Mechanism of Tacrine Block at Adult Human Muscle Nicotinic Acetylcholine Receptors

We used single-channel kinetic analysis to study the inhibitory effects of tacrine on human adult nicotinic receptors (nAChRs) transiently expressed in HEK 293 cells. Single channel recording from cell-attached patches revealed concentration- and voltage-dependent decreases in mean channel open probability produced by tacrine (IC50 4.6 μM at −70 mV, 1.6 μM at −150 mV). Two main effects of tacrine were apparent in the open- and closed-time distributions. First, the mean channel open time decreased with increasing tacrine concentration in a voltage-dependent manner, strongly suggesting that tacrine acts as an open-channel blocker. Second, tacrine produced a new class of closings whose duration increased with increasing tacrine concentration. Concentration dependence of closed-times is not predicted by sequential models of channel block, suggesting that tacrine blocks the nAChR by an unusual mechanism. To probe tacrine's mechanism of action we fitted a series of kinetic models to our data using maximum likelihood techniques. Models incorporating two tacrine binding sites in the open receptor channel gave dramatically improved fits to our data compared with the classic sequential model, which contains one site. Improved fits relative to the sequential model were also obtained with schemes incorporating a binding site in the closed channel, but only if it is assumed that the channel cannot gate with tacrine bound. Overall, the best description of our data was obtained with a model that combined two binding sites in the open channel with a single site in the closed state of the receptor

Comparisons Of Proctored Versus Non-Proctored Testing Strategies In Graduate Distance Education Curriculum

The authors studied the testing pattern grades in four e-campus courses at Troy University with 76 graduate students. In their research, the authors found significant differences in average test grade scores between tests taken electronically without a proctor as compared to those administered using a live or a remote proctor overall. To control for differences among courses, a statistical test was solely conducted on the courses which had the same instructor, same text, and similar tests with comparable results; students scored significantly lower on proctored exams versus non-proctored exams. To enhance the quality of courses in the online environment, the researchers recommend several “best practices” pedagogical strategies based on their findings and an extensive literature review

Gravitational recoil from spinning binary black hole mergers

The inspiral and merger of binary black holes will likely involve black holes with both unequal masses and arbitrary spins. The gravitational radiation emitted by these binaries will carry angular as well as linear momentum. A net flux of emitted linear momentum implies that the black hole produced by the merger will experience a recoil or kick. Previous studies have focused on the recoil velocity from unequal mass, non-spinning binaries. We present results from simulations of equal mass but spinning black hole binaries and show how a significant gravitational recoil can also be obtained in these situations. We consider the case of black holes with opposite spins of magnitude $a$ aligned/anti-aligned with the orbital angular momentum, with $a$ the dimensionless spin parameters of the individual holes. For the initial setups under consideration, we find a recoil velocity of V = 475 \KMS a. Supermassive black hole mergers producing kicks of this magnitude could result in the ejection from the cores of dwarf galaxies of the final hole produced by the collision.Comment: 8 pages, 8 figures, replaced with version accepted for publication in Ap

Cost efficient narrow linewidth laser transmitter for coherent detection

Authors present a cost efficient narrow linewidth laser transmitter for future coherent detection systems. The spectral purity of the laser allows the phase modulation of data signals at bit rates as low as 155 Mb/s

Discrete mode laser diodes with ultra narrow linewidth emission <3kHz

Ex-facet, free-running ultra-low linewidth (<3 kHz), single mode laser emission is demonstrated using low cost, regrowth-free ridge waveguide discrete mode Fabry-Perot laser diode chips

The economic status of older people’s households in urban and rural settings in Peru, Mexico and China: a 10/66 INDEP study cross-sectional survey

Few data are available from middle income countries regarding economic circumstances of households in which older people live. Many such settings have experienced rapid demographic, social and economic change, alongside increasing pension coverage. Population-based household surveys in rural and urban catchment areas in Peru, Mexico and China. Participating households were selected from all households with older residents. Descriptive analyses were weighted back for sampling fractions and non-response. Household income and consumption were estimated from a household key informant interview. 877 Household interviews (3177 residents). Response rate 68 %. Household income and consumption correlated plausibly with other economic wellbeing indicators. Household Incomes varied considerably within and between sites. While multigenerational households were the norm, older resident’s incomes accounted for a high proportion of household income, and older people were particularly likely to pool income. Differences in the coverage and value of pensions were a major source of variation in household income among sites. There was a small, consistent inverse association between household pension income and labour force participation of younger adult co-residents. The effect of pension income on older adults’ labour force participation was less clear-cut. Historical linkage of social protection to formal employment may have contributed to profound late-life socioeconomic inequalities. Strategies to formalise the informal economy, alongside increases in the coverage and value of non-contributory pensions and transfers would help to address this problem

The Zwicky Transient Facility: Surveys and Scheduler

We present a novel algorithm for scheduling the observations of time-domain imaging surveys. Our Integer Linear Programming approach optimizes an observing plan for an entire night by assigning targets to temporal blocks, enabling strict control of the number of exposures obtained per field and minimizing filter changes. A subsequent optimization step minimizes slew times between each observation. Our optimization metric self-consistently weights contributions from time-varying airmass, seeing, and sky brightness to maximize the transient discovery rate. We describe the implementation of this algorithm on the surveys of the Zwicky Transient Facility and present its on-sky performance.Comment: Published in PASP Focus Issue on the Zwicky Transient Facility (https://dx.doi.org/10.1088/1538-3873/ab0c2a). 13 Pages, 11 Figure

Dietary Protein and Bone Health Across the Life-Course : an updated systematic review and meta-analysis over 40 years

Abstract Purpose: This systematic review and meta-analysis analysed the relationship between dietary protein and bone health across the life-course. Methods: The PubMed database was searched for all relevant human studies from the 1st 4 January 1976 to 22nd January 2016, including all bone outcomes except calcium metabolism. Results: The searches identified 127 papers for inclusion, including 74 correlational studies, 23 fracture or osteoporosis risk studies and 30 supplementation trials. Protein intake accounted for 0 - 4% of areal BMC and areal BMD variance in adults and 0-14% of areal BMC variance in children and adolescents. However, when confounder adjusted (5 studies) adult lumbar spine and femoral neck BMD associations were not statistically significant. There was no association between protein intake and relative risk (RR) of osteoporotic fractures for total (RR(random) = 0.94; 0.72 to 1.23, I2=32%), animal (RR (random) = 0.98; 0.76 to 1.27, I2 = 46%) or vegetable protein (RR (fixed)= 0.97 (0.89 to 1.09, I2 = 15%). In total protein supplementation studies, pooled effect sizes were not statistically significant for LSBMD (total n=255, MD(fixed)=0.04 g/cm2 (0.00 to 0.08, P=0.07), I2=0%) or FNBMD (total n=435, MD(random)=0.01 g/cm2 (-0.03 to 0.05, P=0.59), I2=68%). Conclusions: There appears to be little benefit of increasing protein intake for bone health in healthy adults but there is also clearly no indication of any detrimental effect, at least within the protein intakes of the populations studied (around 0.8-1.3 g/Kg/day). More studies are urgently required on the association between protein intake and bone health in children and adolescents. Key Words: Aging, Epidemiology, IGF-1, Nutrition, Osteoporosis, Die

Long-term effects of a protein-enriched diet on blood pressure in older women

Short-term randomised, controlled trials have found that dietary protein relative to carbohydrate can reduce blood pressure. Our objective was to investigate the effects on blood pressure of an increase in protein intake from whey over 2 years in women aged over 70 years. From the general population, 219 women aged between 70 and 80 years were recruited to a 2-year randomised, double-blind, placebo-controlled parallel-design trial: 181 women completed the trial to the end of year 2. Participants were randomly assigned to consume a daily whey protein-based beverage (protein) or an energy-matched low-protein high-carbohydrate beverage (control). Blood pressure measurements were performed at baseline, year 1 and year 2. For protein relative to control, the estimated mean net differences in protein and carbohydrate intakes were 18 (95 % CI 13, 23) and − 22 (95 % CI − 9, − 35) g/d at year 1, and 22 (95 % CI 17, 28) and − 18 (95 % CI − 6, − 31) g/d at year 2. Intention-to-treat analysis found no overall differences between groups in blood pressure (P>0.5). Net differences in systolic and diastolic blood pressure were – 2.3 (95 % CI – 5.3, 0.7) and – 1.5 (95 % CI – 3.6, 0.6) mmHg at year 1, and 1.6 (95 % CI – 1.5, 4.7) and 0.3 (95 % CI – 1.9, 2.4) mmHg at year 2. Similar differences in systolic and diastolic blood pressure at years 1 and 2 were observed with per-protocol analysis. Therefore, the present study did not provide evidence that a higher whey protein intake in older women can have prolonged effects on blood pressure