of 4.8%); and for 1974, 95% (SE of 2.6%). Although a difference is suggested, it is not yet statistically significant (p = .48) due to the small number of valves degenerating. The incidence of porcine bioprosthetic degeneration appears to be decreasing, possibly because valves manufactured later in the series are more durable